discovering dry eye
Of Dry Eye
BY KELLY KINNEY NICHOLS, OD, MPH, PHD
Every practitioner has a memorable dry eye
patient in his or her practice. Contact lens
intolerance, irritation, pain and grittiness are common complaints. Palliative treatments such as artificial tears offer temporary relief at best, and while punctual occlusion can be successful, it may not be optimal. When will medical treatment be available for dry eye?
as artificial tears offer temporary relief at best, and while punctal occlusion can be successful, it may not be optimal. When will medical treatment be available for dry eye?
Currently we have no FDA-approved pharmacologically-active treatments for dry eye; however, FDA trials are currently underway for several potential medications. Inspire Pharmaceuticals, Inc. (Raleigh, NC) recently announced the positive Phase II results of INS365 Ophthalmic for the treatment of dry eye disease. INS365 Ophthalmic is a small-molecule drug that stimulates the P2Y2 receptor, a key mediator of mucosal-surface hydration and lubrication. Based on the positive results seen in the Phase II program, the company expects this new approach will enhance the eye's natural cleansing and protective systems by stimulating the release of salt, water, mucus and other natural tear components, thereby providing hydration and lubrication of the ocular surface.
FDA Phase II Results
The Phase II trial, a double-masked, parallel-group, dose-ranging, placebo-controlled study, was conducted at 12 ophthalmology centers in the United States. The study compared several concentrations of INS365 Ophthalmic topical eye drop solution, ranging from 0.5% to 5%, and placebo in 158 moderate-to-severe patients. The Phase II study showed that INS365 Ophthalmic was very well tolerated and demonstrated a statistically significant improvement over placebo on an important objective efficacy endpoint, corneal staining. This is a key measure of ocular-surface health among clinicians and researchers.
The January issue of Investigative Ophthalmology and Visual Science reports on the use of INS365 in a rat dry eye model, a study that was sponsored by Inspire's Asian partner, Santen Pharmaceutical Co. In this study, a dry eye rat model was used to evaluate the corneal barrier function prior to and after topical INS365 application. INS365 has been shown to stimulate rabbit tear fluid secretion and is being developed for treatment in dry eye syndrome.
The application of INS365 on the ocular surface in four normal rats demonstrated increased tear secretion and glycoprotein release. Application of vehicle (saline) did not increase the Schirmer score. In the rat dry eye model, application of INS365 in concentrations > 3% also increased fluid production. In the dry eye model two months after surgery, corneal barrier function was assessed by measuring fluorescein penetration into the stroma. In the rat dry eye model, fluorescein penetration was 3.5X greater than the normal rat eye. Following application of INS365, corneal epithelial barrier function was restored in a dose-dependent fashion. The effects of 1% and 3% demonstrated 138 percent and 170 percent improvement in barrier function from baseline, respectively. The authors conclude that INS365-containing eye drops may be a promising new treatment for dry eye syndrome. Results from the Phase III trial are expected by the second half of 2002.
Is This the "Cure?"
Following the press hype about the Allergan Cyclosporin A trials, a little caution and a lot of patience is prudent. Regardless of the clinical outcome of the Phase III trial, Inspire should be complemented for moving the field of dry eye forward.
Dr. Nichols is assistant professor of clinical optometry at The Ohio State University College of Optometry in the area of dry eye
Contact Lens Spectrum, Issue: June 2001