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Seminars in Ophthalmology Apr 2024The prevalence of dry eye disease (DED) is rising among visual display terminal (VDT) users, a trend that correlates with the growing use of digital devices. The... (Review)
Review
PURPOSE
The prevalence of dry eye disease (DED) is rising among visual display terminal (VDT) users, a trend that correlates with the growing use of digital devices. The prevalence of VDT-associated DED is reported based on dry eye questionnaires; however, VDT's impact on tear film parameters is less understood.
METHODS
A review of published literature on both the alterations in tear film observed in VDT users and the impact of various interventions on their tear film.
RESULTS
Most studies show reduction in tear stability as well as reduction in the blink rate. The role of lacrimal gland hypofunction in visual display terminal (VDT) users is a subject of ongoing debate. Schirmer test values typically exceed the 10 mm threshold, suggesting normal tear production, and tear osmolarity remains within normal ranges but VDT users consistently present with lower Schirmer values compared to non-VDT users. The effects on Meibomian glands and mucin levels need more research as the numbers studied are small. Very few studies have analysed mucin levels in VDT users with reports of normal or reduced values. Even asymptomatic users can have tear film instability; hence, the diagnostic criteria need to be formulated and validated. Different interventions such as neurostimulation, blink improving apps, eyelid warming devices, moist goggles, and lubricants have been explored in VDT users but without a control arm and in asymptomatic VDT users in most studies.
CONCLUSION
The alterations have been observed on aqueous, lipid and mucin components of the tear film, although the extent of the impact is variable across studies. There is urgent need of well-designed studies for studying the tear film changes and management options for the upcoming lifestyle epidemic in VDT users.
PubMed: 38629642
DOI: 10.1080/08820538.2024.2332355 -
International Journal of Molecular... Apr 2024While the involvement of thermosensitive transient receptor potential channels (TRPs) in dry eye disease (DED) has been known for years, their expression in the...
While the involvement of thermosensitive transient receptor potential channels (TRPs) in dry eye disease (DED) has been known for years, their expression in the meibomian gland (MG) has never been investigated. This study aims to show their expression and involvement in the lipogenesis of the MG, providing a possible new drug target in the treatment of DED. Our RT-PCR, Western blot and immunofluorescence analysis showed the expression of , , and in the MG at the gene and the protein level. RT-PCR also showed gene expression of but not . Calcium imaging and planar patch-clamping performed on an immortalized human meibomian gland epithelial cell line (hMGECs) demonstrated increasing whole-cell currents after the application of capsaicin (TRPV1) or icilin (TRPM8). Decreasing whole-cell currents could be registered after the application of AMG9810 (TRPV1) or AMTB (TRPM8). Oil red O staining on hMGECs showed an increase in lipid expression after TRPV1 activation and a decrease after TRPM8 activation. We conclude that thermo-TRPs are expressed at the gene and the protein level in MGs. Moreover, TRPV1 and TRPM8's functional expression and their contribution to their lipid expression could be demonstrated. Therefore, TRPs are potential drug targets and their clinical relevance in the therapy of meibomian gland dysfunction requires further investigation.
Topics: Humans; Meibomian Glands; Lipogenesis; Meibomian Gland Dysfunction; Blotting, Western; Capsaicin
PubMed: 38612853
DOI: 10.3390/ijms25074043 -
BMJ Open Ophthalmology Apr 2024The objective of this study is to determine the validity and reliability of the red filter meibography by smartphone compared with infrared in assessing meibomian gland...
OBJECTIVE
The objective of this study is to determine the validity and reliability of the red filter meibography by smartphone compared with infrared in assessing meibomian gland drop-out.
METHODS AND ANALYSIS
An analytical cross-sectional study was done with a total of 35 subjects (68 eyes) with suspected MGD based on symptoms and lid morphological abnormalities. Meibomian glands were photographed using two smartphones (Samsung S9 and iPhone XR) on a slit-lamp with added red filter. Images were assessed subjectively using meiboscore by the two raters and drop-out percentages were assessed by ImageJ.
RESULTS
There was no agreement in meiboscore and a minimal level of agreement in drop-out percentages between red filter meibography and infrared. Inter-rater reliability showed no agreement between two raters. Intra-rater reliability demonstrated weak agreement in rater 1 and no agreement in rater 2.
