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A Paraneoplastic Autoimmune Complication

Ying Lu, MD, PhD; Lin Jia, MS; Shirley He, MD, MS; Mary C. Hurley, MS; Monique J. Leys, MD; Thiran Jayasundera, MD; John R. Heckenlively, MD

Arch Ophthalmol. 2009;127(12):1572-1580.

Objectives  To study 11 patients with melanoma-associated retinopathy (MAR) to clarify the reliability of various methods of diagnostic testing, to determine the underlying antigenic retinal proteins, and to study the clinical histories and types of associated melanomas.

Methods  Clinical data were obtained from patients with melanoma who developed marked visual problems. Testing included electroretinography, kinetic visual fields, comparative studies of Western blots, and indirect immunohistologic examination to detect antiretinal antibodies, as well as proteomic studies to identify underlying antigenic retinal proteins.

Results  Patients with MAR typically have rapid onset of photopsias, scotomata, and loss of central or paracentral vision. Ophthalmoscopy seldom shows significant changes early, but electroretinograms are abnormal. Results of Western blots and immunohistologic examination can show antiretinal antibodies but not always. Most patients (9 of 11) had a strong family history of autoimmune disorders. Any type of melanoma (cutaneous, choroidal, ciliary body, or choroidal nevi) may be associated with this paraneoplastic autoimmune reactivity. MAR may precede or follow the diagnosis of melanoma. Patients with MAR have the same antigenic retinal proteins that have been associated with cancer-associated retinopathy. In addition, 2 new antigenic retinal proteins, aldolase A and aldolase C, were found.

Conclusions  There was a high prevalence of positive family histories of autoimmune disease in patients with MAR. To confirm the disorder, multiple clinical and serum diagnostic techniques (Western blot or indirect immunohistologic examination) are needed. Two newly observed antigenic retinal proteins, aldolase A and aldolase C, are associated with MAR.

Author Affiliations: Department of Ophthalmology and Visual Sciences, Kellogg Eye Center (Drs Lu, He, Jayasundera, and Heckenlively and Ms Jia), and Michigan Proteome Consortium (Ms Hurley), University of Michigan, Ann Arbor; and Department of Ophthalmology, University of West Virginia, Morgantown (Dr Leys).

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