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.

Silicone hydrogel versus hydrogel soft contact lenses for differences in patient-reported eye comfort and safety: A Cochrane systematic review summary.

SIGNIFICANCE: This work is significant because it is the first Cochrane systemic review that compares the comfort and safety of hydrogel and silicone hydrogel soft contact lenses (SCL). PURPOSE: This study aimed to conduct a systemic review of randomized trials comparing the comfort and safety of silicone hydrogel and hydrogel SCLs. METHODS: CENTRAL, MEDLINE Ovid, EMBASE.com, PubMed, LILACS, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform were searched on or before June 24, 2022, to identify randomized clinical trials that compared silicone hydrogel and hydrogel SCLs. RESULTS: Seven trials were identified and evaluated. One trial reported Ocular Surface Disease Index results, with the evidence being very uncertain about the effects of SCL material on Ocular Surface Disease Index scores (mean difference, -1.20; 95% confidence interval, -10.49 to 8.09). Three trials reported visual analog scale comfort score results, with no clear difference in comfort between materials, although results were of low certainty; trial results could not be combined because the three trials reported results at different time points. None of the included trials reported Contact Lens Dry Eye Questionnaire 8 or Standard Patient Evaluation of Eye Dryness scores. There was no evidence of a clinically meaningful difference (>0.5 unit) between daily disposable silicone hydrogel and hydrogel SCLs in corneal staining, conjunctival staining, or conjunctival redness (very low certainty evidence). CONCLUSIONS: The overall evidence for a difference between all included silicone hydrogel and hydrogel SCL trials was of very low certainty, with most trials judged as having a high overall risk of bias. There was insufficient evidence to support recommending one SCL material over the other. Future well-designed trials are needed to generate high certainty evidence to further clarify differences in SCL material comfort and safety.

Refitting contact lens dropouts into a modern daily disposable contact lens.

PURPOSE: To determine the number of previous contact lens (CL) wearers who could be comfortably refitted into delefilcon A (DAILIES TOTAL1®) CLs. METHODS: This was a 6-month, three-visit study that recruited subjects who discontinued CLs within the past 2 years because of discomfort or dryness symptoms. Subjects were required to have Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire scores ≤3 and to be able to wear spherical study CLs. Subjects were asked to complete a ±50 comfort visual analogue scale (VAS) at 1 month and a Likert questionnaire after 1 and 6 months of CL wear to understand the subjects' CL experience. RESULTS: All 60 subjects who were fitted with the study CLs were still wearing them after 1 month, while one subject had dropped out by 6 months. Subjects had a median (interquartile range) age of 24.0 (7.0) years (71.7% female). They reported a median VAS score of 44.0 (8.0) units at the 1-month visit, with all reporting a comfortable score. At the 1-month/6-month visits, 98.3%/93.2%, 86.5%/78.0% and 93.2%/91.5% of subjects responded that they were very satisfied or satisfied with their vision, their end-of-day CL comfort and overall CL comfort, respectively. The same subjects responded that they were very likely or likely to continue to wear the study CLs at 1 (89.6%) and 6 months (80.7%) and to recommend the study CLs to a friend at 1 (98.3%) and 6 months (93.2%). CONCLUSIONS: The results suggest that when encountering a CL dropout, a practitioner could educate a patient about trying an alternative CL and consider delefilcon A lenses as an option.

Silicone hydrogel versus hydrogel soft contact lenses for differences in patient-reported eye comfort and safety.

