Comparing meibomian gland visibility on optical coherence tomography and Keratograph 5M images using objective and subjective grading methods.

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.

Cellular senescence promotes meibomian gland dysfunction in a chronic graft-versus-host disease mouse model.

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.

ER-1 deficiency induces inflammation and lipid deposition in meibomian gland and lacrimal gland.

PURPOSE: To investigated the role of estrogen receptor-1 (ER-1) in maintaining homeostasis in ocular surface. METHODS: ER-1-knockout (ER-1KO) mice were studied at 4 months of age. The ocular surface was examined using a slit lamp. Histological alterations in the meibomian gland (MG) and lacrimal gland (LG) were observed with H&E staining. Protein levels of P-ERK, peroxisome proliferator-activated receptor gamma (PPAR-γ), p-NFκB-P65, IL-1ß, aquaporin 5 (AQP-5), fatty acid-binding protein 5 (Fabp5) and K10 were determined by immunofluorescence and Western blotting. Gene expressions of APO-F, APO-E, K10, ELOVL4, PPAR-γ, SCD-1, and SREBP1 were quantified by qPCR. Conjunctival (CJ) goblet cell alterations were detected by PAS staining. Lipid metabolism in MG and LG was assessed using LipidTox. Apoptosis in MG and LG was analyzed through the TUNEL assay. RESULTS: Both male and female ER-1KO mice demonstrated increased corneal fluorescence staining scores. MG showed abnormal lipid metabolism and ductal dilation. LG displayed lipid deposition and reduced AQP-5 expression. CJ experienced goblet cell loss. MG, LG exhibited signs of inflammation and apoptosis. CONCLUSION: ER1 is pivotal for ocular surface homeostasis in both genders of mice. ER1 deficiency induces inflammation and lipid deposition to MG and LG, culminating in dry eye-like manifestations on the ocular surface.

The Yin and Yang of non-immune and immune responses in meibomian gland dysfunction.

Meibomian gland dysfunction (MGD) is a leading cause of dry eye disease and one of the most common ophthalmic conditions encountered in eye clinics worldwide. These holocrine glands are situated in the eyