STUDIES & ARTICLES

The Psychological Effects of LASIK Complications

The psychological impact of a bad refractive surgery can be devastating.

This updated version of the 2003 presentation, prepared by Roger Davis, PhD. Mr. Davis is a Psychologist; Damaged LASIK patient; Co-author of over 20 articles, chapters, and books in clinical psychology; and Founder of VisionSimulations.com. He tells of The Psychological Effects of LASIK Complications.

Submitted to the FDA’s Ophthalmic Panel on April 25, 2008, the presentation I believe is more believable and accurate than what the FDA and refractive industry claims.

Coping with LASIK Complications

Although the marketing of LASIK focuses on quality of life, informed consent does not. Instead, the real risks are hidden in medical jargon that never mentions their true effects, particularly severe depression and suicidal ideation.

Right now, there are many Lasik casualties worldwide struggling to…

  • Cope with depression and suicidal ideation, medical disease syndromes not explicitly mentioned on their informed consent.
  • Cope with the symptoms of post-traumatic stress (PTSD) and other anxiety disorders.
  • Cope with their surgeons telling them that nothing is wrong with their eyes.
  • Cope with “second opinions” designed to protect their surgeon from legal problems.
  • Find a hard contact lens to fit their irregular corneas, often spending thousands and thousands of dollars hunting for a suboptimal solution.
  • Cope with the possibility of losing their jobs, homes, or spouses because of sudden, permanent visual loss.
  • Cope with three, four, or five complications at the same time.
  • Cope with the need to put drops in their eyes every few minutes, to stop a burning that will NOT go away.
  • Cope with the need to drive (provided you still can) while looking at multiple images of traffic and people (or even as a passenger).
  • Cope with the need to work, while being barely able to read for long periods, or even read at all.
  • Cope with intense feelings of guilt and self-blame because they trusted their doctors.
  • Cope with not knowing what the future holds for them or their vision.
  • Cope with pressure from their loved ones who don’t understand to “shape up”.

Lasik surgery has been hailed as the wonder cure for those who have myopia and astigmatism.  For many, it is a blessing.  Many patients have said, “I can see…without my glasses.”  The decision to have Lasik is, for some people, almost instantaneous.  But before you decide, educate yourself first.  Almost certainly, there are many things that you do not know about Lasik.

If you are considered a “Good Candidate,” and have less than 20/40 best-corrected visual acuity (BCVA) then:

  • Second and third opinions are a must.  Most doctors are reluctant to do surgery on people with less than 20/40 BCVA.  Most have protocols and standards by which they abide.  Beware of surgeons that seem all to eager.
  • Make sure the surgeon is reputable.  Plaques and diplomas do not necessarily show the true person.  Certainly there are those that do care, but there are also those that give their clients books and other literature that makes them seem like pioneers.  There are companies that print books with the surgeon’s name apparently as the author, when the surgeon had nothing to do with the writing of the book.
  • If the procedure is going to be done ‘experimentally’, more than likely the surgeon is using a device not yet approved by the Food and Drug Administration (FDA).  Since other devices are already approved, this is rarely to your advantage.
  • Most importantly, no one can guarantee long-term effects. Remember, Lasik is relatively new!
  • Federal Law requires that every patient who is about to undergo a refractive surgery be given a Patient Information Booklet, published by the manufacturer of the laser used in their surgery. If your surgeon does not give you the patient information booklet, this is a violation of federal law, and your surgeon can be charged with not providing you with full informed consent.  Abuse of this FDA mandate is widespread.  Most patients have never seen a Patient Information Booklet, because it contains warnings that your surgeon does not want you to see.  The FDA Mandate can be found at http://www.fda.gov/cdrh/

Based on my experience and that of many others who were not candidates, or have had complications, your decision to have Lasik should be a WISE ONE!!!

FDA’s WEBSITE RISKS - Obtained from the FDA’s LASIK Website:

  • Before undergoing any type of refractive procedure, you should carefully weigh the risks and benefits based on your own personal value system, and try to avoid being influenced by friends that have had the procedure or doctors encouraging you to do so.
  • Some patients lose vision. Some patients lose lines of vision on the vision chart that cannot be corrected with glasses, contact lenses, or surgery as a result of treatment.
  • Some patients develop debilitating visual symptoms. Some patients develop glare, halos, and/or double vision that can seriously affect nighttime vision. Even with good vision on the vision chart, some patients do not see as well in situations of low contrast, such as at night or in fog, after treatment as compared to before treatment.
  • You may be under treated or over treated. Only a certain percent of patients achieve 20/20 vision without glasses or contacts. You may require additional treatment, but additional treatment may not be possible. You may still need glasses or contact lenses after surgery. This may be true even if you only required a very weak prescription before surgery. If you used reading glasses before surgery, you may still need reading glasses after surgery.
  • Some patients may develop severe dry eye syndrome. As a result of surgery, your eye may not be able to produce enough tears to keep the eye moist and comfortable. Dry eye not only causes discomfort, but can reduce visual quality due to intermittent blurring and other visual symptoms. This condition may be permanent. Intensive drop therapy and use of plugs or other procedures may be required.
  • Results are generally not as good in patients with very large refractive errors of any type. You should discuss your expectations with your doctor and realize that you may still require glasses or contacts after the surgery.
  • For some farsighted patients, results may diminish with age. If you are farsighted, the level of improved vision you experience after surgery may decrease with age. This can occur if your manifest refraction (a vision exam with lenses before dilating drops) is very different from your cycloplegic refraction (a vision exam with lenses after dilating drops).
  • Long-term data is not available. LASIK is a relatively new technology. The first laser was approved for LASIK eye surgery in 1998. Therefore, the long-term safety and effectiveness of LASIK surgery is not known.

Additional Risks if you are Considering the Following:

Monovision

  • Monovision is one clinical technique used to deal with the correction of presbyopia, the gradual loss of the ability of the eye to change focus for close-up tasks that progresses with age. The intent of monovision is for the presbyopic patient to use one eye for distance viewing and one eye for near viewing. This practice was first applied to fit contact lens wearers and more recently to LASIK and other refractive surgeries. With contact lenses, a presbyopic patient has one eye fit with a contact lens to correct distance vision, and the other eye fit with a contact lens to correct near vision. In the same way, with LASIK, a presbyopic patient has one eye operated on to correct the distance vision, and the other operated on to correct the near vision. In other words, the goal of the surgery is for one eye to have vision worse than 20/20, the commonly referred to goal for LASIK surgical correction of distance vision. Since one eye is corrected for distance viewing and the other eye is corrected for near viewing, the two eyes no longer work together. This results in poorer quality vision and a decrease in depth perception. These effects of monovision are most noticeable in low lighting conditions and when performing tasks requiring very sharp vision. Therefore, you may need to wear glasses or contact lenses to fully correct both eyes for distance or near when performing visually demanding tasks, such as driving at night, operating dangerous equipment, or performing occupational tasks requiring very sharp close vision (e.g., reading small print for long periods of time).
  • Many patients cannot get used to having one eye blurred at all times. Therefore, if you are considering monovision with LASIK, make sure you go through a trial period with contact lenses to see if you can tolerate monovision, before having the surgery performed on your eyes. Find out if you pass your state’s driver’s license requirements with monovision.
  • In addition, you should consider how much your presbyopia is expected to increase in the future. Ask your doctor when you should expect the results of your monovision surgery to no longer be enough for you to see near-by objects clearly without the aid of glasses or contacts, or when a second surgery might be required to further correct your near vision.

Bilateral Simultaneous Treatment

  • You may choose to have LASIK surgery on both eyes at the same time or to have surgery on one eye at a time. Although the convenience of having surgery on both eyes on the same day is attractive, this practice is riskier than having two separate surgeries.
  • If you decide to have one eye done at a time, you and your doctor will decide how long to wait before having surgery on the other eye. If both eyes are treated at the same time or before one eye has a chance to fully heal, you and your doctor do not have the advantage of being able to see how the first eye responds to surgery before the second eye is treated.
  • Another disadvantage to having surgery on both eyes at the same time is that the vision in both eyes may be blurred after surgery until the initial healing process is over, rather than being able to rely on clear vision in at least one eye at all times.

Finding the Right Doctor

If you are considering refractive surgery, make sure you:

  • Compare. The levels of risk and benefit vary slightly not only from procedure to procedure, but from device to device depending on the manufacturer, and from surgeon to surgeon depending on their level of experience with a particular procedure.
  • Don’t base your decision simply on cost and don’t settle for the first eye center, doctor, or procedure you investigate. Remember that the decisions you make about your eyes and refractive surgery will affect you for the rest of your life.
  • Be wary of eye centers that advertise, “20/20 vision or your money back” or “package deals.” There are never any guarantees in medicine.
  • Read. It is important for you to read the patient handbook provided to your doctor by the manufacturer of the device used to perform the refractive procedure. Your doctor should provide you with this handbook and be willing to discuss his/her outcomes (successes as well as complications) compared to the results of studies outlined in the handbook.

Even the best screened patients under the care of most skilled surgeons can experience serious complications.

During surgery. Malfunction of a device or other error, such as cutting a flap of cornea through and through instead of making a hinge during LASIK surgery, may lead to discontinuation of the procedure or irreversible damage to the eye.

After surgery. Some complications, such as migration of the flap, inflammation or infection, may require another procedure and/or intensive treatment with drops. Even with aggressive therapy, such complications may lead to temporary loss of vision or even irreversible blindness.

Under the care of an experienced doctor, carefully screened candidates with reasonable expectations and a clear understanding of the risks and alternatives are likely to be happy with the results of their refractive procedure.

Advertising

Be cautious about “slick” advertising and/or deals that sound “too good to be true.” Remember, they usually are. There is a lot of competition resulting in a great deal of advertising and bidding for your business. Do your homework.

If you want to know more about advertising ethics, do’s and don’ts, or want to report on false advertising, explore the following websites:

http://www.ftc.gov/bcp/menu-ads.htm

http://www.ftc.gov/bcp/menu-health.htm

This information (risks may be understated) and more can be obtained from the FDA’s website.

http://www.fda.gov/cdrh/LASIK/risks.htm

Post-LASIK Infections – Live virus survives excimer laser ablation

Opthalmology 1999 Aug;106(8):1498-9

Taravella MJ, Weinberg A, May M, Stepp P.

Department of Ophthalmology, University of Colorado Health Sciences Center, Denver, USA.

OBJECTIVES: To determine whether live virus can withstand excimer laser ablation and pose a possible health hazard to medical personnel.

DESIGN: Experimental study.

METHODS: Fibroblasts infected with oral polio vaccine virus were ablated with an excimer laser. The plume was collected using a smoke evacuator and bubbled through viral culture media.

MAIN OUTCOME MEASURES: The inlet tube from the smoke evacuator was swabbed and cultured for virus. Liquid from the bubble trap was also cultured.

RESULTS: Live virus was shown in the material trapped from the laser plume.

CONCLUSIONS: Oral polio vaccine virus can survive excimer laser ablation. Whether other more clinically relevant viruses, such as human immunodeficiency virus, can withstand ablation and remain infectious remains to be determined.

Aerosolization of infectious virus by excimer laser

American Journal of Ophthalmology 1997 March, 123(3):297-302

Moreira LB, Sanchez D, Trousdale MD, Stevenson D, Yarber F, McDonnell PJ. Doheny Eye Institute, Los Angeles, CA 90033, USA.

PURPOSE: To determine the potential for aerosolization of infectious virus present within the tear film during excimer laser photoablation of the cornea.

METHODS: Cell monolayers infected with herpes simplex virus or adenovirus, simulating virus-infected corneas, were ablated with the 193-nm excimer laser. Adjacent dishes containing noninfected cell monolayers were subsequently assayed for viral infection.

RESULTS: Viral spread to sentinel dishes occurred with both herpes simplex and adenovirus. The titer of virus present in the infected cell monolayers influenced the likelihood of spread to adjacent dishes. The presence of a vacuum aspiration system appeared to influence the direction of virus spread, with dishes located in the direction of the vacuum most likely to contain virus.

CONCLUSIONS: The potential for aerosolization of infectious virus exists with photoablation using a large-diameter excimer laser beam. Our experimental design, however, does not prove that spread of infectious virus is likely to occur in the clinical setting. Appropriate measures should be taken to reduce the possibility of the spread of virus from the patient to the surgeon, other medical staff, or other patients.

PMID: 9063238 [PubMed – indexed for MEDLINE]

Epidemic and sporadic cases of nontuberculous mycobacterial keratitis associated with LASIK

American Journal of Ophthalmology Volume 135, Issue 2″ target=”_blank” , Kevin L. Winthrop MD ,  a, Ellen B. Steinberg MD, MPHa, c, Gary Holmes MDd, Marion A., Kainer MBBS, MPHa, S. B. Werner MD, MPHb, Andrea Winquist MDa, b and Duc J. Vugia MD, MPHb

a) Epidemiology Program Office (K.L.W., E.B.S., M.A.K., A.W.), Centers for Disease Control and Prevention, Atlanta, Georgia, USA b) California Department of Health Services (S.B.W., A.W., D.J.V), Berkeley, California, USA c) Division of Public Health (E.B.S.), Georgia Department of Human Resources, Atlanta, Georgia, USA d) Scott and White Clinic (G.H.), Temple, Texas, USA – Accepted 30 August 2002. ; Available online 28 January 2003.

Purpose: To report national case-finding results for nontuberculous mycobacterial keratitis and describe its association with laser in situ keratomileusis (LASIK).

Design: Enhanced passive disease reporting.

Methods: In April 2001, we investigated a California cluster of Myco bacterium chelonae keratitis associated with hyperopic LASIK using a contact lens mask. To identify other possibly related cases, the American Academy of Ophthalmology e-mailed its members asking them to report recent cases of nontuberculous mycobacterial keratitis to the Centers for Disease Control and Prevention.

Results: Forty-three additional cases of keratitis were reported (onsets between August 2000 and June 2001). Of these, 31 occurred as part of two unrelated LASIK- associated outbreaks. The 12 other reported cases occurred in sporadic fashion. Of the latter cases, 4 were associated with LASIK surgery. None of the reported cases were related to the M. chelonae cluster in California.

Conclusions: Laser in situ keratomileusis-associated keratitis with nontuberculous mycobacteria may be more common than previously known.

TOP TEN REASONS NOT TO HAVE LASIK EYE SURGERY

Opinions By Damaged LASIK Patients For Those Considering LASIK

1. LASIK causes dry eye

Dry eye is the most common complication of LASIK. Corneal nerves that are responsible for tear production are severed when the flap is cut. Medical studies have shown that these severed nerves never return to normal densities. Symptoms of dry eye include pain, burning, foreign body sensation, and eyelid sticking to the eyeball. The FDA website warns that LASIK-induced dry eye may be permanent.

2. LASIK results in loss of visual quality

LASIK patients have more difficulty seeing detail in dim light (known as loss of contrast sensitivity), and also experience an increase in visual distortion at night (multiple images, halos, and starbursts). The FDA website warns that patients with large pupils may suffer from debilitating visual symptoms at night.

3. The cornea is incapable of complete wound healing after LASIK

Researchers found that the flap heals to only 2.4% of normal tensile strength. LASIK flaps can be surgically lifted or accidentally dislodged for the remainder of a patient’s life. For these reasons, the FDA website warns that patients who participate in contact sports are not good candidates for LASIK.

Collagen bands of the cornea provide its form and strength. LASIK severs these collagen bands and thins the cornea, resulting in permanent weakening. The thinner, weaker post-LASIK cornea is more susceptible to forward bulging due to normal intraocular pressure, which may progress to a condition known as keratectasia and corneal failure, requiring corneal transplant.

4. The true rate of LASIK complications is unknown

There is no clearinghouse for reporting of LASIK complications. Side effects occur frequently but are downplayed by LASIK surgeons. Moreover, there is no consensus among LASIK surgeons on the definition of a complication.

5. LASIK results in loss of near vision

Nearsighted patients who do not have LASIK retain the ability to see up close naturally after the age of 40 simply by removing their glasses. LASIK patients over the age of 40 may discover they have traded one pair of glasses for another.

6. There are long-term negative consequences of LASIK

LASIK affects the accuracy of intraocular pressure measurements, exposing patients to risk of blindness from undiagnosed glaucoma.

Like the general population, LASIK patients will develop cataracts later in life. Calculation of intraocular lens power for cataract surgery is inaccurate after LASIK. This may result in poor vision following cataract surgery and exposes patients to increased risk of repeat surgeries. Ironically, steroid drops routinely prescribed after LASIK hasten the onset of cataracts.

7. Bilateral simultaneous LASIK is not in patients’ best interest

In a 2003 survey of American Society of Cataract and Refractive Surgery (ASCRS) members, 91% of surgeons who responded did not offer patients the choice of having one eye done at a time. Performing LASIK on both eyes in the same day places patients at risk of vision loss in both eyes, and denies patients informed consent for the second eye.

8. Serious complications may emerge later

The medical literature is filled with reports of late onset LASIK complications such as loss of the cornea due to biomechanical instability, vision-threatening infection, inflammation resulting in corneal haze, flap dislocation, and retinal detachment. Complications may emerge weeks, months, or years after “successful” LASIK.

9. Rehabilitation options after LASIK are limited

LASIK is irreversible, and treatment options for complications are extremely limited. Hard contact lenses may provide visual improvement if the patient can obtain a good fit and tolerate lenses. The post-LASIK contact lens fitting process can be time consuming, costly and ultimately unsuccessful. Many patients eventually give up on hard contacts and struggle to function with impaired vision. In extreme cases, a corneal transplant is the last resort and does not always result in improved vision.

10. Safer alternatives to LASIK exist

Some leading surgeons have already abandoned LASIK for surface treatments, such as PRK, which do not involve cutting a corneal flap. It is important to remember that LASIK is elective surgery. There is no sound medical reason to risk vision loss from unnecessary surgery. Glasses and contact lenses are the safest alternatives.

Flap Studies & Articles

These quick-links will provide you faster access to the studies & articles provided: 

Accidental self-removal of a flap – a rare complication of LASIK surgery – – To report a rare complication in which the patient accidentally removed the LASIK corneal flap.

LASIK Flap Only 2.4% as strong as Normal Cornea – The human corneal stroma typically heals after LASIK in a limited and incomplete fashion; this results in a weak, central and paracentral hypocellular primitive stromal scar that averages 2.4% as strong as normal corneal stroma.

Traumatic corneal flap dislocation one to six years after LASIK in nine eyes with a favorable outcome – To report our experience treating eye trauma after LASIK refractive surgery.

Comparison of residual stromal bed and flap thickness in primary and repeat LASIK in myopic patients – To compare the change in residual stromal thickness and flap thickness between primary laser in situ keratomileusis (LASIK) and repeat LASIK in myopic patients.

Central Flap Necrosis After LASIK With Microkeratome and Femtosecond Laser Created Flaps – To report nine cases of severe central flap inflammation and necrosis after LASIK.

Flap Displacement during Vitrectomy 24 months after LASIK – “The LASIK flap never heals… the LASIK flap can be easily dislodged from simple contact with the eye such as a finger poke.”

Traumatic flap displacement and DLK after LASIK – Traumatic flap displacement and subsequent diffuse lamellar keratitis after laser in situ keratomileusis.

Late-onset flap folds and partial dehiscence of flap – Late-onset repetitive traumatic flap folds and partial dehiscence of flap edge after laser in situ keratomileusis.

Late traumatic dislocation of LASIK flaps  (1) – A case of traumatic flap displacement with a fingernail injury four years after LASIK is reported.

Late traumatic dislocation of LASIK flaps  (2) – The second patient had a blunt trauma that caused a dislocation of the flap.

Flap tearing during lift-flap LASIK retreatment – This report suggests that flaps with margins near the limbus or a corneal pannus may be prone to an earlier and stronger healing process at the edge that may lead to a flap tear during LASIK retreatment.

Precision of flap measurements for LASIK in 4428 eyes – Flap thickness varies significantly depending on the microkeratome used. Factors that influence flap thickness are primarily corneal thickness, patient age, preoperative keratometry, preoperative refraction including astigmatism, and corneal diameter.

Predictability of corneal flap thickness in LASIK using three different microkeratomes – Corneal flap thickness tended to be considerably thinner than expected on both eyes using the ACS and Hansatome.

Inaccurate Flap Cut – Here is a case report of a woman who developed ectasia following LASIK due to in accurate flap cut.

Late traumatic displacement of LASIK flaps – Laser in situ keratomileusis corneal flaps are vulnerable to traumatic dehiscence and dislocation, which can occur more than 2 years after the procedure.

Traumatic flap dislocation 4 years after LASIK – The patient was examined 5 days after being struck in the face and found to have a flap dislocation.

Mismatch between flap and stromal areas after LASIK as source of flap striae – Excess flap area may cause striae because of wrinkling.

Uveitis-associated flap edema and lamellar interface fluid collection after LASIK – To report two cases of corneal pathology associated with anterior uveitis after LASIK.

Noninflammatory flap edema after lasik associated with asymmetrical preoperative corneal pachymetry – To report persistent unilateral flap edema following LASIK in patients with asymmetrical central corneal thickness.

Evaluation of corneal flap dimensions and cut quality using the SKBM automated microkeratome – To evaluate flap dimensions and cut quality with repeated blade use of the automated Summit Krumeich-Barraquer microkeratome (SKBM [LadarVision])

Flap-related complications present challenges for surgeons

Surgeons review some common flap-related problems and how to handle them.

By Amar Agarwal, MS, FRCS, FRCOphth; Jairo Hoyos, MD; Melania Cigales, M

Flap-related problems after LASIK are a concern for any refractive surgeon. Common causative factors are inadequate suction, microkeratome malfunction and corneal curvature anomalies. This article reviews some common complications and ways to avoid or manage them.

Read the FULL ARTICLE

Microstriae

Quote:  Microstriae are very faint, small, disorganized, superficial wrinkles in the LASIK flap. Unlike macrostriae, which result from the flap’s slippage, microstriae are produced by the mechanical forces of a LASIK flap…

Traumatic late flap dehiscence and Enterobacter keratitis following LASIK – To report a case of traumatic flap dehiscence and Enterobacter keratitis 34 months after LASIK.

Flap interface particles are another finding whose clinical significance is undetermined.

A Finnish study found that particles of various sizes and reflectivity were clinically visible in 38.7% of eyes examined via slit lamp biomicroscopy, but apparent in 100% of eyes using confocal microscopy.

Some patients have reported large chunks of metal in their corneas after lasik.

Watch a video of a confocal exam of another LASIK patient with an extraordinary amount of metallic debris from the LASIK microkeratome blade.

Microstriae are very faint, small, disorganized, superficial wrinkles in the LASIK flap. Unlike macrostriae, which result from the flap’s slippage, microstriae are produced by the mechanical forces of a LASIK flap (with unchanged convexity) overlying a newly contoured flap bed (with less convexity). The unchanged arc length of the flap must therefore fit into the shorter arc length of the flap’s bed. This disparity in shapes causes microstriae.

Microstriae can be a frustrating outcome in patients who undergo an otherwise perfect LASIK surgery. This effect is more common in high myopes, probably because more tissue is removed and there is an exaggerated disparity between the flap and its bed in regard to fit. Also, and unfortunately in some cases, the microstriae can have an unwelcome and detrimental effect on vision.

Read the rest HERE

Dr. Terry Kim of Duke University claims infections that may require flap amputation are on the rise

SOURCE

Two cases of air bag deployment injuries

Air bag-induced corneal flap folds after LASIK:

Am J Ophthalmol. 2000 Aug;130(2):234-5.

Norden RA, Perry HD, Donnenfeld ED, Montoya C.  Department of Ophthalmology, University of Medicine and Dentistry, New Jersey, Newark, New Jersey, USA.

PURPOSE: We describe a case of air bag-induced ocular trauma resulting in folds in the corneal flap 3 weeks after laser in situ keratomileusis.

METHODS: Case report. Three weeks after laser in situ keratomileusis, a 20-year-old man was involved in a motor vehicle accident and sustained blunt trauma to the right eye, which caused corneal flap folds, corneal edema, anterior chamber cellular reaction, and Berlin retinal edema.

RESULTS: Six weeks after laser in situ keratomileusis, persistent flap folds necessitated re-operation with lifting of the flap and repositioning. One week after the procedure, the visual acuity improved to 20/20-2, and the folds had cleared.

CONCLUSION: Trauma after laser in situ keratomileusis may produce folds in the corneal flap. With persistence of these folds, management by lifting and repositioning the corneal flap may be necessary to permit recovery of visual acuity.

Partial dislocation of LASIK flap by air bag injury:

J Refract Surg. 2000 May-Jun;16(3):373-4.

Lemley HL, Chodosh J, Wolf TC, Bogie CP, Hawkins TC. Department of Ophthalmology, Dean A. McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, USA.

PURPOSE: A patient developed significant corneal complications from air bag deployment, 17 months after laser in situ keratomileusis (LASIK).

METHODS: Case report, slit-lamp microscopy, and review of the medical literature.

RESULTS: A 37-year-old woman underwent bilateral LASIK with resultant 20/20 uncorrected visual acuity. Seventeen months later, she sustained facial and ocular injuries from air bag deployment during a motor vehicle accident. Examination revealed bilateral corneal abrasions, partial dislocation of the right corneal LASIK flap, and a hyphema in the right eye. The LASIK flap was realigned, but recovery was complicated by a slowly healing epithelial defect and flap edema. One month following the injury, epithelial ingrowth beneath the LASIK flap was noted. Surgical elevation of the flap and removal of the epithelial ingrowth was performed. Eight months later, epithelial ingrowth was absent and the visual acuity was 20/40. Residual irregular astigmatism necessitated rigid gas permeable contact lens fitting to achieve 20/20 visual acuity.

CONCLUSIONS: Air bags may cause significant ocular trauma. The wound healing response of LASIK allows corneal flap separation from its stromal bed for an indeterminate time after surgery. Discussion of the possible risk of corneal trauma as part of informed consent prior to LASIK may be appropriate.

What a dilemma for LASIK patients — accept the risk of dislodging your flaps or disconnect your air bag to protect your corneas and put your life in danger.

Close-up microkeratome blades reveal variation

May 28, 2002

Eurotimes May 2002

A close-up look at a number of different disposable microkeratome blades using electron microscopy revealed considerable variation in size and cutting edge between both different manufacturers and among blades made by the same manufacturer. Researchers examined ten different microkeratome blade types, comparing five blades of each type. They studied scanning electron microscopic images up to a magnification of 700x the original size and measured blade length, width, and cutting edge. The researchers also examined the blades for any irregularities. The researchers looked at blades manufactured by Bausch & Lomb, Nidek, Moria, Allergan, Oasis, Schwind, Beaver, Alcon, and Asclepion-Meditec. They found variations between the ten different blade groups and among the five blades within each microkeratome blade group. The differences noted included length, width and cutting edge. They expressed concern about the diversity of size and cutting edge seen in blades created by different manufacturers for the same microkeratome, which could potentially compromise the procedure’s precision. The blades studied also revealed different degrees of impurities and surface smoothness. These were readily visible at a magnification of 175x. Some blades were coated with impurities or showed deposits. The cutting edge of a particular blade was left relatively unsharpened by some manufacturers. Other blades revealed an additional cutting edge, while the same blade made by another manufacturer lacked it. They noted that some blades were fine, revealing no irregularities along the length of the cutting edge, no impurities or deposits on the blade surface and no variations in size. Such smoothness and consistentency were particularly evident with Amadeus (Allergan) microkeratome blades.

This was published in 2002, and they were doing lasik for years before that. Why would they subject patients to this. Wouldn’t they at least look at the blades before rolling lasik out to millions of people? This doesn’t make sense.

Laceration and Partial Dislocation of LASIK Flaps 7 and 4 Years Postoperatively With 20/20 Visual Acuity After Repair

Journal of Refractive Surgery Vol. 22 No. 9 November 2006George J.C. Jin, MD, PhD; Kevin H. Merkley, MD, MBA

Quote:

Although ocular trauma with corneal laceration can occur, we report that the lamellar flap is still susceptible to ocular trauma 7 years after LASIK. Informed consent should include discussion of long-term flap complications and patients should be advised to protect their eyes after LASIK, especially during high risk activities.

Flap-related complications present challenges for surgeons

Flap-related problems after LASIK are a concern for any refractive surgeon. Common causative factors are inadequate suction, microkeratome malfunction and corneal curvature anomalies. This article reviews some common complications and ways to avoid or manage them.

Buttonholing of the flap

Buttonholing is one of the more dreaded complications of LASIK (Figure 1), as it is often in the visual axis and may heal with scarring (Figure 2) and loss of best corrected visual acuity. Poor quality blades, inadequate IOP, keratome malfunction and steep corneas are predisposing factors. The procedure should be aborted and the flap should be realigned. The patient may require a deeper re-cut with customized ablation or PRK or PTK with mitomycin-C using a transepithelial approach.

Free caps

Free caps are also disastrous complications. The cap should be carefully placed epithelial side down in a drop of balanced salt solution to avoid stromal hydration. Alignment marks on the flap help in identifying the side as well as in realignment. Sufficient time should be given for good flap adhesion  One may secure it either with sutures or a bandage contact lens.

Incomplete or partial flap

An incomplete or partial flap can occur due to a loss of suction midway, any mechanical obstruction to the microkeratome or premature discontinuation of the pass (Figure 4). The surgeon generally has to abort the procedure and make a new flap with a deeper cut 3 to 6 months later. Never attempt to manually dissect as it can lead to loss of BCVA and topographical abnormalities and necessitate procedures such as PTK.

Visually significant striae

If identified, early striae can be treated with flap relifting, hydration (with hypotonic saline) and aggressive stretching for 5 to 8 minutes. In recalcitrant cases, suture placement at the flap edge may be required.

Post-LASIK ectasia

Post-LASIK ectasia may occur in patients with thin corneas, deep ablations or large optic zones. Here, the flap has to be made proportionately thinner. Not maintaining an adequate residual bed thickness causes a long-term increase in the surface parallel stress on the cornea and may lead to post-LASIK ectasia. Progressive ectasia may then need to be treated by deep anterior lamellar keratoplasty, penetrating keratoplasty, intrastromal corneal ring segments or collagen crosslinking with riboflavin treatment.

Epithelial defects

Epithelial defects can occur as a result of poor quality instruments or excessive preoperative anesthetics or in eyes with epithelial basement membrane dystrophy. They are a predisposing factor for infectious keratitis, diffuse lamellar keratitis and epithelial ingrowth.

Epithelial ingrowths

Epithelial ingrowths are seen as a faint white or gray opacity beneath the flap. They are more common after a displaced or torn flap, epithelial defects, or hyperopic or LASIK re-treatment. Treatment by lifting the flap with mechanical removal and irrigation of the surface is indicated if the ingrowth is progressive or extending centrally to the visual axis, associated with stromal melting, distorted flap edge, decreased BCVA or topographical abnormalities.

Read the FULL ARTICLE

Dry Eye Studies & Articles

Dry Eye After LASIK – The risk of chronic dry eye after LASIK was significantly higher in Asian eyes. Contributing factors could include racial differences in eyelid and orbital anatomy, tear film parameters and blinking dynamics and higher attempted refractive corrections in Asian eyes.

Chronic dry eye and regression after LASIK for myopia – The risk for refractive regression after LASIK was increased in patients with chronic dry eye.

The incidence and risk factors for developing dry eye after myopic LASIK – To determine the incidence and risk factors after myopic LASIK.

Autologous Serum Eye Drops for dry eye after LASIK – To evaluate the efficacy of these drops for dry eye after LASIK in a prospective, randomized study. 

Symptoms of dry eye and recurrent erosion syndrome after refractive surgery – These symptoms occurred commonly after excimer laser procedures but were significantly more common, more severe, and more prolonged after PRK.

Dealing With Dry Eye – An article written for FDA Consumer magazine.

Dry Eye and Corneal Sensitivity After High Myopic LASIK – To assess subjective symptoms and objective clinical signs of dry eye and investigate corneal sensitivity after high myopic LASIK.

Pupil Related Studies & Articles

 

Pupil measurement using the Colvard pupillometer and a standard pupil card with a cobalt blue filter penlight – To compare scotopic pupil measurements obtained with a Colvard pupillometer with measurements taken with a printed pupil gauge and penlight with a cobalt blue filter attachment in mesopic and scotopic luminance.

Influence of pupil and optical zone diameter on higher-order aberrations after wavefront-guided myopic LASIK – To investigate the influence of pupil and optical zone (OZ) diameter on higher-order aberrations (HOAs) after myopic wavefront-guided laser in situ keratomileusis (LASIK)

Pupillary Dilation

1) Pupillary dilation from 3 to 7 mm in post-refractive surgery patients found to cause 28- to 46-fold increase in aberrations! – Both photorefractive keratectomy and laser in situ keratomileusis increase the wavefront aberrations of the cornea and change the relative contribution of coma- and spherical-like aberrations.

2) Pupillary dilation from 3 to 7 mm in post – PRK patients found to cause 25-to 32-fold increase increase in aberrations! – After surgery, the same dilation resulted in a 25- to 32-fold increase in the photorefractive keratectomy group and a 28- to 46-fold increase in the laser in situ keratomileusis group.

Pupil Size

Pupil size and night vision disturbances after LASIK for myopia. – Large pupil size measured preoperatively is correlated with an increased frequency of subjectively experienced post-LASIK visual disturbances during scotopic conditions.

Large pupils lead to night vision problems, physicians suggest

SOURCE

 

EyeWorld

November, 2005

Excerpt:

While some studies have suggested pupil size has little to no effect on nighttime vision post-refractive surgery, some ophthalmologists point to new evidence that there is a correlation.

“If you compare patients of the same prescriptions, the larger the pupil size, the bigger the chance that they’re going to have more night vision problems,” said William B. Trattler, M.D., Center for Excellence in Eye Care, Miami.

To back up his assertion, Dr. Trattler performed his own studies, one of which included 119 myopic eyes that underwent LASEK or PRK with either a standard VISX (Advanced Medical Optics, Santa Ana, Calif.) Star S3 or S4 laser.

Using a Larson Glarometer, he found that the radius of starbursts was greater in patients with large pupils compared with those in patients with small ones. Dr. Trattler presentedthe results at the most recent ASCRS•ASOA Symposium & Congress. The Larson Glarometer does not have a corporate manufacturer yet. It was developed and is distributed by Bruce Larson, M.D., Hinsdale, Ill.

Meanwhile, James Salz, M.D., clinical professor of ophthalmology, University of Southern California, Los Angeles, also believes large pupils can lead to night vision complaints after refractive surgery.

“The larger the pupil size, the greater the aberrations will be,” said Dr. Salz.

Pupil diameter changes and reaction after posterior chamber phakic intraocular lens implantation – To compare the different aspects of pupil constriction before and after the implantation of an implantable contact lens (ICL).

Effect of pupil size on visual function under monocular and binocular conditions in LASIK and non-LASIK patients – To compare binocular and monocular vision in patients treated with laser in situ keratomileusis (LASIK) and in non-LASIK patients.

Pupil Size

SOURCE

“Night Glare is common in nearsighted individuals even before any refractive procedure is performed, but increases almost immediately in the healing process and is more common when only one eye is treated. Typically, 6 months after both eyes have been treated, only 2% of patients still experience significant night glare that interferes with their night driving. Severe night glare can impair vision in all reduced lighting conditions producing blurriness, ghosting, or halos. Patients with large pupils and severe myopia and/or significant astigmatism are at greater risk for night glare.”

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http://www.neuroptics.com/images/user/References_abstracts_lasik.pdf

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http://www.lasermyeye.org/keratoscoop/columns/archives.html

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From the FDA website, “When is LASIK not for me?”

SOURCE

Large pupils. Make sure this evaluation is done in a dark room. Younger patients and patients on certain medications may be prone to having large pupils under dim lighting conditions. This can cause symptoms such as glare, halos, starbursts, and ghost images (double vision) after surgery. In some patients these symptoms may be debilitating. For example, a patient may no longer be able to drive a car at night or in certain weather conditions, such as fog.

From the American Academy of Ophthalmology website:

SOURCE

Summary Recommendations for LASIK

Issued March 28, 2002

Patient Examination

In determining suitability, a baseline eye evaluation should include:

Manifest and cycloplegic refraction

Measurement of intraocular pressure

Slit-lamp biomicroscopy

Tear film evaluation

Corneal topography

Evaluation of preoperative corneal thickness

Dilated fundoscopic examination

Measurement of scotopic pupil size

Somebody should report doctors who operates on patients with large pupils to the AAO for violating AAO guidelines. (Not that the AAO is going to do or say anything about it! The AAO protects its own – unless of course any repercussions will make THEM look bad)

From the ASCRS Eye Surgery Education Counsil website, LASIK Patient Screening Guidelines:

SOURCE

  • Measurement of pupil size in dim and room light. Pupil size is an important factor in counseling a candidate about night vision and planning the appropriate laser vision correction strategy.

Even the insurer, OMIC, requires pre-op pupil measurement.

SOURCE

PATIENT SELECTION

As part of the independent evaluation, the surgeon must personally examine the patient’s eyes and ocular adnexa, perform a slit lamp exam, and carefully review topographies, pupil size, pachymetry, refractive stability, eye health history, and prior records.

Notice it said “the surgeon must personally examine the patient’s eye…”

From the Federal Trade Commission website:

SOURCE

Take the following measurements:

The curvature of your cornea and your pupils. You may be rejected if your pupils are too large.

“Aberrometry depends on pupil diameter, as well. HOAs disturb vision increasingly with increasing pupil diameter.”

SOURCE

FDA Ophthalmic Devices Panel meeting

August, 2002

Dr. George Pettit is speaking on behalf of ALCON for approval of it’s wavefront guided platform.

SOURCE

  1. PETTIT: Just to follow up a little bit on an earlier question. This is George Pettit from Alcon.

I think Dr. Matoba asked the question about the pupil sizes and were the patients informed. Given this high-level expectation, it’s important to note that the optical zone was 6.5mm and we informed all patients considering being in the trial that if their natural pupil was larger than 6.5mm, even with this new technology, there was a potential risk for them to have night vision symptoms. So we tried to bring their expectations more in line.

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http://www.pcli.com/lasik/wavefront.html

“With the cornea being 70% water, highly customized treatment is like trying to precisely sculpt Jell-O. Even when everything is done perfectly, creating the LASIK flap and the normal effects of corneal stretching, molding or healing may negate some of the precision of the planned treatment.”

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Brian Boxer Wachler, M.D. on pupil size:

SOURCE

Halos were associated with spherical aberration for the scotopic pupil size.

“I find this as well,” Dr. Boxer Wachler said. “The reason is that if you look at the very center of the topography and look towards the periphery, the corneal power gets steeper. If the steeper power transition occurs relatively close to the center of topography – as in higher myopes, and/or smaller laser optical zones – this causes more spherical aberration.”

Glare also was significantly correlated with spherical aberration and total aberration. Starburst was associated with spherical aberration and total aberration for the scotopic pupil size.

http://www.webmd.com/content/article/22/1728_56108.htm

If you choose LASIK, Boxer Wachler suggests asking the surgeon if the procedure is safe with your pupil size, because people with large pupils are at greater risk for decreased night vision and halos (the glare that appears over certain objects).

Dan Durrie, MD on pupil size:

SOURCE

“Another possible cause of nighttime side-effects is pupil size. At night, the pupil expands to let in more light. Light coming through the peripheral cornea may be out of focus if the pupil opens beyond the laser treatment area. This is why some patients are not good candidates for LASIK if they have very large pupils.”

Barrie Soloway, MD on pupil size:

SOURCE

“Most patients with large pupil sizes who receive laser surgery will experience varying degrees of what’s referred to in the medical field as GASH (Glare, Arching, Star bursts or Haloes) during night-driving. ”

http://www.ihateglasses.com/html/ocular_surgery_news_2_1_01.html

“This study proved that the main reason for poor post-LASIK night vision was in fact the diameter of the laser beam being smaller than that of the pupil.”

Jack Holladay, MD on pupil size:

SOURCE

The High Cost of Inaccurate Pupillometry

“Accurate pupillometry is an essential part of the evaluation for refractive surgery. With reports of halos and glare following refractive surgery on many of the prime-time news shows, pupillometry has become one of the preoperative tests that patients expect. It is very clear from the published and anecdotal reports of nighttime glare and halos that a large pupil is the predominant factor leading to these problems.”

Pupil diameter study shows correlation with aberrations, contrast sensitivity after LASIK

SOURCE

OCULAR SURGERY NEWS 4/12/2006

In eyes with larger pupils who were treated with LASIK, spherical-like aberrations affect contrast sensitivity, whereas in eyes with smaller pupils coma-like aberrations are more likely to affect visual performance.

“In eyes with larger photopic pupil diameter, increases in spherical-like aberration dominantly affect contrast sensitivity, whereas in eyes with smaller pupil size, changes in coma-like aberration exert greater influence on visual performance,” said Tetsuro Oshika, MD.

Out of the 215 eyes tested in 117 patients, 105 of them had a photopic pupil diameter of 4 mm or larger while 110 were smaller than 4 mm. In the former group, there were no significant effects in third-order coma-like aberrations and, in the latter group, there were no significant effects in fourth-order spherical-like aberrations.

Conversely, the larger pupil group showed significant correlation between changes in the area under the log contrast sensitivity function (AULCSF) and a 10% change in low-contrast visual acuity. The smaller pupil group produced significant correlation between the changes in coma-like aberrations and the changes in AULCSF and a 10% change in low-contrast visual acuity.

Corneal Studies & Articles

Wound healing in the cornea: a review of refractive surgery complications and new prospects for therapy – The corneal wound healing response is of particular relevance for refractive surgical procedures since it is a major determinant of efficacy and safety. The purpose of this review is to provide an overview of the healing response in refractive surgery procedures.

Long-term corneal keratoctye deficits after photorefractive keratectomy and LASIK – To measure changes in keratocyte density up to 5 years after photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK).

Estimation of true corneal power after keratorefractive surgery in eyes requiring cataract surgery: BESSt formula – To describe a new formula, BESSt, to estimate true corneal power after keratorefractive surgery in eyes requiring cataract surgery.

Considerations of glaucoma in patients undergoing corneal refractive surgery – Corneal thickness, which is modified during corneal refractive surgery, plays an important role in monitoring glaucoma patients because of its effect on the measured intraocular pressure.

Corneal Keratocyte Deficits After PRK and LASIK – To measure changes in keratocyte density up to 5 years after PRK and LASIK.

Effective corneal refractive diameter as a function of the object tangent angle in visual space – To determine whether the currently accepted method of selecting a minimum optical zone diameter for laser refractive surgery that is equal to or slightly greater than the dark-adapted pupil diameter provides a sufficient diameter of corneal surface to focus light arising from objects in the paracentral and peripheral visual field.

Evaluation of Corneal Sensitivity to Mechanical and Chemical Stimuli After LASIK: A Pilot Study – To evaluate the effect of laser in situ keratomileusis (LASIK) on corneal sensitivity, nerve morphology, and tear film characteristics.

Changes in corneal thickness and curvature after different excimer laser photorefractive procedures and their impact on intraocular pressure measurements – To analyze the changes in central corneal thickness (CCT) and curvature before and after different excimer laser photorefractive procedures and their possible impact on intraocular pressure (IOP) estimations with Goldmann applanation tonometry.

Effect of Corneal Curvature and Corneal Thickness on the Assessment of Intraocular Pressure Using Noncontact Tonometry in Patients After Myopic LASIK Surgery – To evaluate the effect of corneal curvature and corneal thickness on the assessment of intraocular pressure (IOP) using noncontact tonometry (NCT) in patients after myopic LASIK surgery.

Failed LASIK Depleting Supply Of Donor Corneas – Optometrist specializing in post-refractive surgery disaster claims that FAILED LASIK EYE SURGERY IS DEPLETING SUPPLY OF DONOR CORNEAS.

Epidemic of Corneal Weakening After Refractive Surgery – Here is an excerpt and link to a comment posted by Optometrist Dr. Greg Gemoules who specializes in the treatment of patients damaged by refractive surgery by fitting them with rigid gas permeable contact lenses.

Effect of Corneal Curvature and Corneal Thickness on the Assessment of Intraocular Pressure Using Noncontact Tonometry in Patients After Myopic LASIK Surgery -  Even if a residual corneal bed of 300 microm or thicker is preserved, anterior bulging of the cornea after LASIK can occur.

Structural Analysis of the Cornea Using Scanning-Slit Corneal Topography in Eyes Undergoing Excimer Laser Refractive Surgery – Myopic PRK and LASIK induce significant forward shifts of the cornea, which are not true corneal ectasia.

Permanent Disease Changes Present in all Post-LASIK Corneas! – Permanent pathologic changes were present in all post-LASIK corneas. These changes were most prevalent in the lamellar interface wound. These changes along with other pathologic alterations in post-LASIK corneas may change the functionality of the cornea after LASIK.

Corneal Nerve Damage Continues to Increase years 2-3 after LASIK – Both subbasal and stromal corneal nerves in LASIK flaps recover slowly and do not return to preoperative densities by 3 years after LASIK.

Critical thoughts on current laser surgery of the cornea (1995) – If we look at refractive surgery, especially laser photoablation, in the context of the needs for ophthalmic care of the whole world, then this type of surgery is out of proportion.

Theoretical Elastic Response of the Cornea to Refractive Surgery: Risk Factors for Keratectasia – “In particular, a forward shift and an increase in power of the posterior surface was predicted for myopic LASIK, in agreement with previous experimental findings.”

Cohesive tensile strength of human LASIK wounds with histologic, ultrastructural, and clinical correlations – The human corneal stroma typically heals after LASIK in a limited and incomplete fashion; this results in a weak, central and paracentral hypocellular primitive stromal scar that averages 2.4% as strong as normal coeneal stroma.

Pathologic findings in postmortem corneas after successful LASIK – Permanent pathologic changes were present in all post-LASIK corneas. These changes were most prevalent in the lamellar interface wound. These changes along with other pathologic alterations in post-LASIK corneas may change the functionality of the cornea after LASIK.

Ex vivo confocal microscopy of human LASIK corneas with histologic and ultrastructural correlation – Confocal microscopy, along with histologic and ultrastructural correlations, demonstrated that the most prevalent alterations in the centers of LASIK corneas were a slightly thickened epithelium caused by focal basal epithelial cell hypertrophic modifications, random undulations in Bowman’s layer over the flap surface, and a variably thick hypocellular primitive stromal interface scar.

Corneal reinnervation after LASIK: prospective 3-year longitudinal study – Both subbasal and stromal corneal nerves in LASIK flaps recover slowly and do not return to preoperative densities by 3 years after LASIK.

Progression to end-stage glaucoma after LASIK – 2 patients, one a glaucoma suspect because of family history and the other with juvenile glaucoma.

Steroid-induced glaucoma after LASIK associated with interface fluid – To report the ocular manifestations and clinical course of eyes developing interface fluid after LASIK.

Biomechanical modeling of refractive corneal surgery – A biomechanical study before surgery is therefore very convenient to assess quantitatively the effect of each parameter on the optical outcome.

Confocal Microscopy of Corneal Flap Microfolds After LASIK – To describe the morphological characteristics of microfolds that appear at the corneal flap after LASIK, as seen under confocal microscopy.

Objective method to measure corneal clarity before and after LASIK – To develop, evaluate, and use an objective method to determine the effect of LASIK on corneal clarity.

Histopathology of corneal melting associated with diclofenac use after refractive surgery – To describe the histopathology of the cornea in 3 cases of corneal melting associated with diclofenac therapy after refractive surgery procedures.

Central corneal iron deposition after myopic LASIK – To describe central corneal iron deposition after myopic LASIK.

Corneal ectasia after LASIK in patients without apparent preoperative risk factors – To evaluate patients who developed ectasia with no apparent preoperative risk factors.

Interface Corneal Edema Secondary to Steroid-induced Elevation of Intraocular Pressure Simulating DLK – To describe interface corneal edema secondary to steroid-induced elevation of intraocular pressure (IOP) following LASIK.

Delayed Ectasia Following LASIK With No Risk Factors: Is a 300-µm Stromal Bed Enough? – To report a case of ectasia occurring >4 years following LASIK with no risk factors and a residual stromal bed >300 µm.

Steroid glaucoma after laser in situ keratomileusis – A steroid-induced glaucoma may develop after bilateral laser in situ keratomileusis (LASIK)  with normal intraocular pressure in applanation tonometry.

Keratocytes’ Density Remains Low After Refractive Surgery  – According to a paper presented this month at the 6th International Congress on Advanced Surface Ablation and SBK, keratocytes’ density decreases substantially in the anterior stroma of  refractive surgery patients during the first postoperative year and remains low for several years.

Risk Assessment for Ectasia after Corneal Refractive Surgery – To analyze the epidemiologic features of ectasia after excimer laser corneal refractive surgery, to identify risk factors for its development, and to devise a screening strategy to minimize its occurrence.

More on the cornea…

Biomechanics of Corneal Refractive Surgery

JOURNAL OF REFRACTIVE SURGERY

Vol. 22 No. 3 March 2006

Dan Z. Reinstein, MD, MA(Cantab), FRCSC; Cynthia Roberts, PhD

Excerpt: “Some of the evidence pointing to the impact of corneal biomechanical properties on surgical outcomes lies in the measurement of intraocular pressure (IOP), both before and after refractive surgery. It is well known that measured IOP is reduced, on average, following a refractive procedure. It has been assumed that this is the result of reduced curvature and thickness in myopic procedures. However, Chang and Stulting performed a retrospective review of over 8000 myopic LASIK patients, and determined that although measured pressure was reduced on average by approximately 2 mmHg, the range of change was approximately +10 to -15 mmHg. Every patient in this population had reduced thickness and curvature, and yet almost half of them had an increase in measured IOP.

Clearly, the artifact in IOP measurement cannot be explained by thickness alone, and “correction” of measured IOP postoperatively using a linear correction factor based on thickness is problematic. This leads to the conclusion that refractive surgery likely alters the fundamental biomechanical properties of the cornea.

Biomechanical modeling of refractive corneal surgery

  1. Biomech Eng. 2006 Feb;128(1):150-60.

Alastrue V, Calvo B, Pena E, Doblare M.

Group of Structural Mechanics and Material Modelling, Aragon Institute of Engineering Research (13A), University of Zaragoza, Spain.

The aim of refractive corneal surgery is to modify the curvature of the cornea to improve its dioptric properties. With that goal, the surgeon has to define the appropriate values of the surgical parameters in order to get the best clinical results, i.e., laser and geometric parameters such as depth and location of the incision, for each specific patient. A biomechanical study before surgery is therefore very convenient to assess quantitatively the effect of each parameter on the optical outcome. A mechanical model of the human cornea is here proposed and implemented under a finite element context to simulate the effects of some usual surgical procedures, such as photorefractive keratectomy (PRK), and limbal relaxing incisions (LRI). This model considers a nonlinear anisotropic hyperelastic behavior of the cornea that strongly depends on the physiological collagen fibril distribution. We evaluate the effect of the incision variables on the change of curvature of the cornea to correct myopia and astigmatism. The obtained results provided reasonable and useful information in the procedures analyzed. We can conclude from those results that this model reasonably approximates the corneal response to increasing pressure. We also show that tonometry measures of the IOP underpredicts its actual value after PRK or LASIK surgery.

Considerations of glaucoma in patients undergoing corneal refractive surgery

Comment in: Surv Ophthalmol. 2005 Nov-Dec;50(6):611-2; author reply 612.

Bashford KP, Shafranov G, Tauber S, Shields MB.  Department of Ophthalmology and Visual Sciences, Yale University School of Medicine, New Haven, Connecticut; and Glaucoma Consultants of Colorado, P.C., Littleton, Colorado, USA.

Glaucoma patients present a unique set of challenges to physicians performing corneal refractive surgery. Corneal thickness, which is modified during corneal refractive surgery, plays an important role in monitoring glaucoma patients because of its effect on the measured intraocular pressure.

Patients undergo a transient but significant rise in intraocular pressure during the laser-assisted in situ keratomileusis (LASIK) procedure with risk of further optic nerve damage or retinal vein occlusion. Glaucoma patients with filtering blebs are also at risk of damage to the bleb by the suction ring.

Steroids, typically used after refractive surgery, can increase intraocular pressure in steroid responders, which is more prevalent among glaucoma patients.

Flap interface fluid after LASIK, causing an artificially low pressure reading and masking an elevated pressure has been reported. The refractive surgeon’s awareness of these potential complications and challenges will better prepare them for proper management of glaucoma patients who request corneal refractive surgery.

Evaluation of Corneal Sensitivity to Mechanical and Chemical Stimuli After LASIK: A Pilot Study

Eye Contact Lens. 2006 Mar;32(2):88-93.

Stapleton F, Hayward KB, Bachand N, Trong PH, Teh DW, Deng KM, Yang EI, Kelly SL, Lette M, Robinson D.  From the Cornea and Contact Lens Research Unit (F.S., K.B.H., N.B., P.H.T., D.W.H.T., K.M.Y.D., E.I.H.Y.), School of Optometry and Vision Science and Vision Cooperative Research Centre, University of New South Wales, Sydney, Australia; and Sydney Laser and Vision Centre (S.L.K., M.L., D.R.), Bondi Junction, Australia.]

PURPOSE: To evaluate the effect of laser in situ keratomileusis (LASIK) on corneal sensitivity, nerve morphology, and tear film characteristics.

METHODS: A cross-sectional study design was used. Eighteen patients (eight men and 10 women with a mean age of 36.9 +/- 11.2 years) who had undergone bilateral LASIK for low myopia within 18 months of the study and 28 control subjects (16 men and 12 women with a mean age of 27.2 +/- 7.7 years) were enrolled. Central and inferior corneal thresholds to mechanical (air) and chemical (air plus carbon dioxide) stimuli were determined by using a staircase technique. Stimuli of a 1-second duration at 34 degrees C were delivered with a CRCERT-Belmonte aesthesiometer. Images of subbasal nerves in the central cornea were captured with confocal microscopy. Nerve morphology was classified as no nerves, short nerves (<175 mum), or long nerves (>175 mum), with or without interconnections. Noninvasive tear break up time was measured. The phenol red thread test was used to indicate basal tear secretion. Differences between groups were evaluated with analysis of variance, and associations between variables were evaluated with parametric or nonparametric correlation, when appropriate.

RESULTS: Central corneal mechanical sensitivity was significantly reduced in the post-LASIK group compared with the control subjects (P<0.001). Nerve morphology was associated with mechanical threshold. Nerve morphology, mechanical sensitivity, and tear breakup time improved during the first 1 to 3 months after surgery, with little change thereafter. Chemical sensitivity was associated with tear secretion (P<0.05).

CONCLUSIONS: Central corneal mechanical sensitivity is reduced in patients after LASIK, with partial recovery seen 3 months after surgery. A similar recovery trend is seen for nerve morphology.

Cross-linking therapy a promising treatment for keratectasia

SOURCE

TOP STORIES 2/28/2006

SAO PAULO, Brazil — A therapy that uses ultraviolet light and riboflavin to create cross-linking of corneal collagen may be a promising treatment for keratectasia, a preliminary study has shown.

At the World Ophthalmology Congress, Maria Regina Chalita, MD, reported results from a prospective analysis of the treatment in seven patients who had developed corneal ectasia following LASIK surgery. Prior to the treatment, each patient had progression of ectasia documented by at least two corneal topography maps, she said.

Dr. Chalita said the procedure begins with proparacaine topical anesthesia, followed by mechanical epithelial debridement, and then instillation of a riboflavin solution 5 minutes before UV light irradiation using UV-emitting goggles. Patients then wear a bandage contact lens for 4 days after the treatment.

At the 3-month follow-up point, uncorrected visual acuity had improved in the seven patients and best corrected visual acuity remained the same, Dr. Chalita said.

“Most patients reported better [visual] quality than before surgery,” she said.

“We expected to see a lot of change in corneal topography, but we didn’t,” she continued. “There were no reported adverse affects and no patients lost lines [of visual acuity]. No regression was observed at the 3-month follow up.”

Dr. Chalita concluded that corneal cross-linking with riboflavin and UV light seems to be a safe procedure, but longer-term follow up with a larger patient cohort is needed.

Ultrastructure of the lamellar corneal wound after LASIK in human eye

J Cataract Refract Surg. 2001 Aug;27(8):1323-7.

Rumelt S, Cohen I, Skandarani P, Delarea Y, Ben Shaul Y, Rehany U.  Department of Ophthalmology, Western Galilee-Nahariya Medical Center, Israel.

A 30-year-old patient with keratoconus, a stable refraction, and normal central corneal thickness had laser in situ keratomileusis (LASIK). Six months later, she had uneventful penetrating keratoplasty for keratectasia. The lamellar LASIK interface could not be clearly identified by light microscopy. The corneal wound site did not stain for methyl metalloproteinase 1 or 2. Both the corneal flap undersurface and the stromal bed were devoid of interconnections and cells. Throughout the lamellar incision, including the laser-ablated zone, the surface was smooth on scanning electron microscopy. The collagen fibrils on both sides of the incision remained well aligned with one another, indicating good flap apposition. Under higher magnification transmission electron microscopy, some collagen fragments were found in the interface, especially adjacent to the hinge. The diameter of the collagen fibrils along the lamellar wound were identical to those farther from the incision. The absence of bridging collagen fibrils and cells between the flap undersurface and the stromal bed confirms the clinically known lack of wound repair at the interface and explains the easy separation of the flap from the stromal bed months after LASIK and the possible formation of an interface fluid pocket.

Close-up microkeratome blades reveal variation

May 28, 2002

Eurotimes May 2002

A close-up look at a number of different disposable microkeratome blades using electron microscopy revealed considerable variation in size and cutting edge between both different manufacturers and among blades made by the same manufacturer. Researchers examined ten different microkeratome blade types, comparing five blades of each type. They studied scanning electron microscopic images up to a magnification of 700x the original size and measured blade length, width, and cutting edge. The researchers also examined the blades for any irregularities. The researchers looked at blades manufactured by Bausch & Lomb, Nidek, Moria, Allergan, Oasis, Schwind, Beaver, Alcon, and Asclepion-Meditec. They found variations between the ten different blade groups and among the five blades within each microkeratome blade group. The differences noted included length, width and cutting edge. They expressed concern about the diversity of size and cutting edge seen in blades created by different manufacturers for the same microkeratome, which could potentially compromise the procedure’s precision. The blades studied also revealed different degrees of impurities and surface smoothness. These were readily visible at a magnification of 175x. Some blades were coated with impurities or showed deposits. The cutting edge of a particular blade was left relatively unsharpened by some manufacturers. Other blades revealed an additional cutting edge, while the same blade made by another manufacturer lacked it. They noted that some blades were fine, revealing no irregularities along the length of the cutting edge, no impurities or deposits on the blade surface and no variations in size. Such smoothness and consistentency were particularly evident with Amadeus (Allergan) microkeratome blades.

This was published in 2002, and they were doing lasik for years before that. Why they would subject patients to this. Wouldn’t they at least look at the blades before rolling lasik out to millions of people? This doesn’t make sense.

Healing process at the flap edge in its influence in the development of corneal ectasia after LASIK

Curr Eye Res. 2006 Nov;31(11):903-8.

Abdelkader A, Esquenazi S, Shihadeh W, Bazan HE, He J, Gill S, Kaufman HE.

Department of Ophthalmology, LSU Eye and Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.

Quote:

Corneal ectasia may be related to the clinically observed lack of corneal wound-healing at the edge of the flap that allows the cornea to bulge.

Refractive power of the cornea

Compr Ophthalmol Update. 2006 Sep-Oct;7(5):243-51.Ayres BD, Rapuano CJ.Cornea Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, PA.Corneal refractive surgeries, such as laser in situ keratomileusis and photorefractive keratectomy, have become some of the most commonly performed elective surgical procedures today. Many of the patients undergoing these surgeries are beginning to show signs of cataract formation and are in need of surgical correction. A common problem in the postrefractive patient is accurate prediction of the corneal power for use in intraocular lens calculation. The purpose of this article is to review the literature and to discuss why it is difficult to determine the power of the postkeratorefractive cornea, and to describe the multiple techniques used to assist in calculation of the power of the cornea. We will also examine some of the current technological advances that may aid in power calculation. With proper patient history, examination, and careful calculation(s), it is possible to closely estimate the refractive power of the postkeratorefractive cornea.

Spherical Aberrations

Spherical Aberration and Its Symptoms – Theories on why it occurs and how new technology may address the problem.

Spherical Aberrations – Spherical aberration is one of the most important problems that can occur after laser eye surgery, in particular with high myopic corrections.

Femtosecond Lasers & LASIK Studies & Articles

IntraLase: Changing the LASIK Landscape – Though the exact cause of TLS is still uncertain, some surgeons believe that the inflammation is caused by necrotic cellular debris…

Transient light sensitivity a minor complication of IntraLase use – Some users of the IntraLase femtosecond laser keratome first noticed the complication when they began working with the system more than 2 years ago. Since then, the phenomenon has gone under multiple names.

Transient light-sensitivity syndrome after LASIK with the femtosecond laser Incidence and prevention – To describe the incidence of transient light-sensitivity syndrome (TLSS) after laser in situ keratomileusis (LASIK) with the femtosecond laser and to identify preventive strategies.

Flap folds after femtosecond LASIK – To report a case of bilateral flap folds after a laser-assisted in situ keratomileusis (LASIK) procedure in which the flap was created by the femtosecond laser.

Macular hemorrhage after laser in situ keratomileusis (LASIK) with femtosecond laser flap creation – To report the first case of macular hemorrhage following LASIK with femtosecond laser flap creation.

Refractive surgery: lessons to be learned – “Indeed the long-term problems created by laser refractive surgery are not yet a major issue, but soon will be.”

Complications of refractive excimer laser surgery – A German article related to complications.

A comparative confocal microscopy analysis after LASIK with the IntraLase femtosecond laser vs Hansatome microkeratome – To evaluate and compare confocal microscopy findings between a femtosecond laser and a mechanical microkeratome.

Comparison of goblet cell density after femtosecond laser and mechanical microkeratome in LASIK – To study the effect of the LASIK procedure performed with a femtosecond laser and a manual microkeratome on the conjunctival goblet cell and epithelial cell populations.

Researchers analyze femtosecond laser bubble morphology

OCULAR SURGERY NEWS – 3/1/2006

The size and shape of femtosecond laser bubbles do not correlate with the energy applied, a study in eye bank eyes found.

Jared Schultz

Excerpt:

“Probably you can work with energy levels much lower than you do currently, because the levels we are using right now just cause punctual disruption of the stroma, with tissue bridges remaining in between,” he told Ocular Surgery News in an interview. “To open the dissection line, we still need to tear apart these structures.”

He said the researchers did an experimental series using power as high as 15 µJ, which created larger disruption bubbles but still did not yield a clear dissection line.

“You don’t gain better results by just going to a higher energy,” he said.

Dr. Vossmerbaeumer said that one shortcoming of the study was that it is difficult to measure the actual energy output of the laser source.

“On a research basis, it will be perhaps a question to know whether the machine really emits a 4 µJ pulse. It might be that one is a 3 µJ pulse and one is 5 µJ,” he said in the interview. “The femtosecond laser pulses are known not to be perfectly stable, so they oscillate in the energy they emit. That’s important to keep in mind when looking at all these results.”

More from another peer-reviewed journal article discussing Intralase flaps

First Clinical Results With the Femtosecond Neodynium-glass Laser in Refractive Surgery  Journal of Refractive Surgery Vol. 19 No. 2 March/April 2003  Imola Ratkay-Traub, MD, PhD; Istvan E. Ferincz, MSc; Tibor Juhasz, PhD; Ron M. Kurtz, MD; Ronald R. Krueger, MD  

“This figure suggests that the wound healing process was slower compared to conventional LASIK, and may be explained by difficulties encountered in flap elevation; in a few eyes separation of the flap from the stromal bed was not optimum.”

<<>>

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfMAUDE/Detail.CFM?MDRFOI__ID=637281

“It was reported to intralase that subsequent to bilateral “bladeless” lasik, the pt developed severe “dlk,” which was treated with long-term topical and oral steroids. Posterior subcapsular cataracts formed and intrastromal scarring resulted. Cataract surgery will be performed to prevent permanent impairment. It should be noted that the reporting physician assumed this pt’s follow-up care and was not the surgeon who performed the lasik procedure.”

Wavefront Related Studies & Articles

Wavefront analysis in post-LASIK eyes – In post-LASIK eyes, wavefront refraction components were poorly correlated to manifest and cycloplegic components.

Complex wavefront-guided retreatments with the Alcon CustomCornea platform after prior LASIK – To report the results of complex wavefront-guided LASIK retreatments.

Wavefront-guided LASIK and fractional clearance – The optical zone/pupil ratio (fractional clearance, FC) has a significant impact on HOA induction after wavefront guided LASIK.

Predicting Patients’ Night Vision Complaints With Wavefront Technology – To evaluate the accuracy of the diagnostic capabilities of optical metrics generated from wavefront measurements in relationship to post–laser assisted in situ keratomileusis (LASIK) visual complaints as expressed and drawn by patients.

Maximum permissible lateral decentration in aberration-sensing and wavefront-guided corneal ablation – To investigate the lateral alignment accuracy needed in wavefront-guided refractive surgery to improve the ocular optics to a desired level in a percentage of normally aberrated eyes.

Surgeons Opinions on Wavefront: The Demise of Conventional LASIK? – Will customized LASIK procedures replace standard treatments?

Measurement of Contrast Sensitivity and Glare Under Mesopic and Photopic Conditions Following Wavefront-guided and Conventional LASIK Surgery – To compare contrast and glare vision in a prospective study of eyes treated using conventional and wavefront-guided LASIK surgery. The reproducibility of a glaremeter device used to quantitatively measure glare and halo was also determined.

Spot size and quality of scanning laser correction of higher-order wavefront aberrations – To investigate the effect of laser spot size on the outcome of aberration correction with scanning laser corneal ablation.

Retinal Studies & Articles

Full-thickness macular hole after LASIK for the correction of myopia – To describe 19 patients (20 eyes) who developed a macular hole (MH) after undergoing bilateral LASIK for the correction of myopia.

Lattice Degeneration With And Without Atrophic Holes – Illustrates an important point that lattice degeneration is quite common, occuring in 8-11 percent of the population.

Retinal phlebitis after LASIK – To report a case of retinal phlebitis with cystoid macular edema in both eyes 8 weeks after LASIK.

Two cases of retinal detachment – Following laser in Situ keratomileusis repaired by scleral buckling surgery.

Bilateral retinal detachment after laser in situ keratomileusis – Another case of retinal detachment after LASIK.

Early rhegmatogenous retinal detachment following LASIK for high myopia – Four eyes had early rhegmatogenous retinal detachment within 3 months of LASIK for correction of high myopia using the microkeratome, Clear Corneal Molder.

Retinal detachment after Excimer laser (myopic LASIK or PRK) – A retrospective multicentric study: 15 cases.

Proposed mechanism for retinal tears after LASIK: an experimental model – To demonstrate axial length changes associated with anterior shift of the lens/iris diaphragm and anterior vitreous base in human cadaver eyes during suction ring application preceding Moria LASIK, and to propose that these changes may be associated with anterior retinal tears.

Vitreoretinal alterations following laser in situ keratomileusis: clinical and experimental studies – The presence of vitreoretinal changes following laser in situ keratomileusis in myopia is evaluated.

Diffuse lamellar keratitis – Several studies related to Diffuse lamellar keratitis, with (submitted) commentary.

Late Onset Lamellar Keratitis and Epithelial Ingrowth Following Orbital Cellulitis – To report a case of late onset lamellar keratitis and epithelial ingrowth associated with orbital cellulitis 1 month after LASIK surgery.

A predictive model for postoperative intraocular pressure among patients undergoing LASIK – To develop a predictive model based on preoperative variables for estimating postoperative intraocular pressure (IOP) of those eyes undergoing LASIK.

Retinal nerve fiber layer thickness changes after an acute increase in intraocular pressure – To determine whether the increase in intraocular pressure (IOP) for 45 seconds during laser in situ keratomileusis (LASIK) suction can induce a decrease in retinal nerve fiber layer thickness (RNFLT) assessed by a confocal scanning laser polarimeter.

Retinal Nerve Fiber Layer Thickness Change after Photorefractive Surgery – To analyze the retinal nerve fiber layer (RNFL) change after photorefractive surgery.

Surgeon: Be aware of surgeries performed by other subspecialists

TOP STORIES 5/31/2006

OSN Supersite

Klaus Lucke, MD, said refractive surgery can inadvertently impact future retinal surgery.

Excerpt:

During LASIK surgery, removing the suction ring too quickly can lead to retinal problems for the patient as well, Dr. Lucke said. For instance, during suction the eye becomes longer, and when the suction is released, the eye becomes shorter and wider. A rapid increase in the width of the eye can result in retinal detachment, he said.

“Avoid sudden decompression,” he urged.

Contacts, Implants, etc. Related Articles & Studies

Contact Wearers, Beware! – “Many patients in the United States go blind every day from the use of contact lenses (especially when patients sleep in them).” – Dr. William Trattler: July 1999 asklasikdocs forum posting.

Contact lens overrefraction variability in corneal power estimation after refractive surgery – To evaluate the accuracy and precision of the contact lens overrefraction (CLO) method in determining corneal refractive power in post-refractive-surgery eyes.

Contact lens fitting post-refractive surgery – A number of patients who had undergone refractive surgery still required contact lens fitting.

Intrastromal corneal ring implantation for the correction of myopia: 12-month follow-up – To evaluate the efficacy, predictability, and stability of refraction obtained after intrastromal corneal ring segment (ICRS) implantation for low to moderate myopia.

IOL/IOP Related Studies & Articles

A Correction Formula for the Real Intraocular Pressure After LASIK for the Correction of Myopic Astigmatism – To create a correction formula to determine the real intraocular pressure (IOP) after LASIK considering the altered corneal thickness, corneal curvature, and corneal stability.

Measurement of intraocular pressure after LASIK by dynamic contour tonometry – Changes of corneal properties induced by laser in situ keratomileusis (LASIK) results in low inaccurate intraocular pressure (IOP) readings by Goldmann applanation tonometry (GAT).

Early Transient Visual Acuity Loss After LASIK Due to Steroid-induced Elevation of Intraocular Pressure – To report the clinical course of early transient reduction of uncorrected visual acuity (UCVA) after LASIK surgery resulting from steroid-induced elevation of intraocular pressure (IOP).

Change in IOP measurements after LASIK the effect of the refractive correction and the lamellar flap – To study the relationship between intraocular pressure (IOP) readings after LASIK and the amount of refractive correction.

The AS biometry technique-A novel technique to aid accurate intraocular lens power calculation after corneal laser refractive surgery – IOL calculation for cataract surgery has been shown to be inaccurate after PRK, LASEK, and LASIK. This technique is to determine difference to clinical history method (CHM).

Effect of microkeratome suction during LASIK on ocular structures – To study the effect of microkeratome suction on ocular structures during LASIK.

A predictive model for postoperative intraocular pressure among patients undergoing LASIK – To develop a predictive model based on preoperative variables for estimating postoperative intraocular pressure (IOP) of those eyes undergoing LASIK surgery, to predict the amount of underestimated IOP after LASIK for myopia and myopic astigmatism.

Preventing IOP increase after phacoemulsification and the role of perioperative apraclonidine – To evaluate the effectiveness of prophylactic topical apraclonidine 1% in preventing an intraocular pressure (IOP) rise in the early period after uneventful phacoemulsification with intraocular lens (IOL) implantation.

Accurate intraocular lens power calculation after myopic LASIK, bypassing corneal power – To describe a novel method for calculating intraocular lens (IOL) power after myopic laser in situ keratomileusis (LASIK) without using the inaccuracies of the post-LASIK corneal power.

Angle-supported phakic IOLs withdrawn from the French market  – Angle-supported phakic IOLs will no longer be sold and implanted in France due to an alarming amount of endothelial cell loss found in a significant number of patients 2 to 3 years after implantation.

Ocular Structure Changes During Vacuum by the Hansatome Microkeratome Suction Ring – To evaluate whether the vacuum of a microkeratome suction ring induces ocular structure changes.

Patients are not informed that IOP measurements after LASIK are not accurate. This can have serious implications for patients. High IOP must be treated in order to avoid permanent vision loss.

“Another concern is that IOL power calculation in eyes with previous refractive surgery is notoriously inaccurate”

SOURCE

Cataract & Refractive Surgery Today

April 2006

Cataract Surgery in Postrefractive Surgery Patients

By Eric D. Donnenfeld, MD

Quote: The potential intraocular side effects of ocular steroids are well known and include a rise in IOP and the formation of cataracts.

SOURCE

EyeWorld February 2006

PredForte

 

Is your intraocular pressure being monitored on the Pred Forte? Patients who are on this drug for more than 10 days require ongoing IOP monitoring because of the very real risk of inducing glaucoma. Tonometry is known to give falsely low IOP readings after LASIK, so other measures to assess glaucoma (like GDx optic nerve fiber analysis) appear indicated. Have you noticed any visual field losses?. Are your visual fields even being assesed?

Check out this info on ophthalmic PredForte:

http://www.drugs.com/PDR/Pred_Forte_Ophthalmic_Suspension.html

Warnings: Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision, and in posterior subcapsular cataract formation. Prolonged use may also suppress the host immune response and thus increase the hazard of secondary ocular infections.

Various ocular diseases and long-term use of topical corticosteroids have been known to cause corneal and scleral thinning. Use of topical corticosteroids in the presence of thin corneal or scleral tissue may lead to perforation.

