Regional Conjunctival Differences in Glycocalyx Mucin Expression in Dry Eye and Normal Subjects.

Purpose: To compare regional conjunctival expression of membrane-associated mucins (MAMs) MUC1, MUC4, and MUC16 in normal and dry eye (DE) subjects. Methods: Adults with and without signs and symptoms of DE were recruited. Impression cytology was performed to collect MAMs from four bulbar and upper eyelid palpebral conjunctival regions of both eyes. After protein extraction, samples from both eyes of a single subject were pooled by region, and expression was analyzed using a capillary electrophoresis nano-immunoassay system. The chemiluminescence intensity of each antigen binding signal was calculated after normalization to the total protein amount. Statistical analyses were conducted using GraphPad Prime 9. Results: Samples from thirteen to sixteen DE and seven to eleven normal subjects were analyzed. In normal samples, MUC1 expression from the nasal bulbar conjunctiva was significantly greater than superior (P = 0.004) and inferior (P = 0.005). In DE samples, MUC1 expression was highest superiorly. Significant differences in MUC4 and MUC16 expression were not seen in normal samples. MUC4 and MUC16 expression was upregulated superiorly (P < 0.0001) and inferiorly (P < 0.0001) in DE compared with those regions in normal samples. Conclusions: Although MAMs form a hydrophilic barrier called the glycocalyx, each mucin may have unique functions that are currently unexplored. All MAMs were expressed in the upper palpebral conjunctiva. Increased MUC1 expression nasally in healthy subjects suggests a functional need for increased protection. When comparing DE with normal eyes, upregulation of MUC1 superiorly, and in both MUC4 and MUC16 both superiorly and inferiorly, may indicate a need to decrease eyelid friction during blinking, especially in DE.

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.

TFOS lifestyle: Impact of societal challenges on the ocular surface.

Societal factors associated with ocular surface diseases were mapped using a framework to characterize the relationship between the individual, their health and environment. The impact of the COVID-19 pandemic and mitigating factors on ocular surface diseases were considered in a systematic review. Age and sex effects were generally well-characterized for inflammatory, infectious, autoimmune and trauma-related conditions. Sex and gender, through biological, socio-economic, and cultural factors impact the prevalence and severity of disease, access to, and use of, care. Genetic factors, race, smoking and co-morbidities are generally well characterized, with interdependencies with geographical, employment and socioeconomic factors. Living and working conditions include employment, education, water and sanitation, poverty and socioeconomic class. Employment type and hobbies are associated with eye trauma and burns. Regional, global socio-economic, cultural and environmental conditions, include remoteness, geography, seasonality, availability of and access to services. Violence associated with war, acid attacks and domestic violence are associated with traumatic injuries. The impacts of conflict, pandemic and climate are exacerbated by decreased food security, access to health services and workers. Digital technology can impact diseases through physical and mental health effects and access to health information and services. The COVID-19 pandemic and related mitigating strategies are mostly associated with an increased risk of developing new or worsening existing ocular surface diseases. Societal factors impact the type and severity of ocular surface diseases, although there is considerable interdependence between factors. The overlay of the digital environment, natural disasters, conflict and the pandemic have modified access to services in some regions.

A review of meibomian gland structure, function, and contact lens wear.

PURPOSE: To provide a balanced literature review of the studies that have evaluated the effect of contact lenses on meibomian gland (MG) health. METHODS: A PubMed.gov literature search was conducted on or before May 15, 2021. No other time constraints were applied. Search terms included the following: "meibomian gland(s)" plus "contact lens(es)" or "meibography" plus "contact lens(es)". Only full text articles written in English were considered. The reference lists of recovered papers were used to identify articles missed during the primary search. Included articles were required to discuss the impact of contact lenses on MG morphology or function and were graded according to the level of evidence presented. RESULTS: The literature indicates that contact lenses impact MG function; however, the data are equivocal regarding contact lenses inducing MG structural changes. The literature likewise indicates that the mechanism(s) by which contact lenses impact the MGs are likely multifactorial. Recent data suggests that MGs may have some plasticity. Detected differences between studies likely stem from varied populations evaluated, study designs, and the duration of the evaluation periods. CONCLUSIONS: With this literature review finding conflicting relationships between MG health and contact lens use, future longitudinal studies with standardized clinical MG assessments are needed to determine the true impact of contact lenses on MG health. Until these data are obtained, contact lens wearers should undergo a full MG evaluation, especially because recent data suggest that MG treatments may restore MG structure and function.

