Relationship between serum lipid level and meibomian gland dysfunction subtype in Korea using propensity score matching.
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SUBMITTER: Ha M
PROVIDER: S-EPMC8352992 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Instability of the tear film with rapid tear break-up time is a common feature of aqueous-deficient and evaporative dry eye diseases, suggesting that there may be a shared structural abnormality of the tear film that is responsible for the instability. It may be that a change in the normal meibum lipid composition and conformation causes this abnormality. Principle component analyses of infrared spectra of human meibum indicate that human meibum collected from normal donors (Mn) is less ordered than meibum from donors with meibomian gland dysfunction (Md). In this study the conformation of Md was quantified to test this finding.Changes in lipid conformation with temperature were measured by infrared spectroscopy. There were two phases to our study. In phase 1, the phase transitions of human samples, Mn and Md, were measured. In phase 2, the phase transitions of model lipid standards composed of different waxes and cholesterol esters were measured.The phase-transition temperature was significantly higher (4°C) for the Md compared with the Mn of age-matched donors with no history of dry-eye symptoms. Most (82%) of the phase-transition temperatures measured for Md were above the values for Mn. The small change in the transition temperature was amplified in the average lipid order (stiffness) at 33.4°C. The average lipid order at 33.4°C for Md was significantly higher (30%, P = 0.004) than for Mn. The strength of lipid-lipid interactions was 72% higher for Md than for Mn. The ability of one lipid to influence the melting of adjacent lipids is termed cooperativity. There were no significant differences between Mn and Md in phase-transition cooperativity, nor was there a difference between Mn and Md in the minimum order or maximum order that Mn and Md achieved at very low and very high temperatures, respectively. The model wax studies showed that the phase transition of complex mixtures of natural lipids was set by the level of unsaturation. A double bond decreased the phase-transition temperature by approximately 40°C. The addition of a second CH CH moiety decreased the phase-transition temperature by approximately 19°C. Unsaturated waxes were miscible with saturated waxes. When a saturated wax was mixed with an unsaturated one, the saturated wax disproportionately increased the phase transition of the mixture by approximately 30°C compared with the saturated wax alone. Cholesterol ester had little effect on the phase-transition temperature of the waxes. Model studies indicated that changes in the amount of lipid saturation, rather than the amount of cholesterol esters, could be a factor in the observed conformational changes.Meibum lipid compositional changes with meibomian gland dysfunction reflect changes in hydrocarbon chain conformation and lipid-lipid interaction strength. Spectroscopic techniques are useful in studying the lipid-lipid interactions and conformation of lipid from individual patients. (ClinicalTrials.gov number, NCT00803452.).
| S-EPMC3109056 | biostudies-literature
Project description:PurposePatients diagnosed with diabetes are inclined to have abnormalities on stability of tear film and disorder of meibomian gland (MG). This study aims to explore the pathological change of MG induced by diabetes in a rat model.MethodsSprague-Dawley (SD) rats were intraperitoneally injected with streptozotocin (STZ) to establish a diabetic animal model. Lipid accumulation in MG was detected by Oil Red O staining and LipidTox staining. Cell proliferation status was determined by Ki67 and P63 immunostaining, whereas cell apoptosis was confirmed by TUNEL assay. Gene expression of inflammatory cytokines and adhesion molecules IL-1α, IL-1β, ELAM1, ICAM1, and VCAM1 were detected by RT-PCR. Activation of ERK, NF-κB, and AMPK signaling pathways was determined by Western Blot analysis. Oxidative stress-related factors NOX4, 4HNE, Nrf2, HO-1, and SOD2 were detected by immunostaining or Western Blot analysis. Tom20 and Tim23 immunostaining and transmission electron microscopy were performed to evaluate the mitochondria functional and structure change.ResultsFour months after STZ injection, there was acini dropout in MG of diabetic rats. Evident infiltration of inflammatory cells, increased expression of inflammatory factors, and adhesion molecules, as well as activated ERK and NF-κB signaling pathways were identified. Oxidative stress of MG was evident in 4-month diabetic rats. Phospho-AMPK was downregulated in MG of 2-month diabetic rats and more prominent in 4-month rats. After metformin treatment, phospho-AMPK was upregulated and the morphology of MG was well maintained. Moreover, inflammation and oxidative stress of MG were alleviated after metformin intervention.ConclusionsLong-term diabetes may lead to Meibomian gland dysfunction (MGD). AMPK may be a therapeutic target of MGD induced by diabetes.
