Meibography signal intensity as a novel image biomarker for meibomian gland function: evidence from cross-sectional and longitudinal analyses.

Background: Meibomian gland dysfunction (MGD), one of the most common ocular surface diseases, can induce dry eye and reduce patients' quality of life. Methodological limitations have resulted in contradictory interpretations of gland function. This study sought to investigate the correlation between meibography signal intensity (SI) and meibomian gland (MG) function and to validate an MGD classification strategy based on different levels of SI. Methods: A multicenter, cross-sectional analysis was conducted on 817 eyes from 361 patients with MGD and 52 healthy controls. Additionally, 78 eyes from 39 patients with MGD who had undergone LipiFlow treatment were recruited for longitudinal analyses. The SI value was obtained via meibography using an automated analyzer, and all participants underwent ocular surface examinations. A cross-sectional analysis was performed to determine SI distribution and its relationship to clinical characteristics via a generalized estimating equation model. Longitudinal analyses were conducted on the treatment cohort using a mixed-effects model to explore the outcome in different SI levels. Results: Regression analysis revealed significant correlations between SI and lipid layer thickness (ß=0.016), meibum expressibility (ß=-0.676), meibum quality (ß=-0.251), and fluorescein-stained tear-film break-up time (FBUT) (ß=0.064) (all P values <0.001 for the above associations). Low-level SI MGD cases exhibited the most severe clinical signs, including the worst meibum expressibility (16% for level 3) and quality scores (19% for level 3), the shortest FBUT (3.82±0.13 s), and the thinnest lipid layer (65.68±2.58 nm), (all P values <0.05, respectively). Patients with medium SI showed the lowest ocular surface disease index (OSDI) value (26.64±1.06), the longest FBUT (4.56±0.08 s), and the thickest lipid layer (80.20±2.90 nm). After treatment, the high SI values reduced significantly at each follow-up point compared to baseline (all P values <0.05). The medium SI group demonstrated the greatest improvement in symptoms and signs, followed by the high SI group, and the low SI group. Conclusions: Automated measurements of SI can effectively reflect MG secretory activity. The proposed low, medium, and high SI classifications represent different functional subtypes of MGD.

Efficacy and safety of topical azithromycin therapy in patients with blepharitis and meibomian gland dysfunction.

PURPOSE: To assess the effects of 1% azithromycin ophthalmic solution (AZM) in patients with bacterial blepharitis accompanied by meibomian gland dysfunction (MGD). STUDY DESIGN: A multicenter, single arm, prospective interventional study. METHODS: AZM was administered to the affected eyes twice daily for the first 2 days and once daily for the subsequent 12 days. Lid margin hyperaemia/redness, collarette at the root of the eyelashes, conjunctival hyperaemia, foreign body sensation, and epiphora were assessed on Days 1, 14, and 28. The Dry Eye-related Quality of Life Score (DEQS) and objectives related to MGD, including lid vascularity, lid margin irregularity, foaming, lid plugging, keratoconjunctival disorders, Marx line, meibum grade, and tear breakup time, were also assessed. Bacterial culture of the conjunctival sac and meibum was performed on Days 1 and 14. RESULTS: Twenty-four eyes of 24 patients (10 men/14 women, mean age 72.3 ± 13.2) were included. On Days 14 and 28, the total score, lid vascularity, lid plugging, and meibum grade showed significant improvement (p < 0.05). On Day 1, 71 strains were isolated from 22 of the 24 eyes (91.7%). Cutibacterium acnes, Corynebacterium spp., and Staphylococci were detected at high frequencies. The overall disappearance rates of the bacteria in the conjunctival sac and meibum at the end of treatment were 65.7% and 58.3%, respectively. No serious ocular or systemic adverse events were observed. CONCLUSION: Fourteen-day treatment with AZM was effective in patients with blepharitis accompanied by MGD, and the efficacy of AZM persisted for a period after the treatment.

Role of Polyunsaturated Fatty Acids (PUFAs) and Eicosanoids on Dry Eye Symptoms and Signs.

