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

February 23, 2026 updated by: Institute of Oncology Ljubljana

Structural and Functional Retinal Alterations in Patients Under Treatment With BRAF/MEK Inhibitors

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Slovenia
      • Ljubljana, Slovenia, 1000
        • Institute of Oncology Ljubljana

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Retinal Monitoring During BRAF/MEK Inhibitor Therapy
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.
Other: Ophthalmologic Retinal Monitoring During BRAF/MEK Inhibitor Therapy
Participants treated with BRAF/MEK inhibitor combinations undergo ophthalmologic evaluation and retinal functional testing, including best-corrected visual acuity assessment, contrast sensitivity testing, slit-lamp examination, retinal imaging (OCT, infrared imaging, autofluorescence imaging), microperimetry, and electrophysiological testing (electrooculography and multifocal electroretinography when indicated) to detect MEK inhibitor-associated retinopathy (MEKAR) and assess retinal structural and functional alterations during and after therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of MEK Inhibitor-Associated Retinopathy (MEKAR)
Time Frame: Baseline (Day 0) through end of treatment (up to 14 months)
Incidence of MEK inhibitor-associated retinopathy (MEKAR), defined as the proportion of participants who develop MEKAR during BRAF/MEK inhibitor therapy based on predefined clinical criteria and optical coherence tomography (OCT) findings.
Baseline (Day 0) through end of treatment (up to 14 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Retinal Structural Changes Assessed by Optical Coherence Tomography (OCT)
Time Frame: Baseline (Day 0); Week 2; and up to 14 months
Retinal structural alterations assessed by optical coherence tomography (OCT), including presence of neurosensory retinal detachment and other MEKAR-related changes.
Baseline (Day 0); Week 2; and up to 14 months
Change in Best-Corrected Visual Acuity (BCVA)
Time Frame: Baseline (Day 0); Week 2; and up to 14 months
Change in best-corrected visual acuity (BCVA) measured during ophthalmologic examinations to assess visual function during BRAF/MEK inhibitor therapy.
Baseline (Day 0); Week 2; and up to 14 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institute of Oncology Ljubljana

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2023

Primary Completion (Actual)

January 31, 2025

Study Completion (Actual)

January 31, 2025

Study Registration Dates

First Submitted

February 10, 2026

First Submitted That Met QC Criteria

February 23, 2026

First Posted (Actual)

February 24, 2026

Study Record Updates

Last Update Posted (Actual)

February 24, 2026

Last Update Submitted That Met QC Criteria

February 23, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ERIDNPVO-0029/2024
  • 0120-89/2017/11 (Other Identifier: National Medical Ethics Committee of the Republic of Slovenia)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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