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).     

Human Meibum and Tear Film Derived (O-Acyl)-Omega-Hydroxy Fatty Acids as Biomarkers of Tear Film Dynamics in Meibomian Gland Dysfunction and Dry Eye Disease

PurposeTo investigate the association between precorneal tear film (PCTF)– and meibum-derived (O-Acyl)-omega-hydroxy fatty acids (OAHFAs) and PCTF thinning in meibomian gland health and dysfunction.MethodsOf 195 eligible subjects (18–84 years, 62.6% female), 178 and 170 subjects provided both PCTF optical coherence tomography (OCT) imaging and mass spectrometry data for tears (n = 178) and meibum (n = 170). The PCTF thinning rate was measured in the right eye using an ultra-high-resolution, custom-built OCT. Tear and meibum samples from the right eye were infused into the SCIEX 5600 TripleTOF mass spectrometer in the negative ion mode. Intensities (m/z) of preidentified OAHFAs were measured with Analyst 1.7TF and LipidView 1.3 (SCIEX). Principal component (PC) analyses and Spearman''s correlations (ρ) were performed to evaluate the association between OAHFAs and PCTF thinning rates.ResultsIn meibum and tear samples, 76 and 78 unique OAHFAs were detected, respectively. The first PC scores of the meibum-derived OAHFAs had statistically significant correlations with PCTF thinning rates (ρ = 0.18, P = 0.016). Among 10 OAHFAs with the highest first PC loadings, six OAHFAs had negative correlations with PCTF thinning rate (18:2/16:2, ρ = −0.19, P = 0.01; 18:2/30:1, ρ = −0.21, P = 0.008; 18:1/28:1, ρ = −0.22, P = 0.004; 18:1/30:1, ρ = −0.22, P = 0.005; 18:1/25:0, ρ = 0.22, P = 0 .006; and 18:1/26:1, ρ = −0.22, P = 0.006), while one OAHFA had a positive correlation with PCTF thinning rate (18:2/18:1, ρ = 0.48, P = 0.006). Tear film-derived OAHFAs had no association with the PCTF thinning rate.ConclusionsSeveral human meibum-derived OAHFAs showed significant associations with PCTF thinning, suggesting that these OAHFAs could be implicated in the mechanism underlying the stabilization and thinning of the PCTF. The tear-film derived OAHFAs were, however, independent of the rate of PCTF thinning.     

Relationships between ocular surface sphingomyelinases,Meibum and Tear Sphingolipids,and clinical parameters of meibomian gland dysfunction

PurposeSphingolipids (SPL) are a class of lipid molecules that play important functional and structural roles in our body and are a component of meibum. Sphingomyelinases (SMases) are key enzymes in sphingolipid metabolism that hydrolyze sphingomyelin (SM) and generate ceramide (Cer). The purpose of this study was to examine relationships between ocular surface SMases, SPL composition, and parameters of Meibomian gland dysfunction (MGD).MethodsIndividuals were grouped by meibum quality (n = 25 with poor-quality, MGD, and n = 25 with good-quality, control). Meibum and tears were analyzed with LC-MS to quantify SPL classes: Cer, Hexosyl-Ceramide (Hex-Cer), SM, Sphingosine (Sph), and sphingosine 1-phosphate (S1P). SMase activity in tears were quantified using a commercially available ‘SMase assay’. Statistical analysis included multiple linear regression analyses to assess the impact of SMase activity on lipid composition, as well as ocular surface symptoms and signs of MGD.ResultsDemographic characteristics were similar between the two groups. nSMase and aSMase levels were lower in the poor vs good quality group. aSMase activity in tears negatively correlated with SM in meibum and tears and positively with Sph in meibum and S1P in tears. Lower SMase activity were associated with signs of MGD, most notably Meibomian gland dropout.ConclusionThis study suggests that individuals with MGD have reduced enzymatic activity of SMases in tears. Specifically, individuals with poor vs good meibum quality were noted to have alterations in SMase activity and SPL composition of meibum and tears which may reflect deviations from normal lipid metabolism in individuals with MGD.     

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.     