Polyunsaturated fatty acids (PUFAs) generate pro- and anti-inflammatory eicosanoids via three different metabolic pathways. This study profiled tear PUFAs and their metabolites and examined the relationships with dry eye (DE) and meibomian gland dysfunction (MGD) symptoms and signs. A total of 40 individuals with normal eyelids and corneal anatomies were prospectively recruited. The symptoms and signs of DE and MGD were assessed, and tear samples (from the right eye) were analyzed by mass spectrometry. Mann-Whitney U tests assessed differences between medians; Spearman tests assessed correlations between continuous variables; and linear regression models assessed the impact of potential confounders. The median age was 63 years; 95% were male; 30% were White; and 85% were non-Hispanic. The symptoms of DE/MGD were not correlated with tear PUFAs and eicosanoids. DE signs (i.e., tear break-up time (TBUT) and Schirmer's) negatively correlated with anti-inflammatory eicosanoids (11,12-dihydroxyeicosatrienoic acid (11,12 DHET) and 14,15-dihydroxyicosatrienoic acid (14,15, DHET)). Corneal staining positively correlated with the anti-inflammatory PUFA, docosahexaenoic acid (DHA). MGD signs significantly associated with the pro-inflammatory eicosanoid 15-hydroxyeicosatetranoic acid (15-HETE) and DHA. Several relationships remained significant when potential confounders were considered. DE/MGD signs relate more to tear PUFAs and eicosanoids than symptoms. Understanding the impact of PUFA-related metabolic pathways in DE/MGD may provide targets for new therapeutic interventions.

Preventing and Managing Iatrogenic Dry Eye Disease during the Entire Surgical Pathway: A Study Focusing on Patients Undergoing Cataract Surgery.

Patient expectations for cataract surgery are continuously increasing, and dry eye disease (DED) represents a major cause of patient dissatisfaction in eye surgery. The present opinion paper aims to provide useful insights to improve the entire pathway of a patient undergoing cataract surgery, from the preoperative setting to the postoperative one. The available evidence from main clinical trials published on this topic is presented in association with experience-based points of view by the authors. Ocular surface disease (OSD) is common in patients presenting for cataract surgery, and more than half of these patients have DED and meibomian gland dysfunction (MGD), even in the absence of symptoms. Therefore, there is a need to encourage preoperative assessments for the risk of DED development or worsening in all patients as a routine approach to cataract surgery. New all-in-one diagnostic machines allow for fast and noninvasive screening of the ocular surface status. Once a preoperative diagnosis of DED/OSD is reached, ocular surface optimization should be obtained before surgery. In the case of unresolved OSD, the decision to delay surgery should be considered. The surgical procedure can be optimized by avoiding large incisions, limiting microscope light intensity and exposure, and avoiding an aspirating speculum or preserved eye drops. Postoperatively, the continued avoidance of preserved agents is advisable, as well as a limited exposure to epitheliotoxic antibiotics and nonsteroidal anti-inflammatory drugs. Short-term, preservative-free, soft corticosteroids may be useful for patients with extensive or persistent inflammation.

Assessing the Effects of 0.3% Carboxymethylcellulose Tear Substitute Treatment on Symptoms and Signs of Dry Eye Disease in Elderly Population: A Prospective Longitudinal Study.

BACKGROUND: We aimed to evaluate the effects of 0.3% carboxymethylcellulose (CMC) tear substitute treatment in dry eye disease (DED), as well as treatment compliance and adverse events (AEs). METHODS: In this prospective, longitudinal study, a total of 30 eyes receiving 0.3% CMC tear substitute four times daily for DED were evaluated. Clinical endpoints included an ocular surface disease index (OSDI) questionnaire, average non-invasive tear film break-up time (A-NIBUT), lipid layer thickness (LLT), and a Schirmer test with anesthesia (ST). Treatment compliance and AEs were also assessed. All evaluations were performed at 2, 4, and 12 weeks of follow-up. RESULTS: At the end of the follow-up, significant improvement was observed in all clinical endpoints with the following mean values: ΔOSDI questionnaire of -22.53 ± 14.68 points, ΔA-NIBUT of 4.81 ± 2.88 s, ΔLLT of 5.63 ± 6.53 nm, and ΔST of 2.8 ± 2.1 mm (p < 0.001 for all comparisons). Although repeated measures analysis showed that all clinical endpoints presented statistically significant differences (p < 0.001 for all comparisons LLTBaseline-LLT2-weeks (p = 0.460) and LLT4-weeks-LLT12-weeks (p = 0.071) were the only pairs of measures that reported non-statistically significant differences). In addition, treatment compliance was 94.3 ± 5.2% and transient AEs related to the use of 0.3% CMC tear substitute were reported. CONCLUSIONS: 0.3% CMC tear substitute treatment seems to achieve beneficial effects on the OSDI questionnaire, A-NIBUT, LLT, and ST. However, further studies at this concentration are needed to confirm these results.

