Age-related macular degeneration (AMD) is the leading cause of blindness for the elderly in high-income countries. Although multivitamin antioxidant nutrients can slow the progression of intermediate "dry" or nonneovascular AMD, no treatment can halt or reverse any stage of dry disease. Multiple biologic pathways have been implicated in AMD pathobiology, including the complement pathway. These pathways have been targeted by various approaches in clinical trials. To date, no treatment has reached their prespecified primary end point in 2 phase III trials, a requirement by the US Food and Drug Administration for a new drug approval. Here, we describe perspectives on the failures and possible successes of various clinical trials that will guide further investigation. These perspectives will also discuss clinical trial design issues to consider in future investigations, and how recent insights into AMD pathobiology might both provide additional explanation for trials not reaching the prespecified primary end points and offer direction for identifying prioritized treatment targets.
Keywords: AMD, Age-related macular degeneration; CSF, contrast sensitivity; Clinical trial; Complement; FDA, Food and Drug Administration; GA, geographic atrophy; Geographic atrophy; HTRA1, HtrA Serine Peptidase 1; LLVA, low luminance visual acuity; Non-neovascular age-related macular degeneration; RPE, retinal pigment epithelium; VA, visual acuity.
© 2022 by the American Academy of Ophthalmology.