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FDA LASIK Investigation Bogged Down in Controversy, Uncertainty
By Linda Roach
Six years after U.S. regulators began taking a second look at post-LASIK visual quality, the American refractive surgery community still does not know how, or if, the reassessment will affect the FDA’s rules for excimer lasers. But the miasma that has surrounded this lengthy process lingers.
The agency’s decision to sponsor a large, expensive research initiative about post-LASIK patient-reported outcomes (PROs) appears likely to keep this evolving story unsettled for at least another year.
The following developments have occurred during several years of debate and controversy:
- A small group of anti-LASIK activists continues to pepper the FDA with complaints, conspiracy allegations and petitions to ban LASIK. The activists say the procedure has caused an “epidemic” of impaired vision, especially at night. (According to FDA records, a large majority of the complaints filed by LASIK patients since 1998 were about dry eye or optical problems, such as glare, haloes, starbursts and difficulty with night driving.) 
- ISRS, AAO and ASCRS walked away from a joint task force that was designing protocols for the FDA studies after their recommendations about how to respond to patient complaints were not followed. The remaining participants on the task force are from the FDA, the National Eye Institute and the Department of Defense (U.S. Navy).
- In a surprising turn of events, LASIK critics have been joined by Morris Waxler, PhD, the former chief of the FDA branch that approved LASIK in 1998. Now retired and working as a consultant, Dr. Waxler filed a petition in January 2011 asking the FDA to ban LASIK as a threat to public health. More than 500 people have signed an online version of the petition. 
- The FDA-sponsored studies of patient-reported outcomes (PROs) appear to be about a year behind schedule. The original plan was to complete the Navy arm of the studies, PROWL-1 (“Patient-Reported Outcomes With LASIK”), in 2012. However, Capt. Elizabeth Hofmeister, MD, the Navy refractive surgeon leading the study, said that as of Feb. 10, the trial had enrolled only 87 subjects, which is fewer than 20 percent of the needed 550 subjects. The study’s protocol requires all 550 subjects to be followed for at least six months.
- A two-part, multicenter civilian trial is scheduled to begin this spring at five U.S. sites, the FDA says, but it has not identified them publicly.  PROWL-2a will revalidate the online patient questionnaire that was used in the Navy study, and PROWL-2b will use it to gather the PROs data from the civilian cohort. Both civilian studies originally were targeted for completion this year,  but enrollment of the first of 550 patients will not occur until this spring. As in the Navy study, patients will be followed for at least six months.
- In response to patient complaints that they had no idea of how bad their post-LASIK vision might be, the FDA plans to ask laser manufacturers to modify laser labeling to show illustrations of possible visual side effects after LASIK. However, the agency's plan was stymied by uncertainty over what the images should look like. 
- At the FDA’s request, the ANSI Z80 Committee agreed to produce a new ANSI standard for these illustrations, called “Methodology for Representation of Optically-Induced Visual Phenomena.” A subgroup began working in 2009 to develop and validate illustrations for the new standard, known as ANSI Z80.32, which would be separate from the excimer laser standard, ANSI Z80.11. That work is ongoing.
Because international refractive surgeons are not subject to FDA rules, there would be no immediate clinical impact for them if the continuing controversy over LASIK outcomes were to lead to the tightening of U.S. excimer laser rules.
However, the issue bears watching because, over time, new limits would filter into the excimer laser regulations of countries that closely follow FDA actions, predicted Mohamed Hantera, PhD, FRCS, MBA, a cornea and refractive surgery consultant at Magrabi Eye and Ear Centre in Dammam, Saudi Arabia.
In the Middle East, government officials place great weight on the FDA’s conclusions about device safety, Dr. Hantera said. For example, the Saudi Arabian agency that regulates medical devices usually echoes every action taken by the FDA, he said.
“Consequently if any machines or techniques were disapproved, the same thing would happen in Saudi Arabia and Middle East countries,” Dr. Hantera said. “Believe it or not, plenty of my colleagues are using the ‘FDA approved’ label as a marketing tool for their excimer laser.”
Critical Mass at 2008 Hearing
In the U.S., the visibility of the anti-LASIK movement reached a tipping point in print and television media coverage of a meeting of the FDA’s Ophthalmic Devices Advisory Panel in April 2008. More than a dozen witnesses at the hearing rose to denounce LASIK, saying it had ruined their vision and their lives. Leading clinical researchers also testified.
Exasperated clinical scientists complain that the FDA is simply responding to emotional stories from angry patients and ignoring a mountain of safety and patient satisfaction data from controlled clinical trials of LASIK.
“The data from clinical trials and post-approval experience around the world teaches us that serious complications from LASIK are rare. The vocal group of patients who have come forward to express their dissatisfaction with LASIK gives us a golden opportunity to analyze their problems, understand why they occurred, and determine whether they can be prevented by changes in our procedures. This strategy may be more productive and cost-effective, even, than a large, expensive, study to determine the incidence of complications. It’s also what these unhappy patients have asked for,” said R. Doyle Stulting, MD, PhD, a former chair of the FDA’s Ophthalmic Devices Advisory Panel.
Members of the original Joint Task Force that the FDA put together tried unsuccessfully to persuade the agency to first ask an independent third party to examine the medical records of some of the patients who had told the agency of extreme visual disability after LASIK. The FDA refused and ISRS, AAO and ASCRS, three of the largest groups in organized ophthalmology, withdrew from the task force.
