Where does one start when asked to discuss the many myths and misconceptions (M&Ms) that surround the diagnosis and treatment of dry eye disease (DED)? Heck, back in the day, a vast majority of eye doctors, both ophthalmologists and optometrists, were firmly of a mind that DED wasn’t a disease at all; for decades it was more often referred to as “dry eye syndrome.” Even that was a somewhat grudging acknowledgment for many MDs and ODs, most of whom just called it “dry eye.” With the exception of true, end-stage Sjogren’s disease, which requires a struggle to eke out a bare millimeter of tears in an unanesthetized eye, “dry eye” didn’t even rise to the level of capitalization, let alone syndrome. A disease? “Pshaw!” was the reaction from the medical masses.

That was just the first misconception about DED. I will start my demythologizing there, then I will detail — and deconstruct — each major M&M that impedes DED care.

1. DRY EYE IS NOT A REAL DISEASE

As with any true disease, the pathophysiology of DED has been worked out.

DED is a disease in which inflammation exists in some or all of the ocular surface, meibomian glands and the lacrimal glands. This triad has been called the “tear functional unit” (named by Dr. Gary Foulkes).

A complex feedback loop exists between the ocular surface and the brainstem. Dryness, be it due to aqueous deficiency or tear dysfunction, interrupts this feedback loop, creating greater degrees of localized dysfunction that leads to discomfort, visual disturbances or both. Essentially, all of the symptoms most commonly associated with DED can be explained within the context of this pathophysiology.

2. YOU CAN’T ACCURATELY DIAGNOSE DED

Still, contrarians remain who hold that diagnosing DED is a crapshoot. It is true that a disconnect can exist between the severity of symptoms and signs. Who among us hasn’t seen a patient with existential symptoms and nary a single punctate spot lighting up, or conversely one with a cornea as dry as a potato chip but who does not have a single complaint? And yet we think nothing of a patient with arthritis in their hips who bitterly complains about pain in the hip with less disease on X-ray. Like arthritis and many other inflammation-driven diseases, DED is a disease of symptoms that can be characterized by various objective signs that not only confirm the diagnosis but help determine which treatments to consider.

Which leads us quite nicely to …

3. DED IS A “LIFESTYLE DISEASE”

Adherents to this particular canard, which holds that DED is little more than an inconvenience, respond with the pithiest of prescriptions: “Just use some artificial tears, and you’ll be fine.” If only that were true! Imagine all the headaches we could avoid in our offices if we didn’t have to ferret out which medications were covered by which insurance plans so that we could learn who would be putting us on terminal “hold” while we seek prior authorizations.

Sadly, DED is a lifestyle destroyer. Barber et al showed that DED symptoms — at all levels of severity — have a negative effect on visual function, participation in routine activities and workplace production.¹ Hossain and co-investigators looked at symptom severity and found that increasing levels of symptoms had a correspondingly greater negative effect on both quality of life and workplace productivity.²

4. DED IS AN OLD PERSON’S DISEASE

One used to hear that DED is really only present in patients over age 60. The pandemic blew up that M&M, didn’t it? Those of us who treat DED daily have said for years that it is present in both sexes and all ages. Long before COVID-19 drove us all indoors in front of computer screens and in back of masks, evaporative DED in particular was reported in grade school children in Korea³ and adolescents in North Carolina.⁴

A combination of dramatically increased time spent looking at computer screens of all sizes coupled with the “omeganemia” (Hat tip to Dr. Michael Gross) brought on by industrial farming (protein sources are universally fed corn, a grain very low in omega-3 fatty acid) has driven the age of DED sufferers down to the point where literally any patient who eats a normal Western diet and looks at screens walking into your clinic could be a sufferer.

5. CARING FOR DED PATIENTS IS A DRAIN ON A PRACTICE

This is one of the most stubborn M&Ms in the DED world. These patients “take up too much chair time” and fail to generate sufficient revenue to justify including DED in the mix of diseases a practice typically cares for.

This is nonsense. Any practice that has managed to stay in business while treating glaucoma is more than capable of doing an excellent job diagnosing and treating DED.

Like glaucoma (and cataract surgery, etc), DED lends itself to protocol-driven care. A significant amount of data (as well as an account of a patient’s symptoms) can be collected by technicians and reviewed by a doctor. A basic exam for DED is no more involved or time-consuming than that glaucoma exam; both take less time than your typical cataract workup.

So, why is the fallacy that it takes longer to lay out a DED treatment plan than one for glaucoma so persistent? This part of the “drain on the practice” M&M that you can’t recoup your “time investment” was debunked in the early 2000’s through economic research conducted by Allergan’s now-defunct practice consulting service. Allergan applied analytics to DED’s effect on practice revenue that were similar to Allergan’s proprietary glaucoma adherence and persistence analysis of a practice’s billing records.

In addition to exam fees and charges for treatments such as punctal plugs, practice revenue increased contact lens and spectacle sales as well as LASIK and cataract surgery driven by referrals from happy DED patients.

