Combination Therapy May Increase Dry Eye Relief

Cyclosporine and punctal occlusion results in enhanced moisture and ocular surface health.

BY CALVIN W. ROBERTS, M. D.

There are a variety of well-known distinctions among patients with keratoconjunctivitis sicca (KCS) symptoms: some experience the burning, itching, photophobia and redness associated with chronic dry eye syndrome because T-cells in their tears cause inflammation. Other patients are exposed to environmental stressors that exacerbate these irritating symptoms. Still others are women over 40 years of age, so their dry eye may be hormonally mediated.

Common among the estimated 10 to 14 million Americans living with progressive KCS is that, while without effective treatment quality of life diminishes significantly, patients typically want a quick-fix, easy solution. In a recent study, my colleagues and I evaluated the effects of two popular dry eye therapeutics applied separately, as well as in combination, and our findings essentially support what I have experienced with my own dry eye patients: A dual approach with topical cyclosporine A 0.05% (Restasis, Allergan) and punctual plugs (Parasol, Odyssey Medical, Memphis, Tenn.), is the most successful.

The Study

In an effort to compare the effects of topical cyclosporine, punctal occlusion and a combination of the two modalities, we gathered a cohort of 30 test subjects from our pool of dry eye patients and randomized them to one of the three treatments. The first group was treated with topical cyclosporine A 0.05% b.i.d., the second group received punctal plugs and the third group received concomitant topical cyclosporine A 0.05% and punctal plugs.

We assessed the subjects' tear volume, ocular surface staining and artificial tear usage at baseline and then again at 1 month, 3 months and 6 months. Diagnostic staining with either rose bengal or lissamine green drops is considered an objective assessment of dry eye syndrome. In mild cases of dry eye, these dyes stain the conjunctiva, indicating significant goblet cell loss. In instances where the cornea becomes stained, the patient is probably already experiencing symptoms of vision fluctuation. Particularly noteworthy among our findings was that the topical cyclosporine alone and cyclosporine-with-plugs regimens improved lissamine green staining at the 3 and 6 month intervals.

We concluded that combination therapy produced the greatest overall improvements and was superior to plugs alone in decreasing artificial tear usage at 6 months. Interestingly, while all three regimens effectively treated dry eye, the cyclosporine-with-plugs regimen and the plugs alone regimen increased initial wetness and cyclosporine appeared to promote long-term ocular surface health. From a subjective standpoint, we observed that the subjects who were most comfortable based on the number of times they used artificial tears were those in the combination therapy group.¹

Treatment Theory

Current thought suggests that there are benefits to starting dry eye patients on topical cyclosporine to improve the quality of tears and then following up with punctal plugs. Placing plugs in a patient who has inflammatory tears will essentially trap these "toxic" tears and continue to bathe the ocular surface in inflammation. Ophthalmologists who ascribe to this treatment model use an anti-inflammatory therapy such as cyclosporine for several weeks in an attempt to improve the quality of the tear film and then add punctal plugs in a step-wise approach to treatment.

My dry eye treatment approach — punctal occlusion combined with cyclosporine — mirrors the regimen in our randomized study that resulted in subjects being most comfortable and achieving long-term ocular surface health.

Ultimately, when I follow this protocol, my practice and my patients benefit. When we plug these dry eye patients early on, they are the recipient of the best of both modalities. They profit from what plugs do best, which is to increase tear volume so they are less dependent on artificial tears and then over time they reap the rewards of topical cyclosporine A with an improved tear film quality. With this combination, I find that all of their symptoms improve dramatically.

Dry "Refractive Surgery" Eye

It is imperative to quickly improve the ocular surface and tear film quality for patients who are scheduled for refractive surgery. Decreased tear function is more often found in women 40 years of age and older and much less likely in men 25 years of age and younger. That said, every patient who has refractive surgery gets temporarily dry and those who start out dry usually get worse.

I screen every patient prior to refractive surgery with lissamine green staining and apply a subjective scale of my own design that results in any patient who has greater than +1 staining undergoing a dry eye treatment with a course of topical cyclosporine A, 1 month preoperatively and 2 months postoperatively. If the patient is still +1 on the lissamine green staining scale following 4 weeks of preoperative cyclosporine, I hold off on performing refractive surgery until the cyclosporine improves the ocular surface sufficiently.

The prevalence of refractive surgery, environmental trends and even lifestyle and hobby choices, such as excessive computer use and video screen viewing, influence the preponderance of dry eye disease among our patients. In my experience, using all of the available tools — from artificial tears, to cyclosporine, to punctal plugs, as well as the combination approach — is the best solution to what continues to be a growing threat to the quality of life among a significant portion of the population. OM

Reference

1. Roberts CW. Comparison of topical cyclosporine, punctal occlusion and a combination for the treatment of dry eye. Presented at the annual meeting of the Association for Research in Vision and Ophthalmology; May 2005; Fort Lauderdale, FL.

Calvin W. Roberts, M.D., is clinical professor of ophthalmology at Weill Medical College of Cornell University in New York. He can be contacted via phone at 212-734-7788 or email at RobertsMD1@aol.com. Dr. Roberts is a paid consultant for Allergan and has received unrestricted research grants from Allergan.