ImportanceSince fibroblast growth factor receptor inhibitors (FGFRi) are used for treatment of intrahepatic cholangiocarcinoma (iCCA), understanding potential complications following longer-term use in clinical practice settings is warranted. This study describes cataract formation or progression as a complication of FGFRi use for the treatment of iCCA, even after treatment discontinuation.ObjectiveTo describe cases of cataract formation or worsening in patients with iCCA treated with FGFRi and to characterize the ophthalmologic features, risk factors, and outcomes for FGFRi-associated cataracts.Design, Setting, and ParticipantsThis retrospective case series study used data from patients with iCCA harboring FGFR2 aberrations who received FGFRi in clinical trials or as standard therapy from the University of California, San Francisco, Hepatobiliary Tissue Bank and Registry. Data were collected from patient visits between February 2015 and October 2021, and this retrospective investigation was conducted from September 6, 2022, to May 4, 2023. Data analysis was conducted from May 5, 2023, to September 6, 2023.ExposureUse of an FGFRi for the treatment of iCCA.Main Outcomes and MeasuresThe primary outcome was designated as development of a new or worsening cataract after FGFRi initiation. Statistical analysis for the association between cataract formation and clinical covariates was performed using unpaired t tests and Fisher exact tests. A single bivariate logistic regression model was used to examine total duration of FGFRi therapy and age at the conclusion of FGFRi therapy as predictors of cataract development.ResultsA total of 18 patients were included in the study; median (range) patient age was 54 (27-81) years, and 13 patients (72%) were female. Nine patients (50%) developed a cataract or had cataract progression in at least 1 eye after initiation of FGFRi. Of 17 eyes with cataract, 8 eyes (47%) required cataract surgery. One patient rapidly developed a cataract associated with phacomorphic glaucoma, which required urgent surgery. The median (range) time to cataract onset or worsening from initiation of FGFRi was approximately 18 (1-23) months. Five of 9 patients (56%) who developed cataracts or had cataract progression were diagnosed with new or worsening cataracts after discontinuation of FGFRi. Patients who developed cataracts had longer median (range) duration of FGFRi treatment compared with patients who did not develop cataracts (13 months [2-26] vs 5 months [1-11]; odds ratio, 1.01; 95% CI, 1.00-1.02; P = .02).Conclusions and RelevanceWhile this retrospective case series study cannot prove cause and effect conclusively due to the study design, study results highlight cataract formation or progression as a potential adverse effect of FGFRi therapy, supporting consideration of periodic eye examinations in patients who have received this treatment.

中文翻译：

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与胆管癌成纤维细胞生长因子受体抑制剂相关的白内障


重要性由于成纤维细胞生长因子受体抑制剂 （FGFRi） 用于治疗肝内胆管癌 （iCCA），因此有必要了解在临床实践环境中长期使用后的潜在并发症。本研究将白内障的形成或进展描述为使用 FGFRi 治疗 iCCA 的并发症，即使在治疗停止后也是如此。目的描述 FGFRi 治疗 iCCA 患者白内障形成或恶化的病例，并描述 FGFRi 相关白内障的眼科特征、危险因素和结局。设计、设置和参与者这项回顾性病例系列研究使用了来自携带 FGFR2 畸变的 iCCA 患者的数据，这些患者在临床试验中接受了 FGFRi 或作为加利福尼亚大学旧金山分校肝胆组织库和登记处的标准疗法。数据是从 2015 年 2 月至 2021 年 10 月期间的患者访视中收集的，本回顾性调查于 2022 年 9 月 6 日至 2023 年 5 月 4 日进行。数据分析于 2023 年 5 月 5 日至 2023 年 9 月 6 日进行。使用未配对 t 检验和 Fisher 精确检验对白内障形成与临床协变量之间的关联进行统计分析。采用单因素 logistic 回归模型检查 FGFRi 治疗的总持续时间和 FGFRi 治疗结束时的年龄作为白内障发展的预测因子。结果共纳入 18 例患者;中位 （Range） 患者年龄为 54 （27-81） 岁，其中 13 例患者 （72%） 为女性。 9 例患者 （50%） 在开始 FGFRi 后至少 1 只眼睛出现白内障或白内障进展。在 17 只患有白内障的眼睛中，8 只眼睛 （47%） 需要白内障手术。1 例患者迅速发展为与超声形性青光眼相关的白内障，需要紧急手术。FGFRi 开始白内障发作或恶化的中位 （范围） 时间约为 18 （1-23） 个月。9 例发生白内障或白内障进展的患者中有 5 例 （56%） 在停用 FGFRi 后被诊断为新发或恶化的白内障。与未发生白内障的患者相比，发生白内障的患者接受FGFRi治疗的中位（范围）持续时间更长（13个月[2-26] vs 5个月[1-11];比值比，1.01;95% CI，1.00-1.02;P = .02）。结论和相关性虽然由于研究设计的原因，这项回顾性病例系列研究无法最终证明因果关系，但研究结果强调白内障的形成或进展是 FGFRi 治疗的潜在不良反应，支持考虑对接受这种治疗的患者进行定期眼科检查。