| S-EPMC8802017 | biostudies-literature
Project description:BackgroundThere has been controversy regarding the association between primary aldosteronism (PA) and dyslipidemia and few studies considered the effects of diabetes and renal function on lipid metabolism. We analyzed lipid profiles of PA patients and compared them to propensity-score (PS)-matched essential hypertension (EH) patients adjusting for glycemic status and renal function.MethodsPatients who were diagnosed with PA using a saline-infusion test at Seoul National University Hospital from 2000 to 2018 were retrospectively analyzed. EH patients who had aldosterone-renin ratio (ARR) results were selected as controls. Covariates, including diabetes, were PS-matched for patients with PA, lateralized PA, non-lateralized PA, and high ARR to EH patients, respectively.ResultsAmong a total of 80 PA and 80 EH patients, total cholesterol (TC) and triglyceride (TG) levels were significantly lower in the PA patients than in the EH patients (least-squares mean±standard error: 185.5±4.4 mg/dL vs. 196.2±4.4 mg/dL, P=0.047, for TC; and 132.3±11.5 mg/dL vs. 157.4±11.4 mg/dL, P=0.035, for TG) in fully adjusted model (adjusting for multiple covariates, including diabetes status, glycosylated hemoglobin level, and estimated glomerular filtration rate). There were no significant differences in high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol levels between the two groups. According to increments in aldosterone levels, an increasing tendency of HDL-C and decreasing tendencies of TG and non-HDL-C were observed.ConclusionPA patients had lower TC and TG levels than EH patients, independent of glycemic status and renal function.
| S-EPMC8419600 | biostudies-literature
Project description: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. 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. 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). 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.
| S-EPMC7601658 | biostudies-literature
Project description:BACKGROUND:To evaluate the correlations between lipid layer thickness (LLT) and morphology and function of the meibomian glands in patients who were diagnosed as meibomian gland dysfunction (MGD) in different age groups. METHODS:Patients who have diagnosed as obstructive MGD were included in this prospective, cross-sectional study. Patients were divided into three groups: young (ages 20-39?years), middle-aged (ages 40-59?years), and older (aged ?60?years). All patients completed an Ocular Surface Disease Index (OSDI) questionnaire and were evaluated for LLT, tear meniscus height (TMH), noninvasive tear film break-up time (NI-BUT) measurement, invasive TBUT (ITBUT), corneal fluoresceinstaining (CFS) score, eyelid margin abnormalities, Schirmer I test, and MG function and morphology, by using the Keratograph 5 and LipiView interferometer. RESULTS:Two hundred and nine patients (209 eyes) were included. The median LLT of all patient was 57?nm (IQR, 36.5?nm), and the LLT values were significantly different among the young group (median, 51?nm; IQR, 23.5?nm), middle-aged group (median, 59.5?nm; IQR 46.5?nm) and older group (median, 62?nm; IQR, 42.5?nm) (P?=?0.033, Kruskal-Wallis test). In regression analyses controlling for confounder factors sex and MG loss, the LLT was positively correlated with age (??=?5.539, P?=?0.001). There was a negative correlation between LLT and MG dropout in the all (r?=?-?0.527, P?<?0.001), young (r?=?-?0.536, P?<?0.001), middle-aged (r?=?-?0.576, P?<?0.001), and older (r?=?-?0.501, P?<?0.001) groups. LLT was positively correlated with the MG expressibility in the all (r?=?0.202, P?=?0.003), middle-aged (r?=?0.280, P?=?0.044) and older (r?=?0.452, p?<?0.001) groups, but it was no statistical significance in the young group (r?=?0.007, P?=?0.949). CONCLUSIONS:The thickness of LLT was increased with age and significantly correlated with both MG secretion and morphology in middle-aged and older patients with obstructive MGD. LLT measurement is a useful screening tool for detecting obstructive MGD and age as an influential factor should be accounted for when interpreting the meaning of the LLT value. TRIAL REGISTRATION:NCT02481167 ; Registered 25 June, 2015.
