Corticosteroids for treating optic neuritis
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
The objective of this review is to assess the effects of corticosteroids on visual recovery and the neurologic course of patients with acute optic neuritis.
Background
Epidemiology
Optic neuritis is an inflammatory disease of the optic nerve. It is second only to glaucoma as the most common acquired optic nerve disorder in persons under 50 years. The majority of patients with optic neuritis are between the ages of 20 and 50 years, with a mean age around 30 to 35 years. In population‐based studies, the annual incidence of optic neuritis in the US has been estimated to be between one and 5/100,000 (Beck 1998). Koch‐Henriksen and Hyllested reported an annual incidence of 4 to 5/100,000 for new onset optic neuritis cases in Denmark in 1948 to 1964 (Koch‐Henriksen 1988). In Olmstead County, Minnesota, USA the prevalence rate of optic neuritis was estimated as 115/100,000 (Rodriguez 1995). Women are more likely to be affected than men. Optic neuritis is closely linked to multiple sclerosis (MS) and in most cases has a similar pathogenesis. It may be the first manifestation of multiple sclerosis or occur later in its course (Ebers 1985).
Presentation and diagnosis
The presenting symptom is usually abrupt visual loss in one eye over several hours or days, usually accompanied by mild pain. A clinical diagnosis of optic neuritis may be made based on the following: age between 18 and 45 years, sudden visual loss with progression for less than one week, pain on eye movement, no inflammation in the vitreous or anterior chamber, and improvement in vision that begins within three to four weeks. The prognosis for visual recovery after acute optic neuritis is generally good. However, return of visual function is almost never complete. After resolution of acute optic neuritis, virtually all patients show some signs of optic nerve damage, and most are symptomatic. Even when a patient's visual acuity does return to normal, abnormalities frequently remain in other measures such as contrast sensitivity, color vision, and visual field (Sanders 1986; Fleishman 1987).
Treatment options
Although corticosteroids have been used since the early 1950s to treat acute optic neuritis because of their anti‐inflammatory effects, studies to demonstrate their effectiveness had not been satisfactory. Some experts advocated treatment with oral prednisone while others recommended no treatment. In the 1980s, anecdotal reports suggested that high‐dose intravenous corticosteroids might be effective (Spoor 1988). In 1992, the National Eye Institute of the US National Institutes of Health funded a randomized controlled trial to test the efficacy of corticosteroids in the treatment of optic neuritis (ONTT 1992). Based on results of this trial, the current guidelines in the United States suggest either administration of high‐dose intravenous methylprednisolone to hasten recovery of vision or no treatment. There are no other treatments with regard to recovery of vision in acute optic neuritis. Beta interferons have been recently assessed for their value in reducing the progression rate to multiple sclerosis but this is not part of the scope of this review.
Rationale for a systematic review
Prior to the Optic Neuritis Treatment Trial (ONTT 1992) well‐established guidelines for treating optic neuritis did not exist. Brusaferri and Candelise (Brusaferri 2000) published a meta‐analysis of steroids for multiple sclerosis and optic neuritis in 2000, but their manuscript differed from the proposed systematic review on the inclusion criteria for participants and treatment type. We propose to systematically review the evidence for the use of corticosteroid therapy (in any form or dosage with the intention to treat or reduce the symptoms) for acute optic neuritis compared with placebo or no treatment.
Objectives
The objective of this review is to assess the effects of corticosteroids on visual recovery and the neurologic course of patients with acute optic neuritis.
Methods
Criteria for considering studies for this review
Types of studies
This review will include only randomized controlled trials.
Types of participants
We will include trials in which the participants were men and women with acute optic neuritis. There will be no age limitations.
Types of interventions
We will include trials in which the administration of corticosteroid therapy in any form or dosage with the intention to treat or reduce the symptoms of acute optic neuritis has been compared to placebo, no treatment or other treatment. There will be no minimum or maximum limit on the duration of treatment.
Types of outcome measures
The primary outcomes for this review will be visual outcome measured as:
(1) number of people with normal visual acuity at six months or more,
(2) number of people with normal contrast sensitivity at six months or more,
(3) number of people with normal visual field at six months or more.
Secondary outcomes will be immediate response (rate of recovery) measured as:
(1) number of people with normal visual acuity at one month,
(2) number of people with normal contrast sensitivity at one month,
(3) number of people with normal visual field at one month.
Adverse outcomes related to treatment with corticosteroids will be summarized. When available, data on quality of life will be described.
Search methods for identification of studies
Electronic Searches
Trials will be identified from the Cochrane Controlled Trials Register ‐ CENTRAL/CCTR (which contains the Cochrane Eyes and Vision Group specialised register) in the Cochrane Library, MEDLINE, EMBASE and LILACS (Latin American and Caribbean Literature on Health Sciences).
The following strategy will be used to search CENTRAL:
#1 OPTIC‐NEURITIS*:ME
#2 (OPTIC next NEURITIS)
#3 (RETROBULBAR next NEURITIS)
#4 ((#1 or #2) or #3)
The following strategy will be used to search MEDLINE on SilverPlatter:
#1 explode "OPTIC‐NEURITIS"/ all subheadings
#2 (OPTIC or RETROBUL*) near NEURITIS
#3 #2 in TI,AB
#4 #1 or #3
#5 explode "ADRENAL‐CORTEX‐HORMONES"/ all subheadings
#6 explode "GLUCOCORTICOIDS,‐SYNTHETIC"/ all subheadings
#7 (CORTI?COSTEROID* or GLUCO?CORTICOID* or TRIAMCINOLONE or PREDNISONE or METHYL?PREDNISOLONE or PREDNISOLONE) in TI,AB
#8 #5 or #6 or #7
#9 #4 and #8
To identify randomized controlled trials, this search will be combined with the Cochrane Highly Sensitive Search Strategy phases one and two as contained in the Cochrane Reviewers' Handbook (Clarke 2001).
