A Clear View

By treating patients with fenretinide, a synthetic derivative of vitamin A, and a proven arthritis treatment, researchers were able to reduce the risk of developing wet age-related macular degeneration (AMD) in those with dry AMD.

The results of the study were presented at the American Academy of Opthalmology (AAO) — Middle East-Africa Council of Ophthalmology (MEACO) Joint Meeting.

The research also demonstrated that treating these patients with fenretinide reduced geographic atrophy (GA) lesion growth. The reduced growth correlated with lowered blood levels of the biomarker retinol binding protein (RBP), which indicated that fenretinide was working. Patients whose RBP decreased 60% or more also had the most significant reductions in lesion growth. GA lesions degrade the retinal pigment epithelium (RPE), which can result in significant vision loss.

Either form of advanced AMD (wet or dry) can destroy the detailed, central vision needed 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 can sometimes abruptly converts to the wet form.

Fenretinide works on three key AMD disease mechanisms. The drug 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.

The 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.

The side effects included delayed ability to adapt to dark conditions and 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.

The AAO is the world's largest association of eye physicians and surgeons with more than 29,000 members worldwide.

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How will the findings affect future treatment of AMD conditions?