Acute purulent infections of the eye may be masked or activity enhanced by the presence of corticosteroid medication.

If this product is used for 10 days or longer, intraocular pressure should be routinely monitored.

By taking this medicine for 6.5 months you are putting yourself at an increased risk for irreversible blindness due to glaucoma. Has your doctor told you this? You need to pin your doctor down regarding what he/she is treating. If not DLK, then what non infectious situation does he/she think he/she is treating. Treating an infectious keratitis with steroids will only worsen the condition.

Also long term topical opthalmic steroids are known to thin the cornea and can lead to corneal perforation.

The AS biometry technique-A novel technique to aid accurate intraocular lens power calculation after corneal laser refractive surgery

Cont Lens Anterior Eye. 2006 Apr 4;

Sambare C, Naroo S, Shah S, Sharma A.

The Ophthalmic Department, Kempston Road, Bedford Hospital, Bedford MK42 9DJ, UK.

Intraocular lens power (IOL) calculation for cataract surgery has been shown to be inaccurate after photorefractive keratectomy (PRK), laser-assisted subepithelial keratectomy (LASEK) and laser in situ keratomileusis (LASIK).

Many techniques exist to calculate corneal power with varying results and require the clinician to be aware of the pitfalls of IOL power calculation in post-refractive eyes. The AS biometry method proposed here is a simple method which does not rely on the calculation of corneal power. This new method is compared to the current gold standard the clinical history method (CHM). Twenty-nine eyes of 15 patients had routine biometry prior to LASIK, LASEK or PRK. The range of pre-operative spherical equivalent refractive error was -5.37 to +4.00diopters. The post-operative refraction was measured at 3-6 months. The IOL power calculation was calculated using the AS biometry method and the CHM. The two methods were compared using the Student’s paired t-test and the Bland Altman technique. There was no statistical difference between the AS biometry method and the CHM. The paired Student’s t-test comparing the AS biometry method and the CHM showed no statistical difference, t=0.33 with a p-value of 0.75, at a 95% confidence interval. The authors conclude that the AS biometry technique is as accurate as the CHM. The former is a simpler method which avoids many of the pitfalls and confounding factors involved in IOL power calculation following corneal excimer laser surgery. However, like the CHM it requires measurements prior to laser surgery.

IOL power calculation after LASIK is inaccurate

SOURCE

Excerpt:

The topic of IOL implantation after refractive surgery and power calculations arose a few years ago. However, Dr. O’Brien noted that now this situation is arising on a daily basis in practices as the number of refractive procedures increases each year and as the population ages.

“There has been a question of whether laser refractive surgery is accelerating the development of cataract. This is controversial, but I see it more and more often in my practice,” he said. Dr. O’Brien is professor of ophthalmology and director of the Refractive Surgery Service, Bascom Palmer Eye Institute, Miami.

The problem, he pointed out, is that the patients who have undergone refractive surgery and then develop cataract are different in mindset from the traditional patient with cataract in that they have extraordinarily high expectations; they want immediate results; and they want no surgical discomfort, sutures, or downtime after the procedure.

“These patients who develop cataract after refractive surgery want a perfect outcome. They are potentially frustrated and angry because their quality of vision has suffered as the result of the refractive surgery, and the results may be unpredictable. Interestingly, incorrect power is the most common reason for IOL explantation. This is the result of our not being able to determine the power as accurately as we would like,” he stated and advised exercising extra care with these patients.

“However, as more individuals have refractive surgery, the number of cataract patients with this in their history continues to increase, and calculating IOL power in these eyes can be quite problematic.”

SOURCE

Excerpts:

“However, as more individuals have refractive surgery, the number of cataract patients with this in their history continues to increase, and calculating IOL power in these eyes can be quite problematic.”

“The problem is that we can’t do nearly as well with people who have had LASIK, which alters the refractive index of the cornea,” he continues. “We’re getting an increasing number of post-LASIK patients, and I consider that I’ve done well if I get within a diopter of the intended outcome.”

“Most of the surgeons we spoke to agree that the uncertain outcomes that still occur with post-refractive surgery patients necessitate warning these patients in advance. “Despite our good outcomes to date, refractive surprises may still occur,” says Dr. Wang. “It’s important to advise patients of the risk of unacceptably high postoperative myopia or hyperopia, and the possible need for glasses, contact lenses, or additional surgery. Additional surgery could mean corneal refractive surgical enhancement, IOL exchange, or a piggyback IOL.”

“Right now our methods are not accurate enough,” agrees Dr. Packer, “especially since these patients have already paid a lot of money to have refractive surgery. Now they have a cataract and they expect a good refractive result. With current outcomes, 40 to 50 percent of these patients could need a piggyback lens to correct residual refractive error so they can be emmetropic. So, we warn all of them that it’s likely that they’ll need a piggyback implant.”

Other Eye Related Studies & Articles

The Threshold Concept – The point is that refractive surgery has robbed millions of their visual and corneal nerve reserves. Millions of Americans have been pushed nearer the threshold for dry eye, loss of functional night vision, and corneal failure (ectasia).

The Eyes Are The Windows To The Soul – The eyes are the windows to the soul. And the relatively new LASIK procedure supposedly can make those windows crystal clear. An article by Meredith Perry

An Eye For An Eye: Professor O’Reilly Speaks Out – Laser eye surgery is remarkable. Never before in American medical history have 3 million people each year responded to massive advertising by paying for an innovative, elective surgery. Never before have surgeons competed so vigorously on price; and never has a surgery been so skillfully isolated from liability lawsuits. If LASIK eye surgery becomes the Mass Tort of 2025, will Americans regret accepting it as the benign 20/20 solution of today?

Cancer & Laser Eye Surgery – At a time when there has been a significant improvement in the technology of treatment of refractive errors by laser in-situ keratomileusis (LASIK), this author has issued a very timely warning both to patients undergoing the procedure and to the people performing LASIK.

10 million not enough, stronger sales skills needed – Why refractive surgeons must adopt a philosophy of continuous improvement.

What’s OK by the FDA… – A surgeon can give patients 2 diopters of induced astigmatism as long as it’s less than 5% of eyes. That’s a LOT of blurry vision folks, and for the record… induced astigmatism was not in my informed consent materials. Was it in yours?

Surface ablation yielded better biomechanical stability vs. LASIK in study – Regardless of how thick or thin LASIK flaps are made, the flaps cause a considerable reduction in corneal biomechanical stability compared with surface ablation procedures, according to a study presented here.

Visual Field Defect after LASIK – To report a case of visual field defect associated with laser in situ keratomileusis.

Infraorbital nerve palsy: A complication of laser in situ keratomileusis – To report infraorbital nerve dysfunction after laser in situ keratomileusis.

A Cluster of Nocardia Keratitis After LASIK – To report a cluster of Nocardia asteroides keratitis cases after LASIK.

Bilateral Bacterial Keratitis in Three Patients Following Photorefractive Keratectomy – To report clinical manifestations and the bacteriologic profiles of three patients with bilateral bacterial keratitis following photorefractive keratectomy (PRK).

Potential new post-laser refractive surgery complication identified – A new syndrome characterized by noninflammatory corneal opacification  can occur in some patients within 9 days after undergoing LASIK or PRK, according to a study.

Functional optical zone after myopic LASIK as a function of ablation diameter – Glare is induced by rays of light that enter the pupil through the portion of the cornea outside the ablation area.

Vision standards for driving in Canada and the United States – A review for the Canadian Ophthalmological Society.

Dangers of Suction Ring and Laser Acoustic Shock – This barotrauma is analagous to what happens in closed eye injury, and can alter delicate retinal structures, especially small vessels, and induce vitreoretinal traction at the vitreous base and posterior pole.

Effect of microkeratome suction during LASIK on ocular structures – During application of microkeratome suction, the lens thickness decreases, whereas the vitreous distance increases, suggesting anterior traction on the posterior segment.

Survey Finds 1 In 3 Americans Dissatisfied With LASIK – 1 in 3 respondents who encountered post-Lasik problems still wear their glasses or contacts and 1 in 7 of all respondents underwent a second Lasik operation.

13% of post-LASIK eyes have posterior vitreous detachment! – Considering the data from the 100 eyes, this corresponds to 13%;

Plastic particles at the LASIK interface – Numerous plastic particles are generated during microkeratome oscillation and are deposited at the interface during LASIK. The particles persist unaltered for at least 1 year.

Visual symptoms and aberrations – The LADARWave wavefront measurement device is a valuable diagnostic tool in measuring refractive error with ocular aberrations in post-LASIK eyes.

Ocular Surface Before and After LASIK – Sensory denervation of the ocular surface after bilateral LASIK disrupts ocular surface tear dynamics and causes irritation symptoms.

Pharmacological management of night vision disturbances after refractive surgery: – Diluted aceclidine seemed to be an effective and safe treatment for night vision disturbance following refractive surgery.

Patients Never Really Understand… – “What good is making pupil size measurement a part of the standard of care if it is never utilized (by the doctor, or to communicate to the patient the risks it implies about the surgery they are considering)?”

Hot Compresses Fix Nerve Damage? – “that warm compresses along with other therapies can treat even the worst dry eye patients after LASIK.”

Laser Eye Surgery Failure Rate Reported At One In Ten – In 2003, the medical journal Ophthalmology said the failure rate for eye surgery was one in ten, not the one in 1,000 figure widely advertised.

Ectasia known risk of laser vision correction – Ectasia is a known risk of laser vision correction, and if ectasia occurs in a patient following laser vision correction it does not necessarily mean that the patient was a poor candidate for surgery, that the surgery was contraindicated, or that there was a violation of the standard of care.

Floaters – 13% of post-LASIK eyes have posterior vitreous detachment (floaters)! And 25% of high myopes have posterior vitreous detachment after LASIK!

Posterior Vitreous Detachment – Effect of microkeratome suction during LASIK on ocular structures.

Correlations in a change in aqueous tear evaporation with a change in relative humidity and the impact – To establish scientific relationship between relative humidity (RH) and aqueous tear evaporation to elucidate possible significance of this relationship in normals and aqueous tear deficiency patients.

Pressure-induced interface keratitis: a late complication following LASIK – To describe a novel presentation of interface inflammation that resembles DLK in appearance but presents late in the postoperative period, is associated with increased intraocular pressure, and is exacerbated by steroid treatment.

Influence of pupil and optical zone diameter on higher-order aberrations after wavefront-guided myopic LASIK – To investigate the influence of pupil and optical zone (OZ) diameter on higher-order aberrations (HOAs) after myopic wavefront-guided laser in situ keratomileusis (LASIK).

Changes in quality of life after laser in situ keratomileusis for myopia – People presenting for LASIK scored measurably poorer than matched patients not contemplating refractive surgery.

Comparative results of keratometry with three different keratometers after LASIK – This study demonstrates that with common keratometers central corneal power is measured too high after LASIK.

Iris repair after a catastrophic laser in situ keratomileusis complication – This report illustrates the surgical approach to and results of a comples iris reconstruction. The presentation and long-term visual and architectural results (follow-up of 4 years) of the repair of a severe anterior segment injury after entry into the anterior chamber by a microkeratome during LASIK is described.

High Interocular Corneal Symmetry in Average Simulated Keratometry, Central Corneal Thickness, and Posterior Elevation – The purpose of this study was to assess interocular corneal syymetry in average simulated keratometry, corneal thickness, and posterior corneal elevation.

The effect of daily use of brimonidine tartrate on the dark-adapted pupil diameter – To investigate the effect of daily brimonidine tartrate 0.15% on the dark-adapted pupil diameter.

Promises – An insiders journal on the evolution and misinformation of refractive surgery.

An Eye Doctor’s Fly in the Ointment – “Dr. X, for every patient you send to our laser center, we’ll collect the $5000 and we’ll make sure you get back $2000.”  “That’s an extravagant amount,” I said. “Isn’t that a kickback?”

Reasons patients recommend LASIK – To evaluate the reasons patients who have had laser in situ keratomileusis (LASIK) recommend it to others and examine the disparity between high levels of satisfaction and patient reports of night-vision symptoms and/or dry eye after LASIK.

LASIK complication: loss of electricity to the microkeratome – This type of unforeseen microkeratome malfunction may result in serious flap or other complications.

LASIK for myopia and astigmatism – safety and efficacy: a report by the American Academy of Ophthalmology

Evaluation of the prophylactic use of mitomycin-C to inhibit haze formation after photorefractive keratectomy – To evaluate the results of the prophylactic use of mitomycin-C to inhibit haze formation after excimer laser PRK for medium and high myopia in eyes that were not good candidates for LASIK.

Keratorefractive Surgery, Success, and the Public Health – “I hope the reader will understand how a patient may have clinically acceptable 20/20 visual acuity in the daytime and still suffer from clinically dangerous visual aberration at night if that patient’s visual system must cope with an altered refractive error, increased glare, poorer contrast discrimination, and preferentially degraded peripheral vision.

The Pathophysiology of Regression following LASIK – Part of this study determined that there were significant biomechanical and epithelial effects occurring, and that corneal elastic bowing and epithelium changes could practically account for the inaccuracy of LASIK.

Autorefractometry after LASIK – To correlate cycloplegic subjective refraction with cycloplegic autorefractometry in eyes that have had LASIK.

Bacillus megaterium delayed onset lamellar keratitis after LASIK – To report the history and clinical presentation of a 23-year-old man who developed delayed onset lamellar keratitis in his right eye 2 weeks after uneventful LASIK for correction of myopia.

Hyeropic shift after LASIK induced Diffuse Lamellar Keratitis – Diffuse lamellar keratitis (DLK) is a relatively new syndrome that is increasingly being reported after LASIK. We have observed that a hyperopic shift may be associated with the occurrence of this diffuse lamellar keratitis.

Iatrogenic ring scotoma after LASIK – A 37-year-old ophthalmologist had bilateral simultaneous laser in situ keratomileusis (LASIK) for moderate myopia with astigmatism using the Alcon Summit LADARVision laser; an ablation zone of 5.5 mm was used. Five months after surgery, the uncorrected visual acuity was 20/20 and 20/25 but despite regular corneal topographies, the patient experienced prominent ghost images under photopic and scotopic conditions.

Reverse ptosis-induced corneal steepening and decreased vision after LASIK surgery – To report a patient with a past history of LASIK who had decreased vision and induced corneal steepening after lower eyelid ptosis. Surgical correction of lower eyelid ptosis decreased the corneal steepening and improved visual acuity.

Silence is Golden…for the LASIK Doctors? – As Angry Patients Vent Online, Doctors Sue To Silence Them – An article by David Kesmodel, The Wall Street Journal Online.

When doctors sue to silence – What Are They Hiding?

Let’s face it, past and recent articles & studies make a clear case for withdrawal of  FDA approval for the LASIK procedure!

Laser Manufacturers: Studies, Letters, & Complaints

FDA MDR on ALCON/Summit Apex Plus – Pupil size issue: Patient has undergone photorefractive keratectomy (prk) at hospital at hospital in a foreign country with a FDA approved laser, i.e. The ApexPlus of the co Summit technology.

FDA Warning Letter – To ALCON Laboratories dated January 18, 2005.

Subject: LASIK, Bausch & Lomb, and TLC, my thoughts – An ex-employee’s concern for safety and effectiveness.

From the FDA, Summary of Safety and Effective Data – For the Approval of the Bausch & Lomb Technolas 217A.

What’s really the cause of high retreatment rates? – The debate is growing with one laser (ALCON) squarely in the center.

INTRALASE FS 600 C – Laser System (Model 1), Laser Keratome Recall # Z-0147-3.

FDA Warning Letters – To LaserSight Technologies.

FDA MDR Reports – For problems/injuries by VISX Laser.

VISX – Possible Deception? – VISX reported that 97.7% (84/86) of eyes had UCVA of 20/20 or better at 12 months. These 86 eyes represent only 24.5% of patients. Accountability is reported to be 95.6%, despite the fact that 70.7% (248/351) of patients were labeled “not yet eligible” for analysis at 12 months.

Effect of expanding the treatment zone of the Nidek EC-5000 laser – To evaluate the effect of expanding the treatment zone of the Nidek EC-5000 laser.

Ophthalmologist Sues Laser Manufacturer ALCON – Ophthalmologist, Dr. Sandra Brown is acutely aware of what can go wrong when a surgical laser is applied to someone’s eyes. She waited a long time before consenting to laser eye surgery to correct her own flawed vision.

A VERY Interesting Article:

Refractive Surgery – A Ten Year Learning Curve

“Ten years on, LASIK appears to have lived up to its promise, although not for the high refractive errors that had originally been proposed.”

Quotes, Non Peer-Reviewed Articles, and More

Informed Consent

“What concerns me is that if the person informing the patient is themselves poorly or inaccurately informed then how on earth can consent ever be truly informed?” Dr. Sarah Smith.

AND MORE…

Cleaner LASIK: Is it Possible?

http://www.ophmanagement.com/article.aspx?article=86452

 

This from a doctor who was fined $1.1 Million from the FDA for damaging 125 patients…

IOL calculations after refractive surgery need extra care

http://www.ophthalmologytimes.com/ophthalmologytimes/article/articleDetail.jsp?id=302330

Excerpt:  The topic of  IOL implantation after refractive surgery and power calculations arose a few years ago. However, Dr. O’Brien noted that now this situation is arising on a daily basis in practices as the number of refractive procedures increases each year and as the population ages.  “There has been a question of whether laser refractive surgery is accelerating the development of cataract. This is controversial, but I see it more and more often in my practice,” he said. Dr. O’Brien is professor of ophthalmology and director of the Refractive Surgery Service, Bascom Palmer Eye Institute, Miami.  The problem, he pointed out, is that the patients who have undergone refractive surgery and then develop cataract are different in mindset from the traditional patient with cataract in that they have extraordinarily high expectations; they want immediate results; and they want no surgical discomfort, sutures, or downtime after the procedure.

“These patients who develop cataract after refractive surgery want a perfect outcome. They are potentially frustrated and angry because their quality of vision has suffered as the result of the refractive surgery, and the results may be unpredictable. Interestingly, incorrect power is the most common reason for IOL explantation. This is the result of our not being able to determine the power as accurately as we would like,” he stated and advised exercising extra care with these patients.

“Successful LASIK” is an oxymoron

Found on Lasik-Flap bulletin board: http://www.lasik-flap.com/forum

The flap never heals. It cannot heal. All it can do is form a scar at the margin of the flap which is only 28% as strong as a normal cornea. The flap itself does not bond to the underlying cornea and can be dislodged or lifted years later.

The corneal nerves that play a vital role in tear production never fully regenerate. A scientific peer-reviewed study proved that at 3 years post-op the corneal nerves are still less than 60% of pre-op densities. LASIK induced dry eyes is common and for many patients is a life-long sentence.

The suction ring used during the cutting of the flap damages the delicate structures inside the eye including the retina, vitreous, and optic nerve. Many patients report increased floaters (posterior vitreous detachment) after LASIK, and some experience retinal tears or detachment, lacquer cracks, macular holes, macular hemorrhages, optic neuropathy, and retinal vein occlusion.

LASIK corneas are not as stable as normal corneas and can begin to bulge weeks, months, or even years later, potentially resulting in loss of the cornea. This bulging is a response to the normal intraocular pressure. A LASIK-weakened cornea sometimes can no longer withstand this outward force. The FDA used a best-guess safety limit of 250 microns of cornea under the flap when LASIK was approved. Since then it has been shown in the medical literature that 250 is not a safe limit, even though the vast majority of LASIK surgeons, who are too busy doing LASIK to follow the research, are still using an unsafe limit of 250 microns. And the FDA does not have the backbone to modify the approval, allowing the LASIK industry to continue this unsafe practice that jeopardizes the well-being of millions of patients.

There is permanent damage in 100% of LASIK corneas — debris in the space between the flap and the underlying cornea, undulations and microfolds in the Bowman’s layer — presumably because the flap doesn’t fit to the altered corneal bed, haze, epithelial cells under the flap, acutely and chronically reduced keratocytes, epithelial thickening, collagen fibril disorganization, collagen lamellar disarray, and abnormalities of the Descemet membrane.

Quote from one peer-reviewed study: “However, the presence of pathologic findings up to 7 years after LASIK indicates that the process of corneal stroma wound healing never completely regenerates histopathologically normal corneal stroma.”

Loss of night vision quality after LASIK occurs frequently, according to a 2002 report by the American Academy of Ophthalmology. For some patients, particularly those with large pupils, this complication can be debilitating. Since this is a “frequent” problem after LASIK, I wonder how many of the approximately 8 million Americans who have had LASIK are out there on the roads at night endangering their life and the lives of others who share the roads with them? A recent study showed that up to 50% of LASIK patients are impaired when driving at night. Yet this serious threat to the public health is down-played and swept under the rug by the LASIK industry.

And then we have the problem of the white wall of silence. Doctors are pressured by their peers not to testify for patients who are victims of LASIK malpractice. They are threatened by their own insurance carriers, which could put them out of business. And they are concerned about giving LASIK a black eye by helping a patient seek justice for the harm done to him or her in a public forum like a court of law. They cave in to the pressures, leaving patients without any recourse — medical, legal or otherwise. So doctors just get away with it and standard of care and informed consent continue to be basically non-existent. And the FDA says it’s not their problem (they regulate the devices, not the doctors).

So who’s looking out for the patients? Who’s going to warn them that 1/3 of their corneas will be nearly sliced off, leaving them with a structurally weakened cornea that can begin to bulge years down the road? Who’s going to warn them of the seriousness of LASIK-induced dry eyes, that the nerves never regenerate, and that painful dry eyes can be permanent? Who’s going to warn them that LASIK, all LASIK — conventional and custom, induces higher order aberrations in all virgin corneas, effectively reducing the quality of their vision? Who’s going to warn them of the damage the suction ring can do to the structures inside the eye? Who’s going to warn them that the flap never heals?

You would think doctors would be protecting patients. Wake up and smell the coffee. Money is what drives them, not a desire to heal the sick. They don’t deserve to be called doctors. They are no better than used car salesmen.

American Academy of Ophthalmology. For some patients, particularly those with large pupils, this complication can be debilitating. Since this is a “frequent” problem after LASIK, I wonder how many of the approximately 8 million Americans who have had LASIK are out there on the roads at night endangering their life and the lives of others who share the roads with them? A recent study showed that up to 50% of LASIK patients are impaired when driving at night. Yet this serious threat to the public health is down-played and swept under the rug by the LASIK industry.

Mistakes/Errors

JOURNAL OF REFRACTIVE SURGERY Vol. 22 No. 3 March 2006   Dan Z. Reinstein, MD, MA(Cantab), FRCSC; Cynthia Roberts, PhD

Excerpt:  “Some of the evidence pointing to the impact of corneal biomechanical properties on surgical outcomes lies in the measurement of intraocular pressure (IOP), both before and after refractive surgery. It is well known that measured IOP is reduced, on average, following a refractive procedure. It has been assumed that this is the result of reduced curvature and thickness in myopic procedures. However, Chang and Stulting performed a retrospective review of over 8000 myopic LASIK patients, and determined that although measured pressure was reduced on average by approximately 2 mmHg, the range of change was approximately +10 to -15 mmHg. Every patient in this population had reduced thickness and curvature, and yet almost half of them had an increase in measured IOP.

Clearly, the artifact in IOP measurement cannot be explained by thickness alone, and “correction” of measured IOP postoperatively using a linear correction factor based on thickness is problematic. This leads to the conclusion that refractive surgery likely alters the fundamental biomechanical properties of the cornea.

Lasers or Surgeons: What’s really the cause of high retreatment rates?

http://www.eyeworld.org/article.php?sid=2267

EyeWorld
January 2005

“I had one time where I had to put the flap back with a flashlight because the illumination light went off so I couldn’t figure out where the flap was,” Dr. Rubinfeld said.

Interface fluid after LASIK

J Cataract Refract Surg. 2001 Sep;27(9):1526-8.

Fogla R, Rao SK, Padmanabhan P.  Cornea Services, Sankara Nethralaya, Chennai 600 006, Tamil, Nadu, India. mrf@sankaranethralaya.org

We report a case in which raised intraocular pressure (IOP) was associated with interface fluid after uneventful bilateral laser in situ keratomileusis (LASIK). The patient presented with diffuse lamellar keratitis in both eyes 3 weeks postoperatively that was treated aggressively with topical corticosteroids. A steroid-induced rise in IOP resulted in interface fluid accumulation and microcystic edema. Measurements with the Goldmann tonometer revealed an IOP of 3.0 mm Hg in both eyes. However, Schiotz tonometry recorded a pressure of 54.7 mm Hg in both eyes. Reduction in the dosage of topical corticosteroid and medical treatment of the raised IOP resulted in resolution of the microcystic edema and interface fluid accumulation. This case highlights the inaccuracies of IOP measurement after LASIK and the resulting complications.

LASIK: three unexpected complications

J Refract Surg. 2001 Mar-Apr;17(2 Suppl):S177-9.  Rosa DA.

PURPOSE: To report unexpected outcomes in three patients after uneventful laser in situ keratomileusis (LASIK) performed using the Nidek EC-5000 excimer laser and the Hansatome microkeratome (Bausch & Lomb Surgical).

METHODS: LASIK was performed with the Nidek EC-5000 excimer laser and the Hansatome microkeratome (Bausch & Lomb Surgical) in three patients.

RESULTS: In three patients, unexpected outcomes were observed. One patient treated for -3.00 D of myopia presented with a central island. One patient treated for +2.00 D (+1.00 x 90 degrees) of hyperopia in both eyes ended up emmetropic in one eye and overcorrected in the fellow eye. The third patient with -12.00 D (-2.00 x 180 degrees) of myopia was treated as -8.60 -1.00 x 180 degrees and at last examination was +4.00 D. During these sessions, all other patients treated were within +/-0.50 D of emmetropia.

CONCLUSION: After LASIK with the Nidek EC-5000 excimer laser and the Hansatome microkeratome (Bausch & Lomb Surgical), unexpected outcomes may still occur, despite controlling all the usual variables.

Oculocardiac reflex in a nonsedated LASIK patient

J Cataract Refract Surg. 2002 Sep;28(9):1698-9.

Baykara M, Dogru M, Ozmen AT, Ozcetin H.  Uludag University Faculty of Medicine, Department of Ophthalmology, Bursa, Turkey

A healthy 21-year-old man had laser in situ keratomileusis (LASIK) in the right eye for a refractive error of -7.0 diopters. The electrocardiogram findings and heart rate were recorded before LASIK; during eye lid speculum insertion, vacuum application, corneal flap preparation, and excimer laser keratectomy; and after the procedure.

The pre-LASIK heart rate was 90 pulses/min. Severe bradycardia of 40 beats/min developed during vacuum application, and the procedure was terminated. Severe bradycardia caused by an oculocardiac reflex may occur during LASIK, and patients should be closely monitored during the procedure.

LASIK complication: loss of electricity to the microkeratome during the forward pass

Acta Ophthalmol Scand. 2003 Oct;81(5):530-2.

Tuominen IS, Tervo TM.  Department of Ophthalmology, Helsinki University Hospital, PO Box 220, HUS, SF-00029 Helsinki, Finland. ilpo.tuominen@hus.fi

CONTEXT: A 32-year-old woman was scheduled for myopic laser in situ keratomileusis (LASIK) because of myopia and anisometropia caused by retinal detachment surgery.

CASE REPORT: During surgery, a sudden malfunction of the microkeratome during the forward pass was experienced. It was not possible to reverse the blade manually along the suction ring. Moreover, disconnecting the suction from the control unit did not help at first, because the suction ring was firmly attached to the ocular surface. However, detaching the suction line from the control unit aborted the vacuum and allowed the surgeon to turn the whole microkeratome backwards, mimicking the normal blade movement. Finally, an almost normal flap was observed, and the operation was successfully completed. Afterwards, the wire to the electromotor of the microkeratome was found to be broken and subsequently replaced.

CONCLUSION: This type of unforeseen microkeratome malfunction may result in serious flap or other complications.

Refractive surprise after LASIK

Arch Soc Esp Oftalmol. 2005 Sep;80(9):547-9. Related Articles, Links

CASE REPORT: A female patient underwent laser in situ keratomileusis (LASIK) in both eyes. The final degree of astigmatism in her left eye was double the preoperative value due to an error in data management. Complex surgery to both eyes was necessary to resolve the mistake.

DISCUSSION: Complications in refractive surgery can occur, however errors in data management must be minimized by double-checking. Solutions to resolve the errors made can be difficult and the entire staff must share responsibility to avoid these undesirable outcomes.

Failure to verify treatment parameters can lead to LASIK errors

http://www.osnsupersite.com/

TOP STORIES 3/24/2006

Quote: In the last case, the patient allowed the surgeon to call him “José” several times, believing the surgeon was making a joke. Only after one eye had been treated incorrectly did he clarify his name was “Carlos,” Dr. Sonal said.

Turn Around These LASIK Letdowns

Review of Optometry

Excerpt:  For most carefully chosen patients, LASIK continues to improve their quality of life significantly. However, the popular media that once portrayed LASIK as a somewhat miraculous procedure now tell horror stories of people visually disabled by LASIK gone awry.

Read the entire article at:

http://www.revoptom.com/index.asp?ArticleType=SiteSpec&page=osc/oct01/lesson_1001.htm

What’s Next for LASIK?

Ophthalmology Management Issue: September 2004

Outcomes are better than ever, but its place as the dominant refractive procedure is now in doubt.  By Jerry Helzner

http://www.ophmanagement.com/article.aspx?article=86168

EyeWorld

December, 2006 –

http://www.eyeworld.org/article.php?sid=3545

http://www.eyeworld.org/images/New_Articles/2006/12/68.jpg

http://www.eyeworld.org/article.php?sid=2765

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“Make sure the first patient you enroll feels like you have been doing this for years…”

EyeWorld October, 2005

Stephen S. Lane, M.D.:

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“There has been a lot of interest in ectasia worldwide because it is a lose-lose situation for both patients and surgeons.”

http://www.escrs.org/PUBLICATIONS/EUROTIMES/06Oct/pdf/Riskfactorfor.pdf

However, I believe there are too many holes in available literature reports to allow risk factors to be conclusively defined. Likely, there are other variables that are not measured or that we don’t know how to measure that account for this complication,” said Dr Binder. He added, “Any of the current recommendations for safe patient selection are guesswork and unproven.”

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Why do you not use the Excimer laser?

http://www.lcrs.co.uk/menu/FAQ

Other clinics do with very good results, but a higher complication rate. We don’t believe in taking additional risks, so we don’t operate on the line of sight by cutting across the eye and don’t remove any tissue. These are the two main reasons for laser complications. For example, up to 50% of patients permanently lose some night vision, making night driving dangerous and because after LASIK the corneal flap never heals. The cornea is permanently weakened by between 40% and 50% and some cases are require corneal transplants to restore their sight. For more information in LASIK, you can visit www.lasereyedoctor.co.uk or ask for our leaflet: Lasers in refractive surgery.

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Recurrent Regression After Hyperopic LASIK

From Cataract & Refractive Surgery Today, 2003 http://www.crstodayarchive.com/03_archive/0602/crst0602_101.html

Refractive Challenge

By Mitchell C. Shultz, MD Excerpt:

“Through my 6 years’ experience performing refractive surgery, I have found that women in the perimenopausal age group have a significantly increased risk of dry eye syndrome after LASIK when compared to other subgroups of patients. LASIK-induced neurotrophic epitheliopathy (LNE) caused by the transection of the sub-basal nerve fiber bundle and photoablation of the superficial stromal nerves sets the stage for postoperative dry eyes. The combination of LNE and hormonal changes affecting meibomian secretions leads to a chronic tear film dysfunction that is more prevalent in peri- and postmenopausal women. For this reason, I am leery of performing LASIK on these patients.”

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http://www.osnsupersite.com/view.asp?rID=23169Eric D. Donnenfeld, MD:

Quote: A 45-year-old woman came in for routine LASIK. I’m doing my LASIK, I hand off the keratome, and they blow out the keratome. And suddenly there is no flap. Now we’re looking for the flap, but we can’t find it. And all of you know how to find out if spaghetti is done. You throw it against the wall. If it sticks, it’s done. And that’s exactly what happened. The cornea ended up against the wall. We find it, but now it’s been sitting on the wall for about 5 minutes.

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http://www.ophthalmologytimes.com/ophthalmologytimes/article/articleDetail.jsp?id=405941 R. Doyle Stulting MD:

“Ectasia is estimated to occur in one of every 2,500 patients undergoing LASIK, Dr. Stulting said, “but this may be an overestimate because of current exclusion criteria. It also may be an underestimate because of limited follow-up.” Reported cases of ectasia have been diagnosed up to 4 years after LASIK, he added, also noting a case of ectasia that required corneal transplantation 13 years after PRK. “Pathology in this case suggests cell loss and abnormalities of keratocytes, leading us to wonder whether defective keratocyte metabolism could make ectasia more likely and to wonder whether mitomycin C might increase the long-term risk of ectasia,” Dr. Stulting said.”

Analysis of ectasia after LASIK: Risk factors

JCRS Analysis of ectasia after laser in situ keratomileusis: Risk factors Volume 33, Issue 9, Pages 1530-1538 (September 2007) Perry S. Binder

Quote: The mean flap thickness measured at surgery by subtraction pachymetry (n = 350 eyes) was 113.1 ± 29.3 μm (range 29 to 221 μm).  Quote: The RST measured directly after the laser ablation, recorded in 250 eyes, ranged from 102 to 384 μm.

If the eyes in that study had achieved flap thicknesses in excess of 200 μm, which is not uncommon with the microkeratomes used at that time, the residual thicknesses would have been less than 250 μm in all cases.

Correlation Between Attempted Correction and Keratometric Refractive Index of the Cornea After Myopic Excimer Laser Surgery

Journal of Refractive Surgery Vol. 23 No. 5 May 2007 Giacomo Savini, MD; Piero Barboni, MD; Maurizio Zanini, MD Quote:

Inaccurate calculation of intraocular lens (IOL) power after refractive surgery has been the subject of considerable attention in the past decade. It is widely recognized that using videokeratography underestimates corneal flattening after myopic excimer laser surgery. As a consequence, standard keratometric values lead to IOL power underestimation (with subsequent hyperopia) in eyes that have previously undergone myopic photorefractive keratectomy (PRK) or LASIK.1,2

Effect of Punctal Plugs in Patients With Low Refractive Errors Considering Refractive Surgery

Journal of Refractive Surgery Vol. 23 No. 5 May 2007 Monica B. Khalil, MD; Robert A. Latkany, MD; Mark G. Speaker, MD, PhD; Guopei Yu, MD, MPH

Quote: Retreatment rates up to 15% have been reported with conventional LASIK.6 However, retreatment increases risk of complications, such as diffuse lamellar keratitis, epithelial ingrowth, striae, infection, prolongation of dry eye, and flap dislocation. These complications are potential causes of decreased best spectacle-corrected visual acuity (BSCVA).

Role of the endothelial pump in flap adhesion after LASIK

J Cataract Refract Surg. 2004 Sep;30(9):1989-92. Bissen-Miyajima H, Nakamura K, Kaido M, Shimmura S, Tsubota K.

Quote: The mechanism of flap adhesion immediately after surgery is strongly affected by the pump function. In the long term, flap adhesion is more dependent on the epithelium. Pathologic studies of rabbit eyes reveal epithelial hyperplasia at the flap edge.5, 6 Clinically, there have been reports of flap dislocation; however, these cases had evidence of injuries.7, 8 During LASIK enhancement procedures, the edge of the flap is observed to be tightly adhered to the epithelium. Once this tight junction is compromised, the flap can be easily peeled, which underscores the importance of the endothelial pump even in the long term following LASIK.

High Road Ethics for a High-Tech Era

http://www.aao.org/publications/eyenet/200709/feature.cfm

Feature By Miriam Karmel, Contributing Writer

Any physician in practice today can be confronted with a challenging ethical question. But the new technologies of cataract and refractive surgey may present especially complicated—and potentially rewarding—situation.

The dissatisfied patient is nothing new. But last April, following a recent uptick in complaints from angry and disappointed patients, the Academy’s Ethics Committee issued an alert urging doctors to be more mindful of their ethical obligations.

The alert, which is posted here, addressed complaints from patients claiming they hadn’t been adequately informed of the potential visual side effects associated with multifocal or accommodating intraocular lenses. “There’s a perception that experienced cataract surgeons are not increasing their attention to assessment of patient need, and to the learning curve,” said Charles M. Zacks, MD. “That’s resulting in more unhappy refractive patients than ever.” Dr. Zacks, who chairs the Ethics Committee and practices cornea medicine in Portland, Maine, called this “a very big problem. Particularly if patients feel they weren’t adequately informed.”

The prospect for ethical challenges may be especially relevant for the new, high-tech IOLs, but the principles they invoke—informed consent, primacy of the patient’s interest and respect for the learning curve—apply whenever a physician tries incorporating new procedures or technology into clinical practice.

“There’s a lot of new technology in most of the subspecialty fields in ophthalmology,” said Richard L. Abbott, MD, professor of ophthalmology at the University of California, San Francisco. “The challenge, ethically, is which technology to embrace? Where do you draw the line between offering the newest technology over a long-standing proven device or procedure? The bottom line should always be what is in the best interest of your patient.”

More Options Mean More Chair Time

When monofocal IOLs were the only choice, the nature of pseudophakic vision was relatively easy to explain. Now patients have multiple options, which require more discussion and tougher decisions. It’s the surgeon’s responsibility, said Dr. Zacks, to give the patient a realistic impression of what these lenses will and won’t do. Will distance or near vision be important to the patient? How will the patient feel about wearing reading glasses? “Everything’s a trade-off in optics. These lenses can compromise contrast sensitivity and other optical qualities in exchange for multifocality. The patient needs to know the advantages and disadvantages of the lens they’re going to get, in unvarnished terms. Fitting the available technology to the patient is really the goal.

”“If doctors aren’t willing to put time in both before surgery, in terms of education and evaluation, and after, in terms of management to optimize the final result, they shouldn’t be using these lenses.”

Preop hopes meet postop reality. Patients whose expectations aren’t met can be extremely unhappy, said William W. Culbertson, MD, professor of ophthalmology at Bascom Palmer Eye Institute and a member of the Ethics Committee. Take the case of the myopic engineer, a woman in her 50s, who’d been accustomed to taking off her glasses to read the fine print on drawings. Following surgery, her reading varied under different lighting conditions, she could no longer read closely without glasses, and halos put an end to her night driving, said Dr. Culbertson, who saw her by referral. The woman claimed she didn’t know she had multifocal lenses until an optometrist examined her eyes. Perhaps her ophthalmologist had told her, but postoperatively she didn’t recall being told anything about multifocal lenses or their potential optical side effects, Dr. Culbertson said. The point is, she hadn’t been adequately informed of the drawbacks.

“I’m not putting down these lenses,” added Dr. Culbertson, who uses them. “They’re very helpful. But the patient needs to clearly know what’s going on, which takes more chair time,” he said. “You can partially off-load it to brochures and videos and patient counselors. In the end, it comes down to the doctor helping the patient make the best choice and answering all the patient’s questions. If doctors aren’t willing to put time in both before surgery, in terms of education and evaluation, and after, in terms of management to optimize the final result, they shouldn’t be using these lenses.”

New Isn’t Always “Best”

And yet some doctors do regard every patient as a candidate for the new lenses, said Marian S. Macsai, MD, professor and vice chairwoman of ophthalmology, Northwestern University, and chief of ophthalmology, Evanston Northwestern Health Care. She senses “an urgency in the air” to put multifocal lenses into as many patients as possible, as well as an attitude that the cataract surgeon who isn’t using these lenses is behind the times.

Recently, Dr. Macsai heard a doctor say that his goal is “100 percent conversion.” In other words, he would like every one of his patients who comes in with a cataract to walk out with a premium lens upgrade. But these lenses are not for everybody, Dr. Macsai said. There’s no reason, for example, for a doctor to urge multifocal IOLs in a person who doesn’t mind wearing glasses, or for a person whose livelihood depends on driving at night. Similarly, she said, the lenses aren’t suitable for patients who are impaired by other disease, such as age-related macular degneration or diabetic retinopathy, since they lack the visual potential to benefit from multifocals.

When there’s not even a cataract. Then there’s the matter of clear lens exchange. “I’m not sure we should be whipping out lenses of normal people because the technology exists and we want to make money. That’s just not a good enough reason,” Dr. Macsai said. Having said that, she acknowledged a place for them in the armamentarium. “For some patients they’re fabulous. It’s just, ‘Slow down everybody! Make sure we’re doing what’s best for our patients and not our pocketbooks.’”

Physician comfort with the technology. The new technology or device should also be what’s best for the physician in terms of philosophy and comfort level with adopting new procedures. Some physicians adopt new practices more readily than others. “There’s a tension between trying new things, pushing the envelope and what’s safe for the patient,” said Ruth D. Williams, MD, a glaucoma specialist in private practice in Wheaton, Ill. Dr. Williams added that glaucoma specialists, for example, are always trying to think of new ways to do filtering surgery. “When you have a patient in front of you, the question is, ‘We have a gold standard in trabeculectomy, and a gold standard in putting in valves. What are the parameters that make it reasonable to try something else that’s not as proven?’”

In part, the answer rests with personality as well as with responsibility. “Some [physicians] always want to try new things, others want the tried, true and proven. People are different. We need both. Our community needs both,” said Dr. Williams.

Dr. Abbott agrees that some ophthalmologists are greater risk takers than others. “Does that mean they’re doing a better job for their patients? I don’t know. Everybody needs to look within and determine what is his or her own personal comfort level,” he said. “In all cases, however, the bottom line is patient-centered.”

ETHICAL PROBLEM, OR LEGAL?

READ THE FULL ARTICLE

Results of Lasik not always clear – Many angry patients suffer silently with visual defects

By Robert Mitchum | Tribune staff reporter August 21, 2007

Millions of people are estimated to undergo the Lasik procedure each year in the United States at academic clinics, private practices and corporate centers. While the vast majority experience no long-term complications of the surgery, a small percentage find themselves with permanent visual defects that are difficult to treat and hard to live with.

Some of these patients respond in anger; a browse of the Internet will turn up several venomous sites calling for litigation against Lasik surgeons, a horror story from comedian Kathy Griffin and even calls for a ban of the procedure itself. Other patients suffering from post-surgical complications languish in silence, unaware of their options for treatment.

Barbara Berney of Rockford was one of these patients, suffering from a long list of complications after her Lasik surgery in 2001: dry eye, night blindness, dimmed vision and a suite of aberrations, including ghosting, halos and starbursts.

“If you made a list of complications, I’d probably have 70 percent of them,” Berney said. “How I can stay sane, I don’t know.”

After a second surgery did not significantly improve her vision, and after an unsuccessful legal action against her surgeon, Berney decided to start an organization for people in her situation: the Vision Surgery Rehabilitation Network.

Group offers support

The VSRN connects people struggling with Lasik complications with ophthalmologists and optometrists experienced in treating such cases. It also offers a measure of emotional support for people struggling with visual defects.

“I’ve had a couple people commit suicide, who could not imagine living the rest of their lives seeing the way they see,” Berney said.

“You cannot underestimate what loss of vision can do to you, and it’s very difficult to get family members and co-workers to understand just how difficult it is. It’s like trying to explain the color of milk to someone who’s blind.”

Lasik surgery involves opening a flap in the surface of the eye and shaving down the cornea with a laser, which can correct both nearsightedness and farsightedness as well as conditions such as astigmatism. While new technologies have improved some of the more troublesome steps in this procedure, some complications remain.

The most serious, according to Dr. Michael Rosenberg, ophthalmologist at Northwestern Memorial Hospital, are infections and ectasia, a bulging caused by destabilization of the cornea. In extreme cases, these complications may be treated with a corneal transplant; however, their occurrence is very rare.

READ THE FULL STORY

Eye surgery leaves many with problems

http://www.newsobserver.com/front/story/721249.html

Of millions of patients, more than a few have serious, lasting complications

Sabine Vollmer, Staff Writer

Millions of Americans have undergone laser eye surgery to correct bad vision, and along with the procedure’s popularity something else is coming into focus: its hazards.

Advertising stresses the surgery’s safety, and most procedures are successful. Tiger Woods, who relies on keen eyesight as the world’s best golfer, pitches it as a quick and painless way to restore sharp vision. Even the U.S. Air Force, long skeptical of the surgery, changed its policy in May to let people who had LASIK apply for pilot training.

But every year thousands of Americans who undergo LASIK are left with chronic pain, dryness of the eyes, distorted night vision and even blindness, according to Food and Drug Administration statistics.

LASIK — which stands for laser-assisted in-situ keratomileusis — uses lasers to cut and reshape the cornea. It can improve eyesight without complications, but equipment flaws, a surgeon’s error or a failure to screen out patients whose eyes are ill-suited for the treatment can cause the operation to go awry.

The American Society of Cataract and Refractive Surgery, which represents about 9,000 ophthalmologists specializing in laser eye surgery, estimates that only 2 percent to 3 percent of the more than 1 million LASIK surgeries each year are unsuccessful. But Food and Drug Administration records of clinical studies show that six months after the surgery, up to 28 percent of patients complained of eye dryness, up to 16 percent had blurry vision and up to 18 percent had difficulty driving at night.

The Triangle, home to two medical schools, is a hot spot for LASIK; 11 eye centers will perform LASIK on about 8,000 patients this year, according to market research.

One of the leaders is Duke Eye Center, whose LASIK surgeons are among the best-trained and best-equipped in the field. But even surgery at Duke’s level has damaged a few patients’ eyes beyond repair.

One of those patients is Matthew Kotsovolos, 38, of Raleigh. He was the Duke Eye Center’s head of finances and received the surgery for free June 8, 2006. It gave him 20-20 vision but left him with intensely dry eyes and excruciating facial pain. He wakes up with sore eyes every morning, wears special goggles to preserve eye moisture and wonders when the pain in his face will kick in.

“I traded in my glasses for permanent head pain, eye pain and these things,” Kotsovolos said, pointing to the goggles.

Nine months after his surgery, Kotsovolos quit his job at the Duke Eye Center, took a 25 percent pay cut and started work as business manager in the Duke University Medical Center’s gastroenterology division. He is organizing a support group for LASIK patients with complications.

“It may help inform people that this is a surgery with real risks that are understated by LASIK surgeons,” Kotsovolos said.

Alan Carlson, head of the Duke Eye Center, said his experience with LASIK is that complications are rare. Carlson, who did not operate on Kotsovolos, said only a handful of the roughly 6,000 LASIK patients he has treated at Duke since 1996 ended up with problems. The eye center does very well in patient satisfaction surveys, he said.

But Carlson acknowledged that the procedure can cause serious complications.

“It’s imperfect surgery in an imperfect world,” he said.

How many LASIK patients develop post-surgery complications is obscured by a lack of regulation and reporting. Because health insurers don’t pay for LASIK, they generally don’t track complications. The FDA doesn’t require reports from doctors, and regulatory enforcement has been largely limited to recalling malfunctioning lasers.

Post-LASIK lenses

Evidence of problems is accumulating. Some of the strongest is the growing market for contact lenses designed for people who have undergone LASIK and still have vision problems, some seeing worse than before the surgery. One of the leading post-LASIK lens makers is MedLens Innovations, a Front Royal, Va., company founded in 2000.

Robert Breece, an optometrist and MedLens’ president, said his company provides hard contacts to more than 2,500 post-LASIK patients annually and business is increasing about 10 percent every year. Breece said his company serves more than 200 people per year who have been seriously disabled by the surgery.

“I don’t get to talk to happy LASIK patients,” he said.

By the end of the year, SynergEyes of Carlsbad, Calif., plans to bring to market the first line of contact lenses designed specially for laser eye surgery patients with complications who cannot tolerate hard lenses.

A trial version of the SynergEyes contact lenses have given Paula Cofer, 49, of Tampa, Fla., some relief from dry, itchy eyes and night vision so distorted that she sees up to eight moons.

The specially fitted contacts cost $300 every six months, Cofer said. Contact lenses solution, sterile saline solution, artificial tears and lenses rewetting drops run another $150 to $160 per month.

“Life was very simple then,” she said about the 30 years she wore glasses. “Now, it’s very complicated.”

Limitations of LASIK

Patients with complications are starting to fight back on the Internet and through support groups. Medical research in the past three years has come up with insights about LASIK worrisome enough that some eye surgeons have begun to ease away from the procedure.

“We’ve learned the limitations of LASIK,” said Dr. Stephen Pflugfelder, professor of ophthalmology at Baylor College of Medicine in Houston.

An expert in laser eye surgery for more than 15 years, Pflugfelder is increasingly falling back on an older, less invasive procedure known as photorefractive keratectomy, or PRK, which involves only the surface of the eye.

In the past three years, the number of LASIK procedures at Baylor has dropped from about 70 percent to about 50 percent of all laser eye surgeries.

At Duke, LASIK makes up about 80 percent of all laser eye surgeries. Carlson, head of the Duke Eye Center, is comfortable with that.

“Dry eye hasn’t been a big problem,” he said.

The university buys the most sophisticated lasers on the market, he said. Patients are screened for risk factors and informed of what they can and cannot expect from LASIK. A surgeon might even do the surgery on one eye at a time.

Those precautions did not prevent Lauranell Burch, a former Duke medical researcher, from suffering a serious complications after undergoing LASIK at the Duke Eye Center.

Burch 47, said that since the surgery March 31, 2004, her eyes sting and burn all the time, her eye tissue is wrinkled like a Ruffles potato chip and her night vision is distorted.

“[The damage] is noticeable and on the front of your mind all your waking hours,” Burch said. “There’s no escape.”

In the winter, she takes an anti-anxiety pill about 15 minutes before she drives home in the dark from her job in Research Triangle Park. She compares the distortions she sees at night, also known as star bursts, to explosions of light without a bang.

Burch cut short her follow-up treatment at Duke, became an avid patients’ advocate and started to take on LASIK surgeons on the Internet.

Risks of high volume

All LASIK surgeons make an effort to screen patients, and many turn away patients with obvious risk factors.

But LASIK is essentially a buyer-beware procedure.

In choosing a surgeon, patients are usually advised to go with doctors who perform the procedure most frequently. But with LASIK, That advice can be risky.

Dr. Christopher Fleming, a Cary ophthalmologist and former president of the N.C. Society of Eye Physicians and Surgeons, said patients should beware of LASIK surgeons who perform a high volume of operations.

Surgeons who do 10 or 15 LASIK operations a week tend to contract with optometrists who refer patients, Fleming said. In return, the optometrists, who are not medical doctors, screen the patients and do the follow-up care. Some also receive referral fees.

The emphasis on volume, Fleming said, can draw patients into surgery whose eyes are not suited to LASIK. Patients also end up getting follow-up care from optometrists instead of their surgeons.

Fleming performs no more than one or two dozen LASIK surgeries a year and personally screens patients and does the follow-up care. As a result, his patients rarely have complications, he said.

“When you’re high-volume and relinquish part of the care to non-physicians,” Fleming said, “you don’t have time to be thorough. That can lead to problems.”

What deters lawsuits

How many North Carolinians have problems after LASIK is not a public record. Patient complaints filed with the N.C. Medical Board are confidential, and the data are not organized by medical procedure.

Only a few complaints become lawsuits, said Bill Faison, a well-known medical malpractice lawyer in Durham who has represented one LASIK patient in court in the past three years.

What foils most attempts to sue for damages, Faison said, are the costs to mount a legal challenge. Also, carefully worded patient consent forms spell out the risks of the surgery and often require patients to first try to work out their differences with the LASIK center.

“Short of the [LASIK surgeon] being stupid, if it’s just a bad outcome, there’s nothing to recover,” Faison said.

The procedure is safe and effective for many, said Dr. Brad Randleman, a laser eye surgeon at Emory University in Atlanta who has done LASIK on about 1,000 patients over the past five years.

Post-surgical complications such as dry eyes and vision distortions often subside after a few weeks.

“I had nothing but a great experience,” said Jim Branch, 55, a Raleigh real estate developer who had LASIK at Duke about five years ago.

Medical research has found that cutting the cornea permanently weakens it. The severed nerves need years to recover and might misfire pain signals. But those findings have not been conclusively linked to lingering complications from LASIK, said Dr. William Bourne, an ophthalmology professor and LASIK surgeon at the Mayo Clinic in Rochester, Minn.

“I don’t think we’ve proven what it is,” Bourne said.

A better understanding of what causes the complications is essential to screen patients more effectively and eliminate those at risk, he said.

Kotsovolos said he was considered a good candidate for LASIK. His Duke LASIK surgeon blamed part of his problems on an eye inflammation unrelated to the procedure. Another eye specialist has since diagnosed Kotsovolos with a severe dysfunction of the glands lining the eyelids. The condition is considered a red flag when it is found during screening for LASIK.

Charles Hybarger, a building contractor who lives near Chattanooga, Tenn., changed his mind about LASIK after his wife, Kim, a 44-year-old trained nurse, had an unsuccessful procedure Dec. 21 and the complications triggered a deep depression.

Hybarger wonders whether his wife’s rheumatoid arthritis should have eliminated her from having LASIK. Laser eye surgery should not be done on patients with auto-immune diseases.

“I wouldn’t let any doctor cut on me unless it’s life or death,” Hybarger said. “I just wear my glasses and be happy with it.”

News researcher Denise Jones contributed to this report.

sabine.vollmer@newsobserver.com or (919) 829-8992

Industry’s Influence on Medicine

Cataract & Refractive Surgery Today

July, 2007

http://www.crstoday.com/PDF%20Articles/0707/CRST0707_Letters.php

Michael P. Graham, MD

Orlando, Florida

Quote: …the leaders in our field have become so corrupted by accepting large consulting fees from industry that they are no longer unbiased sources of information.

Quote: It is a sad step backward for ophthalmology when, due to the corrupting influence of corporate consulting money, I feel anecdotal evidence is more reliable than clinical studies.

Quote: I would implore our leaders to do something about this sad situation. Please stop relying more and more on consulting fees for your income. You may not realize it or want to admit it, but it is having a huge effect on how you conduct your studies and what you say at meetings. It is also having a detrimental effect on our profession, because we now have nowhere to go to get unbiased medical information except to rely on our anecdotal experience. Please stop being drug representatives and return to being doctors. After all, that is why we all went to medical school in the first place.

Most “leaders” in the LASIK industry are paid consultants to one of the laser manufacturers. Here’s just a small sample of surgeons who are paid consultants:

http://lasik-flap.com/forum/viewtopic.php?t=189

The Dirt on Coming Clean: Perverse Effects of Disclosing Conflicts of Interest

http://www.journals.uchicago.edu/JLS/journal/issues/v34n1/340105/340105.web.pdf

Daylian M. Cain, George Loewenstein, and Don A. Moore

ABSTRACT: Conflicts of interest can lead experts to give biased and corrupt advice. Although disclosure is often proposed as a potential solution to these problems, we show that it can have perverse effects. First, people generally do not discount advice from biased advisors as much as they should, even when advisors’ conflicts of interest are disclosed. Second, disclosure can increase the bias in advice because it leads advisors to feel morally licensed and strategically encouraged to exaggerate their advice even further. As a result, disclosure may fail to solve the problems created by conflicts of interest and may sometimes even make matters worse.

<>

http://www.aao.org/aao/publications/eyenet/200612/opinion.cfm

Quote: Yet physicians are still influenced by gifts or incentives of minimal value.2 So the take-home message is clear. Disclosure may embolden speakers to introduce even more bias than they would otherwise, and listeners may not be able to discount biased information as much as they’d like.

<>

http://www.escrs.com/Publications/Eurotimes/06february/pdf/ETROUNDTABLE.pdf

Jean-Luc Seegmuller: “I don’t think ophthalmologists should admit their mistakes. It’s too dangerous, and I have seen several too-honest colleagues who were in a very bad situation afterwards, and we have tried our best to take them outside but it was very, very difficult.Admit the mistakes? No. Describe the facts and say ‘I have done that,’ but not say it was good or bad, but rather I have done that and this is the consequence and so it was like that, or the complication is like that. It’s too dangerous to say that I have done this and now you are in a bad situation.”

5 Questions with Lucio Buratto, MD

Cataract and Refractive Surgery Today

July, 2006

Excerpt:

“What is the biggest obstacle facing refractive surgery and refractive surgeons today?

In the past, we made similar mistakes around the world. We excited our patients about the possibility of extremely good results, and we treated too many patients (some nonexcellent indications); I would say we treated all (or at least the overall majority) of the patients who entered our respective practices. Not all of the patients we treated were really good candidates for surgery, and not all of them received the treatment with the best machines and technology available. Unfortunately, because we had some bad worldwide results, we received bad publicity in the media.

Therefore, patients may now be skeptical about refractive surgery. I know for sure that when I have the right patient, I can give them excellent results. Patients do not always trust the surgery or the surgeon anymore, because we promised too much in the past.

What advice do you have for new surgeons, with regard to managing their patients’ expectations and outcomes?

I would tell them to do less business and to take care of the patients they currently have. Unfortunately for many refractive surgeons, when they see a patient, they see dollars in their eyes and not a professional opportunity to improve quality of vision and life for their patient. It is not the same way for a cataract surgeon or a retina specialist, but it is a typical approach of a refractive surgeon. They should focus more on their patients and less on their incomes.

Read the entire article

Admit Mistakes, keep good records to protect against malpractice suits

http://www.osnsupersite.com/view.asp?rID=18043

OSN SuperSite Top Story 8/16/2006

BOSTON — Keeping detailed patient charts, documenting informed consent and accepting responsibility for errors when they occur can help refractive surgeons avoid costly malpractice suits, according to two attorneys speaking here.

“Patients lose trust with their doctor if their doctor minimizes or ignores their problems. Physicians should be aware of this, because if patients lose trust, they will look for other doctors or find their way to a plaintiff lawyer,” said Greg K. Zeuthen, a plaintiff attorney.

Mr. Zeuthen and Kevin E. Oliver, a defense attorney, discussed the current medicolegal climate in refractive surgery in two keynote lectures at American Society of Cataract and Refractive Surgery Summer Refractive Congress. They outlined LASIK cases they have handled in court and possible approaches surgeons could employ to avoid litigation.

Mr. Oliver said he tells doctors to imagine a hypothetical situation in which all their charts have court exhibit stickers on them. He then asks them to carefully consider whether those charts are well-documented and adequately clear to be used in a defense or a prosecution.

“You need to chart everything,” Mr. Oliver said.

Mr. Zeuthen noted that draconian documentation is the key to minimizing the risk of legal action. Should a case go to trial, it is also important for mounting a defense.

“Paranoia is not bad at all,” Mr. Zeuthen said. “It’s just a higher state of awareness. If you practice medicine with a higher state of awareness, you’re going to avoid more lawsuits.”

Both lawyers noted that surgeons should be honest when dealing with refractive surgery mistakes or errors. Most refractive surgery patients are highly educated individuals who understand the legal system and will sue if not treated appropriately, they said.

“It’s how a bad outcome is dealt with in your office that determines whether a patient will go to another doctor of to a plaintiff’s lawyer,” Mr. Zeuthen said.

<>

EyeWorld

June, 2000

http://www.eyeworld.org/article.php?sid=1180

Quote: When it comes to dealing with the unhappy patient, the temptation may be for the practitioner to deny that a result is less than optimal or to avoid the patient altogether.

Quote: Maloney spends a half-day a week just dealing with patients with LASIK complications who have been sent to him on referral. “It’s difficult, because generally they don’t get to me until there has been some fracture in the relationship with the surgeon,” he said. If he can, Maloney reassures the patient that the surgeon didn’t make any mistakes.

<>

EyeNet Magazine

February, 2007

Excerpt:

Quote: But what about the patient who is the victim of a medical error?

Most risk management experts, including those at OMIC (Ophthalmic Mutual Insurance Company), recommend immediate and full disclosure of the error, as soon as the patient is able to understand.1 What is not as widely practiced is a heartfelt personal apology to the patient by the physician. An editorial by the chancellor of the University of Massachusetts Medical School, Aaron Lazare, MD, is well worth reading.2 Considerable literature has now accumulated showing that, where it is practiced, disclosure of errors and an apology to the patient has actually reduced the number and cost of malpractice claims. According to Dr. Lazare, there are four parts to an effective apology: acknowledgement of the offense (who, what, where); an explanation of the circumstances bearing on the offense (why); an expression of remorse, shame, humility and a commitment not to repeat the offense; and finally reparation (which could include early scheduling for next appointment, cancellation of the bill, etc.). Not all four parts need be present in every case for an apology to be effective, but an ineffective apology can usually be traced to omission of at least one part.

How do apologies heal? To understand this, it is helpful to examine how a patient feels when he or she learns of a medical error. They often express humiliation, “I was treated like I was on an assembly line,” powerlessness, lack of validation of emotions, the feeling that they were somehow at fault, and, not surprisingly, concern that the same thing could happen to someone else. The longer those feelings fester, the more difficult they are to mitigate through apology. But a prompt and proper apology can make the patient feel cared about by the physician, whose self-humbling has leveled the emotional field between them. Showing a patient how their experience will lead to changes in procedure to avoid recurrence restores their sense of power. Validation of the reasonableness of the patient’s feelings about the error is also helpful in reducing their amplitude.

Read the full article

“In the case of LASIK, patient outcomes showed that visual outcomes became more unpredictable and unstable as refractive error increased.”

Read The Full Story

The Threshold Concept

Most traits we can measure in humans vary continuously. Like blood pressure. Blood glucose levels. Corneal thickness. Plot the measurements you obtain for any such trait across enough individuals and you obtain a bell curve. Individuals at the extremes of the bell curve are more rare… and if the measurement you’re making is a physiological measurement, there may be a disease process associated with occupying the extremes of the bell curve.

Extremely high intraocular pressure may mean glaucoma.

Extremely thin corneas may predispose to ectasia.

The threshold concept: there is a certain physiological value or threshold, when crossed, results in disease symptoms.

LASIK patients, on average, have lost more than 40% of their corneal nerve density 3 years after LASIK. This may leave a young male, who is in a low risk group for dry eye asymptomatic, while a middle aged female who has lost a similar % of her pre-operative nerve density may experience debilitating dry eye.

Same situation with contrast sensitivity. All patients lose contrast sensitivity… depending on age and other factors, not all of them experience this loss as disabling/debilitating.

An important point is that all patients who have LASIK lose some visual and neural reserves. This means as they age they may cross the threshold to a symptomatic and/or disease state sooner.

People who never would have lost their ability to drive at night or enjoy comfortable vision may lose these abilities at middle age or even sooner because of laser eye surgery.

The point is that refractive surgery has robbed millions of their visual and corneal nerve reserves.

Millions of Americans have been pushed nearer the threshold for dry eye, loss of functional night vision, and corneal failure (ectasia).

The Eyes Are The Windows To The Soul

Contributed with permission by Meredith Perry

The eyes are the windows to the soul. And the relatively new LASIK procedure supposedly can make those windows crystal clear.

This quick and painless procedure produces perfect vision.

LASIK surgery has helped millions of people see clearly, yet for a small, but growing number of patients the procedure has not helped, but hurt. For Dominic Morgan the surgery seemed like a dream come true — but turned out to be a nightmare.

“I had my surgery done April 23 and April 30, 1998”.

Dominic’s surgery did not go as planned, and now he suffers the consequences of that ten minute procedure every day of his life.

“I had problems from the get-go”.

Dom’s problems included halos, glare, blurry and fluctuating vision, and starbursts. But for thousands, basic LASIK surgery is simple and harmless.

Dr. Sarah Hay performs LASIK. “I’m going to put drops in your eyes and numb your eyes. The surgery does not hurt. I’ll put the speculum in so you don’t have to worry about keeping your eyes wide open. I’ll put that suction ring on to create the flap, then I’m going to ask you if you see that aiming light. Also when I put that suction ring on you do lose your vision for a little bit, and I’ll remind you of that before I do it. The pressure you feel does not hurt like the pressure on your arm with a blood pressure test. I’ll ask you if you see the aiming light, and it is very important that you tell me you see it, because that is where I need your cooperation. I’ll lock on the tracker and tell you how long it will take for the laser to treat your prescription. Now when you get up some of you will think a miracle just happened, but it is normal for your vision to be blurry. Well, I’ve cut your cornea, fired the laser, rinsed it, reattached it and lubricated it. It is not going to be clear right away. The next day everybody should be functional”

And it was for Dr. Hays’ LASIK patient Jackie Small. The surgery was painless and successful. Can it be this easy? Don’t throw away your glasses quite yet.

Dominic Morgan wanted to get LASIK surgery so he could do just that – throw away his heavy glasses.

“I had big thick glasses, and they kept sliding down in the summer time because the glasses were so heavy”.

LASIK advertisements can be seen everywhere. And they all have one thing in common – promising the end of glasses. So the public is led to believe LASIK equals a life without glasses. That’s not entirely true.

“Then you can have reading difficulty. So that will not change. That deteriorations due to aging is going to happen whether or not you get LASIK. That will still bring about reading deficiency, and you might have to get reading glasses. And a very small percentage will have distance deterioration” says Dr. Ming Wang.

Dr. Ming Wang of Nashville, Tennessee dedicates most of his time to LASIK patients with complications – patients similar to Dominic Morgan. Dom, as he likes to be called, had retinal problems since he was an infant due to his premature birth.

“They (doctors) told me I was a good candidate. I went to their retinal doctor and he said I was fine”.

Dr. John Herman says “My statement to virtually everyone I’ve ever talked to about this – three out of four maybe nine out of ten people who had laser vision correction were not good candidates – meaning the ones with complications”.

Dominic said the same of his doctor “In August I saw another doctor out of curiosity. The doctor told me I should not have been considered for surgery. Every cornea specialist I have talked to since them told me the same thing”.

Dom wishes he would have consulted those doctors before his surgery. His piece of advice is to seek many other opinions before the laser hits your eyes.

Dr. John Herman of Pittsfield, Massachusetts says there are many tests that need to be done before considering LASIK. And most LASIK places overlook them.

“When they look at your eyes before laser surgery there is a lot of things they don’t do. In my opinion it’s an inadequate report that comes out of those places”.

Dr. Ming Wang states – “First and foremost you need to make sure you are a good candidate. Second is the instrumentation. It is very challenging for a person to figure out the differences between all of the lasers. Ask other doctors”.

And Dominic Morgan wished he had done just that. Because if he did he might not be where he is today.

(VISUAL SHOT OF QUESTIONNAIRE) – Dom found out his laser surgeon Anita Nevyas-Wallace had used a non-FDA approved laser. A laser her father Dr. Herbert Nevyas had invented. And later Dom discovered that there were eleven lawsuits because of that laser’s use.

“Since they dismantled their laser two years ago they haven’t had any lawsuits against them”.

Drs. Herbert Nevyas and Anita Nevyas-Wallace of Philadelphia did not hide the fact they used a non-FDA approved laser.

Dom stated – “They give you a series of questions. Afterwards you answer true or false. ‘The excimer laser used for my procedure has been studied and proven by the FDA’. I marked true. It was false”.

Dr. Herbert Nevyas invented the laser and used it on patients for research purposes, including Dom. He hoped to have it approved by the FDA. And Dr. Nevyas did not use the laser only on Dominic, but also on Joe Wills’ husband, Keith.

Joe Wills states “Dr. Nevyas called him to delay the enhancement surgery. At that point he told my husband he would have to wait for the FDA approval. When we got to trial we realized he was using his own invention”.

Both Dominic and Keith sued the Nevyas’ – and they both lost.

” Philadelphia courts ripped my case apart. I was not allowed to bring in anything pertaining to the FDA” Dom said.

Because Dominic could not bring the fact of the non-FDA approved laser into the trial he could only sue on negligence. And Dr. Nevyas said he had no way of knowing the surgery would fail.

Less than one percent of patients who have received LASIK have experienced serious, vision-threatening problems – like Dom’s. The incidence of less serious complications such as halos and glare is between 3 and 5 percent.

Dom states “Nighttime was a joke. I had the glare, I had the ghosting, I had the starbursts. I couldn’t focus on anything. I expressed my concerns to them and they just kept telling me as my eyes healed, I’ll lose all of that and I’ll get better. They told me it would take up to three months the first time. Then three to six months. Six to twelve months, and then after a year they told me because of my problems I had, because of the history I had, it could be longer. And then they told me it could be permanent”.

Joe Wills describes her husband’s adverse effects from the surgery, and they are eerily the same as Dominic’s.

“My husband is legally blind at night and has multiple vision. He has the glare, the halos, the foggy vision”.

And like Dominic, there is no cure for Keith’s vision.

“When my husband had his two year anniversary of his surgery, he was supposed to go in for another evaluation. They told him to go for a second opinion and they evaluated him and told him there was not enough cornea left to repair his eyes”.

So what went wrong with these surgeries? Is the laser to blame? Or the doctor?

Joe Wills – “Dr. Nevyas told him to look at the red light. My husband told him he could not see the red light. And it got real quiet in the operating room and there were whispers amongst the doctor and his assistants. The doctor left the room and then came back in and asked again if he could see the red light. My husband said he couldn’t. The doctor then told him to look as straight as he can and don’t move your eye”.

Dominic was once a mainframe computer operator making 50,000 dollars a year. He is now legally blind and living on disability Social Security.

“I was working, I was driving, I was doing everything anyone else would do. I don’t do anything anymore – I can’t even sit at a computer at length. There’s no clarity to anything. I have total loss of night vision. I did read quite a bit, now I’ll pick up a book, and I was used to going through it in two days. Now it takes me a couple of months. The book is up to my face like this”.

These complications are never mentioned in advertisements.

Dr. Ming Wang States “I think there is too much advertising of only the good in LASIK surgery. The general public should be educated about risks and limitations. LASIK surgery should be looked at with a balanced viewpoint. First and foremost like all medical procedures it has risks and complications. And very often I have patients saying make me have 20/20 vision. And I say can you name a medical procedure that is perfect? Why should the laser vision correction be any different?”

And that is a great point. LASIK has been extensively advertised as being a miracle surgery – but there are risks involved. And as with any surgery some patients come out happy, while others deal with complications. Diana Howard, of Birmingham, Alabama, dealt with the complications. Her eyes were under corrected, and eventually she had to get the surgery done by another doctor, and pay for it a second time.

“I went to this place and I had my surgery done, and I complained because I noticed my eyes were not corrected, and I told them the problems I had and they never called me back. So I sent them a letter saying that I had problems and that I wanted my money back or the surgery to be corrected. I never heard anything from them again. A couple of months later I read in the paper where they had a bunch of people who sued because the place I went for the surgery apparently the calibration of the laser was incorrect. So a lot of people had problems. But I didn’t know about the lawsuit until I read it in the paper. And by that time it was too late to do anything”.

Diana might have thought it was too late for legal action, but Dr. Herbert Nevyas did not. He is now suing Dominic. That’s right – he is suing Dom.

“They are suing me because of my website. The point of my website is to let other people know there are risks, to be very careful if you are not a candidate, such as myself. Don’t be misled”.

WWW.lasikdecision.COM states Dom’s feelings about LASIK and Dr. Nevyas very clearly. But Dom says his intention is not to discredit the Nevyas’.

“My intention is strictly to put the truth out there”.

Dominic’s problems all began with a non-FDA approved laser. Technology causes some of the botched surgery. But lack of training also creates LASIK complications. Currently the medical boards across the country are only requiring a weekend training course for LASIK surgeons.

Dr. Herman states “It turned out they had a training session for optometrists and a training session for surgeons. Well I couldn’t make the session for optometrists so I knew the guy in charge and I called him up, and I went to the one for surgeons. Basically the training session was the same as the weekend before for the optometrists. And I could remember driving home saying to myself these cataract surgeons are going to go do laser surgery next week. So the bottom line is there are no stringent rules applied to the surgeons themselves”.

And Dr. Ming Wang “I think we need to go back. Would you allow a surgeon to perform open-heart surgery if all he got was a weekend training?”

“It’s a weekend course – and they don’t do human eyes. They do cow eyes, and then they are ready to do human eyes? And if you spoke to most surgeons although they would be defensive because it is their system. If you got a couple of beers in them they would say it’s nonsense” says Dr. Herman.

Laser surgeons cut the cornea with a microscopic, hand-held razor during laser surgery. This is the most dangerous part of the procedure and where the most risk is involved.

Dr. Ming Wang states “The cornea is the thickness of a couple of strands of hair, and a laser surgeon has to cut a flap in the cornea using a hand-held razor. They must do this without cutting through the cornea”.

“My guess is there’s more surgical errors than there are bioengineering errors” notes Dr. Herman.

Lawsuits, lasers, insufficient training, the FDA – LASIK surgery has never seemed so complicated. What happened to that quick and painless surgery we all know and love? It never existed.

“Every citizen should go by the fundamentals. Make sure you are a good candidate, make sure you have the best technology. Ask other doctors where you would go for your own eyes” cautions Dr. Ming Wang.

The eyes are the windows to the soul. And you never know what you have until you lose it.

Dom adds, “Socially I use to go out. I use to go to bars. I use to do a lot of traveling – going fishing, casino (laughs), now I don’t like to do anything especially at night. You can’t enjoy what you can’t see”.

Due to litigation from a patient previously interviewed this article has been edited to remove all reference of patient.

