S738 Risk of Vision-Threatening Eye Complications Among GLP-1 Receptor Agonist Users: A Retrospective Cohort Analysis

Introduction: GLP-1 receptor agonists (GLP-1 RAs) are widely prescribed for type 2 DM (T2DM) and obesity, with well-established cardiometabolic benefits. However, emerging reports have raised concerns about ocular complications, particularly ischemic optic neuropathy, optic papillitis, and maculopathy. While the mechanisms remain uncertain, recent evidence suggests that rapid glycemic reduction and immune modulation may contribute to retinal injury. This study assessed the relationship between GLP-1 RA use and vision-threatening eye complications in a large, diverse U.S. cohort. Methods: We conducted a retrospective cohort study using electronic health record data from the NIH All of Us Research Program (2016–2022). Adults with obesity or T2DM were included; individuals with prior eye malignancy or advanced retinal disease were excluded. Eye complications were defined as a composite of ischemic optic neuropathy, optic papillitis, or maculopathy. A 1:1 propensity score matching was used to balance covariates between GLP-1 RA users and non-users based on demographics. Multivariable logistic regression estimated adjusted odds ratios (aORs), controlling for BMI, comorbidities, HbA1c and medications. Results: Among 34,380 matched participants (n = 17,190 per group; mean age 59.3 yrs; 66.6% female), overall eye complications were more common in GLP-1 RA users (4.8% vs 1.3%; P < 0.001). In adjusted analysis, GLP-1 RA use was associated with increased odds of eye complications (aOR: 1.58, 95% CI: 1.32–1.89, P < 0.001). The association was strongest for maculopathy (aOR: 1.64, 95% CI: 1.36–1.98, P < 0.001), while there was no significant association for ischemic optic neuropathy or optic papillitis. Independent predictors included T2DM (aOR: 5.50, 95% CI: 4.02–7.53, P < 0.001), hypertension (aOR: 1.70, 95% CI: 1.48–1.95, P < 0.001) and autoimmune disease (aOR: 1.36, 95% CI: 1.14–1.62, P = 0.001). A positive association was also noted between HbA1c variability and eye complications. Conclusion: GLP-1 RA use was independently associated with increased odds of maculopathy. The lack of association with ischemic optic neuropathy may reflect the anti-inflammatory properties of GLP-1 RA agents on its arteritic subtype. Our findings support the hypothesis that rapid glycemic shifts may underlie GLP-1–associated retinal injury, in line with prior pharmacovigilance data. Proactive ocular surveillance may be warranted in high-risk GLP-1 RA users, especially those with T2DM, autoimmune conditions, or HbA1c variability.