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.

<i>研究目的：</i> 本项元分析旨在评估与MEK抑制剂（MEK inhibitors）相关的眼科不良反应发生风险。<i>研究方法：</i> 本研究在PubMed及Cochrane图书馆中开展文献检索，筛选旨在评估MEK抑制剂疗效与安全性的随机对照临床试验（RCTs）。本次研究的评估结局指标包括眼科不良反应总体风险、脉络膜视网膜病变、视网膜脱离、视物模糊、葡萄膜炎及眼出血。采用合并Peto比值比（ORs）及其95%置信区间（CIs）进行效应量合并，并通过I²统计量评估研究间异质性。<i>研究结果：</i> 本项元分析共纳入13项RCTs。总体而言，MEK抑制剂与眼科不良反应风险升高相关（OR=2.24，95%CI：1.75~2.87，P<0.0001，I²=86.5%）。亚组分析显示，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%）及视物模糊（OR=2.30，95%CI：1.50~3.54，P<0.0001，I²=60.1%）的不良反应风险均显著升高，但未观察到葡萄膜炎（OR=0.99，95%CI：0.14~7.03，P=0.991，I²=2.9%）与眼出血（OR=0.72，95%CI：0.04~12.39，P=0.824，I²=29.8%）的风险升高。<i>研究结论：</i> 采用MEK抑制剂治疗似乎会升高眼科不良反应的发生风险，因此亟需对该类药物的安全性开展监测。监管机构、临床医师及其他医疗专业人员需共同参与此项监测工作。