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  • Ocular Toxicity of Mitogen-Activated Protein Kinase Inhibitors

    By Marianne Doran and selected by Deepak P. Edward, MD
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    Journal Highlights

    JAMA Oncology
    Published online Nov. 17, 2016

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    In a clinical research letter, Purbrick et al. reported that investigators at the Oxford Eye Hospital and Oxford Experimental Cancer Centre collab­orated to study the ocular effects of 3 experimental mitogen-activated protein kinase inhibitors (MEKIs). These drugs are currently in clinical development as treatment for disorders such as ad­vanced cutaneous melanoma. Overall, 18% of patients developed ocular adverse events, the most common of which was central serous chorioreti­nopathy (CSC) or CSC-like changes.

    The investigators reviewed the clinical records of 40 patients enrolled in clinical trials of 3 different MEKIs, including 11, 19, and 10 patients in MEKI trials A, B, and C, respectively. The parameters examined included baseline visual acuity (VA); ophthalmic and general medical history; ophthal­mic imaging data, including macular optical coherence tomography (OCT); and evidence of ocular toxic effects.

    Overall, 7 of 40 patients (18%) de­veloped adverse ocular effects. In trial A, 3 of the 11 patients (27%) developed bilateral CSC, which was multifocal in 1 case. In trial B, 2 of the 19 patients (11%) developed ocular adverse effects; 1 patient had a left central retinal vein occlusion, and 1 patient had bilateral, multifocal CSC-like changes. In trial C, 2 of 10 patients (20%) developed problems: 1 had bilateral, multifocal CSC-like changes, and 1 had a severe increase in intraocular pressure.

    The authors noted that the role of MEKIs in these complications could not be fully assessed, in part because of malignancy-related hypercoagulability in some of the patients and/or concur­rent use of other drugs. However, they recommended that patients receiving MEKI therapy should be monitored prospectively by means of appropriate validated techniques and have a base­line ophthalmic examination before starting treatment, including VA and IOP measurements, dilated fundus examination, fundus photography, and macular OCT. Further studies may help determine which patients are at partic­ular risk of ocular toxic effects.

    The original article can be found here.