Kawashima 2016.

Methods	Study design: randomized, controlled trial Study site(s): single center Number randomized (total and per group): 40 participants in total; 20 participants in each intervention arm Unit of randomization (individual or eye): individual Exclusions after randomization: 1 participant in the omega‐3 treatment group Losses to follow‐up: not reported Unit of analysis (individual or eye): not reported Reported power calculation? (Y/N): Y (80% power) Reported subgroup analysis? (Y/N): N
Participants	Baseline characteristics Country: Japan Age (mean ± SD, range): 41.75 ± 9.39 (range 22 to 57) years in the omega‐3 treatment group; 42.95 ± 6.74 (range 33 to 59) years in the control group Gender: 10 men and 10 women in the omega‐3 treatment group; 11 men and 9 women in the control group Inclusion criterion: 1. Between 20 and 60 years of age who reported subjective symptoms of dry eye Exclusion criteria: 1. Current or previous severe ocular disease(s) such as strabismus, cataract, or glaucoma 2. Risk of developing seasonal allergy between July and September 3. LASIK operation within the previous 3 months 4. Allergy to the test supplement 5. Routinely used other supplements that contained the same ingredients as those of the combined dietary supplement 6. Currently taking medicine to improve vision 7. Receiving medical treatment 8. Receiving long‐term medical treatment for their ocular condition 9. History of any other serious disease requiring medical treatment 10. Participation in another clinical trial within 1 month before the start of the present study 11. Pregnancy or lactation during the study period 12. Presence of any health disorders based on the questionnaire results Equivalence of baseline characteristics? (Y/N): N (Schirmer test was significantly higher in the placebo group compared with the treatment group; P = 0.039)
Interventions	Intervention #1 (treatment group): oral capsule containing 40.5 mg eicosapentaenoic acid and 27 mg docosahexaenoic acid, 2 capsules/time, once daily (daily dose of 81 mg eicosapentaenoic acid and 108 mg docosahexaenoic acid) Intervention #2 (control group): "vehicle" capsules (dose not reported) Length of follow‐up: 8 weeks Notes: none
Outcomes	Primary and secondary outcome measures were not clearly distinguished Specified outcome(s): symptoms of dry eye; TBUT; Schirmer test without anesthesia; fluorescein staining of the cornea and conjunctiva; serum biochemical analysis, each measured at study endpoint Adverse events reported? (Y/N): Y Measurement time points (specify intervals at which outcomes were assessed): baseline, 4 and 8 weeks Other issues with outcome assessment (eg, quality control for outcomes, if any): participant population included individuals who did not have dry eye disease
Notes	Study dates: July 2014 to September 2014 Funding source(s): "this work was supported by Wakamoto Pharmaceutical Co. Ltd. (funding support, supplement capsules, and placebo capsules)… The funding organization had no role in the design or conduct of this research" Conflicts of interest: not reported Publication language: English Registered on clinical trials registry? (Y/N): Y ‐ clinical trial registry (UMIN000014447)
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	Low risk	"Double‐blind" study "Both capsule types were packaged in an opaque bag for blinding"
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	"One subject in the supplementation group was excluded from the efficacy analysis because of a lack of data"
Selective reporting (reporting bias)	High risk	The clinical trial registry entry (UMIN000014447) lists "dry eye symptoms" as the only outcome measure, and it is specified as the "primary outcome," without mention of the other reported outcomes (TBUT, Schirmer test, fluorescein staining score, and serum biochemical analysis, all of which are reported in the manuscript)
Other bias	High risk	Funded by industry; unit of analysis for ocular outcomes is unclear; participants with diagnosis of "non‐dry‐eye" were included in the analyses