Angiogenesis-Based Therapies for Eye Diseases

Age-related macular degeneration (AMD), diabetic retinopathy (DR), myopic choroidal neovascularization (mCNV) and retinal vein occlusion (RVO) taken together are leading cause of blindness worldwide. Neovascularization in these retinal disorders is induced largely by vascular endothelial growth factor A (VEGF-A) and progresses rapidly to blindness if left untreated. VEGF-A, with a central role in both normal and pathologic vascular growth within the eye, binds to VEGF-A receptors (e.g., Flt-1) on the vascular endothelium and promotes angiogenesis in response to hypoxia and other stimuli. The current standard of care in managing AMD, DR, mCNV and RVO is VEGF antibodies administered through intravitreal route to block VEGF activity, which underlies the CNV. Although this therapy improves visual acuity in a substantial proportion of patients, significant number of patients experience persistent CNV leakage, fibrotic scarring and/or geographic atrophy. Most patients do not achieve substantial visual improvement and a third of treated eyes progress to legal blindness. Thus, a novel therapeutic strategy, which improves outcomes while providing inhibition of angiogenesis with acceptable safety profile, is an urgent and unmet medical need. In this review, we discuss the role of VEGF and VEGF receptors in angiogenesis and the current and potential future angiogenesis based therapies for AMD, DR, mCNV and RVO.