Dry Eye Dx and Tx
Checking the Dry Eye Pipeline
BY WILLIAM TOWNSEND, OD, FAAO
Up to 13 percent of Americans suffer from some form of dry eye (Schein et al, 1997). The reported incidence in Asia is even higher at up to 33 percent of the population (Shimmura et al, 1999). This need presents opportunities for pharmaceutical and instrument companies to devise agents and instruments to help provide relief. The following such products are in development or have recently been released.
In April 2010, Novagali Pharma, a French pharmaceutical company, announced the successful completion of a Phase 2 clinical study with Cyclokat, its unique formulation of cyclosporine for the treatment of dry eye. Their product utilizes Novasorb, a proprietary ophthalmic emulsion, as a carrier, thus enabling optimal penetration of cyclosporine into ocular tissue. Alcon Laboratories recently acquired Zyclorin, a topical ophthalmic form of cyclosporine, from Sirion Therapeutics.
Formulating the perfect substitute for tears is perhaps an impossible task; tears contain more than 500 components. Several efforts have been made to develop a tear product that mimics the tear film or at least contributes to its three major layers (aqueous, lipids, and mucins). Alcon’s Systane Balance Ophthalmic Emulsion is currently being investigated in a Phase 3 study for the treatment of meibomian gland dysfunction.
Researchers are constantly looking for “molecules” that enhance or promote tear production. In April 2010, the Japanese Ministry of Health granted approval for Diquas Ophthalmic Solution 3% (diquafosol tetrasodium) (Santen Pharmaceutical Co., Ltd.). Diquas is the first P2Y2 receptor agonist in the world to be approved for formulation as an ophthalmic solution. It treats dry eye by promoting the secretion of water and mucin. This same product has received two approvable letters from the U.S. Food and Drug Adminstration but continues to await approval by the agency.
Declining androgen levels have been identified for some time as a causative factor in dry eye, particularly in females. Unfortunately, systemic androgen therapy is not without complications including secondary sexual characteristics, changes in skin and hair, and increase in serum low density lipids. Allergan currently has a topical form of androgen in phase 2 trials. Androgens exert hormonal control of tear secretion and protect the tear-producing glands.
Alterations in tear film osmolarity have long been recognized as a crucial feature of dry eye disease. Gilbard et al (1978) demonstrated consistently elevated tear film osmolarity in individuals who have dry eye. Their testing used alterations in freezing points to determine tear film osmolarity; this technique required harvesting of micrometric volumes of tears and determining the degree of freezing point depression that resulted from heightened osmolarity. These ex vivo measurements are often plagued by many difficulties, which can result in test-induced alterations in osmolarity. In addition, this type of testing was conducted almost exclusively in research centers.
The TearLab Osmolarity System (TearLab Corporation) may now afford clinicians the opportunity to obtain accurate tear film osmolarity readings. It uses a “card” that touches the tear film, but not the eye per se, and harvests nanometric volumes of tears for evaluation by the instrument. This system may afford a consistent, affordable means of determining tear film osmolarity in dry eye suspects.
Just a Glimpse
While this list is far from inclusive, it gives us some idea of the products and instruments we may have available to us in the not-sodistant future for diagnosing and treating dry eye. CLS
For references, please visit www.clspectrum.com/references.asp and click on document #176.
Dr. Townsend practices in Canyon, Texas and is an adjunct faculty member at UHCO. He has received research funding from Alcon. You can reach him at firstname.lastname@example.org.