FDA Panel to Consider Corneal Collagen Cross-linking

Tuesday, February 24, 2015

By Richard Smith

          As with many regulatory proceedings, a Food and Drug Administration hearing today will have effects reaching far beyond its official topic. An FDA scientific advisory panel is gathering to consider a new treatment for keratoconus, a rare but potentially disabling eye disorder. How the FDA responds could launch a new phase of the Lasik eye surgery boom–with an add-on technology that’s marketed as enhancing patient safety but that in fact greatly increases patient risk.

          First, the basics: Keratoconus affects about 174,000 Americans, with roughly 6,400 new cases a year.[1] An afflicted eye loses structural integrity, and the cornea bulges forward under the eyeball’s internal pressure. Vision may deteriorate severely as the eye gets more and more distorted.

          The procedure under review, corneal crosslinking, is simple compared to many ophthalmologic treatments. The eye is doused with a solution of riboflavin (Vitamin B2) and then exposed to ultraviolet light. This stiffens eye tissues containing collagen. (I imagine damp shoe-leather baking in harsh sunlight.)

          The idea is to help the eye hold its shape, but for minorities of patients the treatment causes problems, including significant loss of corrected distance vision in 2.9 percent; significant scarring, up to 8.6 percent; and corneal ulcers, 7.6 percent.[2] Long-term risks are unknown, but because crosslinking uses a range of ultraviolet light known to alter DNA,[3] there’s a chance it could trigger cancer.

          Such risks aren’t trivial. But the benefits may be substantial: halting the disease’s progression, which can lead to legal blindness, and avoiding corneal transplant, a frequent treatment for severe cases that is nobody’s idea of a picnic.

          But there’s more to the story. Crosslinking is being evaluated as a treatment not just for keratoconus but also for corneal ectasia. Ectasia is a kind of cousin, with the same basic symptoms and course, but unlike keratoconus its cause is known: the laser vision-correction surgery known as Lasik–a medical intervention widely touted as safe and effective.

          How can Lasik lead to ectasia? Refractive surgeries aim to improve vision by reshaping the eyeball so light focuses properly on the retina. Before Lasik, the laser was applied to the eye’s surface. Recovery was slow and painful. Lasik emerged as an easier sell: a thin flap of cornea is shaved and folded aside, underlying tissue is lasered, and the flap is flipped back into place, creating a natural bandage over the wound. Less pain, fast vision improvement–the so-called Lasik “wow!” effect.

          But the cornea doesn’t heal like most body tissues. In fact, the Lasik flap never really heals. In one study, the edge of the flap retained only 28.1 percent of its original tensile strength–and the central area only 2.4 percent.[4] That’s why, years after Lasik, a blow to the eye can knock the flap loose, like an unlatched door, and a surgeon “retouching” your Lasik can simply relift the original flap, like scraping an egg off a griddle.

          The flap’s failure to heal also leaves the cornea weaker–less resistant to the eye’s internal pressure. Sometimes the eye’s shape shifts enough to start undoing Lasik’s correction of vision. Worse corneal bulging can cause ectasia.

          How often this happens isn’t clear, as estimates vary and, as malpractice attorneys have found, some cases are hushed up.[5] Current statistics put the incidence below one percent.[6] That’s less frequent than some of Lasik’s other downsides, such as glare, halos, starbursts, ghosting, and dry eye.[7] But because such symptoms are classified by the FDA as less severe than ectasia, they’ve received less official attention and surgeons have been less concerned with them than with downplaying or even denying the risk of ectasia.[8]

          Now, however, with corneal crosslinking on the horizon, ectasia is back on their radar. In fact, some surgeons and industry leaders advocate adding crosslinking to Lasik as insurance against future deterioration. Avedro, whose procedure comes for FDA review today, is conducting a clinical trial of Lasik and corneal cross-linking performed simultaneously–a double-header already approved in Europe, where Avedro markets it under the trade name Lasik Xtra. Another company, CXLUSA, is running a trial of a Lasik-crosslinking combo for patients known to be at higher risk of ectasia.

          So let’s get this straight. The risk of ectasia after Lasik is less than one percent–way less, surgeons have insisted. But surgeons propose tacking on crosslinking, with risks several times greater than that of ectasia. And the risks of crosslinking would load on top of the known risks of Lasik. These risks have been hotly debated, but one review of FDA documents found that, across studies, 15 percent of Lasik patients had worse or significantly worse night vision than before surgery. Twenty percent had worse or significantly worse dry eye.[9] These outcomes can be far more disabling than they sound–for instance, when a Lasik patient driving at night must try to peer through streetlight starbursts that span the whole road, or when Lasik-induced dry eye hurts so much a person wants to gouge his eyes out.

          The Hippocratic Oath advises doctors, “First, do no harm.” Given that Lasik is medically unnecessary, maybe the simpler solution is not to do it in the first place.

          To make a case for Lasik plus crosslinking, surgeons have had to stop minimizing ectasia’s risks, instead maintaining that those risks justify adding crosslinking. Whatever net effect crosslinking brings to Lasik patients, it also gives crosslinking tech companies and Lasik surgeons a new option they can add to bills for some 600,000 Lasik customers a year. Big money isn’t in treating kerataconus but in promoting Lasik with crosslinking.

          That procedure will come up for FDA approval within the next few years. But if today’s advisory panel recommends approval for crosslinking, doctors could start slapping the procedure onto Lasik even before the safety and efficacy of the combo platter has been adequately studied. Doctors could claim a right to perform the procedure in what’s called an “off-label” use–that is, for purposes other than those officially sanctioned.

