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MEK inhibitor-associated retinopathy (MEKAR) in metastatic melanoma: Long-term ophthalmic effects
U Urner-Bloch1, M Urner2, N Jaberg-Bentele3
1Private Ophthalmic Practice in Cooperation with the Skin Cancer Unit, University Hospital of Zurich, Zurich, Switzerland.
Background:
Mitogen-activated protein kinase kinase (MEK) inhibitors have aroused considerable interest in oncology. Activity has been demonstrated in various types of cancer, especially melanoma. MEK inhibitors induce a transient retinopathy, considered to be a class effect. At present, only sparse data are available on retinal effects with long-term MEK inhibition.
Patients And Methods:
In this prospective, observational study, patients with advanced melanoma participating in different phase 1/2 or phase 3 clinical trials were treated with the MEK inhibitor binimetinib, with a v-Raf murine sarcoma viral oncogene homolog B (BRAF) inhibitor, or with combination therapy. They underwent regular ophthalmological examinations including determination of visual function, biomicroscopy, dilated fundoscopy and optical coherence tomography (OCT) for a period of up to 2 years. Retinopathy was diagnosed on defined OCT criteria.
Results:
Sixty-two patients were investigated between 1st October 2011 and 31st July 2015: 13 were treated with the MEK inhibitor binimetinib alone, 10 with a selective BRAF inhibitor, and 39 with combination therapy. In 92% of patients on monotherapy and 100% of those on combination treatment, binimetinib caused dose-related lesions with serous neuroretinal detachments and oedema, strongly dependent on the time after medication. With continued treatment, retinal volume and thickness decreased to levels below baseline, without any apparent functional deficits or changes in structural integrity.
Conclusions:
Binimetinib induces a specific retinopathy with daily fluctuations depending on the time interval after medication. The retinopathy partially recovers, but can still be detected many months later. Retinal thinning, possible first signs of retinal atrophy have been observed after long-term treatment, but, so far, without functional relevance.
Insights
Binimetinib, a MEK inhibitor, causes temporary retinopathy in melanoma patients, with daily fluctuations and potential long-term thinning. While structural changes occur, functional vision remains unaffected in this study.
Area of Science:
- Oncology
- Ophthalmology
- Pharmacology
Background:
- Mitogen-activated protein kinase kinase (MEK) inhibitors are of significant interest in oncology, particularly for melanoma treatment.
- MEK inhibitors are known to cause transient retinopathy, a class effect with limited data on long-term inhibition.
- Understanding the long-term ocular effects of MEK inhibitors is crucial for patient management.
Purpose of the Study:
- To investigate the ocular effects of the MEK inhibitor binimetinib in patients with advanced melanoma.
- To evaluate the incidence and characteristics of retinopathy associated with binimetinib monotherapy and combination therapy.
- To assess the long-term impact of MEK inhibition on retinal structure and visual function.
Main Methods:
- Prospective, observational study of advanced melanoma patients in clinical trials.
- Treatment with binimetinib (MEK inhibitor), BRAF inhibitor, or combination therapy.
- Regular ophthalmological examinations including visual function, biomicroscopy, fundoscopy, and optical coherence tomography (OCT) for up to 2 years.
Main Results:
- Binimetinib induced dose-related retinopathy in 92% (monotherapy) and 100% (combination therapy) of patients.
- Ocular findings included serous neuroretinal detachments and edema, with daily fluctuations.
- Long-term treatment led to decreased retinal volume and thickness, but without functional deficits.
Conclusions:
- Binimetinib causes a specific retinopathy with daily fluctuations and partial recovery.
- Retinal thinning and potential early signs of atrophy were observed with long-term treatment.
- Despite structural changes, no functional relevance was detected in the study period.
