OBJECTIVE: Aimed to create a nomogram using clinical and eye-specific metrics to predict the efficacy of intravenous glucocorticoid (IVGC) therapy in patients with active and moderate-to-severe Thyroid-Associated Ophthalmopathy (TAO).
METHODS: This study was conducted on 84 eyes from 42 moderate-to-severe TAO patients who received systemic IVGC therapy, and 42 eyes from 21 controls. Data were collected retrospectively from June 2020 to December 2021. The least absolute shrinkage and selection operator (LASSO) method was used to identify predictive factors for \"unresponsiveness\" to IVGC therapy. These factors were then analyzed using logistic regression to create a nomogram. The model\'s discriminative ability was robustly assessed using a Bootstrap resampling method with 1000 iterations for receiver operating characteristic (ROC) curve analysis.
RESULTS: The LASSO analysis identified six factors with non-zero coefficients as significant, including Schirmer I test values, Meibomian gland (MG) diameter, MG length, disease duration, whole capillary vessel density (VD) in the radial peripapillary capillary (RPC), and whole macular VD for the superficial retinal capillary plexus (SRCP). The subsequent logistic regression model highlighted MG length, whole macular VD for SRCP, and disease duration as independent predictors of IVGC therapy response. The constructed nomogram demonstrated an area under the curve (AUC) of 0.82 (95% CI: 0.73-0.91), affirming the model\'s consistent and reliable ability to distinguish between responsive and non-responsive TAO patients.
CONCLUSIONS: Our nomogram, combining MG length (<4.875 mm), SRCP VD (<50.25%), and disease duration (>5.5 months), reliably predicts lower IVGC therapy effectiveness in active, moderate-to-severe TAO patients.

Exposure to particulate matters in air pollution of 2.5 μm or less (PM2.5) was associated with loss of meibomian glands. The aim of this study was to verify that PM2.5 could directly impact meibomian gland epithelial cells and damage their function. To investigate the impact of PM2.5 on meibomian gland, immortalized human meibomian gland epithelial cells were treated with various concentrations of PM2.5in vitro. Meibomian gland cell microstructure, cell viability, expression of proliferating cell nuclear antigen and IL-1β, and intracellular accumulation of acidic vesicles were measured by transmission electron microscopy, cell counting, Western blot and LysoTracker staining, respectively. To further study the effect of PM2.5in vivo, male C57BL/6J mice were treated with 5 mg/ml PM2.5 or vehicle for 3 months. Corneal fluorescein staining and ocular examinations were done before and after the treatment. Eyelids tissues were processed for morphological studies, immunostaining and Oil Red O staining. Our data suggest that exposure to PM2.5 caused significant meibomian gland dropout, clogged gland orifice and increased corneal fluorescein staining that were consistent with the clinical presentations of meibomian gland dysfunction. Prominent changes in the morphology and ultrastructure of meibomian glands was observed with PM2.5 treatment. PM2.5 promoted ductal keratinization, inhibited cell proliferation, induced cell apoptosis and increased Interleukin-1β production in meibomian gland epithelial cells. This study may explain the association between PM2.5 exposure and meibomian gland dropout observed in clinic. PM2.5 resuspension instillation could be used to induce a meibomian gland dysfunction animal model.

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

BACKGROUND: To observe morphologic and functional changes in meibomian glands in pediatric patients with and without lower eyelid epiblepharon.
METHODS: In this prospective observation study, 55 eyes of 55 patients( 24 males, 31 females; mean age ± SD,9.82 ± 2.59 years; range 6-14 years) and 60 eyes of 60 controls ( 32 males, 28 females; mean age ± SD,10.57 ± 2.75 years; range 6-14 years) were included. The following tests were performed: eyelid margin abnormality by slit-lamp examination, measurement of noninvasive keratographic break-up time (NIKBUT), grading of absence of meibomian gland (meibography score) assessed with noncontact meibography, morphologic changes of meibomian glands (thinning, dilatation and distortion), tear production by the Schirmer 1 test, and grading of meibum quality and meibomian gland expressibility.
RESULTS: The morphologic changes in meibomian glands were more common in the epiblepharon group (56.36%) than in the control group (28.33%) (p = 0.002). The meibum quality was worse in the epiblepharon group than in the control group (p = 0.009), and the NIKBUT was significantly shorter in the epiblepharon group than in the control group (p = 0.012). There was no significant difference in the Schirmer 1 test, meibomian gland expressibility, eyelid margin abnormality score or total meibography score between the two groups. Morphologic changes in the meibomian glands in the upper eyelids (38.18%) were more common than those in the lower eyelids (20%) (p = 0.036) in the epiblepharon group, and the meibography score was higher in the upper eyelids than in the lower eyelids (p = 0.001).
CONCLUSIONS: There are morphological and functional changes in meibomian glands in pediatric patients with lower eyelid epiblepharon. Although the inverted eyelashes were located in the lower eyelid, morphological changes in the meibomian glands were more common in the upper eyelid.

