Saturday, May 17, 2008

4/25/08 FDA LASIK Hearing: What happened to compassion?

Expressions of compassion in a public venue can come in many flavors.


I’m not picky. On April 25th, so far as I am concerned, any of the above would have done. It’s not as though I went to the hearing expecting an outpouring of sympathy for complications patients.

I was thinking along the lines of a thimbleful or two of smooth, designed-for-television lip-service to the people who had brought about the hearing, before moving on to happier topics, like the more than 800 ecstatically happy physicians and their families that such and such a speaker has operated on over the years, or the excitement of being landed on an aircraft carrier by a newly lasered F17 pilot whose surgery was performed by such and such a speaker.

But we didn’t get the thimbleful.


You’re in a public venue, you’ve just heard a bunch of people pouring their hearts out about years of emotional and physical suffering from surgical mishaps, botched aftercare and the like. You’ve even seen photos of suicide notes and heard calmly spoken but gut-wrenching stories from loved ones.

It’s as natural to say it as it is unnatural to not say it:

“I’m sorry for the pain you people have been through.”

But no.


It seems to me that logically there are three explanations:

One, you don’t get it.

Two, you get it and you don’t care.

Three, you get it and you care but acknowledging the existence and plight of an unfortunate minority is inexpedient.

Let’s try those one at a time.

1. Is denial a plausible explanation?

The physicians representing the LASIK industry that day are among the best-known and most respected in the country.

I cannot believe that, given their clinical experience and research background, they could have failed to grasp something of the life impact of severe post LASIK dry eye. In fact, I would argue that a working knowledge of the published medical literature on dry eye is all you need.

Furthermore, it is statistically implausible that any of them have not, by now, had some LASIK patients of their own with severe dry eye symptoms, some with distressing vision quality symptoms, and some with both. Even if that were not the case, it is certainly the case that they are all regularly consulted by patients with such symptoms whose surgery was performed elsewhere and who have come to them for a second opinion and further treatment opinions.

They can’t not get it.

To be honest, how anyone can have the audacity to act as though it’s not a problem is beyond me. I go to the trade meetings. Who floods my DryEyeShop booth looking for new dry eye remedies? The techs from the LASIK clinics. On the internet, what dry eye keyphrase fetches the very highest bids for click ads? “LASIK dry eye”.

There are even artificial tears marketed specifically for LASIK dry eye. Why is it we have “Laser Drops” in drugstores, but we don’t have “Sjogrens Drops” or “Menopause Drops” or “Geriatric Drops”? There are an estimated 4 million people in this country with Sjogrens Syndrome, of which severe aqueous deficient dry eye is a hallmark symptom. There are 7 million people who have had LASIK, 95% of whom are reportedly “satisfied”. Even supposing ALL of the “dissatisfied” 5% have dry eye, 350,000 people do not constitute a market for a retail eyedrop. Are pharmaceutical companies stupid, or do they understand patients’ needs that much better than the doctors do?

Denial? No way. The ophthalmic profession knows full well that LASIK dry eye is widespread and that a non-trivial number of the people with LASIK dry eye are in real distress for want of effective remedies.

2. Is sheer callousness to suffering the answer?

Engineer type. Perfectionist mentality. It beats me how these people can keep whining about a little bit of halo and starburst. I mean come on, I got him to 20/15 unaided! ... This gal is always talking about pain. I swear her corneas are white and quiet every single time I’ve looked at them, no staining, no nothing, but she just goes on and on. Another Restasis script and out you go. I’ll give her a couple of extra samples of Optive this time.... Boy, I wish there were a way to screen out the loonies, you never really know when someone’s going to go off the deep end about the slightest thing.... Real shame about this guy’s spherical ab, never seen such high numbers, but what can you do. Can’t take it personally. Stuff happens when you’ve got this many patients.... Why is Mrs. X still coming back? I thought I told you not to schedule any more follow-ups for her. There’s nothing more we can do for her.... Nancy, I overheard a patient talking to somebody in the waiting room about their dry eyes. I told you not to put those types in the general waiting room – use the small one at the back. It was full? Well put them in a room somewhere, don’t leave them out front for heaven’s sakes....