Assessment of the Tear Film Lipid Layer Thickness after Cataract Surgery

Purpose: To evaluate changes in the tear film lipid layer thickness (LLT) after cataract surgery and the effects of cataract surgery on dry eye syndrome (DES) and meibomian gland dysfunction (MGD). Methods: LLT measurements obtained using the LipiView interferometer, tear break-up time (TBUT) measurements, Schirmer’s tests, Oxford staining scores, lid margin and meibomian gland findings, and the Ocular Surface Disease Index (OSDI) questionnaire scores were evaluated before and one and three months after cataract surgery. Results: Forty-three eyes (43 patients) were included. LLT was significantly thinner one month after surgery than at baseline (P = 0.004). TBUT was significantly shorter at both one (P < 0.001) and three (P < 0.001) months after surgery than at baseline. OSDI scores were significantly higher (P < 0.001) and the meibum quality was significantly poorer (P = 0.001) at one month after surgery than at baseline. TBUT was significantly and positively correlated with LLT (r = 0.29, P < 0.001), while the OSDI (r = ?0.38, P < 0.001) and Oxford staining (r = ?0.30, P = 0.001) scores and the meibum quality (r = ?0.21, P = 0.01) were significantly and negatively correlated with LLT. Conclusions: The tear film LLT was significantly thinner and DES and MGD parameters showed deterioration after cataract surgery. In addition, LLT was significantly correlated with DES and MGD parameters. These results suggest that clinicians should consider the tear film lipid layer while managing the exacerbation of DES after cataract surgery.     

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.     

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.     

A clinical study on the correlation between demodex infestation and ocular surface changes in patients with meibomian gland dysfunction

Purpose:To observe the effect of demodex infection on the ocular surface changes of patients with meibomian gland dysfunction (MGD) and analyze the correlation between the number of demodex and the changes of the ocular surface.Methods:Hundred patients with MGD aged 18–70 years who visited the dry eye center of Shanghai Aier Eye Hospital were recruited. All patients were examined with in vivo confocal microscopy to quantify the demodex and divided them into two groups (demodex negative group and demodex positive group) according to the number of demodex mites. The subjects underwent questionnaires of ocular surface disease index (OSDI) and a series of examinations. Parameters including the OSDI score, fluorescein tear film break-up time (FBUT), meibum quality, meibum gland expressibility, meibomian gland dropout (MG dropout), and ocular redness were recorded and compared between the two groups. The correlation between the number of demodex and the ocular surface changes was further analyzed.Results:Among 100 patients, 51 were positive for demodex. The demodex-positive group showed significantly increased scores of OSDI (24.41 ± 3.43 vs 20.98 ± 2.31, P = 0.00), ocular redness score (1.38 ± 0.46 vs 1.00 ± 0.30, P = 0.00), and MG dropout (3.00 ± 1.13 vs 2.18 ± 0.64, P = 0.00) and decreased FBUT (6.40 ± 1.63 vs 6.54 ± 1.83, P = 0.00), compared to the demodex-negative group. A significant correlation was noted between the number of demodex and OSDI, ocular redness, and FBUT.Conclusion:Ocular demodex infestation might play a role in the ocular surface discomfort, inflammation, and meibomian gland dropout in MGD patients. It is necessary to pay attention to the examination and treatment of demodex mite in patients with MGD.     

Meibomian gland dysfunction is suppressed via selective inhibition of immune responses by topical LFA-1/ICAM antagonism with lifitegrast in the allergic eye disease (AED) model

