Version May 2024
INTRODUCTION — Optic neuritis is an inflammatory, demyelinating condition that causes acute, usually monocular, visual loss. It is highly associated with multiple sclerosis (MS), occurring in 50 percent of individuals at some time during the course of their illness [1-4]. Optic neuritis is the presenting feature of MS in 15 to 20 percent of patients.
The prognosis and treatment of demyelinating optic neuritis will be reviewed in this topic. The epidemiology, pathophysiology, clinical features, and diagnosis of optic neuritis are discussed separately. (See "Optic neuritis: Pathophysiology, clinical features, and diagnosis".)
The term "optic neuritis" is sometimes applied to other inflammatory and infectious conditions affecting the optic nerve. These and other causes of optic neuropathy and the management of MS are discussed separately. (See "Optic neuropathies" and "Treatment of secondary progressive multiple sclerosis in adults" and "Initial disease-modifying therapy for relapsing-remitting multiple sclerosis in adults" and "Management of clinically and radiologically isolated syndromes suggestive of multiple sclerosis" and "Evaluation and diagnosis of multiple sclerosis in adults", section on 'NMOSD'.)
PROGNOSIS — Prognostic concerns in patients with optic neuritis are visual recovery, recurrence of optic neuritis, and risk of multiple sclerosis (MS).
Recovery of vision — Without treatment, vision begins to improve after a few weeks [5]. Improvement can continue over many months; 90 percent have 20/40 or better vision at one year. Some patients may have a more or less favorable prognosis:
●Lower visual acuity at the time of presentation is associated with less complete recovery; however, even those who have no light perception at presentation can recover normal vision [6,7]. In the Optic Neuritis Treatment Trial (ONTT), 64 percent of patients whose vision at presentation was no better than light perception achieved a final visual acuity of 20/40 or better [8]. Severe vision loss at one month, however, is less likely to be associated with good visual recovery [9].
●Longer lesions in the optic nerve, as demonstrated on magnetic resonance imaging (MRI), particularly those extending into the optic canal, are associated with poorer visual outcome [10,11]. A number of studies have found that reduced axial diffusivity on diffusion tensor MRI (DTI) correlates with prolonged latency of visual evoked potentials and worse visual outcome on follow-up [12-14].
●African American patients have a worse prognosis for visual recovery in comparison with White Americans [15-17]. Data on 86 patients from one center found that African American patients had more severe visual loss both at presentation (worse than 20/200 in 93 versus 39 percent) and at one year (worse than 20/200 in 17 versus 5 percent) [15]. At one year, only 61 percent of African Americans had better than 20/40 acuity compared with 92 percent of White Americans. A worse visual prognosis has also been described in Black South Africans [18].
●While most children with optic neuritis have a good visual outcome despite a more severe visual deficit on presentation, approximately 20 percent will have persistent functional visual impairment [19-24].
●Patients with MS may have a somewhat less favorable prognosis than those without [25].
●Patients with neuromyelitis optica spectrum disorder (NMOSD), in particular those with aquaporin-4 (AQP4) autoantibodies, are at elevated risk for both recurrent optic neuritis and poor visual outcomes (visual acuity <20/200) [26,27]. (See "Neuromyelitis optica spectrum disorder (NMOSD): Treatment and prognosis", section on 'Prognosis'.)
●Patients with optic neuritis associated with positive serum myelin oligodendrocyte glycoprotein (MOG) antibodies (MOGAD) may be at increased risk for recurrent optic neuritis but typically have better visual outcomes compared with patients with NMOSD optic neuritis [27]. (See "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): Treatment and prognosis", section on 'Prognosis'.)
Visual recovery is typically measured by acuity. However, one study found that patients with recovery of full visual acuity after optic neuritis may have persistent deficits in tasks that require visual motion perception [28].
Recurrence — In the ONTT, there was a 35 percent recurrence of optic neuritis at 10 years: 14 percent in the original eye, 12 percent in the other eye, and 9 percent in both eyes [7]. Other studies have also found high rates of recurrence [29].