Morphological changes in the meibomian gland in children with tic disorders.

Background: Since blinking accelerates meibomian gland (MG) expression, abnormal blinking in children with tic disorders may be associated with the morphological changes of the MGs. Our study aimed to quantitively evaluate the morphology of the MG in these children. Methods: In this prospective case-control study, we examined 68 eyes of 68 children with tic disorders, 47 eyes of 47 children with dry eye, and 45 eyes of 45 healthy children at the Hangzhou Branch of the Eye Hospital of Wenzhou Medical University from October 2020 to March 2021. We used an Oculus Keratograph 5M (K5M) to capture the MG images, noninvasive breakup time (NIBUT), and tear meniscus height (TMH). An automated method was used to analyze MG length, width, area, gland diameter deformation index (DI), and gland signal index (SI). Parameters across the three groups were assessed using Kruskal-Wallis test followed by Mann-Whitney test with Bonferroni correction for multiple comparisons. Results: The eyes in the tic disorders group exhibited lower MG length and area values compared with those of the other groups (all P values <0.001) and lower MG width values compared with those of children in the dry eye group (P=0.009). The tic disorder and dry eye groups both had a larger percentage of eyes with a U-shaped MG duct when compared with the control group (P<0.001 and P=0.017). The dry eye group had the lowest TMH and NIBUT values (both P values <0.001). The NIBUT values in the tic disorder group were lower than those in the control group (P<0.001). No significant correlations were detected between clinical tests and MG morphology in any of the groups. Conclusions: Blinking disorders have a significant impact on MG morphology. In children with tic disorders, more attention should be devoted to monitoring the MG over time.

Meta-analysis of therapeutic effect of intense pulsed light combined with meibomian gland expression on meibomian gland dysfunction related dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To systematically evaluate the efficacy of intense pulsed light(IPL)combined with meibomian gland expression(MGX)in the treatment of meibomian gland dysfunction(MGD)-related dry eye disease(DED).METHODS: Chinese and English databases such as Chinese national knowledge infrastructure(CNKI), Wanfang, VIP, CBM, ClinicalTrials, PubMed, Embase and Web of Science were searched, and clinical randomized controlled trials(RCTs)using IPL combined with MGX in the experimental group and MGX alone in the control group from January 2017 to September 2022 were included. Six outcome indicators including clinical efficacy, ocular surface disease index(OSDI)score, break-up time(BUT), corneal fluorescein staining(CFS)score, tear meniscus height(TMH)and meibomian gland yielding secretion score(MGYSS)were Meta analyzed by Review Manager 5.3 and Stata 14 software.RESULTS: A total of 15 RCTs were included, with 1 345 patients with MGD-related dry eye. Meta-analysis results showed that the treatment of MGD-related dry eye in the experimental group improved better clinical efficacy(OR=4.95, 95%CI: 2.76～8.90, Z=5.35, P&#x0026;#x003C;0.00001), BUT(SMD=1.26, 95%CI: 0.84～1.69, Z=5.78, P&#x0026;#x003C;0.00001), TMH(SMD=0.37, 95%CI: 0.15～0.59, Z=3.33, P=0.0009), and reduced OSDI scores(SMD=-0.86, 95%CI: -1.44～-0.27, Z=2.85, P=0.004)as well as MGYSS(SMD=-2.43, 95%CI: -4.31～-0.54, Z=2.52, P=0.01)than the control group. However, there was no statistically significant difference in CFS scores(SMD=-0.19, 95%CI: -0.46～0.07, Z=1.43, P=0.15).CONCLUSION: IPL combined with MGX in the treatment of MGD related dry eye can increase the overall effective rate and improve the symptoms and signs of patients with MGD related dry eye better than MGX alone.

Optimized combined low level light therapy and intense pulsed light therapy for the treatment of dry eye syndrome caused by Meibomian glands dysfunction.

