Search Results (25)

This study evaluated the efficacy of the TOF-SIMS (time-of-flight secondary ion mass spectrometry) technique for the comprehensive lipidomic analysis of human meibum, a lipid-rich secretion essential for tear film stability, using samples collected from ten participants. The applied methodology proved effective in characterizing the complex chemistry of meibum, confirming the presence of diverse lipid classes, including fatty acids, sterols, and glycerolipids. Multivariate and pairwise statistical analyses, including permutational multivariate analysis of variance (PERMANOVA) and maximum mean discrepancy (MMD),confirmed the significant compositional difference between the two groups. Principal component analysis (PCA) revealed a clear separation between the samples, driven primarily by an elevated ratio of monounsaturated fatty acids (C18:1, C16:1) to cholesterol in the group with MGD compared to healthy controls. These findings demonstrate the utility of TOF-SIMS coupled with multivariate analysis for detecting disease-specific molecular alterations in meibum, highlighting its potential for differentiating ocular surface pathologies. Full article

Background: Type 2 diabetes mellitus (T2DM) is increasingly recognized as affecting not only the retina but also the ocular surface. Chronic hyperglycemia can disrupt meibomian gland function, reduce tear secretion, and impair corneal sensitivity, leading to tear film instability and symptoms of dry eye disease. However, previous studies have reported variable findings, and the extent of these alterations remains uncertain. Methods: Following PRISMA guidelines, this systematic review and meta-analysis evaluated observational studies that compared tear film parameters between adults with T2DM and non-diabetic controls. Eligible studies assessed one or more of the following: invasive or non-invasive tear break-up time, Schirmer test, tear meniscus height, or Ocular Surface Disease Index (OSDI). Results: Twenty-four studies involving approximately 3500 eyes were included. Most reported significantly reduced tear stability and secretion in diabetic participants compared with controls. Tear break-up times were consistently shorter in T2DM, indicating a less stable tear film. Schirmer test results demonstrated lower tear production correlated with diabetes duration and poor glycemic control. Tear meniscus height was modestly reduced in T2DM, reflecting decreased tear reservoir volume. Subjective symptoms, as measured by OSDI, were generally higher among patients with T2DM, suggesting greater ocular surface discomfort. Conclusions: T2DM is strongly associated with tear film instability, reduced tear secretion, and increased dry eye symptoms. These findings suggest that diabetic care should include routine ocular surface assessment and highlight the need for standardized, longitudinal investigations. Full article

Objectives: To compare the safety and efficacy of a prototype electronic heating device, Meiboleyes^®, with the BRUDER Moist Heat Eye Compress for the treatment of Meibomian Gland Dysfunction (MGD). Methods: Adults with evidence of active MGD (Ocular Surface Disease Index [OSDI] score ≥ 13, fluorescein tear break-up time [TBUT] < 10 s and meibomian gland secretion score ≤ 12 for 15 glands of the lower lid) were enrolled in this prospective, randomised, parallel group, investigator-masked dispensing study (Australian New Zealand Clinical Trials Registry–ACTRN12624000175572). Meibomian gland secretion (MGS) score and number of meibomian glands yielding liquid secretion (MGYLS), lipid layer thickness, TBUT, ocular physiology and subjective symptoms were measured at baseline, and 2 weeks and 6 weeks following treatment. Linear mixed model analysis was conducted to compare the two groups and changes over time. Results: Ten participants (average age 38.7 ± 14.5 years) in the Meiboleyes^® test group, and 10 participants (average age 38.9 ± 14.8 years) in the BRUDER control group completed the study. MGS and MGYLS significantly improved in both treatment groups from baseline to the 2-week and 6-week follow-up visits (p ≤ 0.006). Significant improvements in TBUT (5.5 ± 1.8 vs. 8.3 ± 2.1 s, p = 0.044), OSDI scores (45.2 ± 15.1 vs. 27.4 ± 12.9, p = 0.027) and visual analogue scale dryness (55.3 ± 27.2 vs. 28.0 ± 23.9, p = 0.023) were observed in the Meiboleyes^® group only after 6 weeks of treatment. No other significant differences were observed over time or between groups. Eight treatment-related adverse events were reported in the Meiboleyes^® group compared to seven in the BRUDER group. All resolved without sequalae. Conclusions: The prototype Meiboleyes^® device was safe and effective for use as an at-home treatment for MGD when used twice daily for six weeks. Improvements in meibomian gland function were comparable to the BRUDER Moist Heat Eye Compress, but significant improvements in tear film stability and subjective comfort after 6 weeks of treatment were observed in the Meiboleyes^® group only. Full article

