Frequentist Analysis of Death Associated With Intravitreal Anti–Vascular Endothelial Growth Factor Therapy—Reply

In Reply We are grateful to Fau et al for conducting and providing further analyses on our data set,¹ which reinforced our interpretation and the need for further investigation regarding long-term, intensive intravitreal anti–vascular endothelial growth factor (anti-VEGF) treatment. Specifically, the authors remarked on our finding of a potential increase in overall mortality in the subgroup with monthly injections for up to 24 months (odds ratio, 1.89 [95% CI, 1.06-3.36]), which is a key finding of our study.¹ However, we have been conservative in drawing conclusions, because despite a relatively large sample size (8887 trial participants), the number of deaths was only 128 (1.44%). Unsurprisingly, a contrast comparing the 6-month follow-up subgroup and the 24-month follow-up subgroup was not significant in the frequentist meta-analysis. This result was confirmed by bayesian methods.¹