Optic neuritis treatment trial steroid taper

We did not conduct subgroup analyses for this review due to insufficient data. Two trials reported subgroup analyses for different outcomes Kapoor Sellebjerg Therefore, we only documented the results from these trials.

If sufficient and comparable data are reported in future updates to this review, we will conduct subgroup analyses.

The electronic searches for the previous published versions of this review were conducted in January and February and yielded and records, respectively. In the most recent electronic searches performed on 7 April , we identified additional titles and abstracts along with 57 records in trial registers Figure 1.

We identified no new trials for inclusion in this updated review. We included six trials in which a total of participants had been randomized. Detailed characteristics of the individual trials are presented in the ' Characteristics of included studies ' table.

Kapoor included only participants with confirmed multiple sclerosis, while the remaining trials included people with optic neuritis of unknown or demyelinating etiologies.

ONMRG enrolled only participants with acute symptoms of unilateral optic neuritis of unknown or demyelinating origin, with relative afferent pupillary defect and a normal or swollen optic disc in the affected eye.

Sellebjerg included participants with optic neuritis and visual acuity of 0. All trials restricted participants to those with a short period since onset of visual symptoms. The six trials had various comparisons. The description of doses of corticosteroids evaluated in each of the trials in the text of this review refers to the total dose administered over the specified treatment period.

The treatment regimens of the individual trials are described in greater detail in the ' Characteristics of included studies ' table. Because of systemic treatment administration in all included trials, randomization was by participant. Investigators of all trials measured and reported visual acuity as an outcome. In all trials, visual field was measured; Sellebjerg did not assess visual field in a systematic manner personal communication with Dr. Menon also reported stereoacuity and visual evoked response as outcomes.

There was variability in the method employed to assess different outcomes as noted in the ' Characteristics of included studies ' table. Menon presented mean values for visual acuity, visual field data not shown in report , and contrast sensitivity instead of defining normal values for each.

Normal contrast sensitivity was defined as greater than 1. Sellebjerg measured contrast sensitivity using Arden gratings and defined normal as less than or equal to 80 points. Kapoor considered normal contrast sensitivity to be greater than 1. We excluded 21 studies, listed in the ' Characteristics of excluded studies ' table with reasons for exclusion. Figure 2 presents a summary of the 'Risk of bias' assessments for the included trials. For nearly half the total number of domains we could not assess risk of bias from available information and designated the risk of bias to be 'unclear'.

Descriptions of our judgments and classifications for each domain are summarized below. Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

We deemed the remaining two trials as having had unclear risk of selection bias due to inadequate reporting of information Kapoor ; ONMRG We assessed two trials at low risk of performance bias and detection bias as participants, personnel, and outcome assessors were masked Menon ; ONMRG Three trials compared oral administration of corticosteroids with no corticosteroids.

Three trials compared intravenous administration of corticosteroids with no corticosteroids. One trial compared intravenous dexamethasone versus intravenous methylprednisolone followed by oral prednisone for 3 days Menon The risk ratio for normal visual acuity at 6 months was 0.

The risk ratio for normal visual acuity at one year was 1. Comparison 1: Oral corticosteroids versus placebo, Outcome 1: Participants with normal visual acuity. At one month, the risk ratio of contrast sensitivity in the normal range was 1.

Among participants in oral corticosteroids group, 87 had contrast sensitivity in normal range, among participants in placebo group, 82 of whom had contrast sensitivity in normal range RR 1.

At one year, the risk ratio for contrast sensitivity in the normal range was 0. Comparison 1: Oral corticosteroids versus placebo, Outcome 2: Participants with contrast sensitivity in the normal range. The risk ratio for normal visual field at six months was 1. At one month, the risk ratio for normal visual field was 1.

At one year, the risk ratio for normal visual field was 0. Comparison 1: Oral corticosteroids versus placebo, Outcome 3: Participants with normal visual field. The proportion of participants experiencing adverse effects of corticosteroid therapy was not consistently reported by all trials, thereby precluding any comparison.