Dry eye syndrome (DES) is a common disease that can lead to ocular discomfort, reduced visual acuity and reduced quality of life. Meibomian Gland dysfunction plays an important role in most cases. To evaluate the effects of "EyeLight", a novel device delivering combined intense pulsed light (IPL) and low-level light therapy (LLLT), we conducted a retrospective chart review of patients refractory to conventional medical treatment who were treated with "EyeLight" therapy at Laser Vision, Lebanon. Each patient received between 2 to 5 treatment sessions. Clinical measurements were obtained before and after each session, including tear film breakup time (TBUT), ME-CHECK-meiboscale and the ME-CHECK questionnaire to determine the need for an additional session and to monitor progress. The same clinical evaluation was performed 3 to 5 weeks after the final treatment. A total of 52 eyes were included. A significant improvement in objective clinical signs was found, with an increase in TBUT from 6.98±1.41s. to 9.27±1.25s. (P<0.001) and a decrease in ME-CHECK-meiboscale (P<0.001). A reduction of severity level on the ME-CHECK-meiboscale classification was observed in 90%, along with a significant improvement in subjective clinical signs on the ME-CHECK questionnaire (P<0.001). No ocular or facial adverse events were noted. "EyeLight" treatment of 2 to 5 sessions depending on the severity of MGD in each eye showed an improvement in objective clinical signs and subjective symptoms and therefore appears to be an effective treatment for DES related to MGD refractory to conventional treatment.

Bevacizumab Eye Drops Vs. Intra-meibomian Gland Injection of Bevacizumab for Meibomian Gland Dysfunction-Associated Posterior Blepharitis.

Aims: This study aimed to evaluate the efficacy and safety of bevacizumab eye drops compared with those of an intra-meibomian gland (MG) injection of bevacizumab when performed in conjunction with standard lid hygiene in patients with meibomian gland dysfunction (MGD)-associated posterior blepharitis. Methods: This prospective, open-label, observer-blinded randomized controlled trial included 60 eyes of 30 patients with MGD-associated posterior blepharitis who exhibited lid margin telangiectasia, treated at the Chula Refractive Surgery Center of King Chulalongkorn Memorial Hospital. Patients were randomized to receive lid hygiene plus 0.05% bevacizumab eye drops or a single intra-MG injection of 2.5% bevacizumab. All patients were instructed to perform routine lid hygiene care as demonstrated in an instructional video. Primary outcomes included telangiectasia grading and the lid margin neovascularized area (LMNA). Secondary outcomes included the Ocular Surface Disease Index (OSDI) score, corneal staining, meibum quality, meiboscore, conjunctival redness, fluorescein break-up time (FBUT), lipid layer thickness, treatment compliance, and adverse events. All parameters were evaluated before and 3 months after treatment. Results: After treatment, there were no significant differences in telangiectasia grade and LMNA between groups (mean difference, -0.14, 95% CI -0.42 to 0.15, p = 0.338, -0.1, 95% CI -1.1 to 0.8, p = 0.761, respectively); however, the injection group exhibited significant improvements in both telangiectasia grade and LMNA, while, in the eye drop group, only telangiectasia grade showed a significant improvement relative to baseline. The injection group also exhibited significant improvements in corneal staining (mean difference, -0.78, 95% CI -1.29 to -0.27, p = 0.003), meiboscores (mean difference, -0.37, 95% CI -0.52 to -0.21, p <0.001), and FBUT (mean difference, 1.25, 95% CI 0.21-2.29, p = 0.019) compared to the eye drop group. OSDI scores, corneal staining, meibum quality, meiboscores, and conjunctival redness significantly improved relative to baseline in both groups. No local and systemic adverse event was observed at month 3 in both groups. Conclusion: When performed with regular lid hygiene, intra-MG injection and topical application of bevacizumab are safe and effective for improving lid margin telangiectasia and the signs and symptoms of MGD-associated posterior blepharitis. This therapy may represent an alternative or adjunctive treatment for patients with MGD-associated posterior blepharitis.

[A clinical study of thunder-fire moxibustion combined with meibomian gland massage in treatment of meibomian gand dysfunction].

OBJECTIVE: To observe the effect of thunder-fire moxibustion combined with meibomian gland massage in improving meibomian gland dysfunction (MGD) and explore its mechanism. METHODS: Seventy-two MGD patients with 144 eyes in the Jinhua Hospital of Traditional Chinese Medicine from February 2019 to January 2021 were selected and randomly divided into an experimental group (n=36,72 eyes) and a control group (n=36, 72 eyes). Patients in the control group received 0.1% fluo-rometholone eye drops and 0.1% sodium hyaluronate eye drops, 1-2 drops per time, four times per day, and the meibomian glands were massaged once per day. Patients in the experimental group received additional thunder-fire moxibustion on the basis of the treatment of the control group, 10 cones per time, once per day. One month after treatment, meibomian gland function was assessed, and the levels of interleukin-6 (IL-6) and prostaglandin E2(PGE2) in tears were detected. RESULTS: After treatment, the scores of Ocular Surface Disease Index, meibomian hyperemia, meibomian gland opening, meibomian gland loss, and meibomian gland secretion function were lower than those before treatment in the two groups, and the scores of the experimental group were lower than those of the control group (P<0.05). After treatment, the tear break-up time and tear meniscus height were higher than those before treatment in the two groups, which were higher in the experimental group than those in the control group (P<0.05). The post-treatment levels of IL-6 and PGE2 were lower than those before treatment in the two groups, and the levels in the experimental group were lower than those in the control group (P<0.05). CONCLUSION: Thunder-fire moxibustion combined with meibomian gland massage can significantly improve the function of the meibomian glands and lower the levels of IL-6 and PGE2 in tears.

