Epitropoulos 2016.

Methods	Study design: randomized, parallel‐group, controlled trial Study site(s): multi‐center (number of sites not clearly specified) Number randomized (total and per group): 122 participants in total; 61 participants in the treatment group; 31 participants in the placebo group Unit of randomization (individual or eye): individual Exclusions after randomization: none Losses to follow‐up: 17 participants in total; 7 participants in the treatment group; 10 participants in the placebo group Unit of analysis (individual or eye): individual (eye with higher value in tear osmolarity was used for analysis but was not reported for other outcomes) Reported power calculation? (Y/N): N Reported subgroup analysis? (Y/N): N
Participants	Baseline characteristics Country: United States Age (mean ± SD, range): 57.0 ± 16.8 (range 21 to 85) years in the treatment group; 56.5 ± 17.3 (range 22 to 86) years in the control group Gender: 16 men and 38 women in the treatment group; 14 men and 37 women in the control group Inclusion criteria: 1. Over 18 years of age 2. Diagnosis of dry eye disease 3. Meibomian gland dysfunction (MGD) stage 1 or 2 4. Tear osmolarity of 312 mOsmol/L or greater in at least 1 eye using the TearLab Osmolarity System Exclusion criteria: 1. Using topical cyclosporine 0.05%, corticosteroids, non‐steroidal anti‐inflammatory drugs, glaucoma medications, or oral omega‐3 fatty acids within 3 weeks of screening, and anytime during participation in the study 2. Underwent LASIK or PRK surgery within 1 year of screening visit 3. Currently using a systemic medication that might affect the ocular surface Equivalence of baseline characteristics? (Y/N): Y
Interventions	Intervention #1 (treatment group): 4 capsules per day (daily dose of 1680 mg EPA and 560 mg DHA) Intervention #2 (control group): 3136 mg/d linoleic acid (omega‐6) safflower oil Length of follow‐up: 12 weeks Notes: computer use and artificial tears were allowed during the study. Participants were instructed to discontinue contact lenses within 12 hours of any study visit
Outcomes	Primary outcome(s): change from baseline in tear osmolarity Secondary outcome(s): change from baseline in each of TBUT; symptoms of dry eye; omega‐3 index; corneal fluorescein staining; MGD stage; Schirmer test with anesthesia; MMP‐9 (percentage of participants with a positive result on the InflammaDry test) Adverse events reported? (Y/N): N Measurement time points (specify intervals at which outcomes were assessed): baseline, 6 and 12 weeks Other issues with outcome assessment (eg, quality control for outcomes, if any): none
Notes	Study dates: not reported Funding source(s): "A. T. Epitropoulos, E. D. Donnenfeld, Z. A. Shah, E. J. Holland, M. Gross, W. J. Faulkner, C. Matossian, S. S. Lane, M. Toyos, and F. A. Bucci Jr received compensation from PRN Physician Recommended Nutraceuticals for participating in the study. The remaining author has no funding or conflicts of interest to disclose" Conflicts of interest: "A. T. Epitropoulos, E. D. Donnenfeld, Z. A. Shah, E. J. Holland, M. Gross, W. J. Faulkner, C. Matossian, S. S. Lane, M. Toyos, and F. A. Bucci Jr received compensation from PRN Physician Recommended Nutraceuticals for participating in the study. The remaining author has no funding or conflicts of interest to disclose" Publication language: English Registered on clinical trials registry? (Y/N): Y ‐ Although not referenced in the paper, this report appears to relate to the clinical trial registry entry: clinicaltrials.gov (NCT02260960)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Subjects were randomly assigned using a random number‐generated sequence to ingest 4 softgels daily with meals containing a total of either 1680 mg of EPA/560 mg of DHA re‐esterified omega‐3 group or 3136 mg linoleic acid safflower oil as the control group for 12 weeks"
Allocation concealment (selection bias)	Unclear risk	Allocation concealment was not reported
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"Both active and control softgels seemed identical and were supplied in identical containers for masking purposes"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Masking of outcome assessors was not reported
Incomplete outcome data (attrition bias) All outcomes	High risk	17/122 (13.9%) participants who were randomized were not included in the final analysis
Selective reporting (reporting bias)	Unclear risk	Although not referenced in the paper, this study appears to relate to the clinical trial registry entry: https://clinicaltrials.gov/ct2/show/NCT02260960, which lists only "change in tear osmolarity" as the primary outcome measure but does not list any secondary outcome measures
Other bias	High risk	Study was funded by industry (Physician Recommended Nutraceuticals)