CONCLUSION
Validity of the red filter meibography technique by smartphones is not yet satisfactory in evaluating drop-out. Further improvement on qualities of images must be done and research on subjective assessment was deemed necessary due to poor results of intrarater and inter-rater reliability.
Topics: Humans; Meibomian Gland Dysfunction; Smartphone; Cross-Sectional Studies; Reproducibility of Results; Meibomian Glands
PubMed: 38609325
DOI: 10.1136/bmjophth-2023-001266 -
Contact Lens & Anterior Eye : the... Jun 2024To investigate if there is a visible difference in meibomian gland (MG) length between images captured with the Visante optical coherence tomography (OCT;... (Comparative Study)
Comparative Study
PURPOSE
To investigate if there is a visible difference in meibomian gland (MG) length between images captured with the Visante optical coherence tomography (OCT; wavelength = 1,310 nm) and the OCULUS Keratograph 5M (K5M; wavelength = 880 nm).
METHODS
Adults between 18 and 40 years were recruited. Baseline dry eye disease was evaluated with the Standard Patient Evaluation of Eye Dryness (SPEED) and tear meniscus height and tear breakup time with the K5M. Right upper and lower eyelid MGs were imaged with the K5M and Visante OCT. Each image was graded with the 0 to 3 meiboscore scale. The central 5 MGs were evaluated with ImageJ for percent gland length visibility.
RESULTS
Thirty participants were analyzed with a median (interquartile range [IQR]) age of 23.0 (5.0) years (53.3 % female). Overall, participants were asymptomatic and had normal tear films. Meiboscores based on K5M and Visante OCT was significantly different for the lower eyelid (0[1] vs 1[2]; p = 0.007) but not the upper eyelid (0[1] vs 0[1]; p = 1.00). The mean percent gland visibility of the upper eyelid (82.7[9.6] vs 75.2[13.5]; p < 0.001) and the lower eyelid (81.2[12.7] vs 64.1[17.6]; p < 0.001) were significantly greater on the Visante OCT than the K5M images, respectively.
CONCLUSION
OCT images had significantly greater percent visible MG lengths than the K5M images. This suggests viable segments of the MGs may be missed with typical imaging, which may explain how it is possible that studies have found less post-treatment MG atrophy.
Topics: Humans; Tomography, Optical Coherence; Meibomian Glands; Female; Male; Adult; Dry Eye Syndromes; Young Adult; Tears; Adolescent; Reproducibility of Results
PubMed: 38565442
DOI: 10.1016/j.clae.2024.102162 -
International Journal of Molecular... Mar 2024Meibomian 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...
Comparative Characterization of Human Meibomian Glands, Free Sebaceous Glands, and Hair-Associated Sebaceous Glands Based on Biomarkers, Analysis of Secretion Composition, and Gland Morphology.
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.
Topics: Humans; Meibomian Glands; Sebaceous Glands; Tears; Biomarkers; Lipids; Cadherins
PubMed: 38542083
DOI: 10.3390/ijms25063109 -
Ophthalmic & Physiological Optics : the... Jun 2024This study addressed the utilisation of machine learning techniques to estimate tear osmolarity, a clinically significant yet challenging parameter to measure...
PURPOSE
This study addressed the utilisation of machine learning techniques to estimate tear osmolarity, a clinically significant yet challenging parameter to measure accurately. Elevated tear osmolarity has been observed in contact lens wearers and is associated with contact lens-induced dry eye, a common cause of discomfort leading to discontinuation of lens wear.
METHODS
The study explored machine learning, regression and classification techniques to predict tear osmolarity using routine clinical parameters. The data set consisted of 175 participants, primarily healthy subjects eligible for soft contact lens wear. Various clinical assessments were performed, including symptom assessment with the Ocular Surface Disease Index and 5-Item Dry Eye Questionnaire (DEQ-5), tear meniscus height (TMH), tear osmolarity, non-invasive keratometric tear film break-up time (NIKBUT), ocular redness, corneal and conjunctival fluorescein staining and Meibomian glands loss.
RESULTS
The results revealed that simple linear regression was insufficient for accurate osmolarity prediction. Instead, more advanced regression models achieved a moderate level of predictive power, explaining approximately 32% of the osmolarity variability. Notably, key predictors for osmolarity included NIKBUT, TMH, ocular redness, Meibomian gland coverage and the DEQ-5 questionnaire. In classification tasks, distinguishing between low (<299 mOsmol/L), medium (300-307 mOsmol/L) and high osmolarity (>308 mOsmol/L) levels yielded an accuracy of approximately 80%. Key parameters for classification were similar to those in regression models, emphasising the importance of NIKBUT, TMH, ocular redness, Meibomian glands coverage and the DEQ-5 questionnaire.