Individuals with recurrent optic neuritis have a greater risk of developing MS [22,30-33]. Recurrent optic neuritis in combination with seropositivity for the AQP4 autoantibody is diagnostic of NMOSD and predicts an elevated risk of recurrence [32,34]. (See "Neuromyelitis optica spectrum disorder (NMOSD): Treatment and prognosis", section on 'Prognosis'.)
Patients with recurrent optic neuritis that is not associated with MS, neuromyelitis optica (NMO), or MOG should be investigated for other causes. (See "Optic neuritis: Pathophysiology, clinical features, and diagnosis", section on 'Differential diagnosis'.)
Risk of multiple sclerosis — In the ONTT, the five-year incidence of clinically definite MS was 30 percent following a first episode of idiopathic demyelinating optic neuritis [35]. The cumulative incidence increased to 40 percent at 12 years and 50 percent at 15 years [30,36]. The median time to diagnosis of MS was three years. Other series have reported similar results [31,37,38].
Demographic characteristics associated with risk of MS include:
●Age. In many series, the risk of MS appears to be lower if the initial attack of optic neuritis occurs in childhood [20,22]. In one investigation, MS occurred in 13 percent of 94 children at 10 years and in 19 percent at 20 years [22]. However, in two other case series, the cumulative two-year risk of MS in children with optic neuritis was much higher, 36 to 45 percent [24,39].
Among adults, patients who present with optic neuritis at an older age (greater than 35 to 40 years) may be somewhat less likely to develop MS [31,40,41]. Optic neuritis itself is relatively uncommon in individuals over 40 years. (See "Optic neuritis: Pathophysiology, clinical features, and diagnosis", section on 'Epidemiology'.)
●Sex. Females may be somewhat more likely to develop MS after optic neuritis than males. In one prospective investigation of patients with optic neuritis followed for 15 years, MS developed in 74 percent of females and 34 percent of males [42]. A higher risk in females was also reported by the Optic Neuritis Study Group and others [30,31,36]. Others have not found that sex influences MS risk in multivariate analysis [40].
●Ethnic and regional influences. In the United States, Asian Americans appear to be less likely to develop MS after optic neuritis than are White Americans.
The lower incidence rates of MS after optic neuritis in Mexican and South American populations are consistent with the regional variation seen in MS overall [43-45]. Similarly, the reported risks are also lower in Asian countries, while in Australia and Western Europe, incidence rates are similar to those reported in the ONTT [31,41,46,47]. (See "Pathogenesis and epidemiology of multiple sclerosis", section on 'Geographic factors'.)
Clinical and laboratory features at the time of presentation with optic neuritis are also helpful in determining prognosis:
●MRI abnormalities. The presence of characteristic demyelinating lesions on MRI is a strong predictor of developing MS. In the ONTT, the risk of MS after 15 years was 72 percent among those with one or more lesions on MRI versus 25 percent among those with no lesions [30,36]. The risk did not significantly differ between those with single versus multiple lesions. Other studies report similar results, including two in pediatric populations [24,40,48,49].
In the ONTT, an abnormal brain MRI dominated other clinical and demographic risk factors, which were useful in prognosis only among those with a normal brain MRI [30]. No patient developed MS after 10 years of follow-up if they had no white matter lesions on brain MRI along with any one of the following clinical features considered atypical for optic neuritis: no pain, no light perception vision at presentation, severe disc swelling, peripapillary hemorrhage, or retinal exudates.
MRI findings also predict future MS-related disability. In one prospective series of 106 patients with optic neuritis, the presence of baseline gadolinium-enhancing lesions and the presence and number of infratentorial and spinal cord lesions were predictive of disability among those who developed MS [38].
