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

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.

Inclusion criteria

• Adults aged 18 years or older.
• Histologically confirmed malignant melanoma.
• Treatment with combined BRAF and MEK inhibitor therapy as part of standard oncologic care.
• Ability to undergo ophthalmologic examinations and retinal imaging.
• Written informed consent provided prior to participation.

Exclusion criteria

• Pre-existing retinal disease that could interfere with assessment of retinal changes (e.g., central serous chorioretinopathy, macular degeneration).
• History of ocular conditions affecting the macula unrelated to BRAF/MEK inhibitor therapy.
• High myopia greater than -6 diopters.
• Uncontrolled glaucoma.
• Ocular or systemic conditions considered by the investigators to potentially confound study results.