There is no consensus treatment for optic neuritis (ON). The only treatment for idiopathic acute ON is corticosteroids. Chronic treatment involves referral to a multiple sclerosis (MS) specialist for management and consideration of MS immunomodulatory therapy if there is an abnormal MRI scan or other neurological abnormalities.[12]American Academy of Ophthalmology. Optic neuritis - 2012. Jul 2012 [internet publication].
https://www.aao.org/education/clinical-statement/optic-neuritis
Acute episode of ON
Corticosteroids are the treatment of choice for an acute episode of ON, whether that be a first episode or relapse. Corticosteroids are prescribed with the aim of reducing the duration of the acute phase and the risk of recurrence. Acute treatment involves high-dose intravenous corticosteroids (e.g., methylprednisolone) as per the Optic Neuritis Treatment Trial (ONTT) protocol, or no treatment based on the patient’s benefit versus risk ratio.[12]American Academy of Ophthalmology. Optic neuritis - 2012. Jul 2012 [internet publication].
https://www.aao.org/education/clinical-statement/optic-neuritis
[20]Beck RW, Cleary PA, Anderson MM Jr, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group. N Engl J Med. 1992 Feb 27;326(9):581-8.
http://www.ncbi.nlm.nih.gov/pubmed/1734247?tool=bestpractice.com
The ONTT was the first randomised, controlled trial of corticosteroids for ON.[20]Beck RW, Cleary PA, Anderson MM Jr, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group. N Engl J Med. 1992 Feb 27;326(9):581-8.
http://www.ncbi.nlm.nih.gov/pubmed/1734247?tool=bestpractice.com
It provided evidence that there is an improved visual outcome at 6 months (with differences disappeared at 2 years) and a reduced rate of recurrence at 2 years for patients with ON receiving high doses of intravenous methylprednisolone. In a Cochrane review, treatment with either oral or intravenous corticosteroids showed a modest, not statistically significant benefit.[45]Gal RL, Vedula SS, Beck R. Corticosteroids for treating optic neuritis. Cochrane Database Syst Rev. 2015 Aug 14;(8):CD001430.
https://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001430.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/26273799?tool=bestpractice.com
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In people with optic neuritis, what are the effects of corticosteroids?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.1109/fullShow me the answer
The ONTT examined the role of corticosteroid treatment in the management of acute ON and the subsequent risk of development of MS. It randomised 454 patients to receive (i) oral placebo for 14 days; (ii) oral prednisolone 14 days followed by taper over 7 days; (iii) pulse dose intravenous methylprednisolone for 3 days followed by oral prednisolone for 11 days.
The intravenous methylprednisolone group showed a better visual outcome at 6 months (the benefit disappeared at 2 years) and a lower risk of recurrence (conversion to clinically definite MS) than placebo or oral corticosteroids. Therefore, pulse dose intravenous methylprednisolone for 3 days followed by oral prednisolone for 7-11 days has thus been the standard treatment of acute ON. A tapering dose is no longer thought to be necessary. Oral low dose corticosteroids (e.g., prednisolone up to 1 mg/kg) alone are contraindicated because of an increased relapse rate documented during the ONTT and are no more effective than placebo at improving visual outcomes.[20]Beck RW, Cleary PA, Anderson MM Jr, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group. N Engl J Med. 1992 Feb 27;326(9):581-8.
http://www.ncbi.nlm.nih.gov/pubmed/1734247?tool=bestpractice.com
Several studies have shown that the intravenous methylprednisolone dose does not need to be fractionated (i.e., 250 mg every 6 hours) and, thus, 1000 mg/day intravenously in one dose is equally safe and effective. This is how intravenous methylprednisolone is administered routinely in practice currently. In addition, the oral prednisolone tailing after the intravenous dose does not offer additional benefit and, therefore, this is often abandoned in routine practice.[46]Perumal JS, Caon C, Hreha S, et al. Oral prednisone taper following intravenous steroids fails to improve disability or recovery from relapses in multiple sclerosis. Eur J Neurol. 2008 Jul;15(7):677-80.
http://www.ncbi.nlm.nih.gov/pubmed/18459972?tool=bestpractice.com
Studies have shown the non-inferiority of bioequivalent doses of oral corticosteroids.[47]Le Page E, Veillard D, Laplaud DA, et al; COPOUSEP investigators; West Network for Excellence in Neuroscience. Oral versus intravenous high-dose methylprednisolone for treatment of relapses in patients with multiple sclerosis (COPOUSEP): a randomised, controlled, double-blind, non-inferiority trial. Lancet. 2015 Sep 5;386(9997):974-81.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2815%2961137-0/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/26135706?tool=bestpractice.com
[48]Morrow SA, Fraser JA, Day C, et al. Effect of treating acute optic neuritis with bioequivalent oral vs intravenous corticosteroids: a randomized clinical trial. JAMA Neurol. 2018 Jun 1;75(6):690-6.