OBJECTIVE: To explore the long-term course of patients with meibomian gland dysfunction (MGD), and to analyse potential factors affecting the recovery of meibomian gland (MG) dropout.
METHODS: Seventy-nine MGD patients (79 eyes) aged 36.03±15.78 years old who underwent more than one year of follow-up were enrolled in this retrospective study. Corneal fluorescein staining (CFS), tear meniscus height (TMH), noninvasive breakup time (NIBUT), and noncontact meibography at baseline and last visit were collected and analysed. Then an automatic MG analyzer was used to measure the morphological and functional parameters of MGs, including their area ratio (AR), tortuosity index (TI), and signal index (SI). The patients whose AR increased by more than 5% were defined as MG improvement, and AR decreased by more than 5% was MG worsening.
RESULTS: A total of 79 patients (79 eyes) were assessed with at least 1-year of follow-up. More than 1/3 of MGD patients (27 eyes, 34.2%) underwent MG improvement, and 30.4% of MGs became worsened. Age (P=0.002), gender (P<0.001), IPL treatment (P=0.013), the change of CFS (P=0.0015), and the recovery of SI (P=0.035) showed significant differences among different recovery groups. Age(P<0.001), female sex (P=0.003), ΔCFS (P<0.001), AR at baseline (P<0.001) were negative correlation with AR recovery, and the change of SI (P=0.003) and IPL treatment (P=0.003) had a positive correlation with it. Among them, age (P=0.038), the change of CFS (P=0.004), and AR at baseline (P=0.007) were confirmed as negatively correlated factors predicting the long-term change of the MG.
CONCLUSIONS: Although the MGD treatment has continued for more than 1 year, only 34.2% of MGD patients were observed to undergo MG improvement. Younger patients and patients with better CFS recovery seem to have more opportunities to improve their MGs.

OBJECTIVE: Meibomian glands (MGs) are crucial for maintaining tear film stability and ocular surface health. Here, we aim to establish a novel organotypic culture model of MGs and explore the risk factors of MG dysfunction (MGD).
METHODS: We developed a novel organotypic culture model for MGs at the air-liquid interface. The viability and cell proliferation of MGs were assessed using CCK-8, immunofluorescence, and qPCR. Lipid accumulation was evaluated by Nile red staining and microscopic examination. Protein expression levels were evaluated by immunofluorescence and Western blot assay. EdU assay was employed to track the proliferation of acinar cells. The validity of the model was confirmed through culturing MGs from mice of different ages and incorporating certain drugs (Dex) into the culture system.
RESULTS: Utilizing the novel culture model, the MG tissue exhibited sustained viability, cellular division, and continuous production of lipids for a duration of 7 days. Lipid droplets formed were directly visualized using light field microscopy. Through the cultivation of aged mice\'s MGs, it was discovered that aging resulted in diminished proliferation and lipid synthesis, along with an aberrant increase in Krt10 expression. Further application of this model showed that Dex treatment diminished MG\'s proliferation and lipid synthesis. Finally, an in vivo study was conducted to provide additional confirmation of the phenomenon of Dex-induced abnormalities.
CONCLUSIONS: In this study, a stable organotypic culture model of the MGs was established. The organotypic culture model offers a valuable tool to investigate the pathophysiological mechanisms and facilitate drug screening for MG-related diseases.

Meibomian glands (MGs) secrete lipid (meibum) onto the ocular surface to form the outermost layer of the tear film. Proper meibum secretion is essential for stabilizing the tear film, reducing aqueous tear evaporation, and maintaining the homeostasis of the ocular surface. Atrophy of MG as occurs with aging, leads to reduction of meibum secretion, loss of ocular surface homeostasis and evaporative dry eye disease (EDED). Since MGs are holocrine glands, secretion of meibum requires continuous self-renewal of lipid-secreting acinar meibocytes by stem/progenitor cells, whose proliferative potential is dramatically reduced with age leading to MG atrophy and an age-related meibomian gland dysfunction (ARMGD). Understanding the cellular and molecular mechanisms regulating meibocyte stem/progenitor cell maintenance and renewal may provide novel approaches to regenerating MG and treating EDED. Towards that end, recent label retaining cell and lineage-tracing experiments as well as knock-out transgenic mouse studies have begun to identify the location and identities of meibocyte progenitor cells and potential growth and transcription factors that may regulate meibocyte renewal. In addition, recent reports have shown that ARMGD may be reversed by novel therapeutics in mice. Herein, we discuss our current understanding of meibocyte stem/progenitor cells and the hunt for gland renewal.

