To Örebro University

BACKGROUND: Intravitreal Anti-Vascular Endothelial Growth Factor (VEGF) rescues retinal vasculatures and prevents disease progression in patients with neovascular Age-Related Macular Degeneration (nAMD). However, systemic anti-VEGF may increase the risk of thromboembolic related complications including stroke and TIA. This study aims to explore the association between stroke and intravitreal anti-VEGF agents; ranibizumab, aflibercept and bevacizumab.

METHODS: This nationwide, population- registry-based case-control study used registered data 2007-2019. Data from the Swedish Stroke Registry (Riksstroke) and the Swedish Macula Register (SMR) were cross-linked to identify nAMD patients who developed stroke/TIA within 90 days after intravitreal anti-VEGF injection. Each stroke case was matched with three controls from Riksstroke with stroke/TIA but no anti-VEGF treatment.

RESULTS: A total of 33 585 patients with nAMD underwent intravitreal anti-VEGF agent injections. A stroke occurred in 1693 patients of this group, and 936 of them within 90 days of treatment. Compared with nonuse, intravitreal anti-VEGF agent use was associated with an increased risk of stroke within 90 days of anti-VEGF treatment in 2.9% of the nAMD-patients [Risk Ratio (RR) 1.27, 95% confidence interval (CI) 1.22; 1.33] compared to non-users. The RR within 30, 31-60 and 61-90 days were 1.36 (1.15; 1.66), 1.40 (1.09; 1.79) and 0.58 (0.52; 0.65), respectively.

CONCLUSIONS: Even though the risk is small, intravitreal injections with anti-VEGF agents for the treatment of nAMD are associated with an increased risk of stroke/TIA. The risk seems to be higher within 60 days of last injection. An assessment of high-risk populations and risk-benefit weighting is necessary before intravitreal anti-VEGF injections are considered.