An Eye For An Eye: Professor O’Reilly Speaks Out

I wish to acknowledge with much appreciation for contributing with permission to post on this site by Professor James O’Reilly the following study on Lasik liability exceptions:

E-Text Version of article published in 71 Univ. Cincinnati Law Review 541 (2003), copyright Univ. Cincinnati 2003  AN EYE FOR AN EYE:

FORESIGHT ON REMEDIES FOR

LASIK SURGERY’S PROBLEMS  Prof. James O’Reilly1

SUMMARY:

… Laser eye surgery is remarkable. … ” The FDA requires device sponsors to report the number of patients who seek a second LASIK procedure to improve vision after the first surgical results were inadequate, but “no laser company has presented enough evidence for the FDA to make conclusions about the safety or effectiveness of enhancement surgery. … Night vision deficiencies are “one of the main challenges” to improving laser eye surgery. … The bold and attractive promises being made in LASIK advertising by eye surgery marketing corporations, some of whom are publicly traded entities, may give rise to express warranty claims as well as claims against the individual surgeon or the surgeon’s corporate entity as conventional malpractice claims. … The FDA has jurisdiction over the advertisements for a prescription medical device and, although the FDA requires that warnings be stated for prescription drug ads made to consumers, it does not require the same communication about risks in LASIK advertising. … The injured LASIK patient’s compensation claim against a LASIK device maker is likely to be barred by the Supreme Court’s interpretation of the Food Drug & Cosmetic Act to prevent state verdicts asserting design defect claims against FDA– approved medical devices. … 

TEXT:

[*541]

   I. Introduction

   Laser eye surgery is remarkable. Never before in American medical history have 3 million people each year responded to massive advertising by paying for an innovative, elective surgery. Never before have surgeons competed so vigorously on price; and never has a surgery been so skillfully isolated from liability lawsuits. If LASIK eye surgery becomes the Mass Tort of 2025, will Americans regret accepting it as the benign 20/20 solution of today?

   The first decisions in a series of liability suits against LASIK surgeons have been reported, with one plaintiff receiving a $ 4 million verdict. n1 Yet, the procedure is too new for a body of reported appellate precedent, so this review must be a forward-looking prediction of future judicial behaviors. This article examines the conundrum that an injured LASIK patient, whose vision deteriorates several years after the surgery, may be unable to find a viable defendant, thus leaving the customer without an effective remedy.

   II. Understanding the Context

   What is LASIK Surgery?

   Open your eyes, read a newspaper, watch a television, see a billboard, and elective surgery advertising hits your eye. From thousands of dollars down to hundreds, the competition to sell this mass volume elective surgical procedure has driven down prices. The specific service that was to be provided to an estimated 3,135,000 patients in 2002 is LASIK. n2 LASIK is the acronym for “laser in- situ keratomileusis,” a form of computer software-guided cutting of the cornea in the eye using [*542] laser light beams. LASIK and other eye surgery procedures n3 flatten the central curvature of the cornea of the eye, with a flap of skin peeled back in order to effectively alter the ability of the eye to see without external spectacles or contact lenses. A Pennsylvania court summarized the mechanics of the LASIK process in a succinct summary:

   During the LASIK procedure, after the surface of the eye has been anesthetized by eyedrops, a microkeratome is used to create a flap in the outer layer of the cornea which is folded back to allow an excimer laser access to theexposed corneal surface. Computer-controlled laser beams then remove thin layers of corneal tissue to reshape the curvature of the cornea so that visual images will focus directly onto the retina, thereby improving visual acuity. The corneal flap is returned to its original position without utilizing sutures, and a protective “bandage” contact lens is applied to prevent the eyelid from rubbing against the eye surface as the outer layer of cells regrow and the flap re-adheres. n4

   Measurement of the eye and setting the correct parameters into the computer- controlled laser equipment appear to be the principal determinants of surgical success. An experienced surgeon can perform many surgeries in the same day by using the staff of an outpatient surgery facility to prepare the patient. Though the equipment is constantly being improved, the computer controls depend on the accuracy of the data being fed into the system by a skilled surgeon during the pre-surgical evaluation of the patient.

   The reader may choose to read more of the technical details of the surgery elsewhere. n5 This paper will deal with LASIK, but some of the issues are relevant to other processes. Relative to older forms of such refractive surgery, LASIK does not appear to produce greater glare or halo effects during the early stages after surgery. n6 However, the long-term consequences of LASIK are still unknown.

   Is LASIK Surgery Safe?

   As with any surgery penetrating through body tissue, cells are affected by the cutting of corneal tissue. The eye cells heal differently with [*543] different patients whose personal health and other characteristics will affect recovery. In the event that slowly-developing cellular changes in the cornea may cloud the vision of LASIK patients in future years, we simply do not know how a LASIK procedure’s adverse effects will manifest themselves. An experience base of five or more years may be needed to follow the progress of patients whose corneal cellular changes are manifested by slow blurring of the vision or the appearance of nighttime glare effects that hinder their ability to drive. This poses the same causation challenge that lawyers experience in other medical delayed-effects situations: the manifestation of eye deterioration attributable to the cutting of cells may be hard to differentiate from deterioration attributable to the effects of normal aging or of unrelated eye problems. For the short term, LASIK appears to be safe, with a small number of adverse effects, as discussed later in this article.

   Why Is LASIK Different from Other Surgical Procedures?

   Surgery is typically a drastic interventional response to a medical emergency or to the failure of an organ or bone system. Any surgery carries risks, especially the in-patient surgery that involves the risk of hospital-related infections. The development of skilled surgical techniques involving micro-surgical interventions has made American surgical capabilities well respected around the world.

   But not all surgical interventions respond to health necessities. Persons who find contact lenses annoying or spectacles inconvenient are being pressed to “try the safe and affordable alternative: LASIK.n7 Americans are willing to pay for various types of elective surgery for anatomical flaws and cosmetic defects. Because the word “cosmetic surgery” draws angry rebukes from eye surgeons, the LASIK processes can at best be called “improvements on nature,” rather than the classic use of surgery for a needed remediation of injuries. The wave of 3,300,000 annual LASIK procedures in the United States may be the greatest volume of surgical procedures ever voluntarily undertaken by consumers in the history of medicine. n8

   The sales target for expanding LASIK is thirty-five percent of the 180 million Americans who may need vision care. n9 Of course, such a goal is ambitious, and it amplifies the concern that even a small percentage [*544] of damaged eyes might mean that tens of thousands lose their optimal eyesight as a result of flawed surgery. The market’s size is great and the potential downside for a fraction of that population could produce substantial damages. One symptom of the fluid nature of change in this marketplace is the way in which the manufacturers earn their profits: new eye lasers, once approved, are leased to surgeons in return for a per-surgery fee, with new equipment emerging continually in a hot, competitive climate.

   III. The Regulatory Context

   FDA’s Twelve-Month Norm

   A traditional question arises again: how much of a database of safety experience should society demand before a new technology is “safe enough” for use on humans? The Food and Drug Administration (FDA) has statutory jurisdiction over medical devices. n10 The FDA has used this authority to specifically approve numerous laser devices for surgical use on the eye. n11 So, it would then seem that the consumer expects to be fully protected by prior government approval before the LASIK device enters the competitive marketplace.

   But, the human clinical studies of comparative surgical results, needed for FDA approval of a new laser eye device, are only required to study patients in the small test sample for twelve months post-surgery. Some studies go to twenty-four months, continuing after the approval of the new device. n12 The laser device maker must supply extensive information about the machine from which the FDA can evaluate the safety and efficacy of the design, and these “premarket approval applications” can be voluminous. n13 But the experience base is relatively short and cannot be expected to catch long-term deterioration effects on the eye, if such effects occur. This does not mean LASIK is going to be found to have a higher risk than we now expect-we just do not know. If ill effects do not arise among the three million customers per year, then a definitive risk conclusion can be made at some future date.

   [*545]

   A review of the FDA website’s summaries of product safety for the approval of new laser devices n14 consistently shows that manufacturers submit, and the FDA grants approval based upon, twelve months’ experience with the new laserdevices. The FDA examines both the adverse events reported during the twelve month post- surgery follow-up and the complications from surgery reported by the surgeons. The FDA’s Office of Device Evaluation in the Center for Devices & Radiological Health then makes a decision about the product’s acceptability. n15

   The protection of LASIK surgery patients by the regulatory intermediary, the FDA Office of Device Evaluation, is premised on experiences of up to twelve months post- surgery. By its own public admission, the post-approval examination of medical devices “is not working well.” n16 The FDA requires device sponsors to report the number of patients who seek a second LASIK procedure to improve vision after the first surgical results were inadequate, but “no laser company has presented enough evidence for the FDA to make conclusions about the safety or effectiveness of enhancement surgery.” n17 Possibly, vision effects may be manifested after a longer period, as reports slowly arrive that demonstrate evolving patterns of experience with clouding of vision as cells change. Such effects might be noticeable after several years have passed: for example, when a patient changes eye doctors and complains about the results promised by an earlier eye surgeon who sold a LASIK procedure as the ideal solution for that person’s desires.

   In the liability claims context, the time of reported effects becomes significant. Corneal surgery of various types has a long history, but LASIK’s laser/computer interface combined with mass marketing isa relatively recent novelty. A few warning flags are visible in the medical literature, n18 but no one can reliably predict the percentage of ten or twenty-year post-surgical experiences that will be adverse for LASIK patients. It may be that LASIK produces no adverse long- term effects. [*546] On the other hand, LASIK might cause a more rapid and serious cellular degeneration than other causes. The nexus of uncertainties regarding cellular change, rates of deterioration, the value of a twelve month pre-approval study as a predictor, and patient intolerance of vision problems, make for an intriguing challenge to the would-be tort plaintiff.

   How are the Surgeons Regulated?

   The FDA has no jurisdiction over physicians such as the surgeons who use the laser equipment. n19 The FDA requires adequate labeling for proper use by physicians n20 but cannot police the physicians themselves. Surgeons’ performance is left to the state medical boards n21 and to the private malpractice system. n22

   The FDA tracks post-approval rates of injury under its Medwatch program of voluntary adverse effect reports on medical devices, n23 as explained on the FDA’s Center for Devices website. n24 The surgeon who finds a malfunctioning LASIK device could file a report online with the Medwatch system but is not required to do so. Congress responded to complaints by manufacturers and hospitals, severely restricting the FDA’s medical device user reporting authority n25 in the 1997 amendments to the device statutes. n26

   IV. The Liability Context

   Identifying Causes of Action

   At the rate at which LASIK surgery is being sold to new patients, even a small percentage of vision loss claims-a fraction of the millions of cases-could produce a significant volume of potential tort suits. This is a statistical certainty, since the smaller occurrence of adverse eye [*547] effects would become manifest slowly, as the several millions of LASIK recipients age during the years since their eyes were cut by the surgery. n27

   The classic tort negligence test requires a showing of foreseeability of the injury and fault by the responsible product manufacturer or physician. Modern strict liability imposes a compensation obligation on the manufacturer of a defective product regardless of fault n28 and leaves malpractice law to remedy the problems caused by the professional user of the device. Strict liability shifts the costs of injury to the designer and marketer of the product that caused the injury, without the need to show fault or even proof that the injury was foreseeable. n29

   However, strict liability is a policy that carries an important exception-it does not apply if the product offers a special societal benefit like a rabies vaccine or an important pharmaceutical to cure cancer. n30 These latter products were deemed by the creators of modern strict liability to be “unavoidably unsafe,” and, thus, subject only to negligence law norms in order to prevent the advance of medical progress from being retarded by the costs of strict liability. n31

   The Third Restatement Shield

   One of the controversial aspects of the 1997 adoption of the Third Restatement of Products Liability was the virtually complete shield from strict liability for prescription drugs and devices that have any beneficial effect for any class of patients. n32 The concept holds that with the existence of a class of patients that will benefit from the device, the device can be sold for all other classes as well and will be immune from the strict liability analysis. n33 For example, leprosy is rarely encountered among United States residents, but a drug that was beneficial to leprosy [*548] patients would not be vulnerable to challenges against its marketing for some other medical indication, such as cancer. The express predicate for this exclusion from strict liability was that the FDA “adequately review(s) new prescription drugs and devices, keeping unreasonably dangerous designs off the market.” n34 If one believes the FDA achieves this goal, the Third Restatement makes sense.

   Eye laser devices benefit from the protective shield that the Third Restatement seeks to apply to prescription-only products. Arguably, the availability of laser surgical devices benefits some patients whose eyes are medically impaired and for whom the corneal surgery has a therapeutic purpose. A contrary argument can be offered, however, that three million annual uses of a surgical tool for appearance and aesthetics far outweigh the smaller number of uses of these devices for cases of real medical necessity.

   The Case of the Disappearing Defendants

   In the event that even a small number of LASIK patients experience eye difficulties later, a small fraction out of three million customers each year is still a substantial population of potential plaintiffs. A significant concern for these plaintiffs is that tort law lags far behind laser technology. Lasers are improved each year, but liability systems lag behind, so no compensation for injury may be available to the LASIK customer at the time when a belated manifestation of injury to the eye is diagnosed. If vision clouding problems appear, there may be no financially responsible defendant available against whom a plaintiff can obtain sufficient recovery. This is a particular problem when the longer-term cellular effects of today’s LASIK eye surgery manifest themselves years after the surgeon has been paid.

   In part, this tort liability phenomenon of “no viable defendant to sue” reflects business practices that emphasize the very short term orientation of the coverage of malpractice insurance for ophthalmic surgeons. The malpractice insurance industry seems well protected by its preference for “claims-made” policy coverage, the dominant form of new coverage. Such coverage pays claims made during the years for which the insurance was in force. The coverage would not shield the individual surgeon when a claim about delayed corneal blurring effects is made long after the brief LASIK operation is over. This makes a difference for the plaintiff because the absence of an insurance carrier diminishes [*549] the prospects that the plaintiff will ultimately receive damages after a favorable judgment.

   V. The Medical Context

   What Long-Term Issues Exist After LASIK Surgery?

   LASIK is widely performed worldwide “despite the absence of thorough data on the healing response and long-term complications at the tissue level. Clinically visible complications . . . are relatively well known, but the underlying cell biology of these phenomena is less well understood.” n35 One study found a loss of cells in a layer of the eye beginning six months after surgery, but the cause of this diminution is unknown and requires further research. n36 Corneal haze of several types “may degrade the retinal image” and more research is needed about its clinical impact. n37 These concerns are more long-term; issues concerning the flap of corneal tissue cut in the eye are among the near-term concerns of eye surgeons, as illustrated in American Academy of Ophthalmology publications. n38

   A frequently cited challenge for surgeons is “irregular astigmatism.” When the same eye has been subjected to multiple laser surgeries to improve on conditions initially reported by the patient after surgery, “corneal stability in the long-term is still a worrying factor,” and in individuals with a major degree of irregular astigmatism, loss of visual acuity is permanent and symptomatic. n39 Not all irregular astigmatism can be corrected; careful patient selection is often recommended. n40 The LASIK technique is too new for surgeons to understand the natural history of future effects of “central islands” on the cornea, which cause numerous detrimental effects. n41 For the estimated 165,000 photorefractive keratectomy (PRK) procedures done annually, “visually debilitating corneal haze may persist in approximately 5% of all PRK [*550] patients.” n42 Enhanced cellular reflections from high numbers of wound healing keratocytes are an important contributor to haze, and drugs may be useful to aid clarity of vision after PRK. n43 Night vision deficiencies are “one of the main challenges” to improving laser eye surgery. n44 Corneal scarring and keratectasia, or dilation of the eye, were a particular issue with patients who had multiple LASIK surgeries, with cautions for surgeons about third and fourth retreatments of the same eye. n45 A Utah researcher/surgeon noted the “paucity of peer review literature” to substantiate LASIK’s safety and efficacy and expected in a 1998 article that better computer software would reduce the percentage of patients who required retreatment-which was then at about thirty percent. n46 We simply do not yet know enough.

   VI. The Litigation Context

   Are Long-Term Effects Actionable?

   If a patient is dissatisfied with the resulting vision after LASIK, a second surgical procedure may be offered, but the literature cautions about more serious consequences with each successive cutting of the eye tissue. n47 Corneal perforation is rare, but other potential complications include ingrowth of the epithelial layer, infection, severing of the flap of skin cut in the cornea, wrinkling of the flap, and corneal astigmatism. n48 The longer-term effect of the surgery on cellular changes in the complex tissues of the eye is being studied, but time will tell whether the current favorable view of the surgery is altered by future studies showing eventual degradation in vision in a LASIK population compared to an uncut-cornea “control group.” As of now, evidence is unavailable. There are indications that the collective profitability for surgeons performing the procedure may inhibit other doctors from rendering [*551] critical second opinions about LASIK. n49 Regardless, the cases that have reached litigation have involved a variety of vision impairments, including disabling impairments for persons who need excellent night vision, such as pilots. n50

   Whether the individual’s impaired vision effects are worth litigating is a matter of judgment for the patient and counsel. The contingent fee system makes the plaintiff’s counsel somewhat reluctant to challenge multiple defendants on a cause of action that does not yet have substantial case law illuminating the duty and liability of the manufacturer and surgeon. The population of persons paying for this elective surgery tends to be somewhat more affluent than average patients, and for some of them, perhaps a later experience of complications will stimulate the search for legal relief on a fee-paid hourly basis. Counseling such a client to initiate damages litigation involves a number of considerations, including the unavailability of insurance carriers for claims that are made several years after the surgery.

   The causes of action would include defects in LASIK equipment design, defects in the knife-like microkeratome used to slice the cornea, failure to adequately communicate risks to the patient, failure to adequately warn of the long-term effects observed in the LASIK medical literature, and, perhaps, claims of breach of express warranty that the procedure is “safe” for the eye of the patient. The bold and attractive promises being made in LASIK advertising by eye surgery marketing corporations, some of whom are publicly traded entities, n51 may give rise to express warranty claims n52 as well as claims against the individual surgeon or the surgeon’s corporate entity as conventional malpractice claims. n53 Safety advances in the design of machines for laser eye surgery [*552] may have reduced the adverse effects that would have been seen with the earliest LASIK equipment, though an insufficient time has passed to form reliable statistical projections. An elaborate publicity campaign against criticism of LASIK has been launched by a trade group, funded by manufacturers using a national public relations firm. n54

   Plaintiffs confront numerous barriers, including the Daubert standard, n55 which allows equipment makers and surgeons to exclude the testimony of a critic of the LASIK device’s use if that critic had not passed the scrutiny of pre-trial screenings. A climate for product design liability regarding inadequacy of pre-market testing of the machines may exist when future claims are brought. The makers of the expensive laser equipment are rapidly altering and upgrading their machines and software as the marketplace demands rapid responses to competitors’ innovations.

   What Barriers to Recovery Exist?

   The first barrier to recovery will be time: if the now-reasonable balance of risk data and effectiveness were to shift against LASIK after five to ten more years of experience, the patient with blurred eyes must establish a causal connection to his or her present condition. The complexity of medical proof of causation would be formidable because many post-surgery events might have triggered the harm.

   Time also affects the viability of a damages claim by the impact of the statute of limitations on the ability of a plaintiff to sue for an effect that became evident long after the laser surgery was completed. A cause of action would arise either when the surgery was performed or when the plaintiff discovered the connection between the surgery and the plaintiff’s presently deficient vision. Plaintiffs could claim that they sued within a reasonable period after discovering that a tort had been committed, this “discovery rule” in torts would halt the tolling of the statute of limitations. n56 But, the degree to which any belated discovery of blurred vision can be tied to knowledge of the surgery-injury connection will be very fact-specific. This is not an easy issue for the plaintiff to reopen, several years after surgery. State medical [*553] malpractice procedures form an additional barrier against the potential plaintiff’s recovery. n57

   Effects of the Malpractice Crisis

   The second barrier will be a likely absence of malpractice insurance as a force for settlement. An immediately observable injury tied to malpractice can produce a sizeable claim and a large settlement, as demonstrated in a recent Colorado case. n58 But, LASIK’s cellular effect on the eye, if it occurs in a patient, will take time to develop.

   Timing is everything when insurance coverage is at stake, and here it will be central to the plaintiff’s attorney selecting the right contingent fee case to accept. There has been a significant rise in the use of “claims-made” malpractice policy forms, under which most medical malpractice carriers decline to pay claims that have not been presented to the insurer during the contract term or within a short “tail” thereafter. n59 This type of surgical malpractice policy contrasts with the “occurrence” policy covering the acts of the surgeon during the entire policy period, even if the claim is made after expiration of the policy years. n60

   The severe lack of profitability is driving some insurance carriers out of the medical malpractice insurance market. Aggregate 2001 industry statistics n61 show that about $ 10 billion was spent on health care malpractice insurance mechanisms in 2001, of which $ 5,586,584,000 was in insurance premiums. Loss ratios rose to 74.4% in 2000 from 54.3% in 1997. It is estimated that the malpractice insurance carriers’ combined ratios of loss and expense exceeded 133% of the insurance carrier’s income from premiums at the same time that income from [*554] investments was diminished by stock market declines. St. Paul Insurance Company quit the medical malpractice insurance market when its losses became too severe: in 2001, the major malpractice carrier lost $ 940,000,000 on medical malpractice coverage and halted all future policy renewals or new policies. n62

   If an adverse eye effect is only manifested some years after the surgery, the physician’s carrier will decline coverage because the patient’s vision deterioration claim was not presented to the carrier during the contract period of the “claims made” policy. The plaintiff is able to continue the suit against the corporate or individual entity that performed the service, but the likelihood of a major settlement payment diminishes without the presence of an insurance carrier at the negotiating table.

   Once the plaintiff’s lawyer learns that no insurance coverage exists for the belated claim, the corporate structure of the eye surgeon becomes very important to the plaintiff’s recovery efforts. n63 The corporate structures used to protect the surgeon’s own assets in an LLC or professional corporation may have been dissolved by the year when litigation begins. The surgeon is quite likely to have imprinted the corporation’s name on the documents to protect the surgeon’s personal assets. Propensity of the LASIK surgeon’s competitors to cut prices n64 and to reduce overhead leaves less residual cash for an insurance or loss reserve within the surgeon’s LLC. In short, there may be no viable defendant left by the time the plaintiff determines that LASIK caused the vision problems.

   Effects of Consent

   Consent forms present the third barrier to the plaintiff. The attractive models in the LASIK advertisement and the terrific price claims for throwing away one’s glasses will inevitably receive more visible space in advertisements for LASIK than the comparable visuals receive in prescription drug advertisements. That is because the surgical consent forms that contain the warnings only need to be presented at the time [*555] the buyer pays for the service. The FDA has jurisdiction over the advertisements for a prescription medical device and, although the FDA requires that warnings be stated for prescription drug ads made to consumers, it does not require the same communication about risks in LASIK advertising. n65

   The drafting of a surgical consent form is an art, at which defense counsel should excel. Surgeons have listened carefully to their defense counsel. If a LASIK surgeon is sued, the defense will argue that an ironclad consent form was executed by the plaintiff. The consent forms for laser eye surgery may be an extreme readability test for people who have selected one among several competing vendors for cheaper, faster and more efficient service for their eyes. The savvy surgical staff always has “one more form” to hand the patient to be signed. The person who has elected to get the surgery has probably signed the credit card receipt before signing all the other forms, including the surgical consent forms. The buyer of high volume elective surgery may be unaware that among the routine paperwork, the customer is signing away future rights by failing to focus on the consent forms. Breaking through this barrier to attack the failure to adequately warn will be a major inhibitor upon the willingness of the plaintiff’s bar to take these cases on a contingent fee basis.

   Effects of Preemption Defenses

   The reader may expect that, even if the surgeon escapes liability, the device manufacturer is still an available defendant for a compensation claim. Alas, preemption of state tort recoveries by federal statutes is the fourth barrier to be faced by an injured customer. The United States Constitution permits Congress to govern interstate commerce. n66 Congress responded to a concern about medical device safety by regulating the interstate sale of medical devices. n67 At the time the specific authority to approve new medical devices was delegated to the FDA, Congress answered the device manufacturers’ pleas by prohibiting the states from adopting “requirements” for medical devices that differed from federal “requirements.” n68 In the 1976 Medical Device [*556] Amendments, Congress preempted states from imposing medical device requirements that are in addition to or different from federal medical device approval requirements. n69

   In two cases, the United States Supreme Court has interpreted the device legislation to shield virtually all manufacturers of innovative medical devices. The injured LASIK patient’s compensation claim against a LASIK device maker is likely to be barred by the Supreme Court’s interpretation of the Food Drug & Cosmetic Act n70 to prevent state verdicts asserting design defect claims against FDA– approved medical devices. n71 The plaintiff in a LASIK case against a manufacturer must overcome the legacy of the device industry’s landmark victory in the 1996 Supreme Court decision Lohr v. Medtronic, Inc. n72 when combined with both the industry’s successful effort to win 1997 amendments to the FDCA n73 and the 2001 Supreme Court industry victory in Buckman Co. v. Plaintiff’s Legal Committee. n74 These efforts have collectively slammed the door on most causes of action for defective design of a medical device. n75 Suing the LASIK equipment supplier will be unlikely to succeed if the claim is related to design; claims of inadequate warning might also be blocked both by the FDA’s specific product labeling approval n76 and by the patient consent forms, considering the breadth of wording in the pre-surgery consent documents that are routinely signed by LASIK patients.

   Effects of Market Volatility

   Finally, the medical device market is both global and volatile. Rapid changes in technology are altering the competitive landscape. Additionally, the manufacturers of LASIK devices are entering and leaving the market more rapidly than manufacturers in more conventional medical fields. n77 The marketplace of laser makers is [*557] rapidly evolving, with some of the makers of today’s machines unlikely to be found in existence if cases arise several years hence, and others consolidating and merging assets, perhaps without retaining liabilities for past users of the equipment.

   It may be that the maker of the machine used in a 2001 surgery has disappeared entirely or is not doing business in the United States by 2011, when the LASIK customer learns that his or her serious vision problem was triggered by cellular changes in the aftermath of the surgery. Piercing the corporate veil is a rarity n78 and the device makers will presumably have acted within the law in their merger or dissolution of the corporate structures.

   Likewise, the physician who performs LASIK surgery as the agent of a corporation will seek to be shielded by the corporate form under state corporate laws, as occurred in a Pennsylvania LASIK negligence case. n79 The surgeon may attempt to structure the corporate shell as thinly as possible, so that the corporation or limited liability company can be terminated after a few years or will be insufficiently capitalized to pay judgments that arise from later-detected harms.

   The result of this litany of disappearing defendants is that the eye surgery purchaser of 2003 may be unable to gain compensation in 2013, if and when serious eye problems can be diagnostically attributed to the surgery. The maker of the device is shielded; the surgeon is shielded or the surgeon’s corporation is dissolved; and the malpractice carrier is excluded by a claims-made policy format. Clairvoyance is not required to recognize that LASIK’s future problems would bring calls for a legislative solution to the absence of compensation or remedy.

   VII. Solutions

   Suggesting a Pooled Reserve Solution

   A certain portion of those who claim a LASIK-induced eye deterioration will correctly attribute their harm to the surgery. Of course, for some injuries there is no compensation because an act of God or force of nature caused the harm: LASIK surgery, however, is the kind of expensive service for which the injured person will expect to be compensated should an unexpected harm occur. The adverse eye [*558] conditions will diminish occupational abilities for persons like airline pilots and will diminish the quality of life for all who depend on clear vision. Such harm would merit some form of compensation under tort law principles if the surgeon acted negligently, if the device the surgeon utilized was negligently designed, or if the plaintiff received inadequate warnings. But, the legal system involves the various limitations noted above, so tort law will deny compensation in most cases.

   Nature abhors a vacuum-and modern media and politics seem to abhor a remediless injured person. Federal compensation for mass injury situations is requested by victims and their advocates in numerous situations. But the actual passage of federal relief legislation is very rare. Agent Orange compensation to military personnel who had served in Vietnam n80 and swine flu vaccine for persons who developed a rare adverse effect are among the rare few. Relief by federal cash assistance to persons who had elective surgery is quite unlikely in this instance.

   The states can respond to future calls for compensation by requiring the insurance carriers who write surgical malpractice coverage to establish a sufficient reserve to be available for future claims. Perhaps in hindsight, such a reserve compensation pool should have been structured for asbestos and other chronic illnesses with belated onset. However, once the medical signs of future problems appeared for those products, the opportunity had passed. The later claims system has borne the higher transaction costs of that inactivity. A state insurance department imposing a surcharge on surgical malpractice policies could create the pool of funding, allowing for claims on the pool in future years to be adjudicated through the tort system, as it operates in the future. Claims for which a viable defendant or carrier exists would be required to be brought first against those viable parties.

   What Loss-Reserve Structure Could Work?

   In light of the probable unavailability of viable defendants for the compensation of longer-term LASIK injuries, as discussed above, this paper advocates the creation of a state-level statutory “risk reserve pool” to pay claims for which no other resources are available. The fund would be used as a limited compensation vehicle with a cap on individual benefits payable upon proof of the elements warranting compensation. Funding for the risk reserve would come from a required surcharge or supplemental coverage payment for the issuance of malpractice insurance covering physicians who perform elective, non- [*559] emergency eye surgery. The payments into the risk reserve pool would be made by the surgeons or their corporate structure, perhaps in the form of a state surcharge of fifty dollars per non-therapeutically indicated n81 eye surgical operation performed. The pool would be held by the state insurance department in escrow as a funding source for any future claims for compensation. If the funds were not the subject of claims for ten years, which seems unlikely given the size of the patient population receiving LASIK surgery, then the fund would dissolve with the surcharges returned to those physicians who “contributed.”

   In the event that a LASIK patient’s post-operative eye problems are persistent or appear at a point in time set in state legislation, claims would be made against the pool only if normal channels of compensation were foreclosed and only if the surgical event proximately caused the harm to the eye. The long-term negative consequences of these elective eye surgeries might manifest themselves after the plaintiff has found that the conventional routes of compensation, against malpractice coverage of the surgeon or against the device maker, are no longer available. The insurance excise charge would produce the “insurer of last resort” in the state insurance fund.

   Why a State Remedy?

   Since these surgeries are elective purchases of a medical service, n82 they have no federal Medicare cost consequence. These elective sur-geries are not paid for with federal funds, and are not usually provided as an employee benefit, so the federal rules that lead to ERISA pre-emption of state remedies are not likely to inhibit state legislators. At least one court has held that such surgery is not medically necessary but is elective. n83 The state primacy over such surgical activities will be mani-fested by state oversight of malpractice insurance terms and reserves n84 [*560] and by the medical licensure roles of the states. n85 The states that recognize a LASIK compensation issue would be free to employ their authority over insurance carrier policy conditions and loss reserves, as well as the state medical licensing powers over physicians practicing in this area of surgery.

   Of course, how the proposed LASIK injury compensation system will work is yet to be determined. State legislators will first have to hear from a constituency supporting compensation in numbers that can outweigh the power of the medical lobby and the LASIK machine manufacturers’ probable defensive alliances. If the experience with HMO legislation in Congress is any indication, many legislators will undoubtedly approach the task of drafting remedial legislation with a pro-patient approach.

   The compromise legislation that ultimately passes may set a standard for recovery from the fund that requires exhaustion of other remedies before a claim can be made to the state fund. Simplified administrative hearings before an administrative agency physician or panel of physicians, attorneys and administrators might be convened. The hearing could be similar to a disability benefits hearing, without the transaction costs of adversarial litigation. Causation of the eye condition will be the major fact issue for the adjudicator or panel, as a delayed effect of damage to the eye could be causally attributed to the LASIK surgery only after close attention to the eye’s present condition by an expert ophthalmologist employed as advisor to the panel. The plaintiff’s expert would be expected to meet informal norms of qualification, less stringent than the constraints on expert testimony under the Daubert n86 test or other state-law tests of expert witness testimony. Proof of causation could be somewhat relaxed in claims against the fund, perhaps with a set of presumptions concerning the vision deterioration effects of eye surgery and of aging as causal factors, when the legislation establishing the compensation scheme is created.

   The hearing could determine the current amount of eye impairment compared to an age-appropriate eye functions grid, fix the percentage of such current eye condition attributed to the LASIK surgery, and then determine whether another source exists from which benefits would be accessible to the claimant. Payments from the state fund would not be available unless the administrative official in the state department of insurance found sufficient credible evidence from competent medical evaluators that the vision conditions in the patient’s eye had been [*561] adversely affected by the results of the elective LASIK eye surgery and that the impairment of vision as of the time of a benefits application was causally attributable to the surgery. Awards could be set up to a maximum amount of compensation, perhaps $ 50,000. If there were a viable civil tort case to be brought, the compensation would not be pursued or might be deferred by the panel.

   Certainly, proponents of the relief legislation will argue for statutory presumptions that eye surgery caused the compensable deterioration while opponents of the statute, including eye surgeons and their malpractice carriers, will argue that the person who bought the elective surgery should be left with the consequences. The degree of relaxation of such proof of causation would likely draw intense debate in the state legislatures. The factual issue of causation based on competing expert testimony regarding the source of the eye deterioration will pose a tough question for the civil jury. If normal aging of the claimant’s eye tissue exacerbated the adverse effects of the laser slicing of the eye, the expert will need to opine about relative percentages of causation attributable to the effects of the surgery. The standard of proof in a case involving an older adult with other health problems may be especially difficult for the plaintiff.

   VIII. Conclusion

   New issues suggest new solutions. While laser eye surgery seems today to have few near-term problems, the massive numbers in the target population and the vagaries of human optical problems will pose concerns for trial lawyers. Barriers to recovery, when and if problems are found, will be a challenge to the remedial system of the future. State legislative action and insurance regulatory decisions to establish a risk-pool surcharge may be the optimal means to assure that future claims can be compensated. Plaintiffs’ trial counsel will have a role in the creation of this future mechanism for relief, which will entail a focused and intelligent effort for governmental assurance of remedies.

Legal Topics:

For related research and practice materials, see the following legal topics:

TortsMalpractice & Professional LiabilityHealthcare ProvidersHealthcare LawActions Against Healthcare WorkersSurgeonsInsurance LawMalpractice InsuranceClaims Made & Occurrence Policies

FOOTNOTES:

n1 See Diana Digges, $ 4M Award Over Laser-Eye Surgery Breaks New Ground, Law. Wkly. USA, May 27, 2002, at 24.

n2 The author thanks Spectrum Consulting and the media department of the American Academy of Ophthalmology for providing their January 2001 estimates, Spectrum Consulting Associates, 2001 Revised Estimate of the U.S. PRK/LASIK Market & Estimates of PRK/LASIK Breakdown.

n3 In addition to those who purchase LASIK procedures, approximately 165,000 others will purchase photorefractive keratectomy (PRK), another form of eye surgery designed to improve vision. Id.

n4 Oven v. Pascucci, 46 Pa. D. & C.4th 506, 509 n.1 (Pa. Com. Pl. 2000).

n5 A useful reference about LASIK safety is the FDA LASIK, at http://www.fda.gov/cdrh/LASIK/ (last visited Jan. 13, 2003).

n6 Peter Hersh et al., Photorefractive Keratectomy Versus Laser In Situ Keratomileusis, 107 Ophthalmology 925, 931 (May 2000).

n7 Of course, the wording of the advertisements vary with the particular sales approach offered. The emphasis remains on cosmetic appearance benefits, the easier alternatives to glasses, and the affordability of the surgery.

n8 Spectrum Consulting Estimates, supra note 2.

n9 Id.

n10 21 U.S.C. § 321(h) (1999).

n11 Id. § 360E(c) (2000); 21 C.F.R. § 814.20 (2000).

n12 FDA, Checklist of Information Usually Submitted in an Investigational Device Exemption for Refractive Surgical Lasers (Oct. 10, 1996), at http://www.fda.gov/cdrh/ode/2093.html (last visited Sept. 12, 2002).

n13 See FDA-Center for Devices & Radiological Health, Checklist for Filing Decision for PMAs (2001), available at http://www.fda.gov/cdrh/ode/checklist/pma.html (last visited Jan. 13, 2003).

n14 See, e.g. FDA, Center for Devices and Radiological Health Consumer Information: Recently Approved Devices, CDRH Consumer Information Recently Approved Devices at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cftopic/mda/mda -list.cfm?list=1 (last visited Sept. 21, 2002).

n15 See FDA, Checklist of Information Usually Submitted in an Investigational Device Exemption for Refractive Surgical Lasers § 3.2.6 (Oct. 10 1996).

n16 FDA, Performance Plan 2002 § 2.6.1 Program Description, Context and Summary of Performance (2002), at http://www.fda.gov/ope/fy03plan/part2 med.html.

n17 FDA, Center for Devices & Radiological Health, LASIK Eye Surgery: What Should I Expect Before, During and After Surgery?, at www.fda.gov/cdrh/lasik/expect.htm (last updated Oct. 1, 2002).

n18 See infra Part V.

n19 Sigma-Tau Pharms. Inc. v Schwetz, 288 F.3d 141, 145 (4th Cir. 2002).

n20 21 U.S.C. § 352(f) (2000).

n21 See Colo. State Bd. of Med. Exam’rs v. Roberts, 42 P.3d 70 (Colo. Ct. App. 2001).

n22 See, e.g., $ 1,750,000 Settlement in Suit Arising from LASIK Eye Surgery, Verdicts, Settlements, & Tactics, July 2002, at 297; Misassembled LASIK Surgery Implement, 45 ATLA L. Rep. 328 (2002).

n23 21 C.F.R. pt. 803.

n24 http://www.fda.gov/medwatch/articles.htm (last visited Jan. 13, 2003).

n25 21 U.S.C. § 360i(b) (2000).

n26 The device user reporting section was partially repealed by Pub. L. No. 105-115, Title II, sec. 213(a)(1)(E), 111 Stat. 2347 (1997).

n27 The rapid increases in volume of LASIK surgeries “adds to the importance of identifying even small risks associated with these elective procedures.” David O. Mazur et al., Retinal Detachment in Myopic Eyes After Laser in Situ Keratomileusis, 129 Am. J. Ophthalmology 823, 824 (June 2000).

n28 Restatement (Third) of Products Liability § 2 cmt. a (1997).

n29 A product that is defective and unreasonably dangerous will be addressed with strict liability even if the designer was not negligent. Restatement (Second) of Torts § 402A (1965); see also Restatement (Third) of Products Liability § 2 (1997).

n30 Restatement (Second) of Torts § 402A, cmt. k (1965).

n31 Id.

n32 Restatement (Third) of Products Liability § 6(c) (1997): A prescription drug or medical device is not reasonably safe due to defective design if the foreseeable risks of harm posed by the drug or medical device are sufficiently great in relation to its foreseeable therapeutic benefits that reasonable health-care providers, knowing of such foreseeable risks and therapeutic benefits, would not prescribe the drug or medical device for any class of patients.

n33 Id. at cmt. b.

n34 Id.

n35 Minna Vesaluoma et al., Corneal Stromal Changes Induced by Myopic LASIK, 41 Investigative Ophthalmology & Visual Sci. 369, 373 (Feb. 2000).

n36 Id. at 375.

n37 Hersh, supra note 6, at 932.

n38 See, e.g., My LASIK Flap Management Technique, Eye World (Aug. 2002), at http://www.eyeworld .org/aug02/0802p43.html (last visited Sept. 12, 2002).

n39 Jorge L. Alio et al., Selective Zonal Ablations with Excimer Laser for Correction of Irregular Astigmatism Induced by Refractive Surgery, 107 Ophthalmology 662, 670 (April 2000).

n40 Id. at 670.

n41 Yi-Yu Tsai & Jane-Ming Lin, Natural History of Central Islands After Laser In Situ Keratomileusis, 26 J. Cataract & Refractive Surgery 853 (June 2000).

n42 Torben Moller-Pedersen et al., Stromal Wound Healing Explains Refractive Instability and Haza Development After Photorefractive Keratectomy, 107 Ophthalmology 1235, 1236 (July 2000).

n43 Id. at 1243.

n44 Mihai Pop & Yves Payette, Photorefractive Keratectomy Versus Laser in Situ Keratomileusis, 107 Ophthalmology 251, 256 (February 2000).

n45 See Simon P. Holland et al., Avoiding Serious Corneal Complications of Laser Assisted in Situ Keratomileusis and Photorefractive Keratectomy, 107 Ophthalmology 640, 651 (April 2000).

n46 Thomas Clinch, Discussion, commenting on Howard Gimbel et al., Incidence and Management of Intraoperative and Early Postoperative Complications in 1000 Consecutive Laser In Situ Keratomileusis Cases, 105 Ophthalmology 1839, 1847 (Oct. 1998).

n47 See id. at 1847.

n48 Yuichi Hori et al., Medical Treatment of Operative Corneal Perforation Caused by Laser in Situ Keratomileusis, 117 Archives of Ophthalmology 1422 (Oct. 1999).

n49 Posting of letter No One Wins Unless Everyone Wins by Marguerite B. McDonald, Chief Medical Director, Eyeworld, on LasikInfoCenter website (1999) (copy on file with the University of Cincinnati Law Review) (“We are only starting to ride the enormous growth curve of LASIK in this country. There will be more than enough surgeries for everyone to benefit if we keep our heads by sharing information openly and honestly and by resisting the temptation to criticize the work of our colleagues when we are offering a second opinion to a patient with a suboptimal result.”).

n50 See Digges, supra note 1, at 24.

n51 Attractive websites offering “safe” surgery include http://www.sightsolutions.com/index-dhtml.htm (last visited Feb. 21, 2003) (no claim is made that this site or others creates an express warranty; it is used for illustrative purposes only).

n52 Conceptually, eye surgery is a service rather than “goods,” so the conventional treatment of express warranties under Uniform Commercial Code section 2-313 is available only by analogy.

n53 Laser eye surgery is a source of malpractice claims that have successfully asserted “conscious disregard for the rights and safety” of eye patients. See Siuda v. Howard, No. C- 000656, 2002- Ohio-2292, 2002 WL 946188, at *11 (Ct. App. May 10, 2002). Websites critical of LASIK present more reports of verdicts and settlements. See generally www.lasikdisaster.com (last visited Jan. 2003); http://members.tripod.com/lasik facts (last visited Jan. 2003).

n54 Ellen Dean Smith, New Campaign Aims to Tell the Truth About Laser Surgery, Eye World, at http://www.eyeworld.org/june02/0602p13.html (last visited Jan. 13, 2003).

n55 Daubert v. Merrell Dow Pharms., 509 U.S. 579, 592- 93 (1993). This doctrine is followed in seventeen states. See Joseph Eaton, Survival of the Fryest, 30 Prod. Safety & Liab. Rep. (BNA) 333 (Apr. 15, 2002).

n56 See, e.g., Kubrick v. United States, 444 U.S. 111 (1979) (requiring actions to be initiated within a reasonable time after discovery of the malpractice).

n57 These statutes place procedural restrictions upon the malpractice plaintiff and reduce the potential damage awards.

n58 Colo. State Bd. of Med. Exam’rs v. Roberts, 42 P.3d 70 (Colo. Ct. App. 2001).

n59 A major professional liability insurer explains the distinction: “A ‘claims made’ policy protects the policyholder against claims or incidents that are reported while the policy is in force, or during an ‘extended reporting period.’ The negligent act, error or omission must have also occurred during the specific time frame set by the policy.” American International Group, Inc., Frequently Asked Questions, at http://www.aigdirect.com/small business/customer service/faq inde x.cfm? PageID=fq020#top (last visited Jan. 13, 2003).

n60 Experts in malpractice coverage estimate ninety percent of malpractice coverage is on a claims-made basis and assume that “in the next five years or so occurrence [policies] will all but disappear.” E-mail from Jim Kelley, Coverage, Inc., to James O’Reilly, Visiting Professor of Law, University of Cincinnati College of Law (October 29, 2002 10:43:00 EST) (on file with the University of Cincinnati Law Review).

n61 The statistics are taken from A.M. Best reports and other sources, and were presented to the 2002 Annual Meeting of the American Bar Association by malpractice insurance experts. Theresa W. Bourdon, Address at the 2002 Annual Meeting of the ABA, Tort and Insurance Practice Session (Aug. 10, 2002).

n62 The St. Paul Companies, Inc., News, (Dec. 12, 2001) (“The St. Paul Announces Fourth-Quarter Actions to Improve Profitability and Business Positioning,” press release of St. P a u l C o m p a n i e s ) , a t http://www2.stpaul.com/spc/corp/spcnews.nsf/6d54d5b37c9943cc86256 a64006eba96/c007bc65ef 4993c686256b200049e504?OpenDocument (last visited Feb. 21, 2003).

n63 Oven v. Pascucci, 46 Pa. D. & C.4th 506 (Pa. Com. Pl. 2000) (eye laser litigation against corporate provider of the surgical service).

n64 For example, in September 2002, a company called LasikPlus advertised laser vision correction for only $ 299 per eye. Genuine LasikPlus Laser Vision Correction: Now Only $ 299 Per Eye, Cin. Enquirer, Sept. 13, 2002, at D7 (on file with the University of Cincinnati Law Review).

n65 21 U.S.C. § 352(r) (2000) literally covers advertising for “restricted” devices, but in practice the broader class of prescription devices have been within FDA’s advertising controls; see also 21 C.F.R. § 801.109.

n66 U.S. Const. art. I, § 8, cl.3.

n67 21 U.S.C. § 321(h) (2000). The LASIK machinery is classified as a medical device under federal regulations. See 21 C.F.R. § 886.4390 (2000).

n68 21 U.S.C. § 360k(a)(1) (1999).

n69 Id.

n70 Id. at § 360k (1999).

n71 See, e.g., Medtronic, Inc. v. Lohr, 518 U.S. 470 (1996).

n72 Id. (holding that 21 U.S.C. § 360k(a) preempted certain state tort claims).

n73 Pub. L. No. 105-115, 111 Stat. 2296 (1997).

n74 Buckman Co. v. Plaintiff’s Legal Comm., 531 U.S. 341 (2001).

n75 See, e.g., Baker v. Medtronic, Inc., No. 2:99- CV- 1355, 2002 WL 485013 (S.D. Ohio Mar. 28, 2002) (holding that preemption precludes virtually all state tort claims against medical device manufacturers).

n76 The issue remains debatable for medical devices like LASIK equipment. Several courts have held that FDA clearance of a label does not preempt state tort cases for failure to adequately warn. See, e.g., Webster v. Pacesetter, Inc., 171 F. Supp. 2d 1 (D.D.C.,2001) (medical device); Eve v. Sandoz Pharms. Corp., No. IP98-1429-C-Y/S, 2002 WL 181972 (S.D. Ind. Jan. 28, 2002) (drug).

n77 Devices for laser eye surgery incur large development costs, making some companies vulnerable, with corporate survival consequences if the equipment does not achieve the desired results. See S.E.C. v. Schiffer, No. 97 Civ. 5853 (RO), 2001 WL 504860 (S.D.N.Y. May 11, 2001); see also In re VISX Sec. Litig., Nos. C-00-0649 CRB, C-00-0815 CM, 2001 WL 210481 (N.D. Cal. Feb. 27, 2001).

n78 This piercing would mean that parent or related corporations and successors might be held liable for injuries alleged to have been the result of a prior dissolved corporation’s actions.

n79 Oven v. Pascucci, 46 Pa. D. & C.4th 506, 509 (Pa. Comm. Pl. 2000).

n80 38 U.S.C. § 1116(a)(1) (1991).

n81 A norm such as that used by Medicare for “medically necessary” surgical procedures would separate the aesthetic or convenience self-paid surgeries from those where eye surgery had been performed to respond to a medical need. “Under the Medicare Act, a physician’s certification that the ambulance services provided are medically necessary is required before Medicare reimbursement is available.” Howard Med., Inc. v Temple Univ. Hosp., No. 00-5977, 2002 WL 169380 at *4 (E.D. Pa. Feb. 1, 2002) (citing 42 U.S.C. § 1395n(a)(2)(2002)). Since this is not provided as an employee benefit, ERISA preemption is not likely to inhibit state responses.

n82 Steven Z. v. Kimberley Z, No. CN00-7918, 2000 WL 1658620 (Del. Fam. Ct. 2000).

n83 Stasack v. Capital Dist. Physicians’ Health Plan Inc., 736 N.Y.S.2d 764 (A.D. 3 Dept. 2002).

n84 Federal ERISA recognized the primacy of states in regulating insurance within the states, and these malpractice insurance reserve issues are properly within the realm of state insurance departments. 29 U.S.C. § 1144(b)(2)(A) (1991); UNUM Life Ins. Co. v Ward, 526 U.S. 358 (1999).

n85 See, e.g., Colo. State Bd. of Med. Exam’rs v. Roberts, 42 P.3d 70 (Colo. Ct. App. 2001) (LASIK surgical malpractice led to state medical board disciplinary action).

n86 Daubert v. Merrell Dow Pharms., 509 U.S. 579 (1993).

What’s OK by the FDA…

This was found in a hearing for CK approval, but it gives you an idea of what’s OK by the FDA…

A surgeon can give patients 2 diopters of induced astigmatism as long as it’s less than 5% of eyes. That’s a LOT of blurry vision folks, and for the record… induced astigmatism was not in my informed consent materials. Was it in yours?

“As shown in this slide, the absolute change in refractive cylinder remained well below the FDA limit of less than 5 percent of eyes with greater than 2 diopters of induced cylinder at all follow-up examinations.” P36 lines 6-9.

The below was found at: http://www.fda.gov/ohrms/dockets/ac/01/transcripts/3806t1.rtf

UNITED STATES OF AMERICA

FOOD AND DRUG ADMINISTRATION

CENTER FOR DEVICES AND RADIOLOGICAL HEALTH

+ + + + +

OPHTHALMIC DEVICES PANEL MEETING

102ND MEETING

+ + + + +

FRIDAY        NOVEMBER 30, 2001

The panel met at 9:45 a.m. in the Whetstone Room of the Gaithersburg Holiday Inn, Two Montgomery Village Avenue, Gaithersburg, Maryland, Dr. Joel Sugar, Interim Chair, presiding.

Present:

JOEL SUGAR, M.D., Interim Chair

ARTHUR BRADLEY, Ph.D., Voting Member

MICHAEL R. GRIMMETT, M.D., Voting Member

ALLEN C. HO, M.D., Consultant

ANDREW J. HUANG, M.D., Consultant

JANICE M. JURKUS, O.D., Consultant

WILLIAM D. MATHERS, M.D., Consultant

ALICE Y. MATOBA, M.D., Voting Member

RONALD E. McCARLEY, Industry Representative

TIMOTHY T. McMAHON, O.D., Consultant

JOSE S. PULIDO, M.D., Consultant

JAYNE S. WEISS, M.D., Voting Member

SARA M. THORNTON, Executive Secretary

I-N-D-E-X

Call to Order, Joel Sugar, M.D., Interim Chair  4

Introductory Remarks, Sara M. Thornton, Executive Secretary      4

Open Public Hearing     11

Open Committee Session:

FDA Presentation         13

Division Update, A. Ralph Rosenthal, M.D.      18

Branch Updates

Everette T. Beers, Ph.D.           18

James F. Saviola, O.D. 19

PMA P010018            24

Sponsor Presentation    25

Panel Questions            57

FDA Presentation         91

Joel P. Glover   91

Sheryl L. Berman, M.D.           92

Panel Questions for FDA          99

Additional Comments from the Sponsor           101

Committee Deliberations           109

Primary Panel Reviewers:

Arthur Bradley, Ph.D.   109

Michael R. Grimmett, M.D.      125

Jayne S. Weiss, M.D.   139

Open Public Hearing Session    195

FDA – Closing Comments        196

Sponsor – Closing Comments   196

I-N-D-E-X

Voting Options Read    196

Panel Recommendation Taken by Vote 205

Polling of Panel Votes   217

Final Panel Comments  220

Adjourn            221

P-R-O-C-E-E-D-I-N-G-S

(9:49 a.m.)

SUGAR:  I’d like to call this meeting of the Ophthalmic Devices Panel to order.  And have introductory remarks from Sara Thornton.

THORNTON:  Is everybody here?  All present and accounted for?

Good morning and welcome to the 102nd meeting of the Ophthalmic Devices Panel.  Before we proceed with today’s agenda, I’ve a few short announcements to make.

I would like to remind everyone, that’s Panel, public, FDA, to sign in on the attendance sheets in the registration area just outside the meeting room.

All of the public handouts for today’s meeting are available at the registration table.

If there are messages for Panel Members and FDA participants, information or special needs, they should be directed through Ms. Ann-Marie Williams, Ms. Shirley Meeks or Mr. Hashim Khalif, who are available in the registration area.

The phone number for calls to the meeting area here is 301/948-8900 and instruct your people if you contact them in advance for something that they need to just ask for the FDA registration desk.

In consideration for the Panel and the sponsor, the Agency, we ask that those of you with cell phones and pagers either turn them off or put them on vibrator mode while you are in this room.

We ask that all meeting participants please speak into the microphone and give your names clearly, so that the transcribers will have an accurate recording of your comments.

The next Ophthalmic Devices Panel meeting will be on Thursday and Friday, January 17th and 18th, 2002.  All available information for that meeting will be on the Advisory Committee website in approximately one week.

Now at this time I’d like to extend a special welcome and introduce to the public the Panel and the FDA staff, three Panel Consultants who are with us for the first time today and our new Industry Rep.  One of our new consultants, beginning with Dr. Allen Ho comes to us from Philadelphia where he is an Associate Professor of Ophthalmology at the Thomas Jefferson University School of Medicine and an Associate Surgeon with the Retinal Service at the Wills Eye Hospital.  Dr. Ho, we welcome you.

Dr. Andrew Huang is from Minneapolis, Minnesota where he is an Associate Professor and the Director of the Cornea and External Disease Service of the Department of Ophthalmology at the University of Minnesota.  We welcome you also, Dr. Huang.

And our third new Panel Consultant, Dr. William Mathers is from Portland, Oregon where is Professor of Ophthalmology at the Oregon Health Sciences University, Casey Eye Institute and is a specialist in cornea and external disease.  Welcome, Dr. Mathers.

And Mr. Ronald “Rick” McCarley, the Industry Representative to the Panel who is President, CEO and Founder of Ophtec USA, Inc.  Welcome, Rick.

We very much appreciate your commitment to serve and we welcome you, all of us welcome you to the Panel table today.

To continue, will the remaining Panel Members please introduce themselves beginning with Dr. Pulido.

PULIDO:  Jose Pulido, Professor and Head of the Department of Ophthalmology, University of Illinois, Chicago.

McMAHON:  I’m Tim McMahon, Professor, University of Illinois, Chicago.

THORNTON:  I can’t hear Dr. McMahon very clearly.  You want to check that one out.

McMAHON:  Tim McMahon, Professor, University of Illinois, Chicago.

BRADLEY:  Arthur Bradley, Professor of Vision Science, Indiana University.

WEISS:  Jayne Weiss, Professor of Ophthalmology and Pathology, Kresge Eye Institute, Wayne State University, Detroit.

SUGAR:  Joel Sugar, Professor of Ophthalmology, also University of Illinois, Chicago.

GRIMMETT:  Michael Grimmett, Assistant Professor, University of Miami, Bascom Palmer Eye Institute.

MATOBA:  Alice Matoba, Associate Professor, Department of Ophthalmology, Baylor College of Medicine.

JURKUS:  Jan Jurkus, Professor of Optometry, Illinois College of Optometry in Chicago, Illinois.

ROSENTHAL:  Ralph Rosenthal, Director, Division of Ophthalmic and ENT Devices.

THORNTON:  Thank you, Panel.  I’d like to note for the record and with regret, that Ms. Glenda Such, our new Panel Consumer Representative cannot be with us today.  Earlier this week she had to undergo surgery so we wish her a speedy recovery and we look forward to having with us at our January meeting.

SUGAR:  Thank you, Sally.  We now have time for an open public hearing.

THORNTON:  Wait, I’ve got two more things.

SUGAR:  I missed something.  We still have time for that.

THORNTON:  Two more things.  Okay, here we go.  I’d like to read the conflict of interest statement for this meeting.  The following announcement addresses conflict of interest issues associated with this meeting and is made part of the record to preclude even the appearance of an impropriety.  To determine if any conflict existed, the Agency reviewed the submitted agenda for this meeting and all financial interests reported by the Committee participants.  The conflict of interest statutes prohibit special government employees from participating in matters that could affect their or their employer’s financial interests.  However, the agency has determined that participation of certain members and consultants, the need for whose services outweighs the potential conflict of interest involved is in the best interest of the government.  Therefore, a waiver has been granted for Dr. Michael Grimmett, for his imputed interest in a firm at issue that could potentially be affected by the Panel’s recommendations.  The waiver allows this individual to participate fully in today’s deliberations.  Copies of this waiver may be obtained from the Agency’s Freedom of Information Office, Room 12A-15 of the Parklawn Building.

We would also like to note for the record that the Agency took into consideration certain matters regarding Drs. Arthur Bradley, Timothy McMahon and Allen Ho.  These Panelists reported past and/or current financial interests in firms at issue, but in matters not related to today’s agenda.  The Agency has determined, therefore, that they may participate fully in today’s deliberations.

In the event that the discussions involve any other products or firms not already on the agenda for which an FDA participant has a financial interest, the participant should excuse him or herself from such involvement and the exclusion will be noted for the record.

With respect to all other participants, we ask in the interest of fairness, that all persons making statements or presentations disclose any current or previous financial involvement with any firm whose products they may wish to comment upon.

I’d like to now read the appointment to temporary voting status.  Pursuant to the authority granted under the Medical Devices Advisory Committee Charter dated October 27, 1990 and as amended, August 18, 1999, I appoint the following individuals as voting members of the Ophthalmic Devices Panel for this meeting on November 30, 2001:  Drs. Janice Jurkus, Allen Ho, Andrew Huang, Timothy McMahon, William Mathers, Jose Pulido, Joel Sugar.  In addition, I appoint Dr. Joel Sugar to serve as Interim Panel Chair for the duration of this meeting.

For the record, these individuals are special government employees and consultants to this Panel or other Panels under the Medical Devices Advisory Committee.  They have undergone the customary conflict of interest review and have reviewed the material to be considered at this meeting.  This is signed David W. Feigal, Jr., M.D., M.P.H., Director of the Center for Devices and Radiological Health, dated November 16, 2001.

Thank you, Joel.

SUGAR:  Thank you again.  We now have time for open public hearing.  If anyone has public statements to make, they need to identify themselves and state any financial conflicts or potential conflicts.

There is a submission by mail that Sally will read.

THORNTON:  This is a letter submitted to be read at this meeting by Dr. I. Howard Fine, President of the American Society of Cataract and Refractive Surgery, Clinical Associate Professor of Ophthalmology, Casey Eye Institute, Oregon Health and Sciences University.

“Dear FDA Panel Members, unfortunately, I was not able to attend today’s Panel meeting scheduled to review the conductive keratoplasty procedure.  However, in my absence, I would like to request that this letter be read aloud on my behalf.  As part of full disclosure, I would like to inform the Panel that I am a member of Refractec’s Medical Device Advisory Board.  However, I hold this position gratis.  I am not paid for my time to participate on the Board, nor do I have an equity position in the company.  As a Medical Advisor, I feel that the outcomes from the clinical trial are as safe and effective as those presented by other refractive technologies.  I make this statement with confidence as I am current President of the American Society of Cataract and Refractive Surgery and in this role have the opportunity to see and review many scientific presentations on refractive procedures.  One very promising aspect of conductive keratoplasty is the potential for the technique to not induce dry eye post-operatively.  As we all know, Lasik transects the cornea nerves, therefore inducing dry eyes in most patients.  The investigators participating in the conductive keratoplasty trial have all reported little or no dry eyes post-operatively with this technology.  I feel that the addition of another refractive technology will only strengthen our ability to practice medicine and allow us to provide our patients with the most appropriate procedure for them and their condition.  For these reasons, I respectfully ask the Panel Members to approve conductive keratoplasty, allowing the Members of the ASCRS and ophthalmologists throughout the U.S. to utilize this technology.  Sincerely, Dr. Howard Fine.”

Thank you, Dr. Sugar.

SUGAR:  Thank you.  This now closes the open public hearing session and we’ll move on to the open committee session and we’ll begin with a presentation by Dr. Statland from the FDA.

STATLAND:  Good morning.  It’s nice to be here for a number of reasons.  One, it’s always good to get out of the shop occasionally and see the real world events in front of us and this Panel Meeting is an example of a very important real world event.  And second, in a very general way, to acknowledge all of you on the Panel who diligently look at the material given to you, make a scientific, clinical and pragmatic assessment of the information and give us your best recommendations.

I also for the third reason I’m here, is to give some plaques and some awards for individuals who served the FDA and there are four individuals that I’m going to acknowledge today and if you’ll just bear with me.  I have a short paragraph about each of you, so when I mention your name, don’t be too concerned and I’ll give you information.

First of all, one individual who actually received her placque earlier is Marcia, where is she?  Marcia Yaross, Dr. Yaross is the Director of

World-wide Regulatory Affairs and Medical Compliance for Allergen of Irvine, California.  She graduated Reed College in Portland, Oregon with a degree in Biology and completed her doctorate in Cell and Developmental Biology at the University of California in Irvine.  After a career in Biological Research, she entered the field of regulatory affairs as a Regulatory Affairs Coordinator for a major manufacturer of ophthalmic devices and has responsibility for many of the types of devices reviewed by the Ophthalmic Devices Advisory Panel.  And as you know, she was the Industry Representative.  Thank you for time and effort.

Now for the three individuals here on the Panel, okay, the first is for Joel Sugar.  Dr. Sugar, as you probably all know, is a Professor of Ophthalmology, the Director of Cornea Service and Vice Chair of the Department of Ophthalmology at the University of Illinois, Eye and Ear Infirmary in Chicago.  He graduated from the University of Michigan Medical School and completed a residency in Ophthalmology at Washington University in St. Louis and a post-graduate fellowship in Cornea and External Disease at the University of Florida Medical School in Gainesville.  Dr. Sugar is currently on the Board of Directors of the Eye Bank Association of America and also is on the Accreditation Committee and the Medical Advisory Board where he served as Chairman from 1991 to 1996.  He has published extensively and is internationally recognized for his research and publications on many specific aspects of corneal surgery, in addition to addressing numerous issues on corneal diseases, contact lens, intraocular lenses.  Dr. Sugar and the two other individuals will be basically acting as special government employees at this particular meeting, so I will hand to him and to all the others both a letter from Linda Suydam, expressing in the same words of appreciation as well as this placque for recognition of distinguished service.

SUGAR:  Thank you very much.

STATLAND:  My pleasure.  The next individual to be recognized is Dr. Janice Jurkus who is a Professor of Optometry at the Illinois College of Optometry in Chicago.  She received her Optometry degree from the Illinois College of Optometry and a Master’s in Business Administration from Loyola University, also from Chicago.  In addition to her professional involvement as a contact lens clinician, educator and coordinator of practice management, she is chairperson of the Faculty Council Executive Committee.  Dr. Jurkus is a Fellow of the International Association of Contact Lenses Educators, a Fellow of the American Academy of Optometry and serves on the editorial board of Optometric Management.  She has lectured and published extensively on contact lens materials and design, clinical complications, patient education and informed consent and is internationally recognized for her expertise.

JURKUS:  Thank you very much.

STATLAND:  My pleasure.  The last individual to receive the award is Dr. Jose Pulido.  Dr. Pulido is Professor and newly appointed Chairperson of the Department of Ophthalmology, University of Illinois Eye and Ear Infirmary in Chicago.  He received his Bachelor’s and Master’s degrees from the University of Chicago in four years and consequently his M.D. from Tulane University School of Medicine in New Orleans. Following his Ophthalmology residency at the University of Illinois, he completed a fellowship in vitreoretinal surgery at the Bascom Palmer Eye Institute, University of Miami School of Medicine in Miami.  He also has an M.B.A. from the University of Iowa.  He is presently the National Director for Diabetes 2000 and serves as an editor for EyeNet.  In addition, he’s reviewer for numerous publications that include the Archives of Ophthalmology, American Journal of Ophthalmology, and Investigative Ophthalmology and Visual Sciences.  Dr. Pulido is a Member of the Retina Society, the Macula Society, the American Uveitis Society and the American Ophthalmology Society.  Congratulations.

PULIDO:  Thank you very much.

STATLAND:  As I listen to myself speak and realize all the attributes that all of you have and all the other Panelists as well, as I said before, I think we’re so fortunate.  We benefit so much from the excellent input that you give to us.  We listen well, we are interested in what you have to say and just to state one more time that those individuals who have completed their term are acting today as special government employees and we appreciate that as well.  So thank you for giving me this opportunity of being here and making these presentations.  Have a great meeting.

(Applause.)

SUGAR:  Thank you very much. Dr. Statland.

PULIDO:  Mr. Chairman, I would like to say some words, this being my last meeting here and that is over the last few months, we’ve heard a lot about public safety and public safety officers and I can assure you that over these last four years I have had the opportunity to work with some wonderful public safety officers.  These people in the FDA walk a very, very fine line between the needs of our private enterprises here in the United States and the need for public safety and I know that they are extremely pushed to try to do the best they can to serve both their constituencies and it’s been an honor and a privilege to have worked with them.  Thank you.

SUGAR:  I’d like to now move on to the Division Update.  Dr. Rosenthal?

ROSENTHAL:  The only thing I have, Mr. Chairman, is that the — which is not related to Ophthalmology, but is part of the Division, so I will update you, is that we’ve been fortunate enough to attract a new Branch Chief for our Ear, Nose and Throat Branch who is Eric Mann who is an otolaryngologist who comes to us from NIH and you will not have the opportunity and the pleasure to work with him, unless there’s a combined device in which ENT and Eye is developed.  I just wanted you to know that he has joined us and we are overwhelmingly delighted that he has agreed to accept the post.

SUGAR:  Thank you.  Dr. Beers, Donna Lochner and Dr. Saviola, do you want to — Donna is not here?  Okay.

BEERS:  I’m Everette Beers, Chief of the Diagnostic and Surgical Devices Branch.  I just want to update you on some recent PMA approvals.  We approved the VisX for Lasik mixed astigmatism, that was P930016, Supplement 14.  And we approved the LaserSight for Lasik myopic astigmatism, P980008, Supplement 5.  I won’t go into all the indications on that, but those are approvals, supplemental approvals since our last meeting.

The Diagnostic and Surgical Devices Branch has been extraordinarily busy with clinical trials that I can’t discuss here and with other issues that may not be of interest to you, but we are trying to work in everyone’s best interest.  Thank you.

SUGAR:  Thank you, Dr. Beers.  Dr. Saviola?

SAVIOLA:  Good morning.  As the former Acting Chief of the ENT Branch, as well as Branch Chief of the EDB I’m also delighted that Dr. Mann has joined us in the division.

I’d like to update the Panel on recent approvals of two 30-day extended wear contact lenses and give you a little bit of information about what we’re doing with them.  The Focus7 NIGHT & DAY/otrafilcon contact lens was reviewed at the July Panel Meeting and it was approved October 11th.  This soft contact lens is indicated for the correction of refracted ametropia and also a number of alternate designs such as toric and progressive designs were approved with the spherical design.  The lens may be prescribed for daily or extended wear for up to 30 nights of continuous wear, for removal — with removal for disposal or cleaning as recommended by the eye care professional.

A precaution statement was included in the labeling that states at the extremes of the power range above +10.00 or -15.00 diopter oxygen transmissibility is slightly below the established threshold level required to prevent overnight corneal edema.  We did not put a power restriction in the indication itself.

In the clinical study section results there are a few bullets about other important safety results of this study and I’ll just read three of those that 14 of the FOCUS7 9-day subjects experienced infiltrates during the first month of extended wear compared to five of the control and that the FOCUS7 9-day subjects experienced more than one endpoint, excuse me, the FOCUS7 9-day subjects experienced more than one endpoint 70 percent during the first month of the trial.  And for both groups if the subject experienced an infiltrate event in one eye, the risk of a second event in the same or fellow eye was six times more likely as compared to having a first event.

The Bausch & Lomb Purevision balafilcon A contact lens was approved on November 20th under a supplemental submission to the existing PMA.  This lens is indicated for daily or extended wear from 1 to 30 days between removals for cleaning and disinfection or disposal.  We did put a power restriction on this one.  It’s approved from +8.00 D to -2020.00D when prescribed for up to 30 days of extended wear and it already had approval for + or -20.00 for daily wear or extended wear up to 7 days.  And again, a precaution statement is included in the labeling that addresses extremes of the power range above +3.00 and -5.00 diopter.  Also that the rate of infiltrative keratitis was found to be higher with higher lens powers.

Now although this PMA was a second of a kind, it was originally scheduled for discussion at the September 21st Panel Meeting to discuss the need for post-market study and to provide the Panel an opportunity to review clinical data from a contralateralized study.  Two primary Panel Reviews have been completed in preparation for the meeting.

Due to the tragic events of September 11th, the September 21st meeting was canceled.  During subsequent discussion, it was decided that the primary clinical issues in the PMA did substantially duplicate information previously reviewed by the Panel.  Additional homework assignments from two Panel Members were obtained to corroborate the recommendation of the two primary reviewers in lieu of full Panel discussion.

All four Advisory Panel Reviews recommended approval of the supplement from 1 to 30 days.  Therefore, we did not refer to the full Panel for a meeting and discussion.

As to our plans to better communicate the risks to both patients and practitioners, we have placed a variety of restrictions on these two extended wear lenses.  For advertising, the advertising restriction was put into the approval order.  Similar to drug advertisements, print ads for the new extended lenses must include a company information to describe the indications, contraindications, warning and precautions.

The company, in conjunction with FDA, developed a consumer information leaflet in a question and answer format similar to information available for some prescription drugs in order to address this restriction for consumer advertisements, rather than to print the whole technical information from the package insert.

For labeling, practitioners will receive additional information in professional labeling.  The package insert will consider a clinical study result section that describes the study and provides information on demographics, primary safety and efficacy outcome measures and also provides a quick reference to better understand the details of the preapproval study.

A brief description of the study and outcomes of the study will also appear in the patient information booklet as well.

As far as post-approval clinical studies, as a condition of marketing approval, each manufacturer must conduct a post-market study to characterize the risk of microbial keratitis and subsequent loss of best corrective visual acuity in the general population.  Both the Ciba and B & L studies will involve about 100 sentinel monitoring sites.  These prospective active monitoring studies are designed to provide data on 4500 to 5000 patient years of subjects wearing their 1-month lenses during a 1-year period.

The protocols call for monitoring subjects every six months for the one year, without the detailed evaluation of all the parameters usually measured in pre-approval study.

While the scope of these post-approval studies does fall short of the 20,000 subjects it would take to do a statistically rigorous clinical study, they will still provide an early indication for risks in the real world setting and help to answer the questions of long-term safety in the general population.

These labeling initiatives provide a better opportunity for practitioners and patients to make a wearing schedule decision based on an individual patient’s response to lens wear and their acceptable level of risk.

Thank you very much.

SUGAR:  Thank you.  If there’s no other information to be updated from the Agency, I’d like to move ahead to discussion and review of PMA P010018.  We’ll begin with the sponsor presentation.  The sponsor has one hour.  I’d like each presenter to identify themselves at the beginning of their presentation.

GORDON:  Good morning.  My name is Dr. Judy Gordon.  I have the pleasure of representing Refractec today as a regulatory consultant.  Together with Dr. Jon Hayashida, Refractec’s Vice President of Clinical Affairs, we will present to this Panel the clinical trial results submitted to the FDA in P010018 for the ViewPoint Conductive Keratoplasty system.  We will be joined by two of the clinical investigators who participated in the CK trial, Dr. Marguerite McDonald who has also served as Medical Monitor for the study, and Dr. Peter Hersh, who is an investigator.

Dr. Dan Durrie, another of the CK study investigators, has also joined us today add his clinical perspective as a refractive surgeon is involved in multiple clinical trials of new refractive surgery procedures.  We appreciate the opportunity to present to this Panel and hope that our presentation elucidates the clinical data presented in this PMA.

Dr. Hayashida will begin the presentations with a brief discussion of the indication and the technology.

HAYASHIDA:  Thank you, Judy.  Good morning.  I am Dr. Jon Hayashida.  I would like to share with you today some background information on the correction of hyperopia and the conductive keratoplasty procedure.  Historically, the surgical correction of hyperopia has been considerably more challenging than myopic corrections in that it requires steepening of the central cornea.  Currently, this is accomplished by means of excimer laser ablation and collagen shrinkage procedures that apply treatment to the peripheral cornea.

Thermal keratoplasty alters the cornea curvature by heating the stromal tissue in the periphery, causing collagen to shrink.  Achieving an optimal collagen shrinkage thermal profile is critical.  If the temperature profile is too low, minimal collagen shrinkage results.  If the temperature profiles are too high, excessive tissue damage and eventual remodeling and regression of the effect occur.

The heating of corneal tissue can be accomplished by utilizing either laser light energy or radio-frequency energy.

As shown in this photograph, the viewpoint conductive keratoplasty system consists of a portable console that generates the radio-frequency energy, a lid speculum and a handpiece in which a small tip called the keratoplast tip is held.  The keratoplast tip is used to deliver the energy for treatment, while the lid speculum serves as the return.

Conductive keratoplasty, or CD, involves the controlled interstromal delivery of

radio-frequency energy to a depth of approximately 500 microns in the corneal periphery.  RF energy passes from a generator to a probe tip which is 450 microns in length by 90 microns in diameter into the corneal stroma and returns via the lid speculum.

The impedance of the corneal tissue results in a thermal effect that is controlled to  achieve the optimal thermal profile for collagen shrinkage temperature along the entire length of the probe.  This provides a homogenous and uniform cylinder of optimally constricted collagen to a depth of approximately 80 percent of the peripheral corneal thickness.