Statin Use Is Associated With a Lower Risk of Blepharitis: A Population-Based Study.

Background: Blepharitis is a common eye disorder that may be overlooked by patients and clinical practitioners. The symptoms of blepharitis often manifest as irritation, a burning sensation, grittiness, and itchiness and may decrease visual acuity if not treated promptly. Meibomian gland dysfunction (MGD), a common cause of blepharitis, is believed to be associated with increased inflammatory marker levels that may disrupt the composition of lipids produced by the sebaceous glands in the eyelids and ultimately cause tear film instability. Methods: This is a retrospective, population-based study using National Health Insurance Research Database (NHIRD) data from a 14-year period (2000-2015). Pearson chi-squared and Student's t-tests were used to assess the differences in categorical and continuous variables, respectively, between statin users and non-statin users. Univariate and multivariate Cox regression analyses were performed to calculate the hazard ratios (HRs) after adjusting for confounders. Kaplan-Meier analysis was used to assess the cumulative risk of blepharitis between the two cohorts. Results: A total of 67,014 patients who used statins were enrolled as the study cohort, and 268,056 patients who did not use statins were enrolled as the comparison cohort. The incidence of blepharitis was 3.04% with statin treatment and 3.72% without statin treatment (p < 0.001). Patients who used statins had a lower risk of developing blepharitis [adjusted hazard ratio (aHR): 0.746, p < 0.001] than those who did not. In addition, diabetes mellitus (DM), hypertension, coronary heart disease (CHD), stroke, chalazion, rosacea, Sjogren syndrome, psoriasis and atopy were found to be possible risk factors for blepharitis. Conclusion: Statin use can decrease the risk of developing blepharitis. However, further prospective studies are needed to evaluate statin treatment for various subtypes of blepharitis and to identify the associated mechanism.

Alteration in meibum lipid composition and subjective symptoms due to aging and meibomian gland dysfunction.

PURPOSE: To investigate the alteration in lipid composition of meibum, objective clinical signs, and subjective symptoms associated with aging and meibomian gland (MG) dysfunction (MGD). METHODS: In 10 MGD patients [4 males/6 females, mean age: 65.6 ± 7.9 years (range: 50-79 years)] and 24 healthy volunteer subjects [young subjects: 6 males/6 females, mean age: 25.7 ± 3.8 years (range: 20-35 years), elderly subjects: 6 males/6 females, mean age: 58.4 ± 7.5 years (range: 50-79 years)], three objective clinical signs were evaluated: MG orifice obstruction, meibum score, and tear film lipid layer interference pattern. Subjective symptoms were analyzed via a 15-item questionnaire. After careful collection of meibum samples, comprehensive lipid analysis was performed via liquid chromatography-mass spectrometry. Data was analyzed via JMP® ver. 13 (SAS Institute, Inc., Cary, NC) statistical analysis software. RESULTS: In the MGD patients and elderly subjects, there was a significant decrease in non-polar lipids such as cholesterol esters (ChEs), while a significant increase in polar lipids [cholesterol (Ch), (O-acyl)-ω-hydroxy fatty acid (OAHFA), and free fatty acid (FA)] in total lipids (Tukey-Kramer test: p < 0.05). Triglyceride was significantly increased only in MGD patients (p < 0.05). Symptom scores representative of vision quality (i.e., blurred vision/haziness) were significantly negatively-correlated with the ratio of the non-polar lipid ChE, while significantly positively correlated with the polar lipids Ch, OAHFA, and FA (Spearman's rank correlation coefficient: p < 0.05). CONCLUSIONS: Our findings revealed that both MGD and aging affect the composition ratio of major meibum lipids, resulting in the appearance of subjective symptoms.

