Tubingen 1993.

Methods	Method of randomization: “Randomization list was made by the pharmaceutical company” (personal communication with Dr. Trauzettel-Klosinski) Number randomized: 44 of planned 100 patients were admitted and randomized to the study in 7 years Exclusions after randomization: 6 excluded after randomization due to poor adherence (3 in treatment and 3 in control group) Losses to follow up: 6 months: 1 treatment, 2 control; 12 months: 3 treatment, 3 control Method of allocation concealment: The randomization list, prepared by the pharmaceutical company and placed in a closed envelope was kept by a third person of the research group. It was not seen by the investigators before and during the evaluation of the data (personal communication) Participant masking: Yes except for 12 that were unmasked and chose the intervention they would receive (2 treatment, 10 control) Provider masking: Yes except for 12 that were unmasked and chose the intervention they would receive (2 treatment, 10 control) Outcome assessor masking: Yes Intention to treat analysis: No Unusual study design: 12 refused to participate under double-masked conditions and treated in unmasked manner but all were combined for data analysis
Participants	Country and period of study: Germany (1980 to 1986) Age: Mean age was 30.5 years and 29 years in treatment and control groups respectively Sex: 69% were female in treatment group and 74% were female in control group
Interventions	Treatment: Oral methylprednisolone for 24 days: 100, 80, 60, 40, 30, 20, 10, 5 mg for 3 days each Control: Oral Vitamin B1 for 24 days (100 mg/d)
Outcomes	Visual acuity (Snellen) Visual Field (Tubingen manual perimetry: profile perimetry and kinetic perimetry) Contrast sensitivity not reported
Notes	Dr. Trauzettel-Klosinski provided data for 1 month and 6 months in personal communication Criteria for diagnosis of optic neuritis employed for this study: Unilateral reduction of vision occurring over hours or days, at least two objective impairments on visual function including reduced and uncorrectable visual acuity, central scotoma, and pathological result of Aulhorn flicker test in patients with atypical scotoma, afferent pupil defect, normal or swollen optic disc Patients in treatment and control groups were given prophylactic aluminium-magnesium-silicate-hydrate, 550 mg three times a day Follow up at 1, 2, 3, 4, 6, 8 weeks and 3, 4, 5, 6, 9, 12 months
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method of randomization was not reported
Allocation concealment (selection bias)	Unclear risk	Method of allocation concealment was not reported
Masking (performance bias and detection bias)	High risk	“In addition, 12 ON patients who refused to participate under double-blind conditions, were treated in an unmasked manner, two with methylprednisolone and 10 with vitamin B1 according to their own choice” “In all patients their treatment assignment was not known during data evaluation”
Incomplete outcome data (attrition bias) All outcomes	Low risk	Exclusion of six patients after randomization due to poor treatment compliance; three in each treatment arm
Selective reporting (reporting bias)	High risk	“Both randomized groups (n=38) and unmasked group (n=12) were combined to establish a valid comparative evaluation with equal baseline conditions” “We observed in many patients that the parameters reached a nearly normal level very early, but complete normalization could take weeks or months. Therefore, we analyzed the data for each parameter according to the following questions: (1) How much time elapsed until the nearly normal level was reached…(2) How much time elapsed until the normal level was reach…”
Other bias	High risk	-Funded by pharmaceutical industry -There was a deviation from randomization: twelve patients chose the assignment according to their decision (two in methylprednisolone group and ten in vitamin B1 group)