Tshuva-Bitton Raz, Ostrovsky Michael, Vishnevskia-Dai Vicktoria, Agmon-Levin Nancy, Sher Ifat, Rotenstreich Ygal
Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Department of Ophthalmology, Kaplan Medical Center, Rehovot, Israel.
Am J Ophthalmol Case Rep. 2025 Mar 26;38:102307. doi: 10.1016/j.ajoc.2025.102307. eCollection 2025 Jun.
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.
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.
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.
黑色素瘤相关性视网膜病变（MAR）是一种与转移性黑色素瘤相关的罕见自身免疫性副肿瘤综合征。在过去十年中，患者生存率显著提高，主要归功于免疫疗法的发展。然而，缺乏关于MAR患者长期随访及对现代标准治疗反应的数据。本单病例报告展示了一名接受免疫检查点抑制剂治疗的年轻MAR患者的七年多模式随访情况。
一名46岁有皮肤恶性黑色素瘤病史的以色列男性，在诊断后一年半出现双侧突发闪光、闪烁及夜盲症状。此后不久，正电子发射断层扫描-计算机断层扫描显示新的隆突下转移。视网膜电图（ERG）a波和b波反应显著降低，导致诊断为MAR，随后通过高滴度抗视网膜双极细胞自身抗体得以证实。半年后，光学相干断层扫描（OCT）显示黄斑变薄，尤其是在外黄斑环的内核层和内丛状层，外层视网膜无明显变化。静脉注射免疫球蛋白、硫唑嘌呤和泼尼松联合治疗方案在接下来的2.5年允许部分减停类固醇，但显示出严重毒性，且OCT和ERG无明显改善。在转移进展后开始帕博利珠单抗治疗，使患者原发性肿瘤疾病稳定，同时黄斑厚度增加，视网膜功能增强，次年暗适应（DA）b波反应增加超过60%。
MAR可能是系统性转移性黑色素瘤的首个迹象，因此需要高度临床怀疑。在患者随访过程中，OCT和ERG结果大多一致，但ERG被证明是早期诊断MAR更敏感的工具。抗体阳性的MAR患者应考虑早期免疫治疗。