          The FDA regulates drugs and medical devices, not the practice of medicine,so it couldn’t stop off-label uses altogether. But what the agency can do is stipulate that crosslinking, if approved, can be marketed only for the approved purposes–treating keratoconus and ectasia. It could forbid doctors to promote crosslinking as a way to make Lasik safer. Such claims would constitute “misbranding”–essentially, misleading advertising that amounts to fraud. That might give the agency a chance to make a meaningful yes-or-no decision when Lasik Xtra and its competitors come up for approval. Otherwise, Lasik-plus-crosslinking could become so commonplace that future FDA approval would be a foregone conclusion.

          That’s how the Lasik boom got its start two decades ago. In the 1990s, Lasik became what its critics regard as a runaway train when lasers were FDA-approved for an earlier method of eye surgery, and surgeons began using them for Lasik as well–before anyone adequately studied Lasik’s safety and effectiveness. According to Morris Waxler, then branch chief of the FDA’s Center for Devices and Radiological Health, the agency got worried that Lasik was spreading without safety studies or rules, risking not only patients’ eyes but also the FDA’s reputation. So the agency tried to rush Lasik surgeons into the corral of government oversight.[10]

           Predictably, this rushed job was a botched job. For one thing, according to Waxler, the FDA allowed industry too much say in establishing official definitions of safety and effectiveness. Many of the ways Lasik can damage vision and eye health got downgraded from adverse event to complication or side effect–and thus didn’t affect Lasik’s official safety profile.

          The FDA advisory committees reviewing Lasik in the 1990s tried to slow things down. The first one voted the application under consideration nonapprovable–largely because the reported percentage of patients returning for followup evaluation was so low that the data looked cherry-picked. Nonetheless, the agency approved it, fearing a battle with the applicant’s formidable attorney (a former FDA chief counsel).[11]

          During the next round of hearings, NIH ophthalmologist Frederick Ferris acknowledged it was bizarre to see the FDA debating approval of a surgery already in widespread use: “…driving in here I heard a number of advertisements for this procedure…. I thought to myself, Well, people little note nor long remember what we do here because, as near as I know, this train is moving.”[12]

          Now another train is lurching into motion. The FDA needs to hit the brakes.


[1] Figures based on current estimated U.S. population and U.S. incidence rate of 0.002% and prevalence rate of 0.054% reported in Kennedy RH, Bourne WM, Dyer JA. A 48-year clinical and epidemiological study of keratoconus. Am J Ophthalmol. 1986;101:267-73.

[2] Raiskup, F, & Spoerl, E. Corneal Crosslinking with Riboflavin and Ultraviolet A. Part II. Clinical Indications and Results. The Ocular Surface, April 2013, Vol. 11, No. 2. pp. 93-108. p. 98.

[3] Steve Safran, quoted in eyeConnections: Queries about collagen cross linking. ASCRS EyeWorld, April 2010.

[4] Cohesive Tensile Strength of Human Lasik Wounds with HIstologic, Ultrastructural, and Clinical Correlations. Ingo Schmack, MD; Daniel G Dawson, MD; Bernard E McCary, PhD; George W Waring III, MD, FACS, FRCOphth; Hans E Grossniklaus, MD; Henry F Edelhauser, PhD. Journal of Refractive Surgery, 2005;21: 433-445.

[5] Interview with Todd Krouner 9-11-12

[6] Raiskup, F, & Spoerl, E. Corneal Crosslinking with Riboflavin and Ultraviolet A. Part II. Clinical Indications and Results. The Ocular Surface, April 2013, Vol. 11, No. 2. pp. 93-108. p. 98.

[7] LASIK Quality of Life Collaboration Project, FDA/NIH/DOD. Presentation by Malvina B. Eydelman, M.D., Director, Division of Ophthalmic and Ear, Nose, and Throat Devices. ODE/CDRH/FDA. Posted at http://www.fda.gov/downloads/MedicalDevices/ProductsandMedicalProcedures/SurgeryandLifeSupport/LASIK/UCM421193.pdf.

[8] Stephen Slade, quoted in: CXL for Corneal Ectasia: Reshaping the Future of Treatment, by Annie Stuart. EyeNet Magazine, April 2014.

[9] Outcomes of Lasik of Myopia with FDA-Approved Lasers. Bailey, Melissa D, OD, PhD; Zadnik, Karla OD, PhD. Cornea, Vol. 26, No. 3 (April 2007), 246-254.

[10] Interviews with Morris Waxler, December 7, 8, and 9, 2012.

[11] Interviews with Morris Waxler, December 7, 8, and 9, 2012.

[12] FDA–Ophthalmic Devices Advisory Panel, 93rd meeting. July 22, 1999.

Device Maker Slammed by Injured Patients at FDA Meeting

Copyright Dickinson FDA Webview at www.fdaweb.com. Republished by permission.


Avedro Inc. CEO David Muller was verbally battered by several injured LASIK patients during public presentations 2/24 at a joint meeting of two FDA advisory committees as he led his company’s efforts to win an approval recommendation for a new drug/device combination to treat eye disorders progressive kerataconus and ectasia. Muller, the presenters charged, headed Summit Technology in the 1990s when it won a corrupt approval for the first LASIK-indicated excimer laser that permanently damaged their eyesight and “ruined” their lives.

