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Accumulation of these byproducts may lead to increased inflammation, which is implicated in the development of GA. In phototransduction, photoreceptors exert a high metabolic demand, which results in increased production of metabolic waste products. In this review, we examine the past and current research into a pharmaceutical treatment for atrophic AMD.Visual cycle modulators are oral medications that target enzymes in the visual cycle. Due to its complexity, many therapeutic approaches have been considered, including visual cycle modulation, neuroprotection, cell-based therapy, inflammation suppression and complement inhibition. Unfortunately, there has yet to be a similar breakthrough for GA.
Latest Treatment For Wet Degen 2015 Trial Showed ThatThe modified vitamin A forms toxic vitamin A dimers more slowly, which is postulated to slow the accumulation of toxic end products and therefore slow the development and/or progression of AMD. 5ALK-001 is a modified form of vitamin A that replaces natural vitamin A in the body. Unfortunately, the Phase IIb/III clinical trial showed that oral emixustat hydrochloride was ineffective at reducing the progression of GA. In the study, 508 people were enrolled with GA secondary to macular degeneration. 4 It was studied in the Safety and Efficacy Assessment Treatment Trials of Emixustat hydrochloride (SEATTLE) study, a large randomized clinical trial for GA by Bascom Palmer’s Philip Rosenfeld, MD, and co-workers. A drug that can be delivered orally is especially attractive however, a consequence of modulating the visual cycle is that dark adaptation and low-light vision are often adversely affected.Following are the two highest-profile visual cycle modulators that have been studied.Emixustat hydrochloride (ACU-4429) is an oral non-retinoid small molecule that inhibits the visual cycle enzyme isomerohydrolase, RPE65.However, studies in animal models with systemic administration have demonstrated that it also has neuroprotective properties, though clinical trials have yet to confirm similar efficacy in humans. So far, brimonidine tartrate (Allergan) is the only agent that has shown possible neuroprotective properties that might be beneficial in GA.Brimonidine is an alpha-2 adrenergic agonist that’s an established topical ophthalmic intraocular pressure-lowering agent. Pharmacologic agents with cyto- and neuroprotective properties may help protect at-risk neuroretinal tissue by increasing its resilience and resistance to cellular injury, thereby providing a defense against GA progression. It’s currently being studied in a Phase III clinical trial for GA.Neuroprotection has been investigated as a possible solution for the problem of progressive cellular damage and eventual cell loss that occurs in atrophic AMD.
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