However, no comparative quality of life data by assigned treatment arm were available. Comparison 2: Total intravenous corticosteroid dose more than or equal to mg versus placebo, Outcome 1: Participants with normal visual acuity at 6 months.

Comparison 2: Total intravenous corticosteroid dose more than or equal to mg versus placebo, Outcome 2: Participants with contrast sensitivity in the normal range sensitivity at 1 month.

Comparison 2: Total intravenous corticosteroid dose more than or equal to mg versus placebo, Outcome 3: Participants with contrast sensitivity in the normal range at 6 months. Comparison 2: Total intravenous corticosteroid dose more than or equal to mg versus placebo, Outcome 4: Participants with contrast sensitivity in the normal range at 1 year. At one year the pooled risk ratio of normal visual field was 1. Comparison 2: Total intravenous corticosteroid dose more than or equal to mg versus placebo, Outcome 5: Participants with normal visual field at 1 month.

Comparison 2: Total intravenous corticosteroid dose more than or equal to mg versus placebo, Outcome 6: Participants with normal visual field at 6 months. Comparison 2: Total intravenous corticosteroid dose more than or equal to mg versus placebo, Outcome 7: Participants with normal visual field at 1 year.

Adverse events were not reported in Kapoor In ONMRG , hyperglycemia was noted in four participants; constipation, diarrhea, acneiform eruption and hyperlipidemia were reported for two participants; headache and increasing fever were reported for one participant, and transient diarrhea was reported by two participants. Only one trial provided data for this comparison Menon The difference was not statistically significant but favored methylprednisolone group. Limited data were available from Menon regarding visual field outcomes.

Of the two participants in the methylprednisolone group who provided data on visual fields, both had a central scotoma observed in the pretreatment visual field assessment. Four participants were determined to have a central scotoma among the six participants in the dexamethasone group who underwent the pretreatment visual field assessment.

In Menon , six participants were reported to have experienced generalized weakness, one participant had sleep disturbance and weight gain, two participants experienced depression and five participants suffered gastric irritation. Quality of life was not assessed and reported in Menon Acute demyelinating optic neuritis is a common form of optic neuritis, with inflammation of the optic nerve that often is associated with multiple sclerosis.

Optic neuritis is the initial manifestation of multiple sclerosis in some people Kurtzke In this systematic review performed to evaluate the effects of corticosteroid therapy in participants with optic neuritis, we included six randomized controlled trials.

However, ONTT participants treated with oral corticosteroids had a higher rate of new episodes of optic neuritis compared with those in the placebo arm. The pooled risk ratio indicated a statistically significant benefit with respect to achieving a normal visual field at one month for participants treated with intravenous corticosteroids.

Finally, there was no evidence of benefit when intravenous corticosteroids were compared to intravenous followed by oral corticosteroids for the visual acuity and contrast sensitivity outcomes Menon The trials evaluating oral corticosteroids were very heterogeneous in dose of medication, method of corticosteroid delivery, and comparison group.

Oral corticosteroids, however, resulted in statistically significantly fewer ONTT participants who had achieved normal visual acuity by one year compared with the placebo group and was consistent with our review findings. Our review has included no comparison of outcomes between higher and lower doses of corticosteroids.

Adverse effects were inconsistently reported; comparisons of different management strategies were not possible. Therefore, the effectiveness and safety of corticosteroids in treating optic neuritis was not supported by the currently available evidence. Random sequence generation and allocation concealment before randomization were implemented in only two of the six included trials.

Masking of participants, personnel, and outcome assessors was achieved in only two trials. Complete or nearly complete outcome data were reported from four trials.

Only one trial was considered to be at high risk of selective outcome reporting bias. In addition, one trial was judged to have high risk of bias because a subgroup of participants was allowed to select their treatment; four trials were judged to be unclear risk of other bias due to source of funding to conduct the trial.

We are unaware of any potential biases in the review process. We searched multiple databases to identify six RCTs relevant to this review. Data extracted from the trials focused on clinical and functional outcomes and were confirmed by at least two authors.

