Analysis of Factors Associated with Anterior Location of Marx's Line.

PURPOSE: The study aimed to investigate the factors associated with anterior location of Marx's line in ocular surface and living habits, especially in tear film. MATERIALS AND METHODS: This cross-sectional study enlisted 483 participants with meibomian gland dysfunction, who were divided into two groups: 160 participants with mild anterior location of Marx's line and 323 participants with moderate-to-severe anterior location. Participants completed a survey of demographic characteristics (sex, age, length of visual terminal use, sleep duration, skin property), and the Ocular Surface Disease Index and Standard Patient Evaluation of Eye Dryness questionnaires. They also underwent slit-lamp examinations of the lids, and measurements of non-invasive tear break up time, tear meniscus height, fluorescein tear break up time, lipid layer thickness, partial blink rate, lid wiper epitheliopathy, and meibomian gland dropout. RESULTS: The tear meniscus height (mild:0.21(0.18-0.25), moderate-to-severe:0.19(0.16-0.23), p = 0.004), fluorescein tear break up time(mild:3(2-4),moderate to severe:2(1-3), p = 0.000), max LLT(mild:87(62-100), moderate-to-severe:99(69-100), p = 0.04), average LLT(mild:64.5(47.5-96.75), moderate-to-severe:74(53-100), p = 0.012), min LLT(mild:52(38-75), moderate-to-severe:59(41-85), p = 0.029) differed significantly between mild and moderate-to-severe anterior location of Marx's line, and associated to the anterior location of Marx's line(r=-0.134, p = 0.03; r=-0.194, p = 0.000; r = 0.093, p = 0.041; r = 0.119, p = 0.009; r = 0.105, p = 0.022) However, no statistical significance was observed in the OSDI, SPEED, partial blink rate, non-invasive tear breakup time, lipid layer thickness, meibomian gland dropout and lid wiper epitheliopathy(p > 0.05). Meanwhile, in the demographic characteristics, statistically significant correlations were associated with skin property(r = 0.154, p = 0.001) and sleep duration(r=-0.124, p = 0.006), but not with age, sex, and the length of visual terminal use (p > 0.05). CONCLUSIONS: Lower TMH and shorter TBUT positively correlated with anterior location of the Marx's line, and were risk factors. Meanwhile, participants with oily skin and shorter sleep duration were more likely to exhibit anterior location of Marx's line.

Models for Meibomian gland dysfunction: In vivo and in vitro.

Meibomian gland dysfunction (MGD) is a chronic abnormality of the Meibomian glands (MGs) that is recognized as the leading cause of evaporative dry eye worldwide. Despite its prevalence, however, the pathophysiology of MGD remains elusive, and effective disease management continues to be a challenge. In the past 50 years, different models have been developed to illustrate the pathophysiological nature of MGD and the underlying disease mechanisms. An understanding of these models is crucial if researchers are to select an appropriate model to address specific questions related to MGD and to develop new treatments. Here, we summarize the various models of MGD, discuss their applications and limitations, and provide perspectives for future studies in the field.

Perfluorohexyloctane Eye Drops for Dry Eye Disease Associated With Meibomian Gland Dysfunction in Chinese Patients: A Randomized Clinical Trial.

