Macular degeneration and peptides — what the literature actually supports for dry AMD, geographic atrophy, and adjacent retinal pathology

Why this dossier exists

Age-related macular degeneration is the leading cause of irreversible vision loss in adults over 50 in high-income countries, and it is the indication where the standard-of-care landscape moved more in 2023 than in any previous decade. Dry AMD with geographic atrophy — roughly 85–90% of cases — went from "no FDA-approved disease-modifying therapy" to two approved complement-targeting molecules in a single year. Pegcetacoplan (Syfovre), a pegylated C3 inhibitor, was approved in February 2023 on the basis of Heier JS, Lally DR, Staurenghi G et al., Lancet 2023, 402(10411):1434–1448: 22% and 18% reductions in GA lesion growth at 24 months on monthly and every-other-month dosing across 1,211 randomized patients. Avacincaptad pegol (Izervay), a pegylated C5 inhibitor, followed in August 2023 on the basis of Khanani AM, Patel SS, Staurenghi G et al., Lancet 2023, 402(10411):1449–1458: a 14% reduction in GA lesion growth across 448 patients at 12 months. Neither molecule is a peptide. Neither restores vision. Both slow structural progression on autofluorescence imaging without yet demonstrating preserved visual function in their pivotal trials.

That is the editorial context for the peptide-AMD discussion in 2026. The complement-targeting first wave validates the principle that geographic atrophy is pharmacologically modifiable; it does not settle what comes next. The peptide pharmacology question is whether a different mechanism — mitochondrial preservation, cardiolipin stabilization, neurotrophic support — can act earlier in the dry-AMD cascade than complement modulation can. The molecule that has tested the hypothesis most directly is elamipretide (SS-31) in the ReCLAIM-2 Phase 2 trial, where both prespecified clinical-functional primaries missed but a structural ellipsoid-zone secondary signal was significant. That trial is now the editorial center of the peptide-AMD conversation, and Stealth BioTherapeutics has built its Phase 3 ReNEW and planned ReGAIN program on that secondary structural endpoint.

This dossier walks the peptide and peptide-adjacent evidence base across AMD and adjacent retinal and optic-nerve pathology where peptide pharmacology has registered any signal at all: dry AMD with geographic atrophy as the core indication, the GLP-1 / nonarteritic anterior ischemic optic neuropathy (NAION) pharmacovigilance signal as the eye-adjacent safety conversation, neurotrophic keratitis as the ophthalmic-peptide indication closest to commercial approval, and the broader mitochondrial-AMD framing that situates SS-31 alongside other candidate mechanisms. The honest read across the corpus: the peptide-AMD trial evidence as of mid-2026 is one Phase 2 with a missed primary endpoint and a follow-on Phase 3 program enrolling. Anything else is mechanism extrapolation or off-label use built on top of indications other than AMD.