ONTT 1992-2006.

Methods	Method of randomization: Randomized using permuted block design, stratified by clinical center Number randomized: 457 Exclusions after randomization: 2 patients found ineligible after randomization were excluded Losses to follow up: 17 at 6 months Method of allocation concealment: Bottles with pills prepared at a central location with a numbered envelope-type sealed label. Intact label was verified on return of the same to the central area Participant masking: Yes except for IV group Provider masking: Yes except for IV group Outcome assessor masking: Not for IV group. Only 6 % of testing in both the oral treatment arms at 6 months was performed by an individual who randomized the patient. Intention to treat analysis: Yes
Participants	Country and period of study: 15 centers in USA (July 1988 to June 1991) Age: 18 to 46, (mean 32 years) Sex: Overall, 77% were female
Interventions	Treatment 1: Intravenous methylprednisolone 250 mg every 6 hrs for 3 days followed by 1 mg/kg body weight of oral prednisone for 11 days Treatment 2: Oral prednisone 1mg/kg/day for 14 days, tapered with administration of 20 mg on day 15 and 10 mg on days 16 and 18 Control: Oral placebo 1 mg/kg/day for 14 days with similar treatment as oral corticosteroid group on days 15, 16 and 18 Adherence: All but 14 patients (3%) completed their course of treatment. Compliance was evaluated via comparison of the number of pills in each bottle returned to study headquarters, with the number expected from that participant
Outcomes	Visual acuity (Retro illuminated Snellen ETDRS chart) Visual field (Humphrey Visual Field Analyzer and Goldmann perimeter) Contrast sensitivity (Pelli-Robson chart) Quality of life: Assessed using National Eye Institute Visual Function Questionnaire (NEI-VFQ) - administered 5 to 8 years after acute optic neuritis, again at 10 to 12 years, and again at 15 to 18 years after acute optic neuritis
Notes	Data provided by the Jaeb Center for Health Research in personal communication Follow up at days 4, 15; weeks 7, 13, 19; months 1, 6, 12; 2 and yearly thereafter
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	“A permuted-blocks design with a separate sequence for each clinical centers was used to assign patients randomly in equal numbers to three treatment groups”
Allocation concealment (selection bias)	Low risk	“Each bottle for the prednisone and placebo groups had a numbered envelope type sealed label, within which the actual contents of the bottle was identified for emergency purposes. On dispensing the medication a portion of the label was torn off and placed in the patient's chart. Upon completion of treatment, the portion of the label that had been removed was returned to the DCC, which verified that the correct bottle had been dispensed to the patient and that masking had not been compromised (i.e., label intact)”
Masking (performance bias and detection bias)	Unclear risk	“Patients in the oral-prednisone and placebo groups were blinded to their treatment assignment, whereas those in the intravenous-methylprednisolone group were not” “The personnel assessing visual function were always unaware of whether the patient was assigned to the placebo or prednisone group, and as often as possible they were unaware of whether the patient was receiving methylprednisolone” “When examining visual function in the patients in the intravenous-methylprednisolone group, technicians were unaware of the patient's treatment assignment during 86 percent of all follow-up visits overall and 94 percent of the six-month visits”
Incomplete outcome data (attrition bias) All outcomes	Low risk	“The overall rate of visits missed among the seven scheduled follow-up visits in the first six months was 3.4 percent.” - It was unclear how these were distributed across the treatment arms and for what reasons they missed the scheduled follow-up visits
Selective reporting (reporting bias)	Low risk	“Visual field and contrast sensitivity were the primary measures of outcome; visual acuity and color vision were secondary measures”
Other bias	Unclear risk	Study medication was provided by industry