Now he’s seeking approval for an “orphan”-designated NDA for riboflavin ophthalmic solutions with UVA irradiation by Avedro’s KXL System for use in corneal collagen cross linking for the treatment of the conditions underlying progressive keratoconus and corneal ectasia following refractive surgery. Despite its unapproved status in the U.S., the combination is already being promoted on Avedro’s Web site as an integrated enhancement of LASIK surgery outcomes, restoration of corneal strength, halting progression of keratoconus and ectasia, and slowing or eliminating the development of acute keratoconus.

Before they voted 10-4 with one abstention to recommend approval for the keratoconus indication and 6-4 with four abstentions for the ectasia following refractive surgery (LASIK) indication, the Dermatologic and Ophthalmic Drugs Advisory Committee and Ophthalmic Devices Panel of the Medical Devices Advisory Committee heard 14 public commenters give four-minute presentations. The first four urged approval, citing worldwide successful use of the new technology outside the U.S., and the suffering of an estimated 2 million keratoconus American victims who are without access to the therapy.

There were 1,268 corneal transplants performed in the U.S. in 2013, the Cornea Society’s David Glasser told the panel. “I couldn’t be happier if your votes today mean I will have performed my last corneal transplant,” he said.

But the remaining 10 public presenters, while frequently conceding the case for keratoconus victims in Avedro’s new technology, delivered a relentless stream of condemnations of the refractive surgery medical-industrial-FDA collaboration that they complained had ruined their lives, led to depression and suicide through an “epidemic” of dry eye, blurred vision, starbursts, haloes, night-driving difficulties and other vision problems.

The panel also heard a presentation, delivered in his absence, by former CDRH ophthalmic devices branch chief Morris Waxler, who led the team that approved the first Summit Technology LASIK device and has since recanted. Delivering for him, injured LASIK activist Paula Cofer slammed Muller’s role as Summit Technology CEO in introducing the first LASIK lasers through a corrupt FDA evaluation process. She alleged that he was responsible for “thousands, perhaps tens of thousands of LASIK patients who developed ectasia as a result of their trust” in the process. LASIK surgeons, she said, don’t report the ectasia cases they cause, and are complicit in an industry-wide cover-up. If FDA approves Avedro’s combination product, she predicted it will lead to off-label use of Avedro’s next enhancement, LasikExtra, already being promoted on its Web site and in the marketplace.

Then it came Matt Kotsovolos’ turn [speaking for Dean Kantis] to lambaste Muller for “ruining” his vision through “huge” (reportedly $1 million) contributions to the late Sen. Edward Kennedy’s 1994 re-election campaign “in exchange for political FDA access” that led to the Summit device’s approval in October 1995. Kotsovolos also read from what he said was a transcript of a presentation to a professional group by the Cleveland Clinic Foundation’s Cole Eye Institute eye surgeon Ronald R. Krueger, in which he admitted that LASIK-caused ectasia occurred much more frequently than the procedure’s FDA-accepted 1% total adverse event rate.

Muller, who has long bragged about the closeness of his FDA relationships, took to the podium several times during the panel discussions, but he did not respond to his critics. In one appearance he explained that deficiencies in the clinical data supporting the KXL System application, pointed out by many panel members, resulted from data prepared by an unnamed “small German company” that developed the technology and ran out of money before it could complete the studies and Avedro acquired them as-is.

Among the Avedro data deficiencies mentioned by panelists were the NDA’s lack of patient satisfaction surveys, which CDRH ophthalmic devices director Malvina Eydelman told the meeting FDA was “committed to,” and the complete lack of any data from studies done with the KXL device itself ─ instead the panelists were forced to accept Avedro’s contentions that this device was to all important extents, identical to a different device, the UVX which was used in all the studies.

Despite these and other deficiencies, the panel voted with barely muted misgivings for the primary indication, progressive keratoconus, and much more reluctantly for the second ─ and reputedly far more profitable ─ ectasia after LASIK indication.

Ex-FDAer Waxler to Oppose Avedro NDA at Advisory Cte.

By Jim Dickinson


Former CDRH ophthalmic devices branch chief Morris Waxler will next week oppose an Avedro Inc. NDA seeking approval for riboflavin ophthalmic solutions with UVA irradiation for use in corneal collagen cross linking for the treatment of the conditions underlying progressive keratoconus or corneal ectasia following refractive surgery. The venue: the 2/24 joint meeting of the Dermatologic and Ophthalmic Drugs Advisory Committee and Ophthalmic Devices Panel of the Medical Devices Advisory Committee.

The basic issue in Waxler’s opposition is the failure of the applicant to demonstrate long-term product safety in a prior LASIK PMA application as Summit Technology in 1995, which Waxler approved as branch chief.

In a presentation to be delivered in his absence, Waxler says the NDA presents “at least two public health dilemmas” for the committees because the product masks “a high rate of LASIK-induced ectasia” when the true rate is unknown, and “how many legally blind people are acceptable to you for a few years of ’20-happy vision?'”

Waxler’s presentation says that FDA’s “collaboration with the refractive surgery industry has created a LASIK-induced epidemic of sick corneas…. The true rate of LASIK-induced ectasia will be buried forever if the panel recommends approval of FDA’s plans to approve products polymerizing sick corneas.”

Waxler, who unsuccessfully petitioned against his own approval of the LASIK indication for excimer lasers because of alleged data falsification he found later, says FDA leadership on LASIK products “has a long-standing collegial and professional bias towards ophthalmic professionals in the industry. They work out many issues in regular private meetings; I know because I led many of these meetings and know of many others.”

LASIK Activists Petition for Black Box Warning

Copyright Dickinson FDA Webview at www.fdaweb.com.
Republished by permission.