Importance: Meibomian gland dysfunction (MGD) is a leading cause of evaporative dry eye disease (DED). Medical and surgical management for DED is limited; therefore, new treatment options are sought. Objective: To evaluate the efficacy and safety of SHR8058 (perfluorohexyloctane) eye drops in Chinese patients with DED associated with MGD through 57 days. Design, Setting, and Participants: This was a randomized, multicenter, double-masked, saline-controlled, phase 3 clinical trial conducted from February 4, 2021, to September 7, 2022. Patients were recruited from the departments of ophthalmology in 15 hospitals in China. Patients with DED associated with MGD were enrolled between February 4 and July 1, 2021. The diagnosis was based on patient complaint of DED symptoms, an ocular surface disease index of 25 or higher, tear film break-up time of 5 seconds or less, Schirmer I test without anesthesia results of 5 mm or more at 5 minutes, total corneal fluorescein staining (tCFS) score of 4 to 11, and an MGD score of 3 or higher. Interventions: Eligible participants were randomly assigned 1:1 to receive perfluorohexyloctane eye drops or 0.6% sodium chloride [NaCl]) 4 times per day. Main Outcomes and Measures: The primary end points were the changes from baseline in tCFS and eye dryness scores at day 57. Results: A total of 312 participants were included in the analysis: 156 (mean [SD] age, 45.4 [15.2] years; 118 female [75.6%]) in the perfluorohexyloctane group and 156 (mean [SD] age, 43.7 [15.1] years; 127 female [81.4%]) in the NaCl group. Both primary end points were achieved, ie, changes from baseline at day 57 of tCFS score (mean [SD], -3.8 [2.7] vs -2.7 [2.8]) and eye dryness score (mean [SD], -38.6 [21.9] vs -28.3 [20.8]) in the perfluorohexyloctane group were superior to the control group, with estimated mean differences of -1.14 (95% CI, -1.70 to -0.57; P < .001) and -12.74 (95% CI, -17.20 to -8.28, P < .001), respectively. Improvements on both end points appeared to be noted on day 29 and day 15, respectively, and maintained through day 57. Compared with the control, perfluorohexyloctane eye drops also alleviated symptoms including pain (mean [SD] tCFS score, 26.7 [23.7] vs -18.7 [22.5]; P = .003), awareness of DED symptoms (mean [SD] tCFS score, -38.1 [25.1] vs -23.7 [27.6]; P < .001), and frequency of dryness (mean [SD] tCFS score, -43.3 [23.8] vs -29.1 [24.8]; P < .001). Treatment-emergent adverse events occurred in 34 participants (21.8%) and 40 participants (25.6%) in the perfluorohexyloctane and control groups, respectively. Conclusions and Relevance: Results of this randomized clinical trial demonstrate that perfluorohexyloctane eye drops significantly ameliorated the signs and symptoms of DED associated with MGD with a rapid efficacy as well as satisfactory tolerability and safety through 57 days. Findings support the use of these eye drops if results can be confirmed independently and over longer time periods. Trial Registration: ClinicalTrials.gov Identifier: NCT05515471.

Hypochlorous Acid Can Be the Novel Option for the Meibomian Gland Dysfunction Dry Eye through Ultrasonic Atomization.

BACKGROUND: Dry eye is a multifactor disease which needs comprehensive treatments to keep the homeostasis of ocular surface. OBJECTIVE: To explore the effect of hypochlorous acid on the meibomian gland dysfunction dry eye through ultrasonic atomization. METHODS: We set this study of 0.01% HOCL and 0.1% hyaluronate by ultrasonic atomization. All the data was recorded at the 1st, 15th, 30th, and 55th days. The patients' complains, the meibum analysis, conjunctive congestion, corneal staining, Schirmer's I test, and NIBUT were recorded by K5M, the MMP-9, and IL-2 of tear by inflammation kit; the Demodex was recorded by microscopy. RESULTS: 53 patients have joined this study. There is no statistic difference between them on OSDI (day 15: p = 0.061, 30: p = 0.055, 55: p = 0.052); results show the 10.57 ± 0.13 and 12.54 ± 0.17 reduction on OSDI; the differences of both treatments are significant (∗∗ p < 0.01). Increased Schirmer's and TBUT are 3.27 ± 0.10 and 6.29 ± 0.10 (∗∗ p < 0.01) or 7.32 ± 1.72 s and 9.22 ± 1.41 s (∗ p < 0.05); the decreased conjunctive and corneal staining are 0.23 ± 0.07 and 0.45 ± 0.06 (∗∗ p < 0.01) or 0.42 ± 0.03 and 0.37 ± 0.02 (∗ p < 0.05) at both groups. The differences of MMP-9 and IL-2 negative rate are significant (Z = 0.896, ∗∗ p = 0.002 < 0.01; Z = 0.659, ∗∗ p = 0.001 < 0.01); the number of Demodex mites at first is 10 or 11, while the last is 2 or 6 (Z = -4.642, ∗∗ p < 0.01; Z = 2.742, p > 0.05). The Demodex count between them is significant (Z = -2.310, ∗ p = 0.032 < 0.05). The survival times (ST) of each stage at the HOCL are 110.75 (108.50 ± 24.50), 95.50 (90.25 ± 14.50), and 75.25 (73.48 ± 8.50) min which are shorter than those of control which are 155.50 (160.10 ± 21.50), 130.25 (128.25 ± 16.50), and 105.75 (102.50 ± 14.50) min (∗∗ p < 0.01). The Demodex eradication rate of HOCL is statistic significant (∗ p15th vs. 1stday = 0.028 < 0.05; ∗∗ p30th vs. 1stday = 0.002 < 0.01; ∗∗ p55th vs. 1stday = 0.0018 < 0.01). CONCLUSIONS: 0.01% HOCL improves the Demodex eradication by shortening the survival time; the HOCL acts on the ocular surface by reducing the inflammation. The ultrasonic atomization helps for the drug usage.

