Targeting the complement system in geographic atrophy: mechanisms and therapeutics

IntroductionGeographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) and a leading cause of vision loss for which there are currently two FDA-approved treatments (pegcetacoplan and avacincaptad pegol). The complement system, a major effector arm of innate and adaptive immunity, has been implicated in the pathogenesis of GA. This review aims to provide a comprehensive overview of the mechanisms underlying complement dysregulation in GA and the current therapeutic strategies to treat GA via targeting the complement system.Areas CoveredThis review covers the pathogenesis of GA with a focus on the role of the complement system, the mechanisms of complement dysregulation in GA, current therapeutic strategies targeting the complement system for GA, and ongoing clinical trials. We also discuss the challenges and future directions of complement-targeted therapy for GA.Expert OpinionDespite the challenges, the complement system remains a promising target for developing novel therapeutics for GA and AMD. Further research is needed to optimize treatment strategies, identify predictive biomarkers, and understand the contributions of complement dysregulation to the pathological processes in GA and other retinal pathologies.