BACKGROUND: Ocular discomfort is the leading cause of permanent discontinuation of soft contact lens (SCL) wear. Silicone hydrogel and hydrogel materials are the two major categories of SCLs, with silicone hydrogel materials being newer and more breathable than hydrogel materials. Whether comfort is associated with SCL material is controversial despite numerous studies. Similarly, the difference between these materials in terms of safety outcomes (e.g. frequency of microbial keratitis) is unclear. OBJECTIVES: To evaluate the comparative effectiveness and safety of silicone hydrogel compared with hydrogel SCLs on self-reported comfort, dry eye test results, and adverse events in SCL-wearing adults 18 years of age or older. SEARCH METHODS: The Cochrane Eyes and Vision Information Specialist searched the electronic databases for randomized controlled trials (RCTs). 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 (WHO) International Clinical Trials Registry Platform (ICTRP). We also searched the reference lists of identified studies, review articles, and guidelines for information about relevant studies that may not have been identified by our search strategy. Furthermore, we contacted investigators regarding ongoing trials. The most recent database search was conducted on 24 June 2022. SELECTION CRITERIA: Our search selection criteria included RCTs, quasi-RCTs, and cross-over RCTs. DATA COLLECTION AND ANALYSIS: We applied standard Cochrane methodology. MAIN RESULTS: We included seven parallel-group RCTs conducted in the USA, the UK, Australia, Germany, India, and Turkey. A total of 1371 participants were randomized. The duration of SCL wear ranged from one to 52 weeks. Study characteristics and risk of bias The median number of participants per trial was 120 (interquartile range: 51 to 314), and the average age ranged from 20.7 to 33.0 years. Women represented the majority of participants (range 55% to 74.9%; 5 RCTs). Collectively, the included trials compared eight different silicone hydrogel SCLs with three different hydrogel SCLs. Five trials compared daily disposable SCLs, and two compared extended wear SCLs (worn for seven days and six nights). New SCL wearers were enrolled in three trials. Two trials included both new and established SCL wearers, and two trials did not report participants' history of SCL use. Five trials were sponsored by industry. We judged the overall risk of bias to be 'high' or 'some concerns' for the safety and efficacy outcomes. Findings One trial reported Ocular Surface Disease Index (OSDI) results, with the evidence being very uncertain about the effects of SCL material on OSDI scores (mean difference -1.20, 95% confidence interval [CI] -10.49 to 8.09; 1 RCT, 47 participants; very low certainty evidence). Three trials reported visual analog scale comfort score results, with no clear difference in comfort between materials, but the evidence was of very low certainty; trial results could not be combined because the three trials reported results at different time points. The evidence is very uncertain about the effect of SCL material on discontinuation of contact lens wear (risk ratio [RR] 0.64, 95% CI 0.11 to 3.74; 1 RCT, 248 participants). None of the included trials reported Contact Lens Dry Eye Questionnaire (CLDEQ-8) or Standard Patient Evaluation of Eye Dryness (SPEED) scores. There was no evidence of a clinically meaningful difference (> 0.5 unit) between daily disposable silicone hydrogel and hydrogel SCLs in corneal staining, conjunctival staining, or conjunctival redness (very low certainty evidence). Adverse events Very low certainty evidence from two trials comparing daily disposable SCLs suggested no evidence of a difference between lens materials in the risk of vision-threatening adverse events at one to four weeks (RR 0.68, 95% CI 0.08 to 5.51; 2 RCTs, 368 participants). Two trials comparing extended wear SCLs indicated that hydrogel SCLs may have a 2.03 times lower risk of adverse events at 52 weeks compared with silicone hydrogel SCLs (RR 2.03, 95% CI 1.38 to 2.99; 815 participants), but the certainty of evidence was very low. AUTHORS' CONCLUSIONS: The overall evidence for a difference between all included silicone hydrogel and hydrogel SCLs was of very low certainty, with most trials at high overall risk of bias. The majority of studies did not assess comfort using a validated instrument. There was insufficient evidence to support recommending one SCL material over the other. For extended wear, hydrogel SCL may have a lower risk of adverse events at 52 weeks compared to silicon hydrogel. Future well-designed trials are needed to generate high certainty evidence to further clarify differences in SCL material comfort and safety.

Fighting Myopia with Intermittent Nearwork Breaks: 20 Seconds Every 20 Minutes Might Not Be Enough Time.

SIGNIFICANCE: Practitioners commonly prescribe the 20/20/20 rule with hopes that, if patients follow it, they will reduce their myopic progression. This clinical perspective provides evidence that 20-second break from nearwork every 20 minutes are not enough time to impact ocular growth.The ongoing myopia epidemic is a major public health crisis. Although the correlation between nearwork tasks such as reading, computers, and smartphones and myopia development is controversial, multiple lines of research suggest that sustained nearwork contributes to myopia development. Clinicians have proposed that children should take short breaks from nearwork with a 20-second break every 20 minutes being a common suggestion. Animal model data do strongly support the idea that multiple short breaks across time can cancel out the effects of longer periods of myopia-promoting activities. However, the animal model data also suggest that repeated episodes of 20 seconds are ineffective at reducing myopia development and instead indicate that sustained breaks of 5 minutes or more every hour are needed to negate myopiagenic effects.

