VEGF-targeted therapy and beyond: pharmacotherapy and emerging treatments in agerelated macular degeneration.

Treatment of age-related macular degeneration (AMD) has changed dramatically over the last decade. It has evolved from primarily destructive therapies (laser-based treatment strategies) to nondestructive therapies (intravitreal pharmacotherapies that target angiogenesis). Intermittent intravitreal ranibizumab, an inhibitor of VEGF, is currently the gold standard of care for neovascular AMD as it is the only treatment where a significant proportion of treated eyes have been shown to experience improvements in visual acuity. As our understanding of the pathological and molecular mechanisms involved in AMD increases, multiple new treatments are emerging. Distinct therapeutic approaches are being used, including inhibition of oxidative stress, interference with the visual cycle and immunomodulation. Targets within the complex cycle of angiogenesis include upstream pathways, such as mTOR and HIF-α, and downstream targets include integrins, PDGF and receptor tyrosine kinases.