https://jamanetwork.com/journals/jamaneurology/fullarticle/2673723
http://www.ncbi.nlm.nih.gov/pubmed/29507942?tool=bestpractice.com
Three days of intravenous methylprednisolone are as safe, well-tolerated, and effective as 3 days of oral methylprednisolone, with the latter being more convenient.[47]Le Page E, Veillard D, Laplaud DA, et al; COPOUSEP investigators; West Network for Excellence in Neuroscience. Oral versus intravenous high-dose methylprednisolone for treatment of relapses in patients with multiple sclerosis (COPOUSEP): a randomised, controlled, double-blind, non-inferiority trial. Lancet. 2015 Sep 5;386(9997):974-81.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2815%2961137-0/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/26135706?tool=bestpractice.com
Intravenous methylprednisolone has also been shown to be equally effective to oral high dose prednisolone.[48]Morrow SA, Fraser JA, Day C, et al. Effect of treating acute optic neuritis with bioequivalent oral vs intravenous corticosteroids: a randomized clinical trial. JAMA Neurol. 2018 Jun 1;75(6):690-6.
https://jamanetwork.com/journals/jamaneurology/fullarticle/2673723
http://www.ncbi.nlm.nih.gov/pubmed/29507942?tool=bestpractice.com
The argument is increasingly made for a new corticosteroid treatment trial to reassess treatment of acute ON. It has been recommended that the treatment should be initiated ideally in the first 48 hours of the onset of the symptoms, as it could be sight saving in ON that is not associated with MS (e.g., neuromyelitis optica spectrum disorder [NMOSD], ON associated with systemic lupus erythematosus [SLE]) and that it should be introduced before blood test results are known (e.g., aquaporin-4 or MOG antibodies).[49]Petzold A, Braithwaite T, van Oosten BW, et al. Case for a new corticosteroid treatment trial in optic neuritis: review of updated evidence. J Neurol Neurosurg Psychiatry. 2020 Jan;91(1):9-14.
https://www.doi.org/10.1136/jnnp-2019-321653
http://www.ncbi.nlm.nih.gov/pubmed/31740484?tool=bestpractice.com
In general, gastric irritation is not a problem with this corticosteroid regimen, but protective medications (e.g., proton-pump inhibitors) can be used as appropriate.
Refractory ON
If ON is refractory to corticosteroids, treatment with plasma exchange has been shown to be effective.[3]Petzold A, Fraser CL, Abegg M, et al. Diagnosis and classification of optic neuritis. Lancet Neurol. 2022 Dec;21(12):1120-34.
http://www.ncbi.nlm.nih.gov/pubmed/36179757?tool=bestpractice.com
[30]Sellner J, Boggild M, Clanet M, et al. EFNS guidelines on diagnosis and management of neuromyelitis optica. Eur J Neurol. 2010 Aug;17(8):1019-32.
https://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2010.03066.x
http://www.ncbi.nlm.nih.gov/pubmed/20528913?tool=bestpractice.com
Intravenous immune globulin (IVIG) may be an option, but it has not specifically been evaluated in refractory ON and is rarely used in practice.[30]Sellner J, Boggild M, Clanet M, et al. EFNS guidelines on diagnosis and management of neuromyelitis optica. Eur J Neurol. 2010 Aug;17(8):1019-32.
https://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2010.03066.x
http://www.ncbi.nlm.nih.gov/pubmed/20528913?tool=bestpractice.com
Treatment follow-up
A key part of treatment follow-up is monitoring for atypical features. This includes new neurological symptoms, macular star figure, lack of improvement, and treatment adverse effects.[12]American Academy of Ophthalmology. Optic neuritis - 2012. Jul 2012 [internet publication].
https://www.aao.org/education/clinical-statement/optic-neuritis
ON as part of other inflammatory diseases
When ON is present as a part of NMOSD or myelin oligodendrocyte glycoprotein antibody associated neurological disease (MOGAD) there is continuation of the corticosteroid treatment beyond the acute intravenous treatment, usually in the form of oral prednisolone for several months. In addition, for NMOSD and MOGAD with negative prognostic features (e.g., persistently positive MOG antibodies) a corticosteroid-sparing immunosuppressive agent is introduced (e.g., azathioprine, mycophenolate).
