MERTK Inhibitor Associated Retinal Toxicity in a Human
Purpose: The MER proto-oncogene tyrosine kinase (MERTK) is crucial for maintaining the homeostasis of the retinal pigmented epithelium (RPE) and regulating the innate immune system. Consequently, inhibiting MERTK has recently attracted attention as a potential target for cancer therapies. This study reports on retinal toxicity associated with a MERTK inhibitor in a human subject.
Methods: A 43-year-old male with a history of esophageal adenocarcinoma was enrolled in a clinical trial investigating the MERTK inhibitor PF-07265807. According to the study protocol, the patient underwent dilated fundus examinations and ancillary tests every two to three weeks. Relevant data, including the patient’s medical history, ophthalmic exam findings, and imaging results from baseline and subsequent visits, were collected through a retrospective chart review.
Results: At the baseline visit, the patient’s dilated exam and tests showed normal results. However, seven months after starting the MERTK inhibitor, he exhibited subtle but reproducible signs of retinal toxicity, including disruption of the extrafoveal ellipsoid zone on optical coherence tomography and extrafoveal hyper-autofluorescence on short wavelength fundus autofluorescence. Despite these changes, the patient’s vision remained stable throughout the study; nevertheless, the medication was discontinued due to the uncertain ocular effects and the progression of his cancer.
Discussion: Patients receiving MERTK inhibitors should be closely monitored by an ophthalmologist during treatment. If signs of toxicity emerge, it is essential for the patient, ophthalmologist, and oncologist to discuss whether to continue the medication, weighing the risks of potential vision loss against the benefits of the treatment from a cancer management perspective.