Frequency of Contact Lens Complications Between Contact Lens Wearers Using Multipurpose Solutions Versus Hydrogen Peroxide in the United States and Canada.

OBJECTIVES: To retrospectively compare frequency of contact lens (CL) complications in soft CL users of hydrogen peroxide (H2O2) and multipurpose solutions (MPS). METHODS: This was a multicenter, retrospective chart review of CL records from each patient's three most recent eye examinations at academic and private practices. Patients must have used the same solution type for at least 3 years. Univariate analyses were conducted using t tests, and chi-square or Fisher's exact test for categorical measures. RESULTS: There were 1,137 patients included, with 670 (59%) using MPS and 467 (41%) H2O2. In total, 706 (62%) experienced at least one complication; 409 used MPS and 297 used H2O2. There was no difference in the proportion of patients experiencing at least one complication between MPS (61%) and H2O2 (64%) (P=0.38). Multipurpose solutions users were more likely to report discomfort compared with H2O2 users (P=0.04). Presumed microbial keratitis was experienced by 16 MPS and nine H2O2 users (P=0.60). CONCLUSIONS: No significant differences were found in the frequency of CL complications between MPS and H2O2. H2O2 users were less likely to report discomfort and thus switching to a H2O2 system may be an alternative in CL users with discomfort.

Lipid Analysis on Block Copolymer-containing Packaging Solution and Lens Care Regimens: A Randomized Clinical Trial.

SIGNIFICANCE: Lotrafilcon B lenses packaged in and cared for with block copolymer-containing (polyoxyethylene-polyoxybutylene; EOBO) lens care solutions resulted in lower cholesterol extraction than each of the habitual silicone hydrogel lens/multipurpose solution (MPS) regimens tested. PURPOSE: This study aimed to compare the extracted cholesterol of lotrafilcon B lenses packaged in and cared for with EOBO-containing lens care solutions with the extracted cholesterol of habitual silicone hydrogel lenses cared for with MPS not containing EOBO. METHODS: In this prospective, randomized, observer-masked parallel study, habitual wearers of senofilcon C, senofilcon A, comfilcon A, and samfilcon A contact lenses using a non-EOBO MPS were randomized 1:1 to lotrafilcon B lenses packaged in and cared for with EOBO-containing solutions or to their habitual lenses and MPS. Subjects randomized to lotrafilcon B were further randomized to one of two EOBO-containing lens care solutions, OPTI-FREE PUREMOIST or CLEAR CARE PLUS with HydraGlyde (Alcon Laboratories, Inc., Fort Worth, TX). A subset of right eye lenses was collected after wear, and total cholesterol was extracted and measured using a fluorometric enzymatic assay. RESULTS: Of 143 lenses analyzed, 95 were from subjects randomized to their habitual lenses/MPS and 48 to lotrafilcon B + EOBO lenses plus CLEAR CARE PLUS with HydraGlyde or OPTI-FREE PUREMOIST. The mean amounts of cholesterol extracted from lotrafilcon B + EOBO lenses cared for with CLEAR CARE PLUS with HydraGlyde (0.28 ± 0.18 µg/lens) and OPTI-FREE PUREMOIST (0.28 ± 0.48 µg/lens) were significantly lower than those extracted from senofilcon C (4.18 ± 3.25 µg/lens), senofilcon A (2.19 ± 2.69 µg/lens), comfilcon A (2.17 ± 1.47 µg/lens), and samfilcon A (2.07 ± 1.48 µg/lens) lenses used with MPS (P < .0001 each). CONCLUSIONS: Cholesterol sorption was significantly lower in wearers of lotrafilcon B lenses cared for with polyoxyethylene-polyoxybutylene-containing lens care solutions than in users of habitual silicone hydrogel lenses cared for with non-polyoxyethylene-polyoxybutylene MPS.

A Review of Contact Lens Dropout.

