丝裂原活化细胞外信号调节激酶抑制剂致视网膜静脉阻塞文献分析

Literature analysis of retinal vein occlusion induced by mitogen-activated extracellular signal-regulated kinase inhibitors

目的回顾分析丝裂原活化细胞外信号调节激酶(MEK)抑制剂相关不良反应——视网膜静脉阻塞(RVO)的报道,提高医务工作者对相关药物不良反应的认知和防范。方法检索PubMed、Embase等数据库(截至2022年4月8日),收集报道MEK抑制剂相关RVO的病例报告和临床研究等文献,提取患者相关信息进行描述性统计分析,并对临床试验数据进行总结。结果纳入文献共13篇,病例报告及临床试验中累计报道MEK抑制剂相关RVO患者30例。纳入病例分析的4例患者RVO均由荧光素血管造影明确诊断,且经光学相干断层扫描观察到囊样黄斑水肿;4例患者平均年龄为49.8岁,男女各2例,发生RVO的中位时间为服药后6.7个月。临床试验共报道26例MEK抑制剂相关的RVO患者,其中20例明确了RVO不良反应分级(11例为1~2级,9例为3级及以上RVO)。30例MEK抑制剂相关RVO患者中有17例被报道停用了MEK抑制剂,大多数患者在停用MEK抑制剂后RVO症状得以缓解;另外报道了7例患者(其中已知5例患者停用MEK抑制剂)使用抗血管内皮生长因子药物进行干预治疗,其中6例视力恢复至基线水平。结论MEK抑制剂临床应用可能会引起RVO,且该不良反应发生时间跨度较大,定期的眼科检查有助于早期识别,停用MEK抑制剂并采取适当的干预手段可能是缓解RVO症状的关键。

Objective To review and analyze the reports of mitogen-activated extracellular signal-regulated kinase(MEK)inhibitors related retinal vein occlusion(RVO),thus to enhance the awareness of such adverse effect related to MEK inhibitors.Methods Reports of RVO related to MEK inhibitors were collected by searching PubMed,Embase,and other databases up to April 8th,2022.The relevant information and medication status of patients were extracted and analyzed descriptively.Results A total 13 reports were included and 30 cases of MEK inhibitors-related RVO were reported,including 4 case reports and 26 cases from clinical trials.The 4 patients in the case reports were all diagnosed with RVO by fluorescein angiography,and cystoid macular edema was observed by optical coherence tomography;the average age of the 4 patients was 49.8 years old,with 2 males and 2 females,and the median time to RVO onset was 6.7 months after MEK inhibitors were administered.A total of 26 patients with RVO related to MEK inhibitors were reported in clinical trials,for 20 of whom the grade of RVO was defined(11 cases of grade 1-2,and 9 cases of grade 3 or above).Among the 30 patients 17 discontinued MEK inhibitors.Most of RVO symptoms relieved after discontinuation of MEK inhibitors.Seven patients(5 of whom were known to have discontinued MEK inhibitors)were treated with anti-vascular endothelial growth factor drugs and the visual acuity of 6 patients returned to baseline level.Conclusion The clinical application of MEK inhibitors may cause RVO,and RVO occurs in a large time span.Regular eye examinations can help identify RVO in time.Discontinuation of MEK inhibitors and appropriate drug intervention might be the key to relieving RVO symptoms.