Meibum sphingolipid composition is altered in individuals with meibomian gland dysfunction-a side by side comparison of Meibum and Tear Sphingolipids

PurposeSphingolipids (SPL) play a role in cell signaling, inflammation, and apoptosis. The purpose of this study was to examine meibum and tear SPL composition in individuals with poor versus good meibum quality.MethodsIndividuals were grouped by meibum quality (n = 25 with poor quality, case group and n = 25 with good quality, control group). Meibum and tears were analyzed with liquid chromatography-mass spectrometry (LC-MS) to quantify SPL classes. Semiquantitative and relative composition (mole percent) of SPL and major classes, Ceramide (Cer), Hexosyl-Ceramide (Hex-Cer), Sphingomyelin (SM), Sphingosine (Sph), and sphingosine 1-phosphate (S1P) were compared between groups.ResultsDemographic characteristics were similar between the two groups. Overall, individuals with poor meibum quality had more SPL pmole in meibum and tears than controls. Relative composition analysis revealed that individuals with poor meibum quality had SPL composed of less Cer, Hex-Cer, and Sph and more SM compared to individuals with good quality meibum. This pattern was not reproduced in tears as individuals with poor meibum quality had SPL composed of a similar amount of Cer, but more Hex-Cer, Sph and SM compared to controls. In meibum, SPL pmole and relative composition most strongly correlated with MG metrics while in tears, SPL pmole and relative composition most strongly correlated with tear production. SPL in both compartments, specifically Cer pmole in meibum and S1P% in tears, correlated with DE symptoms.ConclusionSPL composition differs in meibum and tears in patients with poor vs good meibum quality. These findings may be translated into therapeutic targets for disease.     

Human meibum and tear film derived (O-acyl)-omega-hydroxy fatty acids in meibomian gland dysfunction

PurposeThe molecular basis of the tear film and lipid layer alterations in meibomian gland dysfunction (MGD) is unknown. This study aimed to identify and compare (O-acyl)-omega-hydroxy fatty acids (OAHFAs) derived from human meibum and tears in MGD.MethodsOf 195 eligible subjects (18–84 years, 62.6% female), 183 and 174 provided samples for tears and meibum, respectively. Subjects were classified into four groups: Normal, Asymptomatic MGD, MGD, and Mixed. Samples from the right eye of each subject were infused into the SCIEX 5600 TripleTOF mass spectrometer in negative ion mode. Lipid intensities identified with Analyst1.7 TF and SCIEX LipidView1.3 were normalized by an internal standard and total ion current, then statistically compared in MetaboAnalyst 4.0.ResultsIn meibum and tears, 76 and 78 unique OAHFAs were identified, respectively. The five most frequent and abundant OAHFAs were 18:2/16:2, 18:1/32:1, 18:1/30:1, 18:2/32:1, and 18:1/34:1. Two OAHFAs, 18:2/20:2 and 18:2/20:1, were identified only in tears. Initial univariate analysis revealed three differently regulated OAHFAs in meibum and eight in tears. Partial Least Square Discriminant Analysis showed 18:1/32:1, 18:2/16:2, 18:1/34:1 and 18:0/32:1 in tears, and 18:2/16:2, 18:1/32:1 and 18:2/32:2 in meibum, had variable importance in projection scores >1.5 and contributed the most to the separation of groups. In both meibum and tears, all OAHFAS except 18:2/16:2 were reduced in MGD compared to the normal group.ConclusionMGD is accompanied by differential expression of specific OAHFAs in meibum and tears. These results suggest OAHFAs play a role in the altered biochemical profile of the tear film lipid layer in humans with MGD.     

Human meibum and tear film derived cholesteryl and wax esters in meibomian gland dysfunction and tear film structure