Meibum—a lipid-rich secretion produced by holocrine Meibomian glands (MG)—plays a central role in maintaining ocular surface homeostasis in humans. Previously, changes in MG lipidomes induced by inactivation of critical genes of meibogenesis, such as Elovl3, Soat1, Awat2, Sdr16c5/Sdr16c6, and others were shown to cause MG dysfunction (MGD) and dry eye in experimental animals. Here, we describe the impact of the changes in the lipid composition of meibum on its protective properties, specifically physiologically relevant thermotropic characteristics, using various mutant and wild-type animal models, and comparing them with healthy human subjects and patients with MGD. Meibum samples were analyzed using liquid chromatography/mass spectrometry (LC/MS) and differential scanning microcalorimetry (DSC). We found that any change in the balance between major lipid classes in meibum—wax esters, cholesteryl esters, triacylglycerols, and free cholesterol—cause detrimental changes in its thermotropic properties, loss of cohesiveness, and abnormal expressibility from MG, resulting in MGD-like phenotypes of the eyes and adnexa. We conclude that tested knockout mice can be valuable models for modeling and studying MGD. A combination of LC/MS and DSC can be a powerful diagnostic tool and may help to diagnose MGD and other pathologies, as well as determine their molecular mechanisms. Full article

Background and Objectives: Dry eye disease (DED) is a multifactorial ocular surface disease that markedly diminishes quality of life. Although diabetes mellitus is well-known for its retinal consequences, anterior segment symptoms including dry eye disease are often overlooked. Chronic hyperglycemia causes metabolic, neurovascular, and immunological changes that undermine tear film stability, corneal innervation, and ocular surface integrity. This review seeks to consolidate existing knowledge regarding the concealed impacts of diabetes on ocular surface homeostasis, highlighting processes, diagnostic difficulties, and treatment prospects. Materials and Methods: A narrative review of the literature was performed by searching PubMed for publications from January 2020 to July 2025 using the terms “diabetic dry eye,” “hyperglycemia AND ocular surface,” “tear proteomics AND diabetes,” “corneal nerves AND diabetes,” and “neurotrophic keratitis.” Eligible studies were experimental research, clinical trials, and translational investigations concerning tear film function, corneal neuropathy, inflammatory indicators, or lacrimal gland dysfunction in diabetes. The exclusion criteria were non-English language, lack of primary data, and inadequate methodological description. Results: Hyperglycemia compromises lacrimal gland functionality, modifies lipid secretion from Meibomian glands, and diminishes corneal nerve density, resulting in neurotrophic deficits. Inflammatory cytokines and oxidative stress compromise epithelial integrity, but proteome alterations in tears serve as sensitive indicators of disease. Diagnosis is impeded by corneal hypoesthesia, resulting in a disconnection between symptoms and findings. Progress in imaging, proteomics, and artificial intelligence may facilitate earlier detection and improved risk assessment. Novel therapeutics, such as neurotrophic drugs, antioxidants, and customized anti-inflammatory approaches, show promise but remain under clinical evaluation. Conclusions: Diabetes-related dry eye disease is a multifaceted and underappreciated condition influenced by systemic metabolic dysfunction. The ocular surface may act as an initial indicator for systemic disease load. Narrative synthesis emphasizes the necessity for customized diagnostic instruments, individualized treatment approaches, and collaborative management. Reconceptualizing diabetic dry eye disease within the context of systemic metabolic care presents prospects for precision medicine strategies that enhance both ocular and systemic results. Full article

