Clinical and Functional Retinal Changes Associated With BRAF/MEK Inhibitor Therapy in Patients With Malignant Melanoma

Overview

Patients with malignant melanoma are increasingly treated with combined BRAF and MEK inhibitor therapy. Although this treatment has significantly improved survival outcomes, it has been associated with specific retinal changes known as MEK inhibitor-associated retinopathy (MEKAR). This observational study aimed to evaluate structural and functional retinal changes in patients treated with BRAF/MEK inhibitors. The study focused on identifying clinical characteristics of MEKAR, assessing retinal function and morphology during therapy, and examining the course of retinal changes after completion of treatment. Patients undergoing standard oncologic treatment with BRAF/MEK inhibitors were followed prospectively with regular ophthalmologic examinations, including visual function testing, retinal imaging, and electrophysiological assessments. The results of this study contribute to a better understanding of retinal alterations associated with BRAF/MEK inhibitor therapy and may support improved recognition, monitoring, and management of MEKAR in clinical practice.

This was a prospective, observational cohort study designed to investigate clinical, morphological, and functional retinal changes in patients with histologically confirmed malignant melanoma treated with combined BRAF and MEK inhibitor therapy as part of standard oncologic care. MEK inhibitor-associated retinopathy (MEKAR) is a recognized adverse effect of MEK inhibitor therapy and is characterized by bilateral, often multifocal serous retinal changes, predominantly involving the outer retinal layers. Although MEKAR is frequently considered reversible, its functional impact and long-term retinal sequelae remain incompletely understood. The primary objective of this study was to assess the impact of BRAF/MEK inhibitor therapy on retinal structure and function. Secondary objectives included characterization of the clinical course of MEKAR, comparison of MEKAR incidence between different BRAF/MEK inhibitor combinations, and evaluation of persistent retinal changes following completion of therapy. Adult patients receiving adjuvant or systemic treatment with combined BRAF/MEK inhibitors were enrolled and followed prospectively. Ophthalmologic assessments were performed at baseline, during therapy, and after completion of treatment. Examinations included best-corrected visual acuity testing, contrast sensitivity assessment, microperimetry, multimodal retinal imaging (optical coherence tomography, infrared imaging, and fundus autofluorescence), and electrophysiological testing (electrooculography and multifocal electroretinography, when indicated). The diagnosis of MEKAR was based on characteristic retinal findings on optical coherence tomography in the absence of alternative ocular or systemic causes. Functional and morphological findings were analyzed longitudinally to assess changes over time and recovery patterns following treatment cessation. This study was conducted in accordance with ethical standards and was approved by the competent national medical ethics committee. All participants provided informed consent prior to inclusion. By systematically evaluating retinal structure and function in patients treated with BRAF/MEK inhibitors, this study provides clinically relevant data on MEKAR and supports improved ophthalmologic monitoring of patients receiving targeted melanoma therapy.