PurposeThis study evaluated the presence and roles of cholesteryl esters (CEs) and wax esters (WEs) from human tear film and meibum in meibomian gland dysfunction (MGD).MethodsOut of 195 enrolled subjects, 164 and 179 subjects provided tear and meibum samples, respectively. Subjects were classified into normal, asymptomatic MGD, MGD, and mixed (MGD & aqueous deficient). The precorneal tear film (PCTF) thinning rate (evaporation) was measured using optical coherence tomography. Lipids extracted from tear and meibum samples were infused into a SCIEX 5600 TripleTOF mass spectrometer. CE and WE intensities quantified with Analyst 1.7 TF and LipidView 1.3 were compared across disease groups in MetaboAnalyst 5.0 and correlated with PCTF thinning rates.ResultsThe numbers of unique CEs and WEs identified in the samples were 125 and 86, respectively. Unsupervised Principal Component (PC) analysis and supervised Partial Least Square Discriminant analysis exhibited little separation among groups for both CEs and WEs in tears and meibum. Spearman's correlation analyses showed no association between either the first or second PC scores with PCTF thinning rates.ConclusionThe abundances of human PCTF and meibum-derived CEs and WEs were independent of MGD disease status and PCTF thinning (evaporation). CEs and WEs alterations do not contribute to alterations in tear film dynamics in MGD, such as has been demonstrated by the (O-acyl) ω-hydroxy fatty acids (OAHFAs).     

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

PurposeTo investigate the alteration in lipid composition of meibum, objective clinical signs, and subjective symptoms associated with aging and meibomian gland (MG) dysfunction (MGD).MethodsIn 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.ResultsIn 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).ConclusionsOur findings revealed that both MGD and aging affect the composition ratio of major meibum lipids, resulting in the appearance of subjective symptoms.     

Human precorneal tear film and lipid layer dynamics in meibomian gland dysfunction

PurposeTo evaluate the precorneal tear film (PCTF) and lipid layer (TFLL) thicknesses and thinning rates in meibomian gland dysfunction (MGD) using a combined ultra-high-resolution optical coherence tomography (OCT) and thickness dependent fringe (TDF) interferometry system.MethodsBased on the Tear Film and Ocular Surface Society (TFOS) International Workshop on Meibomian Gland Dysfunction diagnostic algorithm, the Ocular Surface Disease Index (OSDI) and meibum grade score (MGS) were used to classify subjects into four groups: Normal (OSDI<13 and MGS<10), MGD (OSDI≥13 and MGS≥10), Asymptomatic MGD (OSDI<13 and MGS≥10), and Mixed (OSDI≥13 and MGS<10). The OCT/TDF system was used to capture PCTF and TFLL thicknesses and thinning rates. Kruskal-Wallis was used to compare median PCTF and TFLL thicknesses and thinning rates.ResultsThere were 190 subjects categorized into four groups: Normal (n = 63), MGD (n = 51), Asymptomatic MGD (n = 29), and Mixed (n = 47). The PCTF was significantly thinner in the Mixed group (3.3 [1.2]) than in the Normal (p < 0.001), MGD (p < 0.001) and Asymptomatic MGD (p = 0.009) groups. Relative to the Normal (4.5 [4.5] μm/min) and Mixed (5.0 [2.0] μm/min) groups, the rate of PCTF thinning was faster in the MGD (8.1 [3.0] μm/min, both p < 0.001) and Asymptomatic MGD (6.9 [3.1] μm/min, p = 0.009 and p = 0.04, respectively) groups. The correlation between PCTF thinning rate and TFLL thickness was ρ = −0.46, p < 0.001.ConclusionsSymptomatic and asymptomatic MGD shows rapid PCTF thinning rates (evaporation), while the PCTF thickness was reduced in mixed disease. Thicker lipid layers were associated with slower PCTF thinning.     

Impact of the 2011 International Workshop on Meibomian Gland Dysfunction on clinical trial attributes for meibomian gland dysfunction

PurposeThe 2011 International Workshop on Meibomian Gland Dysfunction was organized to build consensus on various disease aspects of MGD. The purpose of this review was to examine the influence of the MGD Workshop on clinical trials by examining their attributes prior to and after the Workshop.MethodsA search for clinical trials using the terms “Meibomian Gland Dysfunction” was conducted using the “Interventional Studies” filter on ClinicalTrials.gov, and selecting studies with posting and start dates prior to (2004–2010) and after the Workshop (2012–2018). The inclusion criteria, outcome measures, and study designs and rigor were examined.ResultsA total of 32 post-Workshop and 5 pre-Workshop clinical trials were identified with the search. The proportion of pre-Workshop trials using generic diagnosis and systematic assessments to define MGD was similar to that of post-Workshop trials. In both pre- and post-Workshop trials, symptoms, altered gland secretions, and alteration in tear film were the most frequent clinical attributes used to define MGD. The most frequent outcome measures used for pre-Workshop and post-Workshop trials were also similar: symptoms, meibum quality/expressibility, and tear stability.ConclusionsThe nature of the inclusion criteria, and the clinical attributes used to define MGD during the pre-Workshop period were similar to those of the post-Workshop period, suggesting that the MGD Workshop has had a minimal impact on the design of interventional trials for MGD.     