One member of the original task force, Steven C. Schallhorn, MD, said he urged the panel to give weight to the “countless studies” over the last 15 years that have documented that LASIK is safe and effective. Those studies involved thousands of patients, said Dr. Schallhorn, who is medical director for Optical Express and a professor of ophthalmology at the University of California, San Francisco.
Outcome vs. Satisfaction
“Patient satisfaction after LASIK is excellent and higher than that reported for other forms of elective surgery. It has been consistently high over the past decade,” Dr. Schallhorn said. Nonetheless, in a small number of patients, the observed outcome does not correlate with patient satisfaction, he said. 
“While we can identify several clinical reasons for dissatisfaction, sometimes we can’t find a reason. Other factors not directly related to the procedure, such as depression or personality traits, can influence the patient’s appraisal of satisfaction with the visual result after surgery,” Dr. Schallhorn said.
“These complaints appear to be coming from a small number of people who are very, very vocal, and they drowned out everyone else,” he added. In various documents and public statements, anti-LASIK activists claim that ophthalmologists and laser companies have colluded to hide the “true” rate of complications rate after LASIK of 20 percent or more. 
So when researchers led by Kerry D. Solomon performed a literature review and found a patient satisfaction rate of more than 95 percent , the anti-LASIK camp dismissed this as unreliable and accused the authors of financial conflicts of interest.
What the Numbers Say
Publicly-available FDA records lend support to those who doubt the existence of an “epidemic” of severe debilitating postoperative complications among the millions of Americans who have undergone LASIK since its approval in 1998.
Online searches of the FDA’s Manufacturer and User Facility Device Experience (MAUDE) database show that at least 90 percent of the “adverse events” reported to the FDA during the last decade were reports about lasers malfunctioning and were made by physicians or laser companies.
Through around 2005, records show that no more than a few dozen LASIK patients per year complained to the FDA about their postoperative results. However, patient-reported adverse events rose steeply in 2006 after a number of events occurred:
- LASIK became the refractive surgery of choice. It is estimated that more than 16.3 million people have undergone the procedure worldwide to date.
- The FDA issued a warning letter in 2009 reminding physicians to track refractive surgery adverse events and to file reports on them. (The warning, which was repeated in September 2011, also reminded refractive surgeons not to make false claims about LASIK outcomes in their advertising and marketing materials.)
- The Internet gave dissatisfied patients an easy way to recruit new followers and to encourage them to file adverse-event reports, sometimes years after their surgeries. (About 25 percent of the patient-generated reports filed between 2006 and 2011 concerned surgeries performed a decade or more earlier.)
Relatively Few Reports From Patients
From 1998 through 2011, the FDA received approximately 2,300 adverse event reports about excimer lasers, MAUDE data show. Approximately 200 of these reports came from LASIK patients and were filed during the last six years. The remainder came from physicians and laser companies. 
The FDA also gave LASIK critics another public forum, by issuing a call for public comment on post-market experiences with LASIK. After an anemic response by the first deadline in September 2009, the agency extended it another 13 months until November 2010. The public record of these comments also does not support an assertion that there has been an epidemic of severe vision loss after LASIK. 
The FDA received 159 comments, with neither the “pro” nor “con” side dominant. Among the negative commentators were anti-LASIK activists who testified at the 2008 advisory committee hearing, individuals who have petitioned FDA for an end to LASIK, and owners of anti-LASIK web sites.
1. “Waxler’s Regulatory Consultancy LLC - Citizen Petition” (Docket # FDA-FDA-2011-P-0022). Accessed in December 2011 at http://www.regulations.gov/#!documentDetail;D=FDA-2011-P-0022-0001.
2. FDA records are redacted. Full copy of the petition can be downloaded in PDF format at: http://lifeafterlasik.com/LASIK%20Morris%20FDA%20Petition%20Jan%206%202011.pdf
3. U.S. Food and Drug Administration web page, “Latest on FDA's LASIK Program” [Page Last Updated Dec. 20, 2011], accessed online Feb. 21, 2012, at: http://www.fda.gov/MedicalDevices/.../SurgeryandLifeSupport/LASIK/ucm061421.htm
4. U.S. FDA press release, dated Oct. 15, 2009, accessed online Feb. 21, 2012, at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2009/ucm186858.htm
5. “Minutes of the special meeting of Z80 – SC4 to consider proposal to revise Z80.11 – Laser systems for corneal reshaping,” accessed online in February 2012 at: http://ebookbrowse.com/sc4-z80-11-october-meeting-minutes-doc-d97512093.
6. Morse JS, Schallhorn SC, Hettinger K, Tanzer D. Role of depressive symptoms in patient satisfaction with visual quality after laser in situ keratomileusis. J Cataract Refract Surg. 2009;35(2):341-346.
7. Solomon KD, Fernández de Castro LE, Sandoval HP, et al. Joint LASIK Study Task Force. LASIK world literature review: quality of life and patient satisfaction. Ophthalmology. 2009;116(4):691-701.
8. FDA records of adverse events in its Manufacturer and User Facility Device Experience (MAUDE) database. Accessed online in January and February 2012 at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfMAUDE/search.CFM. Search terms: LASIK, and excimer laser.
9. Examination of the FDA’s online records of rules, comments, adjudications or supporting documents for Docket # FDA-2008-N-0488. Accessed in January and February 2012, at www.regulations.gov.
Dr. Hantera has no financial interests to declare.
Dr. Schallhorn is a consultant to AMO.