Objectives: To compare the long-term efficacy and safety of intense pulsed light (IPL) treatments using a 590-nm and an acne filter. Methods: In this prospective, randomized, paired-eye trial study, 30 patients with moderate and severe meibomian gland dysfunction (MGD) were followed up for at least one month after their last treatment. Group A received IPL treatment with an acne filter, a type of notch filter that blocks wavelengths between 600 and 800 nm, allowing IPL to emit wavelengths between 400–600 nm and 800–1200 nm. Group B received treatment with a 590 nm filter, a type of cut-off filter that blocks wavelengths below 590 nm. Clinical parameters, including tear osmolarity, matrix metalloproteinase (MMP)-9 expression, tear break-up time, ocular surface staining scores, Schirmer’s test I, lid margin telangiectasia scores, MG expressibility/secretion scores, and Ocular Surface Disease Index scores, were measured at baseline, 1, 6, and 12 months after their last treatment. Results: In the linear mixed model, significant time effects on all clinical parameters, except for MMP-9 grades and Schirmer’s test I results, were observed within each group. However, interactions between time points (baseline, 6 months, 12 months) and groups (Group A, B) were not significant. The generalized estimating equation model showed no significant interaction between time points and groups for MMP-9 positivity; however, a significant time effect on MMP-9 positivity was observed in Group A, with a decrease at 12 months after their last treatment when compared to baseline and 6 months. Conclusions: The IPL treatment modality for moderate to severe MGD demonstrated a significant therapeutic effect for one year under strictly controlled self-administration of other treatments. IPL treatment using acne filter is a promising treatment option for reducing MMP-9 positivity in MGD patients. Full article

Dry eye disease (DED) has become increasingly prevalent in the digital era, largely due to prolonged screen exposure. The excessive use of digital devices contributes to inappropriate blink frequency and dynamics, leading to ocular surface dryness and discomfort. Additionally, digital screen use has broader implications for systemic health, including visual strain, headaches, and disrupted circadian rhythms caused by blue light exposure. Previous studies have shown that prolonged screen time correlates with altered blink frequency and increased symptom severity in DED patients, exacerbating the imbalance in tear film production and evaporation. Blinking dynamics, particularly blink rate and completeness, are crucial in maintaining ocular surface moisture. Incomplete blinking impairs meibomian gland function, reducing lipid secretion, which is essential for preventing tear evaporation. Raising patient awareness through educational material, ergonomic adjustments, and blinking exercises has been shown to mitigate these effects. Digital tools that provide targeted educational interventions can be particularly effective in improving blink dynamics and overall ocular comfort. This study evaluates the efficacy of digital applications in optimizing blinking dynamics and enhancing tear film stability. The findings suggest that these innovations improve patient outcomes by encouraging healthier eye care practices. However, further research is needed to assess their long-term impact across diverse populations. Full article

Ophthalmic nanoemulsions that can treat the deficiencies of meibum (MGS) in Meibomian gland disease and restore its functionality in the tear film are greatly sought. The Rohto Dry Aid (RDA) formulation employs TEARSHIELD TECHNOLOGY^TM, which uses a multicomponent oil phase of polar and non-polar lipid-like molecules selected to mimic the profiles of healthy meibum. Thus, the interactions of RDA with “diseased” Meibomian (dMGS) films merit deeper analysis, as these interactions might offer important clues for both the development of new ocular formulations and the processes behind the therapeutic action of the nanoemulsions. Pseudobinary dMGS/RDA films were spread at the air–water surface of the Langmuir trough. Surface pressure-area isocycles and stress relaxations were used to access the layer’s response to blink-like cycling and dilatational viscoelasticity, respectively, while film morphology was recorded via Brewster angle microscopy. It was found that RDA is able to reverse the brittleness and to restore the stability of “diseased” MGS films and thus to revert the layer’s properties to the functionality of healthy Meibomian lipids. Therefore, in order to effectively treat dry eyes with MGS-oriented therapy, ophthalmic nanoemulsions warrant more research. Full article

