Geroprotective Agents, Including Glucagon-Like Peptide-1 Receptor Agonists, for Ocular Health.
This narrative review examines the potential ocular effects of geroprotective agents — pharmacologic compounds studied for longevity and systemic aging benefits — with a focus on their relevance to age-related eye diseases including age-related macular degeneration (AMD), diabetic retinopathy (DR), retinal vein occlusion (RVO), and glaucoma. The authors argue that shared mechanisms of neurodegeneration, microvascular injury, and chronic inflammation underlie both systemic aging and major retinal diseases, making geroprotectors a pharmacologically relevant class for ophthalmic consideration. The review covers a broad range of agents: GLP-1 receptor agonists, metformin, SGLT-2 inhibitors, statins, cannabinoids, calcium channel blockers, spermidine, taurine, NAD+ precursors, rapamycin, and mifepristone. The authors note that GLP-1 receptor agonists have been associated with potential glaucoma risk reduction but also with unconfirmed reports of nonarteritic anterior ischemic optic neuropathy. The review acknowledges that ocular effects of these agents are incompletely characterized, variably reported, and sometimes controversial. Key limitations include reliance on heterogeneous observational and preclinical data, absence of dedicated ophthalmic clinical trials, and potential confounding in real-world studies. The authors aim to support clinical awareness and identify gaps for future investigation.
Why this grade: This is a narrative review synthesizing heterogeneous preclinical, observational, and clinical data across multiple agents and conditions, without original data collection or meta-analytic pooling.
Aging has long been implicated in the onset and progression of major retinal diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinal vein occlusion (RVO). Glaucoma is likewise increasingly recognized as an age-related disorder. Across these conditions, converging patterns of neurodegeneration and microvascular injury contribute to age-associated ocular decline. Structural and neuronal degeneration of the retina, including loss of retinal ganglion cell axons, along with impaired microvascular circulation and chronic inflammation, contribute to the pathogenesis of glaucoma, AMD, DR, and RVO. Geroprotectors, a class of longevity-promoting pharmacologic agents investigated for systemic benefits in cardiovascular and neurological aging, have therefore drawn growing ophthalmic interest for their potential relevance to ocular health and the management of age-associated eye diseases. These agents are now frequently encountered as concomitant medications in ophthalmic practice, yet their ocular effects remain incompletely characterized, variably reported, and in some cases controversial. Glucagon-like peptide-1 (GLP-1) receptor agonists, widely used for glycemic control and increasingly for weight management, have been associated with reduced risk of age-related glaucoma but also with unconfirmed reports of severe nonarteritic anterior ischemic optic neuropathy. Similar uncertainties surround other geroprotective, metabolic, and weight-modifying therapies, creating challenges for clinicians attempting to incorporate evolving pharmacologic evidence without compromising patient safety. This review synthesizes reported therapeutic and adverse ocular outcomes across geroprotective agents to support clinical awareness, identify knowledge gaps, and guide future investigation. The agents reviewed include GLP-1 receptor agonists, metformin, sodium-glucose cotransporter-2 inhibitors, statins, cannabinoids, calcium channel blockers, spermidine, taurine, nicotinamide adenine dinucleotide precursors, rapamycin, and mifepristone.
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