The following strategy will be used to search EMBASE on SilverPlatter:
#1 explode "OPTIC‐NERVE‐DISEASE"/ all subheadings
#2 (OPTIC or RETROBUL*) near NEURITIS
#3 #2 in TI,AB
#4 #1 or #3
#5 explode "CORTICOSTEROID"/ all subheadings
#6 explode "GLUCOCORTICOID"/ all subheadings
#7 CORTI?COSTEROID* or GLUCO?CORTICOID* or PREDNISONE or PREDNISOLONE or METHYL?PREDNISOLONE or TRIAMCINOLONE
#8 #5 or #6 or #7
#9 #4 and #8
To identify randomized controlled trials, this search will be combined with the following search:
#1 "RANDOMIZED‐CONTROLLED‐TRIAL"/ all subheadings
#2 "RANDOMIZATION"/ all subheadings
#3 "CONTROLLED‐STUDY"/ all subheadings
#4 "MULTICENTER‐STUDY"/ all subheadings
#5 "PHASE‐3‐CLINICAL‐TRIAL"/ all subheadings
#6 "PHASE‐4‐CLINICAL‐TRIAL"/ all subheadings
#7 "DOUBLE‐BLIND‐PROCEDURE"/ all subheadings
#8 "SINGLE‐BLIND‐PROCEDURE"/ all subheadings
#9 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8
#10 RANDOM* or CROSS?OVER* or FACTORIAL* or PLACEBO* or VOLUNTEER* in TI,AB
#11 (SINGL* or DOUBL* or TREBL* or TRIPL*) near (BLIND* or MASK*) in TI,AB
#12 #9 or #10 or #11
#13 HUMAN in DER
#14 (ANIMAL or NONHUMAN) in DER
#15 #13 and #14
#16 #14 not #15
#17 #12 not #16
LILACS will be searched using the terms (optic or retrobul$) and neuritis.
Manual Searches
Reference lists of identified trial reports will be searched to find additional trials. The Science Citation Index will be used to find studies that have cited the identified trials. Investigators will be contacted to identify additional published and unpublished studies. Manual searches of conference proceeding abstracts will not be conducted specifically for this review.
There will be no language restrictions in the searches for trials.
Data collection and analysis
Assessment of Search Results
Two reviewers will independently assess the titles and abstracts of all reports identified by the electronic and manual searches. The full articles of potentially or definitely relevant studies, which will be identified according to the definitions in the 'Criteria for considering studies for this review', will be reviewed. For non‐English trials identified as potentially relevant, the methods and results sections will be translated and assessed for inclusion. The reviewers will be unmasked to the report authors, institutions and trial results during the assessment.
Once full copies of potentially or definitely relevant reports are obtained, they will be reviewed and categorized by two reviewers as follows: exclude, unclear, or include. The concordance between reviewers will be documented. A third reviewer will resolve disagreements between the two reviewers. Papers identified by both reviewers as 'exclude' will be excluded and documented in the review. Papers identified as 'unclear' or 'include' by either reviewer will be assessed for methodological quality.
Assessment of methodological quality
Two reviewers will assess the sources of systematic bias in trials according to methods set out in Section six of the Cochrane Reviewer's Handbook (Clarke 2001). The following parameters will be considered: method of allocation to treatment and allocation concealment (selection bias), masking of outcome assessment (detection bias), and completeness of follow‐up (attrition bias). All trials will also be assessed on intention to treat.
Each of the parameters will be graded as (A) Adequate, (B) Unclear, and (C) Inadequate. Agreement between reviewers will be documented. If a discrepancy occurs between reviewers a third reviewer will resolve the issue.
The a priori criteria for exclusion will be that trials categorized as Inadequate on randomization or allocation concealment will be excluded. For trials categorized as Unclear, the authors will be contacted to provide more information. If the authors do not respond, the reviewers will assign a grade to the trial based on the information available.
Assessment of study characteristics
In addition to the parameters described above, data will be extracted on the study characteristics, such as details of participants, the interventions, the outcomes, cost and quality of life data, and other relevant information.
Data collection and synthesis
Two reviewers will independently extract the data for the primary and secondary outcomes onto paper data collection forms and then one reviewer will double‐enter the data into RevMan 4.1.
After data are extracted and entered into RevMan, a chi‐square test for statistical heterogeneity will be performed. If no statistical heterogeneity is detected and there is no clinical heterogeneity within the trials, the results of the studies will be summarized using relative risks with 95% confidence intervals. We will use a random effects model unless there are fewer than three trials in the comparison, in which case we will use a fixed effect model. Subgroup analyses according to type of corticosteroid will be performed where sufficient numbers of trials are available.
Sensitivity analysis
Sensitivity analyses will be conducted to determine the impact of changes in inclusion criteria such as:
‐ exclusion of lower quality methodological studies,
‐ exclusion of unpublished studies,
‐ exclusion of industry funded studies,
‐ changing inclusion criteria cut‐off points.