Identifying the content, functionalities, and features of a mobile application for contact lens wearers.

BACKGROUND: Lack of attention to end-users' requirements and preferences may lead to the failure of health information technology (IT) interventions. Identifying users' needs for designing a mobile application can lead to the development of an acceptable intervention. This study aimed to determine the requirements for designing a mobile application to educate and provide needed information to contact lens (CL) wearers. METHODS: A qualitative study was conducted on 24 CL wearers and nine eye care practitioners from the three CL clinics in Iran. Data were collected through semi-structured interviews and analyzed using the conventional content analysis proposed by Lundman and Graneheim. Lincoln and Guba's criteria were used to ensure the trustworthiness of the data. RESULTS: The three main categories that emerged from the interviews were mobile application content, mobile application functionalities, and mobile application features. Ten subcategories and 57 sub-subcategories were also identified. It was determined that mobile content should focus on advice and information for optimizing the CL wearing experience and training regarding the use of CLs. Entering information required for self-care, computational capability, interactivity, updates, and reminders were determined as needed functionalities. The participants recommended features for the structure and user interface of the mobile application and information presentation methods. CONCLUSION: This study identified the information needed to develop a mobile application for CL wearers. This also provides insights regarding required functionalities when applying IT interventions. These findings can be used by CL clinics, developers of health information systems, policymakers, and health planners to design better CL-related care and compliance interventions.

Contact Lens Adaption in Neophytes.

SIGNIFICANCE: Clinicians commonly either recommend patients begin contact lens (CL) wear full time or suggest that patients should gradually increase their wear times during the first few days of wear. This study found no differences between these two wear schedules, suggesting that patient preference may be the best schedule. PURPOSE: The purpose of this study was to determine if there are any clinical differences in neophyte, 2-week, reusable soft CL wearers who were randomized to either a full-time or a gradually increasing wear time schedule. METHODS: This was an investigator-masked, three-visit, randomized, clinical trial. Participants were randomized to wear their CLs full time starting on the first day or gradually starting with 2 hours of wear on the first day and increasing wear by 2 hours each day until 8 hours or more of wear per day was achieved. Symptoms (Ocular Surface Disease Index and visual analog scale) and ocular surface signs (tear breakup time, extent of corneal staining, and Schirmer test I) were evaluated at each visit. RESULTS: A total of 25 participants were randomized, with 21 participants completing at least 1 week of follow-up. Completed participants had a mean ± standard deviation age of 23.5 ± 3.0 years, and 48% were female. No significant between-group differences were found when comparing the full-time and gradual wear time schedule groups at 2 weeks (all, P > .32): Ocular Surface Disease Index (10.8 ± 8.5 vs. 16.3 ± 18.8), visual analog scale (89.0 ± 9.7 vs. 81.8 ± 18.7), tear breakup time (11.7 ± 7.0 vs. 9.8 ± 2.7), extent of corneal staining (0.0 ± 0.1 vs. 0.3 ± 0.5), or Schirmer test I (15.9 ± 8.8 vs. 21.2 ± 12.5). CONCLUSIONS: No between-group differences were found for any metric evaluated, which suggests that the best wear schedule may be the one that best suits the neophyte CL wearer's lifestyle.

Established soft contact lens wearers' awareness of and initial experiences with orthokeratology.

OBJECTIVES: To understand the initial awareness of and experience with orthokeratology in a group of adult, symptomatic, soft contact lens (CL) wearers. METHODS: This was a prospective, 3-month, open-label study of symptomatic soft CL wearers who were between the ages of 18 and 45 years. Baseline measurements were taken and then all subjects were treated with orthokeratology. A dry eye evaluation was completed at baseline prior to orthokeratology treatment. This same dry eye evaluation was completed 1 week and 1 month after orthokeratology treatment. An investigator-designed questionnaire that aimed to understand the subject's initial awareness of and experience with orthokeratology was also administered at the baseline, 1-week, 1-month and 3-month visits (perceptions, knowledge, tolerance and ability to apply and remove orthokeratology lenses). RESULTS: Twenty-nine out of 40 subjects completed this study. Completed subjects (age = 24.28 ± 3.75 years) had significant improvements in ocular comfort over the course of the study compared to their soft CLs. Most subjects were unfamiliar with orthokeratology before the study, were able to quickly adapt to the treatment and were likely to recommend orthokeratology to friends or children for myopia management. CONCLUSIONS: This study found that few subjects knew about orthokeratology before learning about it through this investigation, suggesting that patients should be offered this treatment more regularly. This conclusion is supported by the ability of the subjects to learn and adapt to orthokeratology with ease, and their likelihood to recommend it to a friend or child.