I know this brand of surgeon well. And no, of course I’m not suggesting that leading surgeons think this way. I’m merely pointing out that if wilful ignorance and authentic callousness are not the explanation for the failure to express any compassion towards the casualties of refractive surgery, there is only one other explanation:

3. Expediency.

Expediency carefully measures each and every statement in the light of how it could impact public perception of one’s trade and/or personal standing amongst one’s peers. Expediency consequently refrains from any public acknowledgement that (a) unpleasant outcomes impact significant numbers of people, and (b) for some people there are no successful treatments.

I can see all too easily how one might feel one can’t risk it. You just never know what the press might zoom in on. You’re one of the best-respected refractive docs in the country. You’re up there in the spotlight. Suppose you are the one that unwittingly provides the fatal soundbite to the press admitting that there are some truly unfortunate casualties out there. Think of the repercussions.

So expediency says things like:

There are many exciting new therapies under FDA evaluation....

Ha. Like rebamipide and pimecrolimus? Today’s exciting new therapies are tomorrow’s footnotes in a megapharma’s financials. On my clinical trial roster I have at least 25 exciting new therapies for dry eye in some stage of clinical research. How much money would you stake that 5% of those make it through Phase III clinicals? Restasis, for all its blockbuster sales now that it’s being prescribed for every indication that it was not approved for, narrowly squeaked through approval after failing twice. Once-promising diquafasol failed three times and has had to start over. So far as I know there is currently nothing anywhere near FDA approval. Mind, I’m pleased and very grateful that research is being done, but given the track record of dry eye drug clinical trials, the potential for new drugs is neither an adequate consolation to all the patients currently up a creek nor a sound basis for risk evaluation by future LASIK candidates.

Dry eye syndrome is extremely common... Severe dry eye post LASIK is extremely rare. (Dr. Donnelfeld)

(Dr. Solomon)

(Scott Barnes OBO Doyle Stulting)

(Dr. Schallhorn)

Et cetera.

Dry eye? What dry eye? Perhaps if we don’t talk about it, or if we act like it’s no big deal, the press and the public won’t think about it. After all, that policy has served us well for years. Never mind the evidence in the published literature, in our practice, at the professional meetings, and on the drugstore shelves.

Expediency can somehow hear of 5 different suicides connected to LASIK complications and look supremely unconcerned.

But most significantly:

Expediency diverts attention from real numbers of real, specific, prevalent complications - dry eye syndrome and glare disability - and focuses instead on THE RED HERRING OF PATIENT SATISFACTION. (The topic of my next post – stay tuned.)

But I’m not done with compassion yet.

The people I know with severe LASIK dry eye or other complications are real, live people.

They’re not some nameless, faceless 5% - or “possibly fewer than 1%” depending who you were listening to.

They’re real people.

Soccer moms.
Computer programmers.
Truck drivers.
Insurance adjusters.

They’re real people, and they deserved a lot more from the ophthalmic profession than they got that day.

Tuesday, May 13, 2008

Abstract: Aaaand another plug for... Are we in an echo chamber or something?

Do I seem kind of tough on these guys? Sorry. I just wish somebody would redirect a little of that effort to persuading insurance companies to fund the things that help the severe dry eye patients. I know people who are literally taking out second mortgages to fund their dry eye treatments. If we could just get things like moisture goggles and moisture chambers reimbursed that would be progress, anyway.

Prevalence, burden, and pharmacoeconomics of dry eye disease.
Pflugfelder SC.
Am J Manag Care. 2008 Apr;14(3 Suppl):S102-6.

Data from a large US managed care database suggest that the prevalence of clinically diagnosed dry eye disease (DED) is 0.4% to 0.5% overall, and is highest among women and the elderly. The burden of DED to the patient can be substantial, impacting visual function, daily activities, social and physical functioning, workplace productivity, and quality of life (QOL). Preliminary analysis suggests that DED also has a considerable economic impact in terms of both direct and indirect costs. A number of therapies have been shown to improve DED signs and symptoms, but few clinical trials have addressed QOL and economic issues. Limited data suggest that topical cyclosporine has the potential to reduce physician visits and use of other medications, including artificial tears; however, further research is needed to clarify its impact on both the direct and indirect costs of DED.

Abstract: Another kind of plug for Restasis

Next in the AJMC supplement series...

