Lee 1994.

Methods	Botulinum toxin versus observation of acute onset sixth nerve palsy Allocation: random number table Masking: not achieved Exclusions: 2 due to change in diagnosis Losses: 5 lost to follow‐up Study design: parallel RCT
Participants	Country: UK Number of participants randomised: 54 participants (54 eyes), 22 in BT group and 25 in control group Dates of recruitment: August 1989 to August 1992 Age: Controls: mean 61 years (24‐86 years) BT: mean 63 years (24‐83 years) Gender: Controls: 12 male, 13 female BT: 13 male, 9 female Aetiologies: Controls: multiple sclerosis (2) microvascular (16), sarcoidosis (1), ectatic basilar artery (1), unknown (5) BT: multiple sclerosis (1), microvascular (18), unknown (3) Inclusion criteria: A & E walk‐in — adult sixth nerve palsy Exclusion criteria: change in diagnosis Duration of symptoms: Controls: ≤ 1 week in 17, ≤ 2 weeks in 6, 3 weeks in 1 and 4 weeks in 1 BT: ≤ 1 week in 7, ≤ 2 weeks in 9, ≤ 3 weeks in 5 and 6 weeks in 1 Angle of deviation: Controls: primary position at distance fixation fixing with nonparetic eye; mean 17.8 PD (4 to 40 PD) BT: primary position at distance fixation fixing with nonparetic eye; mean 28.6 PD (6 to 70 PD) Repeat injections: undertaken in 3 participants
Interventions	Treatment: BT: 2.5 units Dysport™ to ipsilateral medial rectus muscle. 3 participants had a second injection when first injection was inadequate Control: observation Duration: 4‐42 months. Participants were followed up at 1 week, 6 weeks and 4 months as a minimum and were discharged at 4 months if fully recovered. Choice of eye for intervention: ipsilateral eye to the cranial nerve palsy — conventional choice
Outcomes	Measurements: Ocular motility range — abduction deficit. Binary response of yes/no. Angle of deviation by prism cover test. Field of binocular single vision. Participant‐reported symptoms. Adverse reactions.
Notes	Health economic costs: not reported Quality of life measures: not reported Funding: None specified Declarations of interest: None specified Trial registration number: None specified
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote "...patients were randomly assigned to "treatment" or "control" groups by reference to a random number table."
Allocation concealment (selection bias)	High risk	Judgement comment: as the treatments were quite different ‐ botulinum toxin versus observation ‐ it is likely that the Investigators were aware of participant allocation.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Judgement comment: as the treatments were quite different ‐ botulinum toxin versus observation ‐ it is likely that the participants and their carers were aware of participant allocation.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Judgement comment: as the treatments were quite different ‐ botulinum toxin versus observation ‐ it is likely that the outcome assessors were aware of participant allocation.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Quote "Of the initial 54 patients, five (four controls, one injection) were lost to follow‐up. A further two patients (both controls) were later excluded because of a change in diagnosis." Judgement comment: follow‐up was clearly described and most participants were followed‐up (47/54, 87%). However, loss to follow‐up appeared to occur predominantly in the control group. It is unclear what impact that would have had.
Selective reporting (reporting bias)	Unclear risk	No access to study protocol or trials registry entry.
Other bias	Unclear risk	Not applicable