Clinical features, imaging findings, and treatment outcomes of optic neuritis associated with anti-CRMP5 antibodies: a systematic review.

Anti-CRMP5/CV2 antibody disease is a rare cause of optic neuritis, therefore the clinical findings, results of neuroimaging, CSF studies and treatment outcomes have been described in case reports or small case series. Here, we performed a systematic review including all published cases of optic neuritis with positive anti-CRMP5/CV2 antibodies. Twenty-four articles comprising 32 patients were included. Median age was 67 years (60-71); 87.1% of patients had clinically symptomatic bilateral optic neuritis, with 64% having a visual acuity worse than 20/200 and ocular pain was uncommon (4.2%). An associated malignancy was identified in 90.6% of cases, most commonly small-cell lung carcinoma (more than 70%) and breast (5%). Optic disc edema occurred in 83.9%, frequently with vitreous (70.8%) and retinal (35%) inflammation. Orbit MRI was normal in 57.1% of cases, but CSF almost universally showed pleocytosis. Overall mortality was 32.1% (9 of 28 patients) at a median follow-up of 9.5 (4-23) months. Absence of tumor response to oncologic treatment was strongly associated with higher mortality (88.9%) and final visual acuity worse than or equal to 20/200 (71.4%), whereas escalation of immunosuppression, such as immunoglobulin, plasmapheresis, and cyclophosphamide, was not associated with improved outcomes. Further investigation into the mechanisms by which CD8+ cytotoxic T-cell recruitment and activation in the pre-laminar optic nerve is essential to develop targeted therapies that can improve visual outcomes.