Artificial tears, steroids, plugs, Restasis. Emphasis on the blockbuster drug. Obligatory nod to lid care. Highly practical suggestion of avoiding exacerbating factors. (Eureka! I'll keep my eyes closed 24/7 so as not to subject them to exacerbating factors like office air, home air, and outdoor air. Golly, why didn't I think of that?)

Yawn. Some things never change.

Management of dry eye disease.
Lemp MA.
Am J Manag Care. 2008 Apr;14(3 Suppl):S88-101

The management of dry eye disease (DED) encompasses both pharmacologic and nonpharmacologic approaches, including avoidance of exacerbating factors, eyelid hygiene, tear supplementation, tear retention, tear stimulation, and anti-inflammatory agents. Artificial tears are the mainstay of DED therapy but, although they improve symptoms and objective findings, there is no evidence that they can resolve the underlying inflammation in DED. Topical corticosteroids are effective anti-inflammatory agents, but are not recommended for long-term use because of their adverse-effect profiles. Topical cyclosporine--currently the only pharmacologic treatment approved by the US Food and Drug Administration specifically for DED--is safe for long-term use and is disease-modifying rather than merely palliative. Treatment selection is guided primarily by DED severity. Recently published guidelines propose a severity classification based on clinical signs and symptoms, with treatment recommendations according to severity level.

Abstract: A plug for Restasis (so to speak)

The April issue of American Journal of Managed Care had a supplement on dry eye, including a few abstracts I'll share here.

This one says (among other things) that (a) Restasis on its own is cheaper than plugs on their own and (b) Fewer people go on to plugs after Restasis than go on to Restasis after plugs, therefore, (c) Adeste fideles, prescribamus Restasis.

Notwithstanding which, I'll pit my rice baggy, Dwelle and a Tranquileyes goggle against either or both of those therapies in a random selection of people with moderate to severe symptoms any day of the week. Oh for a few research dollars.

Utilization characteristics of topical cycolsporine and punctal plugs in a managed care database.
Fiscella RG, Lee JT, Walt JG, Killian TD.
Am J Manag Care. 2008 Apr;14(3 Suppl):S107-12

A retrospective administrative claims analysis of treatment options for dry eye disease (DED) evaluated treatment patterns and utilization characteristics of patients receiving cyclosporine, punctal plugs, or a combination of cyclosporine and punctal plugs, and examined differences in health plan costs with the 2 treatments. A total of 23,821 commercial health plan enrollees that initiated treatment with cyclosporine or punctal plugs between January 1, 2004, and December 31, 2005, were reviewed. There were 9065 subjects in the cyclosporine group, with a mean of 3.93 (median of 3) prescription fills reported in the 365-day follow-up period per subject. The mean health plan cost per patient was $336 (median $228), with total health plan costs of $3.05 million. In the punctal plugs cohort of 8758 subjects, there was a mean of 2.85 punctal plugs procedures per patient in the follow-up period. Total health plan costs for punctal plugs procedures were $3.28 million (mean cost per patient $375). During the follow-up period, 21.1% of punctal plugs patients subsequently received cyclosporine, whereas only 11.4% of topical cyclosporine patients subsequently received punctal plugs. Our results suggest that use of topical cyclosporine before punctal plugs insertion may be of benefit to patients with DED and could result in a savings in overall treatment costs.

Drug news: 3rd SCCO dry eye drug for Argentis

Argentis has in-licensed a third hormone-based drug developed at SCCO (ARG103), this time a combination testosterone and progesterone transdermal treatment they are hoping will help a larger number of post-menopausal women than their ARG101.

Click here for DryEyeZone's clinical trial roster (and if you have any updates please let me know!).

Click here for Argentis press release.

MEMPHIS, Tenn.--(BUSINESS WIRE)--arGentis Pharmaceuticals, LLC announced today that the company has licensed a third treatment for Dry Eye Syndrome (DES) now designated ARG103. This is a continuance of the licensing partnership arGentis has with the Southern College of Optometry (SCO) and becomes the third prospective therapy for DES that utilizes the transdermal delivery of an active pharmaceutical ingredient to affected glands via application of a cream or gel to the outer, upper and lower eyelids.

