rx perspective
New Frontiers in Dry Eye Treatment
For the first time, an eyedrop increases tear production by reducing inflammation.
By Henry D. Perry, M.D., and Eric D. Donnenfeld, M.D.

Most of our dry eye patients have tried everything under the sun for relief, without success. Now they're seeing a glimmer of hope. On Dec. 23, 2002, the FDA approved Restasis, a new topical product for the treatment of chronic dry eye disease that promises to treat the underlying disease -- not just the symptoms.

How It Works

According to Allergan, Restasis is the first and only eyedrop that increases tear production in patients with chronic dry eye resulting from ocular inflammation. Restasis consists of a 0.05% concentration of cyclosporine A -- a powerful immuno-modulator that inhibits the activation of T-cells and has profound anti-inflammatory properties -- in an emulsion formula.

Restasis also reverses the pathologic apoptosis, or programmed cell death, that chronic dry eye disease causes in lacrimal gland tissue. In a healthy eye, lymphocytes live for about 110 days; lacrimal gland tissue usually survives for years. In the disease state, chronic inflammation causes the lymphocytes to live longer and the lacrimal gland tissue to die more quickly. As a result, chronic dry eye patients may eventually lose all lacrimal gland tissue. Restasis prevents this.

Because Restasis doesn't eliminate pre-existing T-cells, it requires at least 3 months for the benefits of treatment to occur as T-cells gradually die and are naturally depleted. Also, the reverse apoptosis that existed before Restasis use can allow some lymphocytes to remain for as long as 6 months. This means that some of the beneficial effects of Restasis take time to appear.

Clinical Results

Allergan recently completed a 6-month Phase III clinical trial evaluating 877 patients. The subjects were divided into three groups: One group received topical cyclosporine 0.05% b.i.d.; a second group received cyclosporine 0.1% b.i.d.; a third group received a castor oil-based topical emulsion vehicle b.i.d. (After 6 months, the third group received cyclosporine 0.1% for an additional 6 months.) Most subjects had significant dry eye disease; 31% had Sjogren's syndrome.

The study showed that corneal staining improved significantly between 4 and 6 months after the use of topical cyclosporine. Seven-teen percent of the subjects reported some ocular burning from the drops, but the drug was well tolerated, safe and effective. (In contrast, patients taking topical anti-inflammatory drugs or using punctal plugs show no increase in tear production.)

The Patient Perspective

In our experience, patients are compliant. They're happy to wait 3 months or more for complete relief once they understand the disease process and the way Restasis works. In addition, some patients report that the Restasis emulsion provides immediate relief.

Patients who have significant disease or require punctal plugs, or who use artificial tears four or more times a day, should benefit most from Restasis. Restasis may also help patients suffering from rheumatoid arthritis, scleroderma, Hashimoto's thyroiditis, systemic lupus erythematosus, progressive systemic sclerosis, polymyositis or Waldenstrom's macroglobulinemia -- conditions associated with either secondary Sjogren's syndrome or keratoconjunctivitis sicca.

It's still too early to know just how big an impact Restasis will have, but its potential is clear. And our patients are thrilled that real relief may be on the horizon.

Dr. Perry is clinical associate professor of ophthalmology at the Weill College of Medicine, Cornell University, serves as medical director of the Lions Eye Bank for Long Island at North Shore University Medical Center and is chief of the cornea service at Nassau University Medical Center. Dr. Donnenfeld is co-chairman of cornea and external disease at Manhattan Eye, Ear and Throat Hospital, surgical director of the Lions Eye Bank for Long Island, and associate professor of ophthalmology at New York University Medical Center.