Paraneoplastic retinopathy associated with antiretinal bipolar cell antibodies in cutaneous malignant melanoma

It has been shown previously that the sera, from patients with visual paraneoplastic syndrome associated with lung cancer, contain immunoglobulins that are reactive with the tumor and with photoreceptor and large retinal ganglion cells. The purpose of this study is to determine the retinal cell population that reacts with immunoglobulins in the sera of patients with melanoma-associated retinopathy. Clinical and electrophysiologic studies were used to determine the locus responsible for the visual defect in each patient. Sera from two patients with melanoma-associated retinopathy, from a patient with herpes zoster, and from a patient who had a colon tumor were obtained. The sera were incubated with sections of retina obtained from a healthy 3-year-old child who had died of asphyxiation. The tissue sections subsequently were incubated with biotin-labeled anti-human immunoglobulin G, and then with streptavidin-labeled peroxidase. Finally, the tissue sections were developed to show peroxidase activity in the targeted retinal cells. Clinical and electrophysiologic studies were consistent with a defect in intra-retinal transmission distal to the photoreceptors. The immunoglobulins from the patients with the melanoma-associated retinopathy reacted selectively with the bipolar cells of the retina; approximately 30% of the bipolar cells were immunoreactive. The sera from the other two patients were not reactive with any of the retinal cells examined. The sera of patients with the paraneoplastic syndrome, melanoma-associated retinopathy, contain high titer immunoglobulins that are reactive only with a subset of the bipolar retinal cells. The clinical, electrophysiologic, and immunologic studies are all consistent with an intra-retinal transmission defect at the level of the bipolar cells.