Developed by Charles Connor, Ph.D., O.D., FAAO, Professor and Director of Research at SCO, ARG103 incorporates a combination of the hormones testosterone and progesterone. A very high percentage of menopausal women respond to ARG101, a testosterone-based transdermal treatment designed for menopausal women who suffer from DES due to waning androgen levels. By combining progesterone with testosterone in ARG103, a larger number of post-menopausal women may respond to treatment. Dr. Connor stated, “One of the key problems with dry eye is inflammation of the surface of the eye. Progesterone provides extra anti-inflammatory power when added to testosterone for dry eye treatment and may even enhance meibomian gland secretion. This treatment addresses two crucial issues in dry eye patients.”

ARG103 will broaden the reach of arGentis’ transdermal ocular technology, which includes ARG101 for use in menopausal women and ARG102, a progesterone-based formulation that treats DES in younger women and men. The company will target the 40 to 60 million dry eye sufferers in the U.S. and over 100 million people worldwide with the three treatments.

“ARG103 strengthens our business and allows arGentis to offer effective treatment options using the novel transdermal delivery method to a larger patient population,” said Tom Davis, CEO of arGentis Pharmaceuticals. “We are very pleased with the research being conducted by SCO and look forward to ushering these treatments into clinical testing this year.”

Monday, May 12, 2008

Study: And speaking of depression!

I know most of you are not interested in retinitis pigmentosa (and many of you probably haven't ever heard of it). My interest in this particular abstract is thus: If somebody has bothered to study depression and quality of life in patients with an eye disease affecting an estimated 100,000 people in the US, surely we've got ample reason to be studying depression in...

1) People who have severe chronic dry eye and/or
2) People who have complications or severe adverse effects from LASIK

BOTH of which groups easily dwarf the RP population and both of which, as anyone from DryEyeTalk or D'Eyealogues can tell you, dramatically affect quality of life.

Doctors treating dry eye, and refractive surgeons, please take note of the last sentence in the abstract. Just substitute "dry eye" for RP.

Depression and the vision-related quality of life in patients with retinitis pigmentosa.
Hahm BJ, Shin YW, Shim EJ, Jeon HJ, Seo JM, Chung H, Yu HG
Br J Ophthalmol. 2008 May;92(5):650-4. Epub 2008 Mar 20.

AIMS: To assess the relationship between depression and the vision-related quality of life in patients with retinitis pigmentosa (RP). METHODS: The study included 144 patients diagnosed as having RP. The mean age of the patients was 38.5 (SD 13.3) years, and 42% of the subjects were women. They answered the National Eye Institute Visual Function Questionnaire (NEI-VFQ) to assess the vision-related quality of life and the Beck Depression Inventory (BDI) to assess depressive symptoms. Patients were classified into groups with and without depression according to the BDI score. The NEI-VFQ composite and subscale scores were compared between groups. The correlations between the BDI and the NEI-VFQ, weighted visual acuity (WVA) and functional vision score (FVS) were investigated. RESULTS: The depressed group had significantly less subjective visual function compared with the non-depressed group. A negative correlation was observed between the BDI and the NEI-VFQ scores, while no correlation was found between the BDI score and WVA or FVS. CONCLUSION: The RP patients with depression had poorer vision-related functions compared with those patients without depression, which cannot be explained by the visual acuity. Interventions to diagnose and treat depression are necessary to enhance the overall quality of life in RP patients.

Sunday, May 11, 2008

4/25/08 FDA LASIK Hearing: My letter to the FDA

Some of you may recall that when the 4/25 meeting was scheduled, the FDA invited the public to submit information in writing and/or request an opportunity to speak at the hearing.

The letters submitted in writing were all made available for viewing at the meeting. I leafed through the binder - there were stacks upon stacks of emails. It was interesting reading. Many were, of course, from complications patients. There were also many testimonials from happy patients.

For what it's worth... here is the text of the letter I sent to the FDA.


Ophthalmic Device Panel
Division of Ophthalmic and ENT Devices
Office of Device Evaluation
Center for Devices and Radiological Health
Food and Drug Administration

To the Members of the Ophthalmic Device Panel:

Re: April 25th meeting / LASIK

I am very grateful for the opportunity you have provided for the public to share their post-market experience with LASIK. I am writing to you on my own behalf and in two additional capacities:

1) As president of LaserMyEye, Inc., a 501(c)(3) nonprofit foundation I helped found which runs an informational website and online support group for people with complications from laser refractive surgeries; and
2) As founder and owner of The Dry Eye Company, which sells consumer products designed to improve quality of life for people suffering from dry eye, runs internet support groups, and collects and disseminates current information about the diagnosis and treatment of dry eye diseases.

