PURPOSE: To evaluate the effectiveness and the safety of LipiFlow for treating signs and symptoms of dry eye disease (DED) in adults. METHODS: The following databases were searched for randomized trials: CENTRAL, MEDLINE Ovid, Embase.com, PubMed, LILACS, ClinicalTrials.gov, and WHO ICTRP on 24 October 2022. The included studies were conducted in adults (≥18 years) with DED or meibomian gland dysfunction (MGD) as defined by the investigators. Standard Cochrane methodology was applied. RESULTS: This study included 13 trials that randomized a total of 1,155 participants (66 % female
age range = 19 to 86 years). Five trials compared LipiFlow with basic warm compresses. Analyzing symptom scores in these trials yielded conflicting evidence of a difference in symptoms between LipiFlow and basic warm compresses after 4 weeks. There was no evidence of a difference in meibomian gland expression, meibum quality, or tear breakup time when comparing LipiFlow with basic warm compresses. Another 5 trials compared LipiFlow with thermostatic devices. Analysis of symptom scores in these trials at 4 weeks showed that thermostatic devices had reduced Ocular Surface Disease Index (OSDI) scores by a mean difference of 4.59 as compared with LipiFlow. The remaining 3 included trials could not be grouped for comparisons. The overall evidence was of low or very low certainty, with most trials being assessed as having a high risk of bias. No trial reported any intervention-related, vision-threating adverse events. CONCLUSIONS: LipiFlow performs similarly to other DED treatments. Further research with adequate masking and a standardized testing methodology is still needed.