| S-EPMC7539430 | biostudies-literature
Project description:Studies have estimated that currently 344 million people worldwide and 16.4 million adults in the US have some form of dry eye disease (DED). It is believed that approximately 70% of DED cases are due to some form of evaporative dry eye, for which Meibomian gland dysfunction (MGD) is the major cause. Unfortunately, currently there is no effective treatment for MGD, and solely palliative care is available. Given the importance of MGD in DED, there has been a growing interest in studying Meibomian gland development, homeostasis and pathology, and, also, in developing therapies for treating and/or preventing MGD. For such, animal models have shown to be a vital tool. Much of what is known today about the Meibomian gland and MGD was learnt from these important animal models. In particular, canine and rabbit models have been essential for studying the physiopathology and progression of DED, and the mouse model, which includes different knockout strains, has enabled the identification of specific pathways potentially involved in MGD. Herein, we provide a bibliographic review on the various animal models that have been used to study Meibomian gland development, Meibomian gland homeostasis and MGD, primarily focusing on publications between 2000 and 2020.
| S-EPMC7700490 | biostudies-literature
Project description:Meibomian gland dysfunction (MGD) may be the leading cause of dry eye syndrome throughout the world. However, the precise mechanism(s) underlying the pathogenesis of this disease is unclear. This study was conducted to identify meibomian gland genes that may promote the development and/or progression of human MGD.Lid tissues were obtained from male and female MGD patients and age-matched controls after eyelid surgeries (e.g., to correct entropion or ectropion). Meibomian glands were isolated and processed for RNA extraction and the analysis of gene expression.The results show that MGD is associated with significant alterations in the expression of almost 400 genes in the human meibomian gland. The levels of 197 transcripts, including those encoding various small proline-rich proteins and S100 calcium-binding proteins, are significantly increased, whereas the expression of 194 genes, such as claudin 3 and cell adhesion molecule 1, is significantly decreased. These changes, which cannot be accounted for by sex differences, are accompanied by alterations in many gene ontologies (e.g., keratinization, cell cycle, and DNA repair). The findings also show that the human meibomian gland contains several highly expressed genes that are distinct from those in an adjacent tissue (i.e., conjunctival epithelium).The results demonstrate that MGD is accompanied by multiple changes in gene expression in the meibomian gland. The nature of these alterations, including the upregulation of genes encoding small proline-rich proteins and S100 calcium-binding proteins, suggest that keratinization plays an important role in the pathogenesis of MGD.
| S-EPMC3088560 | biostudies-literature
Project description:TOPIC:To discuss the pathology, causes, and ocular surface impact of meibomian gland disease (MGD), as well as its relationship to dry eye. CLINICAL RELEVANCE:MGD is a common disorder with various contributing mechanisms and clinical manifestations. Understanding MGD pathophysiology and its relationship to dry eye is important in order to optimize diagnosis and treatment algorithms. METHODS:A review of current literature was performed to discern MGD in terms of pathophysiology, risk factors, and ocular surface impact, and the relationship to dry eye. RESULTS:Meibomian gland obstruction and meibocyte depletion are important components of MGD. Many pathologies can disrupt function of meibomian glands, ranging from congenital to acquired causes. Once gland disruption occurs, the quality and quantity of meibum is altered, with a negative impact on the ocular surface. Increased tear evaporation, tear hyperosmolarity, increased ocular surface staining, increased inflammation, symptomatic irritation of the eyelid and globes, as well as decreased visual acuity have all been observed. CONCLUSION:MGD leads to changes in meibum quality and quantity that can cause evaporative dry eye and ocular surface disruption, leading to dry eye symptoms in some individuals.