TearCare for the Treatment of Meibomian Gland Dysfunction in Adult Patients With Dry Eye Disease: A Masked Randomized Controlled Trial.

PURPOSE: The aim of this study was to demonstrate the safety and effectiveness of a single TearCare procedure compared with a single LipiFlow procedure in treatment of the dry eye disease associated with meibomian gland dysfunction. METHODS: In a multicenter, masked, randomized controlled trial, 135 subjects received a single TearCare (TC) treatment (n = 67) or a single LipiFlow (LF) treatment (n = 68) at baseline and were followed up for 1 month posttreatment. Tear film breakup time, meibomian gland function, and corneal and conjunctival staining scores were assessed as dry eye signs at baseline, 2 weeks, and 1 month; dry eye symptoms were assessed using the Ocular Surface Disease Index, Symptom Assessment in Dry Eye, and eye dryness questionnaires at baseline and 1 month. RESULTS: At 1 month posttreatment, both groups demonstrated significant improvements (P < 0.0001) in mean tear film breakup time and meibomian gland secretion score to 3.0 ± 4.4 and 11.2 ± 11.1 in the TC group and 2.6 ± 3.3 and 11.0 ± 10.4 in the LF group, respectively. The mean eye dryness, Symptom Assessment in Dry Eye, and Ocular Surface Disease Index scores were significantly reduced (P < 0.0001) by 35.4 ± 34.1, 38.2 ± 31.0, and 27.9 ± 20.5 in the TC group and 34.9 ± 26.9, 38.0 ± 25.9, and 23.4 ± 17.7 in the LF group, respectively. There were no statistically significant differences for any result between the groups. However, the TC group demonstrated numerically greater improvements consistently in all signs and symptoms. Device-related ocular adverse events were reported in 3 patients in the TC group (superficial punctate keratitis, chalazion, and blepharitis) and 4 patients in the LF group (blepharitis, 2 cases of foreign body sensation, and severe eye dryness). CONCLUSIONS: A single TearCare treatment significantly alleviates the signs and symptoms of dry eye disease in patients with meibomian gland dysfunction and is equivalent in its safety and effectiveness profile to LipiFlow treatment as shown in this 1-month follow-up study.

Comparative of meibomian gland morphology in patients with evaporative dry eye disease versus non-dry eye disease.

Many recent studies have showed that morphological changes are one of the key signs of meibomian gland disease (MGD). These changes can be seen even before symptom onset, potentially underestimating the prevalence of MGD; however, until now, there is no conclusive information about the impact of meibomian gland (MG) morphology in tear film physiology and disease. This study aimed to investigate the prevalence of anatomical and morphological MG alterations between patients with evaporative dry eye disease (DED) and healthy controls. Retrospective chart review of seventy-five patients with evaporative DED and healthy individuals who had dry eye assessments included Ocular Surface Disease Index questionnaire, meibum quality, meibum expressibility, lid margin abnormality, ocular staining, non-invasive tear film break-up time, and meibography. We did not find significant differences in MG alterations in the upper lid between healthy and DED subjects. Patients with evaporative DED presented MG alterations in the lower lid more frequently than healthy subjects (54.8 vs. 30.3%; p = 0.03). The presence of shortened glands was the only MG alteration that was more prevalent in the lower lid in dry-eye patients than in healthy subjects (p < 0.05). Subjects with evaporative DED presented more alterations in the lower lid than healthy subjects.

Epithelial stem cell homeostasis in Meibomian gland development, dysfunction, and dry eye disease.

