LipiFlow for the treatment of dry eye disease.

BACKGROUND: Meibomian gland dysfunction (MGD) is the most common underlying cause of dry eye disease (DED). MGD leads to pathological alteration of the composition or quantity of meibum, or both, which subsequently results in tear evaporation and the typical signs and symptoms associated with DED. The LipiFlow Thermal Pulsation System (LipiFlow) is a medical device used to treat MGD in office; however, it is unclear if LipiFlow can outperform other DED treatments. OBJECTIVES: To evaluate the effectiveness of LipiFlow for treating DED signs and symptoms and the safety of LipiFlow compared with sham or other available treatments for MGD in adults. SEARCH METHODS: The Cochrane Eyes and Vision Information Specialist searched the electronic databases for randomized controlled trials. There were no restrictions on language or date of publication. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, including the Cochrane Eyes and Vision Trials Register; 2022, Issue 6), MEDLINE Ovid, Embase.com, PubMed, LILACS (Latin American and Caribbean Health Science Information database), ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) electronic databases. We also examined the reference lists of identified trials, review articles, and guidelines for information about relevant trials that may not have been identified by our search strategy. We contacted investigators regarding ongoing trials. The last database search was performed on 24 October 2022. SELECTION CRITERIA: We included studies conducted in adults (over 18 years of age) with DED or MGD as defined by the primary trial investigators. We imposed no restrictions on race, ethnicity, or sex. We considered trials involving contact lens wearers if they were equally represented between groups. DATA COLLECTION AND ANALYSIS: We applied standard Cochrane methodology. MAIN RESULTS: We included 13 trials that randomized a total of 1155 participants (28 to 236 participants randomized per study). Six trials were conducted in the USA, three in China, two in Thailand, one in France, and one in Italy. Eight trials were of single-center design, while four trials were of multicenter design; one trial did not report the number of participating centers. Study characteristics The study population of the included trials was 66% female (range 48% to 80%), with an age range of 19 to 86 years. LipiFlow, used as a stand-alone intervention, was compared with basic warm compresses in five studies, thermostatic device in five studies, oral intervention in one trial, and topical dry eye medications in one trial. LipiFlow was also evaluated together with eyelid hygiene product versus eyelid hygiene products alone in one trial. Findings Five trials compared LipiFlow with a basic warm compress applied for varying durations and frequencies during the trial period; only one of these trials combined a warm compress with eyelid massage. Analyzing symptom scores by different questionnaires (Ocular Surface Disease Index [OSDI] and Standard Patient Evaluation of Eye Dryness [SPEED]) yielded conflicting evidence of a difference in symptoms between LipiFlow and basic warm compresses after four 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 five trials compared LipiFlow with thermostatic devices. Analysis of symptom scores at four weeks showed that thermostatic devices had reduced OSDI scores by a mean difference (MD) of 4.59 (95% confidence interval [CI] 1.23 to 7.95; I2 = 0, P = 0.007; 553 participants; very low certainty evidence) as compared with LipiFlow. When we compared LipiFlow plus eyelid hygiene with eyelid hygiene alone, there was no evidence of difference in signs or symptoms at any time point evaluated. Only one trial compared LipiFlow with a topical DED medication (lifitegrast 5%). The single-trial estimate suggested that 5% lifitegrast may increase meibomian gland expression scores compared with LipiFlow at day 42 (MD -1.21, 95% CI -2.37 to -0.05; 50 participants; low certainty evidence) by using a meibomian gland expression scale of 0 to 8. One trial compared LipiFlow with an oral intervention (doxycycline), finding that LipiFlow may result in significantly better SPEED scores than doxycycline at three months (MD -4.00, 95% CI -7.33 to -0.67; 24 participants; very low certainty evidence). No other significant differences in signs or symptoms were found between LipiFlow and doxycycline at three months. We did not find any other statistically significant differences in symptoms or signs for any other analysis performed in this review at the one- to four-week time point. Adverse events No trial reported any intervention-related, vision-threatening adverse events. AUTHORS' CONCLUSIONS: LipiFlow performs similarly to other commonly used DED treatments with regard to DED signs and symptoms. The best available evidence was deemed to have a high level of bias, leading to low or very low certainty evidence. Additional research with adequate masking, a standardized testing methodology, and a sample representative of the MGD population is therefore needed before any firm conclusions can be drawn regarding comparative benefits and harms.