Improved Dry Eye Symptoms and Signs of Patients With Meibomian Gland Dysfunction by a Dietary Supplement.

Purpose: To explore the therapeutic effect of a dietary supplement on dry eye with meibomian gland dysfunction (MGD). Methods: Sixty patients with MGD-related dry eye were included in this prospective and randomized, placebo-controlled study. All the subjects were treated with eye hot compress, artificial tears, and antibiotic ointment. After that, the patients received dietary supplementary or placebo daily for 12 weeks. The dry eye signs, function of MG, and visual quality of the patients were assessed at 4, 8, and 12 weeks after the treatment. Results: Twelve weeks after the treatment, patients who received dietary supplement had a significantly better improvement of dry eye symptoms, in terms of ocular surface diseases index and tear breaking-up time (TBUT), than those who received placebo (P < 0.05). The functions of MG, in terms of meibum quality and MG exclusion and MG obstruction scores, were significantly improved in both dietary supplement and placebo groups (P < 0.05). Patients who received dietary supplement had a significantly better improvement in the MG structure, in terms of acinar diameter and acinar density, than those who received placebo (P < 0.05). The number of inflammatory cells near MG was significantly lower in the dietary supplement group when compared with the placebo group (P < 0.05). The objective visual quality was significantly improved in the dietary supplement group, but not in the placebo group (P < 0.05). Conclusion: The dietary supplement can effectively improve the symptoms and signs of MGD-related dry eye, reduce the inflammatory reaction of MG, restore the gland structure, and indirectly improve the visual quality.

Aggregated neutrophil extracellular traps occlude Meibomian glands during ocular surface inflammation.

PURPOSE: Obstructive Meibomian gland dysfunction (MGD) is one of the leading causes of evaporative dry eye disease. Meibomian glands at the eyelid secrete lipids that prevent evaporation of the aqueous tear film. The pathogenesis of obstructive MGD is incompletely understood to date. Herein, we aim to investigate the pathogenesis of obstructive MGD using murine and human samples with various forms of ocular surface inflammation. METHOD: The presence of Neutrophil extracellular Traps (NETs) was detected with immunofluorescence analysis of ocular surface discharge and biopsy samples from patients with blepharitis. Tear fluid from patients with MGD and blepharitis were evaluated for the presence of inflammatory mediators using bead based immunoassay. Murine model of allergic eye disease (AED) was performed to investigate the role of NETs in MG occlusion. RESULTS: we show that the ocular discharge from patients with blepharitis contains aggregated neutrophil extracellular traps (aggNETs). Furthermore, the ducts of human Meibomian glands affected by blepharitis were largely congested by aggNETs. Tear fluid from patients with MGD showed elevated neutrophil chemoattractants (C5a, IL6, IL8 and IL18). C5a and IL8 correlated with the degree of deficiency of tear fluid. In the murine model of allergic eye disease (AED), aggNETs accumulated in the MG leading to occlusion of their ducts and the retrograde pent-up of the fluid followed by acinar atrophy. Constraining aggNET formation by genetic or pharmacological inhibition of peptidyl arginine deiminase type 4 (PADI4) effectively reduced MG damage. CONCLUSION: We conclude that aggNETs occlude MG causing MGD after ocular surface inflammation.

Dry Eye Disease: Early Recognition with Guidance on Management and Treatment for Primary Care Family Physicians.

Primary care presentations of dry eye disease (DED) are common and pose a diagnostic challenge due to the variety of symptoms and the absence of certainty for family practitioners. While there are many published articles on the topic, the 2017 Tear Film and Ocular Surface Society Dry Eye Workshop was a landmark report in distinguishing multifactorial differences. Redefined terms clarified the DED disorder. The ocular surface-the tear/air interface-is the primary refractive component of the eye, which is why DED is so significant and impacts vision. There is a high prevalence of DED in the community, ranging from 5% to 30% of people across multiple studies. Elderly patients have up to 75% increased risk of DED and receive more intensive treatment than younger age groups. DED is also more common in women than men, occurring in 9.8% of postmenopausal women. The causes of DED span defective lacrimal apparatus and systemic disorders. Despite its prevalence, up to one-half of patients with confirmed DED do not receive proper alleviating treatment. Risk factors on functional and environmental bases follow. Tools to elicit a diagnosis more confidently are outlined using the Ocular Surface Disease Index (OSDI) and the Symptom Assessment in Dry Eye questionnaires (SANDE). Lacritin, lutein, vitamin A, and balanced nutrition are essential contributors to maintaining healthy eyes with appropriate management and treatment. The authors hope that this paper will prompt a more accurate and expedient diagnosis of DED in primary care practice and an earlier recognition of specialist referrals.