提高对睑板腺功能障碍的认识 重视睑板腺功能障碍相关性干眼的药物治疗

睑板腺功能障碍（MGD）是临床常见的眼表疾病,以睑板腺终末导管的阻塞和／或睑板腺分泌物质或量的改变为特征,导致脂质向泪膜的排出减少,引起泪液蒸发过强。睑缘和睑板腺的炎症是引起睑板腺阻塞,进而导致MGD的直接原因,可引起眼表功能的异常。MGD的诊断主要依靠临床症状与体征,其症状与干眼的症状相似,因此无诊断特异性。体征主要包括睑缘形态的变化、睑板腺分泌异常和睑板腺缺失。MGD的治疗方法包括热敷、清洁睑缘、促进睑板腺的分泌、抗菌、抗炎治疗及润滑眼表,中度、重度MGD患者可给予必要的抗炎治疗,常用的抗炎药物有糖皮质激素、非甾体类抗炎药及免疫抑制剂。临床医师在进行眼部疾病的检查时应重视睑板腺的功能状态,尤其在角膜屈光手术及内眼手术前更应重视MGD的筛查,以免术后引起严重的眼表并发症,有效规避医疗风险。     

Effects of Aging on Human Meibum

PurposeThe purpose of this study was to determine if aging affects meibum lipid composition in non-meibomian gland dysfunction (MGD)/non-dry eye (DE) population. Aging has been repeatedly linked to pathological changes in various tissues and organs, including the onset of MGD and DE, in a number of clinical and population-wide surveys. Both conditions have been associated with abnormal meibum secretion and composition, among other factors. However, the chemical basis for such a connection has not been established yet.MethodsTo identify and characterize possible changes in the meibum and meibogenesis with aging, lipidomic analyses of meibum samples collected from human subjects of two age groups – young (29 ± 5 years, n = 21) and elderly (68 ± 7 years, n = 29) – with similar male to female ratios in each group were conducted. Intact lipid species from major lipid groups of meibum (such as wax esters, cholesteryl esters, free cholesterol, triacylglycerols, etc.) were compared using lipidome-wide untargeted (such as Principal Component Analysis) and targeted (such as Orthogonal Projections to Latent Structures Discriminant Analysis) approaches, along with focused analyses of specific lipid species in liquid-chromatography mass spectrometry (LC-MS) and tandem mass spectrometry (MS-MS) experiments.ResultsExtremely high similarities of meibum lipids in the two age groups were observed, with only minor changes in the individual lipid species. The magnitude of the intergroup variability for tested lipid species was comparable to the intragroup variability for the same meibum components. No statistically significant differences in the lipid esterification, elongation, and unsaturation patterns were observed.ConclusionsChronological aging itself seems to have only minor effect on meibogenesis in healthy, non-MGD/non-DE subjects.     

Association of dyslipidemia with severity of meibomian gland dysfunction in a tertiary care hospital of Uttarakhand region

AIM: To analyse the association between dyslipidemia and severity of meibomian gland dysfunction (MGD) in a tertiary care hospital of Uttarakhand region. METHODS: This prospective observational study was conducted over a period of one year including 50 consecutive patients of MGD. Patients underwent detailed history (including Ocular Surface Disease Index Questionnaire) and examination (including meibum quality, expressibility and numerical staining). MGD was graded according to the guidelines submitted by the International Workshop on Meibomian Gland Dysfunction and Management in 2011. Fasting lipid profile of all the patients was done. Various parameters of lipid profile including total cholesterol (TC), triglycerides (TG), low density lipoproteins (LDL), high density lipoproteins (HDL) and very low density lipoproteins (VLDL) were correlated with MGD severity. Chi-square test was done for statistical analysis (P<0.05). RESULTS: Stage 2 MGD was the most common disease entity (60%, n=30). A significant positive correlation was noted between increasing age and severity of MGD (P=0.004). High TC (>200 mg/dL), TG (>150 mg/dL), LDL (>130 mg/dL) and VLDL (>22 mg/dL) levels had a significant positive correlation with the severity of MGD (P=0.001, 0.019, 0.001, 0.016 respectively). CONCLUSION: Monitoring the fasting lipid levels may aid in establishing the severity of MGD and further studies may be conducted to establish the role of treatment of dyslipidemia in MGD.     