CONCLUSIONS
This study highlights the potential benefits of integrating machine learning into contact lens research and practice. It suggests the clinical utility of assessing Meibomian glands and NIKBUT in contact lens fitting and follow-up visits. Machine learning models can optimise contact lens prescriptions and aid in early detection of conditions like dry eye, ultimately enhancing ocular health and the contact lens wearing experience.
Topics: Humans; Tears; Osmolar Concentration; Machine Learning; Male; Female; Adult; Dry Eye Syndromes; Middle Aged; Young Adult; Contact Lenses, Hydrophilic; Surveys and Questionnaires
PubMed: 38525850
DOI: 10.1111/opo.13302 -
Eye & Contact Lens May 2024The ocular surface inflammatory disorders (OSIDs) comprise a group of conditions characterized by persistent inflammation of the ocular surface and adnexal tissues.... (Review)
Review
The ocular surface inflammatory disorders (OSIDs) comprise a group of conditions characterized by persistent inflammation of the ocular surface and adnexal tissues. Systemic autoimmune diseases and hypersensitivity reactions cause them, and, if left untreated, can result in severe inflammatory dry eye, corneal damage, and vision loss. Ocular graft-versus-host disease (oGVHD) forms part of the ocular surface inflammatory disease umbrella. It is a condition occurring after allogeneic hematopoietic stem cell or bone marrow transplantation, usually in chronic graft-versus-host disease. oGVHD can virtually affect any ocular adnexal tissue, especially the meibomian glands, and cause persistent inflammation, tissue fibrosis, and subsequent chronic, severe dry eye disease. Among the OSIDs, oGVHD has the particularity that it has a "time zero," meaning we know when the disease started. As such, preclinical models have leveraged this to investigate the molecular mechanisms involved in the damage oGVHD causes to the ocular surface. In oGVHD, establishing a "time zero" allows for predicting the clinical course and establishing adequate treatment. This is also possible because the inflammatory infiltration occurs in ocular surface tissues, which are readily accessible. Using oGVHD, we might be able to understand the immune response mechanisms in other OSIDs better (i.e., Sjögren syndrome, Stevens-Johnson syndrome, among others). This review presents an up-to-date overview of the pathogenesis, clinical presentation, and treatment of oGVHD. In addition, we will discuss the value of the "time zero" concept in the study of oGVHD.
Topics: Humans; Graft vs Host Disease; Dry Eye Syndromes; Hematopoietic Stem Cell Transplantation
PubMed: 38518064
DOI: 10.1097/ICL.0000000000001082 -
Graefe's Archive For Clinical and... Mar 2024To quantitatively evaluate the morphological parameters of meibomian glands (MGs) and lipid layer thickness (LLT) in patients with keratoconus (KC).
PURPOSE
To quantitatively evaluate the morphological parameters of meibomian glands (MGs) and lipid layer thickness (LLT) in patients with keratoconus (KC).
METHODS
In this prospective, cross-sectional study, 164 eyes of 164 keratoconus patients and 64 eyes of 64 age-matched control subjects were included. An advanced automatic MG analyzer was used to quantitatively measure the morphological and functional parameters of MGs. Morphological and functional parameters of MGs, LLT, and other ocular surface parameters were compared between the control and KC groups.
RESULTS
The mean meibomian gland diameter, length, square, and gland area ratio (GA) were all significantly decreased in the KC group (all P < 0.05), while no significant difference was observed in the gland tortuosity index (TI) and gland signal index (SI) between the KC and control groups (all P > 0.05). There was no significant difference in the number of total and incomplete blinking among patients with different stages of keratoconus (all P > 0.05). The gland diameter, square, and TI were all negatively associated with KC severity (all P < 0.05), while no significant difference was observed among all stages of KC in gland length, GA, and SI (all P > 0.05). Moreover, the LLTs were positively correlated with the gland diameter, square, GA, and TI and negatively correlated with anterior corneal curvature or KC severity (all P < 0.05).
CONCLUSIONS
Atrophic morphological changes in the meibomian glands were closely correlated with the severity of keratoconus. Gland diameter may be a sensitive functional morphology metric of meibomian glands in patients with keratoconus.
