treatment plan

Future Trials for Dry Eye

BY WILLIAM D. TOWNSEND, OD
AUGUS 1999

Although dry eye is usually thought of simply as a lack of moisture to the eye, it is far more complex and often more serious than its name implies. As we move toward the new millennium of eye care, researchers continue to explore several promising new dry eye therapies that may be available in the near future.

Making the Dry Eye Wetter

The dry eye has increased tear film osmolarity, which draws water out of the tissues, particularly the conjunctiva, and may contribute to the reduction in goblet cell density in dry eye patients. Jeffrey P. Gilbard, M.D., found that treatment with TheraTears (Advanced Vision Research), a hypotonic nonpreserved tear substitute, resulted in increased goblet cell density and a higher goblet cell population. Current research indicates that hypotonic products are the best means of rewetting the ocular surface and restoring goblet cell population.

Gobbels and Spitznas (Ophth., June 1992), demonstrated that drops that contain preservatives increase corneal epithelial permeability in dry eye patients, whereas nonpreserved solutions decrease surface permeability. Patients who use drops frequently should be treated with nonpreserved tear substitutes or products that have "disappearing preservatives." Genteal (CIBA Vision), originally formulated as a solution, was shown to have significantly less of an impact on the corneal epithelium than conventionally preserved solutions and has recently been introduced in gel form. Similarly, Refresh Tears (Allergan) contains a preservative that disappears when instilled in the eye.

Dry Eye is More Than Dryness

Stern, et al., (Allergan) have determined that in normal individuals, T-cells migrate through the main and accessory lacrimal glands. If they fail to detect inflammation, they die by apoptosis. But in dry eye patients, there are reduced androgen levels, which eventually lead to increased inflammation and lymphocyte infiltration of the glands.

The key to long-term dry eye therapy is not just wetting the eye, but also controlling inflammation on the ocular surface and within the lacrimal glands. Perpetual corticosteroid treatment can accomplish this, but its potential side effects make it an unacceptable option.

For many years, cyclosporine has been used successfully to treat dry eye in dogs, but now we may also benefit from its anti-inflammatory properties. Cyclosporine acts by interfering with the T-cell. Used systematically, it can cause hepatotoxicity and nephrotoxicity, and individuals being treated with it are at an increased risk for lymphoma, infection and convulsions. In treating dry eye, it is an immunomodulator rather than an immunosupressant.

Because the drug specifically targets T-helper cells, the instigators in cell-mediated immunity, and does not promote cataract formation or IOP elevation, researchers at Allergan speculate that it will be much safer for long-term use than are steroids.

They have shown that the drug decreases the immune response in the conjunctiva, and in time, increases goblet cell density in dry eye patients. More importantly, it has been shown to reduce the release of inflammatory cytokines and markers. Allergan's ocular form of cyclosporine (Restasis) is now in Phase III clinical trials.

In recent years, new research and technology have provided us with better ways to treat our patients. Although it is unlikely that cyclosporine will relieve all dry eye symptoms, it appears to be a promising step in the future of eye care.

Dr. Townsend is in private practice in Canyon, Texas, and is a consultant at the Amarillo VA Medical Center. (drbill@1s.net)