JAMA Ophthalmol. 2024 Oct 24. doi: 10.1001/jamaophthalmol.2024.4395. Online ahead of print.
ABSTRACT
IMPORTANCE: Since 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.
OBJECTIVE: To 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 PARTICIPANTS: This 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.
EXPOSURE: Use of an FGFRi for the treatment of iCCA.
MAIN OUTCOMES AND MEASURES: The 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.
RESULTS: A 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 RELEVANCE: While 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.
PMID:39446357 | DOI:10.1001/jamaophthalmol.2024.4395
