Adult Optic Neuritis Treatment & Management

Updated: Jan 22, 2021
  • Author: Andrew A Dahl, MD, FACS; Chief Editor: Edsel B Ing, MD, MPH, FRCSC, PhD, MA  more...
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Treatment

Approach Considerations

Finding professional help early in the course of optic neuritis (ON) is important. The Optic Neuritis Treatment Trial (ONTT) was a carefully performed, randomized, clinical trial that yielded useful information. Despite the ONTT, the treatment of ON remains somewhat controversial. [12, 13]  From a vision standpoint, observation without steroid treatment versus intravenous steroid treatment showed no difference in ultimate visual outcome at the 5-year mark. [14]

Eculizumab, a monoclonal antibody that targets C5, is the first drug approved by the FDA for adults with neuromyelitis optica spectrum disorder (NMOSD) who are anti–aquaporin-4 antibody–positive. Approval was based on the PREVENT clinical trial. Results showed that eculizumab reduced the risk for NMOSD relapse by 94.2% compared with placebo (P < .0001). Nearly 98% of eculizumab-treated patients were relapse free at 48 weeks compared with 63.2% of patients in the placebo group. Additionally, compared with placebo, eculizumab reduced the adjudicated on-trial annualized relapse rate by 95.5% (P < .0001). [15]

Inebilizumab is a monoclonal antibody that targets CD19, a protein expressed on a broad range of B cells, including antibody-secreting plasmablasts and plasma cells. After binding to CD19, these cells are rapidly depleted from the circulation. Aquaporin-4 –IgG (AQP4-IgG ) autoantibodies are produced by plasmablasts and plasma cells and bind primarily to astrocytes in the central nervous system (CNS). Binding of AQP4-IgG antibodies to CNS cells is believed to trigger attacks that can damage the optic nerve, spinal cord, and brain. Approval was based on the N-Momentum trial (n = 230). Participants were randomly assigned to treatment and control groups, with 174 participants receiving inebilizumab and 56 receiving placebo. At the recommendation of the independent data-monitoring committee, the randomized controlled period was stopped before complete enrollment because of clearly demonstrated efficacy. Twenty-one of 174 (12%) participants receiving inebilizumab had an attack compared with 22 (39%) of 56 participants receiving placebo (P < .0001). [16]

Satralizumab is the third drug approved by the US Food and Drug Administration (FDA) for adults with neuromyelitis optica spectrum disorder (NMOSD) who are anti-AQP4 antibody–positive. Satralizumab is a recombinant humanized IgG2 antibody targeting the interleukin-6 receptor. The efficacy of satralizumab for the treatment of NMOSD in adult patients was established in 2 studies. SAkuraStar [52]  was a randomized placebo-controlled trial in 64 patients without concurrent immunosuppressive therapy. SAkuraSky [53]  was a randomized placebo-controlled trial in 52 adult patients with concurrent immunosuppressive therapy. In the SAkuraStar monotherapy study, 76.5% of satralizumab-treated patients were relapse free at 96 weeks, compared with 41.1% who received placebo. In the SAkuraSky study, which evaluated satralizumab when used concurrently with baseline IST, 91.1% of satralizumab-treated AQP4 antibody–positive patients were relapse free at 96 weeks, compared with 56.8% who received placebo. [52, 53]

Early reports with a small number of patients demonstrated some benefit with plasma exchange for patients with acute, severe ON. Further controlled studies are recommended. In 2016, a randomized controlled trial of erythropoietin in the treatment of ON was initiated. [54]

Rituximab therapy, used off-label, is considered to be among the most efficient treatments for neuromyelitis optica spectrum disorders (NMOSDs), "even in the absence of class I studies." [55]  In a case series of 20 patients with highly relapsing NMO, Kim and colleagues [56]  reported significantly reduced relapse rates and clinical stabilization or improvement with mitoxantrone treatment. Further studies conducted in a prospective and controlled fashion are required to determine whether mitoxantrone is a viable treatment option.

Intravenous immunoglobulin (IVIg) and plasma exchange (PLEX) are alternative immunomodulatory therapies that may offer additional benefit for treatment of acute ON. It remains to be determined whether IVIg may benefit patients with NMOSD and ON when delivered in conjunction with or after a round of high-dose corticosteroids.

Plasma exchange has been used successfully in the treatment of steroid-refractory ON and NMOSD-ON. Depending on the study, improvement in visual function has been noted in 45% to 55% of treated patients. Unfortunately, because of their retrospective design, these investigations failed to define criteria for the optimal use or timing of PLEX. In many instances, the short interval between completion of IVMP and institution of PLEX makes it unclear how much clinical benefit is related to delayed effects of IVMP. Male sex, lower baseline disability, rapid initiation of treatment, and shorter relapse duration have been associated with greater response to PLEX. Although early initiation of PLEX correlates with treatment response, delayed PLEX therapy may still be a reasonable treatment option for patients with acute ON who may not have immediate access to facilities with the necessary equipment.

Deschamps et al found that half of patients with poor visual recovery (visual acuity worse than or equal to 20/200) after high-dose INSM experienced improvement to visual acuity of 20/30 or better after PLEX (mean time to PLEX, 30 days). [64] Because PLEX incurs significant cost and may result in serious adverse effects such as hypotension, infection, hypocalcemia, and coagulopathy, a randomized, prospective study of PLEX versus IVMP for the treatment of acute NMOSD-ON is warranted.