Thus, the findings regarding the effectiveness of corticosteroids on treating optic neuritis is based on established, reproducible methods. Inadequate reporting of adverse events may have led to underestimation of such outcomes.

Another review on optic neuritis diagnosis and treatment explained corticosteroid treatment in much the same manner, reporting that treatment with corticosteroids hastens recovery but does not affect the final outcome Toosy There was no conclusive treatment benefit with return to normal visual acuity, visual field or contrast sensitivity with either intravenous or oral corticosteroids at the doses evaluated by trials included in this review.

Either no treatment or treatment with intravenous corticosteroid therapy followed by oral corticosteroids is appropriate; intravenous corticosteroids may benefit the patient in terms of faster recovery to normal vision. Among participant cohorts evaluated as part of this review, there was no conclusive treatment benefit with return to normal visual function measures within one year as the outcome of interest.

Future research efforts could focus on the identification of participant subgroups who are predisposed to have permanent visual deficits and would benefit from therapy that could reduce neural damage. The trial database included a total number of participants enrolled in the six trials. Future trials evaluating the role of high dose oral corticosteroids greater than mg as a treatment option for optic neuritis may be warranted.

Protocol first published: Issue 1, Review first published: Issue 1, Randomized Controlled Trial. Controlled Clinical Trial. Cochrane methodology regarding assessments of the risk of bias in included studies have been modified and the review authors updated the 'Assessment of risk of bias in included studies' section of the methods to reflect updated methodological considerations.

National Center for Biotechnology Information , U. Cochrane Database Syst Rev. Published online Aug Author information Copyright and License information Disclaimer. Corresponding author. This article is an update of " Corticosteroids for treating optic neuritis " in volume 4 on page CD This article has been cited by other articles in PMC.

Notes Editorial note This review is out of date as the current understanding of the disease has broadened the diagnostic criteria and there are newer treatments available that should now be reviewed. Abstract Background Optic neuritis is an inflammatory disease of the optic nerve. Objectives The objective of this review was to assess the effects of corticosteroids on visual recovery in eyes with acute optic neuritis.

Selection criteria We included randomized controlled trials RCTs that evaluated systemic corticosteroids, in any form, dose or route of administration, in people with acute optic neuritis. Data collection and analysis We used standard methodological procedures expected by Cochrane.

Main results We included six RCTs with a total of participants. Authors' conclusions There is no conclusive evidence of benefit in terms of recovery to normal visual acuity, visual field or contrast sensitivity six months after initiation with either intravenous or oral corticosteroids at the doses evaluated in trials included in this review.

Plain language summary Corticosteroids for treating optic neuritis Review question We reviewed the evidence about the effects of corticosteroids on visual recovery of people with acute optic neuritis.

Background Description of the condition Optic neuritis is an inflammatory disease of the optic nerve. How the intervention might work By controlling the inflammation associated with optic neuritis, it is believed that visual recovery may be quicker, permanent damage to the optic nerve may be prevented, or both. Methods Criteria for considering studies for this review Types of studies This review included only randomized controlled trials RCTs.

Types of participants We included trials in which the participants had acute optic neuritis. Types of interventions We included trials in which systemic corticosteroid therapy was administered in any form or dosage with the intention to treat or reduce the symptoms of acute optic neuritis and compared with placebo, sham, no treatment, or types of corticosteroid administered via the same route.

Secondary outcomes Secondary outcomes comparison of interventions were immediate response rate of recovery measured as: 1 Proportion of participants with normal visual acuity at one month; 2 Proportion of participants with contrast sensitivity in the normal range at one month; 3 Proportion of participants with normal visual field at one month.

Searching other resources We searched the reference lists of identified trial reports to find additional trials and used the Science Citation Index to find studies that may have cited the identified trials. Data collection and analysis Selection of studies Two review authors independently assessed the titles and abstracts of all records identified by the electronic and other searches. Data extraction and management Two review authors independently extracted data on study characteristics, such as methods, details of participants, interventions, outcomes, and other relevant information.