Tea tree oil for Demodex blepharitis.

BACKGROUND: Demodex blepharitis is a chronic condition commonly associated with recalcitrant dry eye symptoms though many people with Demodex mites are asymptomatic. The primary cause of this condition in humans is two types of Demodex mites: Demodex folliculorum and Demodex brevis. There are varying reports of the prevalence of Demodex blepharitis among adults, and it affects both men and women equally. While Demodex mites are commonly treated with tea tree oil, the effectiveness of tea tree oil for treating Demodex blepharitis is not well documented. OBJECTIVES: To evaluate the effects of tea tree oil on ocular Demodex infestation in people with Demodex blepharitis. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2019, Issue 6); Ovid MEDLINE; Embase.com; PubMed; LILACS; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We used no date or language restrictions in the electronic search for trials. We last searched the databases on 18 June 2019. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared treatment with tea tree oil (or its components) versus another treatment or no treatment for people with Demodex blepharitis. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts and then full text of records to determine their eligibility. The review authors independently extracted data and assessed risk of bias using Covidence. A third review author resolved any conflicts at all stages. MAIN RESULTS: We included six RCTs (1124 eyes of 562 participants; 17 to 281 participants per study) from the US, Korea, China, Australia, Ireland, and Turkey. The RCTs compared some formulation of tea tree oil to another treatment or no treatment. Included participants were both men and women, ranging from 39 to 55 years of age. All RCTs were assessed at unclear or high risk of bias in one or more domains. We also identified two RCTs that are ongoing or awaiting publications. Data from three RCTs that reported a short-term mean change in the number of Demodex mites per eight eyelashes contributed to a meta-analysis. We are uncertain about the mean reduction for the groups that received the tea tree oil intervention (mean difference [MD] 0.70, 95% confidence interval [CI] 0.24 to 1.16) at four to six weeks as compared to other interventions. Only one RCT reported data for long-term changes, which found that the group that received intense pulse light as the treatment had complete eradication of Demodex mites at three months. We graded the certainty of the evidence for this outcome as very low. Three RCTs reported no evidence of a difference for participant reported symptoms measured on the Ocular Surface Disease Index (OSDI) between the tea tree oil group and the group receiving other forms of intervention. Mean differences in these studies ranged from -10.54 (95% CI - 24.19, 3.11) to 3.40 (95% CI -0.70 7.50). We did not conduct a meta-analysis for this outcome given substantial statistical heterogeneity and graded the certainty of the evidence as low. One RCT provided information concerning visual acuity but did not provide sufficient data for between-group comparisons. The authors noted that mean habitual LogMAR visual acuity for all study participants improved post-treatment (mean LogMAR 1.16, standard deviation 0.26 at 4 weeks). We graded the certainty of evidence for this outcome as low. No RCTs provided data on mean change in number of cylindrical dandruff or the proportion of participants experiencing conjunctival injection or experiencing meibomian gland dysfunction. Three RCTs provided information on adverse events. One reported no adverse events. The other two described a total of six participants randomized to treatment with tea tree oil who experienced ocular irritation or discomfort that resolved with re-educating the patient on application techniques and continuing use of the tea tree oil. We graded the certainty of the evidence for this outcome as very low. AUTHORS' CONCLUSIONS: The current review suggests that there is uncertainty related to the effectiveness of 5% to 50% tea tree oil for the short-term treatment of Demodex blepharitis; however, if used, lower concentrations may be preferable in the eye care arena to avoid induced ocular irritation. Future studies should be better controlled, assess outcomes at long term (e.g. 10 to 12 weeks or beyond), account for patient compliance, and study the effects of different tea tree oil concentrations.