Korb 2015.

Methods	Study design: randomized, controlled trial Study site(s): single center Number randomized (total and per group): 26 participants in total; 13 participants in each intervention arm Unit of randomization (individual or eye): individual Exclusions after randomization: none Losses to follow‐up: none Unit of analysis (individual or eye): eye Reported power calculation? (Y/N): Y (˜ 90% power) Reported subgroup analysis? (Y/N): N
Participants	Baseline characteristics Country: United States Age (mean ± SD, range): 38.1 ± 19.9 years in the omega‐3 treatment group; 45.4 ± 19.8 years in the control group Gender: 2 men and 11 women in the omega‐3 treatment group; 3 men and 10 women in the control group Inclusion criteria: 1. Aged ≥ 18 years 2. Existing clinical diagnosis of lipid deficient/evaporative dry eye disease based on the following characteristics: having 6 or fewer functioning lower lid meibomian glands (≤ 6 MGYLS) and also symptomatic for dry eye (Standard Patient Evaluation of Eye Dryness [SPEED] questionnaire score ≥ 6 to ≤ 14) 3. Best‐corrected visual acuity (BCVA, Snellen) of 20/40 or better in each eye Exclusion criteria: 1. Ocular or systemic medical conditions that could, in the opinion of the investigator, preclude study participation 2. Ocular or intraocular surgery or serious ocular trauma in either eye ≤ 6 months before screening 3. Intolerance or hypersensitivity to any component of the study medications 4. Epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella disease of the cornea/conjunctiva, or bacterial/fungal or mycobacterial infection/disease of the eye 5. Use of contact lenses ≤ 1 week before screening 6. Concomitant use of topical ocular medications during the study 7. Use of systemic medications that may contribute to dry eye without a stable dosing regimen for ≥ 30 days before screening and throughout the study 8. Women who were pregnant, may have become pregnant, or were breastfeeding at the time of screening for the study Equivalence of baseline characteristics? (Y/N): Y
Interventions	Intervention #1 (omega‐3 treatment group): lid hygiene with hypoallergenic eyelid cleansing wipes (Systane Lid Wipes; Alcon Laboratories, Inc., Fort Worth, TX, USA) once daily; instillation of 1 drop of lipid emulsion eye drops formulated to restore lipid, aqueous, and mucin components of the tear film (Systane Balance; Alcon) 4 times daily; and 2 oral vitamin supplements containing 1000 mg of omega‐3 fatty acids (Systane Vitamin Omega‐3 Healthy Tears; Alcon), daily for 3 months (daily dose of 2000 mg of omega‐3 fatty acids Intervention #2 (control group): a warm wet microfiber compress (from Terry World Textiles, LLC, Santa Monica, CA, USA) to both eyelids for 8 minutes once daily, for 3 months Length of follow‐up: 3 months Notes: participants were required to discontinue all other meibomian gland dysfunction management before screening and throughout the study
Outcomes	Primary outcome(s): meibomian gland functionality, assessed by standardized diagnostic meibomian gland expression to determine the number of functional meibomian glands, at study endpoint Secondary outcome(s): OSDI and SPEED questionnaires at study endpoint Adverse events reported? (Y/N): Y Measurement time points (specify intervals at which outcomes were assessed): baseline, 1, 2, and 3 months Other issues with outcome assessment (eg, quality control for outcomes, if any): this study has a unit of analysis issue, whereby both eyes from participants were included in the analyses of ocular outcomes, without apparent statistical adjustment for within‐person (between‐eye) correlation.
Notes	Study dates: not reported Funding source(s): "supported by Alcon Research, Ltd, Fort Worth, TX" Conflicts of interest: "D. R. Korb is the inventor or co‐inventor of and has financial interest in commercially marketed products including Systane Balance (Alcon Laboratories, Inc, Fort Worth, TX), Soothe XP, LipiView (TearScience, Morrisville, NC), LipiFlow (TearScience), and the Korb Meibomian Gland Evaluator (TearScience). C. A. Blackie and T. Douglass have financial interest in TearScience. V. M. Finnemore has no funding or conflicts of interest to disclose" Publication language: English Registered on clinical trials registry? (Y/N): Y ‐ clinical trial registry (clinicaltrials.gov ‐ NCT01733745)
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	Allocation concealment was not reported
Blinding of participants and personnel (performance bias) All outcomes	High risk	This was an "open‐label" study
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	"Investigator‐masked" study "Meibography was used to assess the percentage of partial meibomian glands. Results were graded by a single trained masked observer using a scale from 1 (no gland drop out) to 4 (>75% gland drop out)" It is unclear whether assessors of the other outcomes were masked
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing data
Selective reporting (reporting bias)	Low risk	Primary and secondary outcomes are consistent with those listed in the clinical trial registry (NCT01733745)
Other bias	High risk	Funded by industry; unit‐of‐analysis error: "right and left eyes were pooled and treated as independent cases for meibomian gland functionality, itching/ eye rubbing, lid status, and meibography endpoints"