Treating Uncomfortable Contact Lens Wear With Orthokeratology.

OBJECTIVES: Many contact lens (CL) users permanently discontinue wear because of ocular dryness and discomfort. This study aimed to determine whether refitting symptomatic soft CL wearers in to orthokeratology could improve ocular symptoms and signs. METHODS: This was a prospective, 3-month, open-label study of symptomatic (Contact Lens Dry Eye Questionnaire [CLDEQ-8] ≥12) soft CL wearers who were between the ages of 18 and 45 years. All subjects were refit into orthokeratology CLs (Emerald, Euclid Systems). The following tests were completed: CL history, Standardized Patient Evaluation of Eye Dryness (SPEED) questionnaire, CLDEQ-8, CLDEQ-4, logarithm of the minimum angle of resolution visual acuity, pupil size, refractive error, slit-lamp biomicroscopy, noninvasive tear break-up time, tear meniscus height, phenol red thread, conjunctival staining, corneal aesthesiometry, and corneal topography. RESULTS: Twenty-nine of 40 qualifying subjects (age=24.43±4.62 years) completed the study. No significant differences were detected between completed and noncomplete subjects. Completed subjects had significantly better CLDEQ-8, CLDEQ-4, and SPEED scores at 3 months compared with baseline. Completed subjects had significantly better conjunctival staining scores and flatter keratometry values at 1 month compared with baseline. CONCLUSIONS: Although not all symptomatic soft CL wearers were able to be refit into orthokeratology, subjects who were wearing orthokeratology at 3 months had a significant and clinically meaningful improvement in ocular symptoms. Additional work is needed to determine the mechanism leading to improved comfort because few clinical signs were changed after switching to orthokeratology.

Morphological ciliary muscle changes associated with form deprivation-induced myopia.

Myopic children have larger ciliary muscles than non-myopic children, suggesting that the ciliary muscle may have an impact on or be affected by refractive error development. The guinea pig represents an attractive model organism for myopia development research. The purpose of the study was to investigate whether form deprivation-induced myopia in one or more strains of guinea pig causes thickening of the ciliary muscle as seen in human myopia. Thirty-nine guinea pigs were bred from in-house progenitors obtained from Cincinnati Children's Hospital (Cincinnati) and the United States Army (Strain 13). At 2-4 days of age the right eyes of animals were exposed to form deprivation for 7 days while the fellow eyes served as controls. Refractive error was determined with retinoscopy while vitreous chamber depth (VCD) and axial length (AL) were determined with A-scan ultrasound. Ciliary muscle characteristics (ciliary muscle length, cross-sectional area, volume, cell number, cell size, and smooth muscle actin concentration) were determined histologically with antibody labeling and analyzed according to whether the animal developed axial myopia (anisometropia > -2.00 D with VCD and/or AL differences > 0.1 mm) or was unresponsive. This analysis method yielded four groups with Group 1 having no induced myopia but with axial elongation (n = 11), Group 2 having myopia without vitreous or axial elongation (n = 8), Group 3 having myopia with either vitreous or axial elongation (n = 11), and Group 4 having myopia with both vitreous and axial elongation (n = 8). There were no post-treatment inter-ocular differences between strains or for the overall group of animals for any ciliary muscle variable; however, a higher response group number in multivariate ordinal regression was related to having a treated compared to fellow eye that had a lower smooth muscle actin concentration (p = 0.006), with a shorter ciliary muscle length (p = 0.042), and a less oblate eye shape (p = 0.010). Guinea pig ciliary muscle length and smooth muscle actin concentration were significantly less in the treated eyes of axially myopic animals suggesting that 7 days of form deprivation induced ciliary muscle cellular atrophy or inhibited ciliary muscle growth. Form deprivation myopia in the guinea pig does not result in the increase in ciliary muscle thickness associated with human juvenile and adult myopia.

