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    Commentary: The Optic Neuritis Treatment Trial

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    Emmanuel Zótico Orellana Jiménez
    The Optic Neuritis Treatment Trial (ONTT) studied the effects of different corticosteroid regimens on recovery from optic neuritis. It found that intravenous methylprednisolone followed by oral prednisone led to faster visual recovery than oral prednisone or placebo, but did not affect long-term visual outcomes. Patients treated with oral prednisone alone were more likely to experience recurrent optic neuritis. The ONTT demonstrated that oral corticosteroid treatment was not effective and changed clinical practice worldwide.

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    Commentary: The Optic Neuritis Treatment Trial

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    Emmanuel Zótico Orellana Jiménez
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    The Optic Neuritis Treatment Trial (ONTT) studied the effects of different corticosteroid regimens on recovery from optic neuritis. It found that intravenous methylprednisolone followed by oral prednisone led to faster visual recovery than oral prednisone or placebo, but did not affect long-term visual outcomes. Patients treated with oral prednisone alone were more likely to experience recurrent optic neuritis. The ONTT demonstrated that oral corticosteroid treatment was not effective and changed clinical practice worldwide.

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    The Optic Neuritis Treatment Trial (ONTT) studied the effects of different corticosteroid regimens on recovery from optic neuritis. It found that intravenous methylprednisolone followed by oral prednisone led to faster visual recovery than oral prednisone or placebo, but did not affect long-term visual outcomes. Patients treated with oral prednisone alone were more likely to experience recurrent optic neuritis. The ONTT demonstrated that oral corticosteroid treatment was not effective and changed clinical practice worldwide.

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    15 views2 pages

    Commentary: The Optic Neuritis Treatment Trial

    Uploaded by

    Emmanuel Zótico Orellana Jiménez
    The Optic Neuritis Treatment Trial (ONTT) studied the effects of different corticosteroid regimens on recovery from optic neuritis. It found that intravenous methylprednisolone followed by oral prednisone led to faster visual recovery than oral prednisone or placebo, but did not affect long-term visual outcomes. Patients treated with oral prednisone alone were more likely to experience recurrent optic neuritis. The ONTT demonstrated that oral corticosteroid treatment was not effective and changed clinical practice worldwide.

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    Commentary

    The Optic Neuritis Treatment Trial


    Nancy J. Newman, MD - Atlanta, Georgia

    Optic neuritis has been recognized for centuries, as has its recovery within the first 2 weeks after onset, with most
    relationship with multiple sclerosis (MS) and its frequent recovery by the end of 1 month and further slow recovery
    role as a harbinger of that disease. Treatment of optic over several months, even up to 1 year. Lack of at least 1
    neuritis with corticosteroids was commonplace beginning line of visual acuity improvement with the first 3 weeks
    with the introduction of these drugs into clinical practice after onset should be considered atypical.
    in the 1950s. A 1986 United States survey of ophthal- The ONTT also found that among the 389 patients
    mologists and neurologists revealed that 65% of ophthal- without a diagnosis of clinically probable or definite MS at
    mologists and 90% of neurologists treated their optic study entry, the intravenous steroid group showed a lower
    neuritis patients with corticosteroids, 90% of the time in rate of development of clinically definite MS within the first
    oral standard dosing, despite a dearth of prior evidence 2 years (7.5%) than did the placebo (16.7%) or prednisone
    demonstrating efficacy.1 (14.7%) groups.2 Most of this beneficial effect was
    The Optic Neuritis Treatment Trial (ONTT) was the first manifested in those patients who showed abnormal
    multicenter collaborative clinical trial in neuro- baseline magnetic resonance imaging (MRI) results
    ophthalmology to be funded by the National Eye Institute suggestive of demyelinating lesions, but this apparent
    of the National Institutes of Health.2 From 1988 to 1991, 15 protective effect was not sustained at 3 years. Abnormal
    United States clinical centers randomized 457 acute optic baseline MRI results showing 1 or more typical
    neuritis patients within 8 days of onset to treatment with demyelinating lesions proved to be the strongest predictive
    oral prednisone (1 mg/kg daily for 14 days), intravenous factor for the development of clinical MS over the
    methylprednisolone (250 mg every 6 hours for 3 days) ensuing 15 years (approximately 72% risk). Among optic
    followed by oral prednisone (1 mg/kg daily for 11 days), neuritis patients with normal baseline brain MRI results, 5
    or oral placebo.1,2 features were identified that signified 0 risk of MS: no
    The mean age of patients was 32 years, 77% of patients light perception vision, no pain, severe optic disc edema,
    were women, and 85% of patients identified as white. At 6 hemorrhagic optic disc edema, and retinal exudates.2
    months, patients in all 3 treatment groups showed good The impact of the ONTT on clinical practice was felt
    recovery of vision, with a median visual acuity in each even before its first publication. On January 21, 1992, a
    group of 20/16 and less than 10% of patients with a visual clinical alert from the National Eye Institute was sent to all
    acuity of 20/50 or worse. Patients treated with the intrave- ophthalmologists and neurologists informing them of the
    nous steroid regimen recovered vision faster than those in lack of efficacy and the increased risk of optic neuritis
    the other groups, although the difference among the 3 recurrence with standard oral dosing of prednisone. The
    groups by 30 days was insignificant. Patients treated with message in all subsequent publications was loud and clear:
    oral prednisone alone were approximately twice as likely to oral prednisone treatment at conventional dosing of 1 mg/kg
    experience recurrent optic neuritis than patients in the daily should be abandoned. As to the use of intravenous
    intravenous and placebo groups (30% vs. 14% and 16%, methylprednisolone, practitioners were counseled in many
    respectively).1,2 publications in ophthalmology and neurology journals that
    A 1994 publication in Ophthalmology (see page S174) use of this regimen could hasten recovery (on average by
    reported the time course of visual recovery over the first 6 approximately 2 weeks), but would not affect ultimate
    months after acute optic neuritis.3 In almost all patients, visual outcome and temporarily could reduce the risk of MS
    regardless of treatment group and initial severity of visual in those patients at high risk for the disease as established by
    loss, some improvement began within the first 30 days. brain MRI results.2 In a 1999 random sample survey of
    Among the 278 patients with baseline visual acuity of 20/ ophthalmologists and neurologists practicing in the United
    50 or worse, all patients improved by at least 1 line of States, nearly all practitioners (90% of ophthalmologists
    visual acuity, and all but 6 patients improved at least 3 and 95% of neurologists) had reduced their use of oral
    lines by 6 months. Although baseline visual acuity was prednisone alone, substituting a regimen that included
    the best predictor of the 6-month visual acuity outcome, intravenous methylprednisolone (especially among
    even among those patients with severe visual loss of neurologists).4 However, a large proportion of clinicians,
    counting fingers or worse, visual recovery to 20/40 or both ophthalmologists and neurologists, mistakenly
    better occurred in 81.8% of patients. The findings believed that the use of intravenous steroids was to
    emphasized that the expected course of visual function improve final visual outcomes. More recent international
    after a treated or untreated episode of optic neuritis is surveys reported similar findings, although the use of

