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Brief Report
April 22, 2021

Clinical Utility of Antiretinal Antibody Testing

Author Affiliations
  • 1Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota
  • 2Department of Neurology, Mayo Clinic, Rochester, Minnesota
  • 3Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
  • 4Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota
  • 5Department of Ophthalmology, Wills Eye Hospital, Philadelphia, Pennsylvania
  • 6National Eye Institute, National Institutes of Health, Bethesda, Maryland
  • 7Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles
JAMA Ophthalmol. Published online April 22, 2021. doi:10.1001/jamaophthalmol.2021.0651
Key Points

Question  What is the clinical utility of current commercially available antiretinal antibody testing?

Findings  In this cross-sectional study, 13 of 14 samples from patients without autoimmune retinopathy tested positive for retinal antibodies, with a median of 5 antibodies per patient.

Meaning  This study suggests that most retinal antibodies included in antiretinal antibody testing evaluations available on a clinical service basis have limited clinical utility in the evaluation of a patient for suspected autoimmune retinopathy.

Abstract

Importance  The clinical utility of most antiretinal antibodies (retina antibodies) currently available for testing remains unclear and unproven. Despite this, the presence of retinal antibodies is included in current diagnostic autoimmune retinopathy criteria.

Objective  To evaluate the clinical significance of comprehensive retinal antibody evaluations currently offered in North America.

Design, Setting, and Participants  In this cross-sectional study, 14 patients without autoimmune retinopathy were recruited into the Mayo Clinic Neuroimmunology Biorepository for this study between January 1, 2019, and October 1, 2019. These serum samples without autoimmune retinopathy were sent in masked fashion to a Clinical Laboratory Improvement Amendments–certified laboratory. Using similar methods, the Mayo Clinic Neuroimmunology Research Laboratory independently assessed the same sample to ascertain reproducibility of the findings.

Main Outcomes and Measures  Results of the autoimmune retinopathy and cancer-associated retinopathy panels.

Results  Thirteen of 14 (93%; 95% CI, 66%-100%) serum samples tested positive for retinal antibodies, with a median of 5 retinal antibodies (range, 0-8) per patient at the Clinical Laboratory Improvement Amendments–certified laboratory, which provides a specificity of 7% (95% CI, 0%-34%). Confirmatory immunohistochemistry staining in human retina was present in 12 of 14 samples (86%). α-Enolase was found in 9 (64%). The only retinal antibody not present was recoverin. These nonspecific retinal antibody results were replicated at the Mayo Clinic Laboratory on Western blot using pig retina proteins as substrate.

Conclusions and Relevance  The presence of retinal antibodies in 93% of the patients without autoimmune retinopathy indicates a lack of specificity and that most detectable retinal antibodies have limited clinical relevance in the evaluation of patients for suspected autoimmune retinopathy. Current retinal antibody testing, other than recoverin, should be interpreted with caution, especially for cases of low clinical suspicion. The poor specificity is important to recognize to prevent the potentially unnecessary commencement of systemic immunosuppressants that may result in significant extraocular adverse effects. Identification of biomarkers that have a high predictive value for inflammatory or autoimmune retinal diseases is needed to move the field forward.

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