Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG

Abstract

Retinopathy and optic neuropathy are sometimes paraneoplastic. Autoantibodies have defined two paraneoplastic visual disorders related to small-cell lung carcinoma: retinopathy (CAR-IgG [23kDa, recoverin]) and optic neuritis collapsin response-mediated protein 5 (CRMP-5-IgG [62kDa]). The authors identified 16 patients with CRMP-5-IgG and optic neuritis and describe their characteristics. Their mean age was 52 to 74 years; they were all smokers, and nine were women There was evidence of coexisting retinitis in five. None had CAR-IgG. Fifteen had subacute vision loss, swollen optic disks, and field defects. Vascular leakage was evident at and remote from the disk; five of five tested had abnormal electroretinograms. Nine had striking vitreous cells. Vitrectomy showed reactive lymphocytosis (4/4), predominantly CD4+ (1/1). Most patients had multifocal neurological accompaniments. Cerebrospinal fluid contained lymphocytes (7–32), elevated protein, multiple oligoclonal immunoglobulin bands, and CRMP-5-IgG. Three patients superficially resembled Devic disease at presentation. One autopsied patient had predominantly CD8+ T lymphocytes infiltrating optic nerve and spinal cord. Eleven patients had confirmed small-cell carcinoma; one had imaging evidence of lung cancer; three had renal or thyroid carcinoma. Full-length CRMP-5 protein was identified in normal retina and optic nerve by Western blot analyses. Photoreceptor cells, retinal ganglion cells, and nerve fibers exhibited CRMP-5-specific immunoreactivity. In summary, CRMP-5-IgG defines a paraneoplastic ophthalmic entity of combined optic neuritis and retinitis with vitreous inflammatory cells. The authors recommend that adult patients with unexplained subacute painless loss of vision, optic nerve head swelling, and cells in the posterior vitreous be evaluated for CRMP-5-IgG in the serum and cerebrospinal fluid. Positive serology obviates the need for vitreous biopsy and expedites the search for cancer.—Valérie Biousse