PurposeThe etiology of meibomian gland dysfunction (MGD) is incompletely understood, despite being a common ophthalmic condition and an area of unmet medical need. It is characterized by an insufficiency in glandular provision of specialized lipids (meibum) to the tear film and is a major cause of dry eye. Work in the allergic eye disease (AED) mouse model has revealed an immunopathogenic role in MGD causation, now raising interest in the applicability of immunomodulatory therapies. As such, we herein ask whether inhibition of lymphocyte function associated antigen (LFA)-1/intracellular adhesion molecules (ICAM)-1 signaling via topical lifitegrast administration has a therapeutic effect on MGD in AED mice.MethodsMice were induced with AED by i.p. injection of ovalbumin (OVA) mixed with alum and pertussis toxin, followed 2 weeks later by once daily topical OVA challenges for 7 days. Mice were treated topically with 5% lifitegrast ophthalmic solution or vehicle (PBS) 30 min prior to challenge. We developed a clinical ranking method to assess MGD severity, and also scored clinical allergy. Conjunctivae and draining lymph nodes were collected for flow cytometry.ResultsTopical lifitegrast significantly inhibited clinical MGD severity, which was associated with diminished pathogenic T_H17 cell and neutrophil numbers in the conjunctiva. No significant change in conjunctival T_H2 cells or eosinophils, and only marginal differences in ocular allergy were observed.ConclusionsIn AED mice, lifitegrast inhibited MGD severity marked by a reduction in select immune populations in the conjunctiva. Our findings warrant future examination of lifitegrast in the treatment of patients with forms of MGD.     

Identification of phospholipids in human meibum by nano-electrospray ionisation tandem mass spectrometry

Meibum is believed to be the major source of tear film lipids, which are vital in the prevention of excess evaporation of the aqueous phase. The complete lipid composition of meibum has yet to be established. While earlier studies reported the presence of phospholipids in human meibum, recent mass spectrometric studies have not detected them. In this study we use electrospray ionisation tandem mass spectrometry to investigate the presence of phospholipids in meibum and provide comparison to the phospholipid profile of tears.Lipids were extracted from human meibum and tear samples using standard biphasic methods and analysed by nano-electrospray ionisation tandem mass spectrometry using targeted ion scans. A total of 35 choline-containing phospholipids were identified in meibum and the profile of these was similar to that observed in tears, suggesting tear lipids are derived from meibum. The results shown here highlight the need for a combination of optimised techniques to enable the identification of the large range of lipid classes in meibum.     

Saturation of cholesteryl esters produced by human meibomian gland epithelial cells after treatment with rosiglitazone

PurposeThe purpose of this study was to compare the cholesteryl ester (CE) profiles expressed from human meibomian gland epithelial cells (HMGECs) in response to rosiglitazone-induced differentiation to that of normal human meibum.MethodsHMGECs were cultured with rosiglitazone (vehicle control, 20 μM, or 50 μM) and fetal bovine serum (FBS, 2% or 10%) for 2 days or 5 days. Following culture, lipid extracts were processed and analyzed by ESI-MSMS^ALL in positive ion mode. CEs were identified using both LipidView 1.2 and PeakView 2.2 (SCIEX, Framingham, MA) and compared to literature reports of CEs in normal human meibum.ResultsThere were 34 CEs with carbon number ranging from 14 to 34 detected from HMGECs. Across all conditions, HMGECs provided a CE profile that was 14.0% saturated, 60.6% monounsaturated, and 25.4% polyunsaturated. Culturing with 50 μM rosiglitazone and 2% FBS for 2 days resulted in the greatest number of upregulated saturated and monounsaturated CEs and downregulated polyunsaturated CEs. Five CEs were identified as being the most responsive to 50 μM rosiglitazone: CE 24:1, CE 28:1, CE 26:1, CE 18:1, and CE 22:1.ConclusionAlthough differences in the CE profile exist between meibum and HMGECs, rosiglitazone promotes upregulation of highly expressed meibum-relevant CEs and shifts the saturation level toward a more meibum-like profile. The use of rosiglitazone as a differentiating agent is recommended in HMGEC research, and analysis by ESI-MSMS^ALL is encouraged to differentiate meibum-relevant CEs from other nonpolar distractors detected by vital stains.     