Assessment of risk of bias in included studies Two review authors, unmasked to the trial lists, institutions and trial results, assessed included trials for risk of bias in several domains of potential bias according to methods set out in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions Higgins Unit of analysis issues The unit of analysis was the individual participant for all outcomes.

Dealing with missing data We contacted the primary investigators of included trials to obtain data not reported for some participants. Assessment of heterogeneity We assessed clinical and methodological heterogeneity by examining potential variations in participant characteristics, interventions compared, and assessments of primary and secondary outcomes among included trials.

Subgroup analysis and investigation of heterogeneity We did not conduct subgroup analyses for this review due to insufficient data. Results Description of studies Results of the search The electronic searches for the previous published versions of this review were conducted in January and February and yielded and records, respectively.

Open in a separate window. Included studies We included six trials in which a total of participants had been randomized. Types of interventions The six trials had various comparisons. Types of outcomes Investigators of all trials measured and reported visual acuity as an outcome.

Excluded studies We excluded 21 studies, listed in the ' Characteristics of excluded studies ' table with reasons for exclusion. Risk of bias in included studies Figure 2 presents a summary of the 'Risk of bias' assessments for the included trials. Masking performance bias and detection bias We assessed two trials at low risk of performance bias and detection bias as participants, personnel, and outcome assessors were masked Menon ; ONMRG Four of the trial's major findings—the prevalence of fellow eye abnormalities, types of visual field defects, adverse effects of oral corticosteroid treatment, 6 and delay in onset of MS in patients treated with intravenous corticosteroids—were all unanticipated.

Though still controversial, each of these findings has altered our approach to patients with this disorder, provoked much debate, and spawned important subsequent investigations.

The findings of the ONTT, reported in more than 50 publications during the past 20 years, have numerous implications. Although the debate continues over the use of intravenous steroids in the management of acute optic neuritis to modify short-term risk of MS in patients with high-risk magnetic resonance imaging MRI results, there are other important evidence-based conclusions that make the ONTT legacy indisputable.

As a result of the ONTT:. The risk of subsequent MS development can now be reliably estimated and MRI is firmly established as the single most important predictor of risk of developing MS. A low-risk profile normal MRI results in men with poor vision, severe disc swelling, and no pain for subsequent MS development was identified. There is an enormous body of data vision deficits, MRI findings, spinal fluid analysis, neurologic disability, and vision-related quality of life issues characterizing the clinical profile of optic neuritis obtained from analysis of carefully characterized and studied patients.

Computerized threshold perimetry and its analysis were rigorously tested and used to characterize optic nerve dysfunction. Radiologic and laboratory testing of patients with optic neuritis to secure a diagnosis was shown to be unnecessary. Intravenous corticosteroid treatment was shown to be safe and to be associated with minimal adverse effects in this patient group.

Novel electronic methods of data sharing and remote monitoring of clinical trials were established. More evidence-based information concerning the relationship of optic neuritis and MS is available for patients and physicians to discuss.

Fellow eye abnormalities and the possibility of simultaneous bilateral or occult demyelinating disease involving the prechiasmatic and retrochiasmatic pathways were confirmed. Contrast sensitivity and vision testing in general became commonplace and important outcome measures in many MS treatment trials.

Neurologic disability in patients who developed MS after optic neuritis was determined to be mild. An important subset of patients more apt to have permanent visual impairment with more severe initial vision loss was identified as a target group for future clinical trials, perhaps using neuroprotective drugs, myelin restoring compounds, or both.

The ONTT studied patients first seen within 8 days of symptom onset with unilateral vision loss in an eye that had not had optic neuritis. Allowing for differences in study design and patient inclusion criteria, the patients enrolled in ONTT were comparable with those enrolled in other large studies of patients with monosymptomatic demyelinating events. The primary goal was to determine whether oral or intravenous steroids altered the visual outcome in patients with acute optic neuritis.

It would seem that ONTT definitively answered the question. Steroids, if given intravenously, accelerated the recovery of vision, but after 1 month there was no significant difference in visual acuity, visual fields, color vision, or contrast sensitivity. Similar findings have been reported in other studies specifically looking prospectively at the treatment of optic neuritis.