●Recurrent episode of optic neuritis. Recurrent optic neuritis is more common among those destined to develop MS [30,31,37]. Patients with recurrent optic neuritis may be particularly at risk for NMOSD or MOGAD. This is particularly true for patients with a normal brain MRI and those with optic neuritis events in rapid succession. In these patients, testing the serum for AQP4 or MOG antibodies is recommended [32,34,50-52]. (See "Optic neuritis: Pathophysiology, clinical features, and diagnosis", section on 'Antibody testing'.)
By contrast, simultaneous bilateral involvement of the optic nerves at the initial presentation is associated with a lower risk of MS in most but not all studies [22,39].
●Funduscopic examination. The presence of papillitis, especially if it is severe, is associated with a lower risk of MS, particularly among those with normal brain MRI [30,36]. Retinal perivenous sheathing is not a common finding in optic neuritis but when present does suggest a higher risk of MS [37].
●Cerebrospinal fluid (CSF). Studies have had somewhat conflicting results regarding the association between abnormal CSF findings (eg, oligoclonal bands [OCB], pleocytosis, myelin basic protein, immunoglobulin G [IgG] synthesis) and subsequent risk of MS [31,40,48,53,54]. Most studies find that individuals who have OCB in the CSF at the time of the optic neuritis event are at higher risk of developing MS [31,40]. However, OCB are also associated with the presence of white matter lesions on MRI and may not represent an independent risk factor [53-58]. The combination of a normal brain MRI and absent OCB identifies individuals at very low risk of MS.
●Human leukocyte antigen (HLA). The HLA type has been reported to affect the relationship between optic neuritis and MS [59]. One prospective study of patients with optic neuritis found a higher risk for conversion to MS among those with HLA-DR2 alleles [41]. Some investigations have corroborated this association, but others have not [31,40,59,60].
●Serum antibodies. Investigators have sought a specific serum marker for MS, which remains elusive.
Seropositivity for AQP4-specific serum antibody in patients with recurrent episodes of optic neuritis identifies patients with NMOSD, while MOG autoantibodies suggest MOGAD. (See "Neuromyelitis optica spectrum disorder (NMOSD): Clinical features and diagnosis", section on 'AQP4 autoantibody' and "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): Clinical features and diagnosis" and "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): Clinical features and diagnosis", section on 'MOG autoantibody'.)
TREATMENT — Treatments for patients with optic neuritis are focused on improving vision and preventing or ameliorating the development of multiple sclerosis (MS).
Other topics discuss the treatment of MS and the treatment of neuromyelitis optica (NMO). (See "Initial disease-modifying therapy for relapsing-remitting multiple sclerosis in adults" and "Treatment of secondary progressive multiple sclerosis in adults" and "Management of clinically and radiologically isolated syndromes suggestive of multiple sclerosis" and "Evaluation and diagnosis of multiple sclerosis in adults", section on 'NMOSD'.)
Acute treatment
Corticosteroids — Intravenous corticosteroids are used in selected patients with optic neuritis as there is some evidence that this treatment may delay onset of MS and hasten visual recovery. Oral prednisone is generally not used.
Patients in the Optic Neuritis Treatment Trial (ONTT) were randomly assigned to either oral prednisone (1 mg/kg per day) for 14 days with a four-day taper, intravenous methylprednisolone (250 mg four times per day for three days) followed by oral prednisone (1 mg/kg per day) for 11 days with a four-day taper, or oral placebo for 14 days [61]. Patients were treated within eight days of symptom onset. The primary visual outcomes were visual acuity and contrast sensitivity.
●Intravenous methylprednisolone accelerated the recovery of visual function; however, one-year visual outcomes were similar among treatment groups [61]. A meta-analysis of three trials, including this one, that compared treatment with intravenous methylprednisolone to placebo found no benefit of treatment on visual outcomes at six months and at one year [62].
●Intravenous methylprednisolone also reduced the risk of conversion to MS within the first two years in comparison with either placebo or oral prednisone (7.5 versus 14.7 and 16.7 percent) [63]. Among patients with two or more white matter lesions on magnetic resonance imaging (MRI), incidence rates for MS were 16.2 versus 32.4 and 35.9 percent. At five years, however, there were no differences in the rates of MS between treatment groups [35].