物理治疗睑板腺功能障碍的疗效观察

目的:探讨睑板腺开口挑排等物理治疗睑板腺功能障碍(meibomian gland dysfunction,MGD)的疗效。方法:回顾性分析2012-01/12我院收治的MGD患者52例100眼的临床资料,根据临床表现及体征确诊为MGD,随机分为两组,A组(物理治疗组)26例50眼患者给予局部清洗、热敷、睑板腺开口挑排、妥布霉素地塞米松眼膏及人工泪液等综合治疗,B组(对照组)26例50眼患者仅用人工泪液和妥布霉素地塞米松眼膏药物治疗,比较两组治疗前后患者自觉症状、角膜荧光素染色(FL)、泪液分泌和泪膜破裂时间。结果:A组自觉症状好转24例47眼,好转率94%,B组自觉症状好转14例27眼,好转率54%,两组间差异有统计学意义(P<0.01);两组间泪液分泌治疗后无明显统计学差异(P>0.05);泪膜破裂时间(BUT)A组治疗后明显好转,治疗后2,4wk两组间比较有统计学意义(P<0.01);角膜荧光素染色(FL),治疗后2,4wk两组之间有统计学意义(P<0.05)。结论:MGD是一种可致眼表炎症及损伤的慢性疾病,睑板腺开口挑排等物理治疗睑板腺功能障碍疗效确切,患者满意度高。     

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。     

Identification of fatty acids and fatty acid amides in human meibomian gland secretions

PURPOSE: The complex superficial lipid layer of the tear film functions to prevent evaporation and maintain tear stability. Although classes of lipids found in the tear film have been reported, individual lipid species are currently being studied with more sophisticated. METHODS: The purpose of this work was to show the identification of fatty acids and the fatty acid amides in human meibomian gland secretions by using electrospray mass spectrometry. methods. Human meibomian gland secretions (meibum) were analyzed by electrospray quadrupole time-of-flight mass spectrometry (positive- and negative-ion mode). Accurate mass determination and collision-induced dissociation of meibum, and lipid standards were used to identify lipid species. RESULTS: Mass analysis of meibum in an acidic chloroform-methanol solution in positive-ion mode revealed a mass peak of m/z 282.3, which was identified as the protonated molecule of oleamide [C(18)H(35)NO+H](+). The high-resolution mass analysis of the m/z 282.2788 peak (oleamide) demonstrated a mass accuracy of 3.2 parts per million (ppm). Collision-induced dissociation of this species from meibum, compared with an oleamide standard, confirmed its identification. Myristic, palmitic, stearic, and oleic free fatty acids were identified in a similar manner, as were the other fatty acid amides (myristamide, palmitamide, stearamide, and erucamide). CONCLUSIONS: The findings indicate that oleamide (cis-9-octadecenamide), an endogenous fatty acid primary amide, is a predominant component of meibum when examined by electrospray mass spectrometry. The novel finding of oleamide and other members of the fatty acid amide family in the tear film could lead to additional insights into the role of fatty acid amide activity in human biological systems and may indicate a new function for this lipid class of molecules in ocular surface signaling and/or in the maintenance of the complex tear film.     

Decreased tear lipocalin concentration in patients with meibomian gland dysfunction

BACKGROUND/AIM: Recent studies have demonstrated that tear lipocalin (TL) and phospholipids have a crucial role in maintaining tear film stability. The level of TL in patients with meibomian gland dysfunction (MGD) was examined and these data were correlated with the severity of their clinical disorder. METHODS: 12 patients with obstructive MGD, 12 patients with seborrhoeic MGD, and 12 age matched normal control subjects participated in this study. 3 mul of unstimulated tears were collected with a micropipette from the inferior tear meniscus in the right eye of all subjects. Tear samples were fractionated by high performance liquid chromatography, and TL concentrations were assayed with a bicinchoninic acid technique. RESULTS: The mean concentration of TL in patients with obstructive and seborrhoeic MGD was significantly lower than in normal controls. TL concentration correlated positively with tear film break up time and negatively with fluorescein staining scores. CONCLUSION: These results suggest that TL deficiency may be a predisposing factor for the manifestation of symptoms in MGD.     

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.     

Eyelid cleansing with ointment for obstructive meibomian gland dysfunction

Purpose

To investigate the efficacy of eyelid margin cleansing with ofloxacin ophthalmic ointment in obstructive meibomian gland dysfunction (MGD) patients.

Methods

Thirty-one eyes of 31 patients diagnosed with obstructive MGD were enrolled. All subjects were instructed to rub the eyelid edge with ofloxacin eye ointment once daily prior to bathing. Lid margin abnormalities, meibum properties, and tear stability were observed before and 3 months after ointment treatment. A questionnaire relating to the severity of MGD symptoms was administered after the treatment.

