Background/purpose: The MER proto-oncogene tyrosine kinase (MERTK) helps maintain the homeostasis of the retinal pigmented epithelium. In addition, MERTK regulates the innate immune system. As such, inhibition of MERTK has gained recent interest as a target for cancer therapeutics. Herein, we present MERTK inhibitor-associated retinal toxicity in a human.
Methods: A 43-year-old man with 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 2 to 3 weeks for dilated fundus examinations and ancillary testing. Data on the patient's relevant medical history, ophthalmic examination findings, and imaging performed at baseline and subsequent ophthalmology visits were obtained through retrospective chart review.
Results: At the patient's baseline visit, his dilated examination 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 hyperautofluorescence on short wavelength fundus autofluorescence. The patient's vision remained stable throughout the study; however, the medication was stopped because of the unknown ocular effects and progression of the patient's cancer.
Conclusion: 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.
Keywords: MERTK inhibitor; drug toxicity.