For instance, Kapoor et al 12 also demonstrated no long-term benefit of intravenous corticosteroids, and Sellebjerg et al 13 demonstrated an accelerated rate of recovery in patients treated with a high dose of oral steroids, but there was once again no long-term benefit. A Japanese prospective study 15 showed faster recovery of visual acuity among patients receiving intravenous corticosteroids but no long-term effect on visual outcome.

Other early studies, by Rawson et al, 16 , 17 demonstrated accelerated recovery in patients treated with intravenous corticotropin but no long-term difference compared with placebo, a finding that was also reported by Bowden et al.

Although debate has continued since ONTT reported its findings and other literature reviews and meta-analysis have been performed, 19 - 21 most continue to agree that there is no role for oral steroids in the acute management of optic neuritis.

Oral steroids in standard doses had no effect on the rapidity of recovery and were associated with a higher recurrence rate, making them contraindicated in patients with acute optic neuritis, 22 a recommendation that has been widely adopted.

The ONTT data did not answer why increased rates of optic neuritis recurrence a presumed indicator of demyelinating disease activity were not associated with increased rates of MS development. This result has been questioned and may have been influenced by reanalysis bias introduced when the authors focused their attention on this unexpected tertiary outcome, which the trial was not designed to study.

Objective: To determine the efficacy of corticosteroids as treatment for acute demyelinative optic neuritis after completion of 1 year of patient follow-up in the Optic Neuritis Treatment Trial. Design: Randomized placebo controlled multicenter clinical trial. Setting: Fifteen university or hospital-based centers throughout the United States. To determine the natural history of vision in patients who suffer optic neuritis.

To identify risk factors for the development of multiple sclerosis in patients with optic neuritis. Optic neuritis is an inflammatory disease of the optic nerve that typically affects young adults. Women are affected more often than men.

It is second only to glaucoma as the most common acquired optic nerve disorder in persons younger than age In this disorder, closely linked to multiple sclerosis, prognosis for visual recovery is generally good. However, return of visual function is almost never complete.

After resolution of optic neuritis, virtually all patients show some signs of optic nerve damage, and most are symptomatic. Although corticosteroids had been used to treat this disease, studies to demonstrate their effectiveness had not been satisfactory. Some experts advocated treatment with oral prednisone while others recommended no treatment. Anecdotal reports suggested that high-dose intravenous corticosteroids might be effective.

The association between optic neuritis and multiple sclerosis is well established. Optic neuritis may be the first manifestation of multiple sclerosis, or it may occur later in its course. A strong case can be made for "isolated" optic neuritis being a forme fruste of multiple sclerosis, based on similarities between the two in such epidemiologic factors as gender, age, geographic distributions, cerebrospinal fluid changes, histocompatibility data, magnetic resonance imaging MRI changes, and family history.

The magnitude of the risk of multiple sclerosis after optic neuritis is uncertain. Previous studies have reported very disparate results, with the risk being reported to be as low as 13 percent and as high as 88 percent.

The importance of risk factors such as age, gender, and MRI changes in predicting which patients with optic neuritis are most likely to develop multiple sclerosis also is unclear. The study is being conducted at 15 clinical centers in the United States. Resource centers include a data coordinating center and a visual field reading center. Patients were randomized to one of the three following treatment groups at 15 clinical centers:. Each regimen was followed by a short oral taper.

The oral prednisone and placebo groups were double masked, whereas the intravenous methylprednisolone group was single masked. Baseline testing included blood tests to evaluate for syphilis and systemic lupus erythematosus, a chest x-ray to evaluate for sarcoidosis, and a brain MRI scan to evaluate for changes suggestive of multiple sclerosis. The rate of visual recovery and the long-term visual outcome were both assessed by measures of visual acuity, contrast sensitivity, color vision, and visual field at baseline, at seven followup visits during the first 6 months, and then yearly.

A standardized neurologic examination with an assessment of multiple sclerosis status was made at baseline, after 6 months, and then yearly. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below.