Perspectives from clinical trials: is geographic atrophy one disease?

Geographic atrophy (GA) is currently an untreatable condition. Emerging evidence from recent clinical trials show that anti-complement therapy may be a successful treatment option. However, several trials in this therapy area have failed as well. This raises several questions. Firstly, does complement therapy work for all patients with GA? Secondly, is GA one disease? Can we assume that these failed clinical trials are due to ineffective interventions or are they due to flawed clinical trial designs, heterogeneity in GA progression rates or differences in study cohorts? In this article we try to answer these questions by providing an overview of the challenges of designing and interpreting outcomes of randomised controlled trials (RCTs) in GA. These include differing inclusion-exclusion criteria, heterogeneous progression rates of the disease, outcome choices and confounders.