Review of Emerging Treatments for Age-Related Macular Degeneration

In the era of pathway-based therapy, all treatments for AMD will address some step in the pathway that leads from early to late AMD. Steps in AMD pathogenesis that appear to be good targets for drug development include the following: (1) oxidative damage, (2) lipofuscin accumulation, (3) chronic inflammation, (4) mutations in the complement pathway, (5) mitochondrial damage, (6) Alu RNA accumulation in RPE, and (7) BMP-4 accumulation in RPE. Steps in neovascularization that can be targeted for drug development and combination therapy include the following: (1) angiogenic factor production, (2) extracellular factor release, (3) binding of factors to extracellular receptors (and activation of intracellular signaling after receptor binding), (4) endothelial cell activation (and basement membrane degradation), (5) endothelial cell proliferation, (6) directed endothelial cell migration, (7) extracellular matrix remodeling, (8) tube formation, and (9) vascular stabilization. Combination therapy will likely supplant monotherapy as the treatment of choice because the clinical benefits will likely be superior in preventing the complications of AMD.