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Neuromyelitis optica (NMO) is a disabling inflammatory condition that targets astrocytes in the optic nerves and spinal cord. Neuro-ophthalmologists must be particularly aware of this disorder because about half of patients present as isolated unilateral optic neuritis months or years before a disease-defining and often crippling bout of myelitis. NMO is easily confused with multiple sclerosis because it is characterized by relapses that lead to stepwise accrual of deficits. The best predictor of conversion from optic neuritis to clinical definite NMO is the presence of a serum antibody to aquaporin-4 called NMO-IgG. However, this test is currently only about 75% sensitive. Suspicion of NMO should be high in patients who present with vision of light perception or worse or who are left with acuity of 20/50 or worse after optic neuritis and in those with simultaneous bilateral optic neuritis or recurrent attacks. Acute NMO relapses are generally treated with high-dose intravenous steroids, with plasma exchange often used as a rescue therapy for those who do not respond. Preventative strategies against relapses currently use broad-spectrum or selective B-lymphocyte immune suppression, but their use is based on small, generally uncontrolled studies. Hopefully, the future will bring more sensitive tools for defining risk and predicting outcome, as well as more targeted and effective forms of therapy.