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DR Anti-VEGF Associated with Adverse Events

A large cohort study of more than 1.7 million patients found that intravitreal anti-VEGF injections were associated with an increase in the likelihood of systemic adverse events among patients with diabetic retinopathy (DR), a leading cause of visual loss among working-aged adults.

Published in JAMA Ophthalmology,1 the study found an association was maintained when controlling for several factors, including age, sex, race, ethnicity, smoking status, mean haemoglobin A1c levels, statin use, DR severity, and comorbidity burden.

To complete the study, researchers in the United States extracted data through the Corporate Data Warehouse, a large-scale database related to mental and physical health of patients within the Veterans Health Administration (VHA).

The largest integrated health care system in the United States, VHA provides care at 1,240 health care facilities to more than nine million veterans.

The researchers included data for all individuals with diabetes (either with or without DR) who did and did not receive anti-VEGF injections.

They then adjusted the data for DR severity in the regression model. The mean (SD) age of the 1,731,782 patients was 63.8 years, with most being male (95.7% vs. 4.3% female).

DR was present in 27.5% of the veterans and 0.8% received treatment with anti-VEGF injections. The most common anti-VEGF agent used was aflibercept (48%), followed by bevacizumab (35.7%), and ranibizumab (8.7%). Information on the type of anti-VEGF agent used was unavailable for 7.5% of patients. Of the 2,712 patients who received an anti-VEGF injection but did have an associated DR diagnosis, 2,600 (95.9%) had either a retinal vein occlusion or exudative age-related macular degeneration.

The primary outcome of interest was the proportion of patients with any systemic adverse event at one-, three-, and five-year follow-up.

The authors wrote that it was “challenging to study the role of intravitreal anti-VEGF therapy in contributing to systemic adverse event risk in DR because diabetes is associated with cardiovascular disease, and coronary artery disease. Additionally, it is associated with multiple risk factors which promote cardiovascular disease and coronary artery disease, and it acts as an independent risk factor for vascular disease and associated complications, including stroke and myocardial infarction.”

Despite these challenges they found that “intravitreal anti-VEGF therapy was independently associated with a higher likelihood of systemic adverse events, including acute myocardial infarction, cardiovascular disease, and kidney disease”.

“The proportion of patients with any systemic adverse event, acute myocardial infarction, cardiovascular disease, and kidney disease at year five was higher in the injection group vs. the group that did not receive injections. However, the difference in the overall number of injections given among those who developed systemic adverse events vs. those who did not was small (10.2 vs. 10.8, respectively), and the difference is unlikely to be clinically relevant. Additional factors independently associated with systemic adverse events were patient age, sex, race, ethnicity, tobacco use, DR severity, and comorbidity burden.”

They suggested that alternative therapies, such as intravitreal steroids or laser, may be an option for patients with diabetes who are at high risk of systemic adverse events.

Reference
1. Zafar, S., Walder, A., Virani, S., et al., Systemic adverse events among patients with diabetes treated with intravitreal anti–vascular endothelial growth factor injections. JAMA Ophthalmol. 2023;141(7):658–666. doi:10.1001/jamaophthalmol.2023.2098.