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Narrative review of outcome measures for geographic atrophy treatment trials-lessons learned from previous trials
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DOI：10.21037/aes-25-39.png)
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Abstract
En 中文
Background and Objective: Geographic atrophy (GA), an advanced stage of age-related macular degeneration, involves progressive degeneration of retinal pigment epithelium (RPE) and photoreceptors, leading to permanent central vision loss and visual impairment in older adults. While the Food and Drug Administration (FDA)-approved drugs pegcetacoplan and avacincaptad pegol have been shown to slow lesion enlargement and provide structural benefits, their limited impact on visual function highlights the need for more comprehensive outcome measures in GA trials. This paper reviews the current GA outcome measures, identifies their limitations, and proposes future directions for assessing treatment efficacy. Methods: This narrative review examines key studies, including clinical trials of pegcetacoplan and avacincaptad pegol, and related literature on GA, to assess commonly used outcome measures and explore other potential measures. A literature search was conducted using PubMed, Embase, and ClinicalTrials.gov for studies published in English through July 2025, focusing on clinical trial design, functional and structural endpoints, and emerging assessment methodologies. Key Content and Findings: While GA trials demonstrated reductions in lesion growth, these changes have not translated into significant improvements in functional outcomes, including visual acuity (VA). Notably, biomarkers from spectral-domain optical coherence tomography (SD-OCT) and microperimetry, which correlate more directly with functional declines, as well as other functional and structural markers, including low luminance VA, reading speed, and proximity of GA lesions to the foveal center, may serve as more effective outcome measures for GA trials. Conclusions: Although recent GA therapies slow lesion growth, functional improvements remain limited, underscoring a disconnect that affects trial design and endpoint selection. Clinical trials of GA face challenges including patient heterogeneity, endpoint sensitivity, and treatment burden on often elderly, comorbid populations. Ethical considerations highlight the importance of balancing risks and benefits, minimizing participant burden, and considering patient-centered outcomes. Future trials may adopt multidimensional, sensitive outcome measures integrating structural, functional, and patient-reported domains to better reflect meaningful clinical benefits and patient experiences.
Keywords:
Outcome measure
visual function
clinical trials
geographic atrophy (GA)
age-related macular degeneration