Meibomian gland dysfunction (MGD) is one of the main causes of dry eye disease. To better understand the physiological functions of human meibomian glands (MGs), the present study compared MGs with free sebaceous glands (SGs) and hair-associated SGs of humans using morphological, immunohistochemical, and liquid chromatography—mass spectrometry (LCMS)-based lipidomic approaches. Eyelids with MGs, nostrils, lips, and external auditory canals with free SGs, and scalp with hair-associated SGs of body donors were probed with antibodies against cytokeratins (CK) 1, 8, 10, and 14, stem cell markers keratin 15 and N-cadherin, cell–cell contact markers desmoglein 1 (Dsg1), desmocollin 3 (Dsc3), desmoplakin (Dp), plakoglobin (Pg), and E-cadherin, and the tight junction protein claudin 5. In addition, Oil Red O staining (ORO) was performed in cryosections. Secretions of MGs as well as of SGs of nostrils, external auditory canals, and scalps were collected from healthy volunteers, analyzed by LCMS, and the data were processed using various multivariate statistical analysis approaches. Serial sections of MGs, free SGs, and hair-associated SGs were 3D reconstructed and compared. CK1 was expressed differently in hair-associated SGs than in MGs and other free SGs. The expression levels of CK8, CK10, and CK14 in MGs were different from those in hair-associated SGs and other free SGs. KRT15 was expressed differently in hair-associated SGs, whereas N-cadherin was expressed equally in all types of glands. The cell–cell contact markers Dsg1, Dp, Dsc3, Pg, and E-cadherin revealed no differences. ORO staining showed that lipids in MGs were more highly dispersed and had larger lipid droplets than lipids in other free SGs. Hair-associated SGs had a smaller number of lipid droplets. LCMS revealed that the lipid composition of meibum was distinctively different from that of the sebum of the nostrils, external auditory canals, and scalp. The 3D reconstructions of the different glands revealed different morphologies of the SGs compared with MGs which are by far the largest type of glands. In humans, MGs differ in their morphology and secretory composition and show major differences from free and hair-associated SGs. The composition of meibum differs significantly from that of sebum from free SGs and from hair-associated SGs. Therefore, the MG can be considered as a highly specialized type of holocrine gland that exhibits all the histological characteristics of SGs, but is significantly different from them in terms of morphology and lipid composition. Full article

Purpose: To describe the clinical and morphologic changes in the ocular surface microstructure of patients affected with moderate-to-severe Atopic Dermatitis (AD) before and during Dupilumab treatment. Methods: This is a monocentric observational study on thirty-three patients affected with AD before and during Dupilumab treatment. All patients underwent a slit-lamp examination: complete clinical assessment, Break Up Time test (BUT), Schirmer test, and corneal staining grading (Oxford scale) were performed. Meibomian Glands Dysfunction (MGD) evaluation (Meibography), Non-invasive Keratograph Break Up Time test (NIKBUT), Tear Meniscus Height (TMH), and ocular Redness Score (RS) have been investigated using an OCULUS Keratograph. In vivo images of the conjunctiva, cornea, and meibomian glands have been acquired by confocal microscopy. Results: Sixty-six eyes were included in our study: twenty-two eyes of 11 naive patients with indication for treatment but not in therapy yet (Group 1) and forty-four eyes of 22 patients treated with Dupilumab for at least 4 months (subcutaneous administration of 300 mg every 2 weeks) (Group 2). Either patients treated with Dupilumab or naive patients with moderate-to-severe forms of AD had a tear film instability (TBUT and NIKBUT reduced), whereas the quantity of the tear film was overall normal (Schirmer test and TMH), without statistically significant differences between the two groups. When Meibography was performed with the Keratograph, the difference between Group 1 and Group 2 was statistically significant in terms of Meiboscore (p = 0.0043 and p = 0.0242, respectively), as well as the difference in terms of mean RS. These results paired well with the confocal microscopy results in which we found a decrease in the goblet cell population in the conjunctival epithelium in the treated group (5.2 cells/mm), along with inflammatory cells that were more concentrated around the adenoid lumina of the meibomian glands. Conclusions: In recent years, the use of Dupilumab has been increasing, but mild-to-severe conjunctivitis is a common side effect. Our major results demonstrate a loss of meibomian glands at the Keratograph examination: we can assume a reduced meibum secretion and an evaporative dry eye with MGD. We suggest that the inflammation of the ocular surface may involve not only the cornea and the conjunctiva, but also the meibomian glands, and Dupilumab may play a role. However, the frequency of clear conjunctivitis is not as common as reported in the literature. Full article

