Aragona 2005.

Methods	Study design: randomized, parallel‐group, controlled trial Study site(s): single center Number of participants randomized (total and per group): 80 eyes of 40 participants (ie, 40 eyes of 20 participants per treatment group) Unit of randomization (individual or eye): individual Exclusions after randomization: none Losses to follow‐up: none Unit of analysis (individual or eye): individual (right eye) Reported power calculation? (Y/N): N Reported subgroup analysis? (Y/N): N
Participants	Baseline characteristics Country: Italy Age (mean ± SD, range): 36.6 ± 6.7 years for total; 36.9 ± 7.9 years for treatment group; 36.3 ± 5.5 years for control group Gender: 2 men and 18 women in the treatment group; 1 man and 19 women in the control group Inclusion criteria: 1. Age more than 18 years 2. Primary Sjögren’s syndrome, as defined by the American‐European Consensus Group 3. Ability and willingness to participate in the study 4. Stable disease and general therapy for at least 1 month 5. No local treatment other than preservative‐free cellulose‐derivative eye drops 6. Moderate to severe dry eye, as defined by tear basal secretion less than 5 mm/5 min, tear break‐up time (TBUT) less than 7 seconds, and signs of corneal damage demonstrated by corneal fluorescein staining (at least 2+ according to Lemp) Exclusion criteria: 1. Any systemic disease different from Sjögren’s syndrome 2. Menopausal status 3. Presence of systemic treatment with drugs such as β‐blocking agents, benzodiazepines, hormones, or antihistamine agents that could interfere with tear production 4. Use of non‐steroidal anti‐inflammatory drugs (NSAIDs) or steroids Equivalence of baseline characteristics? (Y/N): Y
Interventions	Intervention #1 (treatment group): oral sachets containing linoleic acid 112 mg and γ‐linolenic acid 15 mg, twice daily Intervention #2 (control group'): oral placebo sachets, twice daily Length of follow‐up: 1 month of treatment and 15 days after suspension of treatment Notes: sachets were diluted in water; participants were instructed to follow their usual diets; participants were allowed to continue their general and local therapies
Outcomes	Primary outcome(s): PGE1 content (mg/mL) of tears at study endpoint Secondary outcome(s): subjective dry eye symptoms (burning, itching, foreign body sensation, dryness, mucous discharge, and photophobia); TBUT; corneal fluorescein staining; tear basal secretion (Schirmer test with anaesthesia) at study endpoint Adverse events reported? (Y/N): Y Measurement time points (including intervals at which outcomes were assessed): baseline, 1 month of treatment, and 15 days after suspension of treatment Other issues with outcome assessment (eg, quality control for outcomes, if any): none
Notes	Study dates: not reported Funding source(s): "supported by grants from the National Research Council and Bausch & Lomb" Conflicts of interest: 2 authors were affiliated with Bausch & Lomb (E, F); "The publication costs of this article were defrayed in part by page charge payment. This article must therefore be marked 'advertisement' in accordance with 18 U.S.C. §1734 solely to indicate this fact" 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)	Low risk	"Once recruited, patients were randomly divided into two groups, according to a table of random numbers, and assigned, in a double masked manner, to the treatments"
Allocation concealment (selection bias)	Unclear risk	Allocation concealment was not reported
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	"Once recruited, patients were randomly divided into two groups, according to a table of random numbers, and assigned, in a double masked manner, to the following treatments" Details of masking about participants and personnel were not reported
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"The tear content of PGE1 was evaluated in a masked manner by enzyme immunoassay (EIA), using a commercial kit" (primary outcome. Self‐reported symptoms were graded by means of a questionnaire administered at the beginning of each examination by a different observer (RS) from the one who performed the examinations (PA)" "The statistical analysis of the results was performed in a masked manner"
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	High risk	"Supported by grants from the National Research Council and Bausch & Lomb" Two of the authors were affiliated with Bausch & Lomb (E, F) "The publication costs of this article were defrayed in part by page charge payment. This article must therefore be marked 'advertisement' in accordance with 18 U.S.C. §1734 solely to indicate this fact"