A Meta-Analysis of Cardiovascular Events Associated with Intravitreal Anti-VEGF Treatment in Patients with Retinal Vein Occlusion

Purpose: Retinal vein occlusion is associated with an increased risk of cardiovascular diseases. Anti-vascular endothelial growth factor has been widely used as a treatment option. However, the systemic safety of intravitreal anti-vascular endothelial growth factor for retinal vein occlusion patients is still unclear. Materials and Methods: A meta-analysis was conducted to investigate all randomized controlled trials published up to February 2019 of retinal vein occlusion patients who received intravitreal anti-vascular endothelial growth factor vs. control treatments. Fixed effect models were used and results were reported as odds ratios and 95% confidence intervals. Results: Eight trials that evaluated 2320 patients were retrieved. Anti-vascular endothelial growth factor did not significantly increase the risks of cardiovascular events (odds ratio,1.54; 95% confidence interval, 0.66–3.57), hypertension (odds ratio, 0.92; 95% confidence interval, 0.63–1.33), or heart rate disorders (odds ratio,1.53; 95% confidence interval, 0.37–6.28) when compared with control treatment. Subgroup analyses did not show a significant increase of cardiovascular events in aflibercept (odds ratio,1.96; 95% confidence interval, 0.44–8.81) vs. ranibizumab trials (odds ratio, 1.47; 95% confidence interval, 0.54–4.02); 0.5 mg ranibizumab trials (odds ratio, 1.73; 95% confidence interval, 0.61–4.96) vs. 0.3 mg ranibizumab trials (odds ratio, 0.70; 95% confidence interval, 0.14–3.59); nor branch retinal vein occlusion (odds ratio, 1.32; 95% confidence interval, 0.40–4.33) vs. central retinal vein occlusion trials (odds ratio, 1.93; 95% confidence interval, 0.59–6.29). Conclusions: Intravitreal administration of anti-vascular endothelial growth factor did not significantly increase the risks of cardiovascular events, hypertension or heart rate disorders in retinal vein occlusion patients.