Abstract and Introduction
Abstract
Background: Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome with symptoms of night blindness, light sensations, visual loss, defect in visual fields, and reduced b-waves in the electroretinogram. Patients with MAR often suffer from a sudden onset of ocular symptoms that are believed to result from antibody production against melanoma-associated antigens that cross-react with corresponding epitopes on retinal depolarizing bipolar cells.
Objectives: To correlate the frequency of subclinical symptoms suggestive of MAR in melanoma patients to different stages of disease, patient age, type and thickness of the primary tumour, form of therapy, S-100 level and tumour burden.
Methods: We analysed 28 patients with melanoma in stages I-IV (according to the American Joint Committee on Cancer tumour classification) for the presence of subclinical MAR symptoms using scotopic electroretinography, static and kinetic perimetry and nyctometry.
Results: Seven patients had clinical signs and symptoms consistent with MAR, 18 had some indications, while the remaining three had none. We found no correlation between clinical symptoms and stage of disease, tumour burden or S-100 level, but findings suggestive of MAR were observed more frequently in advanced stages of disease.
Conclusions: Subclinical retinal involvement characteristic of MAR appears to be more common than previously suspected in patients with cutaneous malignant melanoma. Our findings in this small cohort seem to indicate that the percentage of patients with symptoms suggestive of MAR is higher in advanced stages of disease. Further clinical studies are required to evaluate if the presence of subclinical symptoms suggestive of MAR is correlated with a worse prognosis and a shortened progression-free and overall survival.
Introduction
Melanoma-associated retinopathy (MAR) is a rarely reported visual paraneoplastic syndrome occurring most often in males with cutaneous malignant melanoma. Up to now only one patient has been reported with MAR following a choroidal melanoma. Patients typically develop a sudden onset of shimmering, flickering or pulsating photopsias that begin months to years after tumour diagnosis. They often complain of night blindness and a progressive loss of vision. Scotopic electroretinography commonly reveals markedly reduced b-waves with normal dark-adapted a-waves, findings that indicate a dysfunction of depolarizing bipolar cells. The proposed mechanism involves a B-lymphocyte response against yet to be identified melanoma antigens that incite the production of autoantibodies that cross-react with specific retinal cellular components. Evidence of antibody involvement in bipolar inactivation is supported by the work of Lei et al. who showed that injection of IgG from patients with MAR into the vitreous humour of monkeys resulted in transient, altered electroretinogram readings comparable with those of MAR. Using indirect immunofluorescence, Milam et al. showed that serum from two patients with MAR contained antibodies that reacted with the bipolar cell layer of the retina.
A recent search of the relevant literature indicated that most patients with MAR seemed to develop disease progression within weeks or months of the onset of visual symptoms, but this may also be because the onset of symptoms suggestive of MAR (MAR-suggestive, MS) was followed by an intensive staging and the early detection of metastases. MAR antibody production has rarely been linked with a remission or stabilization of the melanoma, indicating that this response may be insufficient to protect against dissemination and that, in general, patients with MAR may have a worse prognosis. We therefore conducted a study to correlate the frequency of subclinical MS in patients with melanoma to different stages of disease, patient age, type of primary melanoma, tumour thickness, form of therapy, S-100 level and tumour burden.