Clinical and morphologic characteristics of fibroblast growth factor receptor inhibitor-associated retinopathy Journal Article


Authors: Francis, J. H.; Harding, J. J.; Schram, A. M.; Canestraro, J.; Haggag-Lindgren, D.; Heinemann, M.; Kriplani, A.; Jhaveri, K.; Voss, M. H.; Bajorin, D.; Abou-Alfa, G. K.; Iyer, G.; Drilon, A.; Rosenberg, J.; Abramson, D. H.
Article Title: Clinical and morphologic characteristics of fibroblast growth factor receptor inhibitor-associated retinopathy
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.. © 2021 American Medical Association. All rights reserved.
Journal Title: JAMA Ophthalmology
Volume: 139
Issue: 10
ISSN: 2168-6165
Publisher: American Medical Association  
Date Published: 2021-10-01
Start Page: 1126
End Page: 1130
Language: English
DOI: 10.1001/jamaophthalmol.2021.3331
PUBMED: 34473206
PROVIDER: scopus
PMCID: PMC8414363
DOI/URL:
Notes: Article -- Export Date: 1 December 2021 -- Source: Scopus
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MSK Authors
  1. Dean Bajorin
    658 Bajorin
  2. Jasmine Helen Francis
    257 Francis
  3. James Joseph Harding
    250 Harding
  4. Ghassan Abou-Alfa
    570 Abou-Alfa
  5. David H Abramson
    390 Abramson
  6. Martin Henner Voss
    288 Voss
  7. Gopakumar Vasudeva Iyer
    345 Iyer
  8. Komal Lachhman Jhaveri
    202 Jhaveri
  9. Alexander Edward Drilon
    633 Drilon
  10. Alison Michele Schram
    123 Schram
  11. Jonathan Eric Rosenberg
    513 Rosenberg
  12. Dianna May Haggag
    3 Haggag