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
Optic neuritis is inflammation of the optic nerve leading to sudden loss of vision that takes place over the course of several hours or days. The optic nerve, which enters the back of the eye, carries visual information from the eye to the brain. When the optic nerve becomes inflamed, damage may occur. Thus information from the eye to the brain is interrupted, resulting in temporary or permanent vision loss. Optic neuritis is closely linked to multiple sclerosis (MS), an inflammatory disease that affects nerve cells generally. Corticosteroids have been widely used in the treatment of optic neuritis due to their anti-inflammatory effects.

Study characteristics
For this systematic review, we identified six trials conducted in Denmark, Germany, India, Japan, United Kingdom, and United States, which included 750 participants. These trials compared corticosteroid treatment with placebo or another treatment; they varied in the way corticosteroids were given and the dose. Two trials compared oral corticosteroids versus placebo; three trials compared intravenous corticosteroids versus placebo; one trial compared two types of intravenous corticosteroids; and one trial with three groups compared oral corticosteroids versus intravenous corticosteroids versus placebo. Participants in all six trials were followed up for at least three months. Outcomes of visual acuity, contrast sensitivity in the normal range and visual field were assessed at 1, 6, and 12 months. Quality of life also was assessed and reported in one trial. The information is current as of 7 April 2015.

Key results
There was no available evidence of beneficial effect from oral or intravenous corticosteroids compared with placebo for the visual acuity, visual field, and contrast sensitivity outcomes. Adverse effects, although not consistently reported, included dermatological symptoms, endocrinological disorders, gastrointestinal problems, headache, fever, sleep disturbance and psychiatric problems. Severe adverse events were reported in the intravenous steroid treatment group of one trial. The investigators of three trials concluded that minor adverse events were more common in steroid groups than in the placebo group.

Quality of the evidence
Out of six trials included in this review, we assessed one trial to have high risk of bias due to including a subset of participants who were allowed to choose their intervention. The remaining five trials were of either low or uncertain risk of biases.

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.

Read the full abstract...
Background: 

Optic neuritis is an inflammatory disease of the optic nerve. It usually presents with an abrupt loss of vision and recovery of vision is almost never complete. It occurs more commonly in women than in men. Closely linked in pathogenesis, optic neuritis may be the initial manifestation for multiple sclerosis. In some people, no underlying cause can be found.

Objectives: 

The objective of this review was to assess the effects of corticosteroids on visual recovery in eyes with acute optic neuritis.

Search strategy: 

We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2015, Issue 4), MEDLINE (January 1950 to April 2015), EMBASE (January 1980 to April 2015), Latin American and Caribbean Health Sciences Literature (LILACS) (January 1982 to April 2015), PubMed (January 1946 to April 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The metaRegister of Controlled Trials (mRCT) was last searched on 6 March 2014. The electronic databases were last searched on 7 April 2015. We also searched reference lists of identified trial reports for additional trials.

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 750 participants. Each trial was conducted in a different country: Denmark, Germany, India, Japan, UK, and United States. Additionally, we identified two ongoing trials not due to be completed until 2016. Among the six trials included in this review, we judged one to be at high risk of bias. The remaining five trials were judged to be at either low or uncertain risk of biases.

Five trials compared only two intervention groups and one trial had a three-arm comparison of oral corticosteroids or intravenous corticosteroids with placebo. Of the five trials with only two intervention groups, two trials compared oral corticosteroids versus placebo, two trials compared intravenous corticosteroids with placebo, and one trial compared intravenous dexamethasone with intravenous methylprednisolone plus oral prednisolone.

Three trials evaluating oral corticosteroids used varying doses of corticosteroids versus placebo. In the meta-analyses to assess visual acuity, the risk ratio (RR) was 1.00 (95% confidence interval (CI) 0.82 to 1.23; participants = 398) at one month; 0.92 (95% CI 0.77 to 1.11; participants = 355) at six months; and 0.93 (95% CI 0.70 to 1.24; participants = 368) at one year. In the meta-analyses of two trials evaluating corticosteroids with total dose greater than 3000 mg administered intravenously, the RR of normal visual acuity (defined as 20/20 Snellen fraction or equivalent) in the intravenous corticosteroids group compared with the placebo group was 1.05 (95% CI 0.88 to 1.26; participants = 346) at six months. The RR of contrast sensitivity in the normal range for the same comparison was 1.11 (95% CI 0.92 to 1.33; participants = 346) at six months follow-up. The RR of normal visual field for this comparison was 1.08 (95% CI 0.96 to 1.21; 346 participants) at six months; and 1.01 (95% CI 0.86 to 1.19; participants = 316) at one year. Four trials reported adverse events primarily related to gastrointestinal symptoms and sleep disturbance; one trial reported minor adverse event of acne.

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