Ocular Changes in Metastatic Melanoma Patients Treated with MEK Inhibitor Cobimetinib and BRAF Inhibitor Vemurafenib

BACKGROUND: Mitogen-activated protein kinase kinase (MEK) inhibitor cobimetinib and V-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor vemurafenib have significantly improved the prognosis of BRAF-mutated metastatic melanoma. Some ocular symptoms and signs were recently recognized to follow this treatment. The study was aimed to investigate ocular toxicity in patients with metastatic melanoma treated with cobimetinib in combination with vemurafenib. PATIENTS AND METHODS: In the prospective, observational study, patients with BRAF-mutated metastatic melanoma treated with cobimetinib in combination with vemurafenib at the Institute of Oncology Ljubljana were asked to participate. Ophthalmic examination was performed including measurement of visual acuity and intraocular pressure, slit lamp examination, funduscopy (CF), infrared-reflectance (IR) imaging and optical coherence tomography (OCT). RESULTS: Five out of 7 patients noticed changes in vision few days after starting the therapy with cobimetinib. In all patients, small circular lesions, described as MEKAR lesions, were documented in outer retinal layers demonstrated with OCT, IR, and CF. Changes were in the center and/or scattered over the retina almost symmetrical in both eyes in 6 patients, and asymmetrical in one patient, the latter presented also with unilateral anterior uveitis and cystoid macular edema. CONCLUSIONS: Multiple bilateral foveal and extrafoveal small retinal lesions in the outer retinal layers develop in patients treated with MEK inhibitor in combination with BRAF inhibitor. Ophthalmologists and oncologists need to be aware of this common, yet relatively benign and often transient ocular side effect to avoid needless intervention, including the discontinuance of a potentially life-prolonging therapy.