Notwithstanding a recent FDA-NIH-U.S. Navy collaborative study that downplayed LASIK vision-altering surgery risks, three activists petitioned FDA commissioner Margaret Hamburg 12/24/2014 to add a black box warning to the labeling of lasers approved for the procedure. The petition alleges a “high incidence of induced visual symptoms (double vision/ghosting, starbursts, glare, and halos) and dry eyes” and asks the agency to send letters to professional organizations “to advise physicians of a black box warning on excimer lasers.”

The petition says the FDA-NIH-Navy study “demonstrated that three months after LASIK eye surgery, up to 45% of patients who had no visual symptoms before LASIK report [them] after LASIK, and up to 30% of patients who had no dry eye symptoms before LASIK report dry eyes after LASIK.” It cites a 2007 published review of data from 12 FDA clinical trials showing that six months after LASIK about 20% of patients reported that visual symptoms and dry eyes were worse than before surgery, much worse than before surgery, moderately severe after surgery, or severe after surgery.

“With millions of people having undergone laser eye surgery with such frequent problems,” the petitioners write, “it follows that there is an epidemic of visual symptoms/night vision problems and dry eyes caused by this unnecessary surgery. Unless the FDA immediately begins to provide adequately strong black box warnings about the risks and adverse effects of laser eye surgery, the epidemic will continue to grow. There have already been several reports of LASIK-related suicide and countless reports of suicidal ideation. A black-box Warning would help reduce the number of such negative outcomes and therefore falls well within the FDA’s mandate of protecting and promoting public health.”

FDA Dims LASIK Harms it Found in ‘Life Quality’ Study

Copyright Dickinson FDA Webview at www.fdaweb.com. Republished by permission.

October 20, 2014

In a long-awaited report on a collaborative study it conducted on the post-surgical quality of life of LASIK patients, FDA is downplaying the harms it found in up to 45% of 572 patients, adopting the industry-favored term “visual symptoms” vs. the agency’s former use of the terms “adverse reactions” or “adverse events.” Delivered by CDRH ophthalmic devices chief Malvina Eydelman at a LASIK-friendly forum staged by the American Academy of Ophthalmology (AAO) 10/17 in Chicago and posted on FDA’s Web site 10/20, FDA’s report said “some” patients in the study developed “problems” after surgery like “difficulty driving at night or in sunshine, [that] severely impacted a patient’s daily living, and included debilitating vision symptoms (seeing starbursts, glare, ghosting, or halos) and severe dry eye.” It says nothing about psychiatric problems, depression and suicide linked to adverse LASIK outcomes; its limited scope (three months post-surgery) and small subject base virtually assured it would not reach those associations.

FDA’s collaborators in the study were the National Eye Institute and the Department of Defense (especially the pro-LASIK Naval Medical Center in San Diego which encourages service personnel to undergo LASIK and performs most of the LASIK procedures that ensue). The overall study consisted of two underlying initial studies known as PROWL-1 and PROWL-2 (for Patient Reported Outcomes With LASIK), the former being among military personnel and the latter among patients of five commercial LASIK surgical facilities, one of which, the 20/20 Institute in Indianapolis, received an FDA warning letter during the course of PROWL-2 for failing to disclose LASIK risks and thereby misbranding the laser it used.

FDA’s report listed its main findings as follows:

  • Up to 45% of participants, who had no visual symptoms before surgery, reported at least one visual symptom at three months after surgery.
  • Participants who developed new visual symptoms after surgery, most often developed halos. Up to 35% of participants with no halos before LASIK had halos three months following surgery.
  • Up to 30% of participants with no symptoms of dry eyes before LASIK, reported dry eye symptoms at three months after their surgery. (This is consistent with previous studies.)
  • Less than 1% of study participants experienced “a lot of” difficulty with or inability to do usual activities without corrective lenses because of their visual symptoms (halos, glare, et al) after LASIK surgery.
  • Participants who were not satisfied with the LASIK surgery reported all types of visual symptoms the questionnaire measured (double vision/ghosting, starbursts, glare, and halos).

“The findings from this study will help to refine our current thoughts on the labeling for LASIK devices which will be incorporated into our patient labeling guidance,” the report says. “In addition, we will ensure our Web site reflects these findings to better inform consumers of the potential outcomes following LASIK.”

Commenting on Eydelman’s 10/17 AAO presentation, which closely tracked the report FDA subsequently posted to its Web site, LASIK-injured patient advocate Paula Cofer picked up on her admission that “dissatisfaction and disabling symptoms may occur in a significant number of patients.” In a Web posting on LASIK Newswire, Cofer quoted Eydelman as saying that further analyses should be done to explore “other associations” with [LASIK patient] dissatisfaction, and that additional longitudinal studies should be conducted to “explore the factors associated with and predictors of poor outcomes.”

“Remarkably,” Cofer comments, “six years and many tax-payer dollars later, Eydelman is suggesting ‘further analyses’ and additional studies. LASIK critics say Eydelman is a pawn of the LASIK industry and should be fired, and the FDA should take immediate action to protect the public by withdrawing its approval of LASIK. Although LASIK critics say they feel vindicated by the early reporting on the LASIK study, they doubt anything will change.”

LASIK Study Shows Significant Number of Problems

October 19, 2014
Preliminary results from FDA study of LASIK show significant number of patients experience problems.

Presenting preliminary results of the long-awaited LASIK Quality of Life Study during a keynote lecture at a meeting of the American Academy of Ophthalmology in Chicago on 10/17/2014, ophthalmologist Malvina B. Eydelman, MD, director of the FDA’s Division of Ophthalmic and ENT Devices, said that “dissatisfaction and disabling symptoms may occur in a significant number of patients”.

