A seven-year electroretinography follow-up of a patient with melanoma-associated retinopathy stabilized on pembrolizumab treatment

Purpose: Melanoma-associated retinopathy (MAR) is a rare, auto-immune paraneoplastic syndrome associated with metastatic melanoma. Over the last decade, patient survival has improved dramatically, mainly due to the development of immunotherapy. However, data on long-term MAR patient follow-up and re...

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Main Authors: Raz Tshuva-Bitton, Michael Ostrovsky, Vicktoria Vishnevskia-Dai, Nancy Agmon-Levin, Ifat Sher, Ygal Rotenstreich
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:American Journal of Ophthalmology Case Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S245199362500060X
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author Raz Tshuva-Bitton
Michael Ostrovsky
Vicktoria Vishnevskia-Dai
Nancy Agmon-Levin
Ifat Sher
Ygal Rotenstreich
author_facet Raz Tshuva-Bitton
Michael Ostrovsky
Vicktoria Vishnevskia-Dai
Nancy Agmon-Levin
Ifat Sher
Ygal Rotenstreich
author_sort Raz Tshuva-Bitton
collection DOAJ
description Purpose: Melanoma-associated retinopathy (MAR) is a rare, auto-immune paraneoplastic syndrome associated with metastatic melanoma. Over the last decade, patient survival has improved dramatically, mainly due to the development of immunotherapy. However, data on long-term MAR patient follow-up and response to modern standard-of-care treatment are lacking. This single-patient case report presents a seven-year, multimodal follow-up of a young MAR patient treated with immune-checkpoint inhibitors. Observations: A 46-year-old Israeli male with a history of cutaneous malignant melanoma presented with sudden onset of bilateral shimmering, flickering, and nyctalopia a year and a half after diagnosis. Shortly thereafter, new subcarinal metastasis was observed on Positron Emission Tomography–Computed Tomography. Significantly reduced electroretinography (ERG) a- and b-wave responses led to a diagnosis of MAR, later confirmed by high titers of autoantibodies against retinal bipolar cells. Half a year later, macular thinning, particularly within the inner nuclear and inner plexiform layers of the outer macular ring, with no substantial change in the outer retina, was observed on optical coherence tomography (OCT). A treatment regimen combining intravenous immune globulin, azathioprine, and prednisone allowed partial steroid tapering over the following 2.5 years but showed substantial toxicity and a lack of significant improvement on OCT and ERG. Pembrolizumab treatment was initiated following metastatic progression and resulted in stabilization of the patient's primary oncologic disease, as well as an increase in macular thickness and enhanced retinal function with an increase of over 60 % in dark adapted (DA) b-wave response over the following year. Conclusions and importance: MAR may be the first sign of systemic metastatic melanoma, thus warranting a high degree of clinical suspicion. While OCT and ERG showed mostly concordant results over the patient's follow-up, ERG proved to be a more sensitive tool for the early diagnosis of MAR. Early immunotherapy treatment should be considered in antibody-positive MAR patients.