| S-EPMC5685175 | biostudies-other
Project description:Cluster randomization trials with relatively few clusters have been widely used in recent years for evaluation of health-care strategies. On average, randomized treatment assignment achieves balance in both known and unknown confounding factors between treatment groups, however, in practice investigators can only introduce a small amount of stratification and cannot balance on all the important variables simultaneously. The limitation arises especially when there are many confounding variables in small studies. Such is the case in the INSTINCT trial designed to investigate the effectiveness of an education program in enhancing the tPA use in stroke patients. In this article, we introduce a new randomization design, the balance match weighted (BMW) design, which applies the optimal matching with constraints technique to a prospective randomized design and aims to minimize the mean squared error (MSE) of the treatment effect estimator. A simulation study shows that, under various confounding scenarios, the BMW design can yield substantial reductions in the MSE for the treatment effect estimator compared to a completely randomized or matched-pair design. The BMW design is also compared with a model-based approach adjusting for the estimated propensity score and Robins-Mark-Newey E-estimation procedure in terms of efficiency and robustness of the treatment effect estimator. These investigations suggest that the BMW design is more robust and usually, although not always, more efficient than either of the approaches. The design is also seen to be robust against heterogeneous error. We illustrate these methods in proposing a design for the INSTINCT trial.
| S-EPMC3407414 | biostudies-literature
Project description:PurposeTo investigate the comparative efficacy of intense pulsed light (IPL) therapy alone with that of IPL plus meibomian gland expression (MGX) for meibomian gland dysfunction (MGD).MethodsThis is a prospective randomized crossover clinical trial. Sixty patients were enrolled and randomly assigned to two groups. All of patients underwent four treatment sessions in total, which were two weeks apart. Group 1 underwent two sessions of IPL therapy with MGX, as well as two sessions of IPL alone. Group 2 received two sessions of IPL therapy alone, and two sessions of IPL therapy with MGX. The following parameters were measured at baseline (BL), 2 weeks after the second treatment session (FU1), and 2 weeks after the fourth treatment session (FU2): tearfilm break-up time (BUT), Oxford grade for corneal staining, meibomian gland expressibility (MGE), meibum quality (MQ), and ocular surface disease index (OSDI). The separate effect of MGX on improvement of MGD parameters was evaluated using generalized estimating equation (GEE).ResultsThe mean age of the participants was 57.52 ± 10.50 years. The BUT, Oxford grade, MGE, MQ, and OSDI of both groups improved significantly (from baseline) by the end of four treatment sessions (FU2 compared to BL; all p-values <0.05). The MGE and MQ significantly improved after the first and second treatment sessions (FU1 compare to BL; all p-values < 0.001). However, the improvement was not statistically significant after the third and fourth treatment sessions (FU2 compared to FU1; p-value of 0.388 for MGE and 0.645 for MQ in group 1, 0.333 for MGE and 0.333 for MQ in group 2). The IPL plus MGX therapy produced greater improvements in the BUT scores than did IPL therapy alone (p = 0.003 by GEE). In contrast, the Oxford grade, MGE, MQ, and OSDI were not influenced by the addition of MGX to IPL (p = 0.642, 0.663, 0.731, and 0.840, respectively by GEE).ConclusionIPL therapy effectively improves the subjective symptoms and objective ocular findings of MGD. MGX enhanced the improvement of BUT driven by IPL therapy. The meibomian gland function (MGE and MQ) recovers faster in response to IPL therapy than did the other parameters.
| S-EPMC7932142 | biostudies-literature