Plans for a study to consider how LASIK impacts patients’ quality of life were initially announced in 2008 around the time of a public meeting of the FDA’s ophthalmic devices advisory committee. The meeting was called in response to growing public criticism of the procedure and widespread reports of serious injuries. Testimony at the meeting from members of the public included reports of life-altering LASIK injuries and stories of LASIK-related suicides. Department of Defense LASIK surgeons and representatives of organized ophthalmology groups strongly defended the surgery.

Although LASIK critics were in favor of re-evaluating LASIK safety, many were incensed at the FDA’s plan to partner with organized ophthalmology groups for a prospective study, accusing the agency of placing the fox in charge of the hen house.

More than a year elapsed with no word on the proposed study. Then in October 2009, the FDA issued a press release announcing plans for a government-funded LASIK Quality of Life Study in collaboration with the National Eye Institute and the US Department of Defense. Mysteriously, military LASIK surgeons had replaced organized ophthalmology groups in the planned 2-part clinical study.

An article in the December, 2009 edition of the Journal of the American Medical Association (JAMA) reported that Steve Schallhorn, MD, Capt, US Navy (Retired) is “confident that once the quality-of-life issues are studied, LASIK will be shown to be even more safe and effective.” LASIK critics accused the agency of trading one embarrassing collaborator with conflicts of interest for another.

As a side note, in January 2011, former FDA branch chief for ophthalmic devices, Morris Waxler, PhD, petitioned the agency to withdraw FDA approval for all LASIK devices and issue a LASIK Public Health Advisory. Waxler had been conducting his own review of LASIK safety, and had concluded that the agency had made a mistake in granting the approval.

Five more years passed after the FDA’s 2009 update on the LASIK study. During the six year wait for the study results, the practice of LASIK continued status quo while LASIK injury reports stacked up at the agency. Currently, there are thousands of LASIK injuries on file with the FDA, although LASIK critics insist most injuries are never reported.

With the LASIK Quality of Life Study finally complete, LASIK critics wait for the manuscript to be published. Meanwhile, they point to data that were reported in Chicago to support their assertion that the procedure does not meet FDA safety requirements and therefore should not be performed.

  • Thirty percent of subjects with no symptoms of dry eyes before LASIK, reported dry eye symptoms at three months after their surgery.
  • Nearly half (45%) of subjects who had no visual symptoms prior to LASIK reported one or more visual symptoms 3 months after LASIK. These include halos at 35 percent, followed by starbursts at 28 percent, glare at 16 percent, and ghosting at 6 percent.
  • Visual symptoms were “very” or “extremely” bothersome in up to 4 percent of subjects.

LASIK critics assert that adverse outcomes are more common than the current study shows, as ‘real world’ outcomes are never as good as those reported in clinical trials. Visual symptoms, which are discounted by the FDA in evaluating LASIK safety, accounted for the majority of dissatisfaction with LASIK.

Ten percent of eyes did not achieve 20/20 vision, although subjects were presumably treated using the “latest technology.” Only 63.1% of subjects in study-1 and 53.5% of subjects in study-2 were “completely satisfied” with their vision at 3 months after LASIK.

The study included only 262 military subjects treated at the US Naval Medical Center San Diego with 6-month follow-up and 312 civilian subjects treated at five clinical sites across the US with 3-month follow-up. LASIK critics point to studies which suggest that LASIK results decline over time and published case reports of sight-threatening late onset complications which indicate that problems may present months or years after seemingly successful LASIK.

Moreover, average nearsightedness of subjects was just 2.5 diopters in study-1 and 3.6 diopters in study-2. Had the investigators included more patients with stronger prescriptions, the outcomes would have been even worse.

In her closing remarks, Eydelman is quoted as saying, “Further analyses are needed to explore other associations with dissatisfaction, and additional longitudinal studies are recommended to explore the factors associated with and predictors of poor outcomes.”

Remarkably, six years and many tax-payer dollars later, Eydelman is suggesting “further analyses” and additional studies. LASIK critics say Eydelman is a pawn of the LASIK industry and should be fired, and the FDA should take immediate action to protect the public by withdrawing its approval of LASIK. Although LASIK critics say they feel vindicated by the early reporting on the LASIK study, they doubt anything will change.
Sources for this article include:
(1) “FDA program tracks post-LASIK patient-reported outcomes.” Ocular Surgery News. Healio. Web. 17 Oct. 2014.
(2) Krader, Cheryl Guttman. “LASIK Quality of Life Collaboration Project characterizes benefit, burden.” Ophthalmology Times. Modern Medicine. Web. 17 Oct. 2014.
(3) Mike Mitka. “FDA Focuses on Quality-of-Life Issues for Patients Following LASIK Surgery.” JAMA.2009;302(22):2420-2422.
(4) Frederick Ferris, MD. PowerPoint presentation at AAO convention. 19 Oct. 2014.
(5) “LASIK Quality of Life Collaboration Project.” FDA. Web. 20 Oct. 2014.
(6) Larkin, Howard. “FDA Releases LASIK Patient Survey, Warns Of Large Numbers Of Dissatisfied Patients.” EuroTimes. Web. 20 Oct. 2014.
(7) Malvina Eydelman, MD. “LASIK Quality of Life Collaboration Project: Study Results Presented at the Refractive Surgery Subspecialty Day of the American Academy of Ophthalmology (AAO) on October 17, 2014” (PDF) FDA. Web. 21 Oct. 2014

Give FDA Authority over All Medical Device Ads?

Copyright Dickinson FDA Webview at www.fdaweb.com. Republished by permission.