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spelling doaj-art-fb742571684e41319c08fb2769b0ef1d2025-08-20T03:53:46ZengElsevierAmerican Journal of Ophthalmology Case Reports2451-99362025-06-013810230710.1016/j.ajoc.2025.102307A seven-year electroretinography follow-up of a patient with melanoma-associated retinopathy stabilized on pembrolizumab treatmentRaz Tshuva-Bitton0Michael Ostrovsky1Vicktoria Vishnevskia-Dai2Nancy Agmon-Levin3Ifat Sher4Ygal Rotenstreich5Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, IsraelFaculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel; Department of Ophthalmology, Kaplan Medical Center, Rehovot, IsraelOphthalmology Department, School of Medicine Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel; The Goldschleger Eye Institute, Sheba Medical Center, Tel-Hashomer, IsraelOphthalmology Department, School of Medicine Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel; Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, IsraelOphthalmology Department, School of Medicine Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel; The Goldschleger Eye Institute, Sheba Medical Center, Tel-Hashomer, IsraelOphthalmology Department, School of Medicine Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel; The Goldschleger Eye Institute, Sheba Medical Center, Tel-Hashomer, Israel; Corresponding author. Goldschleger Eye Institute, Sheba Medical Center, Tel-Hashomer, 5262100, Israel.Purpose: Melanoma-associated retinopathy (MAR) is a rare, auto-immune paraneoplastic syndrome associated with metastatic melanoma. Over the last decade, patient survival has improved dramatically, mainly due to the development of immunotherapy. However, data on long-term MAR patient follow-up and response to modern standard-of-care treatment are lacking. This single-patient case report presents a seven-year, multimodal follow-up of a young MAR patient treated with immune-checkpoint inhibitors. Observations: A 46-year-old Israeli male with a history of cutaneous malignant melanoma presented with sudden onset of bilateral shimmering, flickering, and nyctalopia a year and a half after diagnosis. Shortly thereafter, new subcarinal metastasis was observed on Positron Emission Tomography–Computed Tomography. Significantly reduced electroretinography (ERG) a- and b-wave responses led to a diagnosis of MAR, later confirmed by high titers of autoantibodies against retinal bipolar cells. Half a year later, macular thinning, particularly within the inner nuclear and inner plexiform layers of the outer macular ring, with no substantial change in the outer retina, was observed on optical coherence tomography (OCT). A treatment regimen combining intravenous immune globulin, azathioprine, and prednisone allowed partial steroid tapering over the following 2.5 years but showed substantial toxicity and a lack of significant improvement on OCT and ERG. Pembrolizumab treatment was initiated following metastatic progression and resulted in stabilization of the patient's primary oncologic disease, as well as an increase in macular thickness and enhanced retinal function with an increase of over 60 % in dark adapted (DA) b-wave response over the following year. Conclusions and importance: MAR may be the first sign of systemic metastatic melanoma, thus warranting a high degree of clinical suspicion. While OCT and ERG showed mostly concordant results over the patient's follow-up, ERG proved to be a more sensitive tool for the early diagnosis of MAR. Early immunotherapy treatment should be considered in antibody-positive MAR patients.http://www.sciencedirect.com/science/article/pii/S245199362500060XElectroretinogramImmune checkpoint inhibitorsImmunotherapyMelanoma associated retinopathyOcular coherence tomographyPembrolizumab
spellingShingle Raz Tshuva-Bitton
Michael Ostrovsky
Vicktoria Vishnevskia-Dai
Nancy Agmon-Levin
Ifat Sher
Ygal Rotenstreich
A seven-year electroretinography follow-up of a patient with melanoma-associated retinopathy stabilized on pembrolizumab treatment
American Journal of Ophthalmology Case Reports
Electroretinogram
Immune checkpoint inhibitors
Immunotherapy
Melanoma associated retinopathy
Ocular coherence tomography
Pembrolizumab
title A seven-year electroretinography follow-up of a patient with melanoma-associated retinopathy stabilized on pembrolizumab treatment
title_full A seven-year electroretinography follow-up of a patient with melanoma-associated retinopathy stabilized on pembrolizumab treatment
title_fullStr A seven-year electroretinography follow-up of a patient with melanoma-associated retinopathy stabilized on pembrolizumab treatment
title_full_unstemmed A seven-year electroretinography follow-up of a patient with melanoma-associated retinopathy stabilized on pembrolizumab treatment
title_short A seven-year electroretinography follow-up of a patient with melanoma-associated retinopathy stabilized on pembrolizumab treatment
title_sort seven year electroretinography follow up of a patient with melanoma associated retinopathy stabilized on pembrolizumab treatment
topic Electroretinogram
Immune checkpoint inhibitors
Immunotherapy
Melanoma associated retinopathy
Ocular coherence tomography
Pembrolizumab
url http://www.sciencedirect.com/science/article/pii/S245199362500060X
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