THERAPEUTIC FORUM

Cyclosporin May Treat
Underlying Cause of Dry Eye

by Christopher J. Quinn, O.D.

Ever since we've been treating dry eye, optometrists and other doctors have addressed the symptoms, not the cause. Often the results have been less than optimal. Now, a new topical treatment could be in the offing that would target the underlying etiology of dry eye. 

Dry eye syndrome, of course, represents a spectrum of conditions, all resulting in irritation of the ocular surface. Patients frequently complain of a dry, gritty sensation, burning and irritation, photophobia, increasing contact lens intolerance and even blurred vision. Symptoms are more common in postmenopausal women and often are worse later in the day.

Not only are the symptoms of dry eye annoying, but dry eye patients are susceptible to greater risk of corneal infection and failure of corneal grafts following penetrating keratoplasty. Among patients with dry eyes, many suffer from true aqueous deficiency: a lack of production of the aqueous layer of the tear film.

Traditional treatment of dry eye has been palliative through the use of tear supplementation. Frequent administration of tear supplements often provides transient symptomatic relief, but the success of the treatment is limited by the need for frequent tear instillation and the often toxic reaction of preservatives in artificial tears. Recent advances in artificial tear formulas have improved treatment, but haven't eliminated the need for frequent administration.

Punctal occlusion has also improved our ability to manage dry eyes. Punctal occlusion helps preserve the patient's natural tears and can dramatically reduce the frequency for eye drops in patients with mild to moderate dry eye.

Addressing the Cause
Although improvements in artificial tears and punctal occlusion are worthwhile, researchers are now targeting the underlying cause of dry eye. Evidence suggests that many cases of dry eye are the result of a cytokine-mediated inflammatory process.1 The release of these inflammatory mediators and the activation of T-cells causes tissue destruction in both the lacrimal gland and on the ocular surface. This inhibits tear production which obviously leads to dry eye.

Recently, cyclosporin A in a topical preparation has been tested for the treatment of dry eye. This potentially effective new modality is different from traditional tear supplementation since it may address the underlying etiology of the disease through its immunomodulatory/anti-inflammatory action. Cyclosporin prevents activation of T-cells and production of inflammatory cytokines, the molecules that spark the inflammatory response on the ocular surface.

Cyclosporin A has been used successfully for years to treat systemic immune-mediated conditions. It's most commonly used to help prevent tissue rejection and to treat autoimmune disease.

An 0.05 percent formulation seems to reduce patients' dry eye symptoms, show improvement in corneal staining, improve Schirmer test scores and reduce the frequency of tear supplement administration.

The drug appears to be well tolerated; no significant adverse effects have been reported. Cyclosporin would be administered twice daily, and the benefits of using it in selected patients may continue to rise with longer use (up to six months). Some systemic absorption of the drug has been demonstrated following topical use, but the serum levels are far below those known to be associated with the side effects from the systemic administration of the drug.

Despite the promise of this potential therapy for dry eye, the FDA has recently bounced back Allergan's application for this drug. The company will apparently attempt to meet the FDA's requirements, but it's unclear when the drug will be able to be approved.

1. Stern ME, Beuerman RW, Fox RI, Gao J, Mircheff AK, Pflugfelder SC. The pathology of dry eye: the interaction between the ocular surface and lacrimal glands. Cornea 1998 Nov;17(6):584-9.