Historically, U.S. law has given the Federal Trade Commission (FTC) primary authority to regulate the advertising and other promotion of prescription medical devices not otherwise “restricted” by FDA.

Restriction most commonly occurs in the conditions of approval stipulated in writing by FDA at the time of PMA approval, leaving the overwhelming majority of Class I and II devices unrestricted and therefore subject only to FTC, and thus scant, regulation of their advertising and promotion.

This is in stark distinction to other FDA-regulated prescription medical products, primarily drugs and biologics, which are unequivocally regulated in their promotional activities by FDA.

In practice, this has meant that the advertising and promotion of prescription drugs and biologics have been much more closely regulated than the marketing claims commonly made for most medical devices.

Lacking the in-house scientific backup that FDA has, FTC’s interest in medical devices has been minimal, a neglect that many Washington device lawyers justify by citing a fundamental difference between devices and drugs: the former’s characteristic ongoing and frequent design and materials change throughout the product life cycle, versus the latter’s static adherence to the formula, ingredients and indications as approved by FDA.

Arguments that there should be a public safety-based regulatory consistency for both categories of medical products frequently get short shrift from legal scholars.

But consider the case of hyper-advertised LASIK excimer lasers, which are “unrestricted” Class III devices and are therefore in FTC’s regulatory bailiwick, where they enjoy an unrestricted advertising world of bright-eyed people who’ve thrown away their glasses forever after what the ads portray as a quick and easy, painless procedure with a high-tech laser.

If you listen to CDRH former CDRH Diagnostic and Surgical Devices branch chief Morris Waxler, who approved the LASIK devices and Harvard assistant clinical ophthalmology professor Perry Rosenthal, who has studied their effects, you’ll glimpse the dark underbelly of FDA and FTC regulatory negligence. Here there’s an alleged LASIK adverse event rate that’s 20 times higher than FDA accepted when it approved the LASIK indication, and industry-dependent professional ophthalmology journals that reject papers trying to draw attention to it.

LASIK (laser in-situ keratomileusis) is a popular in-office procedure in which a U-shaped flap is cut by microkeratome blade in the surface of the cornea over the iris, the underlying stroma is contoured with an excimer laser, and the flap then folded back in place. However, untold to patients, the flap never heals, and is always prone to dislodgement and infection in such violent activities as contact sports and accidental trauma.

Waxler, who led the review team that approved the first of these lasers for LASIK in the late 1990s, was content with the decision until 2004, when a volatile and outraged Florida microjet salesman, Dean Kantis, tracked him down, now retired in Madison, Wisconsin.

Kantis operates a flamboyant Web site and belongs to country-wide networks of other injured LASIK patients. All allege they had received no FDA-required patient informed consent, namely the agency’s approved product-specific patient information brochure. LASIK surgeons do not answer to FDA because medical practice is regulated at the state level.

Kantis connected Waxler to other injured patients around the country. At first the retired FDA veteran was wary, but he gradually became sufficiently intrigued to begin personally researching the stories of the severely injured LASIK patients (including the mother of patient she said committed suicide due his LASIK injuries) and re-analyzing the industry-submitted PMA data on which he had relied to approve the devices. After five years in this effort, Waxler petitioned FDA in 2011 to withdraw the devices’ LASIK indication and issue a public health advisory.

Waxler’s conclusion: to get PMA approval, the laser makers had submitted fraudulent data to FDA attesting to a less-than-one-percent incidence of post-LASIK adverse events. Waxler’s re-examination of the PMA data revealed an incidence of more than 20 percent.

On this basis, the other 80 percent have no post-surgery problems, thus explaining, in part, the paucity of public complaints. Also the same devices have therapeutic, non-LASIK uses that are uncontroversial.

Meanwhile, Harvard Medical School assistant clinical professor of ophthalmology Perry Rosenthal had come to a parallel conclusion about the hidden LASIK adverse events.

Rosenthal identified and studied 21 patients who developed “unrelenting agonizing” eye pain following LASIK surgery, pain that had persisted for 2-15 years at the time of the study. He found that their pain was so “devastating and resistant to treatments that most of these patients admitted to thoughts of suicide.”

Rosenthal also discovered that the onset of this “neuropathic” eye pain was delayed in the majority of these patients, sometimes for many years after their eyes had healed and were comfortable. This type of pain had not been reported in the medical literature and because these eyes typically looked normal the sufferers had been accused of exaggerating or fabricating their suicide-provoking pain.

Nevertheless, his paper detailing these findings was rejected by two peer-reviewed ophthalmology journals and Rosenthal says he was forced to post it on his nonprofit Web site to avoid it being buried. He estimates there are 800,000 LASIK procedures every year worldwide and the available pool of surgical candidates is growing by 2 million eyes per year.

Rosenthal’s next step was to send his paper to FDA, despite being warned that the agency would not respond. FDA not only blew off Rosenthal’s study, it also blew off Waxler’s petition, just as it had previously blown off Kantis’ angry and insulting tirades (“Go to FTC,” it told him, but he found that agency to be just as disinterested as FDA).

After a 30-month wait, this past June Waxler received FDA’s formal denial of a petition he had filed seeking removal of the LASIK indication from all excimer lasers.

On July 22, he plunged onward, filing a petition for reconsideration in which he charged that FDA “grossly underestimates the risks of LASIK by conflating data used to legally support the PMAs with LASIK industry information used to promote sales.”

In doing so, he wrote, CDRH had sent two messages: that the LASIK industry could feel secure because “the agency has your back,” and that the public should beware because “FDA does not have your back.”