Dry eye disease affects over 16 million adults in the US, and the majority of cases are due to Meibomian gland dysfunction. Unfortunately, the identity of the stem cells involved in Meibomian gland development and homeostasis is not well elucidated. Here, we report that loss of Krox20, a zinc finger transcription factor involved in the development of ectoderm-derived tissues, or deletion of KROX20-expressing epithelial cells disrupted Meibomian gland formation and homeostasis, leading to dry eye disease secondary to Meibomian gland dysfunction. Ablation of Krox20-lineage cells in adult mice also resulted in dry eye disease, implicating Krox20 in homeostasis of the mature Meibomian gland. Lineage-tracing and expression analyses revealed a restricted KROX20 expression pattern in the ductal areas of the Meibomian gland, although Krox20-lineage cells generate the full, mature Meibomian gland. This suggests that KROX20 marks a stem/progenitor cell population that differentiates to generate the entire Meibomian gland. Our Krox20 mouse models provide a powerful system that delineated the identity of stem cells required for Meibomian gland development and homeostasis and can be used to investigate the factors underlying these processes. They are also robust models of Meibomian gland dysfunction-related dry eye disease, with a potential for use in preclinical therapeutic screening.

Pathophysiology of Meibomian Glands - An Overview.

Purpose: The meibomian glands are located in the tarsal plate of the upper and lower eyelid and are responsible for the production of a lipid-rich secretion, the meibum, which forms the outer component of the tear film. Meibomian gland dysfunction results in excessive evaporation of the tear film and is the leading cause of dry eye disease (DED). Despite the high prevalence of DED, the etiology of meibomian gland dysfunction is only basically understood. In addition, the molecular mechanisms of meibomian gland maturation and physiological function are currently the focus of research.Methods: A systematic literature search was performed using the main scientific databases, including all relevant published articles up to September 2020.Results: This article provides an overview of the current state of knowledge about meibomian gland stem cells, cell surface marker expression and PPARγ signaling, as well as the pathological causes of meibomian gland dysfunction.Conclusion: Androgen deficiency, hyperkeratinization, PPARγ signaling and inflammatory reactions including neutrophil extracellular traps (NETs) seem to be key factors within the pathological processes of the meibomian gland.

Lateral Canthal Sling Procedure for Meibomian Gland Dysfunction? Results of a Pilot Study.

Background: Involutional changes of lid structures often induce horizontal lid laxity; this can result in a reduction of Meibomian gland expression, potentially leading to symptoms of dry eye. The aim of this study was to evaluate the effect of tightening the lower eyelid via a lateral canthal sling (LCS) procedure on dry eye parameters.Methods: Patients with Meibomian Gland Dysfunction (MGD), lower lid laxity (positive Snap-back Test and positive Pinch Test) and no previous lid surgery were evaluated before and 3 months after LCS procedure for symptoms by OSDI. The fellow eye without surgery functioned as a control group. MGD parameters included lipid layer thickness (LLT), non-invasive breakup time (NIBUT), tear meniscus height, loss of Meibomian glands, lid margin parallel conjunctival folds (LIPCOFs), Schirmer's test, the number of expressible Meibomian glands as well as quality of Meibum.Results: Fourteen patients (8 men and 6 women; 79.2 ± 4.0 years) were enrolled in this prospective clinical study. After 3 months, the OSDI showed a significant reduction (preop 42.9 ± 24.7; postop 23.8 ± 21.6; p = .002); NIBUT (5.5 ± 2.6 s to 9.9 ± 6.8 s p = .08) and LLT (64.3 ± 30.4 to 74.1 ± 27.8; p = .025) improved, while Schirmer Test (15.3 ± 4.7 mm to 11.9 ± 2.9 mm; p = .03) and tear meniscus height were reduced (0.8 ± 0.3 to 0.6 ± 0.2; p = .05). Meibomian gland loss scored by the meiboscale slightly increased postoperatively (1.2 ± 0.9 to 1.4 ± 0.9; p = .18). The number of expressible Meibomian glands improved (4.4 ± 2.6 to 6.8 ± 2.1, p = .002) as well as the quality of Meibum (0.9 ± 1.0 to 0.5 ± 0.8, p = .04). Snap back test as well the pinch test were negative in all patients postoperatively.Conclusion: Addressing lower lid laxity with an LCS procedure simultaneously enhances tear drainage, reduces tear film volume parameters and increases tear film stability results with an improvement of dry eye symptoms. It is likely that increased lower eyelid tension and thus excretory pressure on the Meibomian glands is responsible for these alterations.

Preoperative Management of MGD with Vectored Thermal Pulsation before Cataract Surgery: A Prospective, Controlled Clinical Trial.

