Nonparaneoplastic and Paraneoplastic Autoimmune Retinopathies

Autoimmune retinopathy (AIR) is a rare and poorly understood, inflammatory-mediated degenerative retinal disorder characterized by progressive loss of vision, scotomas, and photoreceptor dysfunction, initially described as a paraneoplastic disorder. Retinal dysfunction and vision loss are caused by an aberrant immunologic response involving circulating antibodies that target retinal antigens. Several such antiretinal antibodies have been discovered, but only very few have been definitively identified as pathogenic. A comprehensive understanding of the pathogenesis of AIR is still a subject of research. Diagnosis is based on a constellation of characteristic symptoms, careful ophthalmologic examination and testing, and laboratory evaluation. Fundus examination is usually unremarkable but may display signs of retinal pigment atrophy and vascular attenuation, optic nerve pallor, and minimal, if any, intraocular inflammation. Ophthalmic imaging can support the diagnosis and may show mild retinal vasculitis and macular edema. Electroretinography is characteristically abnormal, with decreased amplitudes of photopic and scotopic responses and prolonged implicit times. Visual fields can show various patterns of vision loss. The presence of specific antiretinal antibodies can aid in this diagnosis, but the overall low specificity and sensitivity of antiretinal antibody testing limit the utility of this test. Given the association of cancer with AIR, a comprehensive evaluation for underlying malignancy is mandatory. Left untreated, patients can have progressive visual decline, and spontaneous improvement has not been reported. Treatment is aimed at modulating the immune response and minimizing inflammatory destruction of the retina. Corticosteroids, traditional immunomodulatory therapies, plasmapheresis, rituximab, and intravenous immunoglobulin have been tried with varying degrees of clinical response. Treatment of the underlying malignancy, if present, has shown mixed responses. There is an expanding literature further characterizing these diseases, their diagnosis, and treatment, but there are not yet any widely accepted standards for diagnosis or treatment.