The main function of exocrine Meibomian glands (MGs) is to produce a lipid-rich secretion called meibum which plays a critical role in maintaining the ocular surface homeostasis of humans and most mammals. The chemical composition of meibum, and its quantity produced by MGs, largely determine whether it can fulfill its role successfully. Aging was frequently associated with the onset of various MG-related pathologies. The goal of this study was to determine how aging affects the chemical composition and quantity of meibum in mice, and identify possible molecular markers of aging. Unbiased, untargeted and targeted lipidomic evaluation of mouse MG lipids was conducted using liquid chromatography—high-resolution mass spectrometry, and the results were analyzed using Principal Component, Orthogonal Projections to Latent Structures Discriminant, and Partial Least Square Discriminant Analyses. We found that aging leads to dysregulation of lipid metabolism in MGs, changing the ratios of major classes of MG lipids (such as wax esters, triacylglycerols, and phospholipids) in a progressive manner. Several lipid species that belong to these groups of MG lipids are proposed as clear markers of aging in a mouse model. Full article

Meibomian gland dysfunction (MGD) is a functional and morphological disorder of the meibomian glands which results in qualitative or quantitative alteration in meibum secretion and is the major cause of evaporative dry eye (EDE). EDE is often characterized by tear film instability, increased evaporation, hyperosmolarity, inflammation, and ocular surface disorder. The precise pathogenesis of MGD remains elusive. It has been widely considered that MGD develops as a result of ductal epithelial hyperkeratinization, which obstructs the meibomian orifice, halts meibum secretion, and causes secondary acinar atrophy and gland dropout. Abnormal self-renewal and differentiation of the acinar cells also play a significant role in MGD. This review summarizes the latest research findings regarding the possible pathogenesis of MGD and provides further treatment strategies for MGD-EDE patients. Full article

The meibomian glands (MGs) within the eyelids produce a lipid-rich secretion that forms the superficial layer of the tear film. Meibomian gland dysfunction (MGD) results in excessive evaporation of the tear film, which is the leading cause of dry eye disease (DED). To develop a research model similar to the physiological situation of MGs, we established a new 3D organotypic slice culture (OSC) of mouse MGs (mMGs) and investigated the effects of melanocortins on exocrine secretion. Tissue viability, lipid production and morphological changes were analyzed during a 21-day cultivation period. Subsequently, the effects on lipid production and gene expression were examined after stimulation with a melanocortin receptor (MCR) agonist, α-melanocyte-stimulating hormone (α-MSH), and/or an MCR antagonist, JNJ-10229570. The cultivation of mMGs OSCs was possible without impairment for at least seven days. Stimulation with the MCR agonists induced lipid production in a dose-dependent manner, whereas this effect was tapered with the simultaneous incubation of the MCR antagonist. The new 3D OSC model is a promising approach to study the (patho-) physiological properties of MG/MGD while reducing animal studies. Therefore, it may accelerate the search for new treatments for MGD/DED and lead to new insights, such as that melanocortins likely stimulate meibum production. Full article