PubMed: 38502350
DOI: 10.1007/s00417-024-06443-8 -
Investigative Ophthalmology & Visual... Mar 2024To validate the adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) expression and distribution in human eyelid tissues and meibomian gland epithelial...
PURPOSE
To validate the adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) expression and distribution in human eyelid tissues and meibomian gland epithelial cells.
METHODS
Meibomian gland tissues from human eyelids were isolated by collagenase A digestion and cultured in defined keratinocyte serum-free medium (DKSFM). Infrared imaging was used to analyze the general morphology of meibomian glands. Hematoxylin and eosin (H&E) staining and Oil Red O staining were used to observe the morphological structure and lipid secretion in the human meibomian gland tissues. Quantitative real-time polymerase chain reaction, western blotting, and immunostaining were used to detect the mRNA and protein expression and cytolocalization of ABCA1 in the meibomian gland tissues and cultured cells.
RESULTS
The degree of loss of human meibomian gland tissue was related to age. Meibomian gland lipid metabolism was also associated with age. Additionally, human meibomian gland tissues express ABCA1 mRNA and protein; glandular epithelial cells express more ABCA1 mRNA and protein than acinar cells, and their expression in acinar cells decreases with differentiation. Furthermore, the expression of ABCA1 was downregulated in abnormal meibomian gland tissues. ABCA1 was mainly localized on the cell membrane in primary human meibomian gland epithelial cells (pHMGECs), whereas it was localized in the cytoplasm of immortalized human meibomian gland epithelial cells (iHMGECs). The mRNA and protein levels of ABCA1 in pHMGECs were higher than those in iHMGECs.
CONCLUSIONS
Meibomian gland tissues of the human eyelid degenerate with age. ABCA1 expression in acinar cells decreases after differentiation and plays an important role in meibomian gland metabolism.
Topics: Humans; Meibomian Glands; Epithelial Cells; Adenosine Triphosphate; Blotting, Western; Membrane Transport Proteins; RNA, Messenger; ATP Binding Cassette Transporter 1
PubMed: 38502139
DOI: 10.1167/iovs.65.3.24 -
The Ocular Surface Apr 2024Aging is a well-established risk factor for meibomian gland dysfunction (MGD). We previously reported an accelerated cellular senescence phenomenon in the lacrimal...
PURPOSE
Aging is a well-established risk factor for meibomian gland dysfunction (MGD). We previously reported an accelerated cellular senescence phenomenon in the lacrimal glands of a murine model of chronic graft-versus-host disease (cGVHD). Herein, we aimed to elucidate the relationship between cellular senescence and MGD in cGVHD mice, utilizing the senolytic agent ABT-263.
METHODS
A cGVHD mouse model was established through allogeneic bone marrow transplantation (BMT) from B10.D2 to BALB/c mice. Subsequently, cGVHD mice were treated with either ABT-263 or vehicle. The eyelids of recipients were analyzed at 4-week intervals post-BMT in both groups.
RESULTS
Meibomian gland (MG) area was significantly smaller in cGVHD mice than in syngeneic control mice. ABT-263-treated mice retained a significantly larger MG area than their vehicle-treated counterparts. Pathological and immunohistochemical examinations revealed significant reductions in eyelid tissue inflammation and pathological fibrosis in the ABT-263 group compared to that in the vehicle-treated group. Additionally, expression of DNA damage markers, senescent cell markers, and senescence-associated secretory phenotype (SASP) factors was elevated in the eyelids of cGVHD mice compared with that in syngeneic mice. The expression of these cellular senescence-associated molecules was considerably suppressed in ABT-263-treated eyelids compared to that in vehicle-treated ones.
CONCLUSIONS
Cellular senescence, along with expression of SASP factors, exhibited increased activity in the eyelids, particularly in the MGs of cGVHD mice. ABT-263 mitigated the severity of MGD. These findings highlight the potential of targeting cellular senescence as an effective approach for MGD treatment in cGVHD.
Topics: Animals; Graft vs Host Disease; Mice; Disease Models, Animal; Mice, Inbred BALB C; Cellular Senescence; Meibomian Gland Dysfunction; Meibomian Glands; Chronic Disease; Bone Marrow Transplantation; Sulfonamides; Aniline Compounds; Female; Male; Immunohistochemistry; Bronchiolitis Obliterans Syndrome
PubMed: 38499288
DOI: 10.1016/j.jtos.2024.03.006