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.

Punctal occlusion for dry eye syndrome.

BACKGROUND: Dry eye syndrome is a disorder of the tear film that is associated with symptoms of ocular discomfort. Punctal occlusion is a mechanical treatment that blocks the tear drainage system in order to aid in the preservation of natural tears on the ocular surface. OBJECTIVES: To assess the effects of punctal plugs versus no punctal plugs, different types of punctal plugs, and other interventions for managing dry eye. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 11), MEDLINE Ovid (1946 to 8 December 2016), Embase.com (1947 to 8 December 2016), PubMed (1948 to 8 December 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 8 December 2016), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com; last searched 18 November 2012 - this resource is now archived), ClinicalTrials.gov (www.clinicaltrials.gov; searched 8 December 2016), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en; searched 8 December 2016). We did not use any date or language restrictions in the electronic searches for trials. We also searched the Science Citation Index-Expanded database and reference lists of included studies. The evidence was last updated on 8 December 2016 SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials of collagen or silicone punctal plugs in symptomatic participants diagnosed with aqueous tear deficiency or dry eye syndrome. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We contacted study investigators for additional information when needed. MAIN RESULTS: We included 18 trials (711 participants, 1249 eyes) from Austria, Canada, China, Greece, Japan, Mexico, Netherlands, Turkey, the UK, and the USA in this review. We also identified one ongoing trial. Overall we judged these trials to be at unclear risk of bias because they were poorly reported. We assessed the evidence for eight comparisons.Five trials compared punctal plugs with no punctal plugs (control). Three of these trials employed a sham treatment and two trials observed the control group. Two trials did not report outcome data relevant to this review. There was very low-certainty evidence on symptomatic improvement. The three trials that reported this outcome used different scales to measure symptoms. In all three trials, there was little or no improvement in symptom scores with punctal plugs compared with no punctal plugs. Low-certainty evidence from one trial suggested less ocular surface staining in the punctal plug group compared with the no punctal plug group however this difference was small and possibly clinically unimportant (mean difference (MD) in fluorescein staining score -1.50 points, 95% CI -1.88 to -1.12; eyes = 61). Similarly there was a small difference in tear film stability with people in the punctal plug group having more stability (MD 1.93 seconds more, 95% CI 0.67 to 3.20; eyes = 28, low-certainty evidence). The number of artificial tear applications was lower in the punctal plug group compared with the no punctal plugs group in one trial (MD -2.70 applications, 95% CI -3.11 to -2.29; eyes = 61, low-certainty evidence). One trial with low-certainty evidence reported little or no difference between the groups in Schirmer scores, but did not report any quantitative data on aqueous tear production. Very low-certainty evidence on adverse events suggested that events occurred reasonably frequently in the punctal plug group and included epiphora, itching, tenderness and swelling of lids with mucous discharge, and plug displacement.One trial compared punctal plugs with cyclosporine (20 eyes) and one trial compared punctal plugs with oral pilocarpine (55 eyes). The evidence was judged to be very low-certainty due to a combination of risk of bias and imprecision.Five trials compared punctal plugs with artificial tears. In one of the trials punctal plugs was combined with artificial tears and compared with artificial tears alone. There was very low-certainty evidence on symptomatic improvement. Low-certainty evidence of little or no improvement in ocular surface staining comparing punctal plugs with artificial tears (MD right eye 0.10 points higher, 0.56 lower to 0.76 higher, MD left eye 0.60 points higher, 0.10 to 1.10 higher) and low-certainty evidence of little or no difference in aqueous tear production (MD 0.00 mm/5 min, 0.33 lower to 0.33 higher)Three trials compared punctal plugs in the upper versus the lower puncta, and none of them reported the review outcomes at long-term follow-up. One trial with very low-certainty evidence reported no observed complications, but it was unclear which complications were collected.One trial compared acrylic punctal plugs with silicone punctal plugs and the trial reported outcomes at approximately 11 weeks of follow-up (36 eyes). The evidence was judged to be very low-certainty due to a combination of risk of bias and imprecision.One trial compared intracanalicular punctal plugs with silicone punctal plugs at three months follow-up (57 eyes). The evidence was judged to be very low-certainty due to a combination of risk of bias and imprecision.Finally, two trials with very low-certainty evidence compared collagen punctal plugs versus silicone punctal plugs (98 eyes). The evidence was judged to be very low-certainty due to a combination of risk of bias and imprecision. AUTHORS' CONCLUSIONS: Although the investigators of the individual trials concluded that punctal plugs are an effective means for treating dry eye signs and symptoms, the evidence in this systematic review suggests that improvements in symptoms and commonly tested dry eye signs are inconclusive. Despite the inclusion of 11 additional trials, the findings of this updated review are consistent with the previous review published in 2010. The type of punctal plug investigated, the type and severity of dry eye being treated, and heterogeneity in trial methodology confounds our ability to make decisive statements regarding the effectiveness of punctal plug use. Although punctal plugs are believed to be relatively safe, their use is commonly associated with epiphora and, less commonly, with inflammatory conditions such as dacryocystitis.

