discovering dry eye

The Future of Dry Eye Research

BY KELLY K. NICHOLS, OD, MPH, PHD
October 2001

Almost every ophthalmic journal or periodical has had at least one dry eye article in that last year, if not the last month. Currently two pharmaceutical companies are in the midst of FDA approval process for a dry eye medication, and news of the ongoing process is readily available. Have we heard or learned enough about dry eye?

True, dry eye is a chronic disorder that can be extremely debilitating for those with severe forms of the disease. However, aren't those patients with mild forms of the disease just complainers? After all, it is nearly impossible to reliably classify these patients on traditional dry eye diagnostic tests for dry eye (e.g. Schirmer test and tear break-up test). On most occasions, patients with mild dry eye may­or may not­fail these tests. Left with only symptoms to go on, concerned practitioners discuss dry eye, dispense artificial tear samples and tell the patient they will see him next year.

I am convinced most dry eye patients aren't complainers. The tests that we use clinically may not be able to detect mild forms of the disease. In truth, we may be measuring the wrong thing. A clinical test that measures a related component of a disease but is not a true measure of the disease is called a surrogate test. In mild cases of dry eye disease, our dry eye tests may all be surrogate tests.

Clinical Trial Test Selection

At the Association of Research in Vision and Ophthalmology (ARVO) annual meeting earlier this year, a group of approximately 40 dry eye researchers, industry representatives, FDA representatives and National Eye Institute organizers discussed dry eye research. Similar to the earlier dry eye workshops in 1993 and 1994 that resulted in the publication "The Report of the NEI/Industry Report on Clinical trials in Dry Eye" (Lemp, 1995), this workshop focused on the tests used to classify dry eye. The 1995 report emphasized several dry eye tests, including the assessment of tear osmolarity, ocular surface staining with fluorescein and lissamine green, and fluorescein tear break-up time. While rough guidelines for each individual test were discussed, consensus regarding the order of tests and the discussion of diagnostic test batteries was limited.

Fast forward eight years, and we are still having the same discussions. While significant advances have been made in understanding dry eye on the molecular lever, these advances have not crossed over to clinical care: the diagnosis and management of dry eye. Over the course of one day at the workshop, five diagnostic tests were discussed in detail: the Schirmer I test, tear break-up time test, the assessment of symptoms, ocular surface staining and tear film osmolarity.

After lengthy discussion, one glaring fact remained: different tests may be needed to differentiate mild dry eye from moderate-to-severe dry eye. In the evaluation of a disease process, researchers hope to select one test to evaluate the disorder across the disease spectrum. Evaluating dry eye symptoms may be the only assessment that spans disease severity. The characterization of symptoms is not without difficulty. Language differences, agreement of the appropriate survey to use and methods of survey data analysis are only a few of the challenges facing researchers.

Dr. Nichols is assistant professor of clinical optometry at The Ohio State University College of Optometry in the area of dry eye research.