Re: Magone et al.: Ocular adverse effects of infigratinib, a new fibroblast growth factor receptor tyrosine kinase inhibitor

Jasmine H. Francis, Md, Facs, Julia Canestraro, Od, David H. Abramson, Md, Facs

Summary

We read with interest the article by Magoneetal.1 The authors provide a useful description of the anterior segment findings in a small cohort of patients. However, we suspect there may be a discrepancy in their description of the posterior segment findings of one patient. They state that “None of the patients developed retinal pathology, including patient number 5, who had a history of reversible in grafit in ib-related bilateral retinal pigment epithelium detachments.” Although no longer present, we feel it important to comprehend thisfundusabnormalityfully.Thebilateralnatureofthese findings and their association with ingrafitinib made us wonder about their interpretation. We believe a careful review of the OCT scan will revealthesebilateraltobefocaldetachmentsoftheneurosensoryretina rather than the retinal pigment epithelium (RPE).
Both mitogen-activated protein kinase kinase (MEK) inhibitors and fibroblast growth factor receptor (FGFR) inhibitors target the mitogen-activated protein kinase pathway and, owing to this common pathway target, they share a BGJ398 similar effect on the retina. In our experience, the fluid foci in patients with MEK inhibitoreassociated retinopathy or FGFR inhibitoreassociated retinopathy occurs between the RPE and interdigitation zone of the neurosensory retina. , This is one of the key features that helps to differentiate these findings from central serous chorioretinopathy.3 Unfortunately, many of the early descriptions of the retinal findings associated with MEK and FGFR inhibitors were incorrectly termed central serous chorioretinopathy and propagation of this description is confusing.3
The importance of carefully distinguishing these 2 entities is clinically important, as is the absence of recurrence with drug rechallenge. The neurosensory detachments associated with MEK and FGFR inhibitors are typicallyself-limited, without residualeffects on the eye or vision, and can be observed while patients remain on the drug. However, a true detachmentof the RPE couldsignify an alternate diagnosis such as central serous chorioretinopathy, and this could lead to cessation of life-preservingorlife-extendingcancertherapy orperhaps cessation of concomitant steroid use, which is often used to mitigate canceredrug toxicity and enhance tolerability in patients.
For these reasons, we appeal to the authors to offer a reinterpretation of their patient’s posterior segment findings or to provide an OCT image of the posterior segment findings of their patient so that the reader can better understand the retinopathy.

References

1. Magone MT, Hartley IR, Fitzgibbon E, et al. Ocular adverse effects of infigratinib, a new fibroblast growth factor receptor tyrosine kinase inhibitor. Ophthalmology. 2021;128: 624e626.