●The oral prednisone arm of the study was found to have a higher two-year risk of recurrent optic neuritis in either eye, when compared with intravenous steroid therapy or with placebo (27 versus 13 and 15 percent) [61]. At 10 years, the risk of recurrent optic neuritis remained higher in the oral prednisone group when compared with the intravenous-treated group (44 versus 29 percent), but there was no longer a significant difference between the oral prednisone and placebo groups [7,30].
While subsequent small randomized trials have suggested that high-dose oral corticosteroids (methylprednisolone 500 mg; prednisone 1250 mg) might have similar efficacy to intravenous agents in regard to vision outcomes, their small size precludes definitive conclusions, and their relatively short follow-up did not address the potential risk of recurrent optic neuritis that was observed in the ONTT [64,65].
Many patients can now be treated with home intravenous infusions of methylprednisolone for episodes of optic neuritis. The side effects of treatment are minimal when given for a brief time course. The most common side effects in the ONTT were mood changes, facial flushing, sleep perturbations, weight gain, and dyspepsia [61].
A decision to treat with intravenous steroids should be made after considering all potential benefits and risks, with the understanding that long-term visual outcome is not affected by this treatment [66,67]. We use intravenous corticosteroid treatment in patients with abnormal white matter lesions on their brain MRI, since this treatment may delay the onset of MS. We also use intravenous corticosteroid therapy in those patients with either severe or bilateral vision loss, as this may hasten the speed of visual recovery. In such patients, in the rare circumstance when intravenous corticosteroids are not available, we suggest the administration of high-dose oral methylprednisolone (500 mg) [64]. The observed risks associated with oral prednisone were seen in just one trial, were unexpected, and their pathologic basis is not understood. However, we do not use oral corticosteroids for treatment of optic neuritis.
Alternative acute immunomodulatory therapy — Alternative treatments used for acute neuroimmunologic disease include intravenous immune globulin (IVIG) and plasma exchange. These do not have established efficacy in the treatment of optic neuritis.
Two randomized trials studied the potential benefit of IVIG in 55 and 68 patients with optic neuritis [68,69]. Neither study found a difference in visual outcomes at six months. MRI outcomes and the incidence of subsequent demyelinating events at six months were also similar between treatment groups [69]. Another report of IVIG treatment in 23 patients with corticosteroid refractory optic neuritis found that 78 percent achieved vision 20/30 or better, compared with 12.5 percent in a nonrandomized, matched control group [70]. The benefit appeared sustained at one year.
Ten patients with severe optic neuritis underwent plasma exchange between 11 to 73 days after presentation and after failing to respond to intravenous corticosteroid therapy [71]. Seven patients appeared to respond with improvements in visual acuity; however, improvement was not sustained in two of these.
There is some evidence now suggesting that patients with optic neuritis due to neuromyelitis optica spectrum disorder (NMOSD) could be treated early with plasma exchange (within 7 to 14 days of symptom onset). Optic neuritis due to NMOSD is associated with poor disease outcome, and some small case series have suggested earlier treatment with plasma exchange may help visual recovery in patients who do not respond to intravenous corticosteroids. However, there are as yet no prospective randomized trials demonstrating the efficacy of this plasma exchange in acute treatment of NMOSD optic neuritis [72,73].
Disease-modifying therapy — We offer treatment with immunomodulatory therapies, so-called disease-modifying therapy (DMT) to patients with optic neuritis and abnormal brain MRIs. Such patients are considered to have a clinically isolated syndrome suggestive of MS. If such patients can tolerate treatment, potential benefits as demonstrated by randomized clinical trials include a longer attack-free interval, reduced number of demyelinating attacks, and a delay to MS-associated disability. The management of patients with clinically isolated syndromes is discussed in detail separately. (See "Management of clinically and radiologically isolated syndromes suggestive of multiple sclerosis", section on 'Management'.)
