Purpose: Mitogen-activates protein kinase (MAPK) inhibitors, particularly MEK inhibitors, have shifted the treatment paradigm for metastatic BRAF-mutant cutaneous melanoma; however, oncologists, ophthalmologists, and patients have noticed different toxicities of variable importance. This review aims to provide an update of the ocular adverse events (OAEs), especially retinal toxicity, associated with the use of MEK inhibitors. Methods: We conducted a scientific literature search using the PubMed database up to July 2018 with the terms “MEK inhibitors” with a “review” filter and “MEK inhibitors” with a “clinical trials” filter. Phase I–III experimental studies and reviews were selected. Current principles and techniques for diagnosing and managing MEK inhibitor retinopathy and other OAEs are discussed. Results: In patients treated with MEK inhibitors, including asymptomatic patients, OAEs occur with an incidence of up to 90%. Mild to severe ophthalmic toxicities are described, including visual disturbances, a 2-line decrease in Snellen visual acuity, dry eye symptoms, ocular adnexal abnormalities, visual field defects, panuveitis, and retinal toxicities, such as different degrees of MEK-associated retinopathy, vascular injury, and retinal vein occlusion. Conclusion: MEK inhibitors can lead to different degrees of retinal, uveal, and adnexal OAE, causing visual disturbances or discomfort. One of the most relevant OAE of MEK therapy is MEK inhibitor–associated retinopathy (MEKAR), which is usually mild, self-limited, and may subside after continuous use of the drug for weeks or months, or discontinuation, thereby restoring the normal visual function of the retina, with some exceptions. Ocular adverse events are often associated with other systemic adverse effects that can modify the dosage of treatment, so the communication with the oncologist is fundamental.
The aim of this report is to describe the resolution of refractory cystoid macular edema (CME) associated to retinitis pigmentosa (RP) with IV tocilizumab in three patients.Methods: Retrospective study of a series of consecutive cases of patients treated with off-label IV tocilizumab (anti IL6) for CME refractory to acetazolamide 250 mg for 3 months. Patients were diagnosed with RP by fundus appearance, electrophysiology, visual fields, and genetic testing. A complete ophthalmic examination including spectral-domain optical coherence tomography was performed.Results: Three patients with RP and CME refractory to acetazolamide 250 mg for 3 months were treated with monthly IV tocilizumab for at least six months. All patients resolved CME and improved visual acuity after the third month of IV tocilizumab, resolving systemic and ocular adverse events related to previous treatments for CME. Tocilizumab was well tolerated with no other adverse events.Discussion: CME causes visual impairment in RP, but current treatments are usually deficient. Tocilizumab has been successfully used as treatment for refractory CME in uveitis, retinal dystrophies, and autoimmune retinopathies. This article reports, for the first time, the long-term resolution of refractory CME in RP with IV tocilizumab.
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