To demonstrate the column of constricted collagen, histology was performed on pig corneas.  The image shown here is a transmission polarization micrograph of a CK treatment spot in a pig cornea which a corneal thickness of about 650 microns as 7 days post-operative.  The CK footprint has also been measured post-operatively in humans, using ultrasound biomicroscopy.  On average, the CK cylindrical footprint measured 405 microns wide by 509 microns deep.  We believe that it is the uniformity and depth of this footprint which contributes to the effectiveness of the CK procedure.

To achieve the optimal configuration for safe and long-lasting collagen shrinkage the CK treatment applications are of consistent power with an increase in the number of rings of applications to achieve greater levels of corneal steepening.  The procedure spares the visual axis, offering an important potential safety feature.

As shown in this videoclip of a CK procedure, the optical zone marks of 6, 7 and millimeters act as a template for the treatment appoliation.  Once the optical zone marks are applied, the surgeon begins applying treatment spots superially and continues in a cross cornea fashion for each ring, moving from the most internal ring at the 6 millimeter zone to the outside ring at the 8 millimeter zone until all of the rings of treatment are complete.

The stop or cuff on the keratoplast tip aids in ensuring that the tip is inserted into the cornea perpendicular to the corneal surface for each spot.

Stria then begin to form between the treatment spots creating a circumferential band of tightening.  It is this tightening of the tissue which results in the steepening of the central cornea.

In fact, with confocal microscopy, we have been able to establish the continued presence of stria between treatment spots at 12 months post-operatively.  These observations are consistent with the clinical effects observed post-CK.

In conclusion, we believe that the application of radio-frequency energy in the conductive keratoplasty procedure has clinical advantages over other methods of collagen shrinkage based on the mechanism of action.  In support of this, Dr. Marguerite McDonald will present the safety and effectiveness data generated in the IDE clinical trial of conductive keratoplasty.

McDONALD:  Thank you, Jon.  Good morning.  I am Dr. Marguerite McDonald and I served as both the Medical Monitor and as principal investigator for the IDE clinical trial of conductive keratoplasty.  I wish to share with you the clinical results of this phase 3 clinical trial designed to evaluate the safety and effectiveness of the Viewpoint CK system for the correction of hyperopia.

This is a list of the principal investigators who participated in the CK trial.  This group represents many leaders in corneal refractive surgery and also represents a mix of private practitioners and academic centers so several types of surgeons contributed to the CK clinical trial and to the understanding of this procedure.  The CK clinical trial was designed and conducted in accordance with FDA guidance for hyperopia treatment.  Eligible eyes within +0.75 to +3.25 diopters spherical hyperopia and had no more than -0.75 diopters refractive cylinder, translating into baseline cycloplegic spherical equivalent of +0.75 to +3.00 diopters.  All treatments were based on pre-op cycloplegic refraction spherical equivalent with a treatment goal of full correction of spherical hyperopia.  No cylinder corrections and no retreatments were performed in this study.

The standard effectiveness measures were improvement in uncorrected acuity, predictability of the refractive outcome, refractive stability, and patient satisfaction.

Safety parameters included measurement of best corrected vision, induced cylinder, endothelial cell loss, patient symptoms and as far as any clinical trial complications and adverse events.

A total of 401 eyes of 233 subjects were enrolled in this study and demographics for this population are shown here.  Consistent with other clinical trials of refractive surgery procedures, a larger number of women than men were enrolled and the mean age of the study population was approximately 55 years.

Critical to any hyperopia study is the exclusion of latent hyperopes, therefore entry criteria for the study required that no more than >.05  diopter difference between the pre-op MRSE and CRSE would be allowed as demonstrated in this slide.  Please note that in the original study protocol, 54 eyes with CRSE of 1.00 to 4.000 diopters were enrolled.  Additionally, you will note that two ineligible eyes were enrolled, accounting for the MRSE range extending to -0.38 diopters.

Approximately half of all eyes enrolled had baseline MRSE and CRSE between 1.00 and 1.99 D and over a third of eyes had baseline MRSE of greater than or equal to 2 D.  As I mentioned on the previous slide, eyes with up to 4.00 diopters of spherical equivalent were enrolled in the initial phase of study prior to a nomagram adjustment that limited the upper range of treatment.

This nomagram adjustment was based on the results of the 54 eyes treated in the initial phase of the CK clinical trial.  Analysis of the outcomes of these eyes revealed overcorrection at the low end of the treatment range and under correction at the upper end of the range.  On the basis of these data, Refractec implemented a reduction in the maximum treatment from 4.00 to 3.25 diopters of spherical hyperopia and the addition of an 8 spot treatment pattern for eyes with base.line CSRE of 0.75 to 0.85 D.

Accountability in the study was excellent with at least 97 percent available eyes examined at each visit.  Ninety-four percent of all eyes enrolled were available for analysis through the 9-month examination and just over 50 percent of eyes had reached the 12-month examination at the time the data base for this PMA was locked.  As the medical monitor for this study, I’ve been very impressed with the effort to ensure that patients’ follow-up is complete.

This flow chart shows the total population of 401 eyes enrolled and the relevant cohorts.  Thirty-eight eyes were not treated with the current nomagram and are therefore not included in the effectiveness cohort of 363 eyes.  The safety cohort includes all enrolled eyes with the exception of a single that was discontinued from the study prior to treatment.

Effectiveness data will be reported for the 363 eyes treated with the current nomagram while safety instability will be presented for all 400 treated eyes.

We will now move on to a review of the effectiveness data generated in the CK clinical trial.  Before describing the effectiveness outcomes in detail, I would like to review this summary of effectiveness.  As you can see from this slide, key effectiveness targets established in FDA guidance were met.  Uncorrected visual acuity of 20/40 or better exceeded the FDA target of 85 percent from the 6-month visit forward as did the proportion of eyes with MRSE within .50 diopter and within 1.00 diopter of plano.  Targets were exceeded for change in MRSE less than or equal to a .50 diopter and less than or equal to 1.00 diopter.  Mean change per month was small, 0.03 diopters between 6 and 9 months and increased nonsignificantly to 0.04 diopters per month between 9 and 12 months.

We will now expand on the effectiveness parameters which included improvement in uncorrected visual acuity, predictability and stability of the refractive outcome and patient satisfaction.

As shown in this slide, uncorrected visual acuity improved over the course of follow-up with the FDA target of 85 percent of eyes with 20/40 or better achieved at the 3-month examination.  While the proportion of eyes with uncorrected acuity of 20/20 or better was low at the 1-month examination, this is likely a result of the slight overcorrection in refraction observed at 1 month.  Additionally, it should be noted that these data reflect the outcomes of a single procedure since no retreatments or enhancements were performed in this study.

As shown in this graphical representation, uncorrected acuity improved from 1 in 3 months to the later examinations and excellent levels of uncorrected acuity were achieved at 9 and 12 months post operative with the FDA target of 85 percent 20/40 or better achieved from 3 months forward.

The FDA targets for predictability of the refractive outcome are defined as MRSE within a .50 diopter of plano for 50 percent of eyes and within 1.00 diopter for 75 percent of eyes.

Accuracy of the CK procedure exceeded the FDA targets at all study visits from 3 months.  At 12 months, close to 60 percent of eyes were within a .50 diopter of plano and 91 percent were within 1 diopter.  This level of accuracy of the refractive outcome is very good, particularly when considering that these results reflect the outcome of only a single procedure with no retreatments.

As shown in this graphical representation of predictability, the FDA targets for proportion of eyes within a .50 diopter of plano and within 1.00 diopter of plano were met and exceeded by the 3-month visit with 56 percent of eyes with .50 diopter of plano and 83 percent within 1.00 diopter.  These values increased at 6 months to approximately 60 percent within a .50 diopter of plano and close to 90 percent within 1.00 diopter of plano for the remaining visits through one year.

When examining a consistent cohort of 158 eyes with all visits through 12 months, the predictability of the CK procedure is further established with approximately 60 percent of eyes within a .50 diopter of the target refraction and 90 percent of eyes within 1.00 diopter of target.

Predictability of the CK procedure is presented here graphically to display the proportion of eyes that were under-corrected and over-corrected.  This shows clearly that the proportion of eyes initially over-corrected decreased substantially after one month and under-correction was limited to a small number of eyes throughout the course of the study.

Refractive stability is another key effectiveness parameter and the FDA has identified four criteria for achieving stability.  These include the proportion of eyes with a change of less than or equal to MRSE of .50 diopter and less than or equal to MRSE of 1.00 diopter.  Mean change in MRSE of less than or equal to .50 diopter on an annualized basis and decreasing to an asymptote of 0, and inclusion of 0 in the 95 percent confidence interval for mean change in periods preceding and after stability is established.

The stability target of 95 percent of eyes with a change of less than or equal to 1.00 diopter in MRSE between two refractions performed at least 3 months apart identified in FDA guidance was achieved at both the 6 to 9 and 9 to 12 month intervals.  Additionally, a paired analysis of mean change per month in MRSE shows very small changes in this parameter over time.  Between months 6 and 9, the mean change per month in the manifest refraction was 0.03 diopters while mean change was 0.04 diopters between 9 and 12 months.  However, these data did not achieve the remaining two FDA criteria for stability, including successive decreases in mean change over time and the confidence interval encompassing zero.

Stability of the cycloplegic refraction is shown in this slide.  It is noteworthy that both the proportion of eyes within the stability parameters and mean change in MSRE over time are consistent with the same measures just shown for manifest refraction.  The close match between the manifest and the cycloplegic refractive stability suggests that eyes with latent hyperopia were effectively screened out of the study, preventing masking of poor visual and refractive outcomes by accommodation.

Consistent with the analysis of stability of MSRE, mean change in CSRE by paired analysis was very small between 6 and 9 and between 9 and 12 months.  The upper limits of the confidence intervals were the same for both 3-month intervals and the standard deviation of the mean decreased over time.

When plotting both mean MSRE and mean CSRE over time, the close match between the manifest and cycloplegic refractions is again observed.  As with all corneal steepening procedures there is an initial overcorrection, but this is relatively small following the CK procedure.  This overcorrection has generally been acceptable to study patients.  Emmetropia is reached at approximately 6 months and there is less than a .25 diopter of change between 6 and 12 months.

To more fully characterize the stability of the refractive outcome following CK, we have also examined how much of the intended correction is retained over time and, as you will see, approximately 90 percent of the intended correction remains at 12 months.

As for any elective surgery, patient satisfaction is a very important measurement of the procedure’s effectiveness.  Overall satisfaction is summarized in this slide.  A large majority of patients were very satisfied or satisfied with the outcome of CK treatment.  Approximately 9 to 12 percent of patients were dissatisfied or very dissatisfied at 9 and 12 months.  It should be pointed out that these findings are consistent with reports from other studies of refractive correction of hyperopia.

This summary slide once again demonstrates the strong effectiveness outcomes following CK with study outcomes meeting targets identified in FDA guidance for uncorrected acuity and predictability of refractive outcome.

As we move to a discussion of safety parameters, please note that safety is reported for 400 treated eyes. Key safety outcomes are summarized on this slide.  As shown here, following the CK procedure, all FDA limits for safety were met in the study population.  Only 1 percent of eyes lost more than two lines of BSCVA and best corrected acuity was 20/40 or better in all eyes at 6, 9 or 12 months

post-operative.  Finally, the incidents of greater than 2D increase in induced cylinder was well below the current FDA guidance of less than 5 percent and consistent with the limit of 1 percent in the proposed draft ANSI guidance.

As shown on the previous summary of safety, this slide specifies the safety parameters evaluated following the CK procedure and we will provide additional detail in each of these parameters beginning with preservation of best corrected acuity.  The limits established in FDA guidance for preservation of best corrected acuity are a loss of more than two lines of BSCVA in less than 5 percent of eyes and a decrease to worse than 20/40 of less than 1 percent in those eyes with pre-op BSCVA of 20/20 or better.

In addition to the limits established by FDA guidance, we are also reporting loss of BSCVA of two lines and BSCVA worse than 20/25 for eyes with pre-op BSCVA of 20/20 or better.  As you can see from this slide in the CK study, loss of best corrected acuity was very low across each measure of this parameter.  A loss of more than 2 lines of BSCVA was reported for only 1 percent of eyes from the 3-month visit.  By 12 months, no eye had this level of loss of BSCVA.  None of the study eyes had best corrected acuity worse than 20/40 on any of these visits.

Of the eyes with BSCVA 20/20 or better at baseline, 1 percent at BSCVA worse than 20/25 at 6 and 9 months, but none was worse than 20/25 at 12 months.

If we look specifically at the population of eyes which lost 2 or more lines of BSCVA over the course of the study, you can see that the majority of these eyes had best corrected acuity of 20/32.  No eyes had BSCVA worse than 20/40.

I will now turn the podium over to Peter Hersh who will present information related to induced cylinder.

HERSH:  Thank you, Marguerite.  Mr. Chairman, Panel Members, I’m Dr. Peter Hersh and I serve as a principal investigator for the conductive keratoplasty clinical trial.  My goal in this section is to present data on induced cylinder following the CK procedure.

FDA’s guidance states that less than 5 percent of eyes are allowed to have an increase from baseline of greater than 2 diopters of cylinder.  We will also report the incidents of induced cylinder greater than 1 diopter since this is the limit reported in labeling for all refractive surgery devices used in the treatment of hyperopia.

Finally, at FDA’s request, we will report a similar analysis using a stratification of greater than or equal to 1 diopter of induced cylinder.

Since concerns have been raised regarding induced cylinder following conductive keratoplasty, and since we will be addressing these with a number of analyses, I first wanted to provide you with a summary of this information.  First, you will see that the incidents of induced cylinder after CK meets the current FDA limit of less than 5 percent of eyes with greater than 2 diopters of induced cylinder.  The cylinder decreases significantly over time and resolves in a large proportion of the eyes.

In eyes with induced cylinder, there was on average one line less improvement in uncorrected visual acuity.  However, uncorrected visual acuity improved over time as the astigmatism resolved.

Finally, and importantly, best spectacle corrected visual acuity was not affected by induced cylinder.

So let’s begin here.  As shown in this slide, the absolute change in refractive cylinder remained well below the FDA guidance of less than 5 percent of eyes with induced cylinder greater than 2 diopters at all follow-up examinations.  From 6 months on, the proportion of eyes with induced cylinder of greater than 2 diopters also met the more stringent proposed limit of less than 1 percent.  Whereas, the frequency of astigmatism was relatively high at the early examinations, this decreased significantly over time.

The same information on absolute change in refractive cylinder is also shown here for the cohort of eyes with all visits through 12 months further demonstrating that induced cylinder decreases over time and meets FDA guidelines.

In a further effort to understand both the magnitude and course of astigmatism after CK, we also examined the mean induced cylinder over time.  Here you can see that the mean induced cylinder decreases to less than .50 diopter at months 9 and 12 and this decrease was statistically significant.  We also performed statistical modeling to determine whether the resolution in induced cylinder over time was associated with a loss of refractive effect with regard to historical hyperopia since this obviously would be of concern.

This modeling revealed that the resolution of induced cylinder was not attributable to regression of the spherical correction.

Next, we attempted to understand the actual clinical impact of induced cylinder.  To do this, the study population was stratified into those eyes with greater than 1 diopter of induced cylinder as compared to eyes with less than or equal to 1 diopter of cylinder.

Now as you can see from the slide, there was no difference between the two groups with regard to loss of spectacle corrected visual acuity at 12 months.  Indeed, there were no eyes in the induced cylinder group that lost 2 or more lines of best corrected vision.

We also examined of the effects on best spectacle corrected vision of manifest cylinder greater than 0.75 diopters combined with an axis shift of 30 degrees or more which the FDA considers clinically significant.  Eyes with this level of cylinder and axis shift had no change in spectacle corrected vision, while there was a loss of lines in 6 percent of eyes in the group with less than 0.75 diopters of manifest cylinder, or no significant axis shift.

In order to evaluate the impact of induced cylinder now on the efficacy of the procedure, we performed an analysis comparing mean lines of improvement in uncorrected visual acuity between eyes with induced cylinder and eyes with less than or equal to 1 diopter of induced cylinder.  This analysis first was performed using two stratifications.  Induced cylinder by absolute magnitude and induced cylinder by vector analysis.  As shown here, the mean UCVA in the induced cylinder group was 20/32 compared with 20/27 in the low cylinder group.

Furthermore, in the induced cylinder group improvement in uncorrected visual acuity was 3.3 lines compared with an improvement of 4.4 lines in the low cylinder group.  As you can see, results of this comparison using the stratifications by vector analysis yielded similar results.

In addition, an analysis was performed for eyes with any increase in cylinder over baseline and axis shifts of 30 degrees or more which was considered by FDA again to be clinically significant.

As shown here, significant shifts in axis combined with any increase in cylinder from baseline had minimal effect on uncorrected vision and no effect on lines of uncorrected visual acuity improvement.

These data thus suggest a difference of approximately 1 line of improvement in uncorrected visual acuity as a result of induced cylinder of greater than 1 diopter.  But only a minimal effect on uncorrected vision of any increase in cylinder over baseline when combined with significant axis shift.

To look further into the effect of induced cylinder on uncorrected visual acuity the change in uncorrected visual acuity over time was evaluated for those eyes with induced cylinder of greater than 1 diopter at the 1-month visit.  Consistent with the resolution of induced cylinder over time, uncorrected visual acuity improved substantially in these eyes from 1 through 12 months.

As shown in this graph, while the proportion of eyes with uncorrected visual acuity of 20/20 or better was low, 79 percent of eyes had uncorrected acuity of 20/25 or better by 12 months and 84 percent had uncorrected visual acuity of 20/32 or better at 9 months.

The FDA target of 20/40 or better in 85 percent of eyes was achieved beginning at 3 months post-operatively.

We next wanted to compare uncorrected acuity of 20/20 or better in eyes with induced cylinder to the eyes with less cylinder at 1 month.  The light blue bars that you see here show the low cylinder group at 1 month, whereas the dark blue bars represent the induced cylinder group.  Consistent with the resolution of induced cylinder over time, uncorrected visual acuity improved substantially in time for both groups and the proportion of eyes achieving UCVA of 20/20 or better was similar for both groups at 12 months.

The same comparison of eyes with induced cylinder versus eyes with less cylinder is now shown here for uncorrected visual acuity of 20/25 or better.  As you can again see from this slide, the proportion of cylinder eyes with uncorrected vision of 20/25 reached 50 percent at 3 months and there was virtually no difference between groups in uncorrected visual acuity at 9 months and at 12 months.

Now finally, when looking at uncorrected vision of 20/40 or better, the low and the high cylinder groups are very closely matched from 3 months forward with virtually no difference in uncorrected visual acuity.  The FDA target of 85 percent at 20/40 or better was achieved at 3 months for both groups.

Now we’re going to shift gears a little bit and look at the data a somewhat different way.  FDA expressed an interest in looking at eyes with greater than or equal to 1 diopter of induced cylinder rather than simply greater than 1 diopter of induced cylinder and comparing these eyes to less than 1 diopter of induced cylinder.  So we’re dealing here with a different stratification.

Consistent with the previous comparison, using the induced cylinder stratification of greater than 1 diopter there was no significant difference in the loss of spectacle corrected vision between these two groups.

As before, we again performed an analysis comparing mean lines of improvement in uncorrected visual acuity between eyes with induced cylinder and those with less induced astigmatism.  Here again, the data suggests approximately a difference of 1 line less improvement in uncorrected visual acuity in the induced astigmatism group and again no effect on uncorrected visual acuity when you look at a group of manifest cylinder greater than 0.75 diopters combined with an axis shift of 30 degrees or more.

Change in uncorrected vision over time was also evaluated for the eyes with one or more diopters of induced cylinder at one month.  Again, consistent with resolution of induced cylinder over time, uncorrected acuity improved substantially through the 12-month follow-up.

Finally, to complete the examination of the impact of induce cylinder after CK we looked at those eyes with induced cylinder at 1 year.  Of the total population of eyes at 1 year, there were 203; 25 had 1 or more diopters of induced cylinder and 13 eyes had greater than 1 diopter of induced cylinder.  Of these, 21 of the 25 and 9 of the 13, respectively, were treated with the current nomagram and therefore could be evaluated for effectiveness.  But first turning to safety, let’s look at best spectacle corrected visual acuity.

Looking at safety, best corrected visual acuity was very similar for the two groups of eyes with induced cylinder.  The UCVA was 20/32 or better for all eyes and all by one eye had best spectacle corrected visual acuity of 20/25 or better.

Looking now at uncorrected visual acuity, there was a substantially lower proportion of eyes with uncorrected vision at the 20/20 and 20/25 levels in the presence of induced cylinder compared with eyes with less cylinder.  However, the proportion of eyes with uncorrected vision, 20/40 or better, was 81 percent for eyes with 1 diopter or more of induced cylinder approximating the FDA guidance target.

Finally, let’s look at the astigmatism outliers at 12 months.  A total of 9 eyes treated with the current nomagram had induced cylinder greater than 1 diopter at 12 months.  This listing presents the uncorrected and best corrected acuities as well as the satisfaction grading for these outlier eyes.

As you can see, post-operative, spectacle corrected visual acuity was 20/25 or better for all of these eyes and the majority of eyes, indeed, had spectacle corrected visual acuity of 20/20 or better.  Uncorrected visual acuity was 20/32 or better in 6 of the 9 eyes, whereas the remaining 3 eyes had UCVA of 20/50.

It’s of interest to note that 5 of the 9 eyes were satisfied or very satisfied with the procedure and 2 were neutral.  One was dissatisfied and finally, one was very dissatisfied.  Overall then, as you can see, uncorrected visual acuity and best spectacle corrected vision, even in these outliers, was quite good.

In summary then the incidents of induced cylinder reported in the CK clinical trials meets the current FDA limit of less than 5 percent of eyes with greater than 2 diopters of induced cylinder as well as the more stringent limit of less than 1 percent which has been identified in the draft ANSI guidance.  The frequency and the magnitude of induced cylinder decreased significantly over time, resolving in a large proportion of the eyes.

Importantly, this resolution of induced cylinder was not attributable to regression of the spherical correction.

Induced cylinder assessed by absolute magnitude, vector analysis and in conjunction with access shift was associated with approximately one line less improvement in uncorrected visual acuity.  UCVA in these eyes improved over time as the induced cylinder resolved.

Finally, induced cylinder had virtually no effect on best corrected visual acuity, irrespective of the analyses performed and therefore does not raise any safety concerns.

Thank you very much.  Dr. McDonald will now continue with her presentation of the safety and effectiveness data.

McDONALD:  Thanks, Peter.  Other safety parameters evaluated included endothelial cell loss, patient symptoms, complications and adverse events.

Specular microscopy, using the noncontact Conan Robocon was performed on a subgroup of eyes enrolled in the CK study and endothelial cell density was analyzed for images obtained centrally,

mid-peripherally and peripherally.  As shown in this slide, endothelial cell density remained relatively constant over the course of follow-up from baseline to 3, 6 and 12 months in all regions evaluated.

The percentage change in endothelial density was similarly constant over the course of follow-up with no changes observed in any of the regions evaluated.  This absence of any change in endothelial cell density or morphology over the course of follow-up, irrespective of the region examined, establishes the safety of radio-frequency energy delivered to the cornea via the keratoplast tip.

Analysis of patient symptoms in determination of the clinical importance of reported symptoms, presented a reporting challenge since no limits had been established by the FDA.  Nor are there standards for collecting and reporting these data.

In the absence of pre-established limits, we have utilized a level suggested by FDA during review of our PMA, an increase of 5 percent or more in moderate to very severe symptoms.

A subjective questionnaire was administered to all study patients pre-operatively and at follow-up examinations.   Patients were asked to rate each of the symptoms  listed on this slide as either none, mild, moderate, marked or very severe.

As mentioned, FDA indicated an interest in subjective symptoms which increased from baseline levels by 5 percent or more in the categories of moderate, marked or very severe.  The symptoms which met this criteria are highlighted on this slide and include dryness, glare, halos, double vision and changes in vision.

The actual incidents reported for each of these symptoms is shown here.  Again, this represents those symptoms for which a 5 percent increase from baseline and moderate and marked symptoms was reported.  It is noteworthy, that there was no significant increase in the very severe rating for any symptom.

When considering the actual percentage increase in the moderate and marked symptoms listed here in detail, it can be observed that all symptoms reported as moderate had an increase of 5 to 7 percent, thus just exceeding the threshold of 5 percent identified by the FDA as clinically relevant.

More importantly, the increase in marked symptoms reported at 6 months decreased at 9 and 12 months and as previously noted, there was no significant increase in the very severe rating for any symptom at any time during the study.

The final component to be evaluated for safety is reports of complications and adverse events.  FDA guidance limits the occurrence of adverse events to not more than 5 percent of eyes, with any single adverse event occurring in less than 1 percent of eyes during the study.

Information on complications and adverse events was collected at each study visit, using the extensive lists of reportable events identified in FDA guidance.  As you can see from this slide, the complication rate for the study was very low, with only a small number of complications reported at any time during the study.

Further confirmation of the safety of the CK is provided by the low incidence of adverse events.  There were only three device or procedure-related events.  In one case, a corneal perforation occurred during the procedure.  Investigation revealed that the glue bond attaching the Teflon top to the CK tip was fractured from a lateral force which may have occurred during removal from packaging allowing the stop to separate from the tip.  This subject was subsequently treated and has had excellent outcomes with uncorrected acuity of 20/16 at 12 months.

Random sampling and testing of keratoplast tips indicates that this occurrence is not design or manufacturing-related and was an isolated event.  To prevent further possible occurrences, additional instructions have been added for the surgeon regarding the safe removal of the keratoplast tip from its packaging.

In two cases, no energy was applied during the initial treatment.  In both cases, an internal connection was found to have a poor solder joint, resulting in no delivery of radio-frequency energy.  A design change to address this was developed and tested and has been implemented following review by the FDA.  This design modification has prevented any additional occurrences.

Of the two eyes that were affected by this complication, one was successfully treated 3 weeks later.  The second eye was determined to be illegible for participation in the study, due to narrow angles and was therefore exited from the study.

Other adverse events are summarized in this slide, including IOP greater than 25 millimeters of mercury in 3 eyes of 2 patients; 1 eye with mild iritis; a retinal break that was successfully treated with argon laser; and a decrease in BSCVA secondary to optic atrophy and inferior attitudinal hemianopsia.

Several non-ophthalmic events were also reported including cancer, heart attack, temporal arteritis, and miscellaneous other unrelated events.

This slide summarizes the safety outcomes following CK and as we’ve seen from the data presented to this point, the study outcomes meet all limits identified in FDA guidance.

Summary and indications for use.  To summarize the effectiveness data presented, the study results for uncorrected visual acuity and accuracy of the refractive outcome exceeded FDA targets for accuracy of MRSE and uncorrected visual acuity.  Furthermore, from the 6-month examination, change in MRSE was less than or equal to a .50 diopter for 85 percent of the study population and the mean in MRSE change per month was small, 0.03 diopters to 0.04 diopters for a total mean change of less than a .50 diopter per year.  Ninety-four percent of the intended correction remains at 12 months by a matched pair analysis.  This is compelling effectiveness data considering that no re-treatments were performed in this study.

All safety limits established by the FDA and the study protocol were achieved in the study population.  Specifically, all criteria related to the preservation of BSCVA were met.  With regard to induced cylinder, the proportion of eyes with more than 2 diopter was below the FDA target throughout the course of the study and induced cylinder decrease in frequency and magnitude over time.  There was no effective induced cylinder on BSCVA and the effective induced cylinder on UCVA was reflected largely in the slightly lower proportion of eyes with UCVA 20/20 or better.

Finally, the incidence of adverse events was very low and all resolved without sequelae.

On this basis, we respectfully request that this Advisory Panel renders an approval determination for this PMA for the conductive keratoplasty procedure with the following indication for use:  CK treatment for the reduction of spherical hyperopia in the range +0.75 to +3.25 diopters of cycloplegic spherical hyperopia; -0.75 diopters or less of refractive astigmatism; +0.75 to +3.00 diopters cycloplegic spherical equivalent; in patients with less than or equal to .50 diopter difference between pre-op, manifest and cycloplegic refractions; in patients 40 years of age or older.  The magnitude of correction diminishes over time with an average loss of approximately 6 percent by MSRE paired analysis of the intended correction at 1 year.  The proportion of intended correction retained beyond 12 months is undetermined.

Thank you for your time and attention.

SUGAR:  Does that end the sponsor’s presentation?  Please stay at the table then.  We are running ahead of time and what we will do is continue — the program has lunch designated at noon.  We still intend to do that, but we will move head.  First, we’ll have the Panel questions for the sponsor and then we will try to move ahead with the FDA presentation, if we can, prior to lunch.

So questions?  Dr. Pulido?

PULIDO:  Yes, thank you very much.  Jose Pulido.  Thank you very much for a very nice presentation and I’m sure that my colleagues will be, from what I’ve been reading, will be delving into the statistics, so my question isn’t in the statistics.  My questions are first, the safety of radio-frequency energy in patients with pacemakers or cochlear implants.

GORDON:  It’s a contraindication.  We were looking back to the Refractec technical —

THORNTON:  Can you identify yourself, Judy, and speak into the microphone?

GORDON:  I apologize.  Judy Gordon and we were referring to Refractec technical personnel who were here and who have communicated that those patients would be contraindicated for this treatment.

PULIDO:  Okay, because that wasn’t in the contraindications and these are elderly patients and these are the people that will have pacemakers and cochlear implants.  And so that needs to be put in there if it ultimately will be accepted.

GORDON:  That can be corrected in the labeling.

PULIDO:  Secondly, slide 22 and slide 79 alluded to a patient that was supposed to have originally received the treatment, but first the machine wasn’t working and then it was determined the patient had narrow angles and therefore did not receive treatment.  That wasn’t one of the contraindications and yet, you said well, he didn’t receive it because the patient had narrow angles and therefore it was determined that that was contraindication.  So are you saying narrow angles is a contraindication?

GORDON:  Judy Gordon again.  Narrow angles is not a labeling contraindication, but it was an exclusion criterion identified in the entry criteria for the study population, so that patient was inappropriately enrolled, meaning it would have been a protocol deviation if the patient had been successfully treated, but in re-screening the patient after the initial failed treatment to re-perform another baseline examination, it was determined that the patient was not eligible and should not have been enrolled in the first place and so the patient was discontinued without treatment.

PULIDO:  How many patients enrolled did have narrow angles and how can you be sure that that is not a contraindication?

GORDON:  I think the issue of narrow angles on a hyperopic population, particularly in the studies, the refractive surgery studies of hyperopia really relate to at least in part the number of cycloplegic refractions that are required in the post-operative period and the risks therein of the cycloplegia and so it’s pretty typical to exclude those patients from these studies, but I think it doesn’t necessarily imply that it would be an appropriate contraindication, but I’ll rely on my clinical advisors here to add commentary on that.

McDONALD:  I think that, as with all studies —

SUGAR:  Again, please identify yourself, Marguerite.

McDONALD:  Dr. Marguerite McDonald.  As with all studies, we were trying to just have the cleanest possible entry criterion be exceedingly careful.  Judy’s comment is correct that we cyclopleged the patients repeatedly, so we were a little worried there an also you know, we really don’t know what happens to the peripheral profile.  Just to be extra careful.  I really don’t think the angle would be affected, but just to be extra careful in the study.  We excluded them.

PULIDO:  Right.  But again, is there

— I don’t have any indication from what I’ve read that there isn’t a change to the peripheral profile into the trabeculum meshwork.

I thought maybe you would have data otherwise that I wasn’t able to find.

DURRIE:  This is Dan Durrie and I’ve been involved in several of these studies and there hasn’t been any evidence in any collagen shrinkage procedure that there is narrowing, but there’s not a good way, we didn’t do ultrasonic measurements.  There’s just not a good way to measure it.

Being involved in the design of these studies it’s exactly true what Judy has said.  This really is a contraindication in the study because we’re going to cycloplege these patients multiple times and that has really been the contraindication on putting patients in, but there’s nothing in this study or other ones that I’ve been involved in that are shown that the angle structure is changed with collagen shrinkage procedures and periphery.

PULIDO:  One other question that I had and that relates to patients, patient number — the hospitalization for tonsillectomy an nasal septum repair.  Now it lists that — if you could turn to — is it Volume II, page 191 and in it, it has the manifest refraction at the 6-month visit with -2.00,

-0.75 at 20 in the right eye and plano -0.5 at 165 in the left.  So this patient had, if he or she was very hyperopic, a marked myopic shift.

We don’t have her pre-op refraction.  What was it?

GORDON:  We can look that up.  Judy Gordon.  We’ll have to pull that information.

PULIDO:  I’d like to know what that was.

GORDON:  We’ll get to you in a few minutes with that information.

SUGAR:  The issue being?

PULIDO:  The issue being just want to make sure the patient was properly enrolled in the study.

SUGAR:  Are there other questions for the sponsor?

Go ahead, Dr. Matoba, and then Dr. Grimmett.

MATOBA:  I would expect, this is Alice Matoba.  I would expect some increase in intraocular pressure immediately following the procedure since you were causing shrinkage of collagen.  I wondered if you had taken an IOPs and if you had some idea of what the magnitude of the change might be?

GORDON:  Judy Gordon.  Intraocular pressure measurements were made at every examination, including post-operative Day 1 and there was no evidence of any change.  We can show you the —

MATOBA:  Actually, I’m talking about acutely, immediately after the procedure, I would expect a rise in pressure.

GORDON:  Measurements were not made in the first 24 hours.

MATOBA:  Okay.  And then my second question is in terms of your endothelial cell loss data which looked great, the n was only 162 and that subsequent patients, I wondered what the treatment parameters were if you had enough patients who had the 32 spot or the higher level of treatment in those patients?

GORDON:  Judy Gordon.  That’s an excellent question and we’ll take a look at that, but again, I can’t answer without looking.

MATOBA:  Okay, then my third question is in regard to patient satisfaction data.  It appeared to me that as you go towards 12 months the percentage of patients who were dissatisfied or very dissatisfied, the combined total appeared to increase compared to the earlier study points and the n was only 198 for 12 months.  I wonder if that trend toward slightly increasing percentage of dissatisfied and very dissatisfied patients holds up, if you look at more patients or it could increase, continue to increase over time?

GORDON:  Judy Gordon, again.  There tends to be considerable variability in these types of subjective questions and I will check with the statistician, but I think that the variances that are observed in those tables were nonsignificant.  We did some extensive statistical testing there, so we can check on that, but we haven’t seen any trends that would indicate any change, dramatic change over time.

GRIMMETT:  Michael Grimmett.  I have one comment and two questions.

SUGAR:  I guess there’s a follow-up comment.

McDONALD:  I’m sorry, Marguerite McDonald.  One last thing, the cyclometric testing pulls different things out.  At one year, Dr. Matoba, 95 percent of patients felt that their quality of vision was improved.  Five percent said no improvement, so those questions pull out different things, but we will look for you.

GRIMMETT:  Mike Grimmett again.  One comment, two questions.  I had a similar thought to Dr. Pulido regarding the pacer issue and I would just add that the FDA or sponsor consider implantable defibrillator devices as well.

Question.  On slide 8 of your presentation that outlined how the spots are placed on that corneal marker, for the last 8 spots when you move from 24 to 32, is there any identifying marker or anything how you pick in between or is it best estimate and how hard is that to do with precision?

McDONALD:  Dr. McDonald.  That’s an excellent question.  The hand-held marker does not have dashes or elements to indicate the last 8 spots.  If you’re doing a maximum treatment of 32, but several things.  The little distance that you’re bisecting is so short, it’s very, very easy to dissect it.  Placement doesn’t actually matter of the last 8 as long as you’re somewhere on that ring because what you’re doing is cinching the periphery, so even if you’re a tiny bit off on dissecting the short distance which would be hard to do, you are still circumferentially shrinking the ring.

Last, but not least, if you add more elements to the marker and then you ink it up with one of the FDA-approved dyes, you start to get a big blue smear and you really can’t see anything, so that’s the maximum that you can practically put on one marker.

GRIMMETT:  Thank you.  And another question, I just want to clarify or reconcile some data in your slides that went by too fast for me to reconcile it.  Slide 64 of Dr. Hersh’s presentation that goes over this cylinder with uncorrected visual acuity, we have in the latter column eyes with greater than or equal to 1.00 diopter of induced cylinder and we see the rates of certain levels of vision, for example, 29 percent have 20/20 or better.

I want to reconcile that with slide 61 that I think is showing the exact same data, trying to show induced cylinder greater than or equal to 1.00 diopter at various vision levels.  The vision level, at least the way I’m reading it on slide 61 says 20/20 or better in 49 percent.  Yet, slide 64 says 20/20 or better in 29 percent.  And the other categories are different as well.  20/25, slide 64, says 52 percent; slide 61 says 80 percent at month 12.

HERSH:  These are —

GRIMMETT:  Go ahead.

HERSH:  Dr. Peter Hersh.  These are actually different groups of patients.  Slide 61 is that group of patients who had greater than or equal to 1.00 diopter of cylinder at the 1-month visit.  So all patients who we saw at 1 month, who had greater than or equal to 1.00 diopter of induced cylinder, we then followed on for the subsequent visits to look at the natural history of the induced cylinder.

Now slide 64 is a snapshot of the group of patients who have reached 12 months.  So it’s simply the group of patients who have reached 12 months looking at those with induced cylinder and those without induced cylinder, so they represent different patient groups.

GRIMMETT:  Great.  Thank you very much.

SUGAR:  I have a question.  In terms of the pattern, you prescribe a pattern of placing the spots.  Was that derived empirically or arbitrarily or how was it derived?

DURRIE:  The pattern — this is Dan Durrie.  The pattern was done off of international investigation that was done previously and then very importantly, the first 54 patients that were done before the nomagram adjustment and I think that that’s why you have a clean group of data done with one pattern that was evolved not only on international experience, but then the experience of the first 54 eyes to come up with the suggested patterns.

SUGAR:  So — Joel Sugar.  So you’re implying that you tested different patterns and this was the most effective and the pattern does make a difference?  Is that the implication from what you just said?

DURRIE:  No.  The situation as far as this particular pattern of only adding one spots and not changing energy, a lot of those things were looked at before, but in this particular thing is the only thing that the surgeon does in which makes this quite easy is adding an additional number of spots for higher diopter correction.

SUGAR:  That, I understand.  I’m talking about the pattern in which they’re applied, given that you decided that you’re going to do 24 spots on a patient with 2 diopters.

McDONALD:  Dr. McDonald.  This pattern was established by the international investigative team, but it’s also the pattern that’s been used historically in the PERK study and other studies because if, for whatever reason, you have to abort a procedure in the middle, you will have induced less cylinder.  If you go around from one spot to the next you could induce a huge amount of astigmatism, if for whatever reason you had to abort.

SUGAR:  Thank you.  Dr. Weiss?

WEISS:  I had three questions.  The first one was that 80 percent and I think in the September document, it was indicated that 80 percent of patients did not need glasses after the procedure.  Considering that two-thirds of patients had 1.9 diopter of hyperopia or less, do you have a percentage of patients who wore glasses at a distance before the procedure, so that we can compare the two numbers?

GORDON:  Dr. Judy Gordon.  No, we did not collect preoperative spectacle correction usage.

WEISS:  Okay.  In the list of side effects patient subjective complaints, mild diplopia increased from a level of 5 percent pre-op to 14 percent subsequently.  Was that correlated with pupil size or refraction?

GORDON:  Judy Gordon.  I can speak to this because I had the pleasure of addressing the challenge of looking at symptoms that are rated on a 5 point scale about 20 symptoms over 6 visits and so in trying to do a meaningful analysis of this and because we had collected pupil diameters, we actually just did a statistical comparison of an overall type of symptomatology for smaller pupils versus larger pupils and we were really gratified to see that there were no differences observed at all.

WEISS:  So we don’t really know why they had that complaint of diplopia.

GORDON:  Correct.

WEISS:  Finally, this is in regard to the indications for the procedure.  On the last slide, you indicated that the proportion of intended correction retained beyond 12 months is not determined, undetermined, and in the physicians reference guide it’s indicated that there is some loss of refractive effect with time.

Are you not saying that this is a temporary procedure?

GORDON:  This is Judy Gordon again.  I think we were attempting to articulate in some fashion that have a body of information and a clear understanding of what occurs during the initial 12-month of follow-up, but not beyond and we’ve attempted to somehow quantify or semi-quantify to patients and physicians what proportion of the effect or the intended effect is retained at 12 months and for that reason we have suggested the 94 percent retained.  But beyond the 12-month period in the absence of data, we’ve added language suggesting that the continued course of refractive correction is undetermined.

WEISS:  Would not the 24-month data, although limited, give you some more indication as to what happens in the patients in whom you have 24-month data?

GORDON:  Yes, absolutely.

SUGAR:  Go ahead, Dr. Mathers.

MATHERS:  Dr. Mathers.  I have a couple of questions.  You mentioned something about that this data was, of course, a single application.  Do you think that there will be for some patients several applications as there are with other refractive procedures and how would you approach that?

GORDON:  Judy Gordon.  The purpose of the study was to evaluate the outcome of a single procedure and we have no information at this time on the effects or benefits of additional applications of spots.

MATHERS:  And some patients will have smaller corneas.  Was there any exclusion criteria regarding the size of the cornea and would you have difficulty in treating more peripheral lesions or making more peripheral lesions in smaller corners.  Some of these hyperopic people might have smaller corneas?

McDONALD:  Dr. McDonald.  We did not measure pre-op corneal diameter, but no one that I’m aware of, none of the investigators complained that they had difficulty placing the spots in any of the corneas.

SUGAR:  Dr. Matoba?

MATOBA:  In your presentation you stated that the induced cylinder resolved over 12 months, but your spherical induced change was stable and why do you think that is?

HERSH:  It seems to be a wound-healing effect that we really see in all refractive surgery procedures that we do.  Wound remodeling, particularly epithelial remodeling has been shown in any number of procedures we do now, PRK lasik tend to resolve astigmatism in topography abnormality over time and I would suspect that it’s a similar case here where wound healing particularly, possibly epithelial remodeling diminishes the cylinder and we so retain the spherical effect.

SUGAR:  Go ahead, Dr. Bradley.

BRADLEY:  Dr. Bradley.  In a lot of the statistics you just presented, the most troubling case was the 1-month data set where some of the FDA marks were not met.  It makes me wonder what happened prior to 1 month.  Do you have data collected during that period, particularly I’m interested in the manifest refractive error, the uncorrected visual acuity and best spectacle visual acuity.  And my concern, of course, is that the patient will be suffering some, albeit temporary, visual disability due to the procedure.

GORDON:  Judy Gordon.  The standards for reporting in these refractive surgery studies is pretty much what we’ve shown and so uncorrected acuity is manifest and we also performed cycloplegic refractions to have more confidence in our outcomes were collected and were reported at 1, 3, 6, 9 and 12 months.

We’ll have further discussion later relative to some additional comments in labeling and we’ve shown that the uncorrected acuities, given the initial overcorrection could lead to some challenges in uncorrected vision.  None of the patients in the studies, either requested or required spectacle correction during the early period, but we’ll propose labeling to suggesting that that may be a concern and that physicians and patients should be aware of that.

BRADLEY:  Can I just come back on that?

SUGAR:  Dr. McDonald wanted to further respond.

BRADLEY:  Can I just clarify something?  You didn’t answer the question.  I asked you if you had any data prior to one month.  You’ve just told me you presented the 1-month data which I’ve seen, of course.  I’ll repeat the question.  Do you have any data prior to one month?

GORDON:  I’ll have to check and find out.  I think that we don’t.

McDONALD:  Dr. McDonald.  Dr. Bradley, we looked at the people at one month who had an MSRV of -1.00 or worse.  Also, the people who at one month were 20/40 or worse than 20/40 uncorrected.  In the first group, the people with an MSRE of -1.00 or greater at one month, that was 23 percent of the population, 81 eyes.  Six patients had same day bilateral in that group.  Of the six patients, two were very satisfied, two were satisfied, two were neutral, but none were dissatisfied or very dissatisfied.  At one month, the 21 percent, n equals 73, who had worse than 20/40 uncorrected.  There were nine patients same day bilateral.  Three of the nine were very satisfied, three of the nine were satisfied, and three of the nine were neutral and no one was dissatisfied or very dissatisfied.  So although they are briefly, either as a percentage of the population, almost a quarter that are briefly more myopic or have worse than driving vision, they are not dissatisfied or very dissatisfied.

BRADLEY:  If I could just comment on that.  In some ways it seems reassuring, but to me it seems quite alarming that the criteria of 20/40 that we are holding out as being so important you find those people who have worse than 20/40 are quite satisfied.  Likewise, people who are 1.00 or more diopter myopic are satisfied and makes one wonder how to interpret the satisfaction data.

McDONALD:  Dr. McDonald.  I think they’re well aware that it’s temporary and I think that’s the key to their satisfaction.

SUGAR:  Dr. McMahon and then Dr. Weiss.

McMAHON:  Tim McMahon.  There was no data presented in your presentation and only minimal data presented in supplemental submission with regard to the near vision.

SUGAR:  Is that microphone on?

McMAHON:  Yes.  Let me repeat that.  Tim McMAhon.  There were two graphs presented in the red book with regard to near vision.  My question is two-fold.  One is can you describe your methodology for correcting for best corrective near vision and how that was measured?

GORDON:  Judy Gordon.  Perhaps I can just comment.  Because near vision was not identified as a primary outcome in this study, we have concerns in evaluating the data as we were preparing the PMA in the rigor of the method and there was inconsistency in the near cards used, so we don’t feel it would be the basis for any claims.  It can give us an indication though of what did occur and that is that we did not see any effect of conductive keratoplasty on best corrected near acuity and there was a pretty substantial improvement in near uncorrected visual acuity from pre-op where about 4 percent of eyes had Yager* 3 or better and that improved to about 40 percent.  We could show you that data.  It’s in one of the later submissions to FDA.  But again, we were reluctant to present that and over-represent it in any way, given that there was not necessarily an adequate level of standardization of the methodology for collecting the information.

McMAHON:  All right, the second one is help me get over my amazement that a substantial percentage of the patients had induced cylinder and/or shifts in cylinder axis with this procedure, yet the percentage of patients who had excellent best corrected acuity seems to defy logic to me.

When you have a focal procedure that affects local areas of the cornea, it seems to me that it would be nearly possible not to have a substantial increase, the amount of irregular astigmatism, yet with a very high percentage of patients having best corrected acuity of 20/20 or close to that, it implies an orthogonal or regular astigmatism.  Can you help me explain how that is?  To me, that just doesn’t wash.

DURRIE:  This is Dan Durrie.  You really bring up an important point and that’s why I wasn’t very impressed with this data, is that this is best corrected spectacle acuity and you would expect if it was irregular astigmatism that they would be losing best corrected vision and in this particular procedure, we have seen that the astigmatism deduced was at least correctable with spectacles and it did not have the induced or regular astigmatism you expect from focal correction.  So I think the data really speaks for itself is the fact that we can’t correct regular astigmatism with spectacles.  We know that.  And the fact that we did preserve best corrected vision I think is a sign that the irregular astigmatism was very small.

McMAHON:  Do you have topography data with this data set?

HERSH:  I’ve done a few analyses simply on my own patients and can’t comment on the entire patient set.  We did not find any correlations, thus far, with topography and a number of outcomes.  We looked at procedure centration which indeed was quite good and that showed no correlation with any outcomes including induced astigmatism.  We looked at loss of spectacle-corrected vision and again, did not find a correlation.  Indeed, the topography, anectdotally, look good and the kind of irregularities that one might see or one saw in PRK, for instance, during the wound healing phase didn’t really again, in my patient subset, appear to obtain.  So potentially working in the periphery, rather than removing tissue essentially gives you a more regular response and the wound healing effects that could lead to irregular topography might be precluded in a peripheral technique like this.

McMAHON:  Thank you.

SUGAR:  Okay, Marguerite and then Dr. Bradley.

McDONALD:  Marguerite McDonald.  Just to add a little more to that comment, I think working in the far periphery is the key and whenever we’ve seen a hand-held procedure very close to the visual axis like hexagonal keratotomy, the incidence of irregular astigmatism goes sky high.  So I think it’s the fact that we’re out in the far periphery.

SUGAR:  Dr. Bradley, then Dr. Huang and then Dr. Jurkus and then Dr. Grimmett.

BRADLEY:  It’s sort of a carry-on question from Dr. McMahon’s question.  If I recall in the data, the subjects who had the largest amount of induced astigmatism did have slightly lower best spectacle corrected visual acuity.  Perhaps you could either confirm or deny that.  If that is the case, my interpretation was, in fact, that along with astigmatism, which we are calling regular astigmatism, there was some induced irregular astigmatism, which was not correctable by the spectacles and in the modern parlance I think we might refer to that as some higher order aberration, probably kerma which one might imagine from some hand-held device which doesn’t have precise positioning.  But I may have misrecalled the data.  Can anyone confirm or deny what I just —

SUGAR:  I thought that they showed that the acuities were actually quite similar.  I’m waiting really for them to give their own data.

BRADLEY:  Then we can forget what I just said if it’s the same, but I thought I remember seeing them differently.

Dr. Weiss is suggesting that maybe my recollection is from the original data set and not the revised data set.

Perhaps if you could just check on that anyway, but the idea being — you’re right, if it is correctable with spectacle lenses, remarkably the induced cylinder is just that, it is induced astigmatism whereas we might have imagined that the measured induced astigmatism is just one component of a myriad of aberrations that are induced by the procedure, and therefore we would imagine that some of these would not be correctable with something we call correcting lens and therefore we would imagine those with large amounts of induced astigmatism would presumably have larger amounts of other aberrations which would not be correctable and therefore best spectacle corrected visual acuity would not quite be as good in that group.

SUGAR:  Is there a comment from the sponsor?  Okay, Dr. Huang?

HUANG:  Andrew Huang.  My concerns the long-term stability of your results.  From 6 to 9 months the regression was .09 diopter and from 9 to 12 months the regression is .12 diopter.  Do you have any evidence suggesting that this rate of regression is stabilized after one year of follow-up or do you think the data in whatever, 24 months, patients you have collected suggesting that this rate of regression is progressive?

GORDON:  We have 24-month data and updated 12-month data that’s been submitted to FDA as we indicated, but they were submitted quite recently, not in anticipation of planning for this Panel meeting.  So we had no plans to show those data, but we can comment that in a very small number of eyes with data through 24 months, the rate of change is quite small, between 12 and 24 months, but it’s a very small population and for that reason we’ve taken the position in our proposed labeling that the loss or the change in refractive effect after 12 months is undetermined at this point in time, based on the data that you have reviewed.

SUGAR:  Dr. Jurkus, I think is next.

JURKUS:  My question goes to the patient satisfaction from draft 1 of pages 26 and 27.  And in looking at them it appears that 1 in 3 people showed an increase of some sort in complaints of halos, fluctuation in vision and variation in dim vision from pre-operative to post-operative.  And to me, this seems like quite a large amount of increase.

Is there any correlation to pupil size or to power or reasons why that, again, 1 in 3 would say that they have more problems with halos and fluctuation in vision after surgery than they did before?

GORDON:  I think there’s two separate issues here.  One is, as I mentioned before, we did do a very thorough statistical analysis relative to pupil size because obviously that would be a concern that one would want to label for and we did not see any effect of pupil size on symptoms.  The other comment is more general and that, as I mentioned, we collect information on a sale, a 5-point scale of 0 to 5 at six periods in time and for about 20 symptoms.  So you tend to see all kinds of changes all over the place.  For that reason, as we struggle to somehow define what would be considered clinically relevant we came up with an — FDA had suggested looking at a greater than or equal to 5 percent increase in the categories beyond mild, so the marked, moderate and very severe.  You see the biggest changes over time in both directions and across these types of studies in the mild where you just get a lot of people marking these things on these forms.  You get the sense of, if you look at these individually as I have over a number of studies and I think Dr. Durrie could comment to that effect as well, so I think the data that we think is clinically relevant is what we showed in terms of greater than or equal to 5 percent increase from baseline and those symptoms that you measured did fall into that category, although they did improve to some extent over time.

JURKUS:  Was there any correlation — Dr. Jurkus again — to the amount of correction?  Did the people who had like the +3 people have more fluctuation than +75 people?

GORDON:  This is Dr. Gordon again.  I would have to confirm that, but I believe that was not the case and one of the things that we noted as we looked at some of the key parameters by dioptric group was that it was in the higher range of hyperopes, that we have the higher levels of satisfaction.  More positive, I think it just has to do with more perceived benefit perhaps, but I don’t believe we saw any difference across dioptric range and symptom reporting that was at any statistical level.

SUGAR:  Dr. Grimmett?

GRIMMETT:  Mike Grimmett.

SUGAR:  I’m sorry, Dr. Ho hasn’t spoken yet.  I’d like to give him an opportunity.

HO:  Allen Ho.  Just a question with respect to the long-term data.  Can you tell me approximately when the last patient was recruited and does our lack of 24-month data indicate a fall off in follow-up compliance or does that indicate that they have not reached those milestones yet?

GORDON:  Judy Gordon again.  Having been very close to this study, but not having managed it myself, I’d have to say and Dr. McDonald commented that the level of compliance was one of the highest I’ve seen, 97 percent.  Over 95 percent at each visit.  And the data that we do have available at 24 months is again 95 percent of the eyes that have hit that window, but a small number of eyes have gotten to that point and I’ll have to defer to when was the last patient enrolled, but in any case, we have at every interval examined accountability because in the absence of having more than 90 percent of data available, we have not reported, we would not report on a parameter, and in all cases wherever we’ve reported, we’ve had more than 95 percent of eyes that were eligible for the examination come in and be examined.

HO:  Allen Ho again.  So in other words, when can we expect to anticipate that the last enrolled patient will have 24-month data if they come?

GORDON:  The last patient was enrolled in December of 2000, so that patient hits one year shortly and two years in about a year from now.

HO:  Thank you.

SUGAR:  And now, Dr. Grimmett?

GRIMMETT:  Mike Grimmett.  I apologize if this was previously stated or if it’s redone — regarding the 24 patients who lost greater than or equal to two lines of best corrected vision in 6 months or later, were any of them contact lens over-refracted as a diagnostic step to rule in a regular astigmatism?

GORDON:  Dr. Gordon.  We’ll find out and get back to you on that.  I don’t have the answer on that.

GRIMMETT:  Okay.

GORDON:  We’re making a list of questions.

GRIMMETT:  Okay, I thought I had missed it.  Sorry.

GORDON:  We didn’t say anything to that effect.

GRIMMETT:  Okay.

SUGAR:  Jayne?

WEISS:  Jayne Weiss.  What did you find the mean dioptric change was on a monthly basis between 12 and 24 months in those patients who you do have data on?

GORDON:  Judy Gordon.  Dr. Rosenthal is shaking his head in a negative direction, so I’m hesitating to respond.

ROSENTHAL:  Dr. Weiss, we normally have data presented here related to what was presented in the PMA submission.  If the Panel feels that they require additional data to be looked at by the Agency, that is one of the things you can consider in your deliberations.

SUGAR:  Dr. Bradley.

BRADLEY:  I just wanted to add a few comments to Dr. Gordon’s reply to Dr. Jurkus’ question about the subjective data.  I would concur with Dr. Gordon that they’re very difficult to interpret and really without an effective placebo group, I really have a lot of trouble making much of those data in the sense that there were no alarming signs in the data set.  But being fully aware that there could be huge biases either plus or minus in that data set, you can easily imagine that patients who just had something done to their eye are extremely observant of any nuance in their sight from that day on and therefore the reporting of adverse symptoms might go up.

Conversely, you can imagine the opposite bias.  They’ve just committed themselves to an irreversible surgical procedure on their eyes, so they’re really biased to think good of what they’ve just done, so that you can imagine bias going either way in that data set and I think when, as I think you’ve observed and reported quite nicely this morning, very small changes or what seemed like very small changes in the reporting, given the potential for bias either way, it’s very difficult to make much of those.  That was my interpretation.

SUGAR:  Dr. Huang and then we’re going to move in about two minutes into the FDA’s presentation.  We also — do you have answers to the earlier questions like endothelial cell count?  After Dr. Huang’s question, we’ll ask for those.

Go ahead, Dr. Huang.

HUANG:  I have two questions regarding the quality of life issue.  Given the fact that greater than 50 percent of the patient went 6 months, still have a significant amount of induced cylinder and a residual undercorrection, and is there any data suggesting some of the patients may need remedial service such as contact lenses or spectacle corrections?

DURRIE:  This is Dan Durrie.  And this is actually the seventh hyperopic clinical trial that I’m involved in so I think that one of the things that I think I’m bringing a perspective of the biases over multiple studies, but I think it was very interesting to me in this study is we didn’t have — I personally did not have a single patient during this time of overcorrection or induced astigmatism that even asked for spectacle correction or asked for a retreatment which has not happened in other clinical trials.  So these patients did not need additional help, did not request it and I think that that was a lot because the overshoot was not that great.  They were always within three quarters diopter on average of the plano mean and also the induced astigmatism did not seem to be that clinically significant to the patients.

You have to remember, these patients, a lot of them were +1.50, +2.00, +3.00 diopter hyperopes who were used to some very poor vision.  The average age was 53 and these patients really weren’t seeing very well.  Any of you who have gotten hyperopic like I did over the years understand that.  I think that these patients were not needing any remedial — not even spectacles, let alone contact lenses during that period.

SUGAR:  Go ahead.

McDONALD:  Marguerite McDonald. We pulled some data, proportion of eyes using distance corrective lenses, eyes treated with current nomagram.  This is 14 percent at 6 months and across all time points, 80 percent of the eyes and more reported no use of corrective lenses for distance vision.

SUGAR:  Did you have —

HUANG:  Could you repeat that?

SUGAR:  Could you go ahead and repeat that?

McDONALD:  Mcdonald again.  Proportion of eyes using distance corrective lenses, eyes treated with current nomagram.  This was 14 percent at 6 months and across all time points, 80 percent of eyes and more reported no use of corrective lenses for distance vision.

SUGAR:  Have you finished with your question, Dr. Huang?

HUANG:  That’s fine, thank you.

SUGAR:  Then do you have a response to the endothelial cell question and the question on contact lenses?

GORDON:  Yes.  We have a couple of responses here.  First of all, this is Judy Gordon again.  Dr. Pulido asked about a specific patient that had nasal septal repair.  The preoperative manifest refraction for that eye was +1.75, -1.75 cell.  So the MRSE was 1.3 and the patient was eligible for enrollment.

PULIDO:  And then she ended up at -2.00 for a while?

GORDON:  That was the 6-month observation.  We’ll check.  I don’t have the full line listing, but we’ll pull that and see what additional follow-up we may have on that patient.  We have almost all 9-month follow-up at least, so there should be another examination.

PULIDO:  That’s very predictive.  Thank you.

SUGAR:  Then the two other.

GORDON:  With regard to endothelial cell density, we did not examine those data by dioptric power.  It was a fairly small number of eyes.  It’s a sub-study.  But we do know that 40 percent of the eyes are somewhere in that neighborhood, were in the higher dioptric range at entry, meaning we had a pretty good distribution of eyes that were greater than 2, up to 3 and a quarter diopter spherical hyperopia, so we would anticipate that there would be a pretty even distribution of those eyes in the endothelial cell study.  And in fact, those eyes were enrolled in the initial phase of study when we were enrolling up a baseline CRSE of 4 diopters, so there should be perhaps even more eyes there that were at the higher range.

SUGAR:  Okay, and then the contact lens question?

GORDON:  Yes, Judy Gordon again.  With regard to contact lenses, contact lens over-refraction was required by the study protocol for eyes with best corrected acuity worse than 20/40 and since all of these eyes were better than that, 20/32 and 20/25, there were none performed.

SUGAR:  Thank you.  I’d like to have the sponsor then move back from the table and have the FDA group come up and give their presentation.

(Pause.)

GLOVER:  Hi, I’m Joel Glover.  I’m the FDA Team Leader for the application.  Since it’s already been introduced, I just have a few brief comments.  First, I want to thank the Panel for reviewing and discussing the application today.  I want to thank the sponsor for being so responsive during the rest of the review and also I’d like to thank the nonclinical review team in FDA for all their work and lastly, I want to introduce Dr. Sherri Berman, the clinical reviewer.

BERMAN:  Okay, good morning.  I’m Sherri Berman, an ophthalmologist and I was the clinical reviewer for this PMA.  First of all, I’d like to thank Refractec for their cooperation in providing us here at FDA in advance with their Panel presentation.  I have for you today six questions for the Panel to consider as part of their discussion today and rather than reiterate what has already been presented by Refractec I have put together myself a few summary tables that I feel are relevant to each of these questions and I’d like to just go through them briefly right now.

The first question that the Panel will be asked is for their concerns regarding the incidents of induced cylinder with significant axis shift and its consequent effect on efficacy.

As part of the surgical procedure with this device, the positioning and angle of the handpiece as it enters the cornea as well as the centration on the pupil are performed manually by the surgeon.  I’ve put together this slide to summarize the difference between pre-op and post-op cylinder magnitudes.  I’ll give you a minute to look it over and as you can see here, for the more than or equal to 1.00 diopter and the greater than 1.00 diopter stratifications, the incidence of induced cylinder was 20 to 30 percent at month 1 and declined over time, but at month 9 and month 12 still a significant proportion of eyes have this level of induced cylinder.

Here you can see a summary of the change in the vector magnitude and again, there’s a significant proportion of eyes that had more than or equal to 1.00 diopter of induced change.

In this table, you can see that approximately 40 to 50 percent of eyes had a shift in cylinder axis of more than 30 degrees and approximately 25 percent had an outcome shift of greater than 60 degrees.  The direction of the final post-op axis appears to be somewhat unpredictable and widely variable.

In this slide of post-op cylinder magnitude, I first want to point out that all eyes as an entry criteria had a baseline cylinder magnitude of three quarters of a diopter or less.  It is of clinical significance that the magnitude of post-op residual cylinder of greater than or equal to 1.00 diopter was 40 percent of eyes at month 6 and 32 percent of eyes at month 12.

Finally, with respect to this first question for the Panel, in order to further assess the clinical significance of induced cylinder, an analysis was requested by FDA of the sponsor and was performed as such.

I want to clarify that the percentages that I’ve put together in this table differ very slightly from those presented in the Panel presentation by Refractec because they presented data on the — I believe 21 eyes from the current nomagram treatment, whereas these numbers represent the total 25 eyes that were treated, but the percentages did not differ by more than a few percentages and here the stratification is eyes with less than a diopter of induced cylinder at 12 months and eyes with more than or equal to a diopter of cylinder and you can see that almost double the proportion of eyes achieved 20/20 with less than a diopter cylinder and significant differences at 20/25 level and the 20/40 level, although not as significant as the difference at the 20/20 level.

And as well, was presented the mean uncorrected visual acuity which I don’t think gives the whole picture.

The second Panel question is as follows:  Is 12-month follow-up sufficient to provide reasonable assurance of safety and efficacy?  There are 21 eyes available at 20 months.  Should data for these eyes be required in the labeling?

In addition, the third question, does the refractive correction obtained with this device in light of the rate of change of mean MRSE over time and the incidence of over and under-correction justify potential risks.

For example, from one of the sponsors PMA analyses, it was presented that only 32 percent of the 363 eyes in the efficacy cohort achieved a final UCVA greater than or equal to their baseline BCVA.

The stability data was presented earlier and I won’t focus on this for too long, but I do just want to point out some numbers because they are pertinent to the requested indication statements and that is when you look at the mean change over time and the extrapolated annual change, I just want to point out that over the 6 to 9 month interval and the 9 to 12 month interval and the 12 month consistent cohort that there certainly is no demonstration of the fact that the rate of refractive regression is slowing down.  And this is confirmed with the larger cohort with two consecutive visits.

Further data to look at for these two questions for the Panel, focus on accuracy of the MRSE and here you can see that the rate of undercorrection was as follows here and when the sponsor stratified this data by the degree of pre-op hyperopia there was a suggestion of a trend of decreasing efficacy with increasing pre-op CRSE.

Here you can also see that a significant percentage of eyes developed early clinically significant myopia, the incidence of which declined dramatically over time.  These patients were like to require spectacle or contact lens correction at least part-time.  Overall, these outcomes are consistent with the post-operative hyperopic shift over time.

The fourth question that the Panel will be asked to consider is as follows:  Are there concerns regarding the increased incidence of visual symptoms from pre-op levels?

As this was also presented extensively by the sponsor, I won’t deliberate here, but you can look over these numbers and I also want to point out that in addition to the moderate and severe symptoms reported, it was also clinically interesting that the proportion of eyes that reported none for each of these symptoms decreased over time for many of the symptoms including halos, diplopia, visual fluctuation and night driving problems so that eyes did not have any symptoms pre-operatively did develop symptoms post-operatively.

In addition, the subjective assessment of overall satisfaction revealed that a rating of dissatisfied or very dissatisfied was reported by 8 percent of subjects at month 6 and 12 percent of subjects at month 12.

The fifth question:  Do the safety and efficacy data presented in this PMA support approval of this device for the requested indication?  Is the requested indication appropriate as worded, based on the study outcome?

I prepared these slides and they were accurate up until about a week ago.  The sponsor had modified somewhat the requested indication down in this area so I’m apologizing that it’s not 100 percent accurate, but I’ve highlighted in yellow the areas of the requested indication statement that I’d like the Panel to address during their deliberations.

And these basically are the upper limit of the cycloplegic spherical equivalent and the wording or such of the statement that the magnitude of correction decreases over time and how much it does so.

In one of the amendments to the PMA, Refractec provided an additional analysis in response to one of the primary Panel reviews which is summarized here.  In this amendment, they concluded a highly significant correlation between baseline CRSE and induced cylinder.  Most pronounced in eyes with a baseline CRSE more than 2.50 diopters.  Due to the small sample size of the eyes with treatment size of eight spots, these numbers cannot be used to make statistically valid conclusions.  The sponsor proposed that these outcomes be addressed by them in the device labeling or alternatively by modification of the upper limit of the refractive range.

At this time I have no further clinical data to present.

Okay, the final question for Panel consideration is a general question, what are your recommendations for labeling regarding regression of effect, induction of cylinder and incidence of visual symptoms?  Are there any additional labeling recommendations?

SUGAR:  Thank you.  Are there questions for Dr. Berman or for the Agency?

If not, I’d like to — go ahead, I’m sorry.

BRADLEY:  Arthur Bradley.  You were apologizing for one item on that segment from last slide being out of date.

Would you mention what has changed?

BERMAN:  Yes.  At the time that I prepared these slides, the requested indication for use from the sponsor, the final bullet here they requested was the statement that the magnitude of correction diminishes over time with an average loss of approximately 10 percent of the intended correction at one year.

I wold have to defer to sponsor —

SUGAR:  It would be slide 85 from the sponsor’s package you have in front of you, where they changed that to 6 percent of the intended correction at one year and they added the statement the proportion of intended correction retained beyond 12 months is undetermined.

If there are no other questions for the Agency, the sponsor will have additional time right after lunch, whether that means we’ll be better able to attend or less, I’m not sure, but I would like to have everybody really get back here at 1 o’clock so that we can proceed to pace.

(Whereupon, at 12:01 p.m., the meeting was recessed, to reconvene at 1:00 p.m.)

A-F-T-E-R-N-O-O-N  S-E-S-S-I-O-N

(1:06 p.m.)

SUGAR:  Okay, if there’s no objection, I’d like to proceed with the additional comments from the sponsor.  They’ve asked for a few more minutes than the 5 minutes on the program and I think that that’s reasonable.  So go ahead.

McDONALD:  Thank you, Dr. Sugar.  We would like to specifically address Dr. Berman’s questions to the Panel.

Question 1 relates to concerns regarding induced cylinder.  As you have seen both in our presentation and presented by Dr. Berman, induced cylinder was observed in a fairly high proportion of eyes at the 1-month examination.  However, the frequency and magnitude decreased significantly over time and was well below the current FDA limit of less than 5 percent.  From 6 months, the proportion of eyes with induced cylinder of greater than 2D also meets the more stringent proposed limit of less than 1 percent.

This graph shows UCVA over time in eyes with greater than 1D induced cylinder at 1 month, consistent with the resolution of induced cylinder over time, uncorrected acuity improved substantially from 1 through 12 months.

Induced cylinder had no affect on BSCVA, with all eyes at 20/32 or better at 12 months.  The magnitude of effect of induced cylinder greater than 1.00 diopter on UCVA was on average one line less improvement, irrespective of whether the analysis was performed using absolute magnitude of induced cylinder or vector analysis.  Similar results were obtained when considering induced cylinder greater than or equal to 1.00 diopter.  There was no effect on UCVA in eyes with manifest cylinder greater than 0.75 D with an axis shift of 30 degrees or more.

In summary, we’ve shown that induced cylinder meets the current FDA limit and decreases significantly over time, resolving in a large proportion of the eyes.  This resolution of induced cylinder was not attributable to regression of the spherical correction.  The presence of induced cylinder greater than 1D and greater than or equal to 1D was associated with a difference of approximately one line of improvement in UCVA.  UCVA improved over time as induced cylinder resolved, and the difference in UCVA translated into a lower proportion of eyes with UCVA of 20/20 or better.  Induced cylinder had no effect on best corrected visual acuity irrespective of the analysis performed.

Question 2 relates to whether a 12-month follow-up is adequate to support safety and effectiveness.  Because the 9-month population of 376 eyes presented in our PMA represents 94 percent of all eyes, and the 12-month population of 203 eyes represents 51 percent of all eyes treated, but 97 percent of the eyes eligible for examination, we believe the available data provide reasonable assurance of safety and effectiveness.  Updated

12-month data and the available 24-month data have been submitted to the FDA for review and the results for key parameters of safety and effectiveness are consistent with the data reviewed by the Panel.  Refractec is more than willing to update all labeling information to reflect the additional data.

Question 3 asks whether the refractive correction effected by CK justifies the risks.  Predictability of the CK procedure is presented here graphically to display the proportion of eyes that were under-corrected and over-corrected.  The proportion of eyes initially over-corrected decreased substantially after one month and under-correction was limited to a small number of eyes throughout the course of the study.

The stability target identified in FDA guidance of change in MRSE within .50 or 1.00 diopter was achieved at both the 6 to 9 and 9 to 12 month intervals.  Using a paired analysis between months 6 and 9, the mean change per month in the manifest or fraction was 0.03D while mean change was 0.04D between 9 and 12 months.  However, these data did not achieve the remaining two FDA stability criteria of decrease in mean change over time to an asymptote and the confidence interval encompassing zero.

As shown in this graph, there was a very close match between the manifest and cycloplegic refractions over the course of the study.  This graph also shows the relatively small initial

over-correction following the CK procedure, particularly in comparison to other refractive procedures for hyperopia correction.  This over-correction has generally been acceptable to patients and that it is mild and temporary.  Hyperopia is reached at approximately 6 months and there is less than a .25 diopter of change between 6 and 12 months.

FDA poses the very fundamental question of whether the potential risks of the CK procedure are justified in light of the rate of change in MRSE over time and the proportion of under-corrections and

over-corrections.  The first point to be made in response to this question is that hyperopic patients seeking correction of their distance vision in this study experienced a significant improvement in UCVA.  Fifty percent of all eyes had UCVA of 20/20 or better and over 90 percent had UCVA of 20/40 or better.  This was accomplished with no serious adverse events or complications, no incursion into the visual axis and no removal of tissue.  Additionally, 95 percent of patients felt that their quality of vision was improved.

We have shown you data establishing the rate of change in MSRE to be very small, less than a .50 diopter per year, based on the mean change from 9 to 12 months.  The concerns regarding

under-corrections and over-corrections are valid, but are also pertinent to all refractive surgery procedures for correction of hyperopia.  As with all corneal steepening procedures, there is an initial over-correction following CK, but those are relatively small and resolves early.  Only a small number of eyes were under-corrected over the course of the study.

To speak to the issue of whether the potential risks of the CK procedure are justified, we ask you to consider the risks associated with Lasik as described in the FDA’s website for patients considering Lasik surgery.  These risks include under treatment or over treatment, loss of vision that cannot be corrected with spectacles or contact lenses and loss of effect over time.  As a refractive surgeon, I can also tell you that I continue to have concerns with regard to Lasik complications such as “Sands of the Sahara” or DLK, micro and macro striae, aborted flaps, lost flaps and of course, the most serious of Lasik complications, entry into the anterior chamber with the microkeratome blade.

We believe that CK offers patients considering vision correction a viable alternative to Lasik and other modalities for the correction of hyperopia with a comparable risk to benefit ratio.

Question 4 relates to the visual symptoms reported in our study.  The increase in symptoms reported as moderate and marked was limited to 5 to 7 percent, thus just exceeding the threshold of 5 percent defined as clinically relevant.  More importantly, the increase in marked symptoms reported at 6 months largely resolved at 9 and 12 months.  Finally, there was no significant increase in very severe symptoms at any time during the study.

Question 5 asks whether the safety and efficacy data support approval of CK for the indication proposed.  To summarize the effectiveness data, you have seen that the results for UCVA and accuracy of the refractive outcome exceeded FDA targets for these parameters.  Stability was not achieved, but the average change per month in MSRE was small, annualized to less than a .50 diopter per year.  Ninety-four percent of the intended correction remains at 12 months and 80 percent of patients reported being satisfied or very satisfied with the results of the procedure.