PURPOSE: Contact lens (CL) dropout is likely a major factor contributing to the near stagnant growth in the CL market. The purpose of this review is to summarize the current state of knowledge related to the frequency of CL dropout and the factors associated with it. METHODS: PubMed.gov was searched on or before March 22, 2020, with the terms "contact lens" with "dropout" or "cessation" or "disruption" or "discomfort". Pertinent articles were collected. The references from these articles were likewise searched to identify additional relevant articles. Only manuscripts written in English were included. No study design or date exclusions were imposed on this review. RESULTS: This literature review found that CL dropout was frequent across developed countries, with a CL dropout frequency that ranged between 12.0% and 27.4% (pooled mean = 21.7%). The top cited reason for CL dropout in established CL wearers was discomfort, while vision was the top reason in neophyte CL wearers. If given the chance, CL dropouts are often able to successfully resume CL wear up to 74% of the time. While the literature is mixed with regard to factors promoting CL dropout, meibomian gland dysfunction appears to promote CL dropout. CONCLUSION: CL dropout is a frequently encountered condition that may be curtailed by early detection, patient education, alterative CL options, or early treatment of underlying ocular surface diseases such as meibomian gland dysfunction.

Tear Film and Meibomian Gland Characteristics in Adolescents.

PURPOSE: To establish normative values of ocular surface parameters in adolescents and explore factors associated with meibomian gland (MG) dropout. METHODS: Subjects between 8 and 17 years of age were enrolled in this cross-sectional study. All subjects were given dry eye and lifestyle questionnaires. Tear film assessments and meibography were performed. Statistical tests included a one-way analysis of variance to test differences in ocular surface parameters between age groups and linear correlations between clinical findings and lifestyle factors. RESULTS: Two hundred twenty-five subjects completed the study. Thirty-four subjects (15%) reported ocular discomfort, primarily itching. Tear meniscus height increased with age and was greatest in the oldest subjects (mean = 0.25 mm, P < 0.01). Across all subjects, meibography showed that 39% of the upper and 39% of the lower eyelids had MG dropout. The average MG dropout score was 0.50 ± 0.57 for the upper eyelids and was 0.67 ± 0.93 for the lower eyelids. There was no correlation between phone/tablet usage and MG dropout for either the upper (P = 0.39) or lower (P = 0.56) eyelids. CONCLUSIONS: The frequency of ocular symptoms in these adolescents was 15%. Because MG dropout is thought to increase with age, it was unexpected to observe that most subjects in this study had mild MG dropout in 1 or both eyelids. Although electronic device usage did not correlate with MG dropout in this study sample, it is still unclear what the effects of long-term digital device usage may have as the subjects age.

Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.

The purpose of this study was to investigate the effect of the Bruder Moist Heat Compress on contact lens (CL) discomfort in subjects with contact lens-related dry eye (CLDE). This was a 4-week, single-center, three-arm, randomized, open-label clinical trial in subjects diagnosed with CLDE using the Contact Lens Dry Eye Questionnaire. Fifty-one CL wearers were randomized to one of three treatment groups: application of the Bruder Compress twice a day, Bruder Compress once a day, or warm washcloth used for ten minutes twice a day without reheating. Subject diaries were monitored for compliance and collected data on daily CL comfort upon awakening and throughout the afternoon. Clinical assessments included tear film break-up time (TBUT), lipid layer thickness (LLT), and meibomian gland evaluation. Statistical tests included a generalized linear model and one-way analysis of variance (ANOVA) to investigate treatment effect on comfortable wear time. Fifty-one subjects (98% female) completed the study. After treatment, subjects using a washcloth reported more uncomfortable contact lens wear time on average (mean = 5.1 ± 2.8 h) when compared with subjects who had used the Bruder Compress in Group 1 (mean = 2.8 ± 1.6 h) (p = 0.02). In the Bruder Compress groups, there was a significant reduction in the blockage of meibomian glands (p < 0.01). No significant difference in uncomfortable wear time was found between subjects using the Bruder Compress twice daily versus once daily (p = 0.48). Subjects using the Bruder Compress once daily had the highest rate of compliance at 90.2% (p < 0.01). No significant improvements were observed in TBUT (p = 0.76) or LLT (p = 0.78). The Bruder Moist Heat Compress resulted in a significant improvement in comfortable CL wear time in subjects with CLDE.