眼部蠕形螨感染影响睑酯菌群组成的相关分析

目的:探讨眼部蠕形螨感染影响睑酯菌群组成的相关分析。方法:采用非干预性、观察性研究的方法,选取2020-07/2021-02我院39例受试者,根据有无蠕形螨感染或有无睑板腺功能障碍(MGD)将受试者分为三组,对照组(14例)、睑板腺功能障碍组(MGD组,14组)、蠕形螨感染组(FM组,11组)。对三组受试者睑板腺睑酯样本进行16S rRNA基因V3～V4片段的高通量测序,测序数据进行生物信息学分析,以研究眼部蠕形螨受试者睑酯菌群的构成及差异。结果:蠕形螨感染组的假单胞菌属和丛毛单胞菌属丰度均显著高于健康对照组和MGD组(P<0.05),罗尔斯通氏菌属丰度显著低于对照组和MGD组(P<0.05)。MGD组和FM组睑酯菌群微生物丰富度、微生物群落多样性显著高于健康对照组(P<0.05)。结论:蠕形螨感染改变了睑酯菌群的构成,并提高了睑酯菌群的微生物丰富度和群落多样性。     

血脂异常与睑板腺功能障碍严重程度的关系

目的：分析北方汉德地区三级保健医院血脂异常与睑板腺功能(MGD)紊乱严重程度的关系。

方法：这项前瞻性观察研究为期1a,共纳入50例MGD患者。患者接受详细病史调查(包括眼表疾病指数问卷)和检查(包括眼底质量、表达能力和数字染色)。根据2011年睑板腺功能障碍与管理国际研讨会提交的指南对MGD进行分级。对所有患者进行空腹血脂测定。总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)和极低密度脂蛋白(VLDL)等参数与MGD严重程度相关。采用Chi-square检验进行统计学分析(P<0.05)。

结果：2级MGD是最常见的疾病(60%,n=30)。年龄的增加与MGD的严重程度呈显著正相关(P=0.004)。高TC(>200 mg/dL)、TG(>150 mg/dL)、LDL(>130 mg/dL)和VLDL(>22 mg/dL)水平与MGD的严重程度呈正相关(P=0.001,0.019,0.001,0.016)。

结论：监测空腹血脂水平可以帮助确定MGD的严重程度,进一步的研究可以确定血脂异常在治疗MGD中的作用。     

炎症在睑板腺功能障碍发病机制中的作用

Meibomian gland dysfunction(MGD) is the main cause of dry eye and is also a common disease in ophthalmology clinic. The main mechanism of MGD is terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretion. The response of meibomian gland to inflammatory stimuli, the antibacterial and anti-inflammatory meibum, androgens and peroxisome proliferator-activated receptor gamma (PPAR-γ) involved in the regulation of inflammation may mediate the meibomian gland's resistance to inflammatory cell infiltration. Dysbacteriosis of meibomian gland and infection of demodex can induce inflammation and thus affect the pathogenesis and development of MGD. To clarify the role and mechanism of inflammation in MGD will provide new ideas and theoretical basis for the prevention and treatment of MGD. (Int Rev Ophthalmol, 2021, 45: 535-540)     

睑板腺功能障碍与分泌物和泪液中前列腺素E2含量的关系

目的：探讨睑板腺分泌物及泪液中前列腺素 E2( prostaglandin E2, PGE2)含量与睑板腺功能障碍的相关性。
　　方法：将72例120眼睑板腺功能障碍患者分为轻中度组36例60眼和重度组36例60眼,采用酶联免疫吸附试验检测睑板腺分泌物和泪液中PGE2的含量。正常人30例60眼设为对照组,只检测泪液中PGE2含量。
　　结果：泪液中PGE2含量在三组间差异有显著统计学意义(F=100.26,P<0.01),重度组泪液PGE2含量高于轻中度组(t=5.789,P<0.01)和正常组(t=7.468,P<0.01),轻中度组泪液PGE2含量与正常组差异无统计学意义( t=0.923,P>0.05);睑板腺分泌物PGE2含量在两组间差异有统计学意义,重度组高于轻中度组( F=151.76, P<0.01);重度组泪液与睑板腺分泌物中PGE2含量呈正相关(r=0.71,P<0.01);轻中度组泪液与睑板腺分泌物PGE2含量呈正相关(r=0.30,P<0.05)。
　　结论：睑板腺分泌物和泪液PGE2含量对判断睑板腺功能障碍的严重程度和指导临床合理用药具有重要作用。     