Background: To assess the clinical efficacy, tolerability and safety of a new-generation ophthalmic solution containing cross-linked hyaluronic acid 0.15% trehalose 3%, liposomes 1% and sterylamine 0.25% (Trimix^® Off Health Italia, Firenze, Italy) (CXHAL) versus trehalose 3% (Thealoz^®, Thea Pharmaceuticals, Clermont-Ferrand, France) (TRS) in subjects with moderate to severe dry eye disease (DED). Patients and methods: In this prospective, observational cohort study, 41 subjects with moderate to severe dry eye were enrolled and divided into two age- and sex-matched groups. Group 1 was treated with CXHA eye drops, and group 2 was treated with TRS eye drops four times daily for 2 months. All subjects were evaluated at baseline (V0) and at day 60 ± 3 (V1). The examination comprised Best Corrected Visual Acuity (BCVA) and Symptom Assessment in Dry Eye (SANDE). Tear osmolarity was evaluated using the TearLab Osmolarity System^®; Keratograph 5M (Oculus, Wetzlar, Germany) was performed to assess tear meniscus height (TMH), fluorescein tear break-up time (TBUT) and corneal and conjunctival fluorescein staining and meibography; furthermore, slit lamp evaluation was performed for eyelid erythema and edema, conjunctival chemosis and hyperemia and Meibomian gland secretion quality. Results: All patients completed the treatment. BCVA remained stable in both groups, and no adverse events were reported. After 2 months, both groups showed statistically significant improvements for SANDE (p = 0.001 and p = 0.012, respectively), TBUT values (p < 0.001 and p < 0.001, respectively) and staining (p = 0.004 and p = 0.001, respectively) as compared to baseline values. Group 1 showed a statistically significant improvement in SANDE frequency and tear osmolarity (p = 0.02 and p = 0.001, respectively), whereas chemosis was significantly reduced in group 2. The amount of TBUT improvement was statistically higher in group 1 compared to that in group 2 (p = 0.041). Conclusion: A new-generation multiple-action ophthalmic solution was safe and clinically effective in the treatment of moderate and severe dry eye, with significant improvements in the main ocular surface parameters. Full article

Meibomian gland orifices (MGOs) are located along the eyelid margin and secrete meibum into the tear film. The profile of resident innate immune cells (ICs) at this site is not well understood. The distribution and phenotype of resident ICs around MGOs in mice was investigated and herein defined as MGO-associated immune cells (MOICs). The effect of topical 0.1% benzalkonium chloride (BAK) on MOICs was also assessed. Eyelids from healthy CD11c^eYFP and Cx3cr1^gfp/gfp mice aged three or seven months were compared. ICs were identified as CD11c⁺, Cx3cr1⁺, and MHC-II⁺ using four-colour immunostaining and confocal microscopy. MOIC density was variable but clustered around MGOs. There were more CD11c⁺ MOICs in three-month-old compared with seven-month-old mice (three-month-old: 893$\pm$449 cells/mm² vs. seven-month-old: 593$\pm$493 cells/mm², p = 0.004). Along the eyelid margin, there was a decreasing gradient of CD11c⁺ MOIC density in three-month-old mice (nasal: 1003$\pm$369 cells/mm², vs. central: 946$\pm$574 cells/mm², vs. temporal: 731$\pm$353 cells/mm², p = 0.044). Cx3cr1-deficient mice had two-fold fewer MHC-II⁺ MOICs, suggesting a role for Cx3cr1 receptor signaling in meibomian gland surveillance. CD11c⁺ MOIC density was lower in BAK-exposed eyes compared to saline-treated controls, suggesting a change in homeostasis. This study provides novel insight into resident ICs located at MGOs, and their contribution to MG homeostasis. Full article