All FDA limits for safety were met in the study population.  Only 1 percent or less of eyes lost greater than 2 lines of BSCVA and no eyes had best corrected acuity worse than 20/40 at 6, 9 or 12 months post-op.  Finally, the incidence of induced cylinder was considerably below the current limit in FDA guidance.

To summarize, we believe that the results of the clinical trial of CK serve to establish the safety and effectiveness of this procedure and also serve to support the proposed indication for use.

Question 6 speaks to recommendations for labeling.  While we welcome further recommendations from the Panel and from the FDA for labeling, we have proposed for your consideration labeling information that serves to address concerns that should be communicated to physicians and patients considering the CK procedure.  Specifically, we suggest that loss of effect over time be communicated by reporting the proportion of intended correction retained at one year in this study population, while noting that loss of effect may continue beyond one year.

With regard to over-correction, it should be communicated that patients may experience an initial over-correction and that this may affect distance vision such that spectacles are required for driving.  Next, although we have not specifically discussed this during our presentations, we have already included information in the labeling, stating that accuracy of the intended correction was slightly lower for eyes in the higher dioptric range.  We will also address the lower proportion of eyes with UCVA 20/20 or better in the higher dioptric range.

With regard to induced cylinder, we propose communicating that induced cylinder greater than 1D was associated with less improvement in UCVA at the 20/20 and 20/25 levels and that achievement of UCVA of 20/40 or better was somewhat delayed.  Information on symptoms has already been included in the labeling in our PMA and can be revised as determined appropriate by Panel and the FDA.

Finally, as suggested in the Panel review, we will add to our labeling a statement indicating that no data are available on re-treatment.

This concludes our presentation.  We would like to thank the Panel Members, particularly the primary reviewers and the FDA personnel for the significant time and effort invested in their thorough and insightful review of the clinical data in our PMA.  We also thank you for your consideration of the CK procedure as a safe and effective refractive surgery option for hyperopic patients.

SUGAR:  Thank you.  We will, I think, reserve the option of asking questions as they arise from you, but it’s fine to go back to the audience.

Now we proceed with the committee deliberations and begin with the primary Panel reviewers.  First will be Dr. Arthur Bradley.

BRADLEY:  Arthur Bradley.  A couple of things to remind everybody here, that I’m not a clinician and the original review of this PMA was done back in August and I had to re-frequent myself with this document a few days ago and some of my comments relate to some of the frustrations experienced at that time.

I want to go through several points here.  First, an issue about presentation of the data.  This really applies to the sponsor and also to the FDA.  I’m trying to think of more effective ways of communicating complicated data sets because I found the current document really quite difficult to manage.  I’m then going to concentrate on what I call the main effect, as the change in manifest refractive spherical equivalent.  The issue there, of course, is over or under correction and much has been said already about stability.  I’m going to add a few comments about stability and we then get into this issue of induced astigmatism and in particular, I’m going to comment on how this might be presented in a more easy to understand way.

I’m then going to talk about interactions with any procedure.  We always look for significant interactions and I found that very difficult to extract from the data set and finally some issues about patient information which, in many ways, don’t stem from my expertise as a scientist, but my position as a potential customer.

Let’s go through one by one.  Presentation of the data.  Indeed, a complicated data set, but hundreds of tables, I’m not really sure exactly how many tables I looked through but my mind was spinning.  I think in the last document I was at Table 109.2, entitled “Induced Cylinder Residual Astigmatic Error at Stability time Point.  All Eyes Treated at Month 12.”  Really, 109 data tables makes me wonder if this is just an inefficient way to present the data.  There might be better ways to do it.  And certainly as a teacher of graduate students, I have to communicate all the time that numerical effectively communicated in a graphical format — tables often do a very poor job of communicating data.

Still, sometimes the main data are never presented or are hidden or are inadequately.

(Laughter.)

Here’s a good example of that.  Look at that.

(Laughter.)

I don’t know what that was all about.  I think the system is reacting to having a McIntosh attached to it, basically.

What have we got here?  The sponsor has presented the data in terms of — yeah, so this last comment really is I think the way the data have been presented.  I think the sponsor has done a fabulous job, by the way of communicating to us what proportion of the data meets certain criteria and the criteria are really, have been dictated by the FDA, a certain number of people have to have uncorrected VA of a certain level.  Residual refractive error must be less than a certain percentage and have more than 1.00 diopter, etcetera.  And in the end, that’s how the data have been communicated and in the teaching environment in which I work, the one thing that I continually have to remind my students of is that before I know the statistics on a data set, I really want to know the data set.  In the end, I think that was what really bothered me and gave me so much trouble with this particular proposal and that was the data were perhaps not presented.  More the analysis of the data was presented.  So if I had an opportunity here to encourage the FDA and the sponsor or future sponsors, is to first present the data and then we’ll have a look at the analysis and if we could see the data directly, I think we would learn quite a bit more.

Here’s just an example.  The most important thing really for us to know is the issue of how much did the refractive error change.  And I looked really hard and I think as my son could tell you, I’m not the best searcher of things in the world, but I couldn’t find a graph that showed the mean spherical equivalent refractive error for this patient set and we’ve seen it this morning, by the way.  A couple of presenters from the sponsor presented this graph.  But it isn’t in the report and that would have helped tremendously.  It turns out the data are shown on Table 69 at page 154 of Volume II, but only after amendment 11, dated September 7th, did the pre and post MRSE appear together as Table 1D.1.  And as far as I could tell the original narrative didn’t even provide that information and it seems to me that is the main reason for doing the procedure.  Surely, this should have had a very prominent position in the report.

Well, I did my own analysis and actually graphed the data and this is the graph we’ve already seen.  It’s the pre-1 month, post 3-months, 6 months, 9 months, 12 months and we’ve got the manifest and the cycloplegic refraction there and you see, as the sponsor has shown us this morning that these are really essentially identical and a couple of things to point out here.  This is the myopic overshoot we’re a bit worried about.  At month 1, it’s still there at month 3.  The mean is about plano at month 6 and drifting slightly into hyperopia by 12 months and that’s exactly the result we’ve seen already.

And these are the average data, so on average we’ve got over-correction early on, under correction later on, but this is for the whole sample.

From the most recent data set, I took out the standard deviation data and simply added those.  That should say one standard deviation here.  And there’s the mean again that I’ve just shown you and that’s one standard deviation in one direction, two standard deviations.  One standard deviation, two deviations.  And there are a couple of important things to note here, particularly in that early time period of one month.  Although the mean is only about .50 diopter here, once we get out at two standard deviations and really that encompasses the whole distribution of plus or minus 2 standard deviations, some people are hovering out there at 2.00 diopters of myopia and these are the ones that worry me the most, these particular patients.

Something that’s quite hard to see in this graph, but I’ll show you in the next graph and something that you should think about is notice the pre-op range of data.  That’s the data here we’ll call time zero.  Time zero here.  It’s ranging from about +2.8 down here to about +.3 or .4, that’s the range.  Notice that the range doesn’t get any smaller.  It turns out the standard deviations actually climb as we — after the procedure.  So the post-op standard deviations are actually larger than the pre-op.  I’ve got a little note down here, expectation.  First of all, we expect the refractive error to converge towards emmetropia after appropriate levels of CK, the idea being is that CK can come, you can have 32, 8, 16, 24 different amounts of the procedure done, all designed to accommodate the pre-op refractive error and target everybody towards emmetropia.  So that’s the goal of having different levels of CK.

We know the mean is myopia and as I said, it’s very significant for some eyes, but here’s the — unusual result.  The refractive error distribution is wider after the procedure.  Now how could that happen because everybody should be targeted to the same results, starting from different locations and the fact that the distribution after the procedure is wider than it is before makes one realize that this is not a highly controlled procedure in which irrespective of starting point we can converge the distribution down on to zero, on to plano.  In fact, the distribution spreads, a larger distribution after than before the procedure, indicating significant course of variability in the procedure.

This is just a graph plotting that. Standard deviation is a function of time, zero being pre-op, standard deviation .6 diopter.  It climbed 60 percent up to that point, 95 percent.  Thing to remember, if you gave every eye the same CK procedure, identical, you would expect the standard deviation to remain constant, but by selecting the appropriate levels of CK we expect the post-op standard deviation to be significantly lower.  In fact, it’s higher.  We really have no explanation for that, except that the procedure is introducing a huge amount of variability and maybe the sponsor could comment on that at some point.

Next issue on my list.  Stability.  Well, we’ve seen lots of talk about it and we’ve seen a variety of numbers thrown around but most striking to me is the commentary and the commentary is this.  We’ve got data at 1 month, 3 months, 6 months, 9 months and 12 months.  And that’s exactly the graph I’ve shown you before and all I’ve done is extrapolated the 9 to 12 month data on out.  So these are all from — that’s real data.  This is extrapolation, extrapolation.  Just to remind everybody, another word for extrapolation is speculation.  We don’t have the data here, here and here, but I’m just extrapolating the last two data points on out.

A couple of things to note.  Indeed, the change from here to here is quite small and we’ve heard the sponsor tell us it’s very small, insignificant, tiny.  In fact, in the original submission this was called stable.  So all I did was extrapolate that.  I remember these are not real data here.  This is all me speculating, based upon a linear extrapolation of the data between 9 and 12 months, the point being that as the sponsor in its amendment 11 or submission 11 gave us this result as a percentage of the targeted refractive change and it was something like 90 percent so there had been a bit of regression, got down to about 90 percent.  The important point to note is you continue that out at four years, the percentage of the refractive error change will be zero.  Like I said, these are not real data.  This is just me making it up.  It would be nice to have these data and if there was some indication of stability here, that is, this change asymptoted out to a flat line, then I think extrapolating that out will be in this direction and indeed, we would be concluding that there was not significant regression, but because the last data set had this slope, if we are extrapolate which I never liked to do, but I’m just doing — my McIntosh will come back.

(Pause.)

Okay, so any way that’s just a little story about stability and I don’t quite know what to say about that.  There is no evidence of stability and you know the alarming thing is that would keep on and we’d have zero correction, but like I say I don’t know that’s going to happen.

Astigmatism.  Does the procedure induce significant amounts of astigmatism?  Now, astigmatism is an inherently two dimensional variable.  We all know that, axis and magnitude.  But the presentation always reduces that down to a one dimensional number.  And it turns out when you do that you end up with some problems and they can be misleading and I’m quite familiar with astigmatism data sets and I really in the end was struggling to understand what had actually happened with induced astigmatism.  For example, did the procedure introduce random astigmatism, was it consistent?  How did the induced astigmatism vary with clinician and number of treatment spots, etcetera?  These are all interesting questions I would have liked to have seen answers to, but I didn’t get them.

This is really by way of tutorial.  I apologize for those of you who know this.  It’s me as a teacher coming in here.  This is the one way we typically present astigmatic data.  It’s called vector analysis in the proposal and in some of the reviews and it’s worth making a couple of points about it so we, in future, maybe could use this as a standard.

This is a little graph and in the graph it’s a two dimensional graph, as you can see, horizontal, vertical axes.  I’ve called this J0 which is sort of vertical horizontal astigmatism, J45 which is oblique astigmatism.  Plus J0 is with the rule, -J0 is against the rule and this over here is one type of oblique astigmatism and this is the opposite oblique astigmatism.  I’ve put three sets of data on here.  One, two and three.  These are three different eyes.  The yellow circle is the astigmatism pre-treatment, pre-CK.

Now again this is all hypothetical, just to make a point.  If the procedure introduced an astigmatism and that was a procedurally introduced astigmatism so we’ve talked about induce astigmatism, let’s say this is it and it’s the same for every eye.  What you could imagine could happen with a stable procedure.  Then that would transfer this data point to there.  This one to there.  This one to there.  It would be a constant effect here.  That is a vector change from here to here.

Well, let’s look at what happens as a result.  Let’s take Case No. 1, a certain amount of astigmatism.  That was that black line here.  We could describe that as its vector.  It changes to this one.  So clearly, there’s a change in axis and there’s a small change in magnitude.  Well, let’s take Case 2.  This is the astigmatism to start with, you add it, you get this.  There is no change in axis at all, none at all, but a large change in magnitude.  Let’s take Case No. 3.  Starts off with this astigmatism.  We add the procedural astigmatism and end up with this.  The actual magnitude is exactly the same as what we started with, but a very large axis change, in this case — plotted here it’s 180, but it ends up being a 90 degree axis change.  So you can see, depending on where you start a constant procedurally induced astigmatism produces quite different results.  Sometimes you get a change in axis, sometimes you get a change in power, sometimes you get both.  Presenting just one of those dimensions alone does not allow us to understand what really happened.  It’s very important with two dimensional data that you present both dimensions.  Otherwise, we can misinterpret it.

Is this academically interesting, but clinically irrelevant?  Good question to ask, especially when I’m talking, but let me give you an example.  Let’s imagine this really is what happened.  Again, this is all just speculation, just an example, but imagine you knew that this patient had this amount of astigmatism and you knew the procedure did this.  The residual astigmatism in this case is going to be much greater than it was at the start.  Whereas for this patient, you know that the final astigmatism is going to be basically the same as it was when it was started, just a different axis.  So this patient might be discouraged from having the procedure.  That would be one direct clinical application of this knowledge.  But without this knowledge, you can’t make that recommendation to a patient.  So it’s very important to present the data in a complete way.

A couple of things to be thinking about, astigmatism can be induced by two very obvious things.  Any meridional anisotropy in the procedure.  This is a hand-held device.  This is an eye.  The eye is moving, the angle at which you enter the needle into the cornea can vary.  Clearly, there’s a lot of opportunity for this and maybe that is the reason for some of the results we see.

The other one is that the misalignment of the procedure axis from the visual axis and really it’s the foveal line of sight.  There are a few details that I would have liked to have seen in the presentation that we didn’t learn about how this procedure axis, that is, the little ring that is inserted, that is painted out of the cornea is lined up with the eye.  Is it really lined up on the foveal line of sight?  How accurate is that misalignment of that as the people who are involved in laser refractive surgery know will induce astigmatism.  So both of these can induce astigmatism.  It would be nice to know which of these is actually involved, but I couldn’t find any data that examined the root cause of the induced astigmatism and because the astigmatic were presented in a one dimensional way, I couldn’t get a handle on what was going on.

Interactions.  With refractive surgery there are always — we’re always very concerned about the procedure, how the procedure interacts with other parameters in the patient.  For example, how does accuracy vary with pre-CK RX.  How does induced astigmatism vary with pre-CK astigmatism?  How does post-CK BSCVA vary with pre-CK VA, etcetera, etcetera.  I mean there are lots of interactions we’d like to know about.  And there is a very effective graphic tool for identifying and visualizing such interactions.  We call it the scattergram and I would have loved to have seen some of these scattergrams, but again, I say no graphs, but I can’t recall seeing a graph and certainly not these scattergrams.  Again, to get a handle on what the actual data were, not whether they met the FDA criteria, it would have been very helpful to see these and I just show again a hypothetical example here.  If this is pre-procedure, MRSE and this is post-procedure MRSE and here’s a little scattergraph of us, so we’re plotting one against the other.  This graph is a very familiar territory for us.  We know if the data fall along the Y equals X line, CK has no effect.  If the data fall along the post-refractive area equals zero, CK is perfect.  If the data fall up here, we’ve got

under-correction.  If it falls down here we’ve got over-correction.  We would have known this right away by looking at that graph.  But we don’t have that graph and I found that difficult to extract and that’s just one example, but I could list tons of these.

Final point, again, this is not really me speaking as a scientist, but as a potential patient, I really feel very strongly about this, the informed consent issue and having dealt with complicated optical effects and trying to communicate those to patients I realize that this is not an easy thing to do.  I just pull out a couple of things.  If I recall in the patient document there was some effort to make sure that the patient knew that they weren’t going to have a laser irradiating their eye which is, of course, a very important thing for the patient to know and patients are quite concerned about lasers, justifiably so.  But it paints the current procedure in a very reassuring light and talks about “gentle heat”.  I wonder what “gentle heat” really meant anyway, but you know I think if you’re going to bring up the alarm bells of lasers, then I think to be fair, maybe you should explain that a sharp needle is going to be inserted into their eye up to 32 times, just to give balance there and so the patient really can make a judgment call.  Do I want a laser or do I want a needle?  As opposed to a laser versus “gentle heat”.  That just didn’t seem to me a very accurate way to prevent a procedure to a patient.

Finally, and I think the sponsor has just discussed this in their final presentation, they are going to and I think it’s essential, that the patient who undergoes this procedure has a very good indication of the likelihood, the magnitude and the consequences of the post-procedure myopia and astigmatism that they are going to experience.  The myopia particularly concerns me because — but I would really like that because I think patients who have been hyperopic all their life to be converted to a myope, even if it’s for a short period of time, they need to know about that and they need to appreciate the consequences, particularly as the sponsor has now conceded with regard to driving and particularly driving at night.

Thank you.

SUGAR:  Thank you.  The  next reviewer is Michael Grimmett.

(Pause.)

BRADLEY:  The system survived a McIntosh.  Only just so.

GRIMMETT:  The following is not intended as a comprehensive substitute for my written comments dated August 11th, but I feel it necessary to highlight some of the notable features of the PMA, primarily as a foundation for my conclusions for the public record.

Regarding the study population, the original PMA only had 20 percent of eyes available at the 12-month interval, increasing to approximately 50 percent at the 12-month interval.  There are no data submitted for the 24-month interval. Therefore, the study is submitted as incomplete.

As we’ve seen the accountability was quite good throughout the study, a greater than 97 percent at all time intervals.

First, I’ll discuss issues related to safety.  An important indicator of the safety of a refractive surgical procedure is no change in the best corrected visual acuity following a surgery.  A month 6, approximately 5 percent lose greater than or equal to two lines of best corrected visual acuity, not an insignificant rate in my book.  Presumably, the higher rates of best corrected visual acuity loss at the earlier time periods are due to corneal irregular astigmatism.  Fortunately, the rates do decrease with time as we see in the graphical presentation that I hope meets Dr. Bradley’s standards.

(Laughter.)

Looking over some subjective symptoms, pre-operatively, 26 percent of patients were complaining of mild, moderate or marked glare symptoms, while post-op 38 percent complained of the same symptoms, an increase.  Pre-op, 10 percent complained of mild, moderate or marked halo symptoms, while post-op, 35 percent complained of the same symptoms, a 3.5 fold increase.  Pre-op, 10 percent complained of mild and marked double vision symptoms, while post-op 24 percent complained of the same symptoms, a 2.4 fold increase.  Regarding fluctuation of vision, 16 percent pre-op complained of mild, moderate and marked fluctuation of vision symptoms, while post-op 40 percent complained of the same symptoms, a 2.5 fold increase.

Pre-op, 25 percent complained of mild, moderate or marked variation of vision symptoms, while post-op, 44 percent complained of the same symptoms, a 1.8 fold increase.  Pre-op, 36 percent complained of mild, marked or very severe night time driving vision problems, while post-op, 42 percent complained of the same symptoms, an increase.

Hence, an increase in glare, halos, double vision, night driving problems, suggest the induction of higher order visual aberrations as a consequence of the procedure, that is, the induction of regular astigmatism, irregular astigmatism or the detrimental alteration of the normal corneal prolate asphericity among others.

An increase in variation of vision and fluctuating vision may be the patient symptom and harbinger of refractive instability as we previously discussed.  Appropriate labeling should include these symptom data.

A large percentage of patients, approximately 1 in 4 had the induction of greater than or equal to 1.00 diopter of astigmatism at the 6-month interval.  Up to one third had the induction of greater than or equal to 1.00 diopter of cylinder at month 1.  By month 12, there’s an approximate two fold increase in the mean cylinder, .32 diopters pre-op to .68 diopters at month 12.  If experiencing induced cylinder greater than or equal to 1.00 diopter, the uncorrected visual acuity declines as shown in Dr. Berman’s slide 8 where 51 percent had 20/20 or better uncorrected vision of less than 1.00 diopter of cylinder and half of that or 24 percent had uncorrected visual acuity of greater than or equal to 1.00 diopter of cylinder.

Presumably, the induction of cylinder is related to asymmetric corneal shrinkage as a consequence of the procedure.  Looking at greater than or equal to 1.50 diopters, approximately 1 in 15 had that level of cylinder induction at the 6-month interval.  Therefore, based on the cylinder data, appropriate labeling should include specific data regarding cylinder induction rates greater than or equal to 1.00, greater than or equal to 1.50 and greater than or equal to 2.00 diopters.  Also include data regarding the loss of uncorrected visual acuity associated with the induced cylinder, and number three, it should delineate the instability of the induced cylinder with time.

Regarding cylinder axis, shifts in axis are somewhat random and generally spread across the range 0 to 90 degrees, a slight weighting towards shifts less than 15 degrees.  Approximately 70 percent at Month 12 shift in axis greater than 10 degrees indicating there’s a high probability that the direction of cylinder will be different post-op as compared to pre-op.  Approximately 50 percent at month 12 shift greater than 30 degrees.  Labeling should therefore indicate that the precise direction of induced cylinder is unpredictable and highly variable.  The labeling should indicate that the axis shifts are more probable than not.  Based on the data submitted, I was unable to determine if the astigmatism meridian is refractably stable in the long run.

Regarding the etiology of the induced cylinder, we can speculate that the high rate of induced cylinder may be due to a combination of factors.  Number one, inaccurate spot placement.  The technique requires a manual spot-by-spot placement on a corneal mark.  It’s improbable that any surgeon can place each spot with 100 percent precision in perfect symmetry.  Also, if the optical zone markers is decentered, treatment asymmetry is a given.

Number two, asymmetric energy uptake, differing corneal thickness we can postulate may lead to asymmetric energy uptake and therefore may lead to asymmetric steepening, for example, the temporal cornea is thinner.

Number three, nonperpendicular needle tracks.  Given the prolate asphericity of the cornea and the manual spot-by-spot placement technique, it’s improbable that any surgeon can place each spot with 100 percent precision regarding perpendicularity.

Number four, a non-uniform needle dept, we can theorize that differing pressure by the surgeon with each spot placement and patient to patient tissue variability may indeed lead to differing treatment depths.  All four of these factors may contribute to the induced cylinder seen with this technique.

Now on to some efficacy issues.  As shown in Donder’s table, accommodation at younger age is significant and can skew uncorrected visual acuity measurements toward better visual outcomes in a hyperopic population.  Importantly, stratification by age in this study did not show a trend toward better uncorrected vision with the younger age group.

The Refractec data did disclose improved uncorrected visual acuity following the procedure as compared to pre-op levels.  If we stratify this by dioptric group it appears reasonably matched at month 6, but the levels achieving 20/20 appear to decline by month 9 and month 12 disclosing lower rates of achieving these visions.  Labeling should incorporate this fact.

For this procedure, as Dr. Bradley pointed out, emmetropia was intended in all cases.  If the predictability of the procedure were good I would certainly expect the post-op standard deviation values to be lower than the pre-op standard deviation values and this is clearly not the case.  Pre-op standard deviation of the mean post-op values are all higher.  This would indicate that a wider spread of the data was created and suggests poor predictability of the procedure.

Looking at intended versus achieved correction.  Fifty-eight percent achieved plus or minus half of intended while 91 percent achieved plus or minus 1 of intended.  These exceed the relevant guidance document target values.  I would simply point out that a patient with a low amount of hyperopia is likely interested in plus or minus a half.  Certainly, a patient entering the study with 1.00 diopter of hyperopia, for example, is not going to care about a 4.00 diopter spread of predictability.  I just want to make sure that labeling includes the range of the data for analysis.

If stratifying by the degree of hyperopia, there’s declining predictability as the level of hyperopia increases as we can see here for both plus or minus a half and plus or minus 1.  This is a find similar to many refractive procedures.

The proportion of under-corrections greater than +1.00 diopter is increased in the higher hyperopic group suggesting decreased efficacy with increasing levels of hyperopia.  Appropriate labeling should delineate the declining procedure effectiveness as the pre-op level of hyperopia increases.

There was an approximate 1 in 10 rate of no or slight improvement in the quality of vision and an approximate 1 in 10 rate of dissatisfaction.  There were no differences found between differing hyperopic groups regarding satisfaction rates.  Appropriate labeling should reflect these data.

Regarding stability, the proportion of over-corrections for the entire cohort decreases with time over the study periods suggesting refractive instability or loss of surgical effect as shown here graphically with time.

Additionally, as we’ve seen this data on a previous slide, the declining levels of induced cylinder with time also argues for refractive instability. It’s reasonable to assume that shifting  astigmatism may lead to complaints of fluctuating vision.

For a consistent cohort of eyes through month 12, the mean refraction does show a continuous rise as shown here, supporting refractive instability of loss of surgical effect.  Over this particular study period, there was a .8 diopter loss from month 1 to month 12 or approximately 30 percent of the refractive effect was lost between month 1 and month 12.  Of note, physiologic drift has been estimated to be less than .08 diopters per year and is therefore not likely to play a significant role in the hyperopic drift seen in this particular study.

If analyzing the mean rate of change per year, there is a 1.00 diopter change per year if you utilize the data between 3 and 6 months.  There’s a .4 diopter change per year if looking at the data from 6 to 9 and a .48 diopter shift per year if looking at the data between 9 and 12 months.  Importantly, the rate of shift is increasing at the latest study interval whose confidence interval does not include zero, indicating that a definitive stability point has not been reached.  The stability of this procedure is therefore unproven.

As a historical perspective, the 10-year PERK Study results caused widespread concern regarding refractive instability when it disclosed a refractive shift of only .06 diopters per year, a rate of refractive change 8 times smaller than the current CK refractive shift from 9 to 12 months.

In support of refractive instability then we have the following features:

Increased variation of vision complaint.

Increased fluctuation of vision complaint.

Progressive declines in astigmatism magnitudes.

Progressive declines in the percentage of over-corrections.

Progressive increase in the mean manifest refraction spherical equivalent in a continuous month to month refractive shift that increases at the latest time interval and whose confidence interval excludes zero.

Hence stability of this surgical procedure has not been established on the basis of these data.  It is therefore mandatory that the study be completed with careful FDA analysis of the completed data set.  There is no doubt that the seemingly temporary nature of the refractive effect is an important material fact for a given patient to understand prior to undergoing or considering this procedure.

The refractive procedure likely causes irreversible structural changes to the collagen fibers of the cornea, making the suitability for future refractive procedures unknown.  There are no data in the submission regarding retreatments.  Appropriate labeling should indeed mention this fact and especially in the light of the substantial refractive drifts seen in the study.  In other words, options to later correct a seemingly temporary nature of the effect are unproven.

Given all the foregoing, if I were advising a patient in a doctor-patient relationship considering this procedure, I would feel obligated to disclose at least the following material facts.

There may be up to 32 individual corneal needle sticks placed manually at 90 percent corneal depth.

Twenty-five percent of patients have greater than or equal to 1 diopter of induced cylinder at 6 months.

A shift in astigmatism axis is more likely than not.

Five percent of patients lose greater than or equal to two lines of best corrected visual acuity at 6 months.

Patients report increased symptoms of glare, halos, double vision, fluctuation of vision, variation of vision and night driving problems following the procedure.

The procedure is unstable with a substantial progressive loss of surgical effect.

The current PMA discloses that the duration of the hyperopic drift is unknown.

Assuming that the patient was competent, had adequate comprehension of the issues and was exercising voluntary choice, I’m hard pressed to say that a reasonably prudent individual would want the particular procedure.  Nonetheless, it’s the charge of this Panel to determine if the data proffered give a reasonable assurance of safety and efficacy if a patient was indeed interested in this procedure.

This Panel is once again faced with a device that has a seemingly temporary refractive effect.  From a prior Panel Meeting, it’s the Agency’s position that “it’s quite reasonable for an Advisory Panel to evaluate a submission which has a nonpermanent use.  There are devices that are just temporary.  There are a lot of them.”

In the past, a marginally effective procedure for hyperopia, the Sunrise LTK procedure, was indeed FDA approved, “for the temporary reduction of hyperopia in 2000.”

Given that refractive instability is a major shortcoming of this procedure, the primary indication statement should delineate two crucial material facts.

Significant hyperopic shift or loss of surgical effect occurs over the study period.

The study fails to prove refractive stability in the long run, that is the drift may be on-going.

It’s important to realize that just as the data do not prove final stability, the data similarly do not prove that the surgical effect completely regresses.  That is, the data are insufficient to prove that the effect is either temporary or permanent, albeit we do know that the surgical effect diminishes over the study period and we do know that it does not stop at a defined point in time.  Rather than a single word like “temporary”, I’d suggest a statement that describes both the loss of surgical effect and the unknown duration of drift such as “refractive stability is unproven for the CK procedure with progressive loss of refractive effect over time.”

I’ll certainly be interested to hear Panel wordsmithing on this particular issue.

In the PMA’s current state, with the major shortcoming of refractive instability, I don’t believe that the application is approvable without conditions.  Therefore, I’d recommend the following conditions for approval.

Complete all enrolled eyes to the 12-month interval with FDA review of all stability analysis and if stability cannot be proven at that time, hold approval and reanalyze at longer time intervals.

Submit all available 24-month data for FDA review prior to considering approval.

The study must be completed to 24 months given all the aforementioned issues.

Post-market surveillance is mandatory to document if and when the regression stops with appropriate labeling revisions.

The labeling should include all relevant material facts.

And rather than listing them I went ahead and put a Panel handout on everybody’s table at the end of my slides listing the types of labeling recommendations that I would like to see for consideration.

If not already done, eliminate the adjustable energy duration controls as this study was really only tested with .6, .6.

That concludes my initial comments.  Thank you so much for your attention.

SUGAR:  Thank you.  Next, Dr. Weiss?

WEISS:  I think my colleagues have very effectively discussed the concerns about this procedure and in the interest of not being repetitive and in the interest of time I will not repeat their comments, but I’ll limit myself to the questions that are before the Panel for discussion.

The first question was are there concerns regarding the incidence of induced cylinder with significant axis shift and its consequent effect on efficacy?  I think all the — Dr. Berman, Dr. Grimmett, Dr. Bradley and myself all have concerns about this.  The best corrected visual acuity is only one criteria to evaluate the efficacy and as Dr. Berman has shown us, of the patients who had more than or equal to 1 diopter of astigmatism induced, they had half the rate of achieving 20/20 as those who had less astigmatism induced.  So even one line of uncorrected visual acuity difference is very significant when we’re dealing with such small amounts of hyperopia.

Nevertheless, I think the way to address this concern is in the patient labeling because there are strict criteria that the FDA has put forward and that the device meets these criteria in terms of the amount of percentages of induction of 2.00 diopters of astigmatism, so this is a patient labeling question that we will sort of hash out.

The second issue is is 12-month follow-up sufficient to provide reasonable assurance of safety and efficacy and should data for the 21 eyes available at 24 months be required in labeling?  We have to apply the FDA criteria for all these questions and in this case we have to admit that the sponsor has met only 2 of the 4 stability criteria at 12 months.  Consequently, stability has not been achieved.

This is a very important question for any patient who’s going to decide to choose a particular type of refractive procedure and they’re entitled to know whether this is a temporary or permanent procedure and we have applied these criteria, namely deciding whether something is temporary or permanent effect to other devices that have come before Panel as was just mentioned the Sunrise laser most recently.

So I think it is incumbent on the FDA and the sponsor to have analysis of the 24-month data to decide at what point, if we can determine, stability is reached and I think this very important to put as well in the labeling that stability has not been reached by 12 months and I would actually prefer to say at 12 months the effect of this device is temporary just so the patient can understand and compare this to other devices that are out there and they are going to be making a selection between.

The third question, does the refractive correction obtained with this device in light of the rate of change of mean MRSE over time and the incidence of over and under-correction justify the potential risk?  And to this I would answer yes.  The criteria that the FDA has put forward have been met by the sponsor and the risk of adverse effects are quite low and so I think that the risks are certainly justified.

Question 4, are there concerns regarding the increased incidence of visual symptoms from pre-op levels?  Well, here I have a slight concern.  The moderate to marked complaints subjectively were a little bit higher than FDA criteria have mandated in the 5 to 7 percent range and I think it’s very important to have in the patient booklet a better reflection of exactly what these complaints have changed from pre-op to post-op values.  For example, mild complaints of halos, blurred vision, double vision, fluctuation of vision actually doubled between the pre-op visit and the month 6 visit and continued at month 9 and month 12 and it’s very important for patients to know not just the percentages, but that these things may be affecting them.

Also, as has been pointed out at the Panel, there appeared to be a slight trend toward increasing dissatisfaction with time, although statistical parameters were not applied and this follows the effect of regression and decrease in

over-correction with time.

Question 5, do the safety and efficacy data presented in the PMA support approval of this device for the requested indication?  I would say yes, with the concerns that I’ve mentioned about the 12 and 24 — bring the data out to 24 months and deciding whether we are going to call this a temporary effect or when stability is defined.

And as to Question 6, the recommendations for labeling regarding regression of effect, induction of cylinder and incidence of visual symptoms, I would address myself again to the question of stability.  I do believe the sponsor is being a little disingenuous by playing around with not being able to see whether this is permanent or temporary and not needing to choose those words, yet at the same time including in the patient labeling a statement saying that LTK reshapes the cornea to temporarily treat hyperopia, as if to make a distinguishing characteristic that LTK is a temporary procedure with this indeed may not.  I think you have to basically decide is this temporary of if you don’t want to say it’s temporary at the 12 months, then bring it out to 24 months and give us a stability time point, but to say that another procedure that a patient may be choosing instead of this is temporary by comparison, I think is a little bit deceptive, just as deceptive as saying you could be treated with a laser versus a warm heat.  That has to be described in a little bit better detail as well.

The incidence of the axis shift and the magnitude of induced cylinder as well as the duration that this is occurring for should also be included in the labeling because this could cause significant visual symptoms, even if the best corrected visual acuity is minimally affected and even if there’s only a line of uncorrected visual acuity deficit, still I think most of us would not have any problems believing that if a patient has an axis shift of 45 degrees they may have a problem with this.

And in addition, the subjective symptoms the patients should have in the patient booklet, the degree of increase between pre-op and post-op of the symptoms.

SUGAR:  Thank you.

ROSENTHAL:  Mr. Chairman?

SUGAR:  Please.

ROSENTHAL:  I think I should say this now before you start your deliberation that as you all know and I think you’ve been very good about it, each PMA has to stand on its own and this data has been discussed on its own.  There has been reference to other decisions the Panel has made.  I think that’s reasonable to make a reference to it, but I think no comparison either by you, the Panel or certainly by the company in its labeling will be appropriate.  So I think you all are aware of that and I think it’s reasonable to point out in historical perspective that the Panel in the past has approved refractive corrections for quote temporary as you have done, but to compare them in any way would be inappropriate.

Thank you.

SUGAR:  Thank you.  I’d like to suggest a format for proceeding, of going through question by question unless there’s objection, and then using that discussion to then come to a motion and discuss motions.

Do you have a comment, Jose?

PULIDO:  Yes, since Dr. Rosenthal brought up the historical perspective, we should also realize that the first time that the LTK came up to Panel it was not accepted.  It was only after the FDA pushed us to saying that temporary is allowed that the Panel then allowed the LTK to go through.

ROSENTHAL:  I think Dr. Grimmett made that clear.  I think he was quoting me.

GRIMMETT:  Yes, I was.

SUGAR:  Okay.  Does anyone object to proceeding question by question?

Then the first question is what are the concerns regarding the incidence of induced cylinder with significant axis shift and its consequent effect on efficacy?  And I’d like to have one of the primary reviewers be the first to answer each of these.

Dr. Bradley, do you want to begin?

BRADLEY:  Well, I think there has to be concern we have a procedure that is inducing cylinder.  We don’t know what the root cause of this induction is and clearly those patients with larger amounts of this induced cylinder are not achieving the uncorrected VA that is achievable by those patients who have lower amounts of the induced cylinder.  So I think whenever that happens we have to be concerned about it and it certainly is compromising the efficacy.  I think as I alluded in my presentation the thing that  concerns me is we have no idea where it’s coming from and there seems no indication in the near future that it could be improved or remedied.

SUGAR:  Thank you.  Other comments concerning this issue?

I think that the Agency has a sense of our concern about the induced cylinder.  In terms of how specific we need to get beyond what’s already been discussed I’m not sure.  Can you comment, Ralph?

ROSENTHAL:  If the Panel feels they’ve discussed this sufficiently —

SUGAR:  I’m not saying we have.  I’m not exactly sure what direction you want us to go.

Bill Mathers?

MATHERS:  Yes, Bill Mathers.  I’m a little concerned, like my colleagues, that we don’t really know why this is occurring and there certainly are several possibilities.  I think it could be possible to find out.  I think that, for instance, topographic ought to indicate if we have a kind of generalized regular astigmatism or if it’s highly irregular and where it is on the cornea and if there’s a possibility of improving this or if the procedure is just intrinsically going to do this.  And so I don’t think the astigmatism is terrible, but I think we don’t know why it’s occurring.  It may be because we’re treating in some cases on visual axis, but some of that is closer to the periphery than — because of the shape of the cornea.  There’s lots of questions here that remain unanswered.

It may not preclude us from granting some kind of approval because of its safety and efficacy, but we don’t know what’s happening.

ROSENTHAL:  May I just interject?  I think there are certain interesting scientific questions that are always raised by devices and Dr. Mathers has raised them, but whether or not — I do not feel that it’s this Panel’s responsibility to try to come to some conclusion as to why there are problems, except if it influences the decision making process and certainly, hopefully, for devices, in general, when they are finally out in the community many of these questions get answered.

SUGAR:  In general, the way we answer these is by dumping them into labeling and the suggestion has been made that the labeling includes cylinder induction by degree of induction, loss of acuity related to cylinder induction, instability of cylinder induction and the unpredictability of cylinder axis and I think it’s important that if these are put in the labeling that the labeling for the patients not say cylinder axis because that’s not meaningful to a patient, but that there be wordsmithing such that it’s understandable to a patient what’s being talked about.

Alice?

MATOBA:  Also in the labeling we should add that the original study only included patients with astigmatism up to .75 diopters and we don’t know whether this effect would be magnified or not in patients with higher levels of astigmatism.

SUGAR:  Although my presumption is we’re considering approval only in the range that’s been studied.

Other comments on cylinder?  Does everyone agree that this needs to be addressed in labeling?  Any other comments on — that’s Question 1.

No. 2, is 12-month follow-up sufficient to provide reasonable assurance of safety and efficacy?  There are 21 eyes available at 20 months.  Should data for these eyes be required in the labeling?

It’s a two-part question, that is, do we have enough follow-up and (2) what should we do with the data that we have?

Jayne?

WEISS:  I think 12-month data is sufficient to assure safety, but I think part of efficacy is whether the effect is stable or not.  So I think I would have questions about efficacy at only 12 months and consequently would like the data from 24 months to be included in the labeling.

SUGAR:  Go ahead.

GRIMMETT:  Michael Grimmett.  As I made in my concluding remarks, with the final interval showing a .48 diopter shift per year whose confidence interval excludes zero and is increasing, I feel that the 12-month data collection should ensue with FDA analysis of that stability to see if it is now decreasing and if the confidence interval includes zero.  I would hold approval until that’s met.

ROSENTHAL:  Excuse me —

SUGAR:  You said 12 months.  In your presentation you said 12 and then you had another clause about 24-month data.

GRIMMETT:  I’d like to see the 24-month data that’s available or have the FDA look at it, but I believe the 12-month data should show stability by the current criteria before it’s let loose.

SUGAR:  So you’re suggesting that we get more complete 12-month data?

GRIMMETT:  Yes.

SUGAR:  And have that re-reviewed —

GRIMMETT:  By the FDA.  That’s correct.

SUGAR:  Dr. Huang?

HUANG:  I have a real reservation about Mike’s final recommendation.  So we know this is going to be a temporary procedure would that be reasonable to impose on the post-market surveillance rather than defer the PMA, otherwise, I don’t think we will ever get enough data.

SUGAR:  Other comments?  Dr. McMahon?

McMAHON:  Tim McMahon.  One of my concerns and maybe one of my questions is with the supposition that this is a transient effect, that if Dr. Bradley’s supposition is even remotely correct has somewhere in the neighborhood of a 4-year duration, then there’s going to be a tremendous stimuli for retreatment and we have absolutely no idea about this.  And I have — do we have the capacity in the labeling to prevent retreatments in the absence of subsequent study data?

I’m worried that additional treatments will increase irregular astigmatism, reduce the best corrected visual acuity and all the things that have escaped this procedure thus far.

SUGAR:  I think in the labeling we can approve it for the indications and say that this has not been — we say that there is not data on retreatment.  What a physician practicing medicine chooses to do is a different issue that I don’t think we can control.

Am I wrong, Ralph?

ROSENTHAL:  That’s — you can put, you can certainly put in labeling that there’s no data on retreatment.  If you have valid scientific justification, you can include in labeling that you do not feel retreatment is warranted, but —

McMAHON:  That’s like proving the negative.

SUGAR:  But it’s hard to do in the absence of data either way.  But your point, I think is well taken.

ROSENTHAL:  Excuse me, Ralph Rosenthal.  You can use precautions and warnings to clarify your issue, but to contraindicate retreatment without having any data and any scientific basis of that is very difficult to do.

SUGAR:  Jayne?

WEISS:  I think we’ve returned to the issue of temporary versus stable and that’s why I think at some point sponsor, as well as FDA has to put our money down and determine which one this is and that will let us go forward in terms of deciding whether delay approval will go ahead with approval.

I would be of the mind to say to go ahead with approval with the 12-month data that we’ve been supplied by saying at this point the effects are temporary and we will need the 24-month data to determine stability as opposed to holding up approval waiting for that stability to happen.

SUGAR:  I would like to wait until Question 5 in terms of that would be the indication rather than labeling, but the use of the word “temporary” and I assume we’ll have a moderately gently heated discussion.

WEISS:  I was just addressing that to Mike’s comment.

SUGAR:  Dr. Huang?

HUANG:  Andrew Huang.

SUGAR:  And then Dr. Ho.

HUANG:  I have a question for the Panelists.  I’m still not clear if the Panel’s responsibility is to approve the device based on the safety or based on the efficacy.

SUGAR:  Both.  And to comment on both and we recommend to the Agency, the Agency then approves or doesn’t approve the device.

Dr. Ho?

HO:  Allen Ho.  My only comment would be that there may not be anything magical about 24-month data and if stability is established prior to that that would be much more comforting to me.

SUGAR:  Okay, so last comment on this question.

BRADLEY:  It’s actually a question.

SUGAR:  Dr. Bradley.

BRADLEY:  I’m surrounded by such esteemed clinicians and I think the sponsor has already mentioned that treatments for hyperopia tend to have the characteristics we’ve seen with this particular treatment, that is, initially there’s an over-treatment and the patient ends up with myopia.  Subsequently, there’s a regression and arguably the regression is greater than some of the earlier devices that have been approved.

I’m just wondering what patients do with that?  I mean surely we have now a data base of how patients handle this.  Are patients opting for some of these other techniques that are out there or are they saying no, I don’t want temporary myopia and I’m not going to have a surgery is then going to regress away.  I’m going to lose the effect.  Because if that’s the case, then I would say perhaps we shouldn’t approve this one, but if patients are quite happy with that, then my opinion would change.  But I have no knowledge of that.

WEISS:  I think our decision should really be made at the Panel just on safety and efficacy requirements and whether or not an individual patient opts for this is a whole separate question which I don’t think we really have to address.  The company and its stockholders will have to address that one.

SUGAR:  Although we can say let the buyer beware and do that in the labeling.

Next is Question 3.

I’m sorry, Bill?

MATHERS:  Bill Mathers.  We can say that it’s effective temporarily at this point because there is some demonstration of efficacy, but we certainly can’t say that we know the nature of the permanent correction and we may not at 24 months either.

SUGAR:  Again, we’ll get to that in the indications and we can also, in addition to these questions, we can recommend post-marketing surveillance and re-review — we cannot recommend post-marketing —

ROSENTHAL:  Rosenthal.  Surveillance, I don’t think is the word.

SUGAR:  I’m sorry.

ROSENTHAL:  You can recommend a post-market evaluation of a cohort.

SUGAR:  No. 3.  Does the refractive correction obtained with this device in light of the rate of change of mean Manifest Refractive Spherical Equivalent over time and the incidence of over and under-correction justify the potential risks.

Go ahead, Dr. Grimmett?

GRIMMETT:  I interpret this question to mean is it reasonably safe despite the limitations of effectiveness.  I believe the answer is yes.  It’s reasonably safe despite the stability questions.

SUGAR:  It’s sort of worded a little ambiguously.  It also says in light of the rate of change of mean Manifest Refractive Spherical Equivalent.  So this is really asking, I think, both of us stability and safety.

GRIMMETT:  Okay.  Well, stability I believe I’ve made my opinion clear that I don’t think the current PMA meets the current FDA definition of stability and I’m uncomfortable approving unstable procedures that don’t meet current FDA definitions, but I do believe that the procedure is reasonably safe.

HUANG:  Andrew Huang.  I feel that the regression is really biphasic as shown by the graph from the presenters.  There’s initial over-correction and there’s later under-correction and so therefore I think the generalize statement by the sponsors generalizing the statements it is 6 to 10 percent decrease loss of the intended correction, I don’t think it’s a fair statement.  I think the sponsors should clarify the issue and report a natural course of this regression to the consumers.

SUGAR:  Again, that’s in terms of how we define the indications, because they’re suggesting, I think that being the indications and I agree, we can suggest rewording.

Other comments?

Arthur?

BRADLEY:  We’re trying to assess whether this procedure justifies the potential risk given what we’ve seen in terms of its effectiveness and it just seems to me that in some ways we’re a bit — we’re forced to make this decision prematurely.  I mean the data, as I show, the procedure itself actually increases the variability in the refractive error distribution.  I can’t imagine how such a procedure can be successful, given in every eye there was a single target end result which is emmetropia.  So it seems to indicate there’s a huge amount of uncontrolled variability in this procedure which is very worrying to me.

We also know that not only the mean, but a significant proportion of the patients are going to have significant, and I mean clinically significant levels of myopia after the procedure, albeit this is a temporary situation for most of those patients.  Again, that worries me in terms of safety, particularly, as I said, these patients have not experienced myopia before.  So this is a first time for them.

In the end, I just worry that we have a procedure that has a lot of uncontrolled variability to it.  It fails to hit its target in the short term and maybe only hits the target at 9 to 12 months because it so happens the regression is passing through zero at that point.  And I just — I’m looking for evidence to say yes, this is an effective procedure.  It actually can render emmetropia is some reasonable way in a large percentage of the people who are treated and I can’t find that.  I’m really having trouble with that.

SUGAR:  Dr. Mathers?

MATHERS:  This is a surgical procedure and all surgical procedures are unstable immediately after the procedure.  We take this to a higher standard with a refractive procedure because we’re dealing with somebody that can see beforehand, as opposed to say an unstable knee that needs a total knee.  But nevertheless, it is a surgical procedure and the fact that it’s not perfect immediately after I think it would be to a higher standard to hold that to make it perfect immediately, in general terms.

BRADLEY:  Maybe I can respond to that.  I think it would be true, if this patient was rushed to the hospital and needed treatment, but that’s not the case.  I mean these patients have alternative modalities which they can use to correct their farsightedness.  So this is an elective procedure and I think we should hold it to a much higher standard.  I’m quite comfortable with that higher standard.

SUGAR:  Additional comments on Question 3?  If not, we’ll move on to Question 4.  Are there concerns regarding the increased incidence of visual symptoms from pre-op levels?

We’re back to you, Arthur?

BRADLEY:  Well, I know we’re not allowed to mention other refractive procedures, Ralph, so I’m not going to.

(Laughter.)

But we clearly know this is a ubiquitous result.  Any time a refractive surgery is done to the cornea, we have loss of best corrected visual acuity which is, by the way, symptomatic of some optical imperfection.  We have increased optical manifestations, also visual manifestations of optical problems:  halos, glare around light sources, transient visual, unstable vision, I mean.  And it seems like this particular procedure is no different.  So it just fits in with the crowd.

SUGAR:  Go ahead.  Janice?

JURKUS:  Janice Jurkus.  I have some very serious concerns regarding the changes from when people were pre-op and they said they had no symptoms to post-op and they said that they did have symptoms, even though they may be mild symptoms.  I think the person can quite easily tell if they have a symptom or not and I understand that the subjective information that patients given can vary from day to day, but when you get the amount of change that was noted in the submission that’s concerning to me, particularly in terms of the halos around lights and the patients having fluctuating vision and having fluctuating vision in dim illumination because again, the age population that this treatment is for is also the age population that may be developed in cataracts and these can be exacerbated to even a further degree.  So that is a very serious concern to me.

SUGAR:  Go ahead, Dr. Ho.

HO:  Allen Ho.  I’m less concerned about those.  Any symptomatology that’s reported in an uncontrolled fashion and I would say that the bottom line here on satisfaction, 9 out of 10 patients were satisfied.

SUGAR:  Okay, other comments?  I think Mike and then Jose.

GRIMMETT:  That’s okay, Jose can go.

PULIDO:  Dr. Ho, where was the — Jose Pulido — where was the 9 out of 10 satisfaction rate?

HO:  Can you guys confirm that?

GRIMMETT:  The relative figure was 1 out of 10 were dissatisfied or very dissatisfied and then the satisfaction rate, you’d have to subtract the neutral category out.

HO:  Right.

GRIMMETT:  So satisfaction may be, if my memory serves me correctly, 70 percent?

PULIDO:  Yes, it wasn’t 9 out of 10.

GRIMMETT:  But you’d have to look at the tables.

HO:  Okay, Allen Ho. I’m corrected, but the point is you have to be very careful about looking at rates of symptoms in the context of an uncontrolled setting.

GRIMMETT:  Mike Grimmett again.  I think — I agree with Dr. Jurkus’ concern over the symptom data and I think those issues can be dealt with in the labeling as given an example of a nice table that Dr. Berman presented on the very next slide, Slide 15, as well as delineating the percent of patients that had no symptoms pre-op, versus no symptoms post-op.  That was the type of data I presented in my presentation.  I just reversed the numbers to yes rather than no, but I think both ways of presenting the data would be appropriate in the labeling.

SUGAR:  I’d like to move on then to Question 5.  Do the safety and efficacy data presented in this PMA support approval of this device for the requested indication?  That’s getting back to the wordsmithing we were talking about.  Is the requested indication appropriate as worded, based on the study outcome?

And then the last page of the sponsor’s presentation, I think, had their recommended wording if I’m correct.

This is CK treatment for the indication of spherical hyperopia in the range of +0.75 to +3.25 diopter for cycloplegic spherical hyperopia, -0.75 diopters or less of refractive astigmatism, +0.75 to +3.00 diopters of cycloplegic spherical equivalent.  In patients with less than .50 diopter difference between pre-operative manifest and cycloplegic refractions who are over 40 years of age, that’s the up front indication in terms of patient refractive error and age.

The magnitude of correction diminishes over time with an average loss of approximately 6 percent by paired analysis manifest refractive spherical equivalent of the intended correction at 1 year.  The proportion of intended correction retained beyond 12 months is undetermined.

I guess I’d like to deal with first the two main bullets, the dioptric correction for sphere and cylinder and the difference between pre-manifest and cycloplegic refractions in patients 40 years of age or older.

Are there comments suggesting to modify those.  Please, Jayne?

WEISS:  Well, I would agree with the three bullets as listed, except would want to — if the device was going to be approved today, I would like to add CK treatment for the temporary reduction and just add the word temporary which can be changed if the 24-month data which will be reviewed by the FDA shows stability at that point.

SUGAR:  Okay, I sort of tried to separate these so that we can — I’m not trying to avoid anything, but — in a way I am, but that’s different.

The last two bullets are really discussing that wording and it could be put up front or at the end that I think ultimately FDA will decide.

WEISS:  Jayne Weiss again.  The erst of the bullets as listed that you’re referring to I would agree with.

SUGAR:  Dr. Huang.

HUANG:  Andrew Huang.  I have a little bit reservation about the proposed three indications.  I think the data presented by the reviewers are stratified patients of pre-operative hyperopia, so you can see there’s a drastic difference between the efficacy between the +2.00 of greater or the +2.00 or lower hyperopia.  So I think maybe we can review the data if the sponsor can stratify the information according to the pre-operative information and then show the efficacy is indeed much better in one group and then we probably can narrow the indication of +.75 to +2.00 or +2.50 instead of all the way to +3.25 to increase the safety margin.

SUGAR:  Okay, there are two different ways that we’ve dealt with this.  One is to change the indication.  The other is to leave the indication, but include in the labeling and physician information require that it be in — that information that there be stratification and demonstration of efficacy and that the patient be told that there are different efficacious at different rates.  I think Mike and then Alice.

GRIMMETT:  Mike Grimmett.  I would favor the latter option that Dr. Sugar discussed of dealing with it in the labeling.  We all know that most of the refractive procedures have decreasing efficacy as the level of emmetropia increases.  I don’t think it would be exactly fair or right to chop it off at the higher range unless there was such a paucity of data at the higher range that it wouldn’t warrant the approval.

I would leave the first three bullet points alone and deal with the decreasing efficacy in the labeling.

SUGAR:  Dr. Matoba?

MATOBA:  Dr. Alice Matoba.  I agree with Dr. Grimmett.  I think the patients who had the higher levels of pre-operative hyperopia were more satisfied and happier with the procedure.

HUANG:  But have less effect.

SUGAR:  That’s correct.  Bill?

MATHERS:  Bill Mathers.  But that is the group actually that needs — that is most interested in having the procedure, so I think that whereas the efficacy, the effect may not be quite as great, it would be unfortunate to remove that group from this.

SUGAR:  Okay, I’d now like to deal with the indication, the wording in the indication for our concern about stability or loss of effect.  The sponsor suggests the magnitude of correction diminishes over time with an average loss of approximately 6 percent of the intended correction at 1 year.

BRADLEY:  I’m a bit worried by this because if we replace one year, perhaps 11 months and 3 days it would be zero percent because there is some point at which that function crosses zero and it may just be fortuitous that the cross over one is close to 1 year and what is misleading about that is the implication that boy, it’s right on target and there is no indication that, in fact, that was a moving target.  So I’m a bit worried about an incorrect implication of that statement.

SUGAR:  Please, Dr. Grimmett?

GRIMMETT:  I agree with Dr. Bradley’s concerns.  I think the comparison to intended correction with the moving target is misleading to consumers.  The way that I looked at it or analyzed it, at pre-op, these patients had a mean hyperopia of 1.86 and at month 1 they were corrected to a mean of -.56 diopters for a mean total of 2.42 diopters of surgical effect at the 1 month visit.  They lost .8.  That’s about a third of the effect was being lost with time, so in my presentation when I said they lost about a third of the surgical effect, that’s the way I was looking at it and I feel the 6 percent figure would give misleading reassurance to consumers.  I’m not in favor of the comparisons to intended correction because it is a moving target.

SUGAR:  Bill?

MATHERS:  Bill Mathers.  I think it would be more accurate at the present time for the public to understand that it’s at about a .50 diopter per year in — but this is only an estimate.  Because they care what happens in the immediate time, but really in terms of what they can look forward to once things settle out, it looks like it’s going to be somewhere on .50 a diopter a year.  And that’s perhaps a closer understanding to — although we don’t know this.

SUGAR:  Jayne?

WEISS:  I would like to put this in terms that anyone could understand and I think without looking at the numbers, basically at one year, this is not stable.  The effect is not stabilized at one year.  I’m not sure that all patients would understand the significance of the .50 diopter versus 1.00 diopter whereas if you say it’s not stable, well, it’s not stable.

SUGAR:  So you’re suggesting?

WEISS:  Well, I would still — I don’t know if I dare to go back to the first line and put in “temporary”, but I won’t say that, but I thought it.  But I would agree with the other two reviewers, the last two statements by the sponsor sort of sanitize and minimize what our concern is that at one year time stability of the refractive effect has not been achieved for the consumer advocate might wordsmith a better way to put this for consumers, but that’s basically what I’d like to convey.

SUGAR:  Rich McCarley?

McCARLEY:  Just a comment.  I mean I don’t know if we’re actually trying to wordsmith it here, but it seems like three comments can solve, I think, at least in my mind, you know, the results may diminish over time or the stability has not been established over time.  Average loss at one year is 6 percent.  Long term stability has not yet been established.  I mean essentially you’re telling them what the truth is.  The long-term stability hasn’t been established.  What we do know at least with the data we have is that at one year it appears to be 6 percent and up front you tell them it may diminish over time.  You don’t know — I’m not sure whether the statement that they have even presented is correct because it says that there’s an average or a mean loss of 6 — a regression of 6 percent, but did all patients regress?  So I think it’s simply being up front and telling them the results may diminish over time, the average loss at one year was 6 percent and the long-term stability has not yet been determined.

SUGAR:  My recommendation would be that if we have a statement similar to where there is significant likelihood of regression of effect over at least 1-year period, over at least a 1-year period of time, which may be too nebulous, but I don’t think — I think that 6 percent is too specific and misleading.

Bill?

MATHERS:  Yes.  I would agree with you.  If you’re going to say something, you can’t say the 6 percent.  I think that that’s too soft.  You either need to be more nebulous or you make it a little more accurate, according to what we currently think.

SUGAR:  Too gentle.  Tim?

McMAHON:  Two things.  I’d actually like to put in Dr. Weiss’ comment on the first line that we do put in the point of the temporary reduction of spherical hyperopia and then to address the bullet point with regard to the 6 percent.  I think you can accomplish that by actually posting what the ranges are for both change from maximum correction as Dr. Grimmett was discussing as well as from intended correction and if you show the breadth of the range, then both physician and patient will have some idea of what that spread is.

SUGAR:  Jose?

PULIDO:  Going back this morning, Joel, you asked me why I brought up that case of the patient with that adverse event.  It was a patient that had a -2.00.  Dr. Bradley later talked about the -2.00 situation as well and my concern and it’s been brought up by the Panel reviewers is the unpredictability and nowhere in this yet have we discussed the fact that it’s not a very predictable procedure.  Do we need to put that somewhere in the labeling?

SUGAR:  I think that there will be agreement to that. Right now, I think we’re still dealing with the indications, but I agree with you wholeheartedly.

Arthur?  I guess I’m not supposed to agree.  I’m supposed to be neutral.

THORNTON:  You can agree.

SUGAR:  I can?  Thank you.

BRADLEY:  I’ll try to preface the agreement with — I’ll try to agree with Joel and with Jose here.  This is Arthur Bradley.  Yeah, I think that second from last bullet is unique, really, compared to the other ones and one wonders if it’s appropriate in the indications for use.  Because really it’s sort of an apology for a statement of the inaccuracy of the procedure.  And it’s only one of the inaccuracies is as I spoke before, the procedure itself has a lot of variability, so inherent inaccuracy and this is just mentioning one summary statistic of a whole variety of errors produced by this procedure and I think if in the indications it’s appropriate to put a summary of the inaccuracies of the procedure, I think that would be fair enough, but this is completely inappropriate as such a summary, but I’m not sure that that would be an appropriate thing to put in the indications, but it seems to me that’s what it is.  It’s a statement of the inaccuracy of the procedure and I think there are a variety of things we’d like to put in such a summary statement.

SUGAR:  Jose?

PULIDO:  So, Joel, you castigated me for putting, for talking about the unpredictability —

SUGAR:  I enjoyed it.

(Laughter.)

PULIDO:  But really, I think it should say something to the effect of CK treatment for the unpredictable and temporary reduction of spherical hyperopia in the range of dah, dah, dah.

SUGAR:  No comment.  Jayne?

WEISS:  I know we’re not supposed to speak about other lasers or other procedures, but I do think we have to apply standard criteria to the devices that we evaluate here and I think putting that in would hold it to a higher level than we’ve been applying to any other device.  I think the indications are meant for what you use it for and the sponsor has indicated that.  We’re discussing how we can indicate in a clearer fashion that there’s not stability at one year, but to talk about the variability, I think that should be put into the labeling as opposed into the indications because that’s the way we usually do it.

SUGAR:  Mike and then Bill.

GRIMMETT:  Mike Grimmett.  I’m not in favor of a single word temporary or permanent.  I just don’t think that the data are sufficient to prove it one way or the other.  We simply don’t know.

What we do know is that the refractive effect diminishes over the study period and we don’t know where it stops, so I would with those two points I would somehow like them in a sentence and I suggested one, but there’s numerous ways to do it to communicate those two particular points.  I’m not a fan of the word temporary.

SUGAR:  Can you restate yours?

GRIMMETT:  Sure.  My was “refractive stability is unproven for the CK procedure, with progressive loss of refractive effective over time.”  I’m certain that can be wordsmithed to something better.

SUGAR:  That’s worded more as a labeling thing rather than as an indication thing, unless you add CK treatment for the reduction of spherical hyperopia, where —

WEISS:  This is just a question to yourself or Dr. Rosenthal.  In terms of the devices that we look at ordinarily, ordinarily does it have permanent versus temporary in the wording?

ROSENTHAL:  This is Rosenthal.  No.  It says for the — I forget what the exact word is — for the correction of, which implies for the correction of.  And for the temporary correction of implies for the temporary correction of.

WEISS:  So this is — Jayne Weiss again.  This is where my concern lies is by not putting the word “temporary” are we implying “permanent”?  And that’s why I’m going back to past experience with other devices, just so that the consumer can have a uniform way of comparing things?

SUGAR:  My sense of the committee is that we all agree that there needs to be some modifier that says — that based on the information we have now it does not appear to be stable and how we say that is what we’re discussing.  I agree.

Bill, I think, was next.

MATHERS:  Well, it was a couple of comments ago, but I think that all of our assessment of both the stability and the accuracy is based on a relative effect and that we — although we don’t talk about other systems, I mean none of this is accurate to the point at which we — and to the level that we can measure.  They’re all inaccurate and this is inaccurate as well, but in my opinion it isn’t so wildly inaccurate that we should particularly characterize it as being an inaccurate approach.

But I do think it is important to address, to not let it stand either through labeling or through this indication use, that it is intended to be permanent because other systems of this are permanent, so this is a little different and somehow we ought to indicate that.

SUGAR:  How would you suggest that we indicate that in the indications?

MATHERS:  Well, if we put temporary in here now or if we recommend that — and we learn later that it is different would it be removed?  Because — I mean we don’t have a complete data set here.

SUGAR:  It could be.

ROSENTHAL:  Rosenthal.  Dr. Mathers, yes.  The company could come back with 2-year or 18-month or 3-year or 6-year and ask for the elimination of the word or change in the indication based upon the data.

MATHERS:  Because if I’m being intellectually honest about how this is now, it is the temporary effect in my mind now.

SUGAR:  Go ahead, Alice.

MATOBA:  Alice Matoba.  I think permanent is actually a relative term when you’re speaking about these sorts of procedures and my question is are these last two bullets really indications?  Shouldn’t they actually belong in another part?  Isn’t it really more like a warning or a labeling?  Couldn’t we just approve the first three bullets and then move on?

SUGAR:  I think that the last two bullets modify the first bullet and certainly that information, this is opinion, should be in the labeling.

MATOBA:  Okay.

SUGAR:  The question is whether we approve this for treatment for the reduction — approve this treatment for the reduction of spherical hyperopia or we approve this treatment for temporary or permanent, whatever.

MATOBA:  Okay, my opinion is that the last two bullets are not indications and they’re just modifications.

SUGAR:  I personally — I said this when we reviewed another hyperopia correction.  I think temporary implies that it is never permanent and I think temporary is an inadequate word to describe what we’re trying to say, but I don’t know what the right word is and I made a suggestion and I think there have been other suggestions.

Is anyone willing to take the bull by the horns, as it were?

Bill?

MATHERS:  If you left the initial bullet to say “for the reduction” and you left the second to the last bullet to say “the magnitude of the correction is temporary” down there, it would still do the same thing, although I do agree both those are —

SUGAR:  Does “diminishes over time” say temporary sufficiently for you or not?

MATHERS:  I think it should say temporary.

SUGAR:  Jayne?

WEISS:  I understand Dr. Matoba’s confusion with the last two statements because I think it’s a way of skirting the issue of whether it’s temporary or not.  And I think they sort of imply it’s temporary, but don’t say it’s temporary and I think it would just be easier to call it for what it is.  At the present point it’s temporary and if we have a 24-month data, if the FDA is now reviewing that and they see that indeed it stabilizes at 18 months, then that can be easily taken out even before it’s on the market.  But if the sponsor is going to come forward to us with incomplete data, then we can only act on what we see and I think it is temporary at 12 months.

SUGAR:  Bill?

MATHERS:  I guess that I kind of agree with you that temporary is a little bit too harsh a statement and if we just said the magnitude of the correction diminishes over time period, then we are vague, but we are conveying that as a statement and you don’t really have to say it’s temporary because temporary really means it’s never permanent.  I agree with you about that.

MATOBA:  We don’t know that.

MATHERS:  No, we don’t know that.

MATOBA:  It could go down for another year and then just — Alice Matoba.  We don’t know that it’s temporary.  It could keep going — the effect could go down for another year and then stabilize completely.

WEISS:  That’s only because we’ve been forced to meet here without the complete data set.

MATHERS:  Correct.

WEISS:  That’s why we don’t know it and the data set is out there, so someone knows it.

MATOBA:  Alice Matoba, so I think we can say neither temporary nor permanent.

WEISS:  That’s my —

SUGAR:  Joel?  Tim?

McMAHON:  I disagree with that.  We’re faced with a set of data that we’re supposed to comment on and it doesn’t show stability on that basis.  The description is more temporary than anything else.  Now whether it’s going to be like years down the line is something we can speculate on, but we’re being asked to advise on and it is not stable and the effect is going away.

SUGAR:  Dr. Ho?

HO:  Allen Ho.  I just wanted to make a specific suggestion to include the first three bullets as indication and then the last two bullets, I would be personally comfortable with, “the magnitude of correction diminishes over time.”  And then the last bullet stands as is.

SUGAR:  Jose?

PULIDO:  Well, Jose Pulido.  Treatment for the unstable reduction of spherical hyperopia.

SUGAR:  I wonder if it’s appropriate or not to mention in another review this committee looked at a suggested indication where the magnitude of correction diminishes over time, where it said treatment for the reduction of hyperopia where the magnitude of correction diminishes over time and we changed that to temporary.  Yeah, I personally favor where the magnitude of correction diminishes over time, but putting it up in the first sentence.

I suspect we’ve given you a sense of where we are.  We haven’t?  Okay.

ROSENTHAL:  Dr. Rosenthal.  You’ve given us a sense.  You’re going to have to vote.  The sense of the Panel has been clarified, but you’re going to have to ultimately vote.

SUGAR:  I understand.  We’re still discussing.

BRADLEY:  The suggestion of Dr. Ho that we simply just include the very first part of that second from last bullet, the magnitude of correction diminishes over time period seems to me a way which accurately describes the result.  It doesn’t put any potentially misleading statistic in there like 6 percent and we don’t have to call it temporary.  We don’t have to call it permanent.  We don’t have to get embroiled in any of that.  We’re just stating a very simple fact.  The fact is the magnitude of the correction diminishes over time.  And then the next bullet comes along basically saying well, we don’t know what’s going to happen beyond 12 months which is correct.  So —

SUGAR:  Although it’s been suggested that that be taken out of the indications, that last bullet and be put in the labeling.

BRADLEY:  I don’t think either of them are indications, but we’re discussing them as indications.  I personally think they should be dropped completely and put in the labeling.  But if we want something like this in the indications, I think what Dr. Ho suggested is a very good suggestion.

SUGAR:  Dr. Weiss?

WEISS:  Jayne Weiss.  The concern or the issue that you just brought up is the concern that I have that we’re applying for similar phenomena to different companies, different wording and some of them may be much more favorable and some of them are less favorable and for a patient who is comparing two potential procedures they can have, I would think it would be clearer for the consumer to have similar wording to convey similar issues.  And that is where my concern is as we recently looked at another device whose name won’t get mentioned because I’m not discussing other devices, but we dealt with the issue of stability and because it was not stable at the time point that was given to us, we said it was temporary.  Now of course, no one knows that’s going to be in 50 years or 20 years.  You can get ridiculous as far as final time points.  Yes, at some point — but all the Panel can do is look at the data we have.  So if we have data at 12 months and it’s not stable at 12 months, then why should we be giving different sets of wording for the same phenomena to different companies?

HUANG:  Andrew Huang.  In addition to the wording, I think that that’s a fair statement, but I think the indication we should look into the substance of the indication.  If we think that two or three similar devices provide similar effect, then if we provide a different range of the allowable correction, then that will be a disfavor to one of the companies.

SUGAR:  Could you clarify?

HUANG:  Well, I’m not sure about an indication of other companies, but obviously —

SUGAR:  That’s not relevant to this.

HUANG:  That’s what I’m saying, but the whole point is if we take into Dr. Weiss’ discussion into consideration that we have to give the fair wording to the indication, labeling for this company, then we should also take into the other factors into consideration in terms of —

SUGAR:  I think we should be fair based on the data that’s presented to us and what Ralph is going to say is not relative to another product.

HUANG:  That brings to mind another point on Dr. Grimmett’s Slide 22 and obviously the amount of under-correction greater than 1.00 diopter is significantly more in the patient in the pre-operative hyperopia of greater than 2.25 diopters.  The difference is 5 or 6 orders of magnitude, so I think that narrowing of the indication probably, should be discussed.

SUGAR:  Actually, we did discuss that earlier and at least the —

HUANG:  I know I may be in the minority.

SUGAR:  No, but that should certainly be in the labeling.  But I think we also — we’re going to go back and vote on these one by one.

Janice was next.

JURKUS:  I just wanted to say that I agree with Dr. Weiss.  I think it should be stated right up front that this is a temporary reduction.  We don’t know if it’s permanent.  And if you don’t put that in it would appear to the consumer and the person buying this device that it would be permanent.  And it can be removed if it needs to be removed at a later time.  I think it’s quite important that it’s put right in the very front.

SUGAR:  Okay, the sixth — I’m taking the prerogative of moving on to the sixth question.

What are your recommendations regarding regression of effect, induction of cylinder and incidence of visual symptoms?  Are there any additional labeling recommendations?

And I’d like to ask Mike to go through this since he listed them I think in his presentation.

GRIMMETT:  Sure.  Mike Grimmett.  On the last page of the copy of the slide handouts I listed suggested labeling considerations.  Everyone should have it in front of them.  We’ve already discussed 3, 4 and 5.  Joel Sugar mentioned about the induction of cylinder data.

These pretty much speak for themselves.  Number 1, include the spectrum of best corrected visual acuity loss at each exam interval and state that of those 24 patients losing best corrected vision at 6 months or beyond, half of those patients are dissatisfied.

No. 2, include the subjective symptom data.  I would suggest to include a slide like Dr. Berman suggested in Slide 15.  And also include those patients who had no symptoms pre-op versus no symptoms post-op.

No. 6, include predictability data.  I don’t think there’s any argument there.

No. 7, I would include a statement regarding Dr. Bradley and my concern regarding the predictability that the post-operative standard deviations of the mean refraction actually increase after this procedure.

No. 8, is getting to Dr. Huang’s concern of including a statement of decreasing efficacy as a pre-op hyperopia increases supported by several features:  (a)  uncorrected visual acuity data showing lower rates of 20/20 or better for higher hyperopes.  (2) the proportion of undercorrection is greater than 1.00 diopter is increased in the higher hyperopic group and (3) the proportion of eyes achieving plus or minus .50 or plus or minus 1.00 of intended decreases as the range of hyperopia increases.

No. 9 was regarding the instability and I listed the five or six features I listed in my slide that we’ve discussed at length already.

No. 10 was an additional issue regarding the reduction in spectacle or contact lens dependence.  I put that in before I knew that — I think Dr. Weiss asked that was the pre-op spectacle dependence known and since it’s not known, I guess I retract No. 10.  I don’t think you can make a comparison when it’s not known pre-op.

  1. SUGAR:  If you take out the word “reduction” you can still ask for the data if they have it.
  2. GRIMMETT:  Yes, they know what the data is post-op.  They include it in Amendment 11.  I think it’s a useful piece of information.  I just now don’t know what to compare it to.

11 was regarding satisfaction data as has been mentioned regarding a 1 in 10 rate of dissatisfaction.

No. 12 is the manufacturer has already suggested to include a statement regarding a lack of retreatment data and therefore the suitability for future refractive procedures is unknown.  I think that’s a crucial issue because of the decline in refractive effect with time.  It’s critical that the patient know that future retreatments, it’s really unknown what effect you’re going to get.

No. 13, we just talked about the indications for statement, so 13 we’ve already discussed.

SUGAR:  In there, there’s not a statement about data beyond 12 months or whatever data is presented is not available at the present time, right?  Should that be in the labeling?

I don’t know if there will be data put in including 24 months, but should there be a statement that data beyond a certain time period is not yet available?

GRIMMETT:  Oh sure.  I would agree with that.

ROSENTHAL:  Mr. Chairman, Rosenthal.  Certainly, the Panel, if they feel data beyond 12 months is required to be put in the labeling, you can request that be done or you can do it in a post-market arena where the labeling can then be altered afterwards.

SUGAR:  Or we can do both.

ROSENTHAL:  You can do both or you can do neither.

SUGAR:  I’m sort of suggesting we do both.

Jose?

PULIDO:  Jose Pulido.  I would also like to include what we talked about this morning, any implant of electrical devices in patients would be a contraindication for use in those cases.

I would like to ask the Panel their feeling about patients that have pre-existing narrow angles.  They were not included in the study.  Should there be something in the warnings and precautions about those patients?

SUGAR:  Again, in the absence of data, it’s worth at least stating that the effect on narrow angles is not yet known.

