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Published on: September 16, 2020
Clinical and Morphologic Characteristics of Fibroblast Growth Factor Receptor Inhibitor-Associated Retinopathy
Jasmine H Francis1,2, James J Harding2,3, Alison M Schram2,3
1Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York.
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.
Insights
Fibroblast growth factor receptor (FGFR) inhibitors can cause retinopathy, leading to temporary vision changes. This condition typically resolves without intervention and does not cause permanent vision loss.
Area of Science:
- Ophthalmology
- Oncology
- Pharmacology
Background:
- Fibroblast growth factor receptor (FGFR) inhibitors are used in cancer treatment and can suppress the mitogen-activated protein kinase (MAPK) pathway.
- A potential side effect of FGFR inhibitors is treatment-related retinopathy, but ocular toxic effects are poorly described.
- Detailed clinical descriptions are needed to explain visual symptoms associated with FGFR inhibitor therapy.
Purpose of the Study:
- To describe the clinical and morphologic characteristics of serous retinal disturbances associated with FGFR inhibitors.
- To correlate optical coherence tomography (OCT) findings with visual acuity changes.
- To assess the reversibility of FGFR inhibitor-associated retinopathy.
Main Methods:
- Retrospective case series of 146 patients receiving FGFR inhibitors for cancer treatment.
- Included 40 eyes from 20 patients with retinopathy confirmed by OCT.
- Analyzed OCT abnormalities, visual acuity at presentation, and outcomes at fluid resolution.
Main Results:
- FGFR inhibitor-associated retinopathy occurred in 13.7% of patients (20 of 146).
- Subretinal fluid was detected a median of 21 days after starting medication.
- Vision decreased in 11 eyes but resolved spontaneously in most cases without treatment interruption; no irreversible vision loss occurred.
Conclusions:
- FGFR inhibitors can cause subretinal fluid, similar to other MAPK pathway inhibitors.
- The retinopathy associated with FGFR inhibitors appears self-limited and does not require medical intervention.
- These findings help explain transient visual symptoms during FGFR inhibitor therapy.