Treatment in children — All of the clinical trials of treatment discussed above were limited to adults. No clinical trial data are available to guide the treatment of children with optic neuritis. Given their lower risk of MS, some modifications in the treatment approach seem reasonable [22].
Intravenous methylprednisolone can be considered for acute treatment for severe debilitating bilateral vision loss in hopes of hastening recovery [1,74,75]. The risk of short-term treatment is low in children. While some clinicians recommend a longer taper rate (four to eight weeks) than is used in adults because of anecdotal reports of relapses of vision loss occurring with a shorter taper in children [74,75], this practice did not appear to lead to improved relapse rates according to one retrospective cohort study [76]. As with adults, case series suggest that the final visual outcome is not altered by this treatment [19,20,76].
The evaluation and use of chronic immunomodulatory therapy (DMT) in children who present with clinically isolated syndromes suggestive of MS are discussed separately. (See "Pathogenesis, clinical features, and diagnosis of pediatric multiple sclerosis", section on 'Clinically isolated syndromes' and "Treatment and prognosis of pediatric multiple sclerosis".)
Investigational treatments
●Dalfampridine (4-aminopyridine; fampridine), a potassium channel blocker, may improve axonal function in patients with demyelinating disease. In one randomized crossover study in 20 patients with optic neuritis of at least six months duration, five weeks of treatment with 4-aminopyridine was associated with improved measures on visual evoked potentials, and a subset analysis showed that some patients had improved visual acuity while on treatment [77]. Further studies are needed to define the role of this treatment in patients with optic neuritis.
While dalfampridine is approved for treatment of gait impairment in MS, the appropriate clinical use has not been clearly defined in that setting. (See "Symptom management of multiple sclerosis in adults", section on 'Dalfampridine'.)
●Erythropoietin has also been investigated in a phase II clinical trial of patients with acute optic neuritis [78]. Compared with placebo, active treatment was safe and associated with reduced retinal nerve fiber layer thinning on optical coherence tomography and shortened latencies on visual evoked potential at 16 weeks.
●Other investigational therapies for the treatment of acute optic neuritis that are being studied in phase I/II clinical trials include phenytoin, amiloride, and anti-LINGO monoclonal antibody [79].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Multiple sclerosis and related disorders".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Optic neuritis (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Clinical course and vision outcomes – Visual recovery begins within a few weeks. Most achieve 20/40 vision or better at one year. When vision is more severely affected at onset, a good prognosis is less certain. (See 'Recovery of vision' above.)
●Risk of multiple sclerosis – In adults, 30 percent of individuals will develop multiple sclerosis (MS) at five years. The risk is higher, 56 percent, in those with two or more typical white matter lesions on magnetic resonance imaging (MRI). Younger children may be less likely than adults to develop MS. (See 'Risk of multiple sclerosis' above.)
●Acute treatment – We suggest treatment with intravenous methylprednisolone for children and adults with either severe vision loss or two or more white matter lesions on MRI (Grade 2A). Treatment is associated with a more rapid recovery of vision and with delayed onset of MS, but does not impact long-term visual function. (See 'Corticosteroids' above.)
We recommend not using oral prednisone, which does not affect short- or long-term visual outcomes in acute optic neuritis and may be associated with an increased risk of recurrent optic neuritis (Grade 1B). (See 'Corticosteroids' above.)
●Disease-modifying therapy for multiple sclerosis – Individuals with acute optic neuritis and two or more white matter lesions on brain MRI are considered to have a clinically isolated syndrome suggestive of MS. If treatment is tolerated, potential benefits as demonstrated by randomized clinical trials include a longer attack-free interval, reduced number of demyelinating attacks, and a delay to MS-associated disability.
Specific recommendations for treatment are provided separately. (See "Management of clinically and radiologically isolated syndromes suggestive of multiple sclerosis", section on 'Management'.)
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