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A dry AMD treatment?; some long-term diabetics escape PDR

CHICAGOAt the American Academy of Ophthalmology (AAO) Middle East-Africa Council of Ophthalmology (MEACO) Joint Meeting today, researchers report progress on two top eye disease challenges: treating advanced "dry" age-related macular degeneration, and preventing blindness in people with diabetes. The Joint Meeting is in session October 16 through 19 at McCormick Place, Chicago. The AAO-MEACO meeting is the world's largest, most comprehensive ophthalmic education conference.

Proven Arthritis Drug Shows Promise versus Dry AMD:

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. Today 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.

Financial disclosures: This research was supported by a grant to the Digital Angiography Reading Center; Dr. Slakter served as a consultant to Sirion Therapeutics.

Clues to Retinopathy from Survivors of 50+ Years of Diabetes:

Doctors assume that the longer a person has diabetes, the more likely he or she is to develop serious eye disease and, if untreated, become blind. But a new study of patients who have had type 1 diabetes for at least 50 years tells a different story. Many of these patients appear to be protected against proliferative diabetic retinopathy (PDR), and the majority of them escape vision loss despite extremely long-duration diabetes, according to Jennifer Sun, MD, Beetham Eye Institute at Joslin Diabetes Center, a Harvard School of Medicine affiliate.

With one exception, development of PDR occurred within the first two decades in these Joslin patients (in 96 of 97 patients). If PDR did not develop during that period, then retinopathy progressed slowly and in some cases stopped altogether. PDR development was associated with higher blood pressure, but not with glycemic (blood sugar) control. This confirmed an earlier, larger study's surprising finding that neither glycemic control nor duration of diabetes correlated with the severity or presence of diabetic retinopathy (DR) in patients who successfully survived 50 or more years with type 1diabetes. Decreased blood levels of the protein tyrosine phosphatase SHP-1 was also associated with protection from development of any DR, and Dr. Sun recommends further study of SHP-1 to learn whether it might be a target for treatment.

"There is no doubt that lack of glycemic control is a major factor in the development of eye complications for patients with shorter-duration diabetes. But our data from this unique group of individuals who have survived extremely long-duration diabetes may help identify other factors that protect against retinopathy complications," said Dr. Sun. "These findings also suggest that protective mechanisms are activated very early in diabetes."


Contact: Mary Wade
American Academy of Ophthalmology

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