Results

Vascular engorgement, meibum, dandruff-like debris, and fluorescein staining scores significantly decreased after the treatment, whereas tear break-up time significantly increased (p < 0.05). Symptoms related to MGD improved after the treatment in 86.2 % of cases.

Conclusions

Cleansing treatment ofloxacin ophthalmic ointment at the eyelid margin may be effective for patients with obstructive MGD.

     

Tear evaporation dynamics in normal subjects and subjects with obstructive meibomian gland dysfunction

PURPOSE: To test a newly developed tear evaporimetry system that detects real-time changes in tear evaporation rates and shows the tear film stability in patients with obstructive meibomian gland dysfunction (MGD). METHODS: A ventilated chamber system with high-sensitivity microbalance sensor was used to evaluate tear evaporation. Tear evaporation rates and dynamic changes in them in response to blinking ("flip heights") were measured. Both were compared in 38 eyes of 22 normal subjects and 32 eyes of 21 patients with obstructive MGD, in a prospective case-control study. The relationship between tear evaporation rates and flip heights to meibomian gland orifice obstruction was also analyzed. RESULTS: Changes in tear evaporation rates produced by blinking were detected. The tear evaporation rates in the patients' group were 5.8 +/- 2.7(10(-7)) g/cm(2) per second, significantly higher than in normal subjects (4.1 +/- 1.4[10(-7)] g/cm(2) per second; P = 0.0008). The flip heights in the obstructive MGD group were 0.58 +/- 0.33(10(-7)) g/cm(2) per second, significantly higher than in normal subjects (0.39 +/- 0.27[10(-7)] g/cm(2) per second, P = 0.02). The correlations between both tear evaporation rates and flip heights to the meibomian gland orifice obstruction score were statistically significant (P < 0.0001 and P = 0.004, respectively). CONCLUSIONS: This new system was helpful in differentiating MGD patients from normal subjects. These significantly higher evaporation rates and higher flip heights reflect the unstable tear evaporation and may well indicate unstable tear film in patients with obstructive MGD with abnormal evaporative tear loss.     

Kinetic analysis of tear interference images in aqueous tear deficiency dry eye before and after punctal occlusion

PURPOSE: Kinetic analysis of sequential tear interference images was used to investigate how the precorneal lipid film spread and distributed in aqueous tear deficiency (ATD) dry eye. METHODS: One eye of 17 patients with ATD was randomly selected for this noncomparative case series. Twelve patients also had noninflamed meibomian gland dysfunction (MGD). Sequential images were digitized and analyzed on computer. Data were further compared in 9 of the 17 cases before and after punctal occlusion (PO). Outcome measures included speed and pattern of lipid spread and resultant lipid layer thickness in the superior, central, and inferior cornea. Intensity and red/green/blue (RGB) color spectra of the tear interference image were compared before and after PO. RESULTS: After lid blinking, it took a longer time (2.2 +/- 1.1 second) to reach a stable lipid film in all eyes with ATD compared with normal subjects (P < 0.0001). Because of this retarded spread, the thickest lipid film was located at the inferior cornea adjacent to the lid margin, with a gradient spreading toward the superior cornea (P = 0.01). As a result, the lipid film was thinner than normal on the superior cornea in 10 of 17 (59%) ATD eyes. Fifteen of 17 eyes (88%) showed vertical streaking, rather than a normal horizontal propagation pattern on the superior cornea. Such a lipid-deficient state and uneven distribution did not correlate with the presence or absence of MGD. The lipid spread time was shortened (P = 0.008), the distribution of the lipid film was more even, and the thickness approached normal in all nine eyes after PO. CONCLUSIONS: In this study, kinetic analysis of tear interference images provided evidence that retardation of lipid spread is, but MGD is not, the main reason for the increased thickness of precorneal lipid film in the inferior cornea of eyes with ATD. As a result, lipid film is deficient in the superior cornea and unevenly distributed, further destabilizing the tear film. The fact that PO significantly improves lipid spread, evenness, and thickness suggests that the performance of lipid film is also dictated by the amount of aqueous tear fluid. These findings provide new insight into the interaction between the lipid film and the aqueous tear fluid.     

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.