Over the counter (OTC) artificial tear drops for dry eye syndrome.

BACKGROUND: Over the counter (OTC) artificial tears historically have been the first line of treatment for dry eye syndrome and dry eye-related conditions like contact lens discomfort, yet currently we know little regarding the overall efficacy of individual, commercially available artificial tears. This review provides a much needed meta-analytical look at all randomized and quasi-randomized clinical trials that have analyzed head-to-head comparisons of OTC artificial tears. OBJECTIVES: To evaluate the effectiveness and toxicity of OTC artificial tear applications in the treatment of dry eye syndrome compared with another class of OTC artificial tears, no treatment, or placebo. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to December 2015), EMBASE (January 1980 to December 2015), Latin American and Caribbean Health Sciences (LILACS) (January 1982 to December 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and the US Food and Drugs Administration (FDA) website (www.fda.gov). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 4 December 2015. We searched reference lists of included trials for any additional trials not identified by the electronic searches. SELECTION CRITERIA: This review includes randomized controlled trials with adult participants who were diagnosed with dry eye, regardless of race and gender. We included trials in which the age of participants was not reported, and clinical trials comparing OTC artificial tears with another class of OTC artificial tears, placebo, or no treatment. This review did not consider head-to-head comparisons of artificial tears with another type of dry-eye therapy. DATA COLLECTION AND ANALYSIS: We followed the standard methodological procedures expected by Cochrane. Two authors independently screened the search results, reviewed full-text copies for eligibility, examined risk of bias, and extracted data. We performed meta-analysis for trials that compared similar interventions and reported comparable outcomes with sufficient data. We summarized all other included trial results in the text. MAIN RESULTS: We included 43 randomized controlled trials (3497 participants with dry eye). Due to the heterogeneity of study characteristics among the included trials with respect to types of diagnostic criteria, interventions, comparisons, and measurements taken, our ability to perform meta-analyses was limited. The review found that, in general, there was uncertainty whether different OTC artificial tears provide similar relief of signs and symptoms when compared with each other or placebo. Nevertheless, we found that 0.2% polyacrylic acid-based artificial tears were consistently more effective at treating dry eye symptoms than 1.4% polyvinyl alcohol-based artificial tears in two trials assessing this comparison (175 participants). All other included artificial tears produced contradictory between-group results or found no between-group differences. Our review also found that OTC artificial tears may be generally safe, but not without adverse events. Overall, we assessed the quality of evidence as low due to high risks of bias among included trials and poor reporting of outcome measures which were insufficient for quantitative analysis. Furthermore, we identified an additional 18 potentially eligible trials that were reported only in clinical trial registers with no associated results or publications. These trials reportedly enrolled 2079 total participants for whom no data are available. Such lack of reporting of trial results represents a high risk of publication bias. AUTHORS' CONCLUSIONS: OTC artificial tears may be safe and effective means for treating dry eye syndrome; the literature indicates that the majority of OTC artificial tears may have similar efficacies. This conclusion could be greatly skewed by the inconsistencies in study designs and inconsistencies in reporting trial results. Additional research is therefore needed before we can draw robust conclusions about the effectiveness of individual OTC artificial tear formulations.

Associations with Meibomian Gland Atrophy in Daily Contact Lens Wearers.

