Article Date: 7/1/2009

The Future of Dry Eye Treatment
dry eye dx and tx

The Future of Dry Eye Treatment

BY KATHERINE M. MASTROTA, MS, OD, FAAO

Expanded understanding of the ocular surface has prompted a worldwide push in research and development of products aimed at managing dry eye. Following are products in development that may one day be instrumental in daily practice.

New Twists on Cyclosporine

Cyclosporine A (Restasis, Allergan) has proven successful in treating ocular surface disease. Sirion Therapeutics' ST-603 has twice the concentration (0.1%) of cyclosporine A as in Restasis.

Novagali Pharmaceuticals' (France) drug Nova22007 (Cyclokat) is cyclosporine in a proprietary carrier, Novasorb. Novasorb's cationic emulsion technology increases drug absorption through electrostatic attraction between the therapeutic emulsion's positive charge and the eye's negatively charged mucus, cornea, and conjunctiva. Cyclokat has completed Phase II studies.

Battling Inflammation

Ciliomast, a phosphodiesterase IV inhibitor, exerts pro-secretory and anti-inflammatory effects. Alcon has entered into a licensing agreement with GlaxoSmithKline for global ophthalmic rights.

Both Phase I drug LX214, voclosporin (Lux Biosciences), and Phase II drug CP-6900550 (Pfizer) are immunosuppresive compounds being studied for ophthalmic use in dry eye.

SAR 1118 (Sarcode Corporation and Sunesis Pharmaceuticals, Inc.) is a small-molecule lymphocyte function-associated antigen 1 antagonist. Topical SAR 1118 reduced ocular surface inflammation and improved aqueous tear production in canine dry eye and is in Phase I development.

RX-10045 (Resolvyx Pharmaceuticals) has promoted tissue repair in human corneal epithelial cells in vitro. It is a resolvin, which are naturally occurring, small-molecule lipid mediators that protect healthy tissue during an immuno-inflammatory response and then resolve inflammation and promote healing after the insult has passed. RX-10045 is currently in Phase II study.

EyeGate Pharmaceuticals, in partnership with Ophthalmic Research Associates, has completed Phase II studies of EGP-437, a corticosteroid. Its EyeGate II Delivery System works through iontophoresis, a method of transdermal drug delivery in which an electrical field created by a low level of electrical current is used to ionize a drug and to modify the permeability of the cells for delivery to targeted areas.

Alacrity Bioscience is developing a formulation of non-antimicrobial doxycycline (ALTY-0501) that has completed a Phase II clinical trial. It blocks activation of proteases and cytokines, inhibits matrix metalloproteinase, and maintains epithelial barriers.

Enhancing the Tear Film

Diquafosol tetrasodium (Prolacria, Inspire Pharmaceuticals) is designed to stimulate fluid, mucin, and lipid secretion by stimulating P2Y2 receptors on the ocular surface. Inspire has initiated a Phase III clinical trial to evaluate its efficacy and safety.

Ecabet sodium (Ista Pharmaceuticals, under license from Senju Pharmaceuticals, Japan), in Phase II studies, increases the quantity and quality of mucin produced by conjunctival goblet cells and corneal epithelia.

In Phase III development, rebamipide ophthalmic suspension (Acucela Inc. and Otsuka Pharmaceutical Co., Ltd., Tokyo) increases mucin levels in tears.

Civamide (Opko Health, Inc/Winston Labs) increases tear production. Civamide is a TRPV1 receptor modulator and neuronal calcium channel blocker. TRPV1 receptors are involved in transmission and modulation of pain.

Lubrication

Vismed (Lantibio Inc.), currently marketed in Europe, has a purified fraction of sodium hyaluronate (0.18%), is preservative-free, and possesses mucoadhesive properties. Acon has licensed the U.S. marketing rights. Phase III studies are ongoing. CLS


Dr. Mastrota is secretary of the newly formed Ocular Surface Society of Optometry (OSSO). She is center director at the New York Office of Omni Eye Services and is a consultant to Allergan, AMO, B&L, Inspire, and Cynacon OcuSoft.



Contact Lens Spectrum, Issue: July 2009