Liu Wensheng, Ye Xuan, Shan Han, Wang Mengmeng, Wang Yingbin, Guo Zihan, Liu Jiyong, Du Qiong
Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Clin Ther. 2024 Dec;46(12):1049-1058. doi: 10.1016/j.clinthera.2024.09.019. Epub 2024 Oct 19.
Ocular adverse events (oAEs) are a class of adverse events associated with oxaliplatin that are realistically observed in real-world settings. Herein, we aim to describe the clinical characteristics of oAEs associated with oxaliplatin through a systematic review of case reports and to assess a potential safety signal.
PubMed, Embase, and Cochrane Library databases were used to retrieve case reports. The global disproportionality study was performed leveraging the US Food and Drug Administration Adverse Event Reporting System database from January 2004 to September 2023. Bayesian information component (IC) and reporting odds ratio (ROR) were applied to identify and evaluate potential oAEs associated oxaliplatin.
A total of 20 cases from the systematic case review (of 13 screened articles) were reported on oAEs associated with oxaliplatin, with ages between 26 and 76 years. Therein, 16 (84.2%) cases described loss of vision, and the remaining cases presented with bilateral blepharoptosis, papilledema, and optic disc swelling. Insights from the US Food and Drug Administration Adverse Event Reporting System database showed that oAEs accounted for 4.28% (n = 1194) of the overall oxaliplatin-related adverse event reports, of which 1140 (95.48%) had a serious outcome. The median (interquartile range) onset time of oAEs with oxaliplatin was day 1 (0-25; n = 649). Disproportionality analysis revealed that ocular injuries NEC (n = 28, ROR, 22.72; lower limit of the 95% 2-sided CI for IC, 3.12) was the most significant signals detected. Additionally, unexpected significant oAEs, including eyelid ptosis, eyelid edema, eye movement disorder, blepharospasm, periorbital edema, swelling of eyelid, ophthalmoplegia, retinal vein thrombosis, cataract nuclear, blindness cortical, cataract subcapsular, and lacrimation disorder, were also reported disproportionality.
Our study systematically described the characteristics and outcomes of oxaliplatin-related ocular toxicity and also uncovered potential oAEs that were not disclosed in the package insert. Further prospective epidemiologic studies to validate these findings are warranted.
眼部不良事件（oAE）是一类与奥沙利铂相关的不良事件，在现实世界中切实可见。在此，我们旨在通过对病例报告的系统回顾来描述与奥沙利铂相关的oAE的临床特征，并评估潜在的安全信号。
使用PubMed、Embase和Cochrane图书馆数据库检索病例报告。利用美国食品药品监督管理局不良事件报告系统数据库进行2004年1月至2023年9月的全球不成比例性研究。应用贝叶斯信息成分（IC）和报告比值比（ROR）来识别和评估与奥沙利铂相关的潜在oAE。
系统病例回顾（从13篇筛选文章中）共报告了20例与奥沙利铂相关的oAE，年龄在26至76岁之间。其中，16例（84.2%）描述了视力丧失，其余病例表现为双侧上睑下垂、视乳头水肿和视盘肿胀。美国食品药品监督管理局不良事件报告系统数据库的见解显示，oAE占奥沙利铂相关不良事件报告总数的4.28%（n = 1194），其中1140例（95.48%）有严重后果。奥沙利铂相关oAE的中位（四分位间距）发病时间为第1天（0 - 25；n = 649）。不成比例性分析显示，未另行分类的眼损伤（n = 28，ROR，22.72；IC的95%双侧CI下限，3.12）是检测到的最显著信号。此外，还报告了意外的显著oAE，包括眼睑下垂、眼睑水肿、眼球运动障碍、眼睑痉挛、眶周水肿、眼睑肿胀、眼肌麻痹、视网膜静脉血栓形成、白内障核、皮质盲、白内障后囊下和泪液分泌障碍的不成比例性。
我们的研究系统地描述了奥沙利铂相关眼部毒性的特征和结果，还发现了药品说明书中未披露的潜在oAE。有必要进行进一步的前瞻性流行病学研究以验证这些发现。
