Retinal Structural and Functional Changes in Patients Treated With BRAF/MEK Inhibitors

Institute of Oncology Ljubljana

Status: Completed

Conditions: Malignant Melanoma; MEK Inhibitor-Associated Retinopathy

Treatments: Other: Ophthalmologic Retinal Monitoring During BRAF/MEK Inhibitor Therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT07431489

ERIDNPVO-0029/2024

0120-89/2017/11 (Other Identifier)

Details and patient eligibility

About

Patients treated with BRAF/MEK inhibitor combinations for malignant melanoma may develop retinal changes known as MEK inhibitor-associated retinopathy (MEKAR). These changes can affect the structure and function of the retina and may cause visual symptoms.

This prospective interventional study evaluates structural and functional retinal alterations in patients receiving BRAF/MEK inhibitor therapy. The study aims to determine how often MEKAR occurs, describe its clinical characteristics and course, compare its incidence between different BRAF/MEK inhibitor combinations, and assess possible long-term retinal changes after treatment discontinuation.

Participants undergo structured ophthalmologic examinations, including visual acuity testing, retinal imaging, and functional retinal testing before treatment, two weeks after treatment initiation, during therapy if visual symptoms occur, and, when indicated, after treatment completion.

Full description

BRAF/MEK inhibitor combinations are commonly used in the treatment of malignant melanoma, including adjuvant and metastatic settings. During therapy, some patients develop retinal structural and functional alterations referred to as MEK inhibitor-associated retinopathy (MEKAR).

This study is designed as a prospective, longitudinal, interventional clinical study conducted at the Institute of Oncology Ljubljana. All eligible adult patients with histologically confirmed malignant melanoma who initiate treatment with a BRAF/MEK inhibitor combination (dabrafenib/trametinib or vemurafenib/cobimetinib) are invited to participate.

Participants undergo standardized ophthalmologic evaluations before initiation of therapy, two weeks after therapy initiation, and during treatment if visual symptoms occur. When MEKAR is diagnosed, follow-up examinations are performed at least six months after completion of therapy.

The ophthalmologic assessment includes best-corrected visual acuity measurement, contrast sensitivity testing, slit-lamp examination after pharmacologic dilation, retinal imaging using optical coherence tomography (OCT), infrared and autofluorescence imaging, microperimetry, and electrooculography. In patients receiving adjuvant therapy who develop MEKAR involving the fovea, multifocal electroretinography is additionally performed at diagnosis and repeated after treatment completion.

The study evaluates the incidence of MEKAR, changes in visual function, structural retinal alterations, differences between BRAF/MEK inhibitor combinations, and potential long-term retinal outcomes after therapy discontinuation.

Enrollment: 30 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients aged 18 years or older
• Histologically confirmed malignant melanoma
• Treatment with a BRAF/MEK inhibitor combination (dabrafenib/trametinib or vemurafenib/cobimetinib)
• Willingness to participate and provide written informed consent

Exclusion criteria

• Intraocular inflammation.
• Uncontrolled glaucoma.
• Retinal diseases (e.g., central serous chorioretinopathy).
• Macular disorders.
• High myopia (> -6 diopters).
• Other ocular or systemic diseases that could influence study results.

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Retinal Monitoring During BRAF/MEK Inhibitor Therapy

Experimental group

Description:

Participants treated with BRAF/MEK inhibitor combinations undergo structured ophthalmologic examinations and retinal functional testing, including best-corrected visual acuity assessment, contrast sensitivity testing, retinal imaging (OCT, infrared imaging, autofluorescence), microperimetry, electrooculography, and multifocal electroretinography when indicated, to detect and characterize MEK inhibitor-associated retinopathy (MEKAR) and evaluate retinal structural and functional changes during and after therapy.

Treatment:

Other: Ophthalmologic Retinal Monitoring During BRAF/MEK Inhibitor Therapy