Meibomian gland dysfunction (MGD) is a group of disorders linked by functional abnormalities of the meibomian glands. Current studies on MGD pathogenesis focus on meibomian gland cells, providing information on a single cell\'s response to experimental manipulation, and do not maintain the architecture of an intact meibomian gland acinus and the acinar epithelial cells\' secretion state in vivo. In this study, rat meibomian gland explants were cultured by a Transwell chamber-assisted method under an air-liquid interface (airlift) in vitro for 96 h. Analyses for tissue viability, histology, biomarker expression, and lipid accumulation were performed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and TUNEL assays, hematoxylin and eosin (H&E) staining, immunofluorescence, Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), transmission electron microscopy (TEM), and western blotting (WB). MTT, TUNEL, and H&E staining indicated better tissue viability and morphology than the submerged conditions used in previous studies. Levels of MGD biomarkers, including keratin 1 (KRT1) and 14 (KRT14) and peroxisome proliferator-activated receptor-gamma (PPAR-γ), along with oxidative stress markers, including reactive oxygen species, malondialdehyde, and 4-hydroxy-2-nonenal, gradually increased over culture time. The MGD pathophysiological changes and biomarker expression of meibomian gland explants cultured under airlift conditions were similar to those reported by previous studies, indicating that abnormal acinar cell differentiation and glandular epithelial cell hyperkeratosis may contribute to obstructive MGD occurrence.

To test the changes of meibomian gland (MG) morphology using an artificial intelligence (AI) analytic system in asymptomatic children wearing overnight orthokeratology (OOK) and soft contact lens (SCL).
A retrospective study was conducted including 89 participants treated with OOK and 70 participants with SCL. Tear meniscus height (TMH), noninvasive tear breakup time (NIBUT), and meibography were obtained using Keratograph 5 M. MG tortuosity, height, width, density, and vagueness value were measured using an artificial intelligence (AI) analytic system.
In an average of 20.80 ± 10.83 months follow-up, MG width of the upper eyelid significantly increased and MG vagueness value significantly decreased after OOK and SCL treatment (all P < 0.05). MG tortuosity of the upper eyelid significantly increased after OOK treatment (P < 0.05). TMH and NIBUT did not differ significantly pre- and post- OOK and SCL treatment (all P > 0.05). The results from the GEE model demonstrated that OOK treatment positively affected MG tortuosity of both upper and lower eyelids (P < 0.001; P = 0.041, respectively) and MG width of the upper eyelid (P = 0.038), while it negatively affected MG density of the upper eyelid (P = 0.036) and MG vagueness value of both upper and lower eyelids (P < 0.001; P < 0.001, respectively). SCL treatment positively affected MG width of both upper and lower eyelids (P < 0.001; P = 0.049, respectively) as well as MG height of the lower eyelid (P = 0.009) and tortuosity of the upper eyelid, (P = 0.034) while it negatively affected MG vagueness value of both upper and lower eyelids (P < 0.001; P < 0.001, respectively). However, no significant relationship was found between the treatment duration and TMH, NIBUT, MG morphological parameters in OOK group. SCL treatment duration negatively affected MG height of the lower eyelid (P = 0.002).
OOK and SCL treatment in asymptomatic children can influence MG morphology. The AI analytic system may be an effective method to facilitate the quantitative detection of MG morphological changes.

BACKGROUND: Orthokeratology lenses, which are worn overnight, are recommended for reducing myopia progression. They lie on the cornea and can influence the ocular surface by temporarily reshaping the corneal surface through a reverse geometry design. This study investigated the effect of overnight orthokeratology lenses on tear film stability and meibomian gland status in children aged 8-15 years.
METHODS: This prospective, self-controlled study included 33 children with monocular myopia who were prescribed orthokeratology lenses for at least one year. The experimental group (ortho-k group) comprised 33 myopic eyes. The control group comprised the emmetropic eyes of the same participants. Tear film stability and meibomian gland status were measured using a Keratograph 5M (Oculus, Wetzlar, Germany). Paired t-tests and Wilcoxon signed-rank tests were used to compare the data between the two groups.
RESULTS: At the one-year visit, the non-invasive first tear film break-up time (NIBUTf) values were 6.15 ± 2.56 s and 6.18 ± 2.61 s in the experimental and control groups, respectively. The lower tear meniscus height was 18.74 ± 0.05 μm and 18.65 ± 0.04 μm in these groups, respectively. No significant difference was observed in loss of meibomian glands or non-invasive average tear film break-up time between the experimental and control groups using Wilcoxon signed-rank tests.
CONCLUSIONS: The stability of the tear film and meibomian gland status were not significantly affected by wearing orthokeratology lenses overnight, indicating that continuous use of orthokeratology lenses for 12 months has a minimal effect on the ocular surface. This finding can help guide the clinical management of tear film quality with respect to the use of orthokeratology contact lenses.