Ocular Toxicity of Mitogen-Activated Protein Kinase Inhibitors

Abstract

The Oxford Eye Hospital and the Oxford Experimental Cancer Centre collaborate in monitoring patients in a number of early-phase clinical trials.In this study, we report the ocular toxic effects of 3 different mitogen-activated protein kinase inhibitors (MEKIs) currently at independent stages of clinical development, including ongoing studies.Methods | Forty clinical records of patients enrolled in clinical trials of 3 different MEKIs (including 11, 19, and 10 patients in MEKI trials A, B, and C, respectively) were reviewed from March 16, 2011, to April 25, 2013.Baseline visual acuity and ophthalmic imaging data, including macular optical coherence tomography, relevant ophthalmic and general medical history, evidence of ocular toxic effects in addition to the clinical course, and relevant interventions, were recorded and analyzed.This study was approved by the Oxford Research Ethics Committee.Appropriate written informed consent was obtained from all patients, and data were deidientified.Results | Seven of 40 patients (18%) developed ocular adverse effects.In the MEKI A group, 3 of 11 patients (27%) developed bilateral central serous chorioretinopathy (CSC) (Figure, A and B), which was multifocal in 1 case.In the MEKI B group, 2 of 19 patients (11%) developed ocular adverse effects; 1 patient had a left central retinal vein occlusion (Figure, C), and 1 patient had bilateral, multifocal CSC-like changes.In the MEKI C group, 2 of 10 patients (20%) developed problems; 1 had bilateral, multifocal CSC-like changes (Figure, D), and 1 had a severe increase in intraocular pressure.Figure.Clinical Images From Patients 1, 4, and 6 Normal OCT in both eyes A Left central retinal vein occlusion C Bilateral central serous chorioretinopathy B Bilateral, multifocal central serous chorioretinopathy D A and B, Patient 1 (upper image is the right eye).A, Baseline (normal) macular optical coherence tomogram (OCT); B, 1 day after starting mitogen-activated protein kinase inhibitor (MEKI), the macular OCT shows bilateral central serous chorioretinopathy (CSC)-like changes.C, Patient 4. Color fundus photograph of left eye showing central retinal vein occlusion with dilated, tortuous retinal veins, hemorrhagic optic disc swelling, widespread deep retinal hemorrhages, and macular edema.D, Patient 6 (upper image is the right eye).Macular OCT showing multifocal CSC-like changes.