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Potential treatments for the management of dry age-related macular degeneration are numerous, but so far, studies still are ongoing as to their therapeutic benefit.
Philadelphia-Potential treatments for the management of dry age-related macular degeneration (AMD) are numerous, but so far, studies still are ongoing as to their therapeutic benefit, said David S. Boyer, MD, here at the Macula 2011 and Atlantic Coast Retina Club meeting of the Wills Eye Institute.
"Currently, the only approved treatment of dry AMD is the use of vitamins based upon the results of the Age-Related Eye Disease Study (AREDS) that showed a reduction of both a loss of visual acuity and of progression of dry AMD," said Dr. Boyer, who is with Retina Vitreous Associates Medical Group, Los Angeles, and a clinical professor of ophthalmology, University of Southern California/Keck School of Medicine, Los Angeles. "Patients with geographic atrophy, however, did not seem to have a reduction in formation or progression."
Several neuroprotective agents currently are under investigation for the treatment of dry AMD. Among them are NT-501, brimonidine tartrate, and topical tandospirone.
• NT-501 (Neurotech) consists of encapsulated human retinal pigment epithelium (RPE) cells genetically modified to secrete ciliary neurotrophic factor (CNTF). CNTF is a growth factor capable of rescuing dying photoreceptors and protecting them from degeneration. It has been shown to inhibit photoreceptor apoptosis in an animal model of retinal degeneration.
Using encapsulated cell technology that permits CNTF-producing transfected RPE cells to be implanted into the vitreous cavity, this agent has a sustained-release platform that produces CNTF for a year or longer. The phase II study is completed and data analysis did not show a statistically significant decrease in growth of the geographic atrophy. However, it did show a trend toward improvement in both macular volume measurements and vision in patients with good beginning visual acuity, compared with control or low dose, Dr. Boyer said.
Other neuroprotective agents currently under investigation for dry AMD include a brimonidine tartrate intravitreal implant (Allergan) and topical tandospirone (Alcon Laboratories).
• Brimonidine tartrate is an alpha-2 adrenergic receptor agonist that has been found to be neuroprotective in a variety of animal experiments. It is injected intravitreally using the same injector as the long-acting dexamethasone implant. It is currently in phase II trials to compare the use of 200 or 400 µg, with the other eye as a control.
• Tandospirone (AL-8309B) is a selective serotonin 1A agonist that has been shown to be neuroprotective in animal models. This drug appears to provide a dose-dependent protection of photoreceptors and RPE cells from photo-oxidative stress. The ongoing GATE trial has more than 500 participants.
Reduce byproduct accumulation
Amyloid beta has been discovered in pathologic studies of drusen. Based on this observation, several compounds that reduce the accumulation of amyloid beta are being studied. Two currently under investigation include glatiramer acetate and RN6G (PF-4382923) a humanized monoclonal antibody versus ABeta40 and ABeta42.
Glatiramer acetate (Copaxone, Teva Pharmaceutical Industries) is a treatment approved by the FDA to treat multiple sclerosis. This agent may reduce drusen over a period of 3 or 4 months when patients are treated with weekly injections. Its effects may be neuroprotective, and currently, several small studies are under way to examine this as a potential treatment.