In patients with proven or suspected NMOSD or MOGAD, plasma exchange or IVIG can be introduced in conjunction with oral corticosteroids.[30]Sellner J, Boggild M, Clanet M, et al. EFNS guidelines on diagnosis and management of neuromyelitis optica. Eur J Neurol. 2010 Aug;17(8):1019-32.
https://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2010.03066.x
http://www.ncbi.nlm.nih.gov/pubmed/20528913?tool=bestpractice.com
In patients with NMOSD for an acute or relapse attack, not responding to corticosteroids alone, plasma exchange has shown benefit as an adjunct including promise when initiated early during an attack and in patients taking preventive immunosuppressants.[19]Petzold A, Plant GT. Chronic relapsing inflammatory optic neuropathy: a systematic review of 122 cases reported. J Neurol. 2014 Jan;261(1):17-26.
http://www.ncbi.nlm.nih.gov/pubmed/23700317?tool=bestpractice.com
[50]Srisupa-Olan T, Siritho S, Kittisares K, et al. Beneficial effect of plasma exchange in acute attack of neuromyelitis optica spectrum disorders. Mult Scler Relat Disord. 2018 Feb;20:115-21.
http://www.ncbi.nlm.nih.gov/pubmed/29414283?tool=bestpractice.com
[51]Abboud H, Petrak A, Mealy M, et al. Treatment of acute relapses in neuromyelitis optica: steroids alone versus steroids plus plasma exchange. Mult Scler. 2016 Feb;22(2):185-92.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795457
http://www.ncbi.nlm.nih.gov/pubmed/25921047?tool=bestpractice.com
[52]Bonnan M, Valentino R, Debeugny S, et al. Short delay to initiate plasma exchange is the strongest predictor of outcome in severe attacks of NMO spectrum disorders. J Neurol Neurosurg Psychiatry. 2018 Apr;89(4):346-51.
http://www.ncbi.nlm.nih.gov/pubmed/29030418?tool=bestpractice.com
[53]Kleiter I, Gahlen A, Borisow N, et al. Apheresis therapies for NMOSD attacks: a retrospective study of 207 therapeutic interventions. Neurol Neuroimmunol Neuroinflamm. 2018 Nov;5(6):e504.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192689
http://www.ncbi.nlm.nih.gov/pubmed/30345331?tool=bestpractice.com
[54]Deschamps R, Gueguen A, Parquet N, et al. Plasma exchange response in 34 patients with severe optic neuritis. J Neurol. 2016 May;263(5):883-7.
http://www.ncbi.nlm.nih.gov/pubmed/26964539?tool=bestpractice.com
[55]Mason MC, Marotta DA, Kesserwani H. Steroid-resistant double-seronegative optic neuritis responds favorably to plasma exchange. Cureus. 2021 May 26;13(5):e15260.
https://www.doi.org/10.7759/cureus.15260
http://www.ncbi.nlm.nih.gov/pubmed/34188998?tool=bestpractice.com
[56]Chen JJ, Flanagan EP, Pittock SJ, et al. Visual outcomes following plasma exchange for optic neuritis: an international multicenter retrospective analysis of 395 pptic neuritis attacks. Am J Ophthalmol. 2023 Aug;252:213-24.
https://www.ajo.com/article/S0002-9394(23)00066-1/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/36822570?tool=bestpractice.com
Intravenous immune globulin has also been used for corticosteroid-resistant relapses of ON.[57]Mimura O, Ishikawa H, Kezuka T, et al. Intravenous immunoglobulin treatment for steroid-resistant optic neuritis: a multicenter, double-blind, randomized, controlled phase III study. Jpn J Ophthalmol. 2021 Jan;65(1):122-32.
https://www.doi.org/10.1007/s10384-020-00790-9
http://www.ncbi.nlm.nih.gov/pubmed/33469728?tool=bestpractice.com
Eculizumab (a complement inhibitor) in patients with AQP4-IgG-positive NMOSD has a significantly lower risk of relapse compared with placebo.[58]Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med. 2019 Aug 15;381(7):614-25.
https://www.doi.org/10.1056/NEJMoa1900866
http://www.ncbi.nlm.nih.gov/pubmed/31050279?tool=bestpractice.com
When ON is present as a part of other systemic or central nervous system inflammatory diseases (e.g., SLE, sarcoidosis), the treatment is aimed at the underlying inflammatory disease. This is usually with corticosteroids in various regimens, often including high-dose intravenous or oral corticosteroids for protracted periods of time. Corticosteroid-sparing immunosuppressive treatments (e.g., azathioprine, cyclophosphamide) are often used. When conditions such as sarcoidosis are treated with tumour necrosis factor (TNF) alpha inhibitors (e.g., infliximab), the development of ON may represent a rare complication of treatment rather than a manifestation of sarcoidosis.