MERTK Inhibitor Associated Retinal Toxicity in a Human.

Abstract

The MER proto-oncogene tyrosine kinase (MERTK) helps maintain the homeostasis of the retinal pigmented epithelium (RPE). Additionally, MERTK regulates the innate immune system. As such inhibition of MERTK has gained recent interest as a target for cancer therapeutics. Herein, we present on MERTK inhibitor associated retinal toxicity in a human. A 43-year-old male with past medical history of esophageal adenocarcinoma was enrolled in a trial studying the MERTK inhibitor PF-07265807. As part of the study protocol, the patient was seen every two to three weeks for dilated fundus exams and ancillary testing. Data on the patient's relevant past medical history, ophthalmic exam findings, and imaging performed at baseline and subsequent ophthalmology visits was obtained via retrospective chart review. At the patient's baseline visit, his dilated exam and testing were normal. Seven months after starting the MERTK inhibitor the patient developed subtle but reproducible signs of retinal toxicity with disruption of the extrafoveal ellipsoid zone on optical coherence tomography and extrafoveal hyper-autofluorescence on short wavelength fundus autofluorescence. The patient's vision remained stable throughout the study; however, the medication was stopped due to the unknown ocular effects as well as progression of the patient's cancer. Patients taking MERTK inhibitors should be monitored by an ophthalmologist while on the drug. If toxicity develops, discussion of whether to continue the medication should take place between the patient, ophthalmologist, and oncologist, with consideration of the risks of vision loss versus benefits of taking the medication from a cancer perspective.