PULIDO:  And also, I would like to know from the Panel what they feel about the part where it says onset of cataracts unrelated to age, systemic disease or trauma as a potential adverse effect of the device.  I guess they’re alluding to the fact that this is microwave energy and microwaves can cause cataracts.

We don’t know — this was —

ROSENTHAL:  This is not microwave.  This is radio frequency.

PULIDO:  It’s not microwave?  Okay.  So radio frequency, do we know the effects of these radio frequencies on cataracts?

SUGAR:  Why doesn’t the sponsor come to the table and answer so we can get it on the record.

You were reading from their proposed contraindications or proposed —

PULIDO:  Yes, correct.

SUGAR:  This is just to answer a specific question.  You’ll get your —

DURRIE:  I think we’re all familiar as ophthalmic surgeons to electro cautery that we use, bipolar cautery which is the same radio frequency waves and there’s nothing I know of that has caused cataracts with the bipolar uses of cautery in the operating room.

So this is not microwave.  It’s radio frequency, like bipolar cautery.

SUGAR:  Dr. Ho?

HO:  I’m just trying to puzzle through what I think is an important point.  In Michael Grimmett’s statement regarding reduction in spectacle or contact lens usage.  I think that’s a very important point for a consumer to try and appreciate.  On the other hand, I think we’re a little tight because we don’t have the data from what the pre-procedure usage was.  Can the sponsors comment to at least give me a sense for what the post-procedure dependence upon other correction was?

SUGAR:  While they’re coming up, I can make a comment that we have in other labelings asked them to supply data of what, how many proportion of patients still use spectacles after the procedure.

HO:  It’s a figure that will just hang out there in my mind as someone who is a trialist, but it’s clearly and I’m a retina surgeon so I don’t talk to patients too much about this, but that is clearly the driving force behind people even beginning to consider their options for refractive surgery.  It’s a lessened dependence upon encumbering devices.

SUGAR:  So you’re supporting there being that data?

HO:  I’d like to hear what the data is first.

McDONALD:  Marguerite McDonald.  Fourteen percent of patients reported using distance spectacle correction at 6 months and at no time point at 3 months or later did more than 20 percent of patients use spectacle correction for distance.

SUGAR:  So you’re suggesting that there be some statement including that information?

HO:  I’d like to puzzle through it with the committee, because I think in terms of language for labeling that is a very important point.  Perhaps something that will hang in a patient’s mind more so than cylinder shifts and diopter shifts, etcetera.  So I’d like to hear other comments.

SUGAR:  Jayne?

WEISS:  Jayne Weiss, is there any way for the sponsor subsequently to get that information, how many patients had pre-op contacts or distance glasses?

SUGAR:  Dan?

DURRIE:  I think we need to remember, I think 100 percent of these people wore glasses pre-op.  I mean that’s why they came in.  On all of the patients I know of, we didn’t ask that in the questionnaires, but these patients came in not because they were doing well and didn’t need glasses.  They all came in and had this procedure because they were wearing glasses and having problems with it.  This was a distance only study, so this wasn’t done to get rid of the reading glasses.  So these were 53-year-old hyperopes who were having problems, that’s why they came in.  So I would say that 90 percent plus of them were wearing glasses pre-op for distance or they wouldn’t have even thought about having this procedure.

SUGAR:  Did you have an additional comment?

WEISS:  I would assume there would be a certain number of the +.75s or the +1.00s or the +1.25s for vanity’s sake, whatever, that might have been walking about blurred, so we would need the data if we’re going to put it in there, the actual numbers.

HO:  In Philadelphia, some of the +3.00s walk around.  They just can’t see and they’d be very happy with this surgery, no matter what.  But seriously, I think that number is a very important number and Dr. Durrie’s comments stand to reason, it would be more comfortable having that, perhaps making a disclaimer about not knowing exactly the number of patients that had used glasses for distance preoperatively would be fair and accurate and saying this is the results that we have after the procedure.

SUGAR:  I personally think it doesn’t matter what it was before.  What matters to the patients is what is after, but the sense of it is that we want information on — and/or contact lens dependence following the procedure.

Jayne?

WEISS:  Jayne Weiss.  I would like something in the labeling for the patients to sort of convey that initially they may expect an over-correction and some myopia and that there is a gradual drop off and not to expect the semi-final result until 6 to 9 months so that patients understand this is going to be a long process.

SUGAR:  Okay.  The sirens are not coming for us yet, I don’t think.  I think we have dealt with adequately or inadequately all six questions.  Are there additional issues that the Panel would like to raise?  The process would be then to have open public hearing:  FDA posing statements, sponsor posing statements and then we’ll go through the formal proposal, formal motion and discussion and voting options.

Tim?

McMAHON:  Tim McMahon.  I didn’t see this raised and if I missed it, I apologize, but there’s been nothing mentioned about the immediate post-operative pain levels, duration and management issues.  I was wondering if any of the investigators or the sponsor wants to comment on that?

SUGAR:  Dr. McDonald?

McDONALD:  Marguerite McDonald.  The immediate post-op discomfort is minimal.  People either report no sensation whatsoever or a mild foreign body sensation for 2 to 4 hours.  Most report taking no pain killers or maybe a Tylenol, so it’s very minimal.

McMAHON:  Thank you.

SUGAR:  Dr. Bradley?

BRADLEY:  Just to remind us of something, I and a couple of other people mentioned earlier, I think it’s important for the patients to have a good indication of what the actual procedure is and describing it as gently heating your cornea really is an inadequate description.  It might work for marketing, but it’s not adequate for FDA patient information.

SUGAR:  So that’s suggesting changing the wording in the patient information booklet.

Okay.  Hearing no additional discussion, I’m sorry, I hear additional discussion.

MATHERS:  You might say controlled heating rather than gentle.  Because on a relative scale it is controlled.

BRADLEY:  I think if I hold a match to my cornea it’s fairly well controlled, but —

(Laughter.)

I’m not sure I want to admit to that last comment.

SUGAR:  Okay, we’ll now move on to the open public hearing session.  Is there anyone from the public that would like to make a comment, a relevant comment?

(Pause.)

Hearing no such interest, the FDA now has five minutes for its closing comments and I will hold them to that five minutes.

ROSENTHAL:  I’d like to thank the Panel for an excellent discussion of the issues and am particularly to the primary reviewers for very thoughtful reviews.

SUGAR:  Would the sponsor like to comment?

GORDON:  Judy Gordon.  We, too, would like to thank the Panel and FDA for some very good comments and I think we’ll endeavor to communicate the gist of everything that’s been discussed here as best we can in an articulate fashion in the labeling and particularly in the patient information brochure so that we convey the information accurately.  So thank you again for your input.

SUGAR:  Next, Sally Thornton will read our voting options.

THORNTON:  These are the options for the Panel recommendation on this pre-market approval application.

The medical device amendments to the Federal Food, Drug, and Cosmetic Act is amended by the Safe Medical Devices Act of 1990, allows the Food and Drug Administration to obtain a recommendation from an expert advisory panel on designated medical device pre-market approval applications or PMAs that are filed with the Agency.

The PMA must stand on its own merits and your recommendation must be supported by safety and effectiveness data in the application or by applicable publicly available information.

Safety is defined in the Act as reasonable assurance based on valid scientific evidence that the probably benefits to health, under conditions on intended use outweigh any probable risk.

Effectiveness is defined as reasonable assurance that in a significant portion of the population the use of the device for its intended uses and conditions of use when labeled will provide clinically significant results.

Your recommendation options for the vote are as follows:

Approval, if there are no conditions attached.

Approvable with condition.  The Panel may recommend that the PMA be found approvable subject to specified conditions such as physician or patient education, labeling changes or further analysis of existing data. Prior to voting all of the conditions should be discussed by the Panel.

Not approvable.  The Panel may recommend that the PMA is not approval if the data do not provide a reasonable assurance that this device is safe or if a reasonable assurance has not been given that the device is effective, under the conditions of use prescribed, recommended or suggested in the proposed labeling.

Following the voting, the Chair will ask each Panel Member to present a brief statement outlining the reasons for their vote.

SUGAR:  Thank you.  I would like to ask for a motion to be made from the floor concerning this PMA.

GRIMMETT:  Mike Grimmett.  I’d like to make a motion that the Refractec PMA is approval with conditions.  I assume we’re going to talk about the indications statement separately.  Is that right?  Vote on it separately?

SUGAR:  No.  I think your motion should be — the —

GRIMMETT:  Let’s leave it at approvable with conditions and we will discuss each condition and vote on them separately.

SUGAR:  That’s fine.

THORNTON:  Each one has to be discussed and voted on separately.

SUGAR:  But it could be also approval for the following indication and then with conditions.

A motion has been made.  Is there a second to the motion?

[Motion was seconded.]

SUGAR:  Then we vote on this motion?  No.

THORNTON:  You go through each condition, vote on each condition.

SUGAR:  This is where I need help.

THORNTON:  That’s okay.

SUGAR:  So a motion has been made and seconded that this be approvable with conditions.  We’d like to now flesh out the conditions, and I’d like to first ask that the indications be stated.

Jane would like to do that.

WEISS:  Jayne Weiss.  I would propose that the indications for the procedure be listed as follows:  CK treatment for the temporary reduction of spherical hyperopia in the range of +.75 to +3.25 diopters of cycloplegic spherical hyperopia, -0.75 diopters or less of refractive astigmatism, +0.75 to +3.00 diopters of cycloplegic spherical equivalent.

And would you like me to continue through this whole sheet or do you want to go through each thing and vote on it separately?

SUGAR:  I’d like to, if you could state the indications and then we can vote on that as a single unit.

WEISS:  Second point being in patients with less than or equal to 0.5 diopters difference between preoperative manifest and cycloplegic refractions in patients 40 years of age or older, refractive stability is unproven for the CK procedure.  The proportion of intended correction retained beyond 12 months is undetermined.

SUGAR:  Is there a second to that?  Is there a different motion?

McMAHON:  Jayne, would you accept an amendment to incorporate Dr. Ho’s comment about that one bullet, about the magnitude of correction which read as “the magnitude of correction diminishes over time.”

SUGAR:  The period meaning that the last two clauses that Jayne had would not be in the statement?

McMAHON:  The last part of the second to the last bullet would not be, but the very last bullet would.  So it would be “the magnitude of correction diminishes over time.”  The next bullet:  “The proportion of intended correction retained beyond 12 months is undetermined.”

SUGAR:  Is there a second to that?

GRIMMETT:  Did she accept the amendment?

SUGAR:  Okay, I guess you can — her motion was a not seconded —

WEISS:  Jayne Weiss.  So just to clarify, you would agree with CK treatment for the temporary reduction of spherical hyperopia and then everything else that I mentioned stayed the same except for the last two bullets, the magnitude of correction diminishes over time and the proportion of intended correction retained beyond 12 months is undetermined.  I would second that.

SUGAR:  Discussion?  Dr. Pulido?

PULIDO:  Jose Pulido.  Again, my concern is the last two bullets have nothing to do with indications.  It’s labeling.  And by putting “temporary” you already have taken care of the last two bullets and you can — I would rather have that shifted — those last two bullets some modification of the last two bullets shifted over to the labeling.

SUGAR:  Other comments?

McCARLEY:  Yes, may I suggest that we keep the first three bullets as they are and simply have a footnote at the word “reduction” and indicate the last two items with some wordsmithing to take out the percentage and so forth, so there’s a clarification of what reduction of spherical hyperopia means and then again include this language in the labeling portion of it.

SUGAR:  So you’re not including the word “temporary” or are you including the word “temporary”?

McCARLEY:  I am not.  I am defining it with the use of the last two paragraphs.  I would also — yes, I would also include the word “temporary.”

SUGAR:  Okay.

McCARLEY:  But I would do it as a footnote along with the last two points.

SUGAR:  Okay.  Certainly that’s gentler.  Further discussion of that?

I think that we need to have the motion — I guess we’re still discussing a motion that’s been seconded and the discussion has suggested that the last two bullets be eliminated from the indications and that the word “temporary” be included, although a suggestion has been made that the “temporary” be footnoted and the other two things be footnoted.

I’d like to ask our expert on footnoting to discuss this.  Mike?  Dr. Grimmett, the footnote expert.  For those of you who didn’t read his review, it was highly footnoted.

GRIMMETT:  I would, if the word “temporary” is going to be used and the pro for the word “temporary” is that it’s easily understandable by the consumer.  It’s easily recognizable.  If the word “temporary” is going to be used, I would put it in the first sentence.  I wouldn’t footnote it.  It’s either there or not.  I wouldn’t put it down, but the word “temporary”, I agree with Dr. Pulido that the last two bullets, the word “temporary” replaces those.  You’re saying the same thing in a different way.  I don’t think you need to double say it.  You either say “temporary” or you say the last two bullets, one or the other.

SUGAR:  Jayne?

WEISS:  Jayne Weiss.  I think I could agree with that because it wold be easily understandable, succinct and the other two statements could be put in labeling, if necessary.  I would like the word “temporary” though, not to be footnoted because I think it makes it less clear, less obvious and less understandable.

SUGAR:  Okay, this is Tim’s motion?  Am I correct?  Whose motion is it?

WEISS:  Actually, Tim’s was an amendment to mine and Jose’s was an amendment to Tim’s, so I think we’re at Dr. Pulido’s at this point.

SUGAR:  So you’ve restated your motion that it’s the first three bullets with the word “temporary” added?

WEISS:  Yes.

SUGAR:  Is there any additional confusion?  Any additional discussion?

Please.

MATHERS:  This is going to be seen as one way of handling this problem.  We might also consider a different motion, but we’re going to vote on this motion now as it stands, is that right?

SUGAR:  There’s a motion on the floor that needs to be dealt with and then we could proceed with whatever other motions seem appropriate.

So we’re going to vote on this, yes.  And I think it’s now appropriate to vote.  All those in favor of the motion, signify by raising their hand?

THORNTON:  Wait, could you just read

SUGAR:  Yes, the motion is the indication for use is CK treatment for the temporary reduction of spherical hyperopia in the range of +.75 to +3.25 diopters of cycloplegic spherical hyperopia; -3.75 diopter or less of refractive astigmatism, +.75 to +3.00 diopters of cycloplegic spherical equivalent in patients with less than .50 diopter difference between preoperative manifest and cycloplegic refraction who are 40 years of age or older.

[Vote taken.]

All those in favor of motion?  Seven.

All those opposed?  Two.

The motion carries.

THORNTON:  Wait.

SUGAR:  Am I wrong?  We have 12.

THORNTON:  We have 10 votes all together.  Could you raise your hands?

SUGAR:  There are supposed to be 12 people and there were 7 and 3.

THORNTON:  Okay, sorry.

SUGAR:  Seven to three.  I abstained.

ROSENTHAL:  What was the tally?

SUGAR:  Seven to three.  We now move on to specifying the conditions because we now have the indication.  We’ve specified the conditions and I’d like a motion concerning — I’m doing it wrong.

THORNTON:  The condition that you just discussed was the change in indication.  The next condition that you’re going to discuss is probably a labeling going on into your labeling.  But the change in indication is one of the conditions of the approval.  I just wanted to clarify that.

SUGAR:  One of the problems we get into is wordsmithing the words, concerning the wordsmithing of the other words, but additional conditions.

GRIMMETT:  Mike Grimmett.  There are some additions to the labeling list that I provided that will be a separate consideration because I don’t have them written down.  Did you write them down, Dr. Weiss?

WEISS:  I wrote them down as you were commenting.

GRIMMETT:  Okay.  I make a motion to include the labeling issues as I’ve typed in my sheet dated November 30th with the following modification:  the No. 10, we were going to change the reduction of to include statement regarding the spectacle or contact lens dependence and No. 13 we just dealt with, so eliminate No. 13.

If I could make a motion that those following labeling suggestions be accepted.

SUGAR:  Is there a second?

ROSENTHAL:  Rosenthal.  Could you just — I don’t want you to go through all of the — if you could just go through the category, you know —

GRIMMETT:  Sure.

ROSENTHAL:  Labeling issues relating to blah, blah, blah.

GRIMMETT:  Sure.

ROSENTHAL:  So we can have it on record.

THORNTON:  Read the complete list as you have discussed and are adding on the complete list into the record, please.

ROSENTHAL:  I’ll just clarify with Nancy Pulowsky.  We don’t need to go over every single one, but I think the general idea of —

THORNTON:  Right, right.

SUGAR:  He can’t just say number 1, number 2, number 3?

GRIMMETT:  Labeling issues, No. 1, best corrected visual acuity loss greater than or equal to two lines.

No. 2, issues related to subjective symptom data.

No. 3, issues related to inductive of cylinder data.

No. 4, data regarding loss of incorrect visual acuity with induced cylinder.

No. 5, data or statement regarding cylinder axis shifts.

No. 6, predictability data.

No. 7, statement regarding or data regarding post-operative standard deviations of the mean being wider than the pre-op standard deviation of the mean refraction.

No. 8, statement regarding decreased efficacy as the level of pre-op hyperopia increases.

No. 9, statement regarding that the procedure is refractively unstable.

No. 10, statement regarding the spectacle of contact lens dependence following the procedure.

No. 11, a statement regarding rates of dissatisfaction and quality of vision improvement.

No. 12, a statement regarding lack of retreatment data.

SUGAR:  And that has been seconded?

WEISS:  I’ll second that.

SUGAR:  Okay.  And are there amendments to the motion?

Jayne and then Jose.

WEISS:  Jayne Weiss.  I would just add some amendment as I was scribing the suggestions that have been added to this point, one being I think Dr. Pulido’s recommendation that implantable electrical devices are contraindications for this procedure.  I think Dr. Pulido also suggested that the effect in patients with narrow angles is not known.

Dr. Bradley had wanted labeling to include a better description of the procedure for the patient, including the fact that it involved needle placement in the cornea and the fact that data beyond 12 months is not available at this point.

SUGAR:  Was there also something about over-correction and the word “gentle heating.”

WEISS:  Yes, Jayne Weiss.  I did leave out my suggestion which is that the patient be informed that initially there would be an overshoot or over correction and that it might take 6 to 9 months before most of the result is reached and also Dr. Bradley’s suggestion that the word “gentle heating” be removed.

SUGAR:  Is there a second to the amendment?

Jose, do you have more to add?

PULIDO:  No, I second her appended amendment.

SUGAR:  Is there discussion of the motion with its 17 points?  All those in favor of the listed additional conditions, signify by raising their hand?

HO:  There’s a comment over there.

SUGAR:  I’m sorry, please.

MATOBA:  Yes, Alice Matoba.  My comment was simply that Dr. Weiss’ last addition that the data, we do not have data after 12 months.  That should be placed in 9 so that when we say it’s unstable, it’s understood that we only have data up to 12 months and we don’t know whether it’s stable or unstable after that time period.

SUGAR:  Do you accept that, Jayne?

WEISS:  Yes, I do.

SUGAR:  And Jose?

PULIDO:  I would, yes.

SUGAR:  So Ralph, has it been adequately stated?

ROSENTHAL:  You’ve included all the labeling issues?

SUGAR:  I believe so.  Are there additional labeling issues that anyone would like to add?

Yes?

HUANG:  Andrew Huang.  I’d like to add.  I think we should probably clarify one of the labeling indications that the higher amount of hyperopia has less effect, but you probably included it in one of the points.

GRIMMETT:  I believe that’s No. 8.

SUGAR:  Okay.

GRIMMETT:  I included it by stating three pieces of information that support that tenet.

SUGAR:  Okay, is there any confusion about the motion?

This condition with its numerous points is now up for vote.  All those in favor, signify by raising their hand.

[Vote taken.]

SUGAR:  Those opposed?  Those abstaining?  So none opposed, one abstaining, nine in favor.

I believe that we have covered everything that’s been presented thus far.  Is there anything that we have missed?  Are there any additional motions that anyone would like to make or any additional modifications?

Please?

HUANG:  I would like to recommend to the sponsor to continue to monitor the patient beyond 24 months.

SUGAR:  Okay, a suggestion has been made that we request additional follow-up data from the sponsor.

ROSENTHAL:  Could you put that in as a motion?

SUGAR:  As a condition of approval which is clarified to us as to what exactly you want.

SUGAR:  So if we could form that up a little better, go ahead.

GRIMMETT:  Well, I have a question first.  Mike Grimmett.  Isn’t it tacitly assumed that since the study was designed for 24 months, they’re at least going to go to 24 months and submit the data?

No?

SUGAR:  It doesn’t hurt to ask for it anyway, I think.

ROSENTHAL:  I don’t think you can tacitly assume anything.

GRIMMETT:  Okay.

ROSENTHAL:  We’re asking for your recommendations.

GRIMMETT:  I’d like to make the first motion that this study be completed to the 24-month interval with submission of the data for FDA review.

SUGAR:  As a condition for approval or subsequent to approval?

GRIMMETT:  Post-market evaluation that the study simply needs to be continued and not stopped at this time point.

SUGAR:  Was that the sense of your motion?

HUANG:  Yes.

SUGAR:  So the motion has been made and effectively seconded, is that fair?

GRIMMETT:  Yes.

SUGAR:  Discussion?  All those in favor?

[Vote taken.]

SUGAR:  Nine.  Opposed?  Abstaining?  One.

Any additional conditions or motions?

McMAHON:  Would it be reasonable to ask the sponsor to supply data on retreatments,

post-market study?

SUGAR:  I guess we can discuss that as an issue, not as a motion.  One of the conditions we had was the statement that there is lack of retreatment data.  Whether we — and we can say what we want, but whether we want to make that a condition for the approval or not, I think is the issue at hand here.  Does anyone — are you suggesting that as a motion, Tim, or not?

McMAHON:  It’s an issue that has me a little bit concerned and I guess I’d want this erred before we leave as to whether the rest of you feel the same way and want to make that a higher priority issue and a part of the approval process.

SUGAR:  My question, if it’s appropriate for me to comment is whether — we would love to have that information.  I presume the sponsor would too.  Whether it’s appropriate in approving what’s been presented to us or not approving what’s been presented to us to ask for that or not, I don’t know.  I don’t — this process —

McMAHON:  That’s why I raised it as a question is I don’t know if it’s an appropriate question.

SUGAR:  Ralph?

ROSENTHAL:  We’re asking for a Panel recommendation and I really don’t want to comment what’s appropriate or what’s inappropriate.  I mean you have to consider least burdensome issues and you have to consider what is scientifically required and you have to consider what is necessary to label the PMA.

SUGAR:  Dr. Ho, did you want to comment?

HO:  In my view, I think that’s a very important issue, but I think that I would not require it as a condition of approval of this particular PMA.  I think there are potentially incentives for the company and for the public, later on, as a separate study for that to be performed, but I would not view that as a condition for approval of this PMA.

SUGAR:  Is there additional discussion of the nonmotion?  Are there any additional issues?  Please.

GRIMMETT:  Mike Grimmett.  We just discussed and approved a motion for post-market evaluation to 24 months.  I think that assumes that stability will be at least established or reached during that time interval.  I just would like to raise the point what if stability is not reached by 24 months?  Would people be in favor of having the study continued longer or what’s the sense about that?

SUGAR:  Jose?

PULIDO:  Jose Pulido.  I don’t think so because the 2-year point we’re doing just to see if it continues to be a temporary — to leave it as a temporary situation.  If at two years the company sees that there still hasn’t been any stability, then they can’t come back to us and say well I want to change this.  So it’s now on the company’s side to determine whether they want to continue it past the 2-year point or not.

SUGAR:  Please.

McCARLEY:  I’d simply suggest that if you’re going to ask for the 2-year data as a condition of approval, then the company be permitted or required, whichever way you want to look at this, to put that in the labeling when that information becomes available and it’s been reviewed by FDA because then you’re going to know what you want to know now and it may be in their favor.  It may be still a question.

SUGAR:  The sense I have is that that’s implied in our motion, is that correct?

THORNTON:  Yes.

MATOBA:  I think we’re ready for voting on the main motion with its conditions, including the changes in indication, the labeling changes and the continuation of the study for 24 months.  Is there anything we have missed?

So that motion, I guess, was the original motion, so we need to vote on the package.  And no additional motion needs to be made, correct?

So can I say all in favor?

THORNTON:  Yes.

SUGAR:  Thank you.  All those in favor, signify by raising their hand?  All those opposed?  One opposed.

[Vote taken.]

SUGAR:  So the motion carries and we now poll the Panel for a comment on their vote.  We should be in with Dr. Pulido.

PULIDO:  Jose Pulido.  I voted approvable with conditions.  And I believe that this is a device that can temporarily and unpredictably diminish hyperopia and with these conditions that shows that is the case.

McMAHON:  Tim McMahon.  I voted for approval with conditions for essentially the same reasons.

BRADLEY:  Arthur Bradley.  I voted against approval.  Basically, I think the CK procedure has been shown to be unreliable, inaccurate and unstable.  However, the accuracy and reliability did improve during the first year post-op and results from previous thermal keratoplasty procedures make it likely that the rate — sorry, make it likely that the rate of change of regression will decline within the second year.  Therefore, I feel that it’s premature at this time to approve this device and I would like to wait until evidence of stability before voting for approval.

WEISS:  Jayne Weiss. I voted approvable with conditions because I think the sponsor has satisfactorily met the criteria set forth by FDA.  I have concerns about the shifting axis and amount of astigmatism, but that will be addressed in patient labeling.  I also have concerns about the fact that stability had not been reached at 12 months, but I think the consumer is protected by indicating at the present time this is a temporary correction of hyperopia.

GRIMMETT:  Michael Grimmett.  I unenthusiastically voted approvable with conditions as I believe the procedure is reasonably safe, yet only marginally effective.  I’m uncomfortable with the lack of stability of the procedure, but with the conditions and labeling conditions that we approved, I feel the consumer should have an adequate chance of achieving the appropriate information in order to make an informed consent about this procedure.

MATOBA:  Alice Matoba.  I voted for approval with conditions.  I think the procedure is reasonably safe and fairly effective and the sponsors did meet the criteria set by the FDA.

HO:  Allen Ho, approvable with conditions.  I think that this a safe procedure.  Its efficacy seems to be marginal to fair in my view.  I think they’ve met the criteria set forth by the guidelines of the FDA a priori and with the conditions that are specified in the labeling, I’m comfortable with that.

JURKUS:  Jan Jurkus.  I voted approvable with conditions since the conditions that we had so thoroughly discussed adequately reflected my concerns with this product.

MATHERS:  Bill Mathers.  I voted approvable with conditions.  I believe that the device fulfills the FDA’s requirements and is reasonably effective and reasonably safe and that the labeling will indicate to the public how it can understand the proper use of the device.

HUANG:  Andrew Huang.  I voted for approval with conditions based on the fact that I think this is a relatively safe procedure, yet the effect is unsustained.  But I do believe that with the condition provided by the Panel that physicians, as well as the patient, now can make an informed decision on this procedure.

SUGAR:  Thank you.  PMA P010018 then has been dealt with.

I’d like to just make a statement.  This is the end of my tenure on the Committee and as Chair of the Committee, even though it was brief, I went to the American Academy of Ophthalmology a couple of weeks ago and there was a videotape presented by Bobby Osher that was titled “FDA or DWB”, something like that, FDA meaning you guys or DWB which is Doing What’s Best and I having come into this a little bit skeptically have learned that the people here are doing what is best under the circumstances with which they have to work and I’ve been extremely impressed with people at all levels of the FDA involved with CDRH and have enjoyed working with them.  Thank you.

THORNTON:  Thank you, Joel.  We have enjoyed very much working with you and we’re sorry to have had to have you for Chair for such a short time.  It’s been a pleasure working with all of you and I’d like to welcome again our new consultants to the table and our new industry rep and hopefully this hasn’t been total shock treatment, but you’ll be willing to come back and help us out in the future.

At this time I’d just like to reiterate that we will be having a meeting January 17th and 18th next year.  Until that time — what?

SUGAR:  Do you leave the papers?

THORNTON:  Yes.  I’d like all the — by the way, but I did want to say until that time I hope that you all have a happy and a safe holiday.

I’d like the Panel to leave all materials that were issued to them to review for this meeting at the table.  And please fill out for your benefit at future meetings, please fill out this evaluation form that I left at your table at the beginning of the meeting.

Thank you again.

(Whereupon, at 3:46 p.m. the meeting was adjourned.)

CANCER & LASER EYE SURGERY

A recent study on the effects of the excimer laser on corneal tissue: Joshua Ben-num (Tzriffin, Israel)

Photorefractive Keractectomy and Laser in situ Keratomileusis: A Word From the Devil’s Advocate.

Archives of Ophthalmol. Vol.118, Dec.2000, p.1706-1707.

At a time when there has been a significant improvement in the technology of treatment of refractive errors by laser in-situ keratomileusis (LASIK), this author has issued a very timely warning both to patients undergoing the procedure and to the people performing LASIK.

The procedure involves a laser beam at 193nm that evaporates part of the cornea, breaking cells and molecules to create the smooth corneal surface necessary for best optical results.

The creation of free radicals, is an inseparable part of the cornea reshaping process.

Both photorefractive keratectomy (PRK) and LASIK are known to cause keratocyte apoptosis in the cornea of laboratory animals and hence, though there is no short-term damage, long-term damage must be considered.

These procedures are also known to have caused biochemical and ultrastructural modifications in the lens, both of which are markers of cataractogenesis. The vitreous base, located just posterior to the lens may be affected by the same process that affects the cornea, anterior chamber and the lens. Free radicals damage the vitreous collagen, leading to vitreous liquefaction. They have also been shown to promote tumours.

PRK might initiate a cascade of events leading to slowly developing abnormalities of the cornea, lens, vitreous retina and choroid.

On one hand there is a marked increase in the popularity of LASIK promulgated by massive advertisement. Hence there is an urgent need for intensive research into the potential threats to ocular function caused by LASIK which may occur in patients decades after the initial procedure, slowly but almost surely.

Fatal Focus, a novel by Jonathan Maxx

The long-term effects of photorefractive eye surgery remain unknown. It’s clear that LASIK and other forms of eye surgery using the excimer laser are not as promised –“quick, painless and effective.” And we know that some people will never recover their vision, lost as a result of this next “miracle of modern medicine.” If, after ten years, we look back and see that laser eye surgery was simply a mistake, a risk-prone procedure imprudently pushed for the sake of the money to be made, it will indeed be a sad day for the medical profession. However, might there be an even greater evil lurking?

The excimer laser is a source of ultraviolet radiation, a form of energy closely associated with mutagenicity and carcinogenesis. For more than a decade, researchers have questioned whether this laser-generated radiation might trigger the growth of cancer in human tissues. A clear-cut answer has never been obtained.

While some researchers proclaim that the 193 nanometer argon-fluorine laser does not produce radiation in the known mutagenic wavelengths, (the blanket statement that even the primary radiation from the 193 nm laser is entirely safe is not presently accepted by all researchers), and therefore cannot be mutagenic, others have pointed out that the interaction of human tissues with laser radiation causes the radiation to change— changing its wavelength into the mutagenic ranges. What is the effect of this “secondary radiation?”

Consider the facts. Last year over 800,000 people underwent laser refractive eye surgery. In each instance the patient’s eye was irradiated with ultraviolet radiation. The secondary radiation produced during the photoablative process has the potential of scattering into the surrounding tissues. Since this secondary radiation falls into the known mutagenic ranges, these tissues may be genetically altered by this radiation, and some cells may become malignant. If only one-half of one percent of those 800,000 patients sustained DNA damage—that may be as many as four thousand people whose lives are NOW threatened by the onset of cancer.

There is practically no research being conducted into the long-term effects of laser eye surgery. Is there a lack of interest? Or, is it more a matter of the ostrich hiding its head in the sand? At this time more than 1 million people have been prompted to undergo laser eye surgery. If laser radiation triggers cancer it may become apparent soon. (Alternatively, the histopathological effects may mimic the effects of x-ray exposure, and become apparent after several years.) However, determining the existence of a correlation between photorefractive surgery and cancer depends entirely on whether or not researchers are looking for it.

Jonathan Maxx is the author of the fictional novel entitled, “FATAL FOCUS”, which follows the lives of two physicians attempting to publish research about the potential deadly effects of the excimer laser. A portion of the proceeds from this book will go to long-term research concerning laser eye surgery.

Available by e-mailing the author, Jonathan Maxx.

Bibliography

 

Gebhard, E., Lang G.K., Tittelbach, H., Rau, D., Naumann, G.O. (Institut fur Humangenetik, Universitat Erlangen-Nurnberg) “Chromosome mutageniticy of a 193 nm Excimer laser” Fortchr Ophthalmol 1990; (3):229-33

Green, H., Boll, J., Parriesh, J.A., Kochevar, I.E., Oseroff, A.R.

“Cytotoxicity and mutagenicity of low intensity, 248 and 193 nm excimer laser radiation in mammalian cells.” Cancer Res. 1987 Jan. 15, 47 (2) : 410-3

Kochevar, I.E. (Wellman Laboratories, Mass. General Hosp., Boston) “Cytotoxicity and mutagenicity of excimer laser radiation.” Laser Surg. Med 1989; 9(5): 440-5

Lubatschowski, H., Kermani, O. (Institut fur Anewandte Physik, Universitat Bonn.) “193 nm Excimer laser photoablation of the cornea. Spectrum and transmission behavior of secondary radiation.” Ophthalmologe 1992 Apr: 89(2): 134-8

Muller-Stolzenburg N., Schrunder S., Helfmann, J., Buchwald, H.J., Muller, G.I. “Fluorescence behavior of the cornea with 193 nm excimer laser irradiation.” Fortschr Ophthalmo; 87(6): 653-8 1990

Phillips, A., McDonnell, P.J. (Doheny Eye Institute, Los Angeles) “Laser-induced fluorescence during photorefractive keratectomy: A method for controlling epithelial removal” Amer. Jour. Opht. 1997 123; 42-47

Seiler, T., Bende, T., Wincker, K., Wollensak, J. “Side effects in excimer corneal surgery. DNA damage as a result of 193 nm excimer radiation” Graefes Arch Clin Exp Ophthalmol, 1988; 226(3): 273-6

Trentacost, J., Thompson, K., Parrish, R.K., Hajek, A., Berman, M.R., Ganjei, P. “Mutagenic potential of a 193 nm excimer laser on fibroblasts in tissue culture: Ophthalmology; 94(2): 125-9 1987

Email Author

Reasons patients recommend LASIK

J Cataract Refract Surg. 2004 Sep;30(9):1861-6.

Bailey MD, Mitchell GL, Dhaliwal DK, Wachler BS, Olson MD, Shovlin JP, Pascucci SE, Zadnik K.

Ohio State University College of Optometry, Columbus, OH 43210, USA.

PURPOSE: To evaluate the reasons patients who have had laser in situ keratomileusis (LASIK) recommend it to others and examine the disparity between high levels of satisfaction and patient reports of night-vision symptoms and/or dry eye after LASIK.

SETTING: Northeastern Eye Institute, Scranton, and the University of Pittsburgh, Pittsburgh, Pennsylvania, and the University of California at Los Angeles, Los Angeles, California, USA.

METHODS: Questionnaires assessing symptoms and satisfaction after LASIK were mailed to 2,100 patients. The questionnaires included items about night-vision symptoms and satisfaction and an open-ended question for patients to give their reasons for recommending LASIK to others. The open-ended responses were categorized and tabulated.

RESULTS: Four hundred thirty-four patients provided reasons for recommending LASIK to others. Sixteen categories of reasons were identified. “No more spectacles/contact lenses” was listed by 180 patients (42%), followed by “better vision” (21%) and “convenience” (15%). Women were significantly more likely to cite “better comfort” (27 women versus 3 men; chi square = 8.99, P =.003) and “better quality of life” (41 women versus 9 men; chi square = 7.36, P =.007) as a reason for recommending LASIK. Of the 35 patients who reported dissatisfaction with post-LASIK vision, 20 (57%) would recommend LASIK to a friend because “LASIK helps others.”

CONCLUSIONS: Categories of reasons for recommending LASIK to others were similar to reasons given by patients for seeking LASIK. Some patients who reported dissatisfaction with their vision said they would recommend LASIK, suggesting that recommendation of LASIK to others is not necessarily a measurement of the quality of a patient’s vision after LASIK.

Dangers of Suction Ring and Laser Acoustic Shock

JRS September/October 2005 21:5 p502.
Lin and Tsai.
Retinal Plebitis After LASIK

Excerpt:

“An IOP of at least 65mmHg is necessary to create a corneal flap with the microkeratome. During this time, the shape of the anterior segment may change rapidly and structures posterior to the suction ring are also compressed in sequence. When the suction stops and the suction ring is released, ocular decompression leads to dynamic equatorial elongation and anterior-posterior contraction. This barotrauma is analagous to what happens in closed eye injury, and can alter delicate retinal structures, especially small vessels, and induce vitreoretinal traction at the vitreous base and posterior pole. Sudden elevation of IOP also disturbs the retinal circulation and increases venous pressure, which results in retinal ischemia. All of these conditions may aggravate the original impaired blood-retinal barrier in highly myopic eyes and increase vascular permeability, leading to the loss of integrity of tight junctions of endothelial cells. Laser in-situ keratomilieusis-induced shock waves can generate up to 100atm. Although the pressure decreases steadily to values below 10 bars toward the retina, we believe it may still cause mechanical stress to the retina, resulting in structural damage and intraocular inflammation.
In addition, total energy and duration increase with higher refractive error and the effect of mechanical stress may be more severe in higher myopia, which has more liquification of the posterior vitrous gel.”

Quotes, Non Peer-Reviewed Articles, and More

Informed Consent

“What concerns me is that if the person informing the patient is themselves poorly or inaccurately informed then how on earth can consent ever be truly informed?” Dr. Sarah Smith.

AND MORE…

Cleaner LASIK: Is it Possible?

SOURCE

This from a doctor who was fined $1.1 Million from the FDA for damaging 125 patients…

Fixing a lost or slipped flap

SOURCE

EyeWorld

November 2006

Quote:

“Lost flaps usually will occur in the operating room where the microkeratome just made too superficial a cut,” Dr. Geggel said. “Surgeons have to be comfortable knowing how to take the microkeratome apart, because the lost flap is usually going to be somewhere within the machine.”“Make sure the first patient you enroll feels like you have been doing this for years…”

SOURCE

Stephen S. Lane, M.D.:

EyeWorld

October, 2005

IOL calculations after refractive surgery need extra care

SOURCE

Excerpt:  The topic of  IOL implantation after refractive surgery and power calculations arose a few years ago. However, Dr. O’Brien noted that now this situation is arising on a daily basis in practices as the number of refractive procedures increases each year and as the population ages.  “There has been a question of whether laser refractive surgery is accelerating the development of cataract. This is controversial, but I see it more and more often in my practice,” he said. Dr. O’Brien is professor of ophthalmology and director of the Refractive Surgery Service, Bascom Palmer Eye Institute, Miami.  The problem, he pointed out, is that the patients who have undergone refractive surgery and then develop cataract are different in mindset from the traditional patient with cataract in that they have extraordinarily high expectations; they want immediate results; and they want no surgical discomfort, sutures, or downtime after the procedure.

“These patients who develop cataract after refractive surgery want a perfect outcome. They are potentially frustrated and angry because their quality of vision has suffered as the result of the refractive surgery, and the results may be unpredictable. Interestingly, incorrect power is the most common reason for IOL explantation. This is the result of our not being able to determine the power as accurately as we would like,” he stated and advised exercising extra care with these patients.

“Successful LASIK” is an oxymoron

Found on Lasik-Flap bulletin board: http://www.lasik-flap.com/forum

The flap never heals. It cannot heal. All it can do is form a scar at the margin of the flap which is only 28% as strong as a normal cornea. The flap itself does not bond to the underlying cornea and can be dislodged or lifted years later.

The corneal nerves that play a vital role in tear production never fully regenerate. A scientific peer-reviewed study proved that at 3 years post-op the corneal nerves are still less than 60% of pre-op densities. LASIK induced dry eyes is common and for many patients is a life-long sentence.

The suction ring used during the cutting of the flap damages the delicate structures inside the eye including the retina, vitreous, and optic nerve. Many patients report increased floaters (posterior vitreous detachment) after LASIK, and some experience retinal tears or detachment, lacquer cracks, macular holes, macular hemorrhages, optic neuropathy, and retinal vein occlusion.

LASIK corneas are not as stable as normal corneas and can begin to bulge weeks, months, or even years later, potentially resulting in loss of the cornea. This bulging is a response to the normal intraocular pressure. A LASIK-weakened cornea sometimes can no longer withstand this outward force. The FDA used a best-guess safety limit of 250 microns of cornea under the flap when LASIK was approved. Since then it has been shown in the medical literature that 250 is not a safe limit, even though the vast majority of LASIK surgeons, who are too busy doing LASIK to follow the research, are still using an unsafe limit of 250 microns. And the FDA does not have the backbone to modify the approval, allowing the LASIK industry to continue this unsafe practice that jeopardizes the well-being of millions of patients.

There is permanent damage in 100% of LASIK corneas — debris in the space between the flap and the underlying cornea, undulations and microfolds in the Bowman’s layer — presumably because the flap doesn’t fit to the altered corneal bed, haze, epithelial cells under the flap, acutely and chronically reduced keratocytes, epithelial thickening, collagen fibril disorganization, collagen lamellar disarray, and abnormalities of the Descemet membrane.

Quote from one peer-reviewed study: “However, the presence of pathologic findings up to 7 years after LASIK indicates that the process of corneal stroma wound healing never completely regenerates histopathologically normal corneal stroma.”

Loss of night vision quality after LASIK occurs frequently, according to a 2002 report by the American Academy of Ophthalmology. For some patients, particularly those with large pupils, this complication can be debilitating. Since this is a “frequent” problem after LASIK, I wonder how many of the approximately 8 million Americans who have had LASIK are out there on the roads at night endangering their life and the lives of others who share the roads with them? A recent study showed that up to 50% of LASIK patients are impaired when driving at night. Yet this serious threat to the public health is down-played and swept under the rug by the LASIK industry.

And then we have the problem of the white wall of silence. Doctors are pressured by their peers not to testify for patients who are victims of LASIK malpractice. They are threatened by their own insurance carriers, which could put them out of business. And they are concerned about giving LASIK a black eye by helping a patient seek justice for the harm done to him or her in a public forum like a court of law. They cave in to the pressures, leaving patients without any recourse — medical, legal or otherwise. So doctors just get away with it and standard of care and informed consent continue to be basically non-existent. And the FDA says it’s not their problem (they regulate the devices, not the doctors).

So who’s looking out for the patients? Who’s going to warn them that 1/3 of their corneas will be nearly sliced off, leaving them with a structurally weakened cornea that can begin to bulge years down the road? Who’s going to warn them of the seriousness of LASIK-induced dry eyes, that the nerves never regenerate, and that painful dry eyes can be permanent? Who’s going to warn them that LASIK, all LASIK — conventional and custom, induces higher order aberrations in all virgin corneas, effectively reducing the quality of their vision? Who’s going to warn them of the damage the suction ring can do to the structures inside the eye? Who’s going to warn them that the flap never heals?

You would think doctors would be protecting patients. Wake up and smell the coffee. Money is what drives them, not a desire to heal the sick. They don’t deserve to be called doctors. They are no better than used car salesmen.

American Academy of Ophthalmology. For some patients, particularly those with large pupils, this complication can be debilitating. Since this is a “frequent” problem after LASIK, I wonder how many of the approximately 8 million Americans who have had LASIK are out there on the roads at night endangering their life and the lives of others who share the roads with them? A recent study showed that up to 50% of LASIK patients are impaired when driving at night. Yet this serious threat to the public health is down-played and swept under the rug by the LASIK industry.

Mistakes / Errors

JOURNAL OF REFRACTIVE SURGERY Vol. 22 No. 3 March 2006   Dan Z. Reinstein, MD, MA(Cantab), FRCSC; Cynthia Roberts, PhDExcerpt:  “Some of the evidence pointing to the impact of corneal biomechanical properties on surgical outcomes lies in the measurement of intraocular pressure (IOP), both before and after refractive surgery. It is well known that measured IOP is reduced, on average, following a refractive procedure. It has been assumed that this is the result of reduced curvature and thickness in myopic procedures. However, Chang and Stulting performed a retrospective review of over 8000 myopic LASIK patients, and determined that although measured pressure was reduced on average by approximately 2 mmHg, the range of change was approximately +10 to -15 mmHg. Every patient in this population had reduced thickness and curvature, and yet almost half of them had an increase in measured IOP.

Clearly, the artifact in IOP measurement cannot be explained by thickness alone, and “correction” of measured IOP postoperatively using a linear correction factor based on thickness is problematic. This leads to the conclusion that refractive surgery likely alters the fundamental biomechanical properties of the cornea.

Lasers or Surgeons: What’s really the cause of high retreatment rates?

SOURCE

EyeWorld
January 2005

“I had one time where I had to put the flap back with a flashlight because the illumination light went off so I couldn’t figure out where the flap was,” Dr. Rubinfeld said.

Interface fluid after LASIK

J Cataract Refract Surg. 2001 Sep;27(9):1526-8.

Fogla R, Rao SK, Padmanabhan P.  Cornea Services, Sankara Nethralaya, Chennai 600 006, Tamil, Nadu, India. mrf@sankaranethralaya.org

We report a case in which raised intraocular pressure (IOP) was associated with interface fluid after uneventful bilateral laser in situ keratomileusis (LASIK). The patient presented with diffuse lamellar keratitis in both eyes 3 weeks postoperatively that was treated aggressively with topical corticosteroids. A steroid-induced rise in IOP resulted in interface fluid accumulation and microcystic edema. Measurements with the Goldmann tonometer revealed an IOP of 3.0 mm Hg in both eyes. However, Schiotz tonometry recorded a pressure of 54.7 mm Hg in both eyes. Reduction in the dosage of topical corticosteroid and medical treatment of the raised IOP resulted in resolution of the microcystic edema and interface fluid accumulation. This case highlights the inaccuracies of IOP measurement after LASIK and the resulting complications.

LASIK: three unexpected complications

J Refract Surg. 2001 Mar-Apr;17(2 Suppl):S177-9.  Rosa DA.

PURPOSE: To report unexpected outcomes in three patients after uneventful laser in situ keratomileusis (LASIK) performed using the Nidek EC-5000 excimer laser and the Hansatome microkeratome (Bausch & Lomb Surgical).

METHODS: LASIK was performed with the Nidek EC-5000 excimer laser and the Hansatome microkeratome (Bausch & Lomb Surgical) in three patients.

RESULTS: In three patients, unexpected outcomes were observed. One patient treated for -3.00 D of myopia presented with a central island. One patient treated for +2.00 D (+1.00 x 90 degrees) of hyperopia in both eyes ended up emmetropic in one eye and overcorrected in the fellow eye. The third patient with -12.00 D (-2.00 x 180 degrees) of myopia was treated as -8.60 -1.00 x 180 degrees and at last examination was +4.00 D. During these sessions, all other patients treated were within +/-0.50 D of emmetropia.

CONCLUSION: After LASIK with the Nidek EC-5000 excimer laser and the Hansatome microkeratome (Bausch & Lomb Surgical), unexpected outcomes may still occur, despite controlling all the usual variables.

Oculocardiac reflex in a nonsedated LASIK patient

J Cataract Refract Surg. 2002 Sep;28(9):1698-9.

Baykara M, Dogru M, Ozmen AT, Ozcetin H.  Uludag University Faculty of Medicine, Department of Ophthalmology, Bursa, Turkey

A healthy 21-year-old man had laser in situ keratomileusis (LASIK) in the right eye for a refractive error of -7.0 diopters. The electrocardiogram findings and heart rate were recorded before LASIK; during eye lid speculum insertion, vacuum application, corneal flap preparation, and excimer laser keratectomy; and after the procedure.

The pre-LASIK heart rate was 90 pulses/min. Severe bradycardia of 40 beats/min developed during vacuum application, and the procedure was terminated. Severe bradycardia caused by an oculocardiac reflex may occur during LASIK, and patients should be closely monitored during the procedure.

LASIK complication: loss of electricity to the microkeratome during the forward pass

Acta Ophthalmol Scand. 2003 Oct;81(5):530-2.

Tuominen IS, Tervo TM.  Department of Ophthalmology, Helsinki University Hospital, PO Box 220, HUS, SF-00029 Helsinki, Finland. ilpo.tuominen@hus.fi

CONTEXT: A 32-year-old woman was scheduled for myopic laser in situ keratomileusis (LASIK) because of myopia and anisometropia caused by retinal detachment surgery.

CASE REPORT: During surgery, a sudden malfunction of the microkeratome during the forward pass was experienced. It was not possible to reverse the blade manually along the suction ring. Moreover, disconnecting the suction from the control unit did not help at first, because the suction ring was firmly attached to the ocular surface. However, detaching the suction line from the control unit aborted the vacuum and allowed the surgeon to turn the whole microkeratome backwards, mimicking the normal blade movement. Finally, an almost normal flap was observed, and the operation was successfully completed. Afterwards, the wire to the electromotor of the microkeratome was found to be broken and subsequently replaced.

CONCLUSION: This type of unforeseen microkeratome malfunction may result in serious flap or other complications.

Refractive surprise after LASIK

Arch Soc Esp Oftalmol. 2005 Sep;80(9):547-9. Related Articles, Links

CASE REPORT: A female patient underwent laser in situ keratomileusis (LASIK) in both eyes. The final degree of astigmatism in her left eye was double the preoperative value due to an error in data management. Complex surgery to both eyes was necessary to resolve the mistake.

DISCUSSION: Complications in refractive surgery can occur, however errors in data management must be minimized by double-checking. Solutions to resolve the errors made can be difficult and the entire staff must share responsibility to avoid these undesirable outcomes.

Failure to verify treatment parameters can lead to LASIK errors

SOURCE

TOP STORIES 3/24/2006

Quote: In the last case, the patient allowed the surgeon to call him “José” several times, believing the surgeon was making a joke. Only after one eye had been treated incorrectly did he clarify his name was “Carlos,” Dr. Sonal said.

Turn Around These LASIK Letdowns

Review of Optometry

Excerpt:  For most carefully chosen patients, LASIK continues to improve their quality of life significantly. However, the popular media that once portrayed LASIK as a somewhat miraculous procedure now tell horror stories of people visually disabled by LASIK gone awry.

Read the entire article at:

http://www.revoptom.com/index.asp?ArticleType=SiteSpec&page=osc/oct01/lesson_1001.htm

What’s Next for LASIK?

Ophthalmology Management Issue: September 2004Outcomes are better than ever, but its place as the dominant refractive procedure is now in doubt.  By Jerry Helzner

http://www.ophmanagement.com/article.aspx?article=86168

These additional studies (all PDF documents) also interesting to read:

Adhesion abnormalities associated with LASIK  Intralase causes macular hemorrhage RGP discontinuation before LASIK
Artificial cornea transplant  Intralase vs microkeratomes Severe central epithelial defects
Contrast sensitivity function  LASIK causes glaucoma Thick and thin LASIK flaps
Cornea donation  Measuring cornea thickness Visx – Measuring Pupil Size Preoperatively
Corneal reinnervation after lasik  Microkeratome assessment Visx Requirement of Patient Information Booklet 
Donnenfeld flap experiment  Microkeratome evaluation 1
Ectasia after LASIK  Microkeratome evaluation 2
Environmental factors myopic LASIK  Microkeratome evaluation 3
Epithelial adhesion abnormalities  Microkeratome evaluation 4
Flap complications aborted surgery Night vision complaints 1
Flap tear during enhancement  Night vision complaints 2
Gayton rejects LASIK  Night vision complaints 3
Humidity temperature risks  Non-surgical eyewash problems
Infections following LASIK Peripheral relaxing incisions after LASIK
Informed consent doctor tool Pupil size night vision

 

 

Comparative results of keratometry with three different keratometers after LASIK
SOURCE

Klin Monatsbl Augenheilkd. 2005 May;222(5):419-23.

[Article in German]

Schafer S, Kurzinger G, Spraul CW, Kampmeier J.

Augenklinik, Universitatsklinikum Ulm.

BACKGROUND: Postoperative hyperopia is a frequent result of cataract surgery in eyes after previous myopic kerato-refractive surgery. One reason for the underestimation of intraocular lens (IOL) power is the wrong corneal refractive power measurement obtained by keratometers and corneal topography systems after LASIK. The aim of this study was to compare the precision of measurements of three different keratometers after LASIK.

METHOD: We studied 58 eyes of 34 refractive patients aged between 20 and 51 years. The preoperative measurements and the measurements one month after LASIK were performed with the Keratometer (Zeiss), the corneal topograph (EyeSys Technologies) and the IOL-Master (Zeiss). We compared our postoperative measurement results obtained with the three keratometers with the results obtained by using the clinical history method (chm).

RESULTS: The smallest mean deviation was achieved with the IOL-Master (measured mean +/- SD: 38.94 +/- 1.88 D, vs. chm: 38.35 +/- 2.13 D). The Keratometer (Zeiss) showed a larger deviation (measured: 39.12 +/- 1.76 D, chm 38.34 +/- 2.07 D) and the largest deviation was shown with the corneal topograph (measured: 39.84 +/- 1.85 D, chm: 38.86 +/- 2.10 D), which measured in mean one diopter higher than what was obtained utilizing the chm. A positive correlation between corrected myopia and the postoperative difference between the measured and calculated value for each keratometer was found.

CONCLUSION: This study demonstrates that with common keratometers central corneal power is measured too high after LASIK. For IOL calculation in patients after LASIK, the wrongly positive deviation from measured central corneal power has to be taken into account.

 

Mitomycin C (MMC) Studies & Articles
Dry eye after PRK with adjuvant mitomycin C

J Refract Surg. 2006 May;22(5):511-3.

Kymionis GD, Tsiklis NS, Ginis H, Diakonis VF, Pallikaris I.

Department of Ophthalmology, Institute of Vision and Optics, University of Crete, Heraklion, Greece. kymionis@med.uoc.gr

PURPOSE: To report a patient with dry eye after bilateral photorefractive keratectomy (PRK) with mitomycin C treatment in one eye.

METHODS: A 29-year-old woman underwent PRK for moderate myopia. The left eye was randomly assigned and intraoperative topical mitomycin C was administered. The right (control) eye was treated with intraoperative corticosteroid only.

RESULTS: The patient developed dry eye symptoms and superficial punctuate keratopathy in the eye treated with mitomycin C. Fifteen months after surgery no improvement was noted.

CONCLUSIONS: Photorefractive keratectomy with mitomycin C treatment could induce or exacerbate dry eye.

Mitomycin C in the Aqueous Following Corneal Application

http://www.aao.org/education/sit_cornea/0019.cfm

Specialty News and Views: Cornea/External Disease – April 2006

The Specialty News and Views section represents the opinions of the contributing authors and does not imply endorsement by the American Academy of Ophthalmology. The Cornea/External Disease team members are: Donald Stone, MD; Surendra Basti, MD; Thomas Harvey, MD; Saiyid Hasan MD; and Ivan Schwab, MD.

A recent animal study showed that mitomycin C (MMC) was consistently detected in the aqueous following a 2 minute application of the solution to corneas with and without an intact epithelium.1 The primary intent of Torres and colleagues was to study eyes where MMC had been applied following photorefractive keratectomy (PRK).

After applying MMC 0.02% for 2 minutes to 2 groups of hen eyes—those that had PRK and those with intact corneal epithelia—the researchers sampled aqueous humor at different time points (10, 30, 60, 360, and 720 minutes). High performance liquid chromatography detected significant quantities of MMC in both groups up to 60 minutes after application. Eyes with PRK had higher levels and could be seen up to 360 minutes later. No drug was undetectable in any eye at 12 hours.

While the presence of MMC in the aqueous following application during glaucoma filtration procedures has been documented, there has been a paucity of literature regarding aqueous levels in eyes following application to the ocular surface. This study unequivocally demonstrates that MMC remains in the aqueous in all eyes following topical application.

MMC is a potent wound healing modulator used by glaucoma, refractive, and corneal surgeons. Advocates of its use have extrapolated success of this agent in decreasing failure of filtration blebs to areas of refractive and corneal surgery. Its efficacy has led to a progressive widening of its applications in recent years. However, this antineoplastic agent can have potential long-term consequences on intraocular structures, because it blocks DNA-RNA replication and protein synthesis.

Previous studies involving topical application of MMC 0.04% at 3-4 times a day have demonstrated ocular surface toxicity on impression cytology and suggested a radiomimetic effect for at least 8 months following therapy.2,3 It is also believed that the toxic effects of MMC can be delayed and cumulative. In light of these facts, it is evident that more investigations of the pharmacokinetic and cytotoxic effects of MMC are needed, particularly with regard to aqueous levels. In the interim, it may be prudent to limit the use of this agent as well as to provide informed consent about the lack of knowledge regarding the long-term effects of MMC.

REFERENCES:

1. Torres RM, Merayo-Lloves J, Daya SM, et al. Presence of Mitomycin-C in the Anterior Chamber After Photorefractive Keratectomy. J Cataract Refract Surg. 2006;32: 67-71.

2. McKelvie PA, Daniell M. Impression cytology following mitomycin C therapy for ocular surface squamous neoplasia. Br J Ophthalmol. 2001;85:1115-1119.

3. Dogru M, Erturk H, Shimazaki J, Tsubota K, Gul M. Tear function and ocular surface changes with topical mitomycin (MMC) treatment for primary corneal intraepithelial neoplasia. Cornea. 2003;22:622-639.

Presence of mitomycin-C in the anterior chamber after PRK

J Cataract Refract Surg. 2006 Jan;32(1):67-71.

Torres RM, Merayo-Lloves J, Daya SM, Blanco-Mezquita JT, Espinosa M, Nozal MJ, Bernal JL, Bernal J.

Instituto Universitario de Oftalmobiologia Aplicada, Universidad de Valladolid, Spain.

PURPOSE: To assess the presence of mitomycin-C (MMC) in hen aqueous humor after photorefractive keratectomy (PRK).

SETTING: Instituto Universitario de Oftalmobiologia Aplicada, Faculty of Medicine, University of Valladolid, and Department of Analytical Chemistry, Faculty of Sciences, University of Valladolid, Valladolid, Spain.

METHODS: Mitomycin-C 0.02% was applied topically for 2 minutes to a right hen’s eye after PRK (Group A) and to the left eye with intact epithelium (Group B). At different time points (10, 30, 60, 360, and 720 minutes), aqueous humor was extracted and high-performance liquid chromatography was performed to detect and quantify MMC levels.

RESULTS: The mean maximum drug concentration of MMC measured in the aqueous humor was 187.250 microg/L +/- 4.349 (SD) in Group A and 93.000 +/- 4.899 microg/L in Group B, both detected 10 minutes after topical application. Statistically significant differences were found between Groups A and B at 10, 30, and 60 minutes, with decreasing MMC levels in both groups but a higher concentration in Group A. After 360 minutes, MMC levels were undetectable in Group B and after 720 minutes in Group A.

CONCLUSIONS: Mitomycin-C was detectable in the aqueous humor of the hen eye after topical application in PRK-treated eyes and in eyes with intact epithelium. The presence of MMC is of concern as it may lead to ocular toxicity in the long term.

Impression cytology following mitomycin C therapy for ocular surface squamous neoplasia

Br J Ophthalmol. 2001 Sep;85(9):1115-9.

McKelvie PA, Daniell M.

Department of Anatomical Pathology, St Vincent’s Hospital, Melbourne, Victoria, Australia. mcelevpa@svhm.org.au

BACKGROUND/AIMS: Topical mitomycin C (MMC) therapy has been used for treatment of ocular surface squamous neoplasia (OSSN) since 1994. Relatively few studies have reported the cellular changes in ocular surface following MMC.

METHODS: Impression cytology was studied in four patients with ocular surface squamous neoplasia, either primary or recurrence after previous excisional biopsy. The authors studied samples obtained using Millipore filters at intervals between 4 and 17 weeks after commencement of MMC, and compared them with pretreatment cytology.

RESULTS: MMC induced changes of cytomegaly, cytoplasmic vacuolation, nucleomegaly with nuclear wrinkling, and binucleation or multinucleation were seen in some cells in all samples. However, nuclear/cytoplasmic (N/C) ratio in these enlarged cells was normal. These changes mimicked those seen following radiation therapy in uterine cervix. Changes of increased nuclear and cell size with increased N/C ratio were seen in some dysplastic cells. The predominant form of cell death was apoptosis with fewer cells showing necrosis.

CONCLUSIONS: MMC appears to produce cell death in OSSN by apoptosis and necrosis. Cellular changes related to MMC mimic those caused by radiation-cytomegaly, nucleomegaly, and vacuolation. MMC related changes may persist in ocular surface epithelium for at least 8 months following MMC therapy.

Tear function and ocular surface changes with topical mitomycin (MMC) treatment for primary corneal intraepithelial neoplasia

Cornea. 2003 Oct;22(7):627-39.

Dogru M, Erturk H, Shimazaki J, Tsubota K, Gul M.

Uludag University, Faculty of Medicine, Department of Ophthalmology, Bursa, Turkey. muratodooru@yahoo.com

PURPOSE: To evaluate the tear function and ocular surface alterations in patients with primary CIN before and after treatment with topical mitomycin (MMC).

PATIENTS AND METHODS: We describe seven patients with unilateral CIN treated with 0.04% topical MMC three times daily until full eradication of the lesion. The patients underwent tear and ocular surface examinations including Cochet-Bonnet corneal sensitivity measurements, tear film break-up time (BUT), Schirmer test, and Rose-Bengal staining before, at the time of resolution of the CIN, and at the final follow-up. Conjunctival impression cytology was performed before treatment and at the last visit.

RESULTS: The mean pretreatment corneal sensitivity was 30.3 +/- 7.4 mm and improved to 55 +/- 5 mm at the final visit (P < 0.05). There were no aqueous-deficient eyes. The BUT values and Rose-Bengal staining scores also showed significant improvement at the last follow-up compared with the pretreatment values (P < 0.05). Initial impression cytology specimens showed goblet cell loss, higher grades of squamous metaplasia, areas of isolated keratinized, binucleated, and actively mitotic disfigured epithelial cells in all patients. The mean goblet cell density and squamous metaplasia grade were observed to improve significantly at the last visit (P < 0.05). MMC-induced cytologic changes were seen to persist long after cessation of treatment in some patients. All eyes remained free of recurrence and complications during the follow-up period.

CONCLUSION: We found 0.04% topical MMC treatment tid until full eradication to be effective in the management of CIN. The ocular surface disease of CIN was characterized by disturbance of tear film stability, goblet cell loss, and increased squamous metaplasia in all patients. Impression cytology proved useful in attaining the diagnosis of CIN, evaluating the effect of treatment, and showing MMC-related long-term changes on the ocular surface.

Early corneal edema following topical application of mitomycin-C

J Cataract Refract Surg. 2004 Aug;30(8):1742-50.

Chang SW.

Department of Ophthalmology, Far Eastern Memorial Hospital, 21 ZSection 2, Nan-Ya South Road, Ban-Chiao, Taipei 220, Taiwan. swchang@mail.femh.org.tw

PURPOSE: To determine the effect of mitomycin-C (MMC) on the cornea after a single intraoperative application.

SETTING: Department of Ophthalmology, Far Eastern Memorial Hospital, Ban-Chiao, Taipei, Taiwan.

METHODS: Mechanical epithelium debridement of the central 10.0 mm of the cornea was performed in 63 pigmented rabbits. One group of corneas (MMC1, n = 42) was soaked with MMC 0.01% solution for 2 minutes; the second group (MMC2, n = 42) was soaked with MMC 0.02% solution for 2 minutes. Control corneas (n = 42) were soaked with balanced salt solution for 2 minutes. Changes in the central corneal thickness, clarity, epithelial defect size, endothelial cell density, and endothelial apoptosis in the 3 groups were examined on days 0, 1, 2, 3, 5, 7, and 14.

RESULTS: There was a dose-dependent increase in corneal thickness, decrease in corneal clarity, and increase in endothelial apoptosis after a single intraoperative application of MMC. The endothelium was significantly swollen and became pleomorphic and polymegethic with a concomitant decrease in endothelial cell density, also in a dose-dependent manner.

CONCLUSIONS: A single application of MMC on the corneal surface caused dose-dependent corneal edema and endothelial apoptosis in the rabbit model. Further clinical study of human eyes is warranted.

Intraoperative mitomycin C and the corneal endothelium

Acta Ophthalmol Scand. 1998 Feb;76(1):80-2.

Sihota R, Sharma T, Agarwal HC.

Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi.

PURPOSE: Mitomycin-C (MMC) is a useful adjunct to high risk glaucoma surgery. No clinical data regarding the deleterious effect of mitomycin-C on the corneal endothelial cells are available.

METHODS: Thirty eyes of 28 adult patients with high risk glaucomas were randomized to three groups. Group-I underwent a trabeculectomy alone, Group II, trabeculectomy with intraoperative 0.2mg/ml MMC and Group III, trabeculectomy with intraoperative 0.4mg/ml MMC. Preoperative and 3-month postoperative corneal endothelial cell counts were analysed.

RESULTS: The percentage cell loss in Group I was 3.73+/-2.73%, in Group II 13.90+/-4.69% and in Group III 14.52+/-7.8%. Statistical analysis revealed a significant difference in cell loss between Group I and Group II and Group I and Group III, but not between Group II and Group III.

CONCLUSION: There is a significant loss of corneal endothelial cells three months after trabeculectomy with adjunctive MMC.

Non-peer reviewed:

http://www.ophthalmologytimes.com/ophthalmologytimes/article/articleDetail.jsp?id=405941

R. Doyle Stulting MD:

“Ectasia is estimated to occur in one of every 2,500 patients undergoing LASIK, Dr. Stulting said, “but this may be an overestimate because of current exclusion criteria. It also may be an underestimate because of limited follow-up.”

Reported cases of ectasia have been diagnosed up to 4 years after LASIK, he added, also noting a case of ectasia that required corneal transplantation 13 years after PRK.

“Pathology in this case suggests cell loss and abnormalities of keratocytes, leading us to wonder whether defective keratocyte metabolism could make ectasia more likely and to wonder whether mitomycin C might increase the long-term risk of ectasia,” Dr. Stulting said.”

Corneal keratocyte deficits after photorefractive keratectomy and LASIK

Am J Ophthalmol. 2006 May;141(5):799-809.

DR STEVEN E. WILSON:

Quote:
I encourage you to use the same technology to look at patients who are having mitomycin prophylactic treatment for prevention of haze; probably 90 percent of refractive surgeons are using mitomycin without any long-term data as to the effect. It is clear the reason mitomycin works so well is that it eliminates 100 percent of all corneal cells in about 20 percent of the anterior cornea. Similar to your concerns, I think they are even magnified in those patients because data after six months in the animal model shows that none of those cells have returned. What happens in the future since we have limited experience with these types of patients? In 10 to 20 years, are we going to see anterior corneal necrosis or other problems? Your type of study could give us more data about that in humans.

This one is not peer-reviewed:

Mitomycin-C can reduce corneal haze after laser refractive surgery

http://www.osnsupersite.com/view.asp?rID=20313

OCULAR SURGERY NEWS U.S. EDITION February 1, 2007

Francesco Carones, MD, explains how MMC can be used to treat or prevent haze.

By Francesco Carones, MD

Quote:
The major criticism in the use of MMC after laser refractive surgery refers to the potential side effects and complications associated with its long-term cytostatic action on tissues when applied in a topical fashion on the corneal stroma. Several researchers have reported corneoscleral melt after MMC application after pterygium excision. Also, the long-term integrity of the endothelial layer is supposed to be at risk.

LASEK, epi-LASIK to remain niche procedures despite some advantages, surgeon says

http://www.osnsupersite.com/view.asp?rID=26511
OSN SuperSite Breaking News 2/20/2008

Excerpt:

Quote:
“This is, in my opinion, the only potential benefit of these procedures: They minimize the risk of haze without the use of mitomycin-C, which is not such an innocent drug,” she said.

She strongly emphasized that the use of mitomycin-C by refractive surgeons should strictly be limited to high-risk eyes. Cases of scleral melting were found, in her personal experience, 3 to 4 years after using the drug in pterygium surgery, and the need for dilution poses further problems.

 

Endothelial Decompensation Following Epithelial LASIK With Loss of Epithelial Flap

Journal of Refractive Surgery Vol. 25 No. 1 January 2009
Sameer Kaushal, MD; Gaurav Prakash, MD; Namrata Sharma, MD; Jeewan S. Titiyal, MD

Quote:
Apart from excimer laser or suction ring, other potential factors include postoperative medications. Pfister has reported a case of endothelial decompensation due to the use of topical mitomycin C eye drops for the treatment of corneal haze. He postulated that the absence of the epithelial barrier allowed significant penetration of the drug into the anterior chamber, damaging the corneal endothelial cells.

Quote:
Mitomycin C treatment after PRK or other surface ablation procedures has been used empirically for years to block haze formation.14 Recently, animal studies have been performed to determine the mechanisms through which mitomycin C blocks the haze response. Although mitomycin C augments the normal apoptosis response that occurs after epithelial scrape performed during PRK,15,16 Netto et al16 demonstrated that the most notable effect is in the inhibition of mitosis of cells that function to repopulate the anterior stroma (Fig 7). Thus, progenitor cells to myofibroblasts, in addition to keratocytes, are blocked from proliferating. The end result of this treatment is that the anterior stroma has profoundly diminished cell density lasting for more than 6 months after mitomycin C treatment.16 It has not been determined when, if ever, more normal keratocyte density is restored in the anterior stroma after mitomycin C treatment. Because keratocytes function to maintain collagen, glycosaminoglycans, and other matrix materials in the stroma, there is concern regarding the long-term effects of mitomycin C, possibly measured in decades, on corneal morphology and function.16

Marcella Q. Salomao, MD and Steven E. Wilson, MD. Corneal Molecular and Cellular Biology Update for the Refractive Surgeon. J Refract Surg. 2009 May

One-year outcomes of a bilateral randomised prospective clinical trial comparing PRK with mitomycin C and LASIK

A D Wallau and M Campos

Br J Ophthalmol 2009 93: 1634-1638 originally published online November 4, 2009

Quote:
The concern for mitomycin C use stems from complications arising in scleral and corneoscleral procedures with mitomycin C, including peripheral keratolysis and scleral melting.13 Although these effects have not been shown to occur in cases of topical MMC use during surface refractive surgery, some concern still exists for MMC long-term toxicity to keratocytes, endothelial cells, and intraocular structures. Some studies have reported a decrease in endothelial cell count and detection of MMC in the anterior chamber in eyes that had received MMC after surface laser ablation.

http://bjo.bmj.com/content/93/12/1634.full.pdf

PROMISES

The Promise of Refractive Surgery: A Promise Not Kept
An Insiders Journal on the Evolution and Misinformation of Refractive Surgery
Dedicated to:
And the thousands of others whose quality of life has suffered greatly as a result of
believing the professionally communicated promise of refractive surgery
Table of Contents
Section Page

Introduction 2

Refractive Surgery and Misinformation 3

Fundamentals of LASIK 5

  •  LASIK’s surgical landscape: the Cornea
  •  Asphericity and imaging of light rays on the retina
  •  The loss of contrast sensitivity and quality of vision
  •  Dry eye
  •  DLK (diffuse lamellar keratitis)
  •  Accuracy of the microkeratome
  •  Enhancements and the use of misleading terms

 

Informed Consent 12

  •  The absence of incidence data
  •  A physician’s internally developed data
  •  Physician use of manufacturer sales aids
  •  Physician’s and conflicts of interest
  •  Referrals to LASIK surgeons
  •  Looking through a patient’s eyes
  •  Websites
  •  Recent FTC actions

 

FDA Approvals 16

  •  Adverse events, complications, and visual symptoms
  •  LASIK – an unapproved, off-label use of medical technology
  •  LASIK – the initial & unusual FDA approval

o Day One

o Day Two

  •  “Company Sponsored” LASIK PMAs

o Approval for the Bausch & Lomb Technolasâ„¢ 217A

Excimer Laser for LASIK

o University of Rochester Survey of FDA Approved

Lasers

Reported Patient Problems and Their Incidence 20

Discerning the Truth About the “Next Big Thing” 23

  •  Wavefront guided LASIK
  •  IntraLASIKâ„¢ (Intralaseâ„¢ LASIK)
  •  LASEK (an emerging off-label procedure)
  •  Radio-frequency based procedures for hyperopia
  •  Lens Based Refractive Surgery

o The ICLâ„¢ (implantable contact lens)

o The Artisanâ„¢ Lens

Summary 31

Appendix A 32

INTRODUCTION

The practice of businesses selectively using information to market products is widespread. Selectivity is a critical tool in marketing. But is it ethical in the marketing of therapeutic products and/or services in healthcare? Isn’t there more at stake when a manufacturer, a health system, and/or a health professional selectively uses information to move a medical or surgical therapy than when a business executive tries to move a product? Isn’t the obligation to tell the truth heightened when something to treat and possibly alter a person’s state of health is being proposed? Are not roles in healthcare clearly distinguished by their unique moral responsibility?

Unfortunately, the selective use of information in the marketing of healthcare products and services is rampant and growing. When I entered medicine years ago, the promise was to heal. Today, the promise of medicine has become money – to doctors, providers, and suppliers. This change in focus necessitates that we, as patients, more than ever, must take responsibility for our health.

