Functional endpoints in patients with geographic atrophy: What to consider when designing a clinical trial

There is an unmet need in patients with geographic atrophy (GA) for treatments that preserve and improve functional vision to maintain their independence and quality of life. The limited number of available treatments for GA have demonstrated structural benefits, but none have consistently shown significant functional outcomes in clinical trials. Currently, best-corrected visual acuity (BCVA) is considered the gold standard functional endpoint in clinical trials; however, in the case of GA, it cannot fully evaluate visual impairment or treatment response, particularly in fovea-sparing GA lesions. In addition, BCVA may not fully capture the functional impact of foveal and parafoveal scotomas. There is emerging evidence for the utility of other functional assessments that may provide a more robust representation of the functional impact of GA; however, the current utilization of these tests in GA clinical trials varies widely. This review aims to evaluate current functional endpoints in GA and their strengths and limitations based on characteristics such as strength of structure-function correlation, practicality and feasibility, and patient perspective. There are many factors to consider when choosing a functional vision assessment when designing a GA clinical trial, and each functional vision assessment has several advantages and disadvantages, which are summarized in this review article.