Supplementary Material for: Risk of Ophthalmic Adverse Effects in Patients Treated with MEK Inhibitors: A Systematic Review and Meta-Analysis

<i>Objectives:</i> This meta-analysis aims to evaluate the risk of ophthalmic adverse effects associated with MEK inhibitors. <i>Methods:</i> A literature search was conducted in PubMed and the Cochrane Library to identify randomized clinical trials (RCTs) which have been designed to evaluate the efficacy and safety of MEK inhibitors. Overall risk of ophthalmic adverse effects, chorioretinopathy, retinal detachment, blurred vision, uveitis, and eye haemorrhage were the assessed outcomes. Peto odds ratios (ORs) with their 95% confidence intervals (CIs) were pooled. Between-study heterogeneity was assessed using I2 statistics. <i>Results:</i> Thirteen RCTs were included in this meta-analysis. Overall, MEK inhibitors were associated with an increased risk of ophthalmic adverse effects (OR 2.24; 95% CI 1.75-2.87; p &lt; 0.0001; I2 = 86.5%). An increased risk was also estimated for chorioretinopathy (OR 5.44; 95% CI 2.89-10.23; p &lt; 0.0001; I2 = 0%), retinal detachment (OR 6.54; 95% CI 3.28-13.03; p &lt; 0.0001; I2 = 0%), and blurred vision (OR 2.30; 95% CI 1.50-3.54; p &lt; 0.0001; I2 = 60.1%), but not for uveitis (OR 0.99; 95% CI 0.14-7.03; p = 0.991; I2 = 2.9%) or eye haemorrhage (OR 0.72; 95% CI 0.04-12.39; p = 0.824; I2 = 29.8%). <i>Conclusions:</i> Treatment with MEK inhibitors seems to increase the risk of ophthalmic adverse effects. A need for monitoring the safety of this class of drugs exists. Regulators, clinicians, and other health care professionals must, together, be involved in this process.

**研究目的**：本荟萃分析旨在评估与丝裂原活化蛋白激酶激酶抑制剂（MEK inhibitors）相关的眼科不良事件发生风险。
**研究方法**：本研究通过检索PubMed及Cochrane图书馆数据库，筛选旨在评估MEK抑制剂疗效与安全性的随机对照试验（randomized clinical trials, RCTs）。本研究的评估结局包括眼科不良事件总体发生风险，以及脉络膜视网膜病变、视网膜脱离、视力模糊、葡萄膜炎与眼部出血的发生风险。采用合并Peto比值比（ORs）及其95%置信区间（CIs）进行统计分析，并通过I²统计量评估研究间异质性。
**研究结果**：本荟萃分析共纳入13项随机对照试验。总体而言，MEK抑制剂可显著升高眼科不良事件的发生风险（比值比OR=2.24，95%置信区间CI：1.75~2.87；P<0.0001；I²=86.5%）。此外，本研究还发现，MEK抑制剂可显著升高脉络膜视网膜病变（OR=5.44，95%CI：2.89~10.23；P<0.0001；I²=0%）、视网膜脱离（OR=6.54，95%CI：3.28~13.03；P<0.0001；I²=0%）及视力模糊（OR=2.30，95%CI：1.50~3.54；P<0.0001；I²=60.1%）的发生风险，但未显著升高葡萄膜炎（OR=0.99，95%CI：0.14~7.03；P=0.991；I²=2.9%）或眼部出血（OR=0.72，95%CI：0.04~12.39；P=0.824；I²=29.8%）的发生风险。
**研究结论**：使用MEK抑制剂治疗似乎会升高眼科不良事件的发生风险，因此临床需加强对该类药物安全性的监测。药品监管机构、临床医师及其他医护人员需共同参与该监测流程。