But “Patient Power” in this changing landscape requires full knowledge, not a biased selection of facts. Knowledge that is unbiased, truthful, and complete. This puts the burden on the manufacturers, health systems, and healthcare professionals to provide patients with all unbiased, truthful information on expected costs, outcomes, and complications. Good, informed patient decisions cannot be made with selective information. Anything less than full disclosure is a disservice to the patient, the healthcare system, and society.

I have seen refractive surgery grow to 100,000 US procedures per year three years after 1978 introduction of RK (radial keratotomy). As long-term complications became known, it dropped to 30-40,000 procedures per year in the mid-1980’s. RK was reinvented in the early 1990’s emerging as “Mini-RK,” with shorter incisions and enhancements. It fell victim to laser based procedures in the mid-1990’s with the FDA approval of PRK, and then, the off-label LASIK procedure. Laser based procedures, mainly on the strength of LASIK, topped out at 1½ million procedures per year in 2000.

My concern for the patient has also grown with the introduction of each new procedure and the increasing numbers of procedures. The accuracy, breadth, and depth of the information used to move patients to a decision have been deficient. Concerns and knowledge on both outcomes and complications by the medical community have not been fully disclosed to an unsuspecting public. This is unacceptable as these procedures are elective, cosmetic, and irreversible.

Defense lawyers and doctors will point to a signed “informed consent” as proof that the patient’s are informed. But as you will learn, patients have been left out in the cold on key facts, and have been misled by clever copy. This began with the introduction of RK and has continued ever since. For instance, did RK patients, or even the more recent mini-RK patients, know that 40% of the corneas with RK after ten years were unstable and experienced progressive hyperopia? While evidence of these untoward outcomes were known in the late 1980’s, they were not communicated to patients.

Refractive procedures, with one exception, are permanent and irreversible. While permanence, at first blush, appears to be a positive attribute, it has a dark side – permanent problems, permanent outcomes, and no upgrades. The so called permanent correction (outcome) will not be so pleasing as one ages since the optical system changes with age. The required visual correction at one point in life may not be the desired correction later. Upgrades to improved or newer ways to correct vision will be ruled out since most of the present procedures involve permanent changes to the corneal structure (permanent removal of tissue). Those opting for these procedures are locked-in. Imagine being locked into a clunky 1980 car phone with no chance to upgrade to a newer, smaller, portable, feature laden, cell phone. I, like many who are interested, wear contact lenses and would like to be rid of them. But the question for me has always been at what risk? With what I know from surgeon’s private hallway conversations, I prefer my contact lenses, and will have them for some time. I will get rid of contacts when something comes along with these proven attributes:

  •   minimal risk
  •   great vision
  •   no maintenance
  •   allows prescription changes as my visual system changes with age
  •    allows me to upgrade to newer procedures as they are introduced
  •   reasonably priced
  •   and allows me to undergo effective, proven therapies I may need as I age for glaucoma,

cataracts (IOLs), and macular degeneration. Then I will put my contact lenses aside, and become an enthusiastic refractive surgery supporter and patient.

”Letters to the Editor, Re: Corneal refractive power after myopic LASIK,” Ophthalmology,” September, 2003

(These letters refer to the difficulty of determining which IOL should be used in cataract surgery following LASIK. Since the cornea is now abnormal, there is some uncertainty on what should be done.)

Vahid Feiz, MD, Little Rock, Arkansas; Mark J. Mannis, MD, FACS, Sacramento, California

“The recent article by Hamed et al1 addresses an emerging problem that many ophthalmologists will be facing in the relatively near future. It has two main conclusions: (1) when manual keratometry and topography are used for intraocular lens (IOL) calculations after myopic LASIK, the power is underestimated, and (2) there is a direct, linear relationship between the degree of corneal refractive surgery and IOL power error as evidenced by regression analysis…What exactly is the source of error in determining true corneal power after keratorefractive surgery? The answer most commonly cited is the alteration in the relationship between the anterior and posterior corneal surface that results in a change in refractive index…In summary, the authors’ conclusions and recommendations appear to verify the results of previously published studies.2,4 The most accurate method of calculating IOL power at this point remains use of refractive change induced by LASIK and a fudge factor to compensate for the change in refractive index of the cornea. In doing so, the relationship between corneal power and refraction needs to be considered…”

Douglas D. Koch, MD and Li Wang, MD, PhD, Houston, Texas

“We enjoyed reading Drs. Feiz and Mannis’ letter and welcome the study of new approaches for calculating intraocular lens (IOL) power in patients who have undergone LASIK and photorefractive keratectomy. However, we do not feel that their letter accurately characterizes their method or the current state of knowledge regarding this challenging problem…

We are surprised by their comment that the clinical history method “still underestimated the IOL power.” Asthey state in their article, none of these methods has been tested in a clinical series…Therefore, any comparative evaluation of these methods is purely speculation, pending further clinical study…the ultimate goal is the development of accurate methods of measuring true corneal power.”

REFRACTIVE SURGERY AND MISINFORMATION

Misinformation and hype in refractive surgery began with the introduction of RK and has followed a predictable pattern ever since. With the introduction of each new and/or improved procedure, the problems of older procedures, which were previously misrepresented or not even discussed, were made public. When “mini-RK,” an “improved” RK procedure, emerged in the early 1990’s, the real problems (and their probable incidence) of the “older RK” procedure were fully disclosed. The case for an improved procedure had to be made so that the new “mini-RK” would be adopted.

When the FDA approved PRK, the problems of the “mini-RK,” heretofore denied, were now openly discussed in light of an even better procedure. When LASIK gained momentum in the late 1990’s, PRK’s problems, again accepted privately but previously denied publicly, were publicly discussed to move surgeons and patients to LASIK. And with the introduction of laser-based procedures, new stakeholders – optometrists, manufacturers and emerging commercial refractive chains – joined the refractive surgeons in misinformation and hype. The “refractive surgery industrial-medical complex” was born.

We are now moving into the era of Wavefront, IntraLASIK, LASEK, and various intraocular lenses. LASIK, which surgeons, optometrists, refractive surgery chains, and manufacturers just three short years ago said had “1 in 10,000 problems”, “Throw your glasses away forever,” and “100% of the outcomes are 20/20”, etc., will now be beaten up with the unvarnished truth about its outcomes and complications. Unfortunately, the new and/or improved procedures will be marketed as LASIK was – with misinformation and hype. The truth on these newer procedures will emerge from the “refractive surgery industrial-medical complex” only when there is a need to obsolete them with “the next big thing”. And pay close attention to the spokesperson surgeons for the new procedures, they are the same people who hyped, with selective information, the procedures being abandoned.

Where have the Medical Societies been? Medical Societies need revenues to survive. They cease to exist without dues paying members and the financial support of industry. Industry provides financial support through medical journal advertising, medical meeting participation, and support to various causes vital to the member interests. Taking a stand, which can impact the revenues of an important member and industry group, can be difficult. One society did take a stand against RK in the early 1980’s and suffered. A lawsuit was filed and was successfully litigated against this society for interfering with the commercialization of RK (free speech).

More recently in 2002, some surgeons, concerned with lawsuits, have discussed in their doctor-to-doctor web based chatrooms the blackballing of those doctors who serve as expert witnesses for plaintiffs. At the annual meeting of the American Academy of Ophthalmology in 2002, a Canadian surgeon, who testified in an Arizona malpractice case resulting in a $4 million judgment, was accosted by fellow US surgeons. His mistake was testifying for the plaintiff. Remarkably, this doctor had changed his view saying that he mis – spoke under oath at the jury trial. The ruling has been set aside and the case is waiting to be retried. Fear of retribution permeates the field of ophthalmology. Patient’s, with legitimate malpractice issues, now have difficulty finding an “expert” surgeon who will testify on their behalf. Rather than taking responsibility, refractive surgeons are shifting guilt to the patient and to those trying to help the patient. Misplaced guilt is not restricted to business and politics!

And where has the FDA been? While the FDA can regulate manufacturers, they cannot regulate doctors. Physician advertising is the responsibility of the FTC. This complicates the communication of accurate, nonselective information as cross-jurisdictional responsibilities dilute the effort.

“Vision Quest: Laser eye surgery has worked for millions but goes awry for 18,000 patients a year. A new approach aims to fix that.” Mary Ellen Egan, Forbes, September 15, 2003, pg. 222.

“…Two years ago Heinbockel had a new kind of eye surgery called wavefront, approved by the Food & Drug Administration in October 2002…Though some 3.7 million Americans have had successful surgery since 1995, problems such as night vision, cloudiness, glare and halos occur in about 3% of patients – upwards of 18,000 per year. The new wavefront approach reduces flaws to just 1% of cases and fixes vision problems LASIK cannot…The procedure costs about $2,500 per eye, or 20% more than LASIK…But LASIK and wavefront are as different as ordering a suit off the rack and being fitted for a custom-tailored one… Thomas Wilson, 57, had two LASIK surgeries that left him with halos and night vision problems…His original LASIK doctors “thought I should be satisfied with my results,” he fumes.

“Lens-based refractive procedures offer advantages over LASIK,” William F. Maloney, MD, Ocular Surgery News Europe/Asia Edition, September 2003

“The limitations of LASIK and other keratorefractive procedures are increasingly difficult to ignore. The aberrations inherent in corneal reshaping methods simply do not always allow the accuracy and predictability most refractive surgery patients have come to expect. Anatomical limitations (there is only so much cornea that can be ablated) combined with functional limitations (treatment zone vs. pupil size, etc.) have resulted in the realization that LASIK just cannot do it all, as many had hoped it would 5 years ago. The steady reduction in the amount of ametropia that can be reliably corrected with corneal refractive techniques has left surgeons looking elsewhere…the IOL has clearly emerged to fill this void… Lens -based refractive surgery also brings us back to basics, in the sense that surgical skill is a prerequisite to successful outcomes and satisfied patients. It seems to me that at least part of the appeal of LASIK and other corneal procedures was perhaps that they presented an opportunity to circumvent this basic issue, but this did not happen…

“Ten-Year Results on Radial Keratotomy Released,” National Eye Institute Information Office, NEI Press Release, October 13, 1994

“…the study found that more than 40 percent of RK-operated eyes continued to have a gradual shift toward farsightedness. This finding suggests that some people who have RK may need glasses at an earlier age for poor close-up vision, a common problem after age 40, than if they had chosen not to have the surgery. ‘Based on these findings, it may be that some people will be pleased with their vision shortly after having RK, but their opinion may change five, ten, or fifteen years down the road,’ said Peter J. McDonnell, M.D., of the Doheny Eye Institute at the University of Southern California and the study’s co-chairman. Today’s findings, published in Archives of Ophthalmology, were issued from the Prospective Evaluation of Radial Keratotomy (PERK). The PERK study is the first large, well-designed clinical study to evaluate the long-term effects of radial keratotomy on the eye and vision.

RK is performed to improve poor distance vision, called myopia, which affects millions of Americans. For some people with myopia, RK offers the prospect of good distance vision without the need for glasses or contact lenses.

The surgery changes the shape of the cornea, the clear, rounded tissue at the front of the eye. It is performed by making spoke-like, partial-thickness incisions into the healthy cornea. These wounds cause the cornea to flatten, producing clearer distance vision. Today, about 250,000 RK surgeries are performed annually in the United States, up from 30,000 operations just five years ago. However, eye care professionals still have little scientific information about the procedure’s long-term effects on the cornea and vision.

To provide these data, PERK clinicians periodically examined the eyes of the 435 participants since the study began in the early 1980s. Based on these examinations, researchers have published occasional reports in medical journals, including the results issued today. At the PERK’s 10-year mark, researchers reported that RK effectively reduced but did not completely eliminate myopia in all patients. They found that 53 percent of the RK-operated eyes registered 20/20 vision, while 85 percent of the eyes had 20/40 uncorrected vision or better (required for a driver’s license in most states). Approximately 70 percent of study participants said they did not wear corrective lenses for distance vision at the 10-year mark.

RK also had “a reasonable margin of safety,” resulting in few vision-threatening complications. However, the researchers noted that 3 percent of operated eyes had poorer distance vision with glasses one decade after surgery, although none had corrected vision worse than 20/30.

Interestingly, the PERK scientists reported that 43 percent of the RK-operated eyes continued to have a gradual change toward farsightedness, called hyperopic shift. In fact, 36 percent of the eyes had become farsighted at the 10-year point…According to the researchers, this shift was detected in some affected patients as soon as six months after surgery and continued to progress a decade later. They said they do not know when and if this change will cease in the future. The scientists noted that the shift in vision was not related to the patient’s age or post-surgical outcome. They added that they could not predict based on the PERK data which patients will develop the hyperopic shift. They did note, however, that the shift was more common in those who had RK surgery using longer incisions in the cornea, a common technique in younger and/or more myopic patients. Participants (in this study) were examined before and after surgery at two weeks, three months, six months, annually for five years, and again at 10 years.”

FUNDAMENTALS OF LASIK

LASIK has inherent problems due to the nature of the procedure. These problems occur whether $499 or $5000 is paid for the procedure. It has been frustrating to observe the “refractive surgery industrial-medical complex” position the higher priced procedure as providing better outcomes and fewer complications. There are no unbiased scientific studies to support this.

LASIK’s surgical landscape: the cornea

Go to www.surgicaleyes.org for a complete description of LASIK and other refractive procedures. The cornea, the part of the eye operated on during LASIK, is the front most tissue of the eye. It is normally transparent and does not contain blood vessels. The cornea is only 0.5 to 1 mm thick, and is generally thinner centrally than peripherally. The cornea provides two-thirds of the eye’s image focusing (“refracting”) power. The other one-third is provided by the eye’s internal lens, which is not involved in LASIK. The cornea has five layers, and two of these are very important in LASIK. The outermost layer, the epithelium, is a highly sensitive tissue about six cells thick. It acts as a barrier between the inner eye and the outside world, much as skin does for the rest of the body. It also provides a smooth surface allowing light rays to pass into the eye without being distorted. The epithelium has a bas ement membrane that helps it to adhere to the cornea’s middle layer, the stroma. If the epithelium and/or its basement membrane are abnormal, the cornea may not heal properly, and an irregular surface and/or scarring may result.

The cornea’s middle layer, the stroma, is the layer at which most of the LASIK procedure is performed. The stroma accounts for about 90% of the cornea, and is made up mostly of water and layered narrow bands of collagen/protein fibers. These bands crisscross the cornea and are under tension, much like the rubber bands in golf balls. The stroma consists of about 500 layers of these bands. Scarring in this layer can result in loss of corneal transparency.

LASIK makes the stromal layer thinner by removing tissue, and cuts through the collagen bands, severing them, to the depth of the flap. These bands never reconnect making the cornea both weaker and nonhomogeneous.

Enhancements make the cornea thinner and sever more collagen/protein bands . The severing of the bands allows a surgeon to lift the flap years after the procedure. The cornea is sealed around the periphery (minimal risk of infection) but never heals to its original anatomy. One of the biggest unknowns is what happens over time to the weakened cornea. It is under constant outward pressure from the intraocular pressure in the eye. Mechanics of materials would suggest that the cutting of the collagen bands would be a prime suspect in a serious complication called ectasia. Ectasia is the bulging of the cornea outward, and leads to progressive hyperopia and/or serious complications that may lead to a corneal transplant. How many LASIK’s would have been done if patients were informed that the flap never healed, that the cornea was no longer anatomically homogenous, that the cornea had been weakened considerably, and that the cornea was under constant outward stress due to intra-ocular pressure? How many patients know that this could lead to ectasia, an unnatural and unforgiving bulging of the cornea?

“Epithelial in-growth after laser in situ keratomileusis: a histopathologic study in human corneas,” Naoumidi I. Et al. Archives of Ophthalmology, Volume 121, (7): 950-5, July 2003

Corneal epithelial cells lose their characteristic morphologic features and eventually degrade in the metabolically “unusual” environment of the flap interface. Concurrently, a capsule of connective tissue similar to scar tissue forms, separating them from healthy cornea.

“Histological and immunohistochemical findings after laser in situ keratomileusis in human corneas,” Philipp WE, Speicher L, Gottinger W., J Cataract Refract Surgery, 2003;29(4):808-20.

This study, conducted in Austria, described histopathological and immunohistochemical findings in human corneas after myopic laser in situ keratomileusis (LASIK), followed by iatrogenic keratectasia and after hyperopic LASIK…Researchers concluded that the wound-healing response is generally poor after LASIK, which may result in significant weakening of the tensile strength of the cornea after myopic LASIK, probably due to bio-mechanically ineffective superficial lamella. After LASIK in patients with high hyperopia, compensatory epithelial thickening in the annular mid-peripheral ablation zone might be partly responsible for regression.

“Late-onset traumatic laser in situ keratomileusis (LASIK) flap Dehiscence,” American Journal of Ophthalmology, April 2001

“ A 37-year-old male had bilateral laser in situ keratomileusis (LASIK) surgery performed on November 5, 1999 in Canada…On May 16, 2000 a tree branch snapped into his left eye…He noted an immediate decrease in vision and went to a local emergency room. The on-call ophthalmologist diagnosed a corneal flap dehiscence…Visual acuity, LE, was count fingers (CF at 6 inches)…the patients clinical status did not change over the next three months. This case has several interesting clinical lessons. Patients often ask when the LASIK flap will be finally healed. Since there is minimal wound healing except at the edges of the flap, given enough force directed against he cornea, the flap may become dislodged months and even years after uneventful surgery. Patients should be educated about this possibility and wear eye protection when performing potentially hazardous activities…This patient originally had low myopia and a photorefractive keratectomy (PRK) procedure would have been equally effective and obviously would not have led to this complication.”

“The Cornea is Not a Piece of Plastic,” Cynthia Roberts, PhD, Journal of Refractive Surgery, Volume 16, July/August 2000

Page 409+. A conceptual model is presented in Figure 4 that predicts biomechanical flattening as a direct consequence of severed corneal lamellae. Rather than a piece of plastic, the cornea can be conceived as a series of stacked rubber bands (lamellae) with sponges between each layer (interlamellar spaces filled with extracellular matrix). The rubber bands are in tension, since there is a force pushing on them underneath (intraocular pressure), and the ends are held tightly by the limbus (the peripheral edge of the cornea where the clear cornea merges with the white of the eye). The amount of water that each sponge can hold is determined by how tautly the rubber bands are pulled. The more they are pulled, the greater the tension each carries, the more water is squeezed out of the interleaving sponges, and the smaller the interlamellar spacing. This is analogous to the preoperative condition in Figure 4A. After laser refractive surgery for myopia, a series of lamellae are severed centrally and removed, as shown in Figure 4B. The remaining peripheral segments relax, just like the taut rubber bands would relax once cut…This allows the periphery of the cornea to thicken. Postoperative corneal shape, and thus visual performance, is a function of at least three factors: the ablation profile, the healing process, and the biomechanical response of the cornea to a change in structure.

Letters, American Journal of Ophthalmology, Volume 130 Issue 2 (August 2000) Pages 258-259

“In the interesting article by R Lin and RK Maloney (Am J Ophthalmology) 127:129–136, January 1999), they confirm earlier reports that flap-related complications after laser in situ keratomileusis (LASIK) occur in 5.0% to 8.7% of cases…

Complications continue to be reported after LASIK, including unexplained delayed-onset keratectasia after treatment of moderate myopia…These reports indicate that LASIK weakens the structural integrity of the cornea and that the list of complications is as yet incomplete. We feel that fast and painless recovery after LASIK and the marginally better UCVA of 20/20 or greater may not outweigh the risks of this procedure in myopia less than -6.0 diopters…”

Letters, by Brauweiler, MD, Wehler, MD, and Busin, Ophthalmology, September 1999, pgs 1651-1655.

“It is my opinion that PRK and LASIK should not have been approved beyond 8.00 diopters. Beyond this limit many corneas will have had too much stroma removed to allow long-term stable vision. …Carmen Barraquer responded that 100% of eyes that had undergone similar thinning technique, known as myopic keratomileusis lost effective correction (in many cases up to 50%) over a twenty year period…Essentially what this means is that all eyes over 8 diopters that have their corneas thinned by laser surgery will result in significant return of their myopia…the main purpose of this communication is to alert patients to ask their patients physicians how much of their cornea is being removed before it is irreversibly vaporized.

“Iatrogenic Keratectasia Following Myopic LASIK of Between <4 and 7 Dioptres,” S. Percy Amoils, et al, Poster, Annual meeting of the American Cataract and Refractive Surgery Society, Seattle, Washington, April 1999

”Results: The cases show progressive ectasia that developed from 1 week to 27 months after LASIK…Conclusions: LASIK surgery can cause permanent weakening and ectasia of the cornea even in low myopia…LASIK has certain intrinsic problems and the combination of incisional surgery and laser ablation has the potential for serious short and long term problems. Thinning and thus weakening of the stromal bed as well as the minimum strength inherent in the flap are the causative factors for the development of keratectasia.”

Asphericity and imaging of light rays on the retina

Think of the eye as a camera. Parallel light rays enter the eye through the transparent cornea. The cornea (and the eye’s internal lens) then focus the light rays in much the same manner that the lens of a camera would, by bending the light rays so that they come to a single clear focus at a specific distance. This process of bending light is called refracting. In a normal eye, the cornea focuses light at a distance that produces a single sharp image on the retina, the neurosensory tissue that is akin to the film in a camera.

Light rays that are bent too little or too much do not focus at the correct distance, and a blurred image results from this refractive error. How much or little a cornea refracts light depends on the cornea’s curvature. That is why refractive surgery seeks to change the refracting power of the eye by changing the cornea’s curvature.

In nearsightedness (myopia), the cornea is too steeply curved, giving it too much focusing power and causing light rays to focus before they reach the retina. In myopia, the eyeball itself may also be elongated, contributing to the problem of light focusing in front of instead of on the retina. Conventional spectacle or contact lenses seek to optically decrease the focal power of the cornea, and thus correct the myopia, by placing a concave spherical lens (a “minus lens”) in front of the eye. LASIK seeks to achieve the same result by removing tissue from the central cornea, flattening the cornea’s overall curvature and thus reducing the cornea’s focusing power. Exactly the reverse is true in farsightedness (hyperopia). Astigmatism is different from myopia and hyperopia, and it can occur concurrently with either condition. But changing the curvature of the cornea is not simplistic, as some make it out to be. The natural shape of the cornea is what the medical community calls aspheric which means that it is steeper in the center and flatter in the periphery. If one were to focus light rays from any angle outside the cornea, the aspheric shape would bend them so that they would fall in a small area on the back of the eye on the retina, called the “the center of least confusion.” This small area acts like a data collection plate for our human computer, the brain. The more data (light rays) that get to this collection plate, the more data the brain has to process for good vision. Since laser procedures get their effect by flattening the center of the optical zone, the cornea does not end up aspheric but oblate. After the procedure, the cornea is flatter in the center, and steeper in the periphery, causing light rays to fall outside the data collection plate. While this causes few problems in bright sunlight, since we do not need a lot of information to process a good image (much like a camera), it does cause problems as the Iris opens up seeking more data in low light or nighttime situations. Vision is not as sharp and is degraded. This can be demonstrated by testing for the loss of contrast sensitivity. Most, if not all, laser procedures today work by flattening the central optical zone creating the oblate (reverse of aspheric) surface. For Wavefront Guided LASIK (discussed later), an aspheric surface can be created, but it requires deeper tissue removal (and weakening) in the periphery.

The cornea has two surfaces that contribute to its refractive power, the front surface, which you see, and the back of the cornea, which you cannot see as it is inside the eye. It would be wonderful if these surfaces were uniform. If they were, then one could change the front curvature of the eye, in an aspheric shape, without concern for the back and its refractive power. Neither the front nor the back surfaces are uniform in their shape, which means that they are irregular. Therefore, cutting in the front, which is done at present, is not being done with the back surface taken in consideration. This can lead to refractive differences and/or uneven corneal thickness across the front of the eye. The thinner areas will be weaker than the thicker areas.

The loss of contrast sensitivity and quality of vision

Visual problems come with the creation of an oblate surface, uneven thicknesses, and with the transition zone from the flap to the untouched cornea. The most important diagnostic test for the quality of vision is the test for contrast sensitivity. Arthur Ginsburg, PhD, developed this test for the U.S. Air Force. The AF wanted to learn why some pilots who tested for 20/20 (quantity of vision) were missing objects while others who were 20/20 were seeing them with ease. The Air Force learned that the Snellen Eye test (black letters on a white background) is not a good test for vision quality. While one may see 20/20 after LASIK, and be counted as a LASIK success, one may actually have degraded vision. There can be a significant difference between the quantity of vision and the quality of vision.

Years ago, hearing tests were crude and involved the movement of a single sound frequency towards the person being tested. When the person heard it, hearing ability was determined – 20/20, 20/100 hearing etc. Researchers then realized that we heard sounds across a range of frequencies and this test-measured sound only at one frequency. The audiometer was then developed to measure hearing losses/gains across the full range of frequencies required for high quality hearing. If you were to suffer from a hearing loss, it would be described as a low frequency, middle frequency, high frequency or multi-frequency loss. And fortunately, tunable hearing aids are now available to amplify sounds in regions where the loss(es) exist. The full range of frequencies has also been translated into improving the listening pleasure of car radios, stereo systems, etc. Today we have the use of equalizers for audio sound allowing us to amplify selected frequencies (high, lows, middle range) for our listening pleasure.

Vision is very similar to hearing in that the quality of vision is not a function of one frequency but rather a range of frequencies. In the case of vision, these frequencies are spatial frequencies. The Snellen Eye Chart is crude and tests vision at one spatial frequency, providing woefully incomplete data on the quality of vision. The test for Contrast Sensitivity test measures vision across the full range of frequencies needed for quality vision, like the audiometer does for hearing. We know that any hearing frequency loss can interfere with the ability to discriminate what is heard. And we now know that any vision frequency loss can interfere with the ability to discriminate what is seen. This becomes particularly acute in low-light and/or nighttime situations, and explains why so many refractive patients like the vision they have in bright light but have significant difficulties in low light or nighttime situations. Bright light produces high contrast. Unfortunately, we do not have tunable eyewear to make up for these losses. For a much more complete description of contrast sensitivity, go to either www.surgicaleyes.org or www.vsrc.com (Dr. Ginsburg’s site).

“Post-LASIK changes in Corneal Asphericity,” Optometric Physician May 2003, (SOURCE: Anera RG,

Jimenez JR, Jimenez del Barco L, et al. Changes in corneal asphericity after laser in situ keratomileusis. J

Cataract Refract Surg 2003;29(4):762-8)

This Spanish study analyzed the origin of the changes in corneal asphericity (p-factor) after laser in situ keratomileusis (LASIK) and the effect of post-surgery asphericity on contrast-sensitivity function (CSF) under photopic conditions.

Clinicians measured the p-factor and CSF (best corrected before surgery and one, three and six months after surgery) in 24 eyes. They noted an increase in the p-factor after LASIK; there was an 87.2 percent change in the asphericity using the paraxial formula of Munnerlyn and coauthors. Other factors such as decentration, type of laser, optical role of the flap, wound healing, biomechanical effects, technical procedures and reflection losses of the laser on the cornea could account for the greater than expected increase (12.8 percent) in the p-factor. The CSF measurements deteriorated after LASIK; the change was significant in patients with myopia worse than -4.00D at frequencies of 9.2, 12, 15 and 20 cycles per degree. The increase in corneal asphericity after surgery, greater with a higher degree of myopia, and the deterioration in CSF with high myopia justify new ablation algorithms and further study of the variables that could modify the ablation unpredictably.

“Capriati troubled by night matches,” www.SportingNews.com , August 9, 2002

MANHATTAN BEACH, Calif. — Jennifer Capriati is wary of playing night matches because the court lights

affect her ability to see the ball.

Capriati, the No. 2 seed, struggled for more than two hours before beating No. 16 Tamarine Tanasugarn of Thailand 6-3, 6-7 (3), 6-2 in the third round of the JPMorgan Chase Open on Thursday night. “Maybe I just started rushing a bit. I got thrown off a bit as soon as it was getting dark,” she said. “I have problems playing at night. I was shanking some balls on my groundstrokes.” Capriati, who had Lasik eye surgery two years ago, also had trouble picking up the ball in a night match at last week’s Acura Classic, where s he lost in the quarterfinals.

“I feel like it’s wearing off a little bit,” she said of the surgery. At Manhattan Country Club, the light poles are low on stadium court. “At night, lights can start to become very bright,” Capriati said, describing the effect on her vision. “When they’re really low like that, it just feels like there’s a flashlight on me constantly.”

She didn’t react well to the glare, double-faulting numerous times in the second set. “In the second set, I just stopped hitting the ball and she started really dictating the points,” said Capriati, who was cheered on by her friend, actor Matthew Perry.

At most tournaments, the top players are required to play at least one night match to draw crowds. Having survived that obligation, Capriati said officials here know not to schedule her under the lights again. “I know there’s going to be night matches, especially at the U.S. Open, so what am I going to do?” she said.” For more on this, go to http://www.capriati.host.sk/a15_02.htm

ASCRS, 2000 Presentation by William Jory, consultant eye surgeon at the London Centre for Refractive Surgery on Contrast Sensitivity.

Dr. Jory, in his study, found that Contrast Sensitivity was impaired in 58% of the patients who had LASIK – to the point that these people were not fit to drive safely at night. The Department of Health took this study seriously, in conjunction with a separate study at the University of Ottawa, and recommended that any patient who had refractive surgery should have a night driving test performed before a driving license is granted. Jory said that nighttime vision problems did not seem to be related to high corrections.

“Determining Medical Fitness to Drive,” published by the Canadian Medical Association in 2000.

In this booklet, laser eye surgery was added to the list of risk factors for unsafe driving. See Canadian Press Newswire for full press release, August 27, 2000. This recommendation was later overturned after pressure was brought to bear by the Canadian Ophthalmology Association.

“Functional Vision and Corneal Changes After Laser In Situ Keratomileusis Determined by Contrast Sensitivity, Glare Testing, and Corneal Topography,” Jack T. Holliday, MD, MSEE, et al, Journal of Cataract and Refractive Surgery, Volume 25, May 1999.

Conclusions: Functional vision changes do occur after LASIK. The optical quality of the cornea is reduced and asphericity becomes oblate. Changes in functional vision worsen as the target contrast diminishes and the pupil size increases. These findings indicate that the oblate shape of the cornea following LASIK is the predominant factor in the functional vision decrease.

Guest Editorial, Michael Mrochen, PhD, Department of Ophthalmology, University of Zurich, EyeWorld Week, April 2001

“Refractive corneal surgery currently focuses on the correction of spherocylindrical errors as the most apparent and disturbing optical aberrations of the human eye. Unfortunately, a significant increase in higher order aberrations accompanies these corrections; thus, higher-order optical errors such as coma and spherical aberration have become more common…(this) correlates with a significant decrease in the quality of vision, especially under scotopic conditions.

“Inside LASIK – Screening the keratorefractive big picture show”, Maxine Lipner, EyeWorld, April 2001

Quotes attributed to James T. Schweigerling, PhD, Assistant Professor, University of Arizona… “Current refractive techniques, such as PRK and LASIK, dramatically increase aberrations in the eye.” After such procedures, a wave may look spherical in the center, but tends to deviate due to distortions in the corneal periphery. “What happens is light going through the edge of the pupil tends to focus in front of the retina, whereas light going through the center ..tends to focus on the retina. This gives you a multifocal effect…In areas with such spherical aberrations, patients can still see sharp points of light, but the contrast is reduced and images appeared blurred and hazy.” In effect, during the day, the patient sees very well however, as the pupil dilates, the error increases dramatically.

Quotes attributed to Leo Maguire III, MD, Associate Professor, Mayo Clinic… “It (refractive surgery) threatens public health to the extent that it degrades optical performance and impairs the public’s ability to perform visually challenging tasks.” Maguire also reminds practitioners of refractive surgery…that changes will occur in the eye with aging, independent of refractive surgery, and that patients in the keratorefractive market of today will grow old like everyone else. He is concerned about how well these patients with seemingly insignificant higher-order aberrations today will perform when their visual systems are later taxed by conditions, such as, early lenticular opacity, macular degeneration, and a decrease in psychophysical compensation. “By 2025, one in four drivers in the US will be over the age of 65…Patients with degraded night vision and increased glare present a danger, not only, to themselves, but to others who share the roadway.”

Dry eye

Dry eye occurs naturally with age. Temporary relief from dry eye comes from the use of artificial tears. For some, it means eye drops every few hours; for others, it means infrequent use of eye drops. Drug companies and the NIH (The National Institute of Health, our tax dollars at work) have spent millions seeking a cure, and, at the very least, developing possible treatments.

It is now known that LASIK causes dry eye in a large number of patients. When the flap is cut, the microkeratome cuts the nerves in the front part of the cornea. Some believe that these nerves never heal completely interrupting the communication between the nerves and the tearing mechanism. Others believe that the unnatural post-LASIK oblate shape hinders proper tear flow across the cornea. Regardless of the cause, many feel that dry eye is the Achilles heel of LASIK.

Many surgeons implant “punctal-plugs” in the ducts that drain the tears to alleviate the symptoms of dry eye. These plugs prevent the tears from draining. Sales of punctal-plugs have skyrocketed with the introduction of LASIK. For those who still need relief, artificial tears are prescribed. The sales of tears have also skyrocketed. LASIK has expanded the problem of dry eye from being a naturally occurring phenomenon to being a surgically induced problem.

DLK (diffuse lamellar keratitis)

DLK is classified as a “real” complication in the FDA classification system. Little is known about its cause

and its incidence may be much higher than what is being reported.

“Bilateral diffuse lamellar keratitis following bilateral simultaneous versus sequential laser in situ

keratomileusis,” McLeod SD, Tham VM, et al, British Journal of Ophthalmology, 2003;87:1086-1087

”…A retrospective non-comparative case series of 1632 eyes that had undergone bilateral, simultaneous or sequential LASIK between April 1998 and February 2001 at a university based refractive centre by three surgeons…The main outcome measure was the incidence of unilateral and bilateral isolated, non-epidemic DLK…Of 1632 eyes, 126 eyes (7.7%) of 107 patients developed at least grade 1 DLK. In six operating sessions, DLK was observed in more than one patient per session…CONCLUSION: In isolated, nonepidemic bilateral DLK, a similar incidence (of DLK) was observed regardless of whether the surgery was simultaneous or sequential, suggesting an underlying intrinsic cause for DLK.”

Accuracy of the microkeratome

Laser based refractive procedures were initially marketed to a wary public as space age technology with space age precision (laser accuracy is to the micron level). Since this was technology driven, not surgical skill driven, there was little to worry about. While surgeons today are trying to differentiate themselves by skill (to avoid price competition), the precision of the laser is still marketed as an attribute of the LASIK procedure.

What the “refractive surgery industrial-medical complex” does not talk about is the inaccuracy of the microkeratome that is used to cut the flap. If the desired depth of cut for a flap is 200 microns, the actual cut may be plus or minus 16-20% of this desired depth. The variation of the microkeratome has been a weakness of LASIK from the beginning. The creation of the flap, its depth, and its thickness are not only important to the visual outcome, but also to the potential for long-term complications such as progressive hyperopia and ectasia.

“Some foresee limitations in wavefront technology.” Ocular Surgery News, August 1, 2002

Noel Alpins, MD, said, “No matter how finely tuned a microkeratome is, it’s still a gross change to the cornea as opposed to the changes required with wave-front guided treatments.” The flap presents a problem.

Enhancements and the use of misleading terms

The term enhancement originated with the mini-RK in the early 1990’s. The mini-RK involved making a small incision RK followed by a waiting period. For those who had good visual outcomes, nothing more was done. For those that did not, another procedure was done that involved slightly longer incisions. If this too failed, another procedure followed with even longer incisions. Rather than call these re-operations, ophthalmologists created a patient friendly but misleading term, enhancements. The term has continued with all subsequent refractive procedures.

One of the problems with the term is that it sounds like the procedure is benign. Does enhancing make it better? This is a matter of semantics. For LASIK and RK outcomes that are under-corrected, more tissue is removed or deeper, longer incisions are made respectively. While in some cases, vision can be improved; permanent damage to the cornea is increased. For LASIK and RK outcomes that are over-corrected, tissue cannot be added back to the cornea nor can permanent incisions be reduced or eliminated. In short they cannot be enhanced.

These procedures are not as flexible as some would have you believe nor are they upgradeable. While the cornea is further flattened, it is also made thinner, and weaker by the removal of more tissue. Enhancement are a one-way street and are irreversible. Additional terms that are now finding their way into the vocabulary of refractive surgery include “Tear Savers” for the use of punctal-plugs (you still have symptomatic dry eye), “Advanced Surface Ablation” for PRK (once trashed, some are now trying to reintroduce it), “Blended Vision” for mono-vision (this is not like Varilux lenses where one lens is blended, but rather one eye is corrected to see far objects and the other eye is left untouched to see near objects), and most recently, “HD LASIK”, high definition LASIK (is it really high definition for all? all the time? for many years?). Each of these terms provides a message to the patient that is selective, and misleads.

INFORMED CONSENT

Patient informed consent while critical in all medical treatments takes on special importance in refractive surgery since patients are electing to undertake the risk of irreversibly altering an otherwise healthy eye. Information provided by advertising, promotional materials (brochures, etc), in-office staff, referring doctors, and the surgeon are all considered part of the legal informed consent. The truthful setting of expectations regarding potential outcomes and complications in all of these communication tools is crucial to making an informed decision.

Refractive patients seeking information on refractive procedures should know that doctors, their staffs, an referring professionals have been well schooled (“in-practice marketing skills sessions”) on how to handle difficult questions and concerns in an effort to keep interested candidates “in play” for the procedure. “Inpractice marketing” covers every contact the patient has with the practice. Training programs have been developed and offered by manufacturers to be given off-site or at the practice site. Many of these trainers/courses provide the doctor and his associates with tools to overcome patient objections. One of the pioneering laser manufacturers created their own teaching “University” to educate surgeons and their staffs The “University” goal was to increase patient throughput and profitability for the physician and the manufacturer (the manufacturer received $250 per procedure until 2000 when it was reduced to $100-150). The course was offered to those who purchased the company’s laser (a $450,000 purchase).

The absence of incidence data

The “Informed Consent” document was developed to provide a legal defense for doctors in the event of a lawsuit. It was also designed so patients would not be discouraged from the procedure. Many Informed Consents list possible adverse events, complications, and/or visual complications, including death (even though no one knows of anyone who has died from a procedure). And most do not list the incidence (how often something occurs) specifying only that a specific complication “may” occur. The inclusion of  significant life-changing event, death, that never happens, creates, by comparison, the perception that many of the other complications that “may” occur” are rare and “may” never happen as well. For full disclosure, informed consents must list the incidence of complications to insure. There is a big difference between “may” occur and a 20% occurrence rate when one is making an irreversible decision.

What would you do if you were told that a car you were considering “may” have a problem with the front brakes, and in the context of “may,” you were led to believe that it was 1%? What if it were 20%? 40%? You will see later in this document that the incidence of many refractive surgery problems warrant incidence percentages and not the word “may.”

Today, when having a refractive procedure with a FDA approved (excepting the first LASIK approval) Class III technology, manufacturers are required by law to provide booklets noting the incidence of each untoward effect. The doctors, in-turn, are required to include these booklets as part of the informed consent to prospective patients. Read the booklet carefully, and do not let anyone lead you to believe that the outcomes and incidence of problems will be any different. Some doctors will try to tell you that “his/her” patients do not seem to have these problems. Don’t believe it for a minute! A hangover from the first FDA laser approvals is that many of the original laser machines are still being used. These approvals did not have great incident data when approved, nor were the manufacturers and doctors compelled to provide FDA reviewed booklets to the patients. As a result, the vast majority of LASIK patients did not receive full and accurate information on outcomes and complications.

Going forward, interested parties should stick to data generated from FDA studies (excepting the original LASIK study) to insure that apples are being compared to apples. All FDA studies must follow the same format. Be wary of non-FDA studies that create expectations of better outcomes and/or fewer problems. Pay very close attention to the inclusion criteria (who can be considered a candidate). Data can vary according to the type and size of correction required. The data generated for the FDA approval relate to a specific, well defined population of people. For those who do not fit the study population, extrapolation of the results is problematic.

A physician’s internally developed data (personal studies)

Some doctors may show you his/her own data, collected from his practice on a refractive procedure, and say that his/her data is m uch better than the FDA data. Be cautious! Have my colleague put this in writing. The differences between a surgeon study and a FDA study are significant. FDA post-procedure exams take about three hours. And, a third party, who has no vested interest, must do post procedure follow-up exams. If a surgeon followed this rigor, he/she would lose control and money. They simply cannot afford the rigor required by the FDA in a commercial setting. A decision based on a physicians’ data is speculative at best.

Physicians’ use of manufacturer sales aids

When a doctor uses marketing materials, ask who developed the pieces, and ask if the FDA had approved the materials. The FDA has authority to insure that outcome and safety data from a manufacturer are provided accurately. Unfortunately, this is not true for physician developed marketing pieces. The FTC (Federal Trade Commission) has jurisdiction over physicians. Individual physicians are of little interest to the FTC so an interested patient must be on guard with non-manufacturer developed material. It even pays to scrutinize manufacturer materials, one well-known laser manufacturer created a physician sales support piece showing the comparison of several procedures. It was done in such a way that the competitive procedures were misrepresented. The FDA called them on it and asked them to desist. They, however, were not asked to recall the sales piece, so it was in use long after the FDA warned them. This type of marketing was done not for the benefit of the patient but for the benefit of the manufacturer.

Physicians and conflicts of interest

We have the problem of multiple conflicts of interest (payments, free use of lasers & equipment, travel) in the medical community. Surgeons are not immune. It is important for patient’s to understand what a physician’s and/or refractive surgery centers ties are. One doctor takes great pride in having no conflicts as he consults for all manufacturers, pulling in over $1 million per year. It is not what he does for his clients , it is what he does not do…like talk about the complications that beset each category of procedures. The “Informed Consent” should include all conflicts so those seeking opinions and/or procedures can discern the ties of the physician or practice to outside forces.

Medical opinion Leaders, medical publication authors, optometrists, surgeons, and manufacturers all are suspect. Since many of these people are conflicted, the patient must be responsible for demanding full disclosure. One way to insure disclosure is to have my colleague state in writing that he/she has received no payments (cash, equipment, trips, discounts) in kind from any manufacturer.

Referrals to LASIK surgeons

Many LASIK surgeons, LASIK centers, and National Chains have built their LASIK business on referrals. Most often these come from Optometrists (OD). Referrals generally involve payments to the referring doctor. Since kickbacks are illegal, a co-management arrangement is generally put in place. These payments, in the good days of 1998-2000, approached $1000/eye. An OD could make much more from one referral than several contact lens or eyeglass fittings. Today, with the economic downturn and reduced LASIK pricing, referral payments have been reduced, and in some cases, eliminated. This change raises some serious questions – ‘how much co-management was really being done?’ and ‘was co-management really a cover for a kickback” – which need to be answered.

If you are being referred, find out what the referral arrangement is, and find out how much the doctor has earned from referrals over the past three years. You may be dealing with someone who is seriously conflicted.

Looking through the patient’s eyes

The article that follows, which recently appeared in the New York Times (2003), addresses the issue of patient information and perception. It underscores the need for complete disclosure so patients can make an

informed decision. These situations are fraught with misunderstanding, particularly when many sources are involved with providing information.

“Seeing Risk and Reward Through a Patient’s Eyes”, Robert Klitzman, MD, New York Times, May 27, 2003

“But more important, many doctors weigh the risks and potential benefits of treatments in ways different from their patients without realizing that wide contrasts exist. Risks, after all are relative: what one person considers too dangerous, another might not. The way risks are presented and framed shapes our perceptions of them…In research too, (medical) investigators are supposed to warn of possible dangers. Yet, at times, they minimize such hazards and promote only the benefits…According to research, humans do not always think rationally about risks…they see patterns where none exist…With a side effect, too, it is one thing to say that the odds of its occurring are 30 percent. But the importance or unimportance of that symptom may range widely between people in ways that doctors do not take into account. Doctors often have trouble dealing with the inadvertent, side effects of their own treatments.”

Websites

Patient information websites are sponsored by doctors, refractive surgery centers, independent physician groups (many who have a vested interest in one procedure or another), former patients, manufacturers, and the FDA.

Surgical Eyes (SE) www.surgicaleyes.org is the best. Any person considering refractive surgery, as part of the informed consent, should be sent to SE during the consideration process. SE provides the other side of the story. It is a counterweight to the hype of the refractive surgery community (optometrists, surgeons, and manufacturers). Ron Link has done a real service for patients, and while some may disagree, he has done a service for the surgeons as well. The more the patient knows, even if it results in fewer procedures, the healthier the industry will be.

Misleading information characterizes most other websites and their chatrooms. Some website chatrooms have permanent contributors who post frequently as “independent experts”. Be careful, some of these are not independent and are deeply vested. Discernment falls squarely on the shoulder of the reader. A appropriate caution for all is to know whom the expert is, and to know what financial ties they have to refractive surgery. If the person is a physician that does the procedure, find out how many procedures he/she had done and his/her annual income level from refractive surgery.

The procedure history is also important. For most, a high number would indicate experience and expertise. For some of us, a high number would indicate the physician’s vulnerability as problems surface. One would expect the higher the number, the greater the emotional investment in believing he/she did the right thing, and the stronger the defense of his/her actions.

“LASIK complications and the Internet: Is the Public Being Misled?” Fahey, Weinberg, Journal of Medical Internet Research, Vol. 5, No. 1, March 2003.

Conclusion: the quality and quantity of the information on the Web on the complications of LASIK are poor. More work is required to encourage clear, accurate, up-to-date, clearly authored, and well-referenced, balanced ophthalmic information. “The poor quality of the information represents a negligent omission, as the public are being misled into believing that LASIK is without risk,” Fahey concluded. “This may lead to liability cases by patients with complications whose decision to have LASIK was based on the information they read on the Web site.” Dr. Fahey said he believes that if a surgeon is responsible for the content of the site, he or she bears the burden to ensure that the information “is accurate, well-referenced and balanced.”

“Surfer Beware: Don’t Trust All Online LASIK Info: Online LASIK info incomplete, study finds,” December 13, 2002

NEW YORK (Reuters Health) – Consumers who turn to the Internet for information about LASIK eye surgery should know it’s a surfer-beware environment, according to a team of eye specialists who evaluated online information and reported their results Friday at the American Optometric Association meeting in San Diego, California.

Dr. James O. LaMotte, a professor of optometry at the Southern California College of Optometry, Fullerton, and his colleagues used 10 search engines to find sites on LASIK…Next, using a 74-topic checklist derived from the Food and Drug Administration, the researchers then rated the sites for accuracy, awarding one point for accurate information on each of 74 topics related to the eye surgery.

Only 26% of the sites were rated as “markedly informative,” with 28% moderately and 46% minimally informative, LaMotte said. A site had to contain at least 67% of the total possible points to win a label of markedly informative. The minimally informative sites contained less than 33% of the possible points. “What the LASIK Web sites did was tend to talk about the benefits of LASIK and to ignore the risks and contraindications,” he said. Misinformation on the Internet is nothing new, LaMotte told his colleagues. Previous studies have found misleading or even harmful information disseminated on the Internet about fever in children and vascular surgical procedures. Other sites contain misleading information on age-related macular degeneration, an eye condition that can lead to blindness, LaMotte stated.

“ Medical Ethics and the Excimer Laser”, Samuel Pecker, MD, Archives of Ophthalmology, May 1997

”…the marketing required to achieve economic viability (of PRK laser surgery, and fits LASEK as well) is something that medical professionals are either uncomfortable with or would rather have someone else do.” ”This new technology and this new partnership (with laser companies) have the potential to create notable ethical problems, in such areas such as (1) agency, (2) conflicts of interest, (3) informed consent, (4) marketing and advertising, and (5) social issues – the relationship of medicine to society. At the least, rule 15 of the American Academy of Ophthalmology’s Code of Ethics would be observed. It reads, ‘Disclosure of professionally related commercial interests is required in communications to patients, the public, and colleagues.’

The marketing and advertising of PRK will put an increased burden on the ophthalmologist when it comes to informed consent because the cus tomer will come to the physician’s office with preconceived ideas obtained from the media and because the physician is assumed to be a trusted agent for a patient.”

Recent FTC actions

The US Federal Trade Commission (FTC) recently took action against two companies that were considered to be advertising unsubstantiated claims for LASIK. The actions, taken against The Laser Vision Institute and Lasik Plus, are the first of their kind.

Despite welcoming its moves, Ron Link, Surgical Eyes, is concerned that the FTC can only take action against national chains. “It’s a pragmatic position to take, but how does the local violator (your local doctor) get addressed? I don’t have an answer.”

FDA APPROVALS

By law, anyone bringing medical technology (device, instrument, etc.) to the US market must seek FDA approval prior to commercialization. The three classes of devices and required approvals can be found at the FDA’s website. Class III devices are generally the most innovative, having no precedent, and are the most regulated. A Class III device requires that safety and clinical data be provided to the FDA for analysis, prior to approval. The development of these data must adhere to guidelines issued by the FDA. Most (99%) of the submissions to the FDA are made by manufacturers seeking commercial approval of a product that they have developed or want to distribute. These are called company sponsored IDEs/PMAs. Companies must follow strict guidelines in the selection of their clinical investigators, the patients that enter the study, how the procedure is provided, and how data is collected before and after the procedure. The firs laser clinical studies which were for PRK (it does not involve the cutting of the corneal flap) were staged, with approvals for subsequent stages coming only after rigorous review of the previous stage, and took many years before completion of the third and last stage. In addition, the FDA required data from follow-up exams for up to two years before approval was even considered These studies, which were sponsored by companies, were required to have and did have high percentages of follow-up. These were over 95%, which means that 95% of their trial patients completed all of the required pre-operative and post-operative exams. These data were used to determine safety and efficacy. The higher the percentage, the higher is the confidence that the data truly reflects the outcomes and side effects.

Radial keratotomy (RK), which preceded PRK, did not require FDA approval. The device, a surgical scalpel, required for doing the procedure, was commercially available when the procedure was introduced in the US. Surgeons who wanted to provide this to the public were in business immediately. Unfortunately while the procedure was available, clinical data, and science-based information on outcomes/risks were not. Since this is what is considered an off-label use of a device/technology, the physician assumed full responsibility for liability.

Adverse events, complications, and visual symptoms

The FDA’s published refractive surgery clinical study guidelines establish three categories for the reporting of untoward consequences – adverse events, complications, and visual symptoms. The problem with this classification system is that patients with a serious “visual symptom” feel that they have a complication, a real problem. This classification methodology is not relevant to the consumer/patient and can lead to mischief. What will the patient be told when asking about complications?

When someone has significant visual symptoms – dry eye, loss of night vision, starbursts, etc. – their quality of life is truly impacted. Just go to www.surgicaleyes.com to their chatroom to see how much. A LASIK patient may be spending $1000 per year for artificial tears, may have given up driving at night, may suffer with fluctuating vision, may have a whole host of other problems, and may still be counted as a LASIK success. He/she only suffers from a visual symptom!

LASIK – an unapproved, off-label use of medical technology

Once the laser was approved for PRK in 1996, it became a candidate for any off-label use. Surgeons were free to use the laser as they saw fit. Prior to the PRK approval, surgeons outside the US (Italy, Greece, and Columbia) frustrated with some of the consumer unfriendly issues (pain, long term healing, and spontaneous corneal clouding) related to this procedure, began to apply both the laser and a device called th microkeratome. The resulting procedure becam e known as LASIK. LASIK seemed to be an improvement. It appeared to overcome many of the barriers (mentioned above) slowing the consumer adoption of PRK. Since the microkeratome was approved for another use and was already available in the US market, US surgeons were free, after FDA approval of the laser for PRK, to combine the laser with the microkeratome for LASIK. As with RK, though, FDA clinical data and science-based information on outcomes and risks were not available. (Some will argue that data was available from outside the US, but this was no acceptable science-based clinical data). US Surgeons initially limited LASIK to patients who required more than 6 diopters of correction leaving PRK for those who required less. PRK had proven to be problematic with higher corrections. They were also concerned about the long term effects of cutting the flap and felt that LASIK was warranted for those requiring significant corrections since they were handicapped when they were without corrective lenses.

LASIK- the initial FDA approval

Refractive surgeons early-on were concerned about offering an “off-label” procedure which put them at risk if anything should go wrong. The FDA, at the same time, was concerned about the growth of what was becoming a very popular unapproved “cosmetic” surgical procedure.

Surgeons met with the FDA to find a path for gaining the FDA’s approval. If successful, an approval would get them off the liability hook, and they could offer it as “FDA Approved.” The FDA wanting to get a handle on this fast growing procedure agreed to letting the surgeons sponsor a clinical study. The FDA agreed to review the data. The FDA would grant approval if the procedure were “proven” safe and effective. In reviewing the FDA Panel discussion and approval, one can only wonder why the FDA approved LASIK after a clinical study that was incomplete, had minimal follow-up, and did not meet the same rigor manufacturers were required to follow.

LASIK received its initial FDA approval in 1999, based on two physician-sponsored, not manufacturer sponsored studies – one for the VISK laser and one for the Summit laser. The manufacturers chose not to sponsor these studies – their products were on the market and expensive studies were not required to sell equipment. With an approval to sell, and with momentum building for LASIK, they needed to focus only on marketing, sales, and equipment service.

The FDA’s Ophthalmic Panel reviewed the two studies for approval in July 1999, three years after LASIK was introduced in the US and after several millions of LASIK patients. The transcripts of these proceedings are publicly available. They are PMA’s 990010 and P930034/S13 and are a most worthwhile read. The data used for the approval was deficient prompting key panel mem bers to abstain from the final vote. Below are some key excerpts and the panel votes.

Day One

PMA 990010 (VISX Star laser model C used with the Chiron ACS micro-keratome)

Page 42 – Follow-up or “accountability as shown here with 90.3% at 3 months, dropping to 76.3% at 6months….”

Page 67 – Dr. Pulido: “I would like some clarification from Jan Callaway about the patient accountability concerns and how she feels about the fact that there was 43 percent exclusion of the data”

Page 82 – Dr. Bullimore: “…The biggest is this issue of accountability…One characteristic of the PMA is the very variable accountability of these clinics. Overall the accountability is less than 75 per cent at 3 months and less than 63 percent at 6 months…So, the potential for patient bias or surgeon bias or investigator bias is considerable because of this at best mediocre accountability…The range of approval, also, has relevance to the question of corneal ectasia, and there are a number of reports and comments in the literature by very distinguished people in the field about the risk of corneal ectasia above minus 10…I would point out that the potential for long-term changes in refractive error still exist. Only going to six months would not, for example, demonstrate the long-term hyperopic shifts that we saw in the PERK Study (for RK).”

Page 89 – Dr. Pulido: “…but I have strong concerns regarding accepting the study as a whole because of the data set and if the FDA accepts this kind of study were accountability is only 57%, only because there was a large number of patients where will we stop?…the doctors should be chided for bad science..”

Page 92 – Dr. Yaross: “I think one of the messages that intended or not is sometimes perceived is that there are different standards for investigator-sponsored PMAs brought to this panel than for industry sponsored PMAs, and I think that is something the panel should be aware of.”

Page 96 – Dr. Ferris (National Eye Institute): “…and the fact that there is even the 15 or 20 percent missing inform ation when we have bars that say you cannot have more than 5 percent of this or 1 percent of that…that tells me that as you added more patients you are reducing the mean and suggesting that the missing information might be in the direction of more harm or at least less efficacy and that is the concern…”

Page 96 – Dr. McCulley (Panel Chairman): “In the guidance document there is a target, yes.”

Page 96 – Dr. Matoba: “Ninety percent, So, okay.”

Page 101 – Dr. Rosenthal (FDA): “…the guidance is guidance, and as you know the office has I think quite publicly stated that is general for the office of Device Evaluation an 80 percent level is generally acceptable of accountability.”

Page 143 – Dr. McCulley: “..so just for the data as presented does the Panel feel like there is sufficient follow-up for the correction of myopia with or without astigmatism in the ranges indicated?’

Vote – 2 were yes, six were no.

Page 147 – Dr. Ferris: “And I take it this is an issue because the guidance suggests 1 year (follow-up). Is that right?”

Page 182 – Dr. Van Meter: “…why are you unhappy with less than 90 percent data now when you have not been happy in the past?’

Page 190 – Dr. McCulley: “…All right, we have a motion on the floor for approvable with the conditions that have been read into the record, and it has been seconded…All those in favor of the motion, please raise your right hand high?”

On the vote for approvable, there were 9 yeas, 0 noes, two abstentions.

Page 192 – Dr. Macsai: “I abstained because there is a body of information out there that is in the scientific literature that has undergone peer review regarding this subject which provides knowledge regarding this procedure. However, I cannot assess that true safety and efficacy has been established due to the lack of accountability.”

Page 193 – Dr. Ferris: “I abstained from the vote because it is my belief that the data that were included I this PMA are not scientifically adequate for approval.”

The Panel Session ended with this recommendation to approve this LASIK application, with labeling conditions, as sponsored by the physician group. The uniqueness of this approval concerns itself with the low “accountability” and the short six months follow-up. No company would even be allowed to go to panel with data this inadequate. In the preceding fall, this panel recommended 3 year follow-up as a guideline for refractive IOLs.

Day Two

PMA P930034/S13 (Summit Apex Laser with unspecified microkeratome)

Page 100 – Dr. Kezirian: “ You will see that the PMA cohort has, at three months, an accountability rate of 89.6%, and at six months, 84 percent.”

Page 131 – Dr. Sugar: “We discussed this issue at very great length yesterday (VISX approval), and I don’t think it needs to be reviewed, but I think that the exclusion of sites that did badly is not an appropriate way to present data, either badly in accountability or any other regard.”

On the vote for approvable, there were 9 ayes, 0 noes, one abstention.

Page 172 – Dr. Ferris: I abstained from the vote of approvable with conditions, in part to be consistent, but also because I think in an issue of a degree of public health importance such as this, and where the side effects, statisticians always say compared to what…I believe with a follow-up of missing information of this magnitude, that I can’t adequately assess what that is…I am not a corneal surgeon…so I don’t want to vote against it, but neither do I feel I can vote for it.”

The panel session ended again with a recommendation to approve with conditions.

Unfortunately, the study as we shall see in future years was incomplete and flawed. Many refractive surgeons downplayed the physician study saying that improvements in technology had been dramatic since the study, and in their hands, outcomes were significantly better. Of course, there was no scientifically based proof to support this. “They are out of date.” “I get better results.” “They did not consider the new (whatever they wanted to emphasize) in doing their studies.” This refrain (since the days of RK) is repeated after each new study is released since most study results do not agree with what is being advertised to consumers. Unfortunately, time has proven that claims like these are to be taken lightly and these boasts of better results are overstated. FDA study results (with the exception of this first, physician sponsored study) should be taken seriously. Because as you will see shortly, physician generated data (even this so called physician sponsored PMA) does not jive with what we now know about LASIK, its outcomes and its complications.

“Company Sponsored” LASIK PMAs

Note the data set – the complications and incidence of these complications – provided in this, the first company sponsored FDA study of LASIK. The data set differs significantly from the physician sponsored FDA study, and gives cause for concern about what was marketed to an unsuspecting public.

Approval for the Bausch & Lomb Technolas â„¢ 217A Excimer Laser for LASIK

The following data were presented to the FDA for the Bausch & Lomb Technolasâ„¢ 217A Excimer Laser System for LASIK. The date of this document is 2/28/00 and is publicly available.

This is the first company sponsored PMA for a laser used in LASIK. Therefore these are the first data presented in the more rigorously controlled company sponsor clinical trial. These data come from a rigorously controlled study with the normally high accountability.

Note that while some people had improved symptoms, others had worsening symptoms Approval, I believe, was based on the fact that the “improved” vs. “worsened” averaged out. This was good news for those whose conditions improved, but bad news for those whose condition worsened. These data suggest that symptoms LASIK patients were complaining about were real and more significant than what patients had been told since the introduction of LASIK to the US. And the incidence levels were more significant than what the informed consent’s use of the word may” suggested.

Data was presented for both 3 and 6 months for “eyes treated without astigmatism” and for “eyes treated for astigmatism.” Only one set of data is shown since “without astigmatism” is considered to be “best case” forany refractive procedure, and since six months is the longest time presented after surgery. To see all of the data, this document is available in the FDA archives. It is marked 217A-PINFO.

Eyes Treated Without Astigmatism at six months*

Visual Symptom Better No Change Worse

Dryness 21.6% 52.3% 26.1%

Halos 4.5% 76.1% 19.3%

Fluctuations of vision 6.8% 73.9% 19.3%

Variation of vision in dim light 14.8% 67.0% 18.2%

Light Sensitivity 14.8% 67.0% 15.9%

Blurred Vision 11.4% 73.9% 14.8%

Night Driving Vision 22.7% 63.6% 13.6%

Glare 10.2% 77.3% 12.5%

Variation of vision in bright light 6.8% 86.4% 6.8%

Redness 20.5% 73.9% 5.7%

Variation of vision in normal light 1.1% 93.2% 5.7%

Headaches 12.5% 83.0% 4.5%

Gritty feeling 18.2% 78.4% 3.4%

Tearing 9.1% 88.6% 2.3%

Burning 6.8% 90.9% 2.3%

Ghost images 1.1% 96.6% 2.3%

Double vision 3.4% 95.5% 1.1%

  • While it is not stated, some of the symptoms may occur in conjunction with other of these symptoms.

University of Rochester survey of FDA approved lasers

The University Of Rochester Medical Center presently has a Summary of Surgical Results Data for all FDA LASIK approved Laser Systems (The University of Rochester states all source data can be downloaded from www.fda.gov/cdrh/lasik/lasers.html ) Note the percentage who achieved “20/20 or better” by amount of required correction. This is certainly not 90% or 100%. It falls way short. Those who miss the mark will either have re-operations (enhancements) or will have to live with much less than perfect eyesight (even in high contrast environments).

They promote this to highlight the data from the newer B&L systems, which they use, and are promoting.

For systems other than the newer B&L systems, it shows uncorrected Snellen* results** as follows :

For -1.00 to –1.99 diopters of correction 46.4 to 88.2% achieved 20/20 or better**

For -2.00 to -2.99 diopters of correction 51.5 to 73.4% achieved 20/20 or better.

For -3.00 to -3.99 diopters of correction 41.7 to 67.9% achieved 20/20 or better.

For -4.00 to -4.99 diopters of correction 45.7 to 64.3% achieved 20/20 or better.

For -5.00 to -5.99 diopters of correction 40.5 to 50.0% achieved 20/20 or better.

For -6.00 to -6.99 diopters of correction 27.8 to 51.1% achieved 20/20 or better.

For -7.00 and above 32.0 to 49.1% achieved 20/20 or better.

* these data do not measure the quality of vision, eg. contrast sensitivity. The Snellen eye test was used and only measures vision in high contrast situations.

** depending on system used.

The Medical Center’s (which appears to be marketing LASIK as StrongVision) stat sheet goes on to show that patients done on the B&L system achieve 20/20 or better 84.8 to 87.3% of the time. These data do not, to my knowledge, include re-operations, which are called enhancements. With re-ops, some of these may achieve 20/20.

REPORTED PATIENT PROBLEMS AND THEIR INCIDENCE

As you read the following publications, note the incidence of visual symptoms. These were not listed in the physician sponsored PMA data set (discussed previously), clearly supporting the abstentions by those who were concerned that the study was incomplete and insufficient. Unfortunately, for the millions of patients who underwent LASIK, either pre- or post- FDA approval, they made their decision on incomplete and insufficient data.

“Patient Satisfaction and Visual Symptoms after Laser In Situ Keratomileusis (LASIK),” Bailey, OD, MS, et al, Ophthalmology, Volume 110, Number 7, July 2003

“97% would recommend the procedure to a friend…Halos were reported by 30%, glare by 27%, and starbursts by 25% of all subjects…The 25-30% rates of night vision symptoms here are higher than another previous study with a higher survey response rate but similar to or lower than other studies of PRK and LASIK…Increased age is associated with decreased satisfaction…Prospective LASIK patients still should be informed that LASIK has been associated with decreased satisfaction, and we specifically found that there is a 50% increased odds of dissatisfaction for every 10-year period increase of age.”

“LASIK Has a 10% “failure” rate”, Michael Hatcher, www.optics.org, May 8, 2003

“That’s the conclusion of a study by researchers at the New Jersey Medical School. But because only most only need one eye retreated, it means that one in five patients actually undergo a second LASIK procedure.

…This is something we have been saying for a very long time – people are not being fully appraised of their degree of risk as it applies to their own set of eyes,” said Link (Ron Link, Executive Director of The Surgical Eyes Foundation).”

 “Night Vision Disturbances After Corneal Refractive Surgery”, Fan-Paul, MD, MPH et al, Survey of Ophthalmology, November-December, 2002

“A certain percentage of patients complain of ‘glare’ at night after undergoing a refractive surgical procedure.

When patients speak of glare they are, technically, describing a decrease in the quality of vision secondary to glare disability, decreased contrast sensitivity, and image degradations, or more succinctly, ‘night vision disturbances.’ …In most cases of corneal refractive surgery, there is a significant increase in vision disturbances immediately following the procedure. The majority of patients improve between 6 months to 1 year post-surgery…

With the exponential increase of patients having refractive surgery, the increase of patients complaining of scotopic or mesopic vision disturbances may become a major public health issue in the near future….” In the conclusion, the authors note with regards to existing testing methods, “ …lack of standardization, lack of scientific validity, hard to interpret by physician, time to administer test, hard to interpret by patient, cost, lack of correlation with symptoms, lack of familiarity with test, and superfluous…”

They go on to state, “an aging population with perplexing night vision impairments such as developing cataracts, dry eyes, or age-related macular degeneration may have worsening problems which may have a significant impact on public safety and health (in conjunction with previous refractive surgery).”

“Most Patients seem Happy after LASIK But They Still May be Having Vision Problems, German Study Suggests,” John F. Henahan, www.escrs.org, October, 2002

“Although most patients who undergo myopic LASIK appear to be quite happy with the vision they achieve after surgery, they may, in fact, have measurable and sometimes significant problems with glare, halos and contrast sensitivity…However, when they were examined with a variety of objective measuring instruments, their vision was not really as good as they thought…When the Regensburg investigators used objective measurements to determine contrast sensitivity, they found that 24% had worse vision after surgery than they did before. That level of contrast sensitivity corresponds to dim -light conditions on a late autumn afternoon, and the difference was statistically significant. In addition, at 5% contrast, which simulates to night –time vision, 54% had problems…(for glare testing) 53.8% had significant problems with this test, which could be considered serious enough reduced their vision to the extent that it would interfere with their ability to drive a car…In another test (for halos), 60% were found to have some level of halos, although only 32% of the patients had subjective complaints…Therefore, even when our BCVA Snellen measurements tell us that the patient is seeing quite well, these (other) objective measurements tell us that they may be having problems especially at night…but if they come back and you question them carefully, you may find that they are no longer driving cars anymore or their vision is somewhat disturbed in the evenings.”

“Consumers on LASIK: Down, but Not Out,” Judith Lee, Senior Contributing Editor, Review of Ophthalmology, Vol. No. 139:101, Issue: Oct 15 2002

“…VisionWatch Eyewear—a partnership of NOP/World Group, Jobson Publishing L.L.C. (publisher of Review of Optometry) and Greenfield Online—conducted a telephone survey of 72,000 U.S. consumers between June 2001 and June 2002. All respondents were age 18-65, and either wore some form of vision correction or had undergone refractive surgery.

Most patients surveyed who have had refractive surgery complained of nighttime glare, dry eyes, double vision and/or blurry vision. Still, most say they had recommended the procedure to others. Also, many spectacle or contact lens wearers surveyed say they are aware of refractive surgery procedures,with LASIK the most recognized. About one-third of these patients say they will likely have refractive surgery. The patients who don’t expect to have LASIK or other procedures are most worried about safety or complications. Additional concerns: cost, whether the outcome would be “worth it,” and whether the surgery will be effective as one’s vision changes.

You’re Number 1 (The Importance of the Doctor)

The survey clearly shows that eye doctors have much influence on patients. Of those who had already scheduled refractive surgery or were very inclined to have it, 35% say “my eye doctor” was the most important source of advice regarding surgery. Older patients, those with annual incomes above $60,000, and those living in the West are most likely to take their eye doctor’s advice—although patients across the board list the eye doctor as their top adviser….

LASIK Rules

Only about 1.5% of the total sample had already had a refractive procedure. Of this group, 87% had LASIK, with the rest divided between PRK and LTK. A surprisingly high percentage of people who had already received surgery made less than $40,000 a year. They tended to be young, live in the West or South, and had their surgery more than one year ago…

Nearly 90 % of patients had bilateral surgery, and 83% were myopic. About half were astigmatic. Six of 10 say they have suffered from haloes and glare at night and/or dry eyes. Patients age 35- 44 and those 55 and older complained of dry eyes the most. Patients age 45-54 had the most problems with haloes and nighttime driving…

What Matters

Refractive-surgery candidates are most interested in improving their vision, but also would like to stop wearing glasses or contact lenses. These were the two top reasons given by patients who had already scheduled surgery or were very likely to have it.

Better vision was most important to older patients, those who made less than $40,000 and those living in the South. Eliminating hassle was most important to younger patients, those earning more than $60,000 and those in the West.

When asked about other reasons they would have refractive surgery, patients mention eliminating discomfort of contact lenses or glasses, lower cost over the long term, never getting caught without glasses, and improving self image.

When deciding whether to have surgery, these highly interested patients acknowledge the risk of complications and the cost as concerns. Patients age 18-34, living in the Northeast and making more than $60,000 are most worried about complications. The respondents most worried about cost? Southerners who are 35-44 and make less than $40,000 a year…”

“Laser In Situ Keratomileusis (LASIK) for Myopia and Astigmatism: Safety and Efficacy – A Report by the American Academy of Ophthalmology”, Alan Sugar, MD, MS, Christopher J. Rapuano, MD, et al, Ophthalmology, Volume 109, Number 1, January 2002.

“Conclusions: Serious adverse complications leading to significant permanent visual loss such as infections and corneal ectasia probably occur rarely in LASIK procedures; however, side effects such as dry eyes, nighttime starbursts, and reduced contrast sensitivity occur relatively frequently. Some of the most satisfied eye care patients are LASIK patients, and the goal is to continue to increase the percent of patients who are happy with this surgery.”

“LASIK Patients at Risk for Long-Term Eye Irritation, Study Says,” American Academy of Ophthalmology, Press Release, July 2, 2001

“Based on a July, 2003 study published in Ophthalmology. Authors say that LASIK patients with reduced ocular sensitivity due to long term wear may take years to regain normal ocular surface sensitivity, if ever…fluctuating vision reported by many in study improved after blinking or use of preservative-free artificial tears.”

DISCERNING THE TRUTH ABOUT “THE NEXT BIG THING”

The patient/consumer must be diligent with the introduction of “improved’” and/or “new” refractive methodologies and technologies. The “refractive surgery medical-industrial complex” is looking for “The Next Big Thing.” The refractive surgery market has contracted since its peak in 2000. Today, lasers are underused. Competition for the patient is fierce. Surgeons, national chains, and manufacturers are seeking a real or imagined competitive edge. With high fixed costs in laser based refractive surgery, financial problems lurk for those who fail to achieve adequate patient volume. The environment requires caution and discernment for those interested in “getting rid of their glasses and contact lenses.”

History is a guide to how emerging procedure improvements and new approaches will be marketed to gain a competitive edge. Initially, PRK surgeons advertised that PRK was superior to RK since the procedure was not surgeon skill based but rather technology based. PRK brought to the procedure “Star Wars” technology, and micron accuracy. It was not too long after PRK was introduced that LASIK was introduced and LASIK competed against PRK on the basis of day one results – pain free and great vision. As competition grew, surgeons then competed on experience as LASIK was touted as skill based. Advertising moved to highlighting how many procedures a surgeon had done.

The low price National Chains entered the market in 2001 and price became the differentiator. These Chains believed they could create scale, leveraging the marketing/advertising expenses, and could provide LASIK, without compromising the quality of the procedure, at a much lower cost. The marketing costs per patient in those days were close to $400 per eye.

Those surgeons who were not part of a chain were at a competitive disadvantage, including most of the Academics, and refractive elite. To retaliate, this group began to equate quality with price through advertising, and as spokespeople for local news stories focused on LASIK catastrophes. The overall strategy was to create fear in the mind of the consumer towards a lower priced procedure and national low priced chains.

The latter tactic is interesting. There is no data to support any claim that price is related to the quality of the outcome. In fact, the data presented thus far shows that the procedure has certain flaws, which are not surgeon or price dependent. Patient’s should be concerned more with the procedure than its price. As price and quality became an issue, another group of surgeons, to differentiate themselves, advertised that they were the go-to surgeons for repairing LASIK complications. The message was “we are the best since we do the really tough cases.” Many of these were surgeons who promoted LASIK in its introduction as safe and complication free. Now, it has complications but if you come to me, I know how to deal with them. One reporter I know was confused as she talked to doctors She said that these doctors assured her only one year before that LASIK was problem free. Why were they now pushing their importance as the “go to docs” for LASIK problems. She wondered what problems were being fixed if none existed!

“Off the Cuff: LASIK and Contact Lenses – Can’t We All Get Along?” Arthur B. Epstein, OD, FAAO, Chief Medical Editor, Optometric Physician, June 16, 2003

“Over the past month I’ve seen signs of a ramping up of anti-contact lens activity by some ophthalmologists involved in refractive surgery. It would seem that the success of silicone hydrogel contact lenses is makin LASIK surgeons a bit nervous. After all, continuous wear contact lenses do make an attractive alternative to irreversible refractive surgery for many patients.

