Clinical and Immunologic Characteristics of Melanoma-Associated Retinopathy Syndrome: Eleven New Cases and a Review of 51 Previously Published Cases

Keltner, John L.; Thirkill, Charles E.; Yip, Peter T.

doi:10.1097/00041327-200109000-00004

Cited by 227 publications

(240 citation statements)

References 63 publications

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“…In previous reports of PLEX treatment for CAR, monotherapy was ineffective but combination therapy involving corticosteroids was followed by stabilization or improvement (Table 1). [10][11][12][13] In our patient, PLEX appeared to be effective after other treatments had failed. However, as plasma exchange only transiently lowers circulating antibodies, benefits are not sustained and this patient's relapsing SFPN was evidence of this.…”

Section: Concurrent Paraneoplastic Retinopathy and Neuropathy 407mentioning

confidence: 72%

A Man with Paraneoplastic Retinopathy plus Small Fiber Polyneuropathy Associated with Waldenström Macroglobulinemia (Lymphoplasmacytic Lymphoma): Insights into Mechanisms

Liu

Magro

Loewenstein

et al. 2014

Ocular Immunology and Inflammation

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Section: Concurrent Paraneoplastic Retinopathy and Neuropathy 407mentioning

confidence: 72%

A Man with Paraneoplastic Retinopathy plus Small Fiber Polyneuropathy Associated with Waldenström Macroglobulinemia (Lymphoplasmacytic Lymphoma): Insights into Mechanisms

Liu

Magro

Loewenstein

et al. 2014

Ocular Immunology and Inflammation

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“…The term MEKAR is proposed in analogy to CAR, cancer associated retinopathy or MAR, melanoma associated retinopathy, both rare eye conditions with severe functional deficits observed in metastatic disease [23,24]. Auto-immunologic based cross reactions between tumour antigens and retinal tissues were described.…”

Section: Discussionmentioning

confidence: 99%

MEK inhibitor-associated retinopathy (MEKAR) in metastatic melanoma: Long-term ophthalmic effects

Urner-Bloch

Urner

Jaberg-Bentele

et al. 2016

European Journal of Cancer

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BACKGROUND: Mitogen-activated protein kinase kinase (MEK) inhibitors have aroused considerable interest in oncology. Activity has been demonstrated in various types of cancer, especially melanoma. MEK inhibitors induce a transient retinopathy, considered to be a class effect. At present, only sparse data are available on retinal effects with long-term MEK inhibition. PATIENTS AND METHODS: In this prospective, observational study, patients with advanced melanoma participating in different phase 1/2 or phase 3 clinical trials were treated with the MEK inhibitor binimetinib, with a v-Raf murine sarcoma viral oncogene homolog B (BRAF) inhibitor, or with combination therapy. They underwent regular ophthalmological examinations including determination of visual function, biomicroscopy, dilated fundoscopy and optical coherence tomography (OCT) for a period of up to 2 years. Retinopathy was diagnosed on defined OCT criteria. RESULTS: Sixty-two patients were investigated between 1st October 2011 and 31st July 2015: 13 were treated with the MEK inhibitor binimetinib alone, 10 with a selective BRAF inhibitor, and 39 with combination therapy. In 92% of patients on monotherapy and 100% of those on combination treatment, binimetinib caused dose-related lesions with serous neuroretinal detachments and oedema, strongly dependent on the time after medication. With continued treatment, retinal volume and thickness decreased to levels below baseline, without any apparent functional deficits or changes in structural integrity. CONCLUSIONS: Binimetinib induces a specific retinopathy with daily fluctuations depending on the time interval after medication. The retinopathy partially recovers, but can still be detected many months later. Retinal thinning, possible first signs of retinal atrophy have been observed after long-term treatment, but, so far, without functional relevance.

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“…Sera of MAR patients appear to show reactivity against photoreceptor cells. 12 In addition, AA against two photoreceptor proteins, transducin (Tr) 17 and rhodopsin (Rho), 18 were found in the sera of patients with MAR. These data allow us to suggest that not only bipolar cells but also photoreceptor cells may be involved in the MAR syndrome (for review see Ref.…”

mentioning

confidence: 99%

“…[3][4][5][6][7] Melanoma-associated retinopathy (MAR) is a rare paraneoplastic syndrome in patients with metastatic melanoma characterized by visual disorders and the presence of serum AA against retinal proteins. [8][9][10][11][12][13][14] MAR is closely related to cancer-associated retinopathy, 15 which often occurs in lung cancer patients but differs in ophthalmological symptoms and probably in the antigens recognized, which are unknown today (for review see Ref. 16).…”

mentioning

confidence: 99%

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Cancer‐retina antigens as potential paraneoplastic antigens in melanoma‐associated retinopathy

Bazhin

Dalke

Willner

et al. 2008

Intl Journal of Cancer

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Melanoma-associated retinopathy is a rare paraneoplastic neurological syndrome characterized by retinopathy in melanoma patients. The main photoreceptor proteins have been found to be expressed as cancer-retina antigens in melanoma. Here we present evidence that these can function as paraneoplastic antigens in melanoma-associated retinopathy. Sera and one tumor cell line of such patients were studied and ret-transgenic mice spontaneously developing melanoma were used as a murine model for melanoma-associated retinopathy. Splenocytes and sera were used for adoptive transfer from tumor-bearing or control mice to wildtype mice. Retinopathy was investigated in mice by funduscopy, electroretinography and eye histology. Expression of photoreceptor proteins and autoantibodies against arrestin and transducin were detected in melanoma-associated retinopathy patients. In tumor-bearing ret-transgenic mice, retinopathy was frequently (13/ 15) detected by electroretinogram and eye histology. These pathological changes were manifested in degenerations of photoreceptors, bipolar cells and pigment epithelium as well as retinal detachment. Mostly these defects were combined. Cancer-retina antigens were expressed in tumors of these mice, and autoantibodies against arrestin were revealed in some of their sera. Adoptive transfer of splenocytes and sera from tumor-bearing into wildtype mice led to the induction of retinopathy in 4/16 animals. We suggest that melanoma-associated retinopathy can be mediated by humoral and/or cellular immune responses against a number of cancer-retina antigens which may function as paraneoplastic antigens in melanoma-associated retinopathy. '

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Clinical and Immunologic Characteristics of Melanoma-Associated Retinopathy Syndrome: Eleven New Cases and a Review of 51 Previously Published Cases

Abstract: MAR syndrome demonstrates diverse clinical and immunologic features. Treatment, especially intravenous immunoglobulin and cytoreductive surgery (metastasectomy), improves vision in some cases.

Cited by 227 publications

References 63 publications

A Man with Paraneoplastic Retinopathy plus Small Fiber Polyneuropathy Associated with Waldenström Macroglobulinemia (Lymphoplasmacytic Lymphoma): Insights into Mechanisms

A Man with Paraneoplastic Retinopathy plus Small Fiber Polyneuropathy Associated with Waldenström Macroglobulinemia (Lymphoplasmacytic Lymphoma): Insights into Mechanisms

MEK inhibitor-associated retinopathy (MEKAR) in metastatic melanoma: Long-term ophthalmic effects

Cancer‐retina antigens as potential paraneoplastic antigens in melanoma‐associated retinopathy

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