Effective therapy needed for all stages of dry AMD
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Age-related macular degeneration is a major cause of visual loss in the elderly. As many as 200 million individuals are affected globally.
AMD is usually classified as early, intermediate or late. Late AMD represents about one in 10 patients with AMD and includes wet, or exudative, AMD and geographic atrophy. Each affects about 5 million patients in the U.S. The therapy for wet AMD is well established using intravitreal anti-VEGF therapy.
Long-term intravitreal anti-VEGF therapy for wet AMD can itself result in geographic atrophy. In geographic atrophy, there is complete loss of photoreceptors, the underlying retinal pigment epithelium (RPE) and even atrophy of the choriocapillaris in the affected area. It is clear that geographic atrophy is an aging process. The pathophysiology is likely multifactorial, and oxidative stress, inflammation and vascular insufficiency along with genetic predisposition all play a role.
Today, there is no effective treatment. Oral antioxidants have good level 1 evidence supporting their use in intermediate dry AMD. Their benefit in retarding the progression of geographic atrophy is unproven, but it seems logical to offer antioxidant vitamins to patients with geographic atrophy. Other antioxidants, including N-acetylcysteine, are being studied.
There is no current effective way to treat vascular insufficiency, but behavioral modification with cessation of smoking, management of hypertension, treatment of hyperlipidemia and reduction of obesity all make sense. Most current research is focused on reducing the inflammatory component of geographic atrophy, especially by inhibiting the complement cascade. Inhibitors of C3 and C5 are showing early promise in clinical trials. Once the photoreceptors are dead, along with loss of the supporting RPE, there is no therapy that can regenerate these cells. Transplantation of photoreceptors and/or RPE with subretinal cell injection therapy and even gene therapy have been attempted with minimal success.
Prevention is our best therapy today, which includes behavioral modification at the early and intermediate AMD stage along with antioxidant vitamins and perhaps omega-3 supplementation. In addition, every clinician can help these patients by making a timely referral to an expert provider of low vision aids.
A more effective therapy for all stages of dry AMD is a major unmet need, and any medical or surgical treatment that is proven safe and effective will be a godsend for millions of patients and extremely lucrative for the developer. We can only hope that over the next decade, bright scientists and committed clinicians supported by significant financial capital can make a dent in this major cause of vision loss.
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