Seal 1995

Methods	Study design: randomized, partial cross‐over study Conditions included: chronic blepharitis with and without associated rosacea Enrollment: 61 participants  Exclusions and loss to follow‐up: 18 participants were excluded or lost to follow‐up Study follow‐up: 8 months
Participants	Country: UK Age: not reported Gender: not reported Inclusion criteria: patients with chronic blepharitis Exclusion criteria: 1) known hypersensitivity to fusidic acid, oxytetracycline, or benzalkonium chloride; 2) simultaneous wearing of contact lenses; 3) pregnant or nursing or having childbearing potential; 4) concurrent use of prescribed anti‐infective drugs; 5) other ophthalmic complications; 6) severe renal impairment
Interventions	Fusidic acid (n = 18): topical 1% fusidic acid in a carbomer gel made isotonic by adding mannitol, buffered to pH 5.5, and preserved plus placebo tablet every 12 hours Oxytetracycline (n = 22): oral 250 mg oxytetracycline tablet plus placebo gel every 12 hours Combination (n = 34): both topical fusidic acid and oral oxytetracycline every 12 hours Placebo (n = 61): placebo gel and placebo tablet every 12 hours Study was divided into four 2‐month periods: 1) all participants received placebo gel and tablets, 2) 50% randomized to receive combination and 50% to receive either fusidic acid gel and placebo tablet or placebo gel and oxytetracycline tablet, 3) all participants received placebo gel and tablets, 4) participants who previously received combination were randomized to receive either fusidic acid gel and placebo tablet or placebo gel and oxytetracycline tablet and the remaining participants received combination
Outcomes	Primary outcomes: 1) patients’ subjective improvement of symptoms 2) investigators' assessment of improvement of signs Measurements taken at baseline, and every 2 months for 8 months Unit of analysis: the individual
Notes	Study dates: not reported Funding source: not reported Declarations of interest: 1 study author affiliated with Leo Laboratories Ltd. (Bucks, UK) Publication language: English
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomization was done by the pharmacy.
Allocation concealment (selection bias)	Low risk	The pharmacist distributed the study medications after participants were enrolled.
Masking (performance bias and detection bias) Were participants masked to treatment group?	Low risk	Drugs were dispensed every 2 months to participants by the pharmacy so that they were unaware whether they were entering the placebo or active treatment phase.
Masking (performance bias and detection bias) Were healthcare providers masked to treatment group?	Low risk	Active treatment and combination assignments were masked by use of placebos and pharmacy distribution.
Masking (performance bias and detection bias) Were outcome assessors masked to treatment group?	Low risk	Active treatment and combination assignments were masked by use of placebos and pharmacy distribution.
Incomplete outcome data (attrition bias) All outcomes	High risk	ITT analysis was not followed.
Selective reporting (reporting bias)	High risk	Results were not reported for the end of each treatment phase.
Other bias	Unclear risk	1 of the authors affiliated with industry. Placebo periods (1 and 3) were not parallel with active treatment periods (2 and 4).