My personal experience with LASIK

I underwent bilateral LASIK for high myopia and astigmatism in California in July of 2001. My surgeon is a highly trained cornea fellow with impeccable credentials. The excimer laser was a VISX Star S3, advanced technology at that time and still in common use. I considered myself a well informed patient. I was 32 years old at the time with healthy eyes and a stable refraction, and I was told I was an excellent candidate. I experienced no intra- or post-operative complications. I was given a videotape of my surgery which revealed no obvious errors. Nearly all my refractive error was eliminated in a single procedure.

Notwithstanding this superficially excellent result, I lost five to six lines of best-corrected visual acuity in each eye due to unexplained irregular topographical changes and high order aberrations. I also began to experience severe symptoms of dry eye, which worsened and have continued to this day. After two years of seeking treatment for the vision loss from some of the best international experts, including a second surgery on one eye which resulted in further loss, I had to leave a fulfilling and demanding career in international aviation finance due to poor visual performance and eye pain. I had no income source for approximately three years. I continued to seek treatment with large rigid gas permeable lenses with limited success. In 2006 I was successfully fitted with the Boston scleral prosthetic device (18.5mm custom lathed rigid lenses which hold fluid over my corneas). This has enabled me to work regular hours consistently. I wear these lenses all day, sometimes supplemented with moisture chamber eyewear for additional relief, and I employ various devices and products such as moisture goggles to protect my eyes at night. I am also heavily dependent on eye drops which proved so uniquely effective in my case that I purchased manufacturing rights to them in order to ensure their continued production.

While I have accepted my personal experience of LASIK and I would not hesitate to describe myself as a very happy person, there is no denying that for many years LASIK dramatically impacted my life physically, emotionally, professionally and financially, and it continues to affect me physically on a daily basis.

My qualifications to speak on behalf of other LASIK patients

Not long after my surgery, I discovered large numbers of unhelped and apparently unhelpable complications patients on the internet. I began engaging in informal patient advocacy work. While living in the United Kingdom (2002-2004) I counseled complications patients, undertook speaking engagements at medical conferences, ran a popular website for laser eye surgery patients, and lobbied for, then assisted in the proceedings of a special parliamentary committee to regulate the laser eye surgery industry in the UK

Since moving back to the US, I have engaged full time in helping fellow patients in any way I can devise. I joined with others to form nonprofit LaserMyEye, Inc., which took over the website I had personally formed and added an online community for patients to network. Later, I formed The Dry Eye Company (TDEC), in part to restore to commercial production three ophthalmic demulcents which had been sidelined by the industry but which have been remarkably helpful to many LASIK dry eye patients. TDEC now runs several popular consumer websites, an internet store with more than 75 specialty products for dry eye patients, an online ‘support group’ with more than 2,000 members and several doctor contributors, physician directories, product consumer reviews, newsletters and blogs. While it is aimed at dry eye patients of all kinds, LASIK dry eye patients represent a significant percentage of TDEC’s users and customers.

During the years 2002-2008, first as a patient advocate by hobby, then as founder and president of LaserMyEye, and finally as proprietor of The Dry Eye Company, I have personally interacted with at least 1,500 LASIK patients via telephone, support group meetings, email, and internet forums. Most of the remainder of this letter, in which I outline my key concerns with LASIK, is based upon those interactions and the research I have done on behalf of LASIK patients who have contacted me.

Problem #1: Clinical depression

The single most consistently recurring theme in all my personal dealings with LASIK patients is depression. Based on their own representations to me, I estimate that at least 85% of the patients I have interacted with have experienced clinical depression following their surgery. Furthermore, a disturbing number of these patients indicate they have experienced suicidal ideation. I have personal knowledge of several patients who have planned or attempted suicide and one patient who committed suicide, and I have second-hand knowledge of additional close calls and one further actual suicide.