Immunoadsorption is an alternative form of therapeutic apheresis that allows for selective removal of antibodies from plasma using modified membranes. Therapeutic apheresis offers the potential advantage of removing pathogenic autoantibodies while sparing other plasma proteins, eliminating the need for protein replacement and potentially minimizing complications. Immunoadsorption has been reported to benefit patients with steroid-refractory ON and NMOSD-ON. The relative efficacy and safety of PLEX and immunoadsorption have not been directly evaluated. Immunoadsorption is not approved in the United States.

For individuals who are unresponsive to IVMP and PLEX, immunosuppression with intravenous (IV) cyclophosphamide may represent an avenue of final resort. Although no clinical studies have been published on the response of severe ON to IV cyclophosphamide, a subset of patients with acute transverse myelitis have benefited from this approach. Given the risks of high-dose IV cyclophosphamide, however, careful patient selection and employment of an experienced hospital team are advised.

Other Agents

Early reports with a small number of patients found some benefit with plasma exchange in acute, severe optic neuritis. Further controlled studies are recommended. In 2016, a randomized controlled trial of erythropoietin in the treatment of optic neuritis was initiated. [52]

Rituximab therapy, utilized off-label, is considered to be among the most efficient treatments of neuromyelitis optica spectrum disorders (NMOSDs), even in the absence of class I studies. [53] In a case series of 20 patients with highly relapsing NMO, Kim et al reported significantly reduced relapse rates and clinical stabilization or improvement with mitoxantrone treatment. [54] Further studies conducted in a prospective and controlled fashion are required to determine whether mitoxantrone is a viable treatment option.

Intravenous immunoglobulin (IVIg) and plasma exchange (PLEX) are alternative immunomodulatory therapies that may offer additional benefit for acute ON treatment. It remains to be determined whether IVIg may benefit patients with NMOSD-ON when delivered in conjunction with or after a round of high-dose corticosteroids.

Plasma exchange (PLEX) has been used successfully in the treatment of steroid refractory ON and NMOSD-ON. Depending on the study, improvement in visual function has been noted in 45%–55% of treated patients. Unfortunately, because of their retrospective design, these investigations failed to define criteria for the optimal use or timing of PLEX. In many instances, the short interval between completion of IVMP and institution of PLEX makes it unclear how much clinical benefit is a result of delayed effects of IVMP. Male sex, lower baseline disability, rapid initiation of treatment, and shorter relapse duration have been associated with greater response to PLEX. Although early initiation of PLEX correlates with treatment response, delayed PLEX therapy may still be a reasonable treatment option for patients with acute ON who may not have immediate access to facilities with the necessary equipment. Deschamps and colleagues found that half of the patients with poor visual recovery (visual acuity worse than or equal to 20/200) after high-dose IVSM improved to visual acuity of 20/30 or better after PLEX (mean time to PLEX, 30 days). Because PLEX incurs significant cost and may result in serious side effects such as hypotension, infection, hypocalcemia, and coagulopathy, a randomized, prospective study of PLEX versus IVMP for the treatment of acute NMOSD-ON is warranted.

Immunoadsorption (IA) is an alternative form of therapeutic apheresis that allows for selective removal of antibodies from plasma using modified membranes. Therapeutic apheresis offers the potential advantage of removing pathogenic autoantibodies while sparing other plasma proteins, therefore eliminating the need for protein replacement, and potentially minimizing complications. Immunoadsorption has been reported to benefit steroid refractory ON and NMOSD-ON. The relative efficacy and safety of PLEX and IA are yet to be directly evaluated. Immunoadsorption is not approved in the United States.

For individuals who are unresponsive to IVMP and PLEX, immunosuppression with intravenous cyclophosphamide may represent an avenue of final resort. Although no clinical studies have been published on the response of severe ON to intravenous cyclophosphamide, a subset of patients with acute transverse myelitis have benefited from this approach. Given the risks of high-dose IV cyclophosphamide, however, careful patient selection and an experienced hospital team are advised.

Inpatient care

Patients with neuromyelitis optica often require supportive care because they are prone to many complications, such as deep venous thrombosis, pulmonary embolism, urinary tract infection, decubiti, and contractures related to the myelopathy. Mechanical ventilation may be needed as well because of respiratory compromise.

Consultations

Consultations with ophthalmology and neurology are recommended for complete evaluation and treatment of patients with suspected optic neuritis.

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Steroid Therapy

The ONTT protocol used intravenous steroids (methylprednisolone 250 mg qid for 3 days) with oral steroid taper and showed a decreased short-term risk for development of MS in patients with central nervous system (CNS) white matter plaques, but they had no long-term protective benefit from MS.

Intravenous steroids do little to affect the ultimate visual acuity in patients with optic neuritis, but they do speed the rate of recovery. Some clinicians advocate IV steroids in patients with severe visual loss or bilateral visual loss.

Intravenous steroids are sometimes administered in an outpatient setting or at home. Admission to the hospital is recommended for the duration of high-dose intravenous steroid treatment because of the potential risk for serious adverse effects from this treatment.

The ONTT showed strong evidence against the use of conventional-dose oral steroid monotherapy in the treatment of optic neuritis, since oral steroids alone increased the rate of optic neuritis recurrence. [57, 58]

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Medical Care

For patients with optic neuritis (ON) whose brain lesions on magnetic resonance imaging (MRI) indicate a high risk for development of clinically definite multiple sclerosis (MS), treatment with immunomodulators (eg, interferon beta-1ainterferon beta-1bglatiramer) may be considered. [17] 17 Intravenous immunoglobulin  treatment of acute ON has been shown to have no beneficial effect.

Dress polycarbonate safety glasses are an option for patients whose vision does not completely recover.

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