Beyond glycemic control: ocular effects of GLP-1 receptor agonists across medical and surgical ophthalmology

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become a cornerstone in the management of type 2 diabetes mellitus and obesity because of their proven metabolic and cardiovascular benefits. As their clinical use continues to expand, increasing attention has been directed toward their potential ophthalmic effects. This narrative review summarizes the current evidence regarding the biological mechanisms, therapeutic potential, and ocular safety profile of GLP-1RAs across medical and surgical ophthalmology. Experimental studies demonstrate that GLP-1 receptors are expressed in multiple ocular tissues and that receptor activation exerts anti-inflammatory, antioxidant, vasculoprotective, and neuroprotective effects through modulation of oxidative stress, mitochondrial homeostasis, and retinal cell survival. Clinically, evidence from cardiovascular outcome trials initially raised concern regarding diabetic retinopathy progression, particularly following the SUSTAIN-6 trial. However, subsequent randomized trials, observational studies, and recent systematic reviews have not demonstrated a consistent class-wide increase in diabetic retinopathy risk. Current evidence suggests that the reported retinal complications are more likely associated with advanced baseline retinal disease and rapid glycemic improvement than with direct retinal toxicity. Emerging data also indicate potential applications in glaucoma, retinal neuroprotection, age-related macular degeneration, and ocular surface disease, although these findings remain largely supported by preclinical or observational evidence. A possible association between semaglutide and nonarteritic anterior ischemic optic neuropathy has recently been reported, but available evidence is insufficient to establish causality. Overall, GLP-1RAs appear to maintain a favorable ocular safety profile while offering promising therapeutic opportunities beyond metabolic disease. Future prospective ophthalmology-specific studies are needed to clarify their long-term ocular effects, identify patients at increased risk of retinal complications, and determine whether their experimental neuroprotective properties translate into clinically meaningful benefits.