睑板腺功能障碍临床诊断新进展

睑板腺功能障碍(meibomian gland dysfunction,MGD)是眼科门诊常见的疾病之一,临床上MGD的诊断需根据症状、体征和相应的辅助检查进行综合评估。传统的检查方法如裂隙灯检查、泪膜破裂时间、泪液分泌试验等在MGD的诊断中有着明确的价值,而在2017年我国睑板腺功能障碍诊断与治疗专家共识中,一些新兴的临床检查方法如睑板腺缺失率、泪膜脂质层厚度等也作为MGD的辅助诊断标准。传统的方法和新兴的检测技术结合起来用于MGD的诊断,将会得到更全面、准确的结论。     

Aggregated neutrophil extracellular traps occlude Meibomian glands during ocular surface inflammation

PurposeObstructive 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.MethodThe 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.Resultswe 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.ConclusionWe conclude that aggNETs occlude MG causing MGD after ocular surface inflammation.     

Meibomian gland dysfunction is the primary determinant of dry eye symptoms: Analysis of 2346 patients

PurposeTo determine relative contributions of various ocular surface clinical signs and predisposing factors to the magnitude of dry eye symptoms.MethodsClinical audit data were prospectively collected for newly referred dry eye patients. All 2346 patients had an initial visit evaluation of the Ocular Surface Disease Index (OSDI), and a detailed ophthalmic examination including tear breakup time (TBUT), ocular surface fluorescein staining, Schirmer's I test. Among the participants, 1414 had number of liquid meibum expressing glands (NLMEG) evaluated on standard force expression. Other variables collected included history of glaucoma or glaucoma surgery, and history of allergies.ResultsIn patients aged 46.2 ± 14.8 years, 77.4% were women and 87.1% Chinese. The mean ± SD OSDI was 35.2 ± 21.7. On univariate analysis, higher OSDI was associated with glaucoma diagnosis (p = 0.003), glaucoma surgery (p = 0.002), greater temporal corneal staining (p = 0.002), reduced NLMEG (p < 0.001), and higher inferior forniceal papillary grade (p < 0.001). OSDI was not significantly associated with gender, TBUT, Schirmer's I test values, or the use of cyclosporine eyedrops. On multivariate regression, higher OSDI scores were associated with fewer NLMEG (p = 0.002) and increased lower eyelid forniceal papillary grading (p = 0.002). Corneal staining, glaucoma status and glaucoma surgery were not significantly associated with OSDI. Logistic regression showed that severe symptoms (OSDI>32) was associated with <2 NLMEG [OR(95%CI): 1.34(1.08–1.66)], and presence of inferior eyelid forniceal papillae [1.50(1.17–1.91)].ConclusionsMeibomian gland dysfunction (MGD) and lower forniceal papillary reaction had significant contributions to the severity of symptoms, in contrast to traditional dry eye signs. MGD should be objectively assessed and treated to improve symptoms.     

Comparable meibomian gland changes in patients with and without ocular graft-versus-host disease after hematopoietic stem cell transplantation

PurposeTo compare the presentation and severity of meibomian gland dysfunction (MGD) in patients with and without chronic ocular graft-versus-host disease (coGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).MethodsThis prospective cross-sectional study included 79 patients (47 with coGVHD and 32 without) after allo-HSCT. All participants completed ocular surface disease index questionnaire, and received slit lamp, ocular surface interferometer, meibography and confocal microscopy examination. The prevalence and severity of MGD were compared between two groups and related factors were analyzed. Main outcome measures were lipid layer thickness (LLT) and meiboscore.ResultsSimilarly high prevalence of MGD was detected in coGVHD and non-coGVHD groups (87.2% vs 84.4%, P = 0.977). Among those with MGD, although patients without coGVHD had longer noninvasive break-up time [5.54 (2.87, 9.37) vs 2.29 (0.00, 3.82) s, P < 0.001], patients in two groups presented similarly decreased LLT (53.5 ± 22.3 vs 47.1 ± 25.2 nm, P = 0.286), increased meiboscore (2.7 ± 1.5 vs 3.5 ± 1.8, P = 0.060) and enlarged acinar unit area (1647.7 ± 942.9 vs 1808.8 ± 1211.5 μm², P = 0.592). Meibomian gland inflammation and fibrosis were observed in both groups, but more predominant in coGVHD group. Results were consistent when patients within a comparable post-HSCT time interval were compared. Regression analysis revealed neither LLT nor meiboscore was associated with coGVHD severity. LLT was positively correlated with systemic immunosuppressant use (β = 12.0, P = 0.044), while meiboscore was positively correlated with lymphoma (β = 1.78, P = 0.040) and matched unrelated donor (β = 1.59,P = 0.008).ConclusionsMGD was common and evident in patients after allo-HSCT. MGD is not different between coGVHD and non-coGVHD patients except more inflammation and fibrosis in the former.     

