Recurrent Interdigitation Zone Abnormalities associated with Fibroblast Growth Factor Receptor Inhibitor Futibatinib

To describe the multimodal imaging features and longitudinal course of futibatinib-associated retinopathy, including a recurrent, fluctuating interdigitation zone (IZ) abnormality, a concurrent large retinal capillary aneurysm (LRCA), and an apparent association with self-imposed fasting.

Observational case report of a 44-year-old man receiving futibatinib, a fibroblast growth factor receptor (FGFR) inhibitor, for intrahepatic cholangiocarcinoma. Evaluation included high-resolution spectral-domain optical coherence tomography (OCT), quantitative external limiting membrane-to-Bruch membrane (ELM-to-BM) thickness mapping, multifocal electroretinography, and microperimetry, with serial follow-up.

Approximately 450 days after starting futibatinib, surveillance OCT revealed subtle foveal photoreceptor changes. High-resolution OCT 30 days later confirmed increased visibility, thickening, and splitting of the IZ from the retinal pigment epithelium in both eyes, with a parafoveal LRCA in the right eye and no intraretinal exudation. Best-corrected visual acuity was 20/20 bilaterally; multifocal electroretinography and microperimetry were unremarkable. The drug was continued in coordination with oncology, and the IZ splitting resolved spontaneously within approximately 45 days of initial detection. The IZ abnormality subsequently recurred and then normalized despite unchanged dosing, indicating a fluctuating course; ELM-to-BM thickness mapping objectively tracked this evolution. The patient reported complete water-only fasting coinciding with the period of interval improvement.

Futibatinib-associated retinopathy may follow a recurrent, fluctuating rather than strictly self-resolving course centered on the IZ, and can be objectively monitored with quantitative photoreceptor mapping. An LRCA and a possible relationship to prolonged fasting-regulated FGFR1 ligands are reported as putative additional features, supporting continued therapy with close monitoring in asymptomatic patients with preserved visual function.