Optic neuritis is an inflammatory optic neuropathy that may be idiopathic or associated with underlying demyelinating disease. The typical presentation is one of subacute vision loss and dyschromatopsia (impairment of color vision) over hours to days. Pain with eye movement accompanies these symptoms in the overwhelming majority of patients. The fundoscopic examination is normal in two-thirds of patients, indicating retrobulbar optic nerve inflammation; in the remaining one-third, there is mild disc margin blurring without hemorrhages or exudates. As dyschromatopsia is an important feature, careful testing with color plates must be done to identify impairment in color vision. Treatment with intravenous corticosteroids hastens visual recovery in optic neuritis but does not affect the final visual outcome. In the Optic Neuritis Treatment Trial, at 2 years’ follow-up, intravenous corticosteroids also delayed the development of clinically definite multiple sclerosis (MS), but this benefit did not persist at 5 years.
A lack of pain with eye movement and severe optic disc swelling should prompt consideration of alternative diagnoses, namely nonarteritic ischemic optic neuropathy (NAION). This is also more common in older individuals with vascular risk factors. Leber’s hereditary optic neuropathy is a mitochondrial disease that causes subacute, painless vision loss in one eye followed weeks to months later by involvement of the other eye, primarily in young men. Acute fundus findings—mild disc margin blurring (pseudoedema) and peripapillary telangiectasias—are subtle and can mimic optic neuritis, so a lack of pain with eye movement and/or suggestive family history are important features to consider. Acute idiopathic blind spot enlargement is a group of autoimmune retinopathies characterized by enlargement of the physiologic blind spot. They may be accompanied by mild optic disc edema and as such may mimic optic neuritis; however, they are distinguished by prominent symptoms of photopsias out of proportion to vision loss and typically lack dyschromatopsia.
While MS is associated with an increased risk of uveitis, especially intermediate uveitis, concurrent uveitis and optic neuritis should raise suspicion for atypical inflammatory causes such as sarcoidosis. Neuroretinitis is an inflammatory disorder affecting both the optic nerve and retina and is often postinfectious (especially Bartonella henselae or “cat-scratch disease”) in etiology. It presents with unilateral optic disc edema followed by the development of a macular star, which reflects lipid leakage from capillaries. Macular stars can also occur in other optic neuropathies when optic disc swelling is severe (e.g., NAION), but this would not be expected in optic neuritis.
Neuromyelitis optica (NMO) is a demyelinating disease that causes severe, often recurrent attacks of optic neuritis and longitudinally extensive transverse myelitis. Testing of aquaporin-4 autoantibodies should be considered in any patient optic neuritis, especially when vision loss is severe (no light perception), bilateral or chiasmal, or does not begin to improve after 1–2 weeks. The distinction between NMO and MS is important not only prognostically but also for choosing long-term immunomodulatory treatment, as most disease-modifying treatments for MS are ineffective in NMO, and some (IFN-β, fingolimod, natalizumab) may actually worsen it.
Magnetic resonance imaging (MRI) of the orbits is very sensitive in demonstrating optic nerve thickening, T2 signal abnormality, and gadolinium enhancement, and therefore the absence of these findings should also lead one to question the diagnosis of optic neuritis.
Patients with optic neuritis have an approximately 30% probability of developing MS within 5 years. By far the strongest predictor of MS is the presence of demyelinating-appearing lesions on MRI; in the Optic Neuritis Treatment Trial, the 15-year risk of MS was 72% for patients with abnormal brain MRI compared with 22% with normal brain MRI.