• Vision is impaired, including visual acuity, visual field, and/or color perception.
• Patients typically have eye pain that is worse with eye movement.
• There is a relative afferent papillary defect if only one eye is affected.
• The anterior optic nerve has a normal appearance in two thirds of affected patients.
• Consider IV methylprednisolone (Solu-Medrol) followed by oral steroids.
• Avoid oral steroid monotherapy.
• If brain MRI suggests a high-risk, clinically isolated syndrome, consider disease-modifying therapy to delay progression to MS.
• If the clinical features suggest NMO, consider IV methylprednisolone and plasma exchange therapy
• If the patient’s history suggests MS or NMO, consider treatment for these conditions.
The incidence of optic neuritis is approximately 1 to 5 in 100,000. Though it typically affects women in their fourth decade of life, 1 in 4 patients are male, and patients have been reported ranging from the first to seventh decades of life. Optic neuritis occurs worldwide in persons of various ethnicities.
Optic neuritis can be classified as a clinically isolated syndrome or in association with a disease such as multiple sclerosis (MS) or neuromyelitis optica (NMO). Approximately half of patients with optic neuritis as a clinically isolated syndrome develop MS. A small percentage develop NMO.
A diagnosis of a disease associated with optic neuritis, such as MS or NMO, increases the risk of developing optic neuritis. In one study, more than 70% of patients with MS and 100% of patients with NMO had unilateral optic neuritis at some point.
Most optic neuritis occurs as a result of inflammation causing demyelination of the ganglion cell axons that compose the optic nerve. This is thought to be an immune-mediated process.
Disease-modifying therapies have been shown to reduce risk of neurologic relapses in patients with MS or NMO. These therapies presumably also decrease the risk of MS- or NMO-associated optic neuritis because optic neuritis is a common relapse syndrome in these conditions.
A typical optic neuritis patient experiences acute or subacute loss of vision characterized by decreased visual acuity, visual field loss, and/or color vision loss, accompanied or preceded by pain in the affected eye that is worse with eye movements. However, 8% of patients do not have pain. Other symptoms include positive visual phenomena in 30% of patients. Other signs include a relative afferent papillary defect in cases where one eye is affected and a mildly swollen optic nerve head in approximately one third of patients. Optic neuritis in NMO is more likely to have bilateral involvement and severe visual impairment.
The natural history of clinically isolated optic neuritis includes resolution of pain 3 to 5 days after onset and nadir of vision 7 to 14 days after onset. Spontaneous improvement in vision is typically evident within 3 weeks, and almost 70% of affected patients recover 20/20 visual acuity. Optic neuritis associated with MS shares similar features. Optic neuritis associated with NMO tends to have less recovery of vision.
The diagnosis is based on the clinical presentation. Where there is uncertainty, magnetic resonance imaging (MRI) of the orbits, including fat-saturated sequences (T2 and T1 with and without gadolinium contrast) can help to visualize inflammation in the retrobulbar optic nerve. Changes on MRI involving the chiasm or more than 50% of the optic nerve are suggestive of NMO spectrum optic neuritis.
Optic neuritis is often associated with other demyelinating syndromes, most commonly MS. Therefore it is important to screen for historical and current neurologic impairment through history and examination. MRI of the brain has been shown to be an important prognostic indicator for development of MS in patients who present with their first episode of clinically isolated optic neuritis. MRI of the brain showing 0, 1, or more than 3 lesions typical for MS is associated with a 25%, 60%, and 78%, respectively, risk of progression to clinically definite MS.
Less commonly, optic neuritis is associated with other demyelinating syndromes such as NMO. This should be considered in patients with severe vision loss, bilateral involvement, or history of prior optic neuritis or transverse myelitis. A serum antibody (anti- aquaporin 4 or NMO antibody) has been identified as a pathologic agent in this disorder. Testing for this is commercially available with a published sensitivity and specificity of 63% and 99%, respectively.
Positive testing for anti-AqP4-IgG in a patient is optic neuritis is diagnostic of NMO per recently published consensus criteria.
Other diagnostic considerations in a patient with unilateral painful vision loss without explanatory pathology evident on ophthalmic examination include other optic neuropathies such as those due to sarcoidosis, lupus, vasculitis, neoplastic, vascular, and infectious causes. Atypical features for optic neuritis such as systemic symptoms, history of cancer, pain that persists beyond 2 weeks, progressive vision loss beyond 14 days, no spontaneous improvement in vision, retinal hemorrhages, cotton-wool spots, or macular exudates should prompt diagnostic evaluation for etiologies other than optic neuritis.
Treatment and Monitoring
The Optic Neuritis Treatment Trial (ONTT) was a randomized trial comparing placebo, oral prednisone, and IV methylprednisolone (1 g/day IV for 3 days) followed by oral prednisone (1 mg/kg per day for 11 days) for acute optic neuritis. IV steroids hastened recovery of vision without affecting final visual outcome compared with placebo treatment. Treatment with oral prednisone alone was associated with an increased risk of relapse compared with placebo treatment. The 15- year follow-up results, published in 2008, demonstrated persistence of visual recovery.
Based on the ONTT results, many clinicians offer IV steroid treatment to hasten visual recovery. Monotherapy with oral prednisone should be avoided. Regardless of the decision to treat or not with IV steroids, all patients should be monitored closely.
Continued progression of vision loss, failure to spontaneously recover vision, or persistent pain should prompt additional diagnostic work- up as well as consideration for additional IV steroid therapy for atypical optic neuritis. If this is not effective, plasma exchange has been reported as an effective acute therapy for atypical optic neuritis.
In patients with acute optic neuritis and NMO treatment with plasma exchange or rituxamab should be considered.
In patients with a clinically isolated syndrome, consideration should be given to institution of disease-modifying therapy for MS based on the presence of lesions on brain MRI. Several clinical trials have shown an association between early treatment with MS therapies and decreased incidence of progression to clinically definite MS in patients with a recent clinically isolated syndrome and clinically silent lesions on brain MRI.
In patients who meet diagnostic criteria for either MS or NMO, consideration should be given to treating the underlying disease.
Though more than 70% of patients with optic neuritis recover objectively normal visual acuity, many have residual subjective visual disturbances. These often worsen or recur in heat, which is known as Uhtoff’s phenomenon.
Complications of steroid therapy include insomnia, agitation, and stomach irritation. Long-term side effects of steroid treatment for this condition are rare owing to the brief period of treatment.
Complications of disease-modifying therapies for MS and NMO are reviewed elsewhere.
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