Early Intervention: Dry Eye Disease

Early Intervention: Dry Eye Disease

Early Intervention Can Change the Course of Dry Eye Disease

Sanjay N. Rao, MD

Accelerating the treatment of dry eye disease by using cyclosporine earlier rather than later in the course of the disease appears to slow progression in many patients.

Topical cyclosporine 0.05% (Restasis®; Allergan) treats inflammation associated with dry eye by increasing the eyes' natural tear production. Initially, many eyecare providers reserved cyclosporine for their more serious dry eye cases. However, it now is widely accepted that inflammatory mediators and the immune system cells they activate are key elements in pushing mildly symptomatic dry eye conditions toward potentially serious ocular surface disease. In theory, then, treating dry eye in its early stages should help prevent progression to more debilitating forms of the disease. We designed a study to answer the question: Does early intervention with cyclosporine successfully prevent disease progression?

Cyclosporine and Disease Progression

In this study, patients were randomized to receive either an artificial tear (Refresh Endura® [which has since been renamed Refresh Dry Eye Therapy®]) either alone or with cyclosporine.  Symptoms were measured using the validated Ocular Surface Disease Index (OSDI); signs evaluated included Schirmer testing and measurement of tear film breakup time (TFBUT), goblet cell density, and corneal staining.2  Patients were studied over a 1-year period.
 There were 36 patients in the cyclosporine-plus-arti­ficial-tears group and 22 in the artificial-tears-only control group. Disease severity was graded using the four levels recognized by what has come to be known as the "Delphi Panel" or the International Task Force (ITF).3At baseline, most of the patients in the study were level 2 (mild to moderate).
Several factors give weight to the results of this study: (1) they are in line with and confirm earlier clinical studies; (2) the relatively long study duration; (3) the use of evaluators other than the initial treating physician; and (4) the strong similarity between the two regimens, which eliminated potential confounding factors. (Refresh Endura is the vehicle used in Restasis; the only difference between the groups is the presence or absence of cyclosporine.)

Results

What we found was surprising and challenges the notion that mild dry eye is a relatively stable condition that can be adequately managed with artificial tears alone. By the end of the 12-month study, the cyclosporine group was doing significantly better than the tears-only group in every measure tested (Schirmer, TFBUT, goblet cell density, corneal staining, and ITF level) (Figures 1-3).

Rethinking Dry Eye Disease

The results of the study call for rethinking the conventional wisdom that moderate dry eye is best managed conservatively with artificial tears and that dry eye progresses slowly or not at all in many patients. On the contrary, this study found that there was measurable progression after only 1 year in about a third of the patients treated with artificial tears (Figure 4).

Furthermore, the control group in this study was not untreated. Rather, the controls were treated with a very good artificial tear, which is the standard of care in mild-to-moderate dry eye disease. In addition, the patient demographics in the study make its results clinically relevant for community eyecare practitioners. Two-thirds of the subjects were classified as having ITF level 2, or mild-to-moderate dry eye, the severity level that is most likely to present in a general eyecare practice.

Who Do We Treat?

In short, these results indicate that eyecare practition­ers should consider changing their treatment algorithms for dry eye disease, because treating sooner and more aggressively may prevent a significant number of patients from progressing to more severe levels of the disease.

Unfortunately, there is no single biomarker or other test that can identify which patients will progress. In my own practice, I monitor progress by using a dry eye questionnaire (like the OSDI) in addition to other testing. I then look for the presence of risk factors associated with severe dry eye, as listed in the report of the International Dry Eye WorkShop.4

My rule of thumb is: If patients have level 2 dry eye, plus any risk factors for progression, and are using artificial tears more than 4 times a day, I start them on cyclosporine to improve their dry eye signs and symptoms and, based on the results reported here, limit disease progression. The practical impact has been that about two-thirds of my Level 2 patients receive prescriptions for cyclosporine. Others are monitored and will be more aggressively treated if there are indications of increasing disease severity.

THE BOTTOM LINE

A 1-year study of patients with mild-to-moderate dry eye has shown that this level of disease can progress much more quickly than had been thought. The study also found that cyclosporine 0.05% can prevent progression and, in most cases, significantly decrease signs and symptoms. These findings suggest that eyecare practitioners who treat patients with dry eye should assess patients’ symptoms with a validated questionnaire, such as the OSDI, at every visit to determine whether using cyclosporine is warranted.

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Corneal specialist Sanjay N. Rao, MD, the medical director of Chicago’s Lakeside Eye Clinic. He received an unrestricted educational grant from Allergan to support this continuing research. He received editorial assistance with the article from Refractive Eyecare senior editor Linda Roach.

References         

1. Rao SN. Topical Cyclosporine 0.05% for the Prevention of Dry Eye Disease Progression. Presented at the Association for Research in Vision and Ophthalmology, April 2008, Fort Lauderdale, FL.
2. Schiffman RM, Christianson MD, Jacobsen G, et al. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000;118:615-21.
3. Behrens A, Doyle JJ, Stern L, et al. (Dysfunctional tear syndrome study group.) Dysfunctional tear syndrome: a Delphi approach to treatment recommendations. Cornea. 2006 Sep;25(8):900-7.
4. 2007 Report of the International Dry Eye WorkShop (DEWS). Ocul Surf. 2007;5(2):63-204.