Objective: To synthesize the current preclinical and clinical evidence on the utility and potential mechanisms of glucagon-like peptide-1 receptor agonists (GLP-1RAs) as a therapeutic strategy for major ophthalmic diseases, including diabetic retinopathy, glaucoma, and age-related macular degeneration.
Methods: A comprehensive literature search was conducted to synthesize the current preclinical and clinical evidence. Electronic databases including PubMed, Embase, and Web of Science were searched from inception until August 2025 using keywords such as “GLP-1 receptor agonist,” “diabetic retinopathy,” “glaucoma,” “age-related macular degeneration,” “ocular disease,” and “neuroprotection.” The search focused on identifying preclinical studies, large-scale retrospective cohort studies, and post-hoc analyses of major clinical trials that evaluated the utility and potential mechanisms of GLP-1RAs in ophthalmic diseases. Studies were screened for relevance based on title and abstract, and full texts were retrieved for detailed assessment.
Results: Despite heterogeneity in study designs and populations, a largely consistent association was found between GLP-1RA use and a reduced incidence of glaucoma. For diabetic retinopathy, the evidence was nuanced, indicating potential long-term neurovascular protection but also a risk of transient early worsening. For age-related macular degeneration, findings were dichotomous, suggesting a protective effect against non-exudative forms but a potential increased risk for neovascular disease.
Conclusion: GLP-1RAs show significant promise as a potential disease-modifying therapy for neurodegenerative and inflammatory eye diseases, acting through both systemic metabolic improvements and direct ocular mechanisms, representing a paradigm shift beyond their metabolic indications.
Keywords: Age-related macular degeneration; Diabetic retinopathy; Dry eye disease; GLP-1 receptor agonist; Glaucoma; Neuroprotection; Nonarteritic anterior ischemic optic neuropathy; Ophthalmology.