Barabino 2003.

Methods	Study design: randomized, parallel‐group, controlled trial Study site(s): single center Number randomized (total and per group): 52 eyes of 26 participants; 26 eyes of 13 participants per group Unit of randomization (individual or eye): individual Exclusions after randomization: none Losses to follow‐up: none Unit of analysis (individual or eye): individual (worse eye) Reported power calculation? (Y/N): N Reported subgroup analysis? (Y/N): N
Participants	Baseline characteristics Country: Italy Age (mean ± SD, range): 58.8 ± 10.7 years for total; 63.4 ± 8.2 years for treatment group; 54.3 ± 11.3 years for control group Gender: 4 men and 9 women in the treatment group; 3 men and 10 women in the control group Inclusion criteria: 1. Age more than 18 years 2. Dry eye was identified on the basis of typical symptoms of dry eye (photophobia, burning, foreign body sensation, blurred vision improved by blinking, and pain) measured by a validated questionnaire, Schirmer test scores less than 5 mm/5 min, positive vital staining with 1% lissamine green (graded 0 to 9 according to the van Bijsterveld score system) less than 3.5, and fluorescein TBUT less than 7 seconds Exclusion criteria: 1. Infectious keratoconjunctivitis or inflammatory diseases unrelated to dry eye 2. Concomitant ocular pathologies 3. Previous ocular surgery 4. Eyelid or eyelash abnormalities 5. Alteration of the nasolacrimal apparatus 6. Treatment with drugs affecting tearing 7. Treatment with vitamin supplements 8. Concomitant ocular therapies 9. Topical ophthalmic steroids taken during the 4 weeks before the study 10. Pregnancy 11. Diabetes or other systemic, neurologic, or dermatologic disease affecting the health of the ocular surface Equivalence of baseline characteristics? (Y/N): Y
Interventions	Intervention #1 (treatment group): oral tablets containing linoleic acid 28.5 mg and γ‐linolenic acid 15 mg (Medilar tablets, Fidia Oftal‐Bausch & Lomb Pharmaceuticals), twice daily Intervention #2 (control group): placebo tablets, twice daily Length of follow‐up: 45 days Notes: patients used preservative‐free artificial tears, 4 times daily; patients in both groups were instructed to follow a sensible diet of any kind of food without excess and to record changes in a diary
Outcomes	Primary outcome(s): percentage of HLA‐DR‐positive cells at study endpoint Secondary outcome(s): subjective symptoms; conjunctival lissamine green staining; Schirmer I test; TBUT (paper indicates that these outcomes are measured as change from baseline, but these outcomes are reported as endpoint data) Adverse events reported? (Y/N): Y Measurement time points (specify intervals at which outcomes were assessed): baseline, day 45 Other issues with outcome assessment (eg, quality control for outcomes, if any): none
Notes	Study dates: not reported Funding source(s): not reported Conflicts of interest: "The authors have no financial interest in any of the products or instruments used in this study" Publication language: English Registered on clinical trials registry? (Y/N): N
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method of random sequence generation was not reported
Allocation concealment (selection bias)	Unclear risk	Allocation concealment was not reported
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	"Double‐masked" study, but details of masking about personnel were not reported" "we limited the length of the study to 45 days, and to avoid the well‐known placebo effect, we treated the control group with tablets similar to the one used in the study group, but without an active ingredient"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	"Slides were evaluated by optical microscopy; a researcher masked with respect to the study groups read the results" Masking of other outcome assessors was not reported
Incomplete outcome data (attrition bias) All outcomes	Low risk	There were no missing data
Selective reporting (reporting bias)	Unclear risk	No access to study protocol or clinical trials registry
Other bias	Low risk	No other apparent sources of bias