PURPOSE: To determine associations for contact lenses (CLs) and meibomian gland atrophy in a matched-pair study. METHODS: Contact lens wearers (case) and age- and sex-matched non-contact lens (NCL) wearers with no history of CL use (control) were recruited for a multicenter study. All subjects were administered the Ocular Surface Disease Index questionnaire and a comprehensive battery of clinical tests (e.g., tear breakup time, bulbar and limbal redness, meibography, etc.) were performed. Upper and lower eyelid meibomian gland atrophy were graded with both digital meibography (percent gland atrophy) and visual meiboscore methods. Conditional logistic regression analyses were then used to determine relationships among CL use, meibomian gland atrophy, and ocular surface signs and symptoms. RESULTS: A total of 70 matched pairs were analyzed. The mean (± SD) age of the CL group was 30.6 (± 12.4) years, and that of the NCL group was 30.1 (± 12.2) years. The subjects were 63% female. The association between CL wear and meiboscore was not significant univariately, but the best-fitting multivariate regression model showed that higher meiboscores were associated with being a CL wearer (odds ratio [OR], 2.45) in a model that included eyelid margin erythema (OR, 0.25) and lissamine green staining (OR, 1.25). Percent gland atrophy was not associated with CL wear in regression analysis (p = 0.31). CONCLUSIONS: This study determined inconclusive associations with CLs and meibomian gland atrophy. This study also provided a comprehensive assessment of differences between CL and NCL wearers.

Guinea pig ciliary muscle development.

PURPOSE: The purpose of this study was to develop a method for quantifying guinea pig ciliary muscle volume (CMV) and to determine its relationship to age and ocular biometric measurements. METHODS: Six albino guinea pigs' eyes were collected at each of five ages (n = 30 eyes). Retinoscopy and photography were used to document refractive error, eye size, and eye shape. Serial sections through the excised eyes were made and then labeled with an α-smooth muscle actin antibody. The ciliary muscle was then visualized with an Olympus BX51 microscope, reconstructed with Stereo Investigator (MBF Bioscience), and analyzed using Neurolucida Explorer (MBF Bioscience). Full (using all sections) and partial (using a subset of sections) reconstruction methods were used to determine CMV. RESULTS: There was no significant difference between the full and partial volume determination methods (p = 0.86). The mean (±SD) CMV of the 1-, 10-, 20-, 30-, and 90-day-old eyes was 0.40 (±0.16) mm, 0.48 (±0.13) mm, 0.67 (±0.15) mm, 0.86 (±0.35) mm, and 1.09 (±0.63) mm, respectively. Ciliary muscle volume was significantly correlated with log age (p = 0.001), ocular length (p = 0.003), limbal circumference (p = 0.01), and equatorial diameter (p = 0.003). It was not correlated with refractive error (p = 0.73) or eye shape (p = 0.60). Multivariate regression determined that biometric variables were not significantly associated with CMV after adjustment for age. CONCLUSIONS: Three-dimensional reconstruction was an effective means of determining CMV. These data provide evidence that ciliary muscle growth occurs with age in tandem with eye size in normal albino guinea pigs. Additional work is needed to determine the relationship between CMV and abnormal ocular growth.

Comparing meibomian gland visibility on optical coherence tomography and Keratograph 5M images using objective and subjective grading methods.

PURPOSE: To investigate if there is a visible difference in meibomian gland (MG) length between images captured with the Visante optical coherence tomography (OCT; wavelength = 1,310 nm) and the OCULUS Keratograph 5M (K5M; wavelength = 880 nm). METHODS: Adults between 18 and 40 years were recruited. Baseline dry eye disease was evaluated with the Standard Patient Evaluation of Eye Dryness (SPEED) and tear meniscus height and tear breakup time with the K5M. Right upper and lower eyelid MGs were imaged with the K5M and Visante OCT. Each image was graded with the 0 to 3 meiboscore scale. The central 5 MGs were evaluated with ImageJ for percent gland length visibility. RESULTS: Thirty participants were analyzed with a median (interquartile range [IQR]) age of 23.0 (5.0) years (53.3 % female). Overall, participants were asymptomatic and had normal tear films. Meiboscores based on K5M and Visante OCT was significantly different for the lower eyelid (0[1] vs 1[2]; p = 0.007) but not the upper eyelid (0[1] vs 0[1]; p = 1.00). The mean percent gland visibility of the upper eyelid (82.7[9.6] vs 75.2[13.5]; p < 0.001) and the lower eyelid (81.2[12.7] vs 64.1[17.6]; p < 0.001) were significantly greater on the Visante OCT than the K5M images, respectively. CONCLUSION: OCT images had significantly greater percent visible MG lengths than the K5M images. This suggests viable segments of the MGs may be missed with typical imaging, which may explain how it is possible that studies have found less post-treatment MG atrophy.

