Clinical Utility of Antiretinal Antibody Testing

Abstract

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 PARTICIPANTSIn 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 MEASURESResults 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 RELEVANCEThe 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.

Linezolid optic neuropathy

“…This case suggests that linezolid could also potentially cause retinal dysfunction, but further study is warranted. The autoantibodies in this case, however, likely represent a false-positive result considering one recent study found that 93% of patients positive for antiretinal antibodies did not have autoimmune retinopathy [36 ▪ ].…”

Autoimmune retinopathy with associated anti-retinal antibodies as a potential immune-related adverse event associated with immunotherapy in patients with advanced cutaneous melanoma: case series and systematic review

“…Chen et al found the presence of anti-retinal antibodies against at least one retinal antigen in 13 out of 14 patients without AIR, although 10 of these patients had macular or optic nerve disease. 42 Interestingly, none of these patients tested positive for anti-recoverin antibodies, suggesting that anti-recoverin antibodies may be possibly more specific to AIR. Given the high rate of positivity for anti-retinal antibodies even in patients without AIR, the presence of anti-retinal antibodies would need to be interpreted in the appropriate clinical context.…”

Limited Clinical Value of Anti-Retinal Antibody Titers and Numbers in Autoimmune Retinopathy

“…2,11 ARAs can be found in other ocular diseases such as retinitis pigmentosa, Vogt-Koyanagi-Harada, sympathetic ophthalmia, toxoplasma retinochoroiditis, diabetic retinopathy, exudative age-related macular degeneration, and cystoid macular edema as well as in systemic diseases such as systemic lupus erythematous, multiple sclerosis, Behcet's disease, and inflammatory bowel disease. 12 ARAs may also be absent in diagnosed patients and present in healthy patients 2,13,14 or patients with AIR quiescence for years. 15 Three laboratory techniques have been described for serum ARA detection, including immunohistochemistry (IHC), WB, and enzyme-linked immunosorbent assay (ELIZA), among which IHC and WB are more commonly used.…”