Informing Endpoints for Clinical Trials of Geographic Atrophy
Eleonora M. Lad, Monika Fleckenstein, Frank G. Holz, Liangbo L. Shen, Lucian V. Del Priore, Rufino Silva, Giovanni Staurenghi, Nadia K. Waheed, Usha Chakravarthy
Abstract
Geographic atrophy (GA), the non-neovascular advanced form of age-related macular degeneration, remains an important disease area in which treatment needs are currently unmet. Recent clinical trials using drugs that target the complement pathway have shown modest yet consistent reductions in GA expansion but without commensurate changes in measures of visual function. In this review, we summarize information from the wide range of studies describing the characteristics of GA morphology and enumerate the factors influencing the growth rates of lesions and the directionality of expansion. In addition, we review the relationship between GA growth and the various measures of vision that reflect changes in function. We consider the reasons for the discordance between the anatomical and functional endpoints in current use and discuss methods to align these key outcomes.