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Brief Report
September 2, 2021

Clinical and Morphologic Characteristics of Fibroblast Growth Factor Receptor Inhibitor–Associated Retinopathy

Author Affiliations
  • 1Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York
  • 2Weill-Cornell Medical Center, New York, New York
  • 3Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
JAMA Ophthalmol. 2021;139(10):1126-1130. doi:10.1001/jamaophthalmol.2021.3331
Key Points

Question  What are the clinical and morphological findings of retinopathy in patients taking fibroblast growth factor receptor (FGFR) inhibitors?

Findings  In this single-institution case series including 20 patients, FGFR inhibitors resulted in subretinal foci, which may be asymptomatic, but also may be associated with temporary visual decline.

Meaning  These results provide evidence to support the finding that FGFR inhibitors can exhibit self-resolving retinopathy and may explain visual symptoms while taking the drug, although the precise frequency or magnitude of this adverse effect cannot be determined with certainty from this retrospective investigation.

Abstract

Importance  Fibroblast growth factor receptor (FGFR) 1 to 4 inhibitors are approved by the US Food and Drug Administration and suppress the mitogen-activated protein kinase (MAPK) pathway, with a potential for treatment-related retinopathy. To date, implications of FGFR inhibitor–associated ocular toxic effects are poorly described. Therefore, more detailed clinical descriptions of this ocular toxic effect could help explain visual symptoms while receiving drug therapy.

Objective  To describe the clinical and morphologic characteristics of serous retinal disturbances associated with FGFR inhibitors.

Design, Setting, and Participants  In this retrospective case series, 146 patients receiving FGFR inhibitors as cancer treatment at a single tertiary referral center were included. This study included 40 eyes of 20 patients with retinopathy by optical coherence tomography (OCT). OCTs were obtained on the remaining patients and the results were judged normal. Patients were recruited from March 2012 to January 2021.

Main Outcomes and Measures  Characteristics of treatment-emergent choroidal and retinal OCT abnormalities as compared with baseline OCT, associated with visual acuity at presentation and at fluid resolution.

Results  A total of 20 of 146 patients (13.7%) exhibited FGFR inhibitor–associated retinopathy. Of these 20 patients, 11 (55%) were female, and the median (range) age was 62.6 (42.7-86.0) years. The median (range; mean) time from medication start to initial subretinal fluid detection was 21 (5-125; 32) days. The median (interquartile range [IQR]) baseline logMAR best-corrected visual acuity (BCVA) was 0 (0-0.1). At fluid accumulation, 11 eyes had decreased vision: the median (IQR) subgroup baseline BCVA was 0 (0-0.1); and the median (IQR) BCVA change from baseline to accumulation was −0.1 (−0.2 to −0.1). For 26 eyes (65%) with follow-up, the subretinal fluid resolved without medical intervention or drug interruption in all but 1 patient. At fluid resolution, the median (IQR) BCVA was 0.1 (0-0.1), and the change in median (IQR) BCVA from baseline to fluid resolution was 0 (−0.03 to 0). No patient discontinued drug therapy on account of their retinopathy.

Conclusions and Relevance  FGFR inhibitors result in subretinal fluid foci similar to other drugs that inhibit the MAPK pathway. In this series, FGFR inhibitors did not cause irreversible loss of vision; the retinopathy was self-limited and did not require medical intervention. These results may explain visual symptoms while taking the drug, although the precise frequency or magnitude of this adverse effect cannot be determined with certainty from this retrospective investigation.

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