Comparative Analysis of Systemic Complications of Antivascular Endothelial Growth Factor Therapies in Retinal Diseases

Purpose: To compare the systemic safety profiles of antivascular endothelial growth factor (anti-VEGF) agents using a large real-world dataset. Methods: The TriNetX Research Network database was used to identify adults with macular edema secondary to diabetes, retinal vein occlusion, or age-related macular degeneration who received bevacizumab, ranibizumab, or aflibercept (2012–2022) or faricimab (2022–2024). The bevacizumab cohort was matched with the other cohorts using propensity score matching to account for demographic characteristics and comorbidities. Outcomes included stroke, venous thromboembolism, myocardial infarction, hypertension, brain hemorrhage, and renal function. Results: In the propensity score–matched cohorts comparing outcomes between bevacizumab and aflibercept (each n = 9538), bevacizumab was associated with higher mean blood urea nitrogen level (28.07 mg/dL vs 26.89 mg/dL; P = .017), higher mean serum creatinine level (1.86 mg/dL vs 1.72 mg/dL; P = .004), and lower mean estimated glomerular filtration rate (55.64 mL/min vs 58.01 mL/min; P = .003) at 1 to 6 months’ follow-up. Compared with the faricimab cohort, the bevacizumab cohort (each n = 3500) showed increased risk of stroke (risk ratio [RR], 1.71, 95% CI, 1.19–2.48), venous thromboembolism (RR, 1.80, 95% CI, 1.11–2.93), myocardial infarction (RR, 1.72, 95% CI, 1.19–2.49), and hypertension (RR, 1.47, 95% CI, 1.19–1.83) within 2 years of follow-up. No significant differences were found between the bevacizumab and ranibizumab cohorts (each n = 2211). Conclusions: Bevacizumab may confer an increased risk of cardiovascular events and differences in renal function parameters compared with aflibercept and faricimab, but not ranibizumab. This underscores the importance of tailoring anti-VEGF therapy to patient-specific profiles, particularly in patients with underlying cardiovascular and renal comorbidities. Further studies in lower-comorbidity populations are needed to clarify these associations.