Dry eye disease (DED) poses a diagnostic challenge to primary care physicians. The condition involves the tear/air interface, at the corneal (ocular) surface, where light enters the eye. Any change in light refraction affects regular sight. Symptoms of DED include itching, grittiness, foreign body sensation, redness, excessive tearing, and visual blurring, the lattermost being the most common presentation. Ultimately, the untreated disease leads to continued discomfort and visual deficit, but when severe, it can result in blindness. Up to 30% of the population suffers from DED, with the elderly, particularly women, more affected. Unfortunately, up to 50% of those affected have inadequate treatment. Questionnaires help in diagnosis. Simple office tests can indicate the severity of eye problems. Technology with smartphone photography can take high-resolution images, which are useful in education and teaching. A multitude of conditions cause DED, including blepharitis, an infection of the eyelids. Environmental risks also abound. Proper nutrition is essential in maintaining eye health. Intermittent eye symptoms are likely to be underrated by the public, by purchasing over-the-counter products such as artificial tears rather than seeking a proper medical check. Newer prescription medications are now available for DED relief before advancing to debility requiring specialist treatment. Dry Eye Disease: Early Recognition with Guidance on Management and Treatment for Primary CareFamily Physicians (MP4 95031 kb).

Comparison of the Meibomian Gland Openings by Optical Coherence Tomography in Obstructive Meibomian Gland Dysfunction and Normal Patients.

PURPOSE: The aim of this study was to use swept-source anterior segment optical coherence tomography (OCT) to explore imaging the meibomian gland openings and to identify their in vivo characteristics in patients with obstructive meibomian gland dysfunction (MGD) and healthy participants. METHODS: We enrolled 49 patients with MGD and 54 health controls in this case-control study. Each participant underwent slit-lamp examination, meibography, and OCT scanning. Sixteen patients with MGD underwent a repeat OCT examination after eyelid massage. The outcome measures included determinations of meibomian gland openings (orifices and terminal ducts) from OCT images and comparisons of the meibomian openings between patients with MGD and normal controls before and after meibomian gland massage. RESULTS: Using the same OCT scanning model, the number of visible orifices of the meibomian glands was similar between eyes with MGD and normal eyes (9.2 ± 2.3 vs. 9.7 ± 2.4). The mean diameter of the terminal ducts in patients with MGD was larger (120.22 ± 27.92 µm vs. 100.96 ± 20.30 µm) than in the normal controls, and had a larger coefficient of variation. Significant differences were observed in the mean diameter of the terminal ducts of patients with MGD before and after meibum gland massage (133.73 ± 27.81 µm vs. 102.26 ± 24.30 µm, p < 0.001). CONCLUSIONS: Patients with MGD have more diversified orifices and larger meibomian gland terminal duct diameters than normal subjects. In addition, meibomian gland terminal duct diameters seem to decrease in patients with MGD after meibum gland massage.

Long-term effects of intense pulsed light treatment on the ocular surface in patients with rosacea-associated meibomian gland dysfunction.

PURPOSE: We aimed to determine the long-term effects of intense pulsed light (IPL) treatment in rosacea-associated meibomian gland dysfunction (MGD). METHODS: We enrolled 17 rosacea subjects with moderate and severe MGD who underwent four IPL sessions at 3-week intervals and were followed up for 12 months. The subjects underwent clinical examinations at baseline (first IPL) and at 3 (second), 6 (third), 9 (fourth), and 12 weeks, as well as 6 and 12 months, after baseline. Ocular surface parameters, including the Ocular Surface Disease Index (OSDI), tear break-up time (TBUT), staining score, and noninvasive Keratograph tear break-up time (NIKBUT), as well as meibomian gland parameters, including the lid margin vascularity and meibum expressibility and quality, were evaluated. RESULTS: All ocular surface and meibomian gland parameters for all subjects exhibited significant changes from baseline to the final examination (Friedman, P < 0.050 for all). In particular, improvements in the lower lid margin vascularity, meibum expressibility and quality, and ocular symptoms persisted up to the final examination (Wilcoxon, P < 0.050 for all). However, the improvements of TBUT, staining score, and NIKBUT after IPL were not maintained at 6 and 12 months after baseline. CONCLUSIONS: In rosacea-associated MGD, four IPL treatments at 3-week intervals can improve long-term lid parameters and ocular symptoms without adverse effects.

