Systemic Arterial and Venous Thrombotic Events Associated with Anti-Vascular Endothelial Growth Factor Injections: A Meta-Analysis

To compare risk of systemic arteriovenous thrombotic events between between intravitreal anti-vascular endothelial growth factor (anti-VEGF) and sham injections.Random-effects meta-analysis.A systematic search was performed on OVID MEDLINE, EMBASE, and Cochrane Library from January 2005 to August 2023. Inclusion criteria included randomized clinical trials (RCTs) reporting on systemic arteriovenous events for standard dose intravitreal anti-VEGF agents for any indication.20 RCTs reporting on 12,833 eyes were included. There was no significant difference in the risk of any thrombotic event between bevacizumab 1.25 mg and ranibizumab 0.5 mg (RR= 0.96, 95 % CI = [0.52-1.75], p= 0.89). There was no significant difference between bevacizumab and ranibizumab when restricting to arterial thrombotic events (RR= 0.88, 95 % CI = [0.60-1.30], p= 0.53) or venous thrombotic events (RR= 1.99, 95 % CI =86 [0.68-5.82], p= 0.21). The risk of arterial thrombotic events was similar between aflibercept and bevacizumab (RR= 1.11, 95 % CI = [0.60, 2.07], p= 0.74), between aflibercept and ranibizumab (RR= 0.77, 95 % CI = [0.49, 1.21], p= 0.26), between brolucizumab and aflibercept (RR= 0.67, 95 % CI = [0.32, 1.38], sp= 0.27), and between aflibercept and faricimab (RR = 0.96, 95 % CI = [0.43, 2.17], p=0.93). Compared to sham, neither dose of ranibizumab (either 0.5 or 0.3 mg) showed a higher risk of arterial thrombotic events.There was a similar risk for systemic arteriovenous thrombotic adverse events between anti-VEGF agents and between ranibizumab and sham injections.