GLP-1RAs and Geroprotectors Show Dual Ocular Impact: Glaucoma Risk Reduced, Optic Neuropathy Concerns Highlighted
Background
Age-related macular degeneration (AMD), diabetic retinopathy (DR), retinal vein occlusion (RVO), and glaucoma are major retinal diseases driven by neurodegeneration, microvascular injury, and chronic inflammation. Current treatments often fall short, leading to irreversible vision loss. Geroprotective agents, including GLP-1 receptor agonists, are widely used for metabolic conditions and show systemic longevity benefits, prompting interest in their ocular effects. However, their impact on eye health remains incompletely characterized, with conflicting reports on therapeutic and adverse outcomes, creating a critical knowledge gap for clinicians.
Study Design
This comprehensive review systematically synthesized existing literature on the ocular effects of various geroprotective agents. Researchers compiled reported therapeutic and adverse ocular outcomes for several classes of compounds, including glucagon-like peptide-1 (GLP-1) receptor agonists, metformin, sodium-glucose cotransporter-2 inhibitors, statins, cannabinoids, calcium channel blockers, and spermidine. The primary objective was to consolidate current knowledge, highlight inconsistencies, and identify critical knowledge gaps regarding their impact on age-associated eye diseases, aiming to support clinical decision-making and guide future ophthalmic research.
Results
The review found that glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs), while widely used for metabolic control, present a complex ocular profile. > GLP-1RAs were consistently associated with a reduced risk of age-related glaucoma, suggesting a potential protective effect on retinal ganglion cells and optic nerve health. However, the review also highlighted concerning, albeit unconfirmed, reports of severe nonarteritic anterior ischemic optic neuropathy (NAION) linked to GLP-1RA use, underscoring a critical safety signal requiring further investigation. Beyond GLP-1RAs, the synthesis revealed similar uncertainties and variable reporting across other geroprotective agents, including metformin, SGLT2 inhibitors, statins, cannabinoids, calcium channel blockers, and spermidine. Many agents showed mixed or inconclusive evidence regarding their ocular benefits and risks, indicating significant knowledge gaps. The authors emphasized that the ocular effects of these widely used systemic therapies remain incompletely characterized, necessitating more rigorous, dedicated ophthalmic research.
Why It Matters
Clinicians prescribing GLP-1 receptor agonists and other geroprotective agents must now consider their dual impact on ocular health, balancing potential benefits like reduced glaucoma risk against unconfirmed but severe adverse events such as nonarteritic anterior ischemic optic neuropathy. This review underscores the need for enhanced patient counseling regarding these complex ocular effects, particularly as these medications become more prevalent. For individuals using these compounds, understanding these nuanced risks and benefits is crucial for informed decision-making and proactive monitoring. The findings highlight that while these agents offer systemic advantages, their specific ocular safety and efficacy profiles are still evolving, necessitating further dedicated ophthalmic studies before clear protocols for ocular protection or risk mitigation can be established.