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July/August 2007

 
Clinical Update: Cornea
Dry Eye Gets Some Respect
By Leslie Burling-Phillips, Contributing Writer
 
 

Dry eye disease is one of the most common ocular complaints in the United States. Estimates suggest that approximately 3.23 million women and 1.68 million men—nearly five million Americans—50 years and older have moderate to severe dry eye. And tens of millions more are affected by milder symptoms that occur periodically when triggered by an adverse event or environmental agents. However, the condition is comparatively unrecognized and therefore undertreated. According to some calculations, only 5 percent of people who experience symptoms receive a formal diagnosis.

Recent advances in the understanding of dry eye disease, and the introduction of new products to relieve it, have helped bridge this gap.


Sorting the Complexities

Dry eye disease is a complex condition associated with a wide variety of individual, environmental and disease-related factors. Patients may present with many symptoms or only a few, and often the signs and symptoms described are contradictory. For example, a patient may present with inflammation and redness but experience no discomfort. In contrast, some patients aren’t able to articulate their problem effectively; they merely know that they have ocular discomfort.

“This is one of the biggest challenges in research,” said Gary N. Foulks, MD, professor of ophthalmology at the University of Louisville. “Clinical trials have been hampered by the fact that symptoms and signs do not always match each other, which is a requirement for the approval of drugs.”

Seeking a consensus. In an effort to better define dry eye and resolve these inconsistencies, a Delphi panel of specialists convened several years ago to develop treatment recommendations for dry eye disease. “One of the most important things that came out of the Delphi panel was a consensus on how to identify different levels of dry eye severity,” said Michael A. Lemp, MD, clinical professor of ophthalmology at Georgetown University in Washington, D.C. The panel realized, however, that a more expansive effort was warranted, and called on the Tear Film & Ocular Surface Society for help in organizing the 2007 International Dry Eye Workshop (DEWS). The result was an exhaustive report by DEWS published in the April issue of The Ocular Surface.1


What, Exactly, Defines “Dry”?

According to the DEWS report:

Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance and tear film instability, with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.

Dr. Foulks described the latest thinking on the physiology of tear film. “There are a number of proteins and lipids in the tear film. It was once thought that these components operated independently, with proteins covering the corneal surface and water separating the proteins from the lipids. However, the tear film is a much more interactive fluid than simply a three-layer sandwich, and this interaction has a direct impact on tear film stability.” And since tear film is the most anterior surface of the optical system, any irregularities (rapid tear breakup time, for example) can exert considerable impact on visual acuity.

No shortage of symptoms or causes. Dry eye symptoms may include redness, itchiness, grittiness, stinging, burning, dryness, excessive tearing, blurry vision, increased blinking, mucous discharge and general discomfort. The causes of these symptoms are even more variable and include older age, smoking, contact lens wear, environmental irritants, rosacea, female gender, previous refractive surgery, a variety of medications, certain autoimmune disorders and lacrimal gland trauma.

In some cases, particularly among people who have extended gaze patterns, blinking does not occur frequently enough. As a result, the tears do not get spread across the eye properly and dry eye occurs. In all cases of dry eye, symptoms may develop or become exacerbated when the weather is windy, the air quality is poor or the humidity is low.


A Look at Diagnostics

There are a number of tests used to identify dry eye; unfortunately, each has its shortcomings. Few can be performed quickly and inexpensively.

Schirmer’s. The current gold standard is the Schirmer’s test. However, there is little agreement about its reliability and in which patients its use is most effective. Dr. Foulks said, “There is variability in patients who have early dry eye. When you’re applying a Schirmer’s strip to the eyelid margin, a certain amount of stimulation occurs. If you don’t use an anesthetic, you’re measuring reflex tearing as well as basal tearing.”

William B. Trattler MD, volunteer assistant professor of ophthalmology at the University of Miami, added, “The test is useful in patients who have moderate to severe dry eye. If a patient has a low Schirmer’s score, it will remain relatively consistent over time.” Dr. Lemp noted, “There are a lot of ophthalmologists who don’t use it any more. It’s a valuable test but not useful on every patient. It’s not a test that you can perform one time and obtain the necessary diagnostic information.”

Tear film normalization. Because Robert A. Latkany, MD, founder and director of the Dry Eye Clinic at the New York Eye and Ear Infirmary, believes the Schirmer’s is unreliable, he devised his own test—the tear film normalization test.2 “It’s extremely sensitive and specific. Take into consideration that people with dry eye occasionally have intermittent blurry vision. When I test their vision and they get to a line on the Snellen chart that they find is difficult to read, I administer a low-viscosity drop in their eyes. Then I ask them to look at the line that was blurry before I administered the drop. If they improve one line of vision, they likely have dry eye. If they improve two lines of vision, they definitely have dry eye. If they don’t improve at all, it is almost certain that they do not have dry eye. It’s very simple and straightforward,” said Dr. Latkany.

Staining. Techniques that highlight damaged cells and dry spots on the corneal surface, such as fluorescein, lissamine green and rose bengal staining, are beneficial in detecting dry eye with a slit-lamp biomicroscope. These techniques can also identify abnormalities in the position and functioning of the eyelids as well as dysfunction in meibomian glands that may lead to dry eye. “Lissamine green is better tolerated and is not as likely to damage cells as rose bengal,” said Dr. Foulks.

Asking the patient. “Patient history is an integral part of the diagnostic process,” said Dr. Trattler. “Are medications present that might reduce the production of tears? Do they have any systemic conditions like rheumatoid arthritis or inflammatory conditions like Sjögren’s syndrome? Do they sleep with a fan blowing over their bed? A thorough history is the best place to start, followed by an eye exam.”


Sorting Through Treatments

A topical cyclosporin emulsion (Restasis) was approved several years ago as the first prescription treatment for dry eye. “It’s fairly effective, but it’s not for every dry eye patient,” said Dr. Latkany. Similarly, not all over-the-counter tear supplements work for every patient. “Each of the OTC products addresses various problems that patients experience with dry eye. But figuring out who does best with which product is sometimes like putting pieces of a puzzle together,” he said. At least 17 novel treatments are now in clinical trials. They include anti-inflammatories, secretagogues and androgenic and estrogenic agents (for a full list, visit this story online at www.eyenetmagazine.org).

The tears of the future. The DEWS report is a landmark document for ocular surface medicine. Yet despite its breadth and depth, much is left to learn about dry eye etiologies. The endocrine and immune systems, for example, have considerable effects on the physiology of the lacrimal gland. “Controlling inflammation will continue to be important, particularly in conditions that produce systemic immune-based inflammation. The secretagogues will add to the equation. A combination of testosterone and estrogen may be used,” said Dr. Foulks. “Ultimately, treating dry eye is going to require a combination of treatments.”
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1 Ocul Surf 2007;5:67–199.
2 Cornea 2006;25(10):1153–1157.
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Dr. Foulks has consulted for Alacrity, Alcon, Allergan, Alimera, Bausch & Lomb, Inspire, Ista, Nascent, Novartis, OcuSense and Ostuka and has received research support from Alacrity, Alcon and Allergan. Dr. Latkany is on the speakers’ bureau for Alcon, Allergan and Bausch & Lomb. Dr. Lemp has consulted for Alcon, Allergan, Santen, Novartis, Inspire, Otsuka, Fovea, Novagali, OcuSense, Kolis, Argentis and Kosan and has invested in Inspire and OcuSense. Dr. Trattler has received research support from Allergan, Odyssey Medical and Sirion Ophthalmics, honoraria from Allergan and Inspire and has consulted for Allergan and Inspire.