While ophthalmologists can turn to several medications for patients with vision-threatening "wet" age-related macular degeneration (AMD), there are no effective treatments for advanced "dry" AMD, the more common form. Now a research group led by Jason S. Slakter, MD, New York University School of Medicine, reports on a phase-two clinical trial of fenretinide, a synthetic derivative of vitamin A. Risk of developing wet AMD decreased almost two-fold in dry AMD patients who took the medication. Geographic atrophy (GA) lesion growth was also reduced in the fenretinide group. This reduced growth correlated with lowered blood levels.
of the biomarker retinol binding protein (RBP)-an indication that fenretinide was working. Patients whose RBP decreased 60 percent or more also had the most significant reductions in lesion growth. GA lesions degrade the area of the eye called the retinal pigment epithelium (RPE), which can result in significant vision loss.
Advanced AMD, in either wet or dry form, can destroy the detailed, central vision we need to recognize faces, read, drive, and enjoy daily life. It is a major cause of vision loss in the United States. In the advanced wet form abnormal new blood vessels develop under the retina, then bleed or leak fluid and form scars. Advanced dry AMD sometimes abruptly converts to the wet form.
Fenretinide works on three key AMD disease mechanisms: it has strong anti-inflammatory properties, inhibits abnormal blood vessel growth (angiogenesis) and reduces vitamin-A derived toxins such as A2E and lipofuscin. These toxins accumulate in the RPE and interfere with its ability to nourish light-receptor cells in the retina.
"Evidence from our study and others points to fenretinide's potential to treat and prevent diseases of the retina," Dr. Slakter said.
This randomized controlled trial included 246 patients at 30 sites around the United States. Tests showed that patients' visual acuity and other markers of eye health were not adversely affected by fenretinide. Side effects, including delayed ability to adapt to dark conditions, were minor and reversible when the medication was stopped. Years of use of fenretinide to treat cancers, rheumatoid arthritis, and other diseases have shown it to be safe and well tolerated. ReVision Therapeutics, the company supporting the continued clinical development of fenretinide, is planning a Phase 3 clinical trial to begin in 2011.
This research was presented at the 2010 American Academy of Ophthalmology -- Middle East-Africa Council of Ophthalmology Joint Meeting. The AAO-MEACO meeting is in session Oct. 16-19 in Chicago.
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