Scheie Eye Institute, University of Pennsylvania
Read about the exciting new research for treatment of dry age-related macular degeneration.
Dry age-related macular degeneration (AMD) can be divided into two forms: early and late. In the early form, patients have tiny deposits under the retina, called drusen, which indicate they may lose vision in the future if the disease progresses to the late stage. Patients with late, dry AMD have a form called geographic atrophy (GA), when the vision cells (photoreceptors) in the center of the retina slowly die over time. The following article provides a brief summary of the latest treatment research for dry AMD.
For early, dry AMD, the age-related eye disease studies (AREDS1 and AREDS2) have shown that many patients can reduce their risk of vision loss by taking a specific formulation of antioxidant vitamins. The best vitamin combination is the “AREDS2” formula. Testing of additional antioxidants are underway in mice.
For late, dry AMD (GA), there is no currently approved treatment. However, several clinical trials are underway and showing promise, and studies in mice have suggested additional approaches to stop the progressive death of photoreceptors.
The “complement cascade” is an arm of the immune system that is strongly implicated in AMD. The complement part of the immune system is thought to attack the retina. Inhibiting the complement cascade can protect the retinas of mice. While two phase II trials by Genentech targeting the complement protein called factor D in geographic atrophy patients were not successful, a phase II trial by Apellis targeting a different complement protein called C3 showed promising results. The Apellis drug has now moved into phase III trials. Similarly, another drug called Zimura, which targets the complement protein C5, slowed the growth of geographic atrophy in a phase II trial, and has moved on to a phase II trial. Both of these drugs are injected into the vitreous jelly in the center of eye.
Another approach is to try to inhibit specific immune cells with the oral antibiotic doxycycline. This is in phase II clinical trials.
In an approach to limit the toxic byproducts of vision cells, an oral drug called ALK-001 is being tested in phase II clinical trials for GA. This drug is a modified (deuterated) version of vitamin A that inhibits formation of the toxic byproduct A2E. A different approach is to limit the workload of the photoreceptors (vision cells), thus limiting potentially toxic by-products of that work. The oral drug emixustat is designed to do this by partially inhibiting photoreceptors’ ability to sense light. A potential side effect is some degree of night blindness, or difficulty seeing in low light. Unfortunately, a clinical trial for patients with geographic atrophy showed that this drug did not slow the growth of the atrophy.
In one approach called “neuroprotection,” an implant is surgically placed into the eye so that it will slowly release a potentially protective drug. One drug that showed positive results in a phase II trial is brimonidine, which also lowers eye pressure and is used as an eye drop in glaucoma patients.
Cell transplantation is also being tested. One cell type that degenerates in GA is the retinal pigment epithelial cells (RPE). These cells are important because the photoreceptors die without them. RPE cells can be produced from other cells, then injected under the retina. Early clinical trials have suggested that this approach can be safe. Additional phase 1 and 2 trials are underway.
One drug called MacuCLEAR, an eye drop that may increase blood flow to the retina, could possibly protect against expansion of GA by providing better nourishment to photoreceptors and removing waste products.
Gene therapy experiments underway in mice provide long-term antioxidant or anti-cell death effects. Clinical trials utilizing retinal gene therapy have been successful for treatment of children with hereditary blindness.
In some ways, AMD is similar to atherosclerosis, or hardening of the arteries, as lipid (fat) buildup is involved. Ongoing research is testing whether drugs that control lipids may be helpful.
Intensive research on age-related macular degeneration (AMD) is underway, raising hopes for improved treatments.
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Joshua Dunaief, MD, received his BA magna cum laude in Biology from Harvard (1987), MD/PhD from Columbia College of Physicians and Surgeons (1996), completed ophthalmology residency at the Wilmer Eye Institute, Johns Hopkins in 2000, and medical retina fellowship at Scheie Eye Institute, University of Pennsylvania in 2004.
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