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Beyond Glycemic Control: Ocular Effects of Glucagon-like Peptide-1 Receptor Agonists
Filippo Lixi1, Mario Troisi2, Valerio Calabresi1
1Eye Clinic, Department of Surgical Sciences, University of Cagliari, Via Università 40, 09124 Cagliari, Italy.
Abstract:
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and newer dual-incretin therapies have become central to the treatment of diabetes mellitus and obesity, with benefits extending beyond glycemic control. Their expanding use has prompted growing interest in their potential ocular effects. Experimental data support plausible protective mechanisms, including reduction in oxidative stress and neuroprotective effects on retinal and optic nerve tissues. Clinical evidence, however, remains heterogeneous. In diabetic retinopathy, the main concern appears to be transient early worsening associated with rapid glycemic improvement rather than direct retinal toxicity. A potential semaglutide-associated signal for non-arteritic anterior ischemic optic neuropathy has raised concern, although the absolute risk appears low and causality remains unproven. Emerging studies also suggest possible beneficial associations with glaucoma, ocular surface diseases, and certain retinal vascular outcomes, whereas the evidence regarding age-related macular degeneration and cataract remains conflicting or preliminary. Overall, ocular outcomes associated with incretin-based therapies seem to reflect a complex interplay among drug-specific pharmacology, systemic metabolic changes, and individual patient susceptibility rather than a class effect. Baseline ophthalmic assessment and individualized follow-up may be advisable in selected high-risk patients. Further prospective ophthalmology-focused studies are needed to clarify long-term safety and identify the patients most likely to benefit or develop adverse events.
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