Risk of intraocular hemorrhage among exudative age-related macular degeneration patients treated with different anti-VEGF agents

BACKGROUND: Intraocular hemorrhage is a vision-threatening complication in patients with exudative age-related macular degeneration (AMD) receiving intravitreal anti-vascular endothelial growth factor (VEGF) therapy. We aimed to compare the risk of intraocular hemorrhage requiring vitrectomy among patients with exudative AMD treated with ranibizumab, aflibercept, or brolucizumab. METHODS AND FINDINGS: This nationwide retrospective cohort study used claims data from the Korean National Health Insurance Review and Assessment Service (May 2014-April 2023). Korean patients aged 40 years or older with newly diagnosed exudative AMD who initiated anti-VEGF therapy and had no history of intraocular hemorrhage were included. The primary outcome was intraocular hemorrhage requiring vitrectomy after anti-VEGF initiation. Time-to-event analyses using Cox proportional hazards regression estimated hazard ratios (HRs) and 95% CIs; Kaplan-Meier curves showed cumulative incidence probability, and logistic regression provided complementary risk estimates. Among 75,812 patients, 1,128 (1.5%) experienced intraocular hemorrhage requiring vitrectomy. Compared with ranibizumab, the adjusted risk was higher with brolucizumab (HR, 1.83; 95% CI, 1.18-2.83; P = .007) and aflibercept (HR, 1.31; 95% CI, 1.14-1.49; P < .001). Logistic regression similarly showed higher odds with aflibercept versus ranibizumab (adjusted odds ratio, 1.32; 95% CI, 1.16-1.51; P < .001). Patients with hemorrhage received fewer anti-VEGF injections in the first year than those without hemorrhage (3.15 ± 1.87 vs 4.01 ± 1.85; P < .001). CONCLUSION: In this large nationwide cohort, intraocular hemorrhage requiring vitrectomy after anti-VEGF therapy for exudative AMD was rare but occurred more frequently with brolucizumab and aflibercept than with ranibizumab. Although unlikely to be the primary determinant of anti-VEGF selection, these findings provide adjunctive safety information that may be considered when counseling and monitoring selected patients.