It should be noted that this was more than 10 years prior to the advent of in-office treatments for DED such as vectored thermal pulsation, intense pulsed light and amniotic membrane grafts, each of which result in direct DED-driven revenue. If you can treat glaucoma without going out of business, you can do the same with DED.

Which leaves us with our last great DED M&M …

6. DED TREATMENTS ARE A SHAM

The basis of this M&M can be explained by invoking what I call the “Tylenol society” effect: If you have a headache, you take a Tylenol and in 30 minutes or so, your headache is gone. So, how can we say anything except steroids really work since only steroids really give you speedy relief from DED symptoms? The fact that many or our most commonly prescribed DED treatments can take weeks to months to reduce symptoms gives this M&M life. Long and slow only wins in fables and index-fund investing.

Two of our main treatment strategies run afoul of the “Tylenol society” effect: omega fatty acid replenishment and topical immunomodulator therapy using cyclosporine A (CsA). The DREAM study purported to show no benefit from the use of oral omega-3 fatty acid supplements in treating the signs and symptoms of DED.⁵

Sadly, for a study that was so widely publicized, the methods chosen to study re-esterified fish oil therapy contained too many confounding factors to enable it to isolate a single therapy of any kind. The much more specific approach taken by Epitropoulos and co-authors⁶ demonstrated that treatment with relatively high doses of EPA and DHA resulted not only in significant degrees of symptomatic improvement but also improvement in objective findings including tear break-up times and osmolarity.

Immunomodulators such as CsA continue to be targets of shade cast by a host of skeptics despite what, to us out in the wild, surely feels like efficacy. Yet, for every Seitzman and Leitman criticizing CsA based on the pivotal Phase 3 trials for Restasis⁷ (they are consistent, lining up in support of DREAM and against omega-3 supplementation), we have Hank Perry (and Eric Donnenfeld, among others) in 2006⁸ and 2008⁹ and Wan in 2015¹⁰ showing convincing evidence of improvements in DED symptoms and signs after 3 or more months of treatment with CsA.

The efficacy of omega-3 supplements as well as CsA (and lifitegrast) supports their use as core treatments for DED.

CLEARING THE WAY FOR BETTER CARE

DED is hardly the only case of M&Ms abounding in eye care. How else to explain the fact that such a small percentage of cataract surgeons routinely implant toric IOLs, let alone presbyopia-correcting multifocal and extended-depth-of-focus IOLs? Is it like this in all of medicine?

Thankfully, the biggest challenge posed by M&Ms in DED — that dry eye isn’t a disease at all — is largely a thing of the past. Newer in-office therapies will soon be joined by ever more effective treatments for ocular surface inflammation, meibomian gland dysfunction and inciting factors such as Demodex. All of these will hopefully chip away at whatever myths and misconceptions remain, clearing the way for better care for patients who need and deserve it. OM

REFERENCES

1. Barber L, Khodai O, Croley T, et al. Dry eye symptoms and impact on vision-related function across International Task Force guidelines severity levels in the United States. BMC Ophthalmol. Sept 29, 2018. https://tinyurl.com/yc8xmyvz . Accessed April 5, 2022.
2. Hossain P, Siffel C, Joseph C, et al. Patient-reported burden of dry eye disease in the UK: a cross-sectional web-based survey. BMJ Open. 2021;11:e039209.
3. Moon JH, Kim KW, Moond NJ. Smartphone use is a risk factor for pediatric dry eye disease according to region and age: a case control study. BMC Ophthalmol. 2016;16:188. Published online Oct. 28, 2016.
4. Gupta PK, Stevens NM, Kashyap N, Priestley Y . Prevalence of Meibomian Gland Atrophy in a Pediatric Population. Cornea. 2018 April;37:426-430.
5. Asbell P, Maguire MG, Peskin E, et al. Dry Eye Assessment and Management (DREAM) Study: Study design and baseline characteristics. Contemp Clin Trials. 2018 Aug;71:70-79.
6. Epitropolous AT, Donnenfeld ED, Shah ZA, et al. Effect of Oral Re-esterified Omega-3 Nutritional Supplementation on Dry Eyes. Cornea. 2016 Sep;35:1185-1191.
7. Seitzman G, Leitman T. Dry eye research — still regressing? Ophthalmol. 2019 Feb;126:192-194.
8. Perry HD, Solomon R, Donnenfeld ED, et al. Evaluation of topical cyclosporine for the treatment of dry eye disease. Arch Ophthal 2008 Aug; 126: 1046-1050.
9. Perry HD, Doshi-Carnevale S, Donnenfeld ED, et al. Efficacy of commercially available topical cyclosporine A 0.05% in the treatment of meibomian gland dysfunction. Cornea 2006 Feb: 25: 171-175.
10. Wan KH, Chen LJ, Young AL. Evaluation of topical cyclosporine for the treatment of dry eye disease. Arch Ophthal 2008 Aug; 126: 1046-1050.

Darrell E. White, MD, is an anterior segment surgeon and founder of SkyVision Centers in Westlake, Ohio.

Disclosures: Dr. White is a consultant and speaker for Allergan, Novartis and Sun Pharmaceuticals.