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Updated: Jun 12, 2025
Toxicity Screens in Human Retinal Organoids for Pharmaceutical Discovery
Published on: March 4, 2021
MERTK INHIBITOR-ASSOCIATED RETINAL TOXICITY IN A HUMAN
Anne Strong Caldwell1, Dallin C Milner, Nihaal B Mehta
1Department of Ophthalmology, University of Colorado School of Medicine, Aurora, Colorado.
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.
Insights
This study reports MERTK inhibitor-induced retinal toxicity in a human patient, characterized by optical coherence tomography and autofluorescence changes. Close ophthalmologic monitoring is recommended for patients on MERTK inhibitors.
Area of Science:
- Ophthalmology
- Oncology
- Pharmacology
Background:
- The MER proto-oncogene tyrosine kinase (MERTK) is crucial for retinal pigmented epithelium (RPE) homeostasis and immune regulation.
- MERTK inhibitors are emerging as potential cancer therapeutics.
- Understanding potential side effects, such as retinal toxicity, is critical.
Purpose of the Study:
- To present a case of MERTK inhibitor-associated retinal toxicity in a human.
- To document the clinical and imaging findings of this toxicity.
Main Methods:
- A retrospective chart review of a 43-year-old male patient enrolled in a MERTK inhibitor (PF-07265807) trial.
- Regular ophthalmologic examinations, including dilated fundus exams and ancillary testing, were performed.
- Ophthalmic imaging, including optical coherence tomography (OCT) and fundus autofluorescence (FAF), was utilized.
Main Results:
- The patient initially had normal baseline ophthalmic exams.
- Seven months after initiating the MERTK inhibitor, signs of retinal toxicity emerged, including disruption of the extrafoveal ellipsoid zone on OCT and extrafoveal hyper-autofluorescence on FAF.
- Visual acuity remained stable, but the medication was discontinued due to ocular concerns and cancer progression.
Conclusions:
- Patients undergoing treatment with MERTK inhibitors require vigilant monitoring by an ophthalmologist.
- Development of MERTK inhibitor-associated retinal toxicity necessitates a multidisciplinary discussion regarding risk-benefit assessment for continued treatment.
- Ophthalmologists and oncologists should collaborate to manage potential vision loss versus the oncologic benefits of MERTK inhibitors.
