As GLP-1 receptor agonists (GLP-1s) like semaglutide (Wegovy, Ozempic) and tirzepatide (Mounjaro, Zepbound) become increasingly common in the treatment of diabetes, obesity, and cardiovascular disease, retina specialists are paying close attention to whether the drug therapies may influence ocular disease in already high-risk patients.
“Many patients taking GLP-1 medications are older, vasculopathic, and already carry significant ocular risk factors,” said Rishi P. Singh, MD, chair of the department of ophthalmology at Mass Eye and Ear in Boston, during his presentation at the Retina World Congress in Fort Lauderdale, Florida.
Dr. Singh reviewed the latest evidence examining GLP-1 therapies in relation to diabetic retinopathy (DR), age-related macular degeneration (AMD), nonarteritic anterior ischemic optic neuropathy (NAION), and retinal vein occlusion (RVO). Here is what he shared.
Figure 1. Rapid glycemic improvement with GLP-1 therapies may contribute to early worsening of diabetic retinopathy, particularly in patients with preexisting severe NPDR or proliferative disease.
Diabetic Retinopathy. According to Dr. Singh, the strongest retinal safety signal to date involves DR progression during periods of rapid glycemic improvement (Figure 1). For instance, in the SUSTAIN-6 trial, semaglutide was associated with a significantly higher ratio of retinopathy complications compared with placebo, including vitreous hemorrhage, retinal photocoagulation, and intravitreal therapy. The trial reported a hazard ratio of 1.76 for retinal complications within the first 1 to 2 years of treatment.
However, Dr. Singh emphasized that the phenomenon appears tied to rapid HbA1c reduction rather than direct retinal toxicity from the drug itself. Patients with preexisting retinopathy appear particularly vulnerable to this “early worsening” effect, especially those with severe nonproliferative or proliferative disease. As a result, he recommended baseline retinal examinations before initiating therapy and closer follow-up during periods of aggressive glycemic control. “This is the population to be most worried about if a patient has preexisting retinopathy,” he said.
Dr. Singh added that results from the ongoing FOCUS study—a long-term ophthalmic endpoint trial evaluating semaglutide versus placebo in patients with type 2 diabetes—will be critical in clarifying the long-term retinal safety profile of GLP-1 therapies.
Age-Related Macular Degeneration. Evidence regarding AMD remains conflicting. As an example, Dr. Singh highlighted two 2025 studies: one found GLP-1 use was associated with a lower incidence of progression to advanced AMD, including neovascular AMD and geographic atrophy, while another reported an increased risk of neovascular AMD among GLP-1 users. However, Dr. Singh suggested the discrepancy may stem from the latter study’s design limitations. He noted that exposed and non-exposed patient groups were not adequately stratified by baseline AMD severity, potentially biasing the findings.
Figure 2. Rishi P. Singh, MD, reviewed conflicting evidence regarding semaglutide and nonarteritic anterior ischemic optic neuropathy (NAION). Some studies suggest increased risk, but several large database analyses have not confirmed the association.
Nonarteritic Anterior Ischemic Optic Neuropathy. NAION remains one of the most controversial areas of discussion. Dr. Singh said that studies from Mass Eye and Ear suggest semaglutide users may experience an increased risk of NAION, with one analysis reporting a 4.3-fold higher risk compared with comparators. However, he acknowledged that several large database studies have failed to consistently reproduce the same association (Figure 2).
Retinal Vein Occlusion. The most reassuring findings were those involving RVO, according to Dr. Singh. He cited large population-based cohort studies demonstrating no increased risk among GLP-1 users and even suggesting a possible reduction in the incidence of branch retinal vein occlusion.
Dr. Singh’s overall message was that current evidence does not support withholding GLP-1 therapy solely because of ocular safety concerns. Instead, he advised baseline retinal examinations in patients with diabetes before initiating therapy and closer monitoring for those with severe NPDR or proliferative DR during periods of rapid glycemic improvement (Figure 3). Patients with “disc-at-risk” anatomy or vascular risk factors should be counseled about NAION symptoms, while current data on AMD and retinal vein occlusion do not justify altering GLP-1 therapy. RP
Figure 3. Rishi P. Singh, MD, emphasized that current evidence does not support withholding GLP-1 therapy because of ocular safety concerns, but recommended baseline retinal evaluation and closer monitoring in patients at higher risk for diabetic retinopathy progression or NAION.