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

Purpose: 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.

Design: Retrospective cohort study.

Subjects And Participants: 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.

Main Outcome Measures: 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.

Results: 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.

Conclusions: 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.