Purpose: To investigate the efficacy of preoperative monocular treatment in elderly cataract patients with Meibomian Gland Dysfunction (MGD) utilizing vectored thermal pulsation treatment.Materials and Methods: This study was a prospective, examiner-masked contralateral eye clinical trial. Patients previously diagnosed with MGD undergoing uncomplicated cataract surgery in two eyes were enrolled. The eye perceived by the patient to be more symptomatic of MGD received a 12 min vectored thermal pulsation treatment using the LipiFlow Thermal Pulsation System, and was referred to as the LipiFlow-surgery eye. The contralateral eye then served as the nonLipiFlow-surgery eye. Patients with MGD not undergoing cataract surgery were enrolled as the control group. Within the control group, the eye that received LipiFlow treatment was considered the LipiFlow-nonsurgery eye, while the contralateral eye served as the nonLipiFlow-nonsurgery eye. All patients were examined before treatment and at one-week, one-month, and three-month intervals after treatment. Clinical parameters included dry eye symptoms, average lipid layer thickness (LLT-ave), tear breakup time (TBUT), corneal staining, Schirmer I tests, Meibomian glands yielding liquid secretion (MGYLS), and meibomian gland dropout.Results: A total of 32 patients (64 eyes) were examined during the three-month follow-up. There was a significant reduction in dry eye symptoms in non-surgery patients with monocular treatment of MGD, while no change in surgery patients was observed. Significant improvement of MGYLS in LipiFlow-surgery and LipiFlow-nonsurgery eyes during the follow-up time (p < .001) was reported, while no difference was observed in nonLipiFlow-surgery and nonLipiFlow-nonsurgery eyes. A statistically significant difference was seen in TBUT between LipiFlow-surgery and nonLipiFlow-surgery eyes at one-week and one-month intervals (p = .019 and 0.019, respectively). Differences in other clinical parameters were not statistically significant.Conclusions: Our findings suggest that although subjective symptoms were not alleviated, a single application of LipiFlow treatment before cataract surgery is effective in alleviating blockage of meibomian glands and preventing the decline of TBUT after cataract surgery.

Efficacy of Topical Ivermectin for the Treatment of Cutaneous and Ocular Rosacea.

Purpose: To investigate the efficacy of once-daily topical treatment of ocular and cutaneous rosacea with ivermectin 1% cream (Soolantra®, Galderma).Methods: Ten patients with rosacea were evaluated in a retrospective monocentric pilot study. Subjective symptoms (measured with the Ocular Surface Disease Index), skin findings, and ocular changes (blepharitis with telangiectasia and meibomian gland dysfunction, conjunctival redness, tear breakup time (TBUT), and fluorescein staining of the cornea) were evaluated. The follow-up was 8 months (range: 5-12 months).Results: The OSDI score decreased in the 8th week of treatment (38.5 ± 21.7, P = .004). After 16 weeks, blepharitis (P = .004), and conjunctival redness (P = .008) had strongly improved, and grade 1 was seen in all patients until the end of follow-up. Fluorescein staining of the cornea (P = .001) and TBUT (P = .016) showed significant improvement until the last follow-up visit. No side effects were observed. Conclusion: Topical ivermectin cream 1% given daily is an effective and safe therapy against rosacea.

Morphological Changes of Meibomian Glands in Men With Benign Prostate Hyperplasia.

PURPOSE: Meibomian glands are subject to regulation by sex hormones. We have now investigated the possible relation between benign prostate hyperplasia (BPH) and meibomian gland dysfunction (MGD). METHODS: Men diagnosed with BPH and receiving treatment with tamsulosin and age-matched male control subjects who attended Itoh Clinic, Saitama, Japan, were enrolled. An ocular symptom score, lid margin abnormality score, and superficial punctate keratopathy score as well as the meiboscore (0-6), meibum grade, breakup time of the tear film, and Schirmer test values were evaluated. Male pattern baldness was also graded according to the Hamilton-Norwood scale. RESULTS: Forty-four eyes of 44 men with BPH (mean age ± SD, 76.1 ± 2.2 years) and 46 eyes of 46 control subjects (mean age ± SD, 75.3 ± 6.2 years) were enrolled. The meiboscore in the BPH group (4.5 ± 1.4) was significantly higher than that in the control group (1.8 ± 1.5, P < 0.0001). Breakup time of the tear film was significantly shorter (3.6 ± 1.7 vs. 5.6 ± 2.5 seconds, P < 0.0001), and Schirmer test value was significantly smaller (9.8 ± 4.8 vs. 13.3 ± 8.0 mm, P = 0.048) in the BPH group than that in the control group. Other ocular parameters did not differ significantly between the 2 groups. The proportion of men with androgenic alopecia was also higher in the BPH group than that in the control group. CONCLUSIONS: BPH was associated with meibomian gland loss and instability of the tear film as well as with the presence of androgenic alopecia.