    S172 ª 2020 by the American Academy of Ophthalmology https://doi.org/10.1016/j.ophtha.2019.09.046


    Published by Elsevier Inc. ISSN 0161-6420/20
    Commentary

    conventional-dose oral prednisone persists in some References


    countries.5
    Neuro-ophthalmologists still fondly refer to the ONTT
    as the “clinical trial that keeps on giving.” Not only did it 1. Beck RW, Cleary PA, Anderson Jr MM, et al. A randomized,
    controlled trial of corticosteroids in the treatment of acute optic
    teach us about the effects of treatment with 2 different neuritis. N Engl J Med. 1992;326:581e588.
    corticosteroid regimens, but it provided invaluable infor- 2. Beck RW, Gal RL. Treatment of acute optic neuritis. A sum-
    mation on the clinical characteristics of a large cohort of mary of findings from the Optic Neuritis Treatment Trial. Arch
    acute optic neuritis patients, the natural history of the Ophthalmol. 2008;126:994e995.
    disorder, and the relationship of the presenting clinical and 3. Beck RW, Cleary PA, Backlund JC, Optic Neuritis Study
    paraclinical features of optic neuritis patients to their Group. The course of visual recovery after optic neuritis.
    subsequent risk of MS. Appreciating the expected course Experience of the Optic Neuritis Treatment Trial. Ophthal-
    of visual recovery after typical acute optic neuritis helps mology. 1994;101:1771e1778.
    the clinician to recognize atypical cases promptly, such as 4. Trobe JD, Sieving PC, Guire KE, Fendrick AM. The impact of the
    those that result from antibodies against aquaporin-4 or Optic Neuritis Treatment Trial on the practices of ophthalmolo-
    gists and neurologists. Ophthalmology. 1999;106:2047e2053.
    myelin oligodendrocyte glycoprotein, which likely require 5. Biousse V, Calvetti O, Drew-Botsch CD, et al. Management of
    different management.6 The ONTT has changed the optic neuritis and impact of clinical trials: an international sur-
    practice patterns of ophthalmologists and neurologists vey. J Neurol Sci. 2009;276:69e74.
    worldwide and bettered the care of millions of patients 6. Horton L, Bennett JL. Acute management of optic neuritis: an
    with optic neuritis. evolving paradigm. J Neuroophthalmol. 2018;38:358e367.

    Footnotes and Financial Disclosures


    Financial Disclosure(s): The author(s) have made the following disclo- Correspondence:
    sure(s): N.J.N.: Consultant e GenSight, Santhera, Stealth; Data safety and Nancy J. Newman, MD, Departments of Ophthalmology, Neurology and
    monitoring board e Quark. Neurological Surgery, Emory University School of Medicine, 1365-B
    Clifton Road NE, Atlanta, GA 30322. E-mail: [email protected].

    S173

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