Association of meibum oleic acid with meibomian seborrhea

PURPOSE: We sought to determine whether patient meibum fatty acid unsaturation is associated with meibomian gland secretion consistency. METHODS: Meibomian gland secretions were dissolved in chloroform and separated into lipid classes by thin-layer chromatography. Fatty acids in individual lipid classes were characterized by gas chromatography after transmethylation. RESULTS: Meibum from patients with meibomian seborrhea was higher, and meibum from patients with meibomian keratoconjunctivitis (meibomianitis) was lower in the monounsaturated fatty acid, oleic acid, than that of other disease groups and normal subjects. CONCLUSION: Our results strongly suggest that the melting characteristics of meibum, influenced primarily by the amount of oleic acid in wax and sterol esters and free fatty acids, greatly influence the consistency of meibomian gland secretions.     

Polar lipids in human meibomian gland secretions

PURPOSE: To determine the polar lipid composition of human meibomian gland secretions and their relationship to the preocular tear film. METHODS: Meibomian secretions were collected from normals and patients with chronic blepharitis. These lipids (meibum) were first separated by thin layer chromatography. Polar lipids were then separated utilizing high-pressure liquid chromatography with ultraviolet detection. Individual peaks were identified by comparison with standards. Collected sample peaks were subjected to differential transmethylation with sodium methoxide-methanol and the resulting fatty acid methyl esters were analyzed by gas chromatography-mass spectroscopy. RESULTS: Three phospholipids were identified as phosphatidylcholine, phosphatidylethanolamine and sphingomyelin; other unidentified phospholipids were also present. Also present in secretions were the sphingolipids ceramides and cerebrosides. Fatty acids present were 12-18 carbon chain length. All fatty acids were normal (not branched) saturated fatty acids except in sphingolipids, where hydroxy fatty acids were also present. Unsaturated normal fatty acids were present only in meibum from patients with meibomianitis. CONCLUSIONS: The composition of the polar lipids in meibomian gland secretions is more complex than previously thought. On the other hand, the type and carbon chain length of the polar lipid fatty acids appears strictly controlled. The relationship of these findings to the preocular tear film should be considered in terms of overall functionality. The polar lipid layer most likely is only one to three molecules thick and serves as a surfactant between aqueous tears and the thicker nonpolar lipid layer.     

Dry eye disease in children and adolescents in India

PurposeTo describe the etiological causes and clinical profile of dry eye disease (DED) among children and adolescents seeking eye care in India.MethodsThis was a cross-sectional study of 1023 new patients (≤21 years of age) diagnosed with DED presenting between 2010 and 2018 to a multi-tier ophthalmology hospital network. Children and adolescents with both symptoms and signs of dry eyes were considered as subjects. The data entry and retrieval were done using an electronic medical record system and analyzed using appropriate statistical tests.ResultsThe mean age of the patients was 15.2 ± 5.6 years and 76% were in their early and late adolescence. Overall, the main etiologies responsible for DED in children and adolescents were Meibomian gland dysfunction (MGD) in 49% of cases, Stevens-Johnson Syndrome (SJS) in 33% and Vitamin A deficiency (VAD) in 9%. Aqueous deficiency dry eye (ADDE) because of SJS and VAD accounted for most of the cases in infancy (92%), toddlerhood (96%), early childhood (76%) and middle childhood (68%). While Meibomian gland dysfunction (MGD) related evaporative dry eye (EDE) was the leading cause of DED in early (51%) and late adolescence (66%). Severe visual impairment and blindness was significantly greater in eyes with ADDE as compared to those with EDE (p < 0.0001), 81% of which were affected by SJS.ConclusionThe causes of and visual morbidity due to DED varied significantly in different age-groups. Most of the visual morbidity in children and adolescents was limited to eyes with ADDE due to SJS.