Changes of tear lipid mediators after eyelid warming or thermopulsation treatment for meibomian gland dysfunction.

Meibomian gland dysfunction (MGD) represents a major cause of dry eye and ocular discomfort. Lipid mediators, often termed oxylipins, can be produced enzymatically or non-enzymatically, and may modulate inflammatory processes in MGD. Here, we aimed to assess the longitudinal changes of lipid mediators after various eyelid treatments (eyelid warming and thermopulsation) over 12 weeks. Secondly, we aimed to assess the chirality of mono-hydroxyl lipid mediators from tears of MGD and healthy participants. Tears lipid mediators were extracted from Schirmer's strips and levels were quantified by liquid chromatography mass spectrometry (LC-MS) techniques. We quantified 33 lipid mediators in the tear, 18 of which (including 11-HETE, 20-OH-LTB4, and 15-oxoETE) were reduced significantly after treatment. Changes in concentrations of 10-HDoHE (r = 0.54) and 15-oxoETE (r = 0.54) were correlated to the number of meibomian gland plugs at baseline, so increased severity of MGD was associated with treatment-induced change in lipid mediators. The chiral analysis demonstrated that 5(S)-HETE, 12(S)-HETE, 15(S)-HETE, 14(S)-HDoHE, 17(S)-HDoHE and 11(R)-HETE were produced with significant enantiomeric excess (ee %) in controls compared to patients, due to enantiomer selective enzymatic action, whereas most lipid mediators were racemates in patients, due to dominance of oxidative effects which have no enantiomeric preference. Treatment of MGD restored the concentrations of 15(S)-HETE, 14(S)-HDoHE and 17(S)-HDoHE with significant ee values, suggesting reduction in oxidative action. Overall, MGD therapy reduced pro-inflammatory molecules generated by lipoxygenase and oxidative stress.

Common inflammatory and infectious conditions of the eyelid.

Patients with infection or inflammation of the eyelid will often first present to their primary care physicians with symptoms such as redness, swelling, tearing, itchiness, or a foreign body sensation. There are a variety of conditions that affect the eyelid which can cause such symptoms, and the exam and history can help a provider differentiate some of the more common conditions. This article will provide a comprehensive review of the background, diagnosis and management of dry eye disease, chalazion, hordeolum (stye), and preseptal cellulitis.

Effect of 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A Reductase Inhibitors on the Meibomian Gland Morphology in Patients with Dyslipidemia.

PURPOSE: Previous studies have suggested an association between dyslipidemia and meibomian gland dysfunction (MGD). The aim of this prospective, nonrandomized clinical study is to evaluate the possible association of dyslipidemia and its treatment with meibomian gland (MG) morphologic changes by standardized meibography. DESIGN: Prospective, nonrandomized clinical study. METHODS: Two groups of participants were enrolled: group 1, comprised of patients under regular 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) treatment for dyslipidemia, and group 2, those with newly diagnosed dyslipidemia who were under lifestyle interventions. Meibography was performed at baseline and at both the 6- and 12-month visits and were graded by meiboscores. Participants underwent slit lamp examination for signs of changes in meibum quality and MG lid morphologic features. The Ocular Surface Disease Index questionnaire was given to measure subjective symptoms of ocular surface disease. Dry eye parameters including tear meniscus height, noninvasive first and average tear film break-up time, and Schirmer test results were also recorded. RESULTS: Ninety-eight participants completed this longitudinal study over 12 months. There were statistically significant changes in total meiboscores (P = .01) and upper eyelid meiboscores (P = .012), lid margin abnormality scores (P = .0059), and meibum quality (P = .0002) in the statin group during follow-up visits. Similar changes of upper eyelid meiboscores (P = .046) and meibum quality (P = .046) were noted in the nonstatin group. CONCLUSION: Meibomian gland atrophy and deterioration of meibum quality continued in the long term among participants with dyslipidemia even under statin usage.

Organotypic Culture of Mouse Meibomian Gland: A Novel Model to Study Meibomian Gland Dysfunction In Vitro.

