Collapsin Response-Mediator Protein 5–Associated Retinitis, Vitritis, and Optic Disc Edema

Purpose: Collapsin response-mediator protein 5 (CRMP5) immunoglobulin G (IgG) has been associated with paraneoplastic optic neuritis, vitritis, retinitis, or a combination thereof, but few reports of these findings exist in the literature. We reviewed the neuro-ophthalmic findings and visual outcomes in a large series of CRMP5 IgG–positive patients to characterize further its clinical phenotype and response to treatment. Design: Retrospective case series. Participants: Seventy-six patients with CRMP5 autoimmunity examined at the Mayo Clinic, Rochester, Minnesota. Methods: Single academic medical center chart review of all CRMP5 IgG–positive (serum titer, >1:240) patients seen between 2001 and 2017. Main Outcome Measures: Neuro-ophthalmic manifestations and outcomes of CRMP5 autoimmunity, coexisting neural autoantibody presence and paraneoplastic associations, and the impact of immunosuppressant therapy. Results: Twenty-nine of 76 patients (38%) demonstrated neuro-ophthalmic manifestations. Of the 29 patients with neuro-ophthalmic findings, the median age was 67 years (range, 33–88 years) and 20 (69%) were women. Cancer was diagnosed in 62% of the patients (small-cell carcinoma in 83%). Neuro-ophthalmic symptoms occurred before the diagnosis of cancer in 72%. Seventeen of 29 patients (59%) showed ocular (i.e., anterior visual pathway or intraocular) manifestations; presenting median visual acuity was 20/50 (range, 20/20–counting fingers) and the final median visual acuity was 20/40 (range, 20/20–hand movements). Fourteen of 17 patients (82%) demonstrated optic neuropathy, with 12 of these patients also showing retinitis or uveitis. Three of 17 patients (18%) showed retinitis or uveitis without optic neuropathy. All 12 patients with optic neuropathy and a documented fundus examination at visual symptom onset demonstrated optic disc edema. No patients showed optic nerve enhancement on magnetic resonance imaging. Twelve of 29 patients (41%) demonstrated ocular motility dysfunction consisting of central nystagmus and diplopia. Among those receiving immunosuppressive therapy, visual function improved in 50%. Conclusions: In our cohort of 29 CRMP5 IgG–positive patients with neuro-ophthalmic manifestations, optic neuropathy presented with optic disc edema, often associated with uveitis, retinitis, or both. The combination of retinitis, vitritis, and optic disc edema without optic nerve enhancement should prompt serologic testing for CRMP5 IgG to expedite vision-sparing immunosuppressant therapy and a targeted search for a systemic cancer.