Waxler told the agency that it had “made deals” with the LASIK industry that “degraded the scientific quality of the collection and analysis of adverse event data of LASIK devices.”

He listed alleged deals with the following entities: Kremer Laser, American Society for Cataract and Refractive Surgery, CRS Inc., and more than 100 user facilities that he says received IDEs “to study LASIK in order to minimize their exposure to violating off-label rules.”

Would giving CDRH the authority to regulate all medical device advertising change its subservience to industry?

The only model we have is the more tightly regulated market environment for prescription drugs and biologics at CDRH’s sister Center for Drug Evaluation and Research (CDER), where historically promotional activities have been strenuously regulated. CDRH has a staff of three to review restricted device promotional activity, while CDER boasts a staff of 60 for this kind of work.

Medical device lawyers and proponents abhor the prescription drug regulatory template for the industry’s products, and the 1976 Medical Device Amendments and subsequent legislation have been careful to avoid such an imposition.

But when it comes to marketing and advertising at least, the LASIK experience gives us pause.

Patient Advocate Slams FDA Denial of LASIK Petition

Copyright Dickinson FDA Webview at www.fdaweb.com. Republished by permission.


LASIK patient advocate and former FDA LASIK advisory panel patient representative Paula Cofer has sharply criticized an eight-page FDA letter that denied a citizen petition submitted by former CDER branch chief Morris Waxler seeking the market withdrawal of approved LASIK excimer lasers and a public health advisory on their continued use.

Writing to FDA Webview, Cofer says the letter states that “risks associated with each LASIK device are described in the patient labeling” (patient information booklet), yet in 2006 FDA removed from laser approvals the requirement for patients to be given the patient labeling, stating, “[i]t is the responsibility of the practitioner, who is not regulated by the FDA, to provide the patient information booklet to their patients.”

Prior to 2006, Cofer writes, the conditions of approval for LASIK lasers contained the following or similar language, “[p]rospective patients, as soon as they express an interest in LASIK and prior to undergoing surgery, must receive from the treatment provider the Patient Information Booklet.” However, she says, LASIK patient advocates have repeatedly complained to the agency that LASIK practitioners withheld the booklets ─ “likely because the information contained in them would cause many patients to decline the surgery.”

Cofer says that in addition, FDA denied that it was ‘pressured’ by laser manufacturers to classify post-LASIK glare, halos, dry eyes, and night driving problems as ‘symptoms’ instead of adverse events; however, the agency acknowledged that these problems ‘may occur following LASIK surgery.’ They state that ‘[n]ot all of these visual symptoms are clinically significant enough to warrant classification as an adverse event’ and are often not persistent, according to published literature.

FDA, Cofer writes, “is aware of several LASIK-related suicides due to these types of so-called ‘symptoms,’ and the agency’s own database of medical device-related injuries contains thousands of reports of these very symptoms after LASIK, many of which describe these ‘symptoms’ as life-destroying. The agency states that ‘such visual symptoms are disclosed as potential risks in the patient labeling’ and that the ‘patient labeling for each LASIK device also includes a summary of the data on these visual symptoms observed in the clinical studies submitted in the PMA application.’

Cofer concedes that patient labeling for LASIK devices, “which most patients never see because the agency won’t enforce, discloses that approximately 20% of patients in LASIK clinical trials report halos, glare (starbursts), night driving problems and dryness persisting beyond the endpoint of the trials.

“Furthermore,” she continues, “the agency acknowledges the issue of problems with future cataract surgery raised by Dr. Waxler, but indicates that it has addressed this problem by partnering with the American Academy of Ophthalmology in the development of a patient k-card to record patients’ preoperative eye measurements. Again, the FDA has placed the fox in charge of the hen house. Virtually no LASIK practitioner provides the k-card to patients because doing so would alert patients to long-term consequences of LASIK, which were not disclosed prior to surgery.

Astonishingly, the agency refers to short-term patient satisfaction surveys in disputing points raised by Dr. Waxler in his petition. The scientists and officials at the FDA know full well that use of unvalidated surveys or questionnaires is neither scientific nor a reliable indicator of LASIK safety or efficacy.

“Indeed, the FDA repeatedly takes cover behind the patient labeling in its letter denying Dr. Waxler’s petition while simultaneously refusing to ensure that prospective LASIK patients actually receive the labeling. Dr. Waxler led the team at the FDA that reviewed the original pre-market application for LASIK. He knows what transpired. He was there. This is not simply a case of FDA failure to ensure the safety of a medical device; this is the FDA acting deliberately in the best interest of industry over public health. This is the FDA saying that patients do not have a right to know the hidden risks of LASIK before undergoing this irreversible, unnecessary surgery on their only pair of eyes. Clearly, as long as the current team is in charge at the CDRH and the Division of Ophthalmic Devices, they will continue protecting Big Ophthalmology.”

How FDA Dropped Patient Warning Rule from LASIK Approvals

Copyright Dickinson FDA Webview at www.fdaweb.com. Republished by permission.

FDA explains how a little-noticed change in its conditions of approval for LASIK lasers removed a patient-protection requirement two years before public complaints about eye injuries from the procedure erupted.

Two years before rising complaints erupted in public from LASIK patients with post-surgical vision problems, FDA’s Center for Devices and Radiological Health, on its own initiative, quietly removed a LASIK laser condition of approval that “[p]rospective patients, as soon as they express an interest in LASIK and prior to undergoing surgery, must receive from the treatment provider the Patient Information Booklet.” It took injured LASIK activists seven more years to notice the language change in CDRH laser PMA approval letters.