Purpose: Meibomian glands are essential in maintaining the integrity and health of the ocular surface. Meibomian gland dysfunction (MGD), mainly induced by ductal occlusion, is considered as the major cause of dry eye disease. In this study, a novel in vitro model was established for investigating the role of inflammation in the process of MGD. Methods: Mouse tarsal plates were removed from eyelids after dissection and explants were cultured during various time ranging from 24 to 120 hours. Meibomian gland epithelial cells were further enzymatically digested and dissociated from tarsal plates before culturing. Both explants and cells were incubated in different media with or without serum or azithromycin (AZM). Furthermore, explants were treated with IL-1ß or vehicle for 48 hours. Analyses for tissue viability, histology, biomarker expression, and lipid accumulation were performed with hematoxylin and eosin (H&E) staining, immunofluorescence staining, and Western blot. Results: Higher viability was preserved when explants were cultured on Matrigel with immediate addition of culture medium. The viability, morphology, biomarker expression, and function of meibomian glands were preserved in explants cultured for up to 72 hours. Lipid accumulation and peroxisome proliferator-activated receptor γ (PPARγ) expression increased in both explants and cells cultured in media containing serum or AZM. Treatment with IL-1ß induced overexpression of Keratin (Krt) 1 in meibomian gland ducts. Conclusions: Intervention with pro-inflammatory cytokine IL-1ß induces hyperkeratinization in meibomian gland ducts in vitro. This novel organotypic culture model can be used for investigating the mechanism of MGD.

Infrared thermography: different options of thermal eyelid warming.

PURPOSE: Current therapies of Meibomian gland dysfunction (MGD) include thermal eyelid warming. It was the aim of the study to investigate the temperature run after eyelid warming using 3 different techniques (hot compresses, Blephasteam® (Thea Pharma GmbH, France), and having a sauna) in patients with MGD compared with normal subjects by infrared thermography. METHODS: A prospective case-control study was done. Temperature profiles of the eyelids were investigated in 93 subjects (49 normals, 44 MGD patients) after warming of the eyelids by 3 methods: hot compresses, Blephasteam®, and having a sauna. Temperature runs of the eyelids were measured with an infrared thermal imaging camera (VarioCAM® HD research 675/30 mm, InfraTec GmbH) at baseline and after eyelid warming for 10 min. Statistical analysis were done by Wilcoxon test or t tests for unpaired samples. RESULTS: The initial eyelid temperature was significantly increased after the use of Blephasteam® compared with hot compresses in MGD and normal patients (p < 0.001). Having a sauna showed a similar warming effect of the eyelids than Blephasteam® in normals and MGD patients (p > 0.05). Additionally, the warming effect of the eyelids after having a sauna was significantly longer than after the use of Blephasteam® in MGD (p = 0.016) and normal patients (p = 0.01). CONCLUSION: Eyelid temperature after having a sauna was similar to commonly used warming devices; yet, the duration of the eyelid warming effect was longer. Thus, having a sauna might be an alternative option for warming of the eyelids.

Intense Pulsed Light for Meibomian Gland Disease: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the literature on the efficacy of intense pulsed light (IPL) on the eyelids in the management of meibomian gland disease (MGD) and meibomian gland-related ocular surface disease. METHODS: A literature search was last conducted on May 15, 2019, in the PubMed and Cochrane Library databases for English-language original research that assessed the effect of IPL on MGD in adult patients. Thirty-three articles were identified, and 12 studies were determined to be relevant to the criteria outlined for assessment. The panel methodologist (V.K.A.) assigned a level of evidence rating to each study; 4 studies were rated level II, and 8 studies were rated level III. Five studies had potential conflicts of interest and design limitations that affected interpretation of results. RESULTS: All studies documented improvement in clinically meaningful metrics, including tear breakup time (TBUT), corneal staining and eyelid margin measurements, meibum quality, meibomian gland expressability, ocular surface disease index (OSDI), and standard patient evaluation of eye dryness (SPEED) questionnaire scores. Side effects were relatively uncommon but included discomfort, cutaneous erythema, blistering, eyelash loss, and floaters; these were uniformly self-limited. CONCLUSIONS: Although methodological limitations and potential conflicts of interest in some studies raised concern, the existing body of literature demonstrates improvements in the signs and symptoms of MGD after IPL therapy.