In vitro effects of sex hormones in human meibomian gland epithelial cells.

Meibomian gland dysfunction (MGD) is considered the most common cause of dry eye disease (DED). Sex hormones seem to play a role in the pathogenesis of MGD although their involvement is not completely understood. Therefore, in the present study we evaluated the effect of dihydrotestosteron (DHT) and estradiol (ß-Est) on an immortalized human meibomian gland epithelial cell line (HMGEC). Protein expression of sex hormone receptors in HMGEC was investigated by western blot. Ultrastructural morphology, Sudan III lipid staining, cell proliferation as well as vitality assays were performed. Furthermore, expression of MGD-associated markers for keratinization (hornerin, involucrin and CK6), proliferation (CK5 and CK14) and lipid synthesis (fatty acid synthase and stearoyl-CoA desaturase) were analyzed by real time RT-PCR. Western blot revealed presence of androgen receptor (AR), estrogen receptors α and -ß (ERα, ERß) and progesterone receptor (PR) in HMGEC. PR, ERα and ERß expression was significantly induced under cultivation with serum, whereas sex hormones stimulation showed no further effect on protein expression of PR, ERα and ERß. Our results showed no impact of MGD-associated sex hormones to cellular morphology and lipid accumulation in HMGEC. Cell proliferation was slightly induced through application of sex hormones and supplementation of calcium. However, both sex hormones and calcium altered gene expression of MGD-associated markers. Especially keratinization genes hornerin (HRNR) and cornulin (COR) were induced after application of sex hormones and calcium in serum-free cultivated HMGEC. This may promote keratinization processes that are associated with MGD. Further investigations are necessary to analyze the (hyper)keratinization processes that occur during MGD and using HMGEC as an in vitro model.

Ex vivo heat retention of different eyelid warming masks.

PURPOSE: Meibomian gland dysfunction (MGD) appears to be the most common cause of evaporative dry eye, in which the meibum has an altered chemical structure that increases its melting point. Eyelid warming masks slowly transfer heat, preferably between 40 and 45°C to the inner meibomian glands, in an attempt to melt or soften the stagnant meibum. This ex vivo study evaluates the heat retention properties of commercially available masks over a 12-min interval. METHODS: Five eyelid-warming masks (MGDRx EyeBag®, EyeDoctor®, Bruder®, Tranquileyes™, Thera°Pearl(®) were heated following manufacturer's instructions and heat retention was assessed at 1-min interval for 12 min on a non-conductive surface. A facecloth warmed with hot tap water was used as comparison. RESULTS: All masks reached above 40°C within the first 2 min after heating and remained so for 5 min, with the exception of the facecloth, which lasted only 3 min and quickly degraded to 30°C within 10 min. The Bruder® and Tranquileyes™ reached >50°C, after heating and the Bruder® maintained >50°C for nearly 6 min. The MGDRx EyeBag®, and Thera°Pearl® had the most stable heat retention between 2 and 9 min, remaining between the targeted temperature. CONCLUSIONS: Heat retention profiles are different for commercially available eyelid warming masks. This ex vivo study highlights that despite the popularity of the time-honored facecloth, it is poor at retaining the desired heat over a 5-10 min interval. Clinical studies need to corroborate these results, remembering that ocular tissue parameters may be factors to consider.

Thermal analysis of dry eye subjects and the thermal impulse perturbation model of ocular surface.

In this study, we explore the usage of ocular surface temperature (OST) decay patterns to distinguished between dry eye patients with aqueous deficient dry eye (ADDE) and meibomian gland dysfunction (MGD). The OST profiles of 20 dry eye subjects were measured by a long-wave infrared thermal camera in a standardized environment (24 °C, and relative humidity (RH) 40%). The subjects were instructed to blink every 5 s after 20 âˆ¼ 25 min acclimation. Exponential decay curves were fit to the average temperature within a region of the central cornea. We find the MGD subjects have both a higher initial temperature (p < 0.022) and a higher asymptotic temperature (p < 0.007) than the ADDE subjects. We hypothesize the temperature difference among the subpopulations is due to tear volume and heat transfer mechanisms. To study the validity of our claim, we develop a mathematical model, referred to as the thermal impulse perturbation (TIP) model. We conclude that long-wave-infrared thermal imaging is a plausible tool in assisting with the classification of dry eye patient.