Glucagon-like Peptide-1 Receptor Agonist Impact on Chronic Ocular Disease Including Age-Related Macular Degeneration.

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Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have risen exponentially in usage and have been shown to exert neuroprotective and anti-inflammatory effects across multiple organ systems. This study investigates whether GLP-1RAs influence the risk for age-related ocular diseases. Retrospective cohort study. This study utilized an electronic health records platform of patients in the United States. Patients older than 60 years of age with at least five years of ophthalmology follow-up and medication prescription documentation were included. Patients were categorized into five medication groups: GLP-1RAs, metformin, insulin, statins, or aspirin users. Cohorts were propensity-matched on demographics and chronic health conditions using a greedy matching algorithm. Outcomes of cataract, ocular hypertension, primary open angle glaucoma, non-exudative AMD, and exudative AMD were compared five years following initial medication prescription. We then examined earlier timepoints within the five-year period. Significance was defined as p<0.05 and HR threshold > 1.1 or < 0.9 to improve signal to noise ratio. Of the 9,669 patients taking GLP-1RAs, 84.4 percent were diabetic with an average BMI of 36.2. Propensity matched cohorts demonstrated GLP-1RAs were associated with reduced hazard of non-exudative AMD compared to metformin (HR 0.68, 95%CI: 0.56-0.84), insulin (HR 0.72, 95%CI: 0.58-0.89), and statins (HR 0.7, 95%CI: 0.57-0.87). These findings were validated compared to aspirin and in an independent older cohort of patients. This significant reduction appeared after three years compared to metformin (HR 0.69, 95%CI: 0.52-0.91), insulin (HR 0.66, 95%CI: 0.5-0.87), and statins (HR 0.67, 95%CI: 0.51-0.88). Time course results were validated using independent cohorts of propensity matched patients taking medications for three years. Notably, GLP-1RAs also significantly reduced the risk of exudative AMD (HR 0.7, 95%CI: 0.58-0.84) and POAG (HR 0.58, 95% CI 0.45-0.76) compared to insulin after three years. Usage of GLP-1RAs showed no persistent significant impact on the risk of cataract formation nor ocular hypertension after five years compared other medications. This study suggests GLP-1RAs may reduce the risk of multiple age-related ocular diseases and suggests the need for future prospective studies to validate these findings.