Ocular surface changes in the treatment of rosacea: comparison between low-dose oral isotretinoin and doxycycline / Alterações da superfície ocular no tratamento da Rosácea: comparação entre isotretinoína oral em baixa dosagem e doxiciclina

ABSTRACT Purpose: To compare the impact of ocular changes between systemic treatment with doxycycline and low-dose oral isotretinoin in patients with moderate-to-severe papulopustular rosacea. Methods: Patients were randomized to receive either isotretinoin 0.3-0.4 mg/kg (group A) or doxycycline 100 mg/day (group B) for 16 weeks. Ocular symptoms were searched and evaluated, including best-corrected visual acuity (BCVA), Schirmer test, breakup time, rose bengal staining score, and meibomian gland dysfunction grading. The patients were retested at the end of treatment. Results: The present study included 39 patients (30 females and 9 males). Best-corrected visual acuity was > 20/30 in >90% of patients in both groups and did not change after treatment. After treatment, improvement in ocular symptoms and meibomian gland dysfunction was more pronounced in group B (p<0.05); the other parameters did not reach statistical significance. Conclusion: Doxycycline improved meibomian gland dysfunction, ocular symptoms, and ocular surface in patients with rosacea. Even though some patients experienced worsening meibomian gland dysfunction and symptoms, no subject experienced any serious complications after administration of low-dose isotretinoin.

RESUMO Objetivos: Comparar o impacto das alterações oculares entre o tratamento sistêmico de doxiciclina e isotretinoína em baixa dosagem em pacientes com rosácea papulopustulosa moderada a grave. Métodos: Os pacientes form randomizados para receber isotretinoína 0,3 a 0,4 mg/kg (grupo A) ou doxiciclina 100mg/dia (grupo B) por 16 semanas. Os sintomas oculares foram pesquisados e avaliados, incluindo melhor acuidade visual corrigida, teste de Schirmer, tempo de ruptura do filme lacrimal, coloração de rosa bengala e graduação da disfunção de glândula de Meibomius. Os pacientes foram novamente testados no final do tratamento. Resultados: O presente estudo incluiu 39 pacientes (30 mulheres e 9 homens). A melhor acuidade visual corrigida foi >20/30 em >90% dos pacientes em ambos os grupos e não se alterou após o tratamento. A melhora dos sintomas oculares e da disfunção de glândula de Meibomius foi mais pronunciada no grupo B (p<0,05) após o tratamento; as demais variáveis não atingiram significância estatística. Conclusão: A doxiciclina melhorou a disfunção de glândula de Meibomius, os sintomas oculares e a superfície ocular de pa cientes com rosácea. Mesmo que alguns pacientes tenham piorado a disfunção e os sintomas da glândula de Meibomius, nenhum indivíduo apresentou complicações graves após a admi nistração de baixas doses de isotretinoína.

Functional and Morphological Evaluation of Meibomian Glands in the Assessment of Meibomian Gland Dysfunction Subtype and Severity.

PURPOSE: To classify subtypes of meibomian gland dysfunction (MGD) and evaluate the dependency of dry eye signs, symptoms, and parameters on MGD subtype. DESIGN: Cross-sectional study. STUDY POPULATION: the right eyes of 447 patients with MGD of various subtypes and 20 healthy volunteers. METHODS: Patients were divided into 4 subtypes of MGD based on meibum expression, meibum quality, and MG loss on meibography images (meibograde of 0-6). Subtypes were patients with high meibum delivery (hypersecretory and nonobvious MGD) and those with low meibum delivery (hyposecretory and obstructive MGD). Additional clinical tests included tear film break-up time (TFBUT), ocular staining, osmolarity, Schirmer I, blink interval timing and the Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: A total of 78 eyes had hypersecretory MGD; 49 eyes had nonobvious MGD; 66 eyes had hyposecretory MGD; and 254 eyes had obstructive MGD. Increased tear film osmolarity and lower TFBUT were found in the low-delivery groups; hyposecretory (P = 0.006, P = 0.016) and obstructive MGD (P = 0.008, P = 0.006) relative to high-delivery MGD (hypersecretory and nonobvious groups, respectively). Worse ocular symptoms and ocular staining were also found in low-delivery MGD groups than the high delivery MGD groups (P < 0.01 and P < 0.006, respectively). CONCLUSIONS: Patients with low-delivery MGD had worse dry eye parameters and ocular symptoms than those with high meibum delivery, indicating the pivotal role of meibum secretion in ocular surface health that should be targeted in MGD therapy. Furthermore, nonobvious MGD cannot be diagnosed using conventional dry eye tests and requires morphologic assessment of meibography images to confirm MG loss.