Centre for Ophthalmology and Visual Science (Incorporating Lions Eye Institute), The University of Western Australia, Nedlands, Western Australia, Australia.
Department of Medical Oncology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia.
Clin Exp Ophthalmol. 2021 Aug;49(6):579-590. doi: 10.1111/ceo.13940. Epub 2021 May 26.
To describe ocular adverse events and retinal changes during fibroblast growth factor receptor (FGFR) inhibitor (AZD4547) anticancer therapy.
This is a sub-study examining ocular adverse effects from AZD4547 therapy (single-centre, open-label, single arm phase II clinical trial). Comprehensive ocular examinations were performed 3 weekly in 24 patients. Macular optical coherence tomography (OCT) scan (30 × 25 ) was obtained at each visit and OCT parameters [central 1 mm retinal thickness (CRT) and total macular volume in central 6 mm] extracted. OCT scans were subdivided into outer (ELM to RPE) and inner (ELM to ILM) layers to compare outer and inner retinal changes.
In 24 patients, AZD4547 was associated with eyelash elongation (n = 5, 21%) and punctate corneal erosion (n = 2, 8%). One patient developed clinically significant posterior capsular opacification during the study. OCT data were available in 23 patients, retinal changes ranged from an asymptomatic increased visibility of the interdigitation zone (IDZ) (n = 10, 43%) to multilobular subretinal fluid pockets (n = 5, 22%), which was associated with mild visual acuity loss. In a subset of patients (n = 9) with pre-AZD4547 dosing OCT baseline, CRT increased by mean (SD) of 9 (4) μm in those with IDZ change only compared with 64 (38) μm in those with other retinal changes. Retinal changes tended to be bilateral, self-limiting and improved over time without medical intervention.
The ocular signs and symptoms did not result in dose cessation. Posteriorly, FGFR inhibition leads to outer retinal changes ranging from increased visibility of IDZ to distinct, multiple fluid pockets.
描述成纤维细胞生长因子受体(FGFR)抑制剂(AZD4547)抗癌治疗过程中的眼部不良反应和视网膜变化。
这是一项检查 AZD4547 治疗眼部不良反应的子研究(单中心、开放标签、单臂 II 期临床试验)。对 24 名患者进行每周 3 次的全面眼部检查。每次就诊时均进行黄斑光学相干断层扫描(OCT)扫描(30×25),并提取 OCT 参数[中央 1 毫米视网膜厚度(CRT)和中央 6 毫米的总黄斑体积]。将 OCT 扫描分为外(ELM 到 RPE)和内(ELM 到 ILM)层,以比较外和内视网膜变化。
在 24 名患者中,AZD4547 与睫毛伸长(n=5,21%)和点状角膜糜烂(n=2,8%)有关。一名患者在研究过程中出现了临床显著的后囊混浊。23 名患者的 OCT 数据可用,视网膜变化范围从无症状的 IDZ (n=10,43%)的可见度增加到多叶状的视网膜下液袋(n=5,22%),伴有轻度视力丧失。在有 OCT 基线的亚组患者(n=9)中,与 IDZ 变化仅相关的 CRT 平均(SD)增加了 9(4)μm,而与其他视网膜变化相关的 CRT 增加了 64(38)μm。视网膜变化倾向于双侧、自限性,并随时间改善,无需医疗干预。
眼部症状和体征并未导致停药。后部,FGFR 抑制导致外视网膜变化,从 IDZ 的可见度增加到明显的多个液袋。