The high incidence of depression following LASIK seems to be associated with the following patient experiences:

* Lack of validation:
o Physician disbelief of patient’s reported symptoms, e.g. glare disability; severe dry eye pain
o As a result, physician failure to order appropriate diagnostic tests, e.g. wavefront analysis
* Ineffectual treatment for dry eye pain. It does not seem to be widely recognized in the medical community how intense dry eye pain can be and that unremitting dry eye pain can drive patients do distraction. In TDEC’s online support group (, new members of all ages and walks of life routinely describe how their lives have been completely turned upside down.
* Unexplained and untreated visual symptoms (usually glare disability). As with dry eye, these symptoms can be experienced in a degree which is extremely distressing to the patient while physicians remain dismissive of its impact upon their lives.
* Impact upon work performance, leisure activities, driving ability, and home life.
* Impact upon relationships.
* Sense of isolation (physician says they are “the only one” reporting such symptoms; family and friends do not understand).
* Financial stress from medical costs and fears about future income loss.
* Self-blame due to the elective nature of the surgery.

Problem #2: Lack of remediation for the top two adverse effects of LASIK

Considering that I have dedicated a large part of my professional life to meeting consumer demand for information about treatments for dry eye and vision quality complaints from LASIK, I am well positioned to describe the plight of a special class of LASIK patients: The unhelpables.

LASIK is creating a non-trivial number of “unhelpable” patients. They typically share the following characteristics:

* They suffer from severe dry eye symptoms, reduced vision quality or both.
* Their occupation and personal lives have been profoundly impacted.
* Their relationship with their surgeon or other physician(s) responsible for their post-operative care has been discontinued, due either to frank abandonment (e.g. surgeon tells patient not to come back because s/he cannot do anything more for them) or voluntary departure by the patient because of the surgeon’s evident unwillingness and/or inability to help them.
* They have sought additional opinions from several doctors. Many travel nationally and internationally seeking out the best known specialists.
* They tirelessly research and attempt potential treatments. Some know more about current research, new products, and clinical trials than clinicians.
* They congregate on patient websites trying to glean new information and, most of all, to gain some hope for the future.

Of these, none speaks more plainly to the failure of remediation than patient abandonment, whether occurring in a medico-legal or strictly moral sense.

Why is this happening?

First, there is a persistent reluctance to admit to the troubled patient what is evident throughout published medical literature and is talked about openly in medical circles: that dry eye and vision quality problems are not only real and measurable, but are not even unusual. A problem that is not acknowledged is not treated. Without validation or treatment, the patient’s anxiety escalates, and the relationship rapidly breaks down.

Second, there is a fundamental disconnect between what a surgeon considers to be a successful LASIK procedure, i.e. a patient with a greatly improved uncorrected visual acuity, and what a patient considers to be a successful LASIK surgery, i.e. a surgery that by and large leaves them better off than they were. Patients with enough pain will consider themselves worse off no matter how good their vision is. Patients with severe enough vision quality problems will consider themselves worse off no matter what line they can make out amongst the ghosts and fuzz on the eye chart. Patients with poor vision quality and in pain are just downright miserable by any measure. Yet some LASIK surgeons persist in a kind of willful agnosia for patient complaints if the patient can, squinting and grimacing, make out some characters on the 20/20 line.

A classic example of this appeared in a New York Times article on 3/13/2008. The journalist chronicles her personal experience with LASIK. She is manifestly dissatisfied with her outcome due to persistent dry eye and poor vision quality. Her surgeon, when interviewed for the article, states that she considers the patient’s procedure a success. The surgeon is even quoted as saying “In 18 years of practice, I’ve never had a patient whose symptoms don’t go away.”

There is, of course, a simple explanation for this kind of claim:

The symptoms did not go away. The patients did.

It’s called “lost to follow-up”.

Problem #3: The myth of voluntary post-market reporting

The FDA’s policy of reliance on voluntary reporting of adverse patient outcomes by LASIK surgeons and device manufacturers is an abject failure. Physicians, and possibly manufacturers, have a poor understanding of their reporting obligations. Physicians and manufacturers alike have glaring financial disincentives to report poor patient outcomes. To grasp the reality of this, one need only look at the stark contrasts between adverse event incidence as reported in (a) device labeling, (b) published medical literature, and (c) the FDA’s MAUDE database.


Ocular surface disease and glare disability secondary to LASIK can be so physically and psychologically devastating that they deserve “black box” warnings.


Rebecca E. Petris