Some in the contact lens community believe that the anti-extended wear onslaught of the past decade had politico-economic motivation. Whether this is true will always remain conjecture. However this time around, with some optometric offices filled with LASIK disasters seeking rehabilitation and relief, the shoe can easily be on the other foot…”

Wavefront Guided LASIK

As you read about what is in development pipeline for commercialization, keep in mind the economics of refractive surgery, the economic investment and burden for a surgeon or a center, and the absolute need to increase throughput to remain solvent. Surgeons will adopt new procedures and/or modifications to old procedures, whether they are ready for prime time or not, due to competitive pressure.

Wavefront is a good example. Surgeons, even if they do not believe in it, will adopt it and push it so they will not be left behind. Despite wavefront’s adding little if any value, surgeons and national chains will try to use it to differentiate themselves from others (particularly those who cannot afford the change) and to raise prices. The hype and misinformation have already begun as some of those who have adopted it are already touting it as “safer” than the original LASIK. Since there is no FDA clinical data to support the claim of “safer”, this is a bogus and illegal claim. Like the original LASIK, it involves a flap, and the flap is still the major source of short term and long term “safety” problems.

 “Challenges to Wavefront Correction, Introduction,” George Waring, III, MD, FACS, FRCOphth, Editor-in-Chief, Journal of Refractive Surgery, Volume 18, November/December 2002.

“These, along with dozens of articles in other journals and presentations, can leave the impression that wavefront analysis will lead us to the holy grail of super vision for our patients, most seeing 20/10 without correction. Such a simplistic cartoonish view is, of course, unrealistic and inaccurate.”

“Wavefront technology: A New Advance That Fails to Answer Old Questions on Corneal vs. Refractive Astigmatism Correction,” Noel A. Alpins, FRACO, FRCOphth, FACS, Journal of Refractive Surgery, Volume 18, November/December 2002.

Page 738. “A second issue is that the correction of all ocular aberrations at the corneal surface pays no regard to the effects of corneal irregularities that will be produced by this uneven mode of treatment. Refractive surgeons have long known that corneal regularity (orthogonal and symmetrical astigmatism) is the foundation of a super visual outcome. Corneal irregularity can only increase if all corrections for internal optical errors are surgically sculpted onto the corneal surface without considering any pre-existing corneal topographical irregularities.

Technical challenges also impair our ability to accurately align the ablative patterns to make the focal changes to correct underlying optical aberrations. It is difficult to permanently change regional corneal shape in this uneven manner, especially when the treatment can be neutralized by epithelial healing. Any change in the crystalline lens will also complicate the long-term usefulness of wavefront driven changes.”

“Thirty-four Challenges to Meet Before Excimer Laser Technology Can Achieve Super Vision,” Isaac Lipshitz, MD, Journal of Refractive Surgery, Volume 18 November/December 2002

“In correcting higher order aberrations, minor changes count. Corneal surface changes must reach an accuracy of one micron; only one or two laser shots delivered in a slightly wrong position or incorrect timin will interfere with the desired result…These 34 challenges are divided into four main groups:

  •  Ocular Challenges
  1. Changes in (the eyes) wavefront with age…new aberrations will appear subsequently withage…
  2. Changes of wavefront during accommodation (dynamic vision factor). (Accomodation is your eyes ability to focus far and refocus near) Even if we achieve super vision for distance vision, when looking at near, newly higher order aberrations may occur.
  3. Effect of pupil size on higher order aberrations. Change of pupil size – in light, dark, accommodation, convergence – dramatically affects vision…
  4. Biomechanical differences among corneas before surgery. Corneas differ considerably in their biomechanical properties…depends on age, corneal thickness, hydration, and collagen properties…
  5. LASIK flap biomechanics. Once a LASIK flap is created, the biomechanical properties of the cornea change dramatically depending on the depth of the incision, diameter of the flap, location of the hinge, and uniformity of the flap…even it the flap is returned to its place without ablation – there is a change in the wavefront measurement…
  6. Changes in tear film. Tear film properties in different eyes occur because of common pathologies such as dry eye and blepharitis…
  7. Changes in corneal thickness after laser surgery…affects tear film, the biomechanical properties of the cornea, the healing process, and mechanical strength of the cornea…
  8. Changes in wavefront during cycloplegia…
  9. Variation of ablation rate in different depths of the cornea…
  10. Variation in corneal thickness in different meridians. Usually the cornea is thinnest in the inferior or inferotemporal area, probably because these areas are dryer (they get less tears)…
  •  Uncontrolled Optical Changes During the Healing Process
  1. Corneal epithelium wound healing…
  2. Corneal collagen wound healing…
  3. Effect of corneal biomechanics after surgery…
  •  Technological Limitations of Surgical Equipment
  1. Eye positioning during preoperative measurement and laser treatment.
  2. Accuracy of laser ablation…the exact amount of corneal tissue removed with each laser pulse changes continuously…
  3. Microkeratome accuracy and profile. At a specific setting, microkeratomes cut flaps of varying thickness – varying among manufacturers, among instruments, among eyes, and at different regions in a single flap…
  4. Tracking the location of the laser beam…
  5. Decentration…
  6. Accuracy of the wavefront sensors…
  7. Computer programs for the laser…the current capability of computer programs to integrate this enormous about of data and to give to each piece of data the exact value required by the laser is questionable…
  8. Accuracy of the laser. Two instruments from the same company may work differently…
  9. Consistency of one laser. The laser pulse energy changes all the time, so the instrument calculates and uses an average energy…
  10. Chromatic aberrations are not detected by aberrometers…
  11. Location and shape of wavefront measurements…
  12. Objective aberrometers measure only the optics of the eye…This influence on surgical outcome is now known; perfect optics do not assure perfect vision…
  •  Uncontrollable Surgeon Variables
  1. Dryness of the ablation surface…
  2. Environmental issues during surgery…The temperature changes constantly due to the heat generated by photoablation…
  3. Retinal problems of aberration-free optics. We still don’t know if directing all the rays of light on the fovea (area of least confusion) – which is what we are going to do if we want to create super vision – will cause thermal or toxic damage to the retina. Maybe that’s why there are optical aberrations in our eyes…
  4. Possible worsening of visual performance with inaccurate surgery…
  5. Effect of enhancement procedures on the wavefront. Currently, we have an enhancement rate of 5% to 25%, which is done only for lower order aberrations. If we expect to correct many higher order aberrations, a considerably higher number of re-operations may be needed. But, each enhancement procedure has its own effect on the total higher order aberrations because of lifting and repositioning of the flap.
  6. Positioning the flap after ablation…
  7. Flap edema after ablation…
  8. Curvature of the flap and bed do not fit perfectly after ablation…
  9. 34. Irreversible procedure…the original condition of the eye cannot be restored. …Refractive surgery – especially LASIK – must overcome many challenges to reach this goal (super vision).”

“Biomechanics of the Cornea and Wavefront-guided Laser Refractive Surgery,” Cynthia Roberts, PhD, Journal of Refractive Surgery, Volume 18, September/October 2002

Page S589+. Although it has been demonstrated that image quality after customized procedures is improved over that of standard procedures (based on higher order aberrations), there are still significant aberrations induced after a wavefront-guided procedure that are neither expected or predicted… Figure 1…illustrates a preoperative cornea where the inter-lamellar spacing is defined by parameters including geometry of the system, the tension carried in the lamellae, the internal fluid pressure, the interlamellar cross-linking, and the load imposed by the intra-ocular pressure…Also illustrated is a postoperative cornea…The remaining peripheral lamellar segments are relaxed to the maximum depth of the cut, and cannot bear the same tension as in the preoperative state…(For LASIK) there are only certain shapes the cornea will accept, and the “ideal” shape that produces the “ideal” correction is likely not among them. Any procedure that circumferentially, or near circumferentially, severs corneal lamellae will produce a biomechanical response that will alter corneal shape in a manner that cannot be predicted with wavefront analysis alone.

 “Some foresee limitations in wavefront technology,” Ocular Surgery News, August 1, 2002

Michael Goggin, MD, of Adelaide University said, “Aberrations increase with age. What we do now may lose its effect in ten years. He “wondered whether there would be problems matching IOLs to customized corneas in patients who develop cataracts after wave-front ablations.”

“Effects of Accommodation and Flap Biomechanics May Complicate Quest for Super-Vision,”” EuroTimes, March 2001,

Ionnis Pallikaris, MD, pointed out in his presentation to the Winter Refractive Surgery Meeting in Cannes, that “vision in the human eye is not a static, but dynamic process, and the process of accommodation (adjusting for near and far vision) in a day-to-day basis and as an individual ages can influence the wave front aberration profile of the eye and consequently confound attempts to achieve “super-vision” with LASIK or other refractive procedures.

“Reflections on Refractive Surgery”, Olivia Serdarevic, MD, EuroTimes, March 2001.

Reporting on the Winter ESCRS meeting in Cannes….”There was also a consensus about the frustration with our current incomplete knowledge of and ability to modify many optical, biomechanical and biomolecular effects of refractive surgery…The speakers agreed that the endpoints of 20/10 or better visual acuity and aberration-free vision, which have been promoted not only to ophthalmologists but also to patients, represent very simplistic, naïve and erroneous assessments of our visual function and needs…Wavefront aberrations of the optical system are dynamic.. How can successful integration of wavefront analysis and laser ablation occur before complete standardization of measurement in normal eyes during the performance of different visual tasks over time? …How can we use wavefront information for computer programming of laser ablation in normal eyes before we adequately analyze wavefront aberrations induced by LASIK flaps and existing laser ablation methods and correlate these aberrations with corneal shape, biomechanics and wound healing?…Many…attending the meeting were getting tired and worried about exaggerated and erroneous “super vision correction” claims.”

IntraLASIKâ„¢ (Intralaseâ„¢ LASIK)

IntraLASIK is an all laser procedure that provides, most importantly, a laser alternative to making the flap. It claims to eliminate much of the variation caused by the mechanical microkeratome in flap creation. Some surgeons have purchased this to differentiate themselves from those that use a mechanical device. Some of the surgeons promoting IntraLASIK are promoting it as “safer” than LASIK. There have also been several recent stories in the mainstream news talking about it being safer than traditional LASIK with a mechanical microkeratome. Be aware that there is no FDA data to support this claim and it is illegal to for anyone to make this claim.

While there are trade-offs to using IntraLASIK over the microkeratome, some of which are positive, don’t forget that a flap, regardless, of how it is made, is a flap. The creation of the flap is one of the fundamental flaws of LASIK as it destroys the homogeneity of the cornea, and weakens it. Only time will tell if LASIK and/or IntraLASIK leads to a loss of effect (as the cornea becomes steeper, or bulges out) or in worst case, leads to ectasia.

LASEK (an emerging off-label procedure)

“LASEK learning curve steep, despite experience, surgeons say,” Ocular Surgery News, July, 2003

“Mastering laser epithelial keratomileusis is challenging, and creating the epithelial flap is more difficult than the literature suggests…The study should alert surgeons that ‘LASEK is not a reproducibly easy procedure at its start,’ the authors said. ‘Moreover, additional studies should be conducted with longer follow-up to guarantee that corneal haze (incidence of 65%) is not a long-term problem ….”

“Surface ablation gets high marks at LASEK meeting/ highlights of the international LASEK congress included discussion on corneal haze and night vision,” Nicole Nader, Ocular Surgery News, July 1, 2003

“Laser epithelial keratomileusis is a promising technique, but the pitfalls of older surface ablation techniques (PRK), such as corneal haze, are still an issue….Significant corneal haze ‘may’ occur after LASEK…At 6 months postop, grade 0.5 haze was present in 58% of the patients, grade 1 in 25% and grade 2 in 8% of patients . (‘may’ in this context means an incidence of 91%!!!)…’ninety percent of my patients were testing positive for starburst phenomenon,’ he (Bruce Larson, MD) said….‘Results showed that LASIK produced significantly more starbursts than LASEK’…

LASIK pitfalls discussed….LASIK has the potential for complications that are not seen in other refractive procedures, including increased coma, keratectasia (ectasia) and surgeon-induced irregular flaps, according to a number of presenters…several surgeons described complications seen in LASIK but not in surface ablation procedures such as LASEK.”

Lens-based refractive surgery – Intraocular lense s (phakic IOLs)

Refractive (phakic) IOLs are on the horizon. These include products like the ICL and the Artisan lens. A these products are introduced, their proponents will layout the problems of laser-based procedures (LASIK, wavefront, etc.) as never before. Pay close attention to FDA data on inclusion data (who can benefit), on adverse events, complications, and visual problems. These procedures are the most invasive of any known procedure. The surgeon must go into areas of the eye that are very small and/or dynamic presenting serious new risks. As an analogy, this is comparable invasive surgery for the eye as open-heart surgery is for the heart.

These procedures may be marketed as reversible. Understand completely what that really means. To extract and replace a lens is no simple procedure and can lead to other problems. If someone markets this as reversible, ask to see the FDA outcomes/complication (post removal) data that proves reversibility. Do not accept “personal study” results.

“Some refractive procedures carry higher retinal risks, study finds,” Ocular Surgery News, September 29, 2003, Re: Study published in The Journal of Refractive Surgery, September-October, 2003

“Certain refractive procedures for myopia pose a greater risk of postoperative retinal problems than other refractive procedures, a large cohort study suggests. Phakic IOLs created the highest risk for retinal detachment in the study, followed by LASIK and then photorefractive keratectomy (PRK)…

…Retinal detachment occurred at a mean of 53.6 months after PRK in nine eyes (0.15%), 24.6 months after LASIK in 11 eyes (0.36%) and 20.5 months after phakic IOL implantation in 12 eyes (4%). Choroidal neovascularization occurred in 10 eyes that had undergone LASIK (0.33%), in seven with a phakic IOL (2.38%) and in one that underwent PRK (0.01%).”

”Multifocal phakic IOL an option for hyperopia,” Ocular Surgery News Supersite, September 15, 2003

MUNICH, Germany — A multifocal phakic IOL can be an efficient, potentially reversible refractive surgical option for patients with hyperopia, according to a presentation here. Georges Baikoff, MD, spoke on the use of a bifocal anterior chamber phakic IOLs at the European Societ of Cataract and Refractive Surgeons meeting. He shared the results of his personal study using the lens during a symposium on hyperopia…

…He said there was some incidence of glare and halos, but these were accepted by patients. There was also an acceptable loss of contrast sensitivity compared to preop, he said. “It is mandatory to tell patients that this is a compromise between excellent vision with spectacles and good vision with the IOL,” Dr. Baikoff said.

He noted that in using anterior chamber phakic IOLs, accurate biometry is necessary to ensure that patients have sufficient anterior chamber depths. Shallow anterior chambers are prone to angle closure, and there is risk of endothelial cell loss, he said.

“Lens-based refractive surgery shifting focus from the cornea to the lens,” Nicole Nader, Ocular Surgery News, July 1, 2003

“…on the other hand, lens -based surgery also carries considerable risks: the increased risk of intraocular procedures…, the possibility of complications associated with IOLs, the heightened risk of retinal detachment, and with phakic IOLs, the possibility of inducing secondary glaucoma or cataract…”

The ICLâ„¢ (the Implantable Contact Lens)

The ICL has been commercially available outside the United States for a number of years and is making its

way through the FDA approval process in the US. The ICL is a very small micro lens that is placed in the eye (very invasive surgery) in a very narrow space between the iris and the crystalline lens. It has had a history of problems outside the US with complications that include cataracts and glaucoma. The company that manufactures the lens claims that these problems have been solved. One interesting historical note is that those surgeons promoting the ICL changed the terminology relating to pre-cataract conditions to a new term, ”opacities”. “Opacities” is a benign and misleading term compared to pre-cataract or cataract. From an anatomical point of view, the ICL is being placed in one of the most dynamic and hostile environments of the eye. The iris and the crystalline lens (unless it has been replaced with an intraocular lens) are constantly moving. The iris opens and closes (like a camera lens) to let in the appropriate light rays, while the crystalline lens expands and contracts as it provides zooming power (accommodation) for reading and distant sight. If the ICL touches the iris, pigmentation of the iris, which provides your eye color, will be dispersed. This can lead to glaucoma, which, in turn, can lead to blindness. In addition, if the ICL touches the crystalline lens, the crystalline lens will develop an opacity, which historically has been considered a condition that could lead to a cataract. If it becomes a cataract, the natural lens must be removed and replaced by an intraocular lens. With the IOL, the eye loses its focusing capability. For those who do not need reading glasses, this may become a serious inconvenience. For those who have lost the ability to focus (usually over 50 years of age), this may not be a problem.

The ICL must be place exactly right to avoid complications. When you understand the maneuver that must be made to insert this lens, you will understand that this procedure requires great skill. If a claim,, or any semblance of a claim, of reversibility is made by a doctor, check the FDA approval. It is highly doubtful that the FDA will grant this marketing claim. Removing the ICL can result in touching either or both the iris (pigment dispersion/glaucoma) and the crystalline lens (opacity formation/cataracts). There is little if any margin for avoiding these problems in a removal.

The recent press releases and publications on this procedure need to be reviewed with great care. Hype and misleading statements have begun. For the publications, find out who the authors are and what relationship they have to the company.

One recent study argued that the complications like retinal detachments, glaucoma, and cataract were no different for the general population as they were for ICL patients. This was not a scientific head to head comparative study. The authors, some of whom are paid consultants for the manufacturer, implied that there is no need for concern when these problems occur after an ICL procedure. The study is bogus and the conclusion is not reasonable. For a study to reach this conclusion, it would require a scientific based longitudinal (five years or more) study including a control group that did not have the ICL. Studies and conclusions like this will be developed and promoted by ICL enthusiasts to convince an unsuspecting public of the procedure’s safety and efficacy.

The FDA panel has approved the ICL by a 8-3 vote for commercialization. Note the success rate in the Reuters news story on the approval, and information that the company provided preceding the approval. Note the differences.

UPDATE – US panel urges approval for Staar implanted lens, Lisa Richwine, Reuters, October 3, 2003

“GAITHERSBURG, Md., Oct 3 (Reuters) – A U.S. advisory panel on Friday voted 8-3 to urge approval for Staar Surgical Co.’s (NasdaqNM:STAA – News) implantable lens to correct nearsightedness, a possible alternative to laser eye surgery. If the Food and Drug Administration (News – Websites ) agrees with the panel, which it usually does, the product would be the first implantable lens sold for people whose natural lenses are intact. Implanted lenses on the market now are used to replace lenses following cataract surgery. Staar’s product is a refractive lens that physicians inject through a small incision and place behind the iris. The company aims to market the procedure for people age 21 to 45 with moderate to severe nearsightedness, or myopia. In a trial evaluating more than 500 eyes that had the lens implanted 84 percent had vision of 20/40 or better one week after the procedure. Three years later, 81 percent had that level of vision, the company said. Some patients experienced a gradual loss of cells in the cornea, an issue of concern to the panel. Some loss is normal, but panelists said they could not tell from the current research whether the loss would continue over time and damage the cornea. The company argued the cell loss stabilized in three to four years, but the panel said the research did not prove that was the case. “We don’t know what’s going to happen in 10, 20, 30 years,” said Dr. Marian Macsai-Kaplan, a panel member and chief of ophthalmology at Evanston Northwestern Healthcare in Illinois. The panel, by a 6-5 vote, urged the FDA to require Staar to monitor the cell loss annually for five years in certain patients who took part in the clinical trial. Some who dissented felt the long-term data should be collected before the device is allowed on the market. The Staar lens would offer an alternative to the popular Lasik surgery, in which physicians use a laser to reshape the cornea and correct vision. Staar calls its device an implantable contact lens. Panel member Timothy McMahon, professor of ophthalmology at the University of Illinois at Chicago College of Medicine, said that description was a “euphemism” that could mislead patients and should not be allowed…”

“U.S. Food and Drug Administration clinical trial of the Implantable Contact Lens for moderate to high myopia,” Staar Surgical, Ophthalmology, August, 2003

“Twelve months postoperatively, 60.1% of the patients had visual acuity of 20/20 or better, and 92.5% had an uncorrected visual acuity of 20/40 or better (ed note: 20/40 is required to drive a car without corrective lenses, therefore, 7.5% of ICL patients will not pass the driver’s license exam)…presumably surgicallyinduced anterior sub-capsular opacities (ed note: cataracts) were seen in 11 cases (2.1% of the group)…Patient satisfaction was reported by 92.4% of subjects on the subjective questionnaire.” In its investor related quarterly conference calls., the company has been projecting significant acceptance of the ICL procedure. Note that with an induced cataract incidence of 2.1%, 21,000 out of every million Americans having this procedure will develop cataracts. This will mean further irreversible surgery to remove what was once a healthy crystalline lens. It will be interesting to see how the company and surgeons market this procedure and what role the FDA will play in insuring that communications are not misleading.

“99.4% ICL Patient Satisfaction Level Linked to Superior Image Quality,” Press Release by Staar Surgical, July 24, 2003

The above press release (available on the Staar website) is a company press release reporting on a study conducted by a group of doctors who compared their LASIK results to their ICL results. These doctors are not unrelated parties to Staar Surgical, the manufacturer. These doctors then took their results and created a mathematical model to simulate the visual image of what a patient saw after each surgery. “The comparison clearly demonstrates a sharper and clearer image in ICL patients… the study concluded that the

ICL was safer and more effective than LASIK….and why the ICL will become a prominent choice for vision correction.”

This press release is another example of the care patients must take to discern the facts. First, the referenced study group was very small. The study was not a FDA regulated study. And the claims of “safer and more effective” are not only misleading, but are also illegal. Secondly, patient satisfaction percentages are an exaggeration when compared to the FDA study (which precedes this section). Finally, the creation of a mathematical model requires numerous assumptions. Those who are in experts in mathematical modeling know that the models cannot provide specific, accurate information but only trends.

The Artisanâ„¢ Lens

The Artisan lens is a Dutch (Oftech, Groningen, Holland) developed lens that has been in use outside the US for more than 15 years. The lens is placed in the eye between the cornea and the iris contrasting with the ICL which is placed between the crystalline lens and iris. The company founder, Jan Worst, MD., is one of pioneers in intraocular surgery. Dr. Worst is principled and well-respected. He and his company have historically not oversold any of their products. Unlike other procedures, excepting RK,  the outcomes and complications of the Artisan Lens have been fully characterized over 15+ years. The Artisan is in US FDA clinical trials today.

Since the Artisan may prove to be a formidable competitor with its well-defined outcomes, those vested in other less characterized procedures have already started to put negative spin on the Artisan. One competitive company, in its press releases, calls the Artisan approach archaic and first generation surgery, claiming that surgeons will want something more modern. This company also claims to have the “third generation” product, which is much easier for a surgeon to use. This company has steered clear of the longitudinal (over time) outcome/complication comparison and is focusing investors, surgeons, and interested patients on ease of use. Discerning patients would be well advised to focus on the Artisan’s years proven outcomes, and not something that is “easier to use.” While “ease of use” may save money in the short term for the surgeon, it does little for the quality of life of the patient over a lifetime.

Radio-frequency Procedures for hyperopia

An emerging group of procedures for hyperopia includes using heat to heat up the collagen in the cornea,causing it to shrink, and thereby causing the cornea to become steeper. Radio-frequency generated heat,and holmium laser heat are in this group of procedures. Heating the collagen is a potential solution for hyperopia since the cornea is too flat and needs to be steepened. The good news about these procedures is that they are, to a great extent, reversible. The collagen in the cornea tries to return to its original thickness, and the cornea to its original shape. The bad news is that outcomes are variable, outcomes may be short-lived, and the variability of the outcome will persist as the cornea tries to reach equilibrium.

SUMMARY

  •  Historically, the “refractive surgery medical-industrial” complex has used selective information to move patients to a refractive procedure. Patients must perform adequate diligence on their own to insure that they fully understand the risks and benefits of any procedure. Surgical Eyes, www.surgicaleyes.org, is a very valuable resource for those seeking balance.
  •  An illusion of safety has been created around refractive surgery through selective marketing. Purveyors of the illusion have a vested interest in keeping it going. Interests can range from financial greed, fear of exposure for doing something that can cause harm (thou shall not do harm), to the fear of being sued. The enormous complexities of human behavior that are motivated by greed, a fear of exposure, and financial loss are at work here. Fear leads to oppression and tension. The natural inclination is to hide from failure and to give the impression of perfection. If exposed, public rejection and lawsuits will follow. LASIK surgeons have made their Faustian bargain, and at some level they know it.
  •  LASIK has basic flaws that are independent of a doctor’s skill level (and what you are being charged). These include quality of vision degradation due to loss of asphericity, dry eye due to several anatomical factors, a weakened cornea, due to the creation of a flap. The weakened cornea may lead to the loss of correction effect and ectasia. Ectasia may be the Achilles heel for LASIK as the cornea never regains its initial strength and homogeneity after the flap is cut. Cells may seal the flap preventing infection but the underlying structure never heals and remains in a weakened state. The cornea, with time, may bulge forward due to the internal pressure inside the eye causing a loss of effect and/or irregular bulging.
  •  Dry eye is a troublesome problem. A great deal of money is invested annually in the search for a cure and effective treatment by private industry and the US government (NIH). It is a paradox that while money (taxpayers dollars) is being allocated to solve this problem, refractive procedures now add to the prevalence of this problem.
  •  “Real” complication rates of a procedure are openly discussed, not when the procedure is popular, but rather when providers are pushing newer, “improved” procedures and want to obsolete the older procedure.
  •  The anatomy of the eye is dynamic, changing with age. Optical aberrations are dynamic as well. Irreversible correction of vision (particularly with tissue removal), whether with LASIK or wavefront guided LASIK, only corrects vision at one point in time. This becomes problematic with age when new aberrations are introduced and/or with the onset of certain eye diseases. Upgrades are not anoption!
  •  Reaching 20/20 does not mean a high quality vision outcome. You may still be seeing 20/20 but you may have degraded vision, particularly in low light environments and at night. Nevertheless, with a 20/20 outcome, the “refractive surgery medical-industrial” will consider and promote you as a refractive success.
  •  The use of adverse events, complications, and visual symptoms are medical terms unique to ophthalmology and are easily misunderstood by consumers when asking the incidence of problems. Patients should be informed of the definitions, should consider visual symptoms a complication, and should ask physician/providers for a full accounting, incidence, and severity of all visual symptoms.
  •  Due to the significant upfront investment and operating overhead required to operate a refractive surgery center/practice, throughput (volume of procedures) is critical to financial survival. Investments made include the equipment, a highly trained staff, marketing and advertising, and referral payments to other physicians. High investment and high fixed costs have been key drivers in the marketing of refractive procedures.
  •  There is no science-based study showing that paying a price of $499 versus $1500 will provide you with a better outcome or fewer complications. Those who charge more prefer that patients believe price makes a difference, but only so they can generate more patient traffic at a higher prices. But, the bottom line is a LASIK is a LASIK, cutting a flap is cutting a flap.
  •  Vision is critical to athletic performance. Professional athletes like Jennifer Capriati (tennis), Troy Aikman (football), Tommy Armour III (golf) and Scott Hoch (golf) have had LASIK, and have had their vision and their performance compromised. For example, Armour lost all depth perception after LASIK, nearly lost his PGA exemption, and now wears specialty hard contact lenses to compete. A quick search on www.google.com will yield information about the other athletes. One very special athlete to watch closely is Tiger Woods. Ophthalmology hallway conversation highlights that Tiger had an 11.0 diopter (nearsighted) correction with LASIK, and up to three enhancements. He had problems immediately after the procedure (as reported by him on HBO), appears to have some difficulty on overcast days (lowlight), and is now struggling two years after his procedure. Due to the size of correction (the depth of flap required), Woods is at “high risk” for an unstable cornea and ectasia long term.
  •  Do your homework before you proceed with any irreversible refractive surgery procedure. Investigate all potential conflicts of interests. Make sure that all of the healthcare providers you are dealing with have your well-being foremost in their hearts and minds. You only have one pair of eyes!!
  •  Appendix A contains a recent introspective editorial by WilIiam Maloney, MD. suggesting that the surgical profession must move forward cautiously in adopting new refractive techniques so as not to repeat the mistakes of the recent past. While it is much less detailed and shifts much of the blame to “sales people”, it is a good companion piece to “The Promise of Refractive Surgery: A Promise Not Kept.” The failure of keeping the promise is not a “salesman” problem but rather an industry problem. There has been and continues to be an unconscious conspiracy within the “refractive surgery industrial-medical complex” placing the patient’s interests secondary to vested interests.

APPENDIX A

“Apply lessons of the LASIK experience to refractive lens exchange : Surgeons should take it slow when it comes to this new lens-based refractive technique,” William F. Maloney, MD, OCULAR SURGERY NEWS September15,2003

This month we are going to take a short detour from our discussion of specific techniques used in refractive lens exchange. I would like to bring out an issue that needs to be addressed as this procedure takes center stage. Let us call it the bandwagon effect or “the next new thing” problem. After rereading each of my past columns on refractive lens exchange, I noted a clear sense of concern in comments such as these:

“I am one who feels strongly that the transition from cataract surgery to refractive lens exchange ought not be taken for granted.”

“The techniques are proven and ready. As surgeons are we ready?”

“Performing cataract surgery without the cataract suddenly shifts the outcome equation to results that consistently must be very near perfect. In order to cross the 20/20 threshold responsibly, each surgeon must ask, ‘Have I prepared enough to be sure that I can deliver results at this level on a consistent basis?’”

What concern lies beneath statements like these? Why am I suddenly the sober cautionary voice of restraint? After all, my revolutionary credentials are intact. I was on the barricades teaching phaco and IOL-related innovations throughout the ’80s and ’90s. I have long been on record saying that refractive lens exchange is a procedure whose time has come, predicting that it will play a central role in the future of refractive surgery. Now that the tipping point has arrived and more and more surgeons are reaching the same realization, why am I suddenly feeling uneasy?

I think the answer is that I am concerned for what might happen to refractive lens exchange if it becomes the next new thing. I see increasing signs of hyperbole in such projections as the entire baby boom generation lining up to have their presbyopia corrected at $3,000 per eye just as soon as one of the accommodating IOLs becomes available. If experience with LASIK has taught us anything, it should be that hype is not in the long-term interest of our profession.

Jumping on the bandwagon

Refractive lens exchange, increasingly seen as the fastest growing refractive surgery technique, is currently a whitehot topic. After steadily working with this approach in my cataract patients since 1986, the suddenness with which this procedure has become a front-page feature has begun to make me uneasy.

It reminds me of the first years of PRK and then LASIK, which was almost immediately proclaimed the treatment of choice for all refractive error from +8 D to –20 D. It never happened, of course. As the limitations of LASIK have become increasingly difficult to ignore, the recommended treatment range shrunk steadily to what is now a range somewhere around plano to –8 D. This is close to LASIK’s starting point when it was introduced on the heels of radialkeratotomy.

No one would argue that LASIK is not a major advance over RK. Significant progress was made, but in getting there, we got it backward. Instead of a measured, step-wise advance from —7 D (where RK had brought us), we joined in a collective leap of faith to –20 D and have spent a good part of the past decade backpedaling. How did we manage to get this one so wrong? I think it happened in part because LASIK was arguably our first bandwagon phenomenon — jump on now or risk being left behind. The seeds of the LASIK letdown were sewn from the start when LASIK was snagged by the next new thing phenomenon. The rest is history — a history that we mus t not repeat and with lessons that we must be sure to learn.

Too far, too fast

This bandwagon effect was enhanced by several factors. At least part of its origin can be found in the phaco and IOL revolution. We are all aware that this first technology-driven revolution led to a golden age of unprecedented progress in cataract and refractive surgery. Ophthalmology can be justifiably proud of the truly remarkable accomplishment that is cataract surgery today.

Revolution, however, is almost always a two-edged sword, and history repeatedly tells us that revolutions can end up devouring themselves if they are unchecked and allowed to carry too far. This phenomenon — call it overshoot — typically occurs because of the inevitable transfer of power at the center of every successful revolution. The principal players in the old power structure either capitulate and join the revolt, or they are marginalized. Either way, the old guard’s conservative, usually self-interested voice of restraint and moderation is silenced. Like a coiled spring suddenly released, the momentum of unchecked forces for change can easily carry too far, jeopardizing the original gains of the revolution.

This historical template aligns perfectly with the phaco revolution. After a struggle (Ridley, Kelman and many early pioneers have all described this), the old guard of traditional ophthalmology finally capitulated and joined the ranks of phaco and IOL surgeons. They had seen their influence eclipsed. They had lost the spotlight to a ragtag army of private practitioners who took control of the podium, describing small-incision cataract surgery performed in unprecedented volumes with remarkable efficiency and vastly superior results.

The old guard learned all too well the futility of resisting the power of an idea whose time had come. It is hardly surprising that they were determined not to be on the wrong side of the next revolutionary concept when it first came into view. The stage was set with the bandwagon at the ready. Ophthalmology (surgeons and industry) scanned the technology-laden horizon for the next new thing. It was PRK and then LASIK, and the scramble to get on board erupted with a vengeance.

Progress with precautions

At the core of the next new thing problem is that it does not encourage the slow, steady and thoroughly verified progress that patients assume has already occurred by the time they encounter a new technique. The threshold for accepting and utilizing new technology tends to fall beneath the level required by the more sober long-term demands of our profession. In this overheated environment with a sense of urgency not to miss the boat, our collective point of persuasion can get reset too low, blurring the vital distinction between science and salesmanship.

We practitioners can too easily forget the one thing we must never forget: The industry representatives are the salesmen, and we are the scientists. Hype is often a completely appropriate tool for the sales force with specific short-term financial goals or a strategy for gaining market share. For us physicians, it can only be counterproductive. There is a line at which the interests of the industry and those of our profession, which are usually well aligned, can act at cross-purposes. One of our primary responsibilities as medical professionals is to carefully monitor that line.

Lessons from haiku

The oath we took separates us and defines us as the most esteemed of professions. We have much to lose when we fail to fully honor that oath. This is a wonderful ideal that unfortunately may be at risk of becoming a cliché. Let me conclude with an appeal to resharpen our focus on that sentiment, for in my opinion it lies at the heart of this issue.  There are two Japanese art forms that I have particularly enjoyed since first visiting Japan to teach phaco with Dick Kratz and Dave Dillman in 1988. The first is a form of calligraphy that allows the artist only a single brush stroke. The other is a form of three-line poetry known as haiku in which the poet must follow this highly restrictive format: The first line has five syllables, the second line has seven syllables, and the third and final line has five syllables.  Artists who work in these media are set apart and defined by the restrictions to which they adhere. Their task is more difficult and the product of their efforts is therefore more highly esteemed. Should they fail to adhere to the restrictions then, de facto, they are no longer a member of that artistic group.

In like manner, we physicians have agreed to be restricted by the dictum of the Hippocratic oath, “First, Do No Harm.” Just as with this group of artists, we physicians have accepted the challenge of greater restrictions on our efforts to advance progress with new technology and clinical innovation. By agreeing to do no harm, we accept that we must find ways to accomplish progress without a significant overshoot, without harm. Ophthalmology is not permitted the cyclical approach to progress: three steps forward followed by two steps back. Note that this core principle does not preclude progress. It does, however, require that our progress unfold in smaller, more measured and well-verified steps.

When we succeed, we fulfill our contract to the patient and continue to earn the trust and higher esteem in which physicians have long been held. However, if we sidestep the more measured approach to progress, if we overreach and create a significant innovation overshoot, then we too are de facto, no longer members of our more select professional group. We risk losing that trust and esteem and will eventually be seen as little different from a sales force, which as we know has a different dictum: caveat emptor.

I am not at all anti-industry. I just want to shine a bright light on this crucial fact: Physicians and sales people are defined by different roles and different rules. Only we have the responsibility that accompanies patients’ trust because only we have taken the oath to protect them from harm, even as we advance progress.

So as we move now in earnest toward refractive lens exchange, I would like to appeal for a collective downshift to a lower gear. We may move slower, but as we have seen here, for us physicians that is exactly as it should be and as it must be if we are to continue to earn the trust and esteem that sets us apart.

An Eye Doctor’s Fly in the Ointment

“Dr. X, for every patient you send to our laser center, we’ll collect the $5000 and we’ll make sure you get back $2000.”

“That’s an extravagant amount,” I said. “Isn’t that a kickback?”

“So many people walk around with a meaningless life.  They seem half-asleep, even when they’re busy doing things they think are important.  This is because they’re chasing the wrong things.  Morrie Schwartz, “tuesdays with Morrie”

A few years ago, I stared at the growing stack of invitations, fliers, and letters in a pending file. Fliers to LASIK seminars.  Invitations to dinner with refractive surgeons and LASIK center directors.  Letters to get in on the ground level and invest in LASIK centers.

Out of curiosity, I accepted an invitation to dinner. I was wined and dined.  Take that back.  I was WINED and DINED.  Beneath the glow of dimmed chandeliers in an elegant restaurant, the compliments were blushingly effusive. I was made to feel so very special.  It was seductive.

The pitch came at the end of this dinner: Dr. X, for every patient you send to our laser center, we’ll collect the $5000 and we’ll make sure you get back $2000.” “That’s an extravagant amount,” I said. “Isn’t that a kickback?”  “No, we call it a co-management fee,” was the quick reply.  “You and I will manage the patient together.  A “kickback” lands us both in jail. Hehehe.”

That night, I told my husband, “I didn’t take it personally, but now I know what it’s like to be propositioned!  Optometry has never been paid that well for equivalent services. Call it anything.  A bribe is a bribe is a bribe. Do they really think that doctors are that easily bribed?”

Call me naive, but I was shocked, when within a year, so many doctors were climbing aboard the LASIK bandwagon. This was an experimental surgical procedure, very seat-of-the-pants, without a track record. The referral guidelines were sketchy. The scientific literature was sparse. Yet, knowing so little, they were enthusiastically referring patients to laser centers  –  up the proverbial KAZOO.

With dismay, I witnessed the suspension of previously sound professional judgment, leading me to question:

Had the eye professions gone bonkers?  Were they not hearing the incessant LASIK ads as sheer, unadulterated HYPE?  Hype that trivialized the possible sight-impairing and sight-threatening complications?  Had my peers succumbed to a selective amnesia, forgetting basic cornea knowledge? A cut and partially vaporized cornea is compromised, no matter how you slice it.  Are we so easily bought?  Are we that “bunch of schlocks” that a professor-mentor had exhorted us NOT to be?

Doctors are human.  Oh, so human. And their inner children were being enticed with instant gratification.  Some resisted. Some sat on the fence.  Some yielded. LASIK coincided with a difficult time in my life.  My father was gravely ill.  Feeling down and vulnerable,  I seriously considered leaving my profession, perhaps returning to  teaching college psychology.

I felt ashamed to be a fellow member of the eye professions.  A growing number of its members were failing to profess, i.e., failing to fully inform their patients. I felt embarrassed by the flagrant disregard of  The Hippocratic Oath by those who were putting their own interests ahead of their patients’. I was appalled by the whole sordid “back-room” dealing that I had experienced… as if I were a hooker!  So ashamed, embarrassed, appalled — and incredulous, I avoided the subject whenever it came up among peers.

Experiencing a sympathetic reaction called “Fight or Flight,”  my non-confrontative, peace-loving self chose to flee. I wanted OUT!  And fast.

My father loved living. His passions were reading and traveling, both sight-intensive activities. He lived life to the fullest, and at the end of it, I saw him fighting to keep every ounce of quality in his life. His valiant fight inspired me not to easily give up on what I loved so deeply:

I truly love those I serve; we have consciously cultivated a solid base of quality-minded patients who want the personalized care we offer and are willing to pay fair fees for it.  It has taken years to assemble the best team of conscientious, like-minded staff  members and doctors ever. Together, we have created a caring and joyful country practice in an impersonal, urban setting.  High-tech, from pouring most of its profits back into it, yet beautiful and welcoming, our office is a great place to be.  I love my profession, or at least I did a lot more before LASIK came along.

LASIK had become a fly in the ointment.

When my father crossed over, it was his faith in me and my faith in “I can do all things…” that motivated me to do my best to flick the fly out of the ointment and make a positive difference.

Not wishing to dwell on negative energy and resort to finger-pointing and blaming, I sought to clearly identify the fly in my ointment. If I were to flick it out, I needed to know what the fly was. Was LASIK the fly? No, it’s just a procedure. Were doctors the flies? No, in an imperfect world, good and bad exist in every profession. Besides, judging others is a fruitless endeavor; I leave that stuff to a Higher Power.  Not my job. And then it came to me, clear as day:

The fly in the ointment was THE FAILURE TO FULLY INFORM: the ads and infomercials were not fully informing the public;  many refractive surgeons and referring doctors were not fully informing patients; and refractive surgeons were not fully informing referring doctors of their mounting failures.  Real risks and complications  were being downplayed, even trivialized.  Financial incentives for referring patients was not common knowledge. 

As professionals, we have a moral obligation to FULLY INFORM to the best of our ability, with the patients’ best interests in mind.  Especially when it has to do with our primary sense, sight.

I began a personal campaign to persuade my peers to FULLY INFORM, to think twice before casually referring their patients to LASIK surgeons.  Whenever I attended meetings, conferences, or classes,  I’d bring the subject up with my peers, asking them to review their basic eye anatomy and pay attention to the corneal nerves — the “feelers” of the eye, its biofeedback mechanism — before they sent in their next patient.

Reminding them of the neurotrophic function of these nerves (they help in the maintenance of a healthy cornea),  I reviewed how the microkeratome — “the world’s smallest buzz saw” — sliced these microscopic nerves, millions of them, that do not grow back to its original state and function.

I’d offer the reality check, “Christopher Reeve still does not walk.” Bless that courageous, inspiring man who struggles with dignity and fortitude.

Quizzing my peers, I found that, for many, their knowledge was woefully lacking.  They were not FULLY INFORMED themselves, yet were referring patients. Some had no idea what “Sands of Sahara” was, much less knowing what to do about it if it bit them in their face.

Bringing up consequences that might broadside their pocketbooks, I hoped to make them think twice about their casual referrals:

“The surgeon’s name is on the informed consent form, is yours? You do know that the surgeons have protected themselves from lawsuits with that informed consent form, but you’re left yourself wide open for lawsuit for FAILURE TO FULLY INFORM. You can be held accountable. Complications, especially corneal transplants, can be expensive. If the surgeon’s consent form is “iron-clad,” you’re the next logical person to sue.”

I’d get replies like, “Geez, I never thought of that!”  Unfortunately, thought-provocation didn’t seem to achieve my desired end of slowing down their rapturous, under-informed referrals.  In a short time, referring doctors were insisting on having their names added to informed consent forms.

I’d toss out highly touted percentages of failure, which we belatedly know by personal experience as underestimations:

“For the one, two or three patients out of every hundred you refer to LASIK surgery, the complications are not minor inconveniences, but profound losses in vision acuity, quality and even sight itself. Are you prepared to face that patient who will need a corneal transplant? Are you aware that when surgeries fail, patients, families, networks of friends, colleagues and co-workers suffer?  And all that for an elective surgery? What are you going to say to the patient who says, “Doc, I trusted you to do right by me.  Why didn’t you tell me this could happen to me? Why did you make the complications seem so trivial and unlikely?  I would have thought twice…”

What about the losses in everyday function that are not even counted by the 1-3% statistic?  Those who no longer can work as they once did.  Who no longer read or travel as before LASIK? Who no longer drive safely at night? Those who are now plagued with glare, aberrations, starbursts, and halos (a combination of post-LASIK symptoms so common, it has its own acronym, GASH)? Those who suffer from dry eyes who now spend a $120 a month, $1200 a year for prescription artificial tears?  Would they have chosen this surgery if they had known that these complications would be theirs for keeps?

A common response was one of resignation: “X, if I don’t send them in, someone else is going to do it anyway” or “Everyone else is doing it, and I don’t want to be perceived as being behind the times.” I’d gently remind them to review The Hippocratic Oath and The Golden Rule.

Those overtly milking the LASIK cash cow responded with, “Hey, the money’s too good not to refer,”  or “This is making a nice nest egg for my retirement.”  To them, I was unapologetically pointed, “Hippocratic is not spelled  h-y-p-o-c-r-i-t-i-c.”

In spite of my mild-mannered demeanor, when I smell a rat, especially a hurtful rat who has done a magnificent job of rationalization, I have no problem revealing that rat-ness to him/her self.  I practice The Golden Rule; darn it, if I’m being a hurtful rat without awareness, somebody tell me, so I can snap out of it!

Carrying the “FULLY INFORM” campaign on to the Internet, I e-mailed anyone and everyone in the eye professions. I suspect my e-mails were often deleted as SPAM.  I have a quick finger for it, myself.  For others, I suspect my e-mails were uncomfortable, unwelcome reality checks, but not uncomfortable enough to give up hefty fees.

At first, the positive, supportive replies were a trickle; now, it is a steady stream. This has been a faith-restoring and heartening experience.  I am in honorable company after all; there are many who have refused to make light of our professions’ duties and obligations. Thanks to the Internet, we are finding each other.  I especially like the replies that go: “I thought I was the only one who felt like you…You’re right.  We did take an Oath, “First, do no harm…  What can we do?… Let’s work on this together.

A grassroots effort to FULLY INFORM was born.

Many of the refractive surgeons were not talking up their complications.  There was a FAILURE TO FULLY INFORM referring doctors who were feeding them patients.  Staying mum about their less than stellar results was good for business. Using the Snellen eye chart worked in their marketing favor.  A post-LASIK patient may have a significant decrease in visual acuities under low light conditions, but still be able to handily read a high-contrast eye chart, i.e., stark black letters projected on a stark white background.

Case in point: In March 2000, back in my home state,  I interviewed a post-LASIK patient,  Mary Doe, who related this experience to me:

“I’m not going to talk about me.  But I do have to be out of here by 5 o’clock, as I can’t drive at night anymore.  I want to tell you about my friend, John Doe.  I’m talking for him, because he’s not ready to talk about it yet.

I owe it to him to let you know what happened to him, because I persuaded him into doing the surgery with me.  From the get-go, I was doing great. I was out there  telling everyone, “Do it, do it, do it.”  He was being quiet about it.   Some time later, I asked John how he was doing. He said, “Mary, I’m not doing so well. “Go back to the surgeon,” I urged. “We have a lifetime guarantee on this. They can do a touch-up, an enhancement.”

John said: “I did already.  The technician had me read a line on the chart.  I read it. The surgeon came in and said, “What are you doing here? You’re doing great.  You just read the driver’s test without glasses or contacts.  What’s the problem?” I said, “Doc, like right now, how come when I reach down to tie my shoelaces, I can’t see my shoelaces for my shoe?” The surgeon shook his head and said to me, “You need to see a psychiatrist.”

Grrrrrr.

Hearing John’s story, thanks to Mary,  gave me the push to do more. With crystal clarity, I had a moral obligation to FULLY INFORM her, FULLY INFORM him. I know, as any eye professional knows, the following: John’s and Mary’s refractive surgeon knew darn well that LASIK surgery had decreased John’s ability to see in low light conditions, i.e., there was a reduction in contrast sensitivity.  No only was the surgeon being a complete a**, he was being totally dismissive of the patient’s accurate reporting of a very real and common symptom of LASIK.  Yet, he led John to question his sanity.

A CONSCIOUS FAILURE TO FULLY INFORM.

Like Mary, John no longer drives at night.  Just as John can no longer see his white shoelaces on his white sneakers in a dimmed room, both can’t easily see dark-colored cars and objects on dark roads (your kid hurrying home on a bike? your pet? your spouse jogging? your parent taking an evening stroll? you crossing a street?). Forget looking for matching socks in the morning. He no longer sees numbers well (print on colored paper is difficult), which is essential to his job. He’s thinking about going on disability, and taxpayers will be paying to support him.  John’s life has been complicated, let alone his eyes and vision. But that surgeon will count him and Mary as unmitigated successes.  And the failure rate will remain under-estimated,  deceptively misrepresenting the true numbers to the public, a failure to fully inform.

These days, we are busily FULLY INFORMING one another and the FDA.  We write, share, and collect our case reports on the LASIK failures. We’re sending copies to one another, as well as forwarding copies to the FDA, along with our individual accounts of our personal experiences of backroom deals-making.

The FDA is listening.
URL: http://www.surgicaleyes.org/ubboard/Forum27/HTML/001173.html

These days, we share tips on how to help post-LASIK patients who now seek our care. We learn from them and from caring doctors (like leukoma and DavOD) who generously and anonymously give of  their time and expertise to answer questions and contribute to a growing resource of fully informative accounts at http://surgicaleyes.com.

Whenever one of us has access to the media, thanks to the power of the Internet, we strive to FULLY INFORM the public, e-mailing summaries of case reports, existing studies, and articles on complications.  We suggest interviews with complicated post-LASIK patients (with their permission and willingness,  of course) and refer to actual patient accounts at http://surgicaleyes.com.

The national, state, and local media are reading, listening, and using our information to FULLY INFORM the public in their articles, newscasts, and magazine shows. I am pleased to see that a number of my peers who were initially tempted are finding their way back to what attracted them to our profession in the first place: the caring and helping of people and the preservation of sight.  My faith in my profession is being restored.

Many are no longer sending their patients in for LASIK, realizing first-hand that LASIK is not ready for prime time.  We are all seeing more and more LASIK failures. Sobering failures. Many are discovering true “bigness,” admitting to the casualness of  their early-on referrals and now educate their patients with the intent to FULLY INFORM.  They are apologizing to their patients, and are doing all they can to assist traumatized post-LASIK patients.

Many have come to realize, the hard way, that they “bit off more than they could chew,”  especially when their post-LASIK patients returned with unexpected complications, some irreversible.   Many more are taking classes like “How to Treat Post-LASIK Complications.”  A hardbound text on the subject is now on the market, filled with photos of complicated REAL cases.  Nothing hypothetical or maybe about those damaged-for-life eyes.  We are also preparing ourselves for the long-term effects that will arise for many with age. For some of us, it’s Humpty Dumpty time again. We wrangled with the down-the-road problems of RK — remember that failed “miracle” eye surgery?  Been there, done that.  And here we go again.

Many more are finding out that, when they consciously strive  to FULLY INFORM,  a common phenomenon occurs:  Patients do think twice.  Consciously thinking about what their sight is worth to them, patients make more carefully thought-out decisions, instead of headlong, emotionally-charged ones. Pondering the risks and the gamble involved with a cautious eye to the future,  they come to a full awareness that this is an elective, experimental surgery with the possibilities of significant eye- and life-complications and long-term problems…

They take that critical look before leaping.

AND once FULLY INFORMED, most patients are willing to wait for a less risky procedure, which will happen!  It’s just not here quite yet. For a certain percentage when conventional means do not correct impaired vision, LASIK may make perfect sense.  Remember, this is not about a procedure; it is about FULLY INFORMING.

There are those occasional patients who have been brainwashed by the hype and do not wish to be fully informed, period. They are those who will listen and still decide to do it. We wish them nothing but success and well-being, and let them know that our door is always open for them.

Patients ultimately make their own decisions.  And we respect that right. This is America. There will always be those who live on the edge, sky-dive and climb Everest. The difference is they do so with full knowledge of the possibility of injury or death, no matter what the safety precautions.  Nature has its unforgiving quirks, its vagaries.

Not FULLY INFORMED with the knowledge of the possibilities of injury or (sight) death, LASIK patients are not as prepared. Eyes are Nature’s masterpieces.  Even with the best equipment in the most experienced of surgical hands, eyes can also be as quirky as Nature.

Common laments of those hurt by the FAILURE TO FULLY INFORM include: “Why wasn’t I FULLY INFORMED that this could happen to me?”  “Why were the complications trivialized, glossed over?”  “I had no reality on the complications.”  “I trusted my doctor to have my best interests in mind, and since, I’ve learned about the financial incentives to refer.  Why was this incentive-to-refer not disclosed to me? I would have thought twice!”

Fully informing the patients is simply the right thing to do!  

Those of us who are choosing to FULLY INFORM are making a difference, one person at  a time. One reporter at a time.  One news article at a time. One web page at a time. You will see more and more websites like this one, as more and more of my peers are recognizing the need to be heard, to FULLY INFORM.

But all of this is not enough. And not in time for many.

The irresponsible TV and radio ads, paid by those who wish to sustain their $100,000/day incomes, continue to lure, day in, day out. A percentage of under-informed patients WILL pay the steepest of prices with their sight and well-being by those who FAIL TO FULLY INFORM.

Sadly, those with complications who were casually referred and/or poorly informed are the most embittered. Their primary sense has been compromised, serving as a daily reminder of a broken trust — a sacred trust — for the rest of their lives.

You are invited to join us. Please join us in being proactive in FULLY INFORMING the unwary public. We need your help.  We share the same public.  They need us to help. They are us.Writing this, I have done my best to keep my word impeccable. I am not too proud to beg on behalf of the gift of sight.  Thank you for your attention.

Kindl yours,
Dr. X

P.S. For those who have already done it, stay positive.  We do not wish to rain on your parade. We wish you no ill, ONLY continued success. Be aware. Stay informed, as several long-term problems are avoidable with early intervention.  Many of us doctors are back in school, taking classes to stem the tide of LASIK complications. Much of what we learn is news to us as doctors, and therefore news to you, as patients. Success has been attained in containing the sight-devastating “Sands of Sahara,” which can “melt” the cornea.  Success has been attained with aggressive dry eye syndrome treatments to avoid corneal scarring, abrasion, and erosion, but better results are obtained when started early, when the symptoms may seem subtle and non-threatening. Sight is a cherished gift; do your best to preserve it the best way you can.

P.P.S.  Feel free to publish this.  Make copies, hand out them out.  Share its URL. No permission is needed.  Posted without a motive to derive financial gain, this is a public service to FULLY inform, plain and simple.

This is a grassroots effort that’s worth getting involved with, as it’s about sight. For Heaven’s
Sake.

http://wakeup.to/lasik

Subject: Lasik, Bausch & Lomb, & TLC

My thoughts: A letter written regarding B&L

For 14 years I was involved in the development of the MicroKeratome that were marketed by Bausch & Lomb. I had a great deal of experience with TLC when I worked as the service department supervisor for Bausch & Lomb. 13 years ago I started worked on the prototypes for the ACS MicroKeratome and 3 years ago I was there when Bausch & Lomb bought Hansa Research & Development Corporation, the true developer.

I was the production supervisor in charge of manufacturing parts up until May of 2002. I actually had a hand in the development of the ACS and Hansatome. I am probably one of the top 5 individuals with the most knowledge about its problems and shortcomings. I was discarded during restructuring in May as the local plant began a series of cutbacks.

About TLC? MicroKeratome returned for service from TLC were some of the worst kept medical devices imaginable. Dirty and beat up by a group of doctors that share equipment like you rent bowling shoes. The problem with a group of people sharing the use of delicate equipment is that nobody cares about its upkeep. Units were treated like tools, wrenches and screwdrivers, and tossed around like the toolbox in the trunk of your car. The people at TLC were the worst to deal with. Demanding quick fixes to destroyed equipment and the blame was always the equipment never the user.

Bausch & Lomb has now developed it’s own more serious problems. In January of 2001 a new plant manager took over the facility here in Miami, Florida where the first MicroKeratome was built and where the Hansatome is produced.

From then till now that facility has undergone a series of cutbacks that affected quality and will be the end of the Hansatome project. That new manager had a personal falling-out with the previous manager and decided to replace the entire power structure of the facility to spite him. He has now done that by neutralizing 5 key people. Unfortunately for the project he has neutralized the supporting knowledge base. The people building Hansatomes were once surgical instrument makers and machinist. Now the device is built by housewives and teenagers in an assembly line production. You can figure out what happened to the quality.

Anyway this last year the production has gone down hill fast and here is a copy of my letter to the FDA in June, I fear they will not take is seriously. This facility needs attention.:

Bausch & Lomb Miami

The Bausch & Lomb facility at

7790 NW 55th St.

in Miami Florida is engaged in the production of the surgical instrument known as the Hansatome Micro Keratome. In this last year the quality of the product has deteriorated to a dangerous level. This effort to reduce cost, cut corners and implement assembly line type manufacturing has now out weighed the need to maintain quality, in this product that actually cuts the human eye. Actual patient injuries have occurred as a result of this effort to cut cost while boosting output. The Repair Dept. covers those tracks. Micro Rings and Micro Heads are being produced in volume without the necessary Quality Controls. The current Quality Manager is in the process of being replaced for voicing his concerns.

The rush to bring the new Z-Heads, Micro Suction Rings and the new 20MM Micro Suction Rings into production, was driven by Marketing and should have required a new 510(k). All other factors take a back seat to that need to hit the market with a new generation device. We are engaged in developing the new prototypes and at the same moment the plant manager is cutting resources. Reducing wages for supervisors and reduced hours for employees.

Reduced availability of tools and equipment. Cutting corners. Gages, measuring tools and cutting tools are in short supply. SPC is non existent and created after the fact as needed.

The design measurements and calculations for the calibration of the Z-Heads are flawed. The prototypes used in the clinical tests were re labeled
several times since they did not produce the expected results. They did not cut the correct thickness as predicted by engineering so the numbers on the heads were changed several times. The design was never reevaluated and under pressure from the plant manager the project pushed forward to production and product release in order to meet his timeline. The actual heads used in the clinical evaluation do not match the manufacturing drawings for the release.

Many small changes have gone undocumented in the effort to push forward.

This device is claimed to cause less compression on the flap when in fact it increases the compression of the entire eye and it is much greater pressure than the ACS unit. Several design changes have inched the Micro Keratome head closer to the eye increasing the IOP. So many Micro Heads were produced so fast that the documentation could not keep up causing heads with similar labels in inventory to have differing dimensions. This creates confusion when calibrating and installing these heads in new and service units.

The manufacturing process for Micro Suction rings and the new 20MM Ring has never been perfected even though production of the rings has increased. The development suffered from cutbacks. The FAIR’s on the 20mm rings were done long after the rings were in clinical testing and were not done on the same rings used in the testing. On the Micro Suction rings, discrepancies in the measurements that control the exposure of the cornea above the ring have caused many Free Flaps as noted by the service department. Quality control in the manufacturing is lacking because of increased volume and cutbacks.

Many rings have varying dimensions. Defective rings are taken out of service or modified when found in service units.

There are massive across the board discrepancies in documentation of Prints, PCPs, SOPs and manufacturing procedures that are incorrect. Actual print dimensions are in error in many cases. This is made worse by cutbacks and restrictions in an effort to save money. GMP and ISO are the goals but the facility is in a state of disarray at this moment. The employees are working blind with an ever growing pressure by the manager to produce more volume in less time. When B&L bought this company 2 years ago documentation was minimal. Much of it was created immediately by a remote engineering department in many cases by people with no knowledge of the device. It was incomplete and flawed and in need of repair. In the last 2 1/2 years only small progress has been made in correcting the documentation and in the last year that correction process has been all but abandon. Procedures for such things as Part Machining, Assemble, Heat Treating, Hardness Testing and Servicing are in need of attention. These documents are incomplete and not understood by the employees. This is due to lack of resources, cutbacks in financing and personnel, lack of proper training and the unyielding pressure to produce more with less and to do it in less time.

Steve ____
X Production Supervisor Bausch & Lomb Miami

ICL RISKS – ANY DIFFERENT THAN LASIK?

The risks for Implantable Collamer Lenses (ICL’s) compared to those of refractive surgery are pretty much the same – severely downplayed (but not really any different!). Note the different sources for ICL risks below saying pretty much the same things, and compare to the risks associated with LASIK:

Possible Risks ICL’s

SOURCE

Potential Complications of the Visian ICLâ„¢ and Other Refractive Procedures
As with any type of surgery, the Visian ICL (Implantable Collamer® Lens) carries the risk of complications. To help educate prospective patients, the following information outlines some of the most common risks of the Visian ICL implant procedure and those of corneal refractive surgery. For detailed information regarding all possible complications, please ask your doctor.

•Complications Common among Refractive Procedures

•Complications with Corneal Surgery

•Visian ICL Complications

•Complications Common among Refractive Procedures
Refractive procedures, from LASIK surgery to implantable contact lens insertion, share possible complications.

Overcorrection and Undercorrection
The most common complications with any refractive procedure are overcorrection and undercorrection. A skilled surgeon will take meticulous measurements before surgery to determine the right amount of correction; however, these measurements are not always perfect. No matter the refractive procedure, undercorrection can be fixed with an additional procedure, which could include a second LASIK or PRK surgery or the removal and replacement of the Visian ICL. Continued use of glasses or contact lenses is also a possibility.

Infection
Because all of these procedures involve some form of manipulation (no matter how slight), there is a risk of an infection. Although it is not a common complication, it is important to realize that an eye infection may range from delaying the healing of the eye to serious damage, including possible loss of visual acuity.

Halos and Night Glare
The most common side effects of corneal refractive surgery are halos and glare around lights at night. These problems range in severity from being barely noticeable to severely limiting a person’s visual acuity. In many cases, severe halos and night glare can be reduced with a second surgery, but it is often difficult to eliminate these effects completely.

Loss of Visual Acuity
Although extremely rare, there is the possibility that a refractive procedure can cause damage to the eye including loss of visual acuity.
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Complications with Corneal Surgery
Corneal surgery, including LASIK and PRK, requires that a small portion of the cornea be removed to change the shape and focusing ability of the eye.

Dry Eye
There is increasing concern in the ophthalmic community regarding dry eye and the decision to perform LASIK. Dry eye is a common disease that often causes patients to seek LASIK because of difficulty wearing contact lenses. According to Toda, et al, in the August 2002 Archives of Ophthalmology, “more than 75 percent of the patients undergoing LASIK have preoperative dry eye.” 1

Additionally, some 59.4 percent of those patients who do not have dry eye preoperatively will end up with it postoperatively2. There is also general consensus that worsening of preexisting dry eye occurs after LASIK.

Problems with the Corneal Flap
Some of the complications of LASIK eye surgery stem from the corneal flap. It may be too thin or too thick or sometimes irregular. Diffuse lamellar keratitis, or DLK, describes another flap-related problem that develops when epithelial cells migrate beneath the flap. These complications are not associated with the Visian ICL surgery as the cornea remains untouched.
[back to top]

Visian ICL Complications
Some complications associated with the Visian ICL differ from those associated with LASIK or PRK. For a complete discussion of all complications, please ask your ophthalmologist.

Damage to the Crystalline Lens
Since the Visian ICL is placed inside the eye, potential risk touching the eye’s natural lens may result. Damage to the natural lens may cause an opacity of the lens, in the most serious case, requiring removal and replacement of the natural lens with a synthetic lens. These opacities, requiring surgical intervention, occurred in less than 1 percent of the Visian ICL patients3.

Complications of Iridotomy
One to two weeks prior to the implantation of the Visian ICL, the surgeon will perform a procedure called an iridotomy. Using a YAG-laser, the doctor will make one or two small openings near the edge of your iris. Complications from the iridotomy are rare, but could possibly include natural lens or corneal damage, inflammation, temporary increase in intraocular pressure, bleeding, and scar formation.

Increase in Eye Pressure
In some cases, there may be an increase in eye pressure. If this occurs, a surgeon may quickly remedy the problem with additional medications or surgical intervention.
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Advantages over Laser Refractive Surgery
Many patients who compare the side effects of laser refractive eye surgery and implantable contact lens complications decide that the benefits of the Visian ICL far outweigh the rare risks associated with it. Because implantation of the lens does not physically change any part of the cornea or other part of the eye, side effects such as halos and glare are almost nonexistent. Also, should any problems with the lens arise, the Visian ICL is completely removable. Learn more about the advantages of our phakic IOL.

If you are interested in undergoing the Visian ICL procedure, find a qualified Visian ICL Surgeon in your area who can discuss the risks and benefits as they pertain to your individual medical history and goals. To learn more about the clinical trials that assessed the safety of the Visian ICL, Contact STAAR® Surgical Company today.
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1. Toda I, Asano-Kato N, Hori-Komai Y, Tsubota K. Laser-Assisted In Situ Keratomileusis for Patients With Dry Eye. Archives of Ophthalmology. 2002;120(8):1024-1028
2. Yu E, Leung A, Rao S, Lam DSC. Effect of laser in situ keratomileusis on tear stability. Ophthalmology, 2000; 107:2131-2135
3. ICL in Treatment of Myopia (ITM) Study Group. United States Food and Drug Administration clinical trial of the Implantable Collamer Lens (ICL) for moderate to high myopia. Ophthalmology. 2004;111:1683-1692

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  • Increased risk of retinal detachment: Nearsighted people usually have longer eyes that can result in fragile retinas, which are more prone to retinal holes or tears. Any surgery within the eye carries a risk of retinal detachment, and this risk increases as the amount of nearsightedness increases. The risk of retinal detachment is low for farsighted patients.
  • Risks associated with surgery within the eye: Since an ICL is an intraocular procedure, the risks associated with cataract surgery are also relevant to ICL surgery. The following complications are extremely uncommon, but they can occur: hemorrhage within the eye; infection within the eye; induced astigmatism; swelling around the eye and increased dryness of the eye. Other complications associated with ICL procedures are reflections or slight distortions from the lens implant; an increase in the number, shape or size of floaters; potential for early cataract development; loss of corneal clarity; wound leak; pigment dispersion glaucoma and uveitis (i.e., inflammation). It is worth noting, some complications of intraocular surgery are associated with local anesthesia and are not a concern for people who have topical anesthesia. Typically, surgeons perform ICL surgery using topical anesthesia instead of local anesthesia, which uses needles.
  • Risks associated with removal of ICL: Potential complications of surgery to remove the ICL can include premature cataract formation; corneal damage; inflammation; infection leading to loss of the eye; damage to the iris as well as other
    ocular complications.

Implantable Contact Lens Risks

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When considering refractive surgery of any kind, you should be aware of each procedure’s possible complications. Potential ICL risks include:

Overcorrection – This complication occurs if the prescriptive power of the implanted ICL is too strong. In most cases it can be corrected with corrective eyewear or with an ICL replacement.

Undercorrection – The opposite of overcorrection, undercorrection is the result of an implantable contact lens with too weak of a prescription. Correction methods are similar to those of overcorrection.

Infection – During most surgeries, there is a potential of an infection. Severe infection during ICL implantation is rare.

Increased intraocular pressure – Pressure may build in the eye after an ICL procedure. The sooner a surgeon is alerted to this complication, the greater the chance of avoiding serious damage.

Repositioning or removal of lens –ICLs have the potential, however slight, of needing to be repositioned. The frequency of this complication may vary by implantable contact lens models.

Damage to crystalline lens – Because implantable contact lenses are implanted into the eye, there is a potential that the eye’s natural lens may be damaged during the procedure. If the damage is severe, the crystalline lens may need to be replaced with an intraocular lens.

Cataract development – Over 50 percent of the population will develop cataracts by the age of 65, however, it is believed that the use of some implantable contact lenses may cause cataracts at an earlier age.

Halos, glare, and double vision – Updated ICL models greatly diminish the risks of halos, glare, and double vision.

Retinal detachment – Less than 1 percent of patients in the clinical studies for both the Verisyse™ phakic IOL and the Visian ICL™ were affected by retinal detachment. It should be noted, however, that the occurrence of retinal detachment increased as the degree of myopia increased.

Vision loss – Extremely rare, there is a possibility of vision loss from this refractive procedure. Typically the loss of visual acuity is due to bleeding, severe inflammation, or an untreated infection.

Understanding ICL Risks

It is important to note that several of the ICL risks listed above are potential complications of all refractive procedures, including:

  • Halos, glare, and double vision
  • Infection
  • Overcorrection
  • Undercorrection
  • Vision loss

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Risks of Lens Implantation

As with any surgical procedure, complications are rare but can occur after implantation of phakic IOLs.

Possible complications include increased chance of retinal detachment, loss of cells in the thin layer inside the cornea (endothelium), inflammation, infection and cataracts.

The FDA warns of other potential complications such as sometimes severe vision loss. Problems also can develop with night driving and may include halos, increased eye pressure (intraocular pressure) that can damage the eye’s optic nerve and inadequate lens power that may not properly correct vision. After surgery, your doctor will continue monitoring your endothelial cell counts, an indicator of how healthy your corneas are and how well they heal afterward.

At the 2006 Joint Meeting of the American Academy of Ophthalmology (AAO) and Asia Pacific Academy of Ophthalmology, a researcher said that — when comparing studies of the Verisyse and Visian ICL — the following complication rates were noted:

Visian ICL and Verisyse Complication Rates

Complication Visian ICL Verisyse
Acute glaucoma 1.6 percent 0.19 percent
Endothelial cell loss 6.6 percent 5.0 percent
Cataracts 9.8 percent 1.8 percent
Retinal detachment 1.47 percent 0.46 percent
Notes: Buratto L. “Phakic IOLs: which approaches are likely to be effective and safe?” Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Refractive Surgery Subspecialty Day.

In Visian ICL studies performed after approval, patients had lower rates of glaucoma and endothelial cell loss and higher rates of retinal detachment and cataracts, compared with clinical trials.

All complication rates were lower for the Verisyse in studies conducted after initial FDA approval.

Because phakic IOLs are a relatively new technology, long-term effects and potential risks of lens implantation are unknown.

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I  WHAT ARE THE RISKS?

As with any refractive surgical procedure, there are certain risks and complications associated with the INTACS procedure. These risks include infection, shallow placement of the INTACS inserts into the tunnel, deposits in the tunnel where the INTACS inserts are placed, haze in the incision area, visual symptoms (including discomfort, burning, itching, tearing, double vision, increased sensitivity to light, glare and halos around lights, fluctuating vision, and reduced vision at night), shallow segment placement, a non-infectious healing response and developing blood vessels in the cornea. It is important to discuss these risks with your doctor before you make the decision to have your surgery. If the results of your INTACS procedure are not satisfactory, you may need to have

the INTACS inserts removed or replaced. If your INTACS inserts are removed, you may need to have a corneal transplant procedure. The long-term safety risks of using INTACS inserts in the keratoconus population are unknown. There may be other risks associated with INTACS inserts that cannot be foreseen at this time.

Other Possible Complications: Other possible risks include corneal ulcer formation; endothelial cell loss (loss of cell density in the inner layer of the cornea, possibly resulting in corneal swelling); ptosis (droopy eyelid); corneal swelling; retinal detachment and hemorrhaging. Complications could also develop that require further corrective procedures including either a partial (lamellar) or full-thickness corneal transplant using donor cornea. These complications include loss of corneal disc; damage to the corneal disc; disc decentration; progressive corneal thinning (ectasia). Sutures may also be required, which could induce astigmatism. It is also possible that the instrument that creates the tunnel goes too deep and passes through the back of the cornea and enters the anterior chamber of the eye which may require suturing. This would preclude inserting the INTACS inserts until the eye healed. It is also possible the instrument could create a tunnel that was too shallow and exit the front of the cornea, which may preclude inserting the INTACS inserts until the eye healed. There are also potential complications due to anesthesia and medications that may involve other parts of your body. Since it is impossible to state all potential risks of any surgery or procedure, this Informed Consent form does not provide a comprehensive listing of every conceivable problem that you may encounter.

Employment Risk: You should be aware that having this surgery may affect future employment opportunities with certain military or law enforcement agencies.

Later-Discovered Complications: The INTACS procedure is a relatively new technique. You should be aware that other complications might occur that have not yet been reported. Longer-term results may reveal additional risks and complications. After the procedure, you should continue to have routine check-ups to assess the condition of your eyes. INTACS inserts may not prevent the need for corneal transplant at some point in the future. It is unknown how INTACS inserts will affect the course of your keratoconus. This is why it is important we continue long-term follow-up on you, either in our clinic or through other health care providers, if you live far away.

Risks of Not Undergoing the INTACS Procedure: The risks of not having the surgery are limited to those associated with your current visual condition. These include but are not limited to the dangers that may be associated with losing your glasses or contact lenses, the risks of corneal distortion and/or infection from wearing contact lenses, and the risks of trauma to the eye caused by breakage of glasses or contact lenses in the eye.

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Risks

Although no procedure is risk free, the risks of serious damage to the eye from ICR surgery are minimal and include the possibility of infection introduced at the time of surgery, surface cells of the eye (epithelium) growing into the tracks where the rings have been implanted requiring removal of the ring, and the remote possibility of permanent damage to the cornea or the inside of the eye. Any surgery on the eye can result in a permanent decrease or loss of vision. Fortunately, severe complications are exceedingly low. Side effects of the ICR include glare, halos, difficulty with vision at night, and fluctuation of vision throughout the day.

Even if a complication does not occur, as with all surgical refractive procedures, patients may not be 100% satisfied with the result and/or may require the use of glasses to “fine tune” the vision for distance tasks such as driving by day or night. Additionally, if monovision is not performed, patients over 40 having both eyes corrected for distance will require reading glasses just as they would if they had not had surgery but continued to wear contact lenses.

Reversibility

If for any reason a patient is not satisfied with the vision following implantation of the ring segments, they can be removed. In almost all cases the eye is returned to (or very close to) its original refraction (amount of nearsightedness). In some cases following removal, the amount of nearsightedness and/or astigmatism is not identical to pre-operative levels and a new spectacle (or contact lens) prescription is required. In some cases following removal, the amount of nearsightedness and/or astigmatism is slightly more or slightly less than pre-operative levels. In some cases following removal of the segments there will be a small amount of astigmatism (curvature of the cornea) actually induced by the surgery where none had existed before the surgery.