PEDIG 2012.

Methods	Study design: parallel‐group randomized controlled trial Reported power calculation: yes, 80% Unusual study design? Some of the participants had unilateral NLDO while others had bilateral NLDO. Participants with bilateral NLDO were randomized to the same intervention for both eyes.
Participants	Country: USA Age: unilateral immediate probing mean age = 7.6 ± 1.2 months, unilateral observation/deferred probing mean age = 7.8 ± 1.3 months, bilateral immediate probing mean age = 7.8 ± 1.4 months, bilateral observation/deferred probing mean age = 7.5 ± 1.2 months Sex: unilateral probing 32 (39%) girls and 50 (61%) boys, unilateral observation/deferred probing 42 (52%) girls and 39 (48%) boys, bilateral probing 13 (42%) girls and 18 (58%) boys, bilateral observation/deferred probing 11 (42%) girls and 15 (58%) boys Inclusion criteria: "Major eligibility criteria included age 6 to less than 10 months, onset of NLDO symptoms before age 6 months, presence of at least 1 clinical sign of NLDO (epiphora, increased tear lake, and mucous discharge) in the absence of an upper respiratory infection or ocular surface irritation, no prior NLD surgery, and at least 1 patent punctum in the study eye." Exclusion criteria: "The study excluded children with Down syndrome or craniofacial anomalies." Equivalence of baseline characteristics: not reported Number randomized: Total: 220 (163 participants with unilateral NLDO and 57 with bilateral NLDO) Per group: immediate office‐based probing: 113 (82 unilateral, 31 bilateral); observation/deferred facility‐based probing: 107 (81 unilateral, 26 bilateral) Exclusions after randomization: none Losses to follow‐up: 9 immediate probing dropped; 14 observation/deferred dropped at 6 months visit Number analyzed: Total: 140 unilateral Per group: immediate office‐based probing: 73; observation/deferred facility‐based probing: 67 Unit of analysis: some of the participants had unilateral NLDO while others had bilateral NLDO. Sometimes results were presented on the participant level and sometimes on the eye level.
Interventions	Intervention 1: immediate office‐based probing Intervention 2: 6 months of observation followed by facility‐based probing if needed (lacrimal massage as indicated: performed twice daily when discharge was present, and antibiotic eyedrops as indicated: tobramycin sulfate 0.3% or moxifloxacin hydrochloride 0.5% when discharge was purulent) Length of follow‐up: until age 18 months
Outcomes	Primary outcome, as defined in study reports: treatment success, defined as the absence of clinical signs of NLDO assessed by a blinded examiner at 6 months Secondary outcomes, as defined in study reports: secondary procedure performed within six months Adverse events reported: yes, "No complications were reported for any surgery." Intervals at which outcomes assessed: 6 months after randomization, at age 18 months
Notes	Type of study report: published (protocol, journal articles, and abstracts) Funding sources: "This study was supported by grants EY011751 and EY018810 from the National Eye Institute of the National Institutes of Health, Department of Health and Human Services. Alcon Laboratories, Inc provided antibiotic eyedrops and antibiotic/corticosteroid eyedrops at no cost to the study. The sole purpose was to standardize the drugs used in the study; no comparisons were made between the drugs." Disclosures of interest: "Dr. Lee received support for travel to meetings for the study of other purposes and payment for writing or reviewing the manuscript from the Jaeb Center for Health Research. Ms. Chandler's institution received money from a grant from the National Eye Institute. Dr. Repka's institution received a grant from the National Eye Institute and consultancy for American Academy of Ophthalmology. His institution also received money for support for travel to meetings for the study of other purposes, fees for participation in review activities, such as data monitoring boards, statistical analysis, etc, and payment for writing or reviewing the manuscript from the Jaeb Center for Health Research. Ms. Melia's institution received a grant from the National Eye Institute and was paid for a board membership (Thomas Jefferson University; Alimera Science) and employment by the Jaeb Center for Health Research. Dr. Frick received consulting fees or honoraria from the Jaeb Center for Health Research. Dr. Beck's institution received a grant from the National Eye Institute. Dr. Summers received consultancy fees from BioMarin and Plancon. Ms. Foster's institution received a grant from the National Eye Institute. Mr. Kraker's institution received money from a National Eye Institute grant." Study period: November 2008 to September 2010 Reported subgroup analyses: yes (separate reports for patients with unilateral vs bilateral NLDO) Trial registration: NCT00780741
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Clinic personnel entered data on the PEDIG website to randomly assign each patient (using a permuted block design stratified by site) with equal probability to 1 of 2 treatment groups"
Allocation concealment (selection bias)	Low risk	"Clinic personnel entered data on the PEDIG website to randomly assign each patient (using a permuted block design stratified by site) with equal probability to 1 of 2 treatment groups"
Masking of participants and personnel (performance bias)	Low risk	The participants and personnel cannot be blinded because of the nature of the treatments, but we do not suspect performance bias for the primary outcome.
Masking of outcome assessment (detection bias)	Low risk	"The primary efficacy outcome was treatment success, defined as the absence of clinical signs of NLDO assessed by a masked examiner at the age 18 months visit."
Incomplete outcome data (attrition bias) All outcomes	High risk	Reasons for loss of follow‐up were not clearly stated. Over 10% losses of follow‐up in each treatment group ‐ 100/113 (88%) in the immediate probing group and 96/107 (90%) in the deferred probing group completed the 18‐month primary outcome examination
Selective reporting (reporting bias)	Unclear risk	The protocol is available and pre‐specified outcomes have been reported. However, data analysis was reported separately for participants with unilateral and bilateral NLDO, but this analysis plan was not described in the protocol.
Other bias	Low risk	None