OphthoEvidence Report: Comparative effects of treatments for geographic atrophy secondary to age-related macular degeneration: A protocol for a living systematic review and network meta-analysis

Background: Geographic atrophy (GA), an advanced form of age-related macular degeneration (AMD), leads to legal blindness in approximately 16% of affected individuals within 6 years. Numerous trials have evaluated interventions to slow GA progression, and many studies are ongoing. However, the comparative benefits and harms of treatments within this rapidly evolving therapeutic landscape have not yet been systematically synthesized. Objectives: To present a protocol for a living systematic review and network meta-analysis (NMA) addressing the effects of available interventions for the management of GA. Methods: We systematically searched Medline, EMBASE, Cochrane CENTRAL, Web of Science, and ClinicalTrials.gov from inception for randomized controlled trials comparing any pharmacologic or non-pharmacologic treatment versus another, placebo, sham, or standard care in adults with unilateral or bilateral GA secondary to AMD. Paired reviewers will independently screen studies, extract data, and assess risk of bias. Outcomes of interest include best-corrected visual acuity (BCVA), untransformed and square root-transformed total GA lesion area, vision-related quality of life, low luminance BCVA, reading speed, mean macular sensitivity, adverse events leading to discontinuation, macular neovascularization, need for rescue treatment, ischemic optic neuropathy, serious ocular adverse events, and serious non-ocular adverse events. For each outcome, if feasible, we will conduct frequentist random-effects NMAs. We will assess the certainty of evidence and interpret findings using the GRADE approach. To maintain this review as a living systematic review, we will conduct updates every six months. Discussion: This review will provide a comprehensive, trustworthy, and up-to-date summary of evidence on treatments for GA secondary to AMD. Registration: Open Science Framework (https://doi.org/10.17605/OSF.IO/W4JHR).