In Reply We have read the letter by Kanclerz et al with great interest. The authors have raised some interesting points.

Our meta-analysis¹ included only randomized clinical trials and most of the trials were not designed to assess the risk of major adverse cardiovascular events (MACE) or mortality in patients receiving intraocular anti–vascular endothelial growth factor (VEGF) therapy. The risk of MACE in our main comparison was assessed between patients receiving anti-VEGF and patients receiving non–anti-VEGF treatments as a control group (sham, laser, or dexamethasone). We further restricted our data collection until 10% or more of the patients in the control group had crossed over to anti-VEGF treatment. Therefore, we tried to reduce the risk of bias in the pooled estimates of MACE and mortality of anti-VEGF vs control in our meta-analysis. Furthermore, it is true that our results may be applicable only to patients similar to those enrolled in the included trials. The exclusion of patients with a history of cardiovascular disease from several trials, the absence of data regarding patients’ comorbidities, the challenges of adjusting for such comorbidities, and a relative short mean follow-up period can limit the validity of the risk assessment for patients in clinical practice. These are limitations that we acknowledged and discussed in our article,¹ which led us to grade the level of evidence of our results as low according to the GRADE recommendation (Grading of Recommendations, Assessment, Development, and Evaluations).

作为回复，我们怀着极大的兴趣阅读了 Kanclerz 等人的来信。作者提出了一些有趣的观点。

我们的荟萃分析¹仅包括随机临床试验，并且大多数试验并非旨在评估接受眼内抗血管内皮生长因子（VEGF）治疗的患者发生主要不良心血管事件（MACE）或死亡率的风险。在我们的主要比较中，我们在接受抗 VEGF 治疗的患者和作为对照组（假手术、激光或地塞米松）接受非抗 VEGF 治疗的患者之间评估了 MACE 风险。我们进一步限制了我们的数据收集，直到对照组中有 10% 或更多的患者接受抗 VEGF 治疗。因此，在我们的荟萃分析中，我们试图降低 MACE 和抗 VEGF 与对照死亡率的汇总估计中的偏倚风险。此外，我们的结果确实可能仅适用于与纳入试验的患者相似的患者。将有心血管疾病病史的患者排除在几项试验之外、缺乏有关患者合并症的数据、调整此类合并症的挑战以及相对较短的平均随访期可能会限制对患者进行风险评估的有效性在临床实践中。这些是我们在文章中承认和讨论的限制，¹这导致我们根据 GRADE 推荐（推荐、评估、发展和评估的分级）将我们的结果的证据级别评为低。