Last week, activist Paula Cofer questioned the approval letters’ language change in an email to FDA Webview editor Jim Dickinson, who in turn asked FDA for an explanation, and whether the change had been sought by the LASIK laser industry or by eye surgeons’ representatives. Both communities had been accused by activists for years of not passing on FDA-approved patient labeling to prospective patients prior to LASIK surgery. Although Cofer says their adequacy “is all over the place,” FDA-approved LASIK Patient Information Booklets often contain objective risk-benefit information, precautions and warnings.

In a response from FDA public information officer Synim Rivers, the agency acknowledged that it had used the missing language prior to 2006 as a condition of approval, and that it still requires final labeling (professional-use and patient labeling) from manufacturers during the review of marketing applications. “During this review,” Rivers’ response said, “we ensure that adequate safety/risk/procedural information is accurately conveyed in plain, understandable language. The manufacturer, in return, is required to provide this patient information booklet to the practitioner.

“In 2006,” the response continued, “we internally revisited the conditions of approval with respect to FDA’s regulations, and revised the conditions of approval for subsequent LASIK approvals. It is the responsibility of the practitioner, who is not regulated by the FDA, to provide the patient information booklet to their patients.”

As for whether the language change had been sought by industry or professional organizations, the response asserted that “the changes to our approval letter were not the result of external organizations or inquiries from external organizations. Instead, the changes were a direct result of internal discussions.”

Cofer told FDA Webview the agency’s explanation for dropping the Patient Information Booklet requirement “doesn’t hold up to the smell test,” especially since the change occurred shortly after the responsible CDRH review division was taken over by an ophthalmologist (Malvina Eydelman). “Malvina attends their conferences and rubs elbows with the leading refractive surgeons,” Cofer said.

“Why would FDA require patient labeling for LASIK devices, but not communicate the necessity of providing it to prospective patients? And how is this any different from a pharmacist negligently not providing patients with drug labeling? Why are patients’ rights more protected when they pop a pill than when they undergo an irreversible elective surgery on their eyes?

“Why not just clarify in the approval letter that the manufacturer is required to provide practitioners with patient labeling, and practitioners are required, in turn, to provide the patient labeling to ‘prospective patients as soon as they express an interest in LASIK and prior to undergoing surgery’, rather than simply eliminating the mandate from the approval letters altogether? This deliberate omission of the patient labeling mandate from the approval letters indicates that the agency is more concerned about protecting refractive surgeons than in ensuring that patients are fully informed of the known risks of LASIK.”

LASIK is safer than contact lenses MYTH

October 8, 2013

“LASIK is safer than contact lenses” is a myth that began with a letter from three biased LASIK surgeons, Mathers et al, to the editor of the journal Archives of Ophthalmology in 20061. In the letter, Mathers and colleagues draw some bizarre conclusions about the safety of contact lenses vs. the safety of LASIK, based upon a couple of published articles of eye infections from contact lenses and LASIK.

You’ve heard the phrase, “Lies, damned lies, and statistics”… The logic of Mathers and colleagues is so ridiculous that even other ophthalmologists have scoffed at it. But it does make a really good marketing soundbite, and so it has been widely adopted by LASIK surgeons seeking to scare patients into having LASIK. (Note: In 2009, Mathers co-authored a LASIK vs. contact lenses “decision analysis” based on a literature review2, which again failed to make the case that LASIK is safer than contact lenses.)

LASIK frequently leads to chronic dry eyes and night vision problems.3,4 Some patients suffer lasting eye pain. The bottom line is this: If you follow proper lens hygiene and don’t sleep in your lenses, contacts may be worn safely for a lifetime. LASIK, on the other hand, is an unnecessary surgical procedure performed on a very necessary organ of your body, which leads to permanent consequences such as incomplete healing of the flap with associated lifelong risk of flap dislocation, reduced and disordered corneal nerves which may lead to persistent pain and dry eye disease, risk of corneal ectasia (bulging) with associated vision loss, problems with future cataract surgery and glaucoma screening, and increased risk of eye infections. Furthermore, if you wear contacts and your vision changes, you can simply get a new pair. If you’ve had LASIK and your vision changes, you’ll face increased risk with repeat surgeries.

Any LASIK surgeon who employs the scare tactic “LASIK is safer than contact lenses” is a menace to society!

Update August 2015: The U.S. Center for Disease Control (CDC) issued a press release concerning risk behaviors associated with contact lens-related eye infections. A survey of contact lens wearers found that more than 99 percent of respondents reported at least one risky behavior. Clearly, if contact lens wearers clean, disinfect, wear, and store their contact lenses as directed, the risk of infection is extremely low — much lower than the risk of complications from LASIK.


1. Mathers WD, Fraunfelder FW, Rich LF. Risk of Lasik surgery vs contact lenses. Arch Ophthalmol. 2006 Oct;124(10):1510-1.

2. McGee HT, Mathers WD. Laser in situ keratomileusis versus long-term contact lens wear: decision analysis. J Cataract Refract Surg. 2009 Nov;35(11):1860-7.

3. Sugar A, Rapuano CJ, Culbertson WW, Huang D, Varley GA, Agapitos PJ, de Luise VP, Koch DD. Laser in situ keratomileusis for myopia and astigmatism: safety and efficacy: a report by the American Academy of Ophthalmology. Ophthalmology. 2002 Jan;109(1):175-87.

4. Bailey MD, Zadnik K. Outcomes of LASIK for myopia with FDA-approved lasers. Cornea. 2007 Apr;26(3):246-54.