Wnt signaling genes of murine chromosome 15 are involved in sex-affected pathways of inflammatory arthritis.

OBJECTIVE: Sex disparities in rheumatoid arthritis (RA) are well documented despite the lack of any known major RA susceptibility genes mapped to sex chromosomes. Murine chromosome 15 carries the sex-affected Pgia8 locus that mediates proteoglycan-induced arthritis, and homologous human loci are associated with RA. This study was undertaken to identify genes/mechanisms implicated in sex disparities in arthritis. METHODS: Gene expression analysis was performed using RNA isolated from the paws of male and female Pgia8-congenic mice with collagen antibody-induced arthritis. Results were corroborated by reverse transcription-polymerase chain reaction, and mice were also studied prior to disease onset. Ingenuity Pathways Analysis of the expression patterns and gene functions was used to discover locus-specific and sex-affected signature transcripts. RESULTS: We found that the Pgia8 locus regulates antibody-mediated inflammatory arthritis differently in males and females. In Pgia8-congenic males, arthritis severity was 30% less (P < 0.005) than in wild-type males, but the antiinflammatory effect was similar in wild-type and congenic females. Transcriptome analysis indicated that 12 genes within the locus were significantly dysregulated in arthritic joints of congenic mice; expression of these genes was also sex specific. The genes that correlated most highly with arthritis severity included those for collagen triple-helix repeat-containing 1 (Cthrc1), metalloproteinase (Adamts12), R-spondin (Rspo2), and syndecan (Sdc2) (r = 0.87-0.91). The level of Cthrc1 message also correlated with that of the genes for the proinflammatory cytokines interleukin-1ß and interleukin-6. CONCLUSION: These results indicate that sex-specific disparities in RA are linked to transcriptional regulation of genes involved in cartilage degradation (Adamts12) and canonical and noncanonical Wnt signaling (Cthrc1, Rspo2, Sdc2).

Real-Time Ocular Comfort Reporting in Monthly Replacement Contact Lens Wearers.

Purpose: To map contact lens (CL) comfort over the full wear day and across 1 month's wear in established, asymptomatic to minimally symptomatic, reusable, soft CL wearers. Methods: Adult, 18- to 45-year-old, participants were recruited and required to have 20/20 best-corrected visual acuity or better and must have been asymptomatic to minimally symptomatic CL wearers. Participants were required to be able to wear TOTAL30® sphere CLs and have minimal astigmatism. Participants were fit in the study CLs and asked to wear these CLs daily for the next month for 16 hours per day each day. Participants were asked to complete a visual analog scale (VAS) survey via text message at time of CL application and after 8, 10, 12, 14, and 16 hours of wear and at CL removal on days 1, 2, 3, 4, and 5 and at 2 weeks and 1 month. The utilized VAS had a ±50 scale with positive scores being comfortable, negative scores being uncomfortable, and scores of 0 being neutral comfort. Results: Forty-eight participants were recruited who had a mean ± SD age of 26.2 ± 5.2 years (71% female). Mean initial VAS CL comfort scores at initial CL dispense were 45.56 ± 9.20 units. Mean CL wear times for any of the days evaluated were at least 14.80 ± 2.41 hours per day and did not differ across the study (p = 0.77). Mean comfort VAS scores significantly decreased over the wear day (all days p ≤ 0.02), yet there were no significant differences in VAS comfort scores across the same time of day for the duration of the study (all times p ≥ 0.06). Conclusion: This study determined that while CL wearers were slightly less comfortable at the end of the day compared to application, this comfort change was minimal given that the average participants had overwhelmingly good comfort at all time-points evaluated. Comfort scores were likewise consistent across 1 month of wear.