Complement Inhibitors for Advanced Dry Age-Related Macular Degeneration (Geographic Atrophy): Some Light at the End of the Tunnel?

Abstract

Geographic atrophy (GA) affects around 5 million individuals worldwide. Genome-wide, histopathologic, in vitro and animal studies have implicated the activation of the complement system and chronic local inflammation in the pathogenesis of GA. Recently, clinical trials have demonstrated that an intravitreal injection of pegcetacoplan, a C3 inhibitor, and avacincaptad pegol, a C5 inhibitor, both statistically significantly reduce the growth of GA up to 20% in a dose-dependent fashion. Furthermore, the protective effect of both pegcetacoplan and avacincaptad appear to increase with time. However, despite these anatomic outcomes, visual function has not improved as these drugs appear to only slow down the degenerative process. Unexpected adverse events included conversion to exudative NV-AMD with both drugs. Occlusive retinal vasculitis and anterior ischemic optic neuropathy have been reported in pegcetacoplan-treated eyes.