Tejedor 1999.

Study characteristics
Methods	Study design: parallel‐group randomized controlled trial Number randomized (in total and per group): 55 participants in total, 27 in BTX group (number of eyes unclear) and 28 in surgery group (56 eyes) Unit of randomization (individual or eye): individual Number analyzed (in total and per group): 55 participants in total, 27 in BTX group (number of eyes unclear) and 28 in surgery group (56 eyes) Unit of analysis (individual or eye): individual Exclusions and losses to follow‐up (total and per group): none How were missing data handled?: NA Length of follow‐up: mean 3.75 years (SD 0.12) in surgery arm and mean 3.5 years (SD 0.21) in BTX arm Minimum 36 month follow‐up Reported power calculation (Y/N), if yes, sample size and power: not reported
Participants	Country: Spain Setting: Hospital Ramón y Cajal, (university hospital) Baseline characteristics 1. Botulinum toxin injections, n = 27 Age (mean ± SD, range): 14.25 ± 3.12 months (at initial surgery, age at reoperation was not reported) Time between initial and secondary treatment: 5.5 ± 0.45 months Gender: 15 male and 12 female Angle of deviation: mean 24.12 PD (SD 16.02) at near fixation and mean 20.27 PD (SD 15.15) at distance fixation 2. Surgical intervention, n = 28 Age (mean ± SD, range): 15.33 ± 3.31 months (at initial surgery, age at reoperation was not reported) Time between initial and secondary treatment: 6.25 ± 1.60 months Gender: 15 male and 13 female Angle of deviation: mean 28.87 PD (SD 12.41) at near fixation and mean 25.40 PD (SD 11.35) at distance fixation Overall, n = 56 Age (mean ± SD, range): not reported Gender: not reported Inclusion criteria: patients with a history of esotropia present in the first 6 months of life, no accommodative element, retreated within 12 months Exclusion criteria: patients with a distance to near difference of at least 10 PD or in whom the correction of hypermetropia with spectacles improved or corrected the esotropia. Children with vertical deviations greater than 4 PD, and those with medical or neurological disease Baseline equivalence: comparable
Interventions	The participants in the two groups had been treated with only one previous documented operation. Initial surgery was a bimedial recession procedure. Intervention: "Botulinum toxin type A (Botox, Allergan) was administered under topical anesthesia alone (0.5% proxymetacaine (proparacaine) hydrochloride) or in combination with mild general anesthesia (ketamine intramuscularly/intravenously or nitrous oxide inhalation). We used the maximal dosages suggested by Scott et al. The toxin was injected into one or two (when total dose >5 U) recti muscles with electromyographic control. " Comparator‐surgery: "Reoperation was performed by the same surgeon with careful dissection of muscles and removal of fibrotic tissue. In under‐corrected children we made bilateral lateral rectus resection, following previously published guidelines. When restriction was detected medially by forced duction at the time of reoperation we did small amounts of bilateral medial rectus recession, and the conjunctiva was always recessed. For over‐corrections we carried out bilateral lateral rectus recession, unless we found weakness in adduction, for which we preferred to advance the medial recti muscles."
Outcomes	Outcomes reported: the motor success rate and percentage net change in the deviation (preoperative deviation − postoperative deviation/preoperative deviation × 100%); successful motor alignment defined as a distance deviation of 8 PD or less by the simultaneous prism and cover test. Fusion was detected by the Worth 4 dot at near and the Bagolini lenses, and the presence of stereopsis with the Randot circles (at least 400 seconds of arc) and TNO test (at least 480 seconds of arc). Adverse outcomes: "Ptosis occurred transiently in 10 of the 27 patients injected with botulinum toxin (37.03%) and vertical deviation was also temporary in five of them (18.51%)" Measurement time points: 6 months, 1 year and 3 years after the second treatment
Notes	Study period: from 1990 to 1994 Publication language: English Trial registration: not reported Conflicts of interest: "None of the authors has any interest in the products or devices mentioned in the paper" Funding source: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Participants were randomized, but the method of random sequence generation was not described.
Allocation concealment (selection bias)	Unclear risk	Allocation concealment was not described.
Blinding (performance bias and detection bias) Investigators	High risk	Investigators could not be masked due to the nature of interventions.
Blinding (performance bias and detection bias) Participants	High risk	It was not possible to mask participants to the different treatment options.
Blinding (performance bias and detection bias) Personnel	Low risk	Although masking of outcome assessors was not described, the outcome was unlikely affected by knowledge of interventions received.
Incomplete outcome data (attrition bias) All outcomes	Low risk	There were no missing outcome data.
Selective reporting (reporting bias)	Unclear risk	Neither protocol nor trial register was not publicly available.
Other bias	Unclear risk	Information on funding, conflict of interests, sample size calculation, and trial register was unclear as this was an old trial.

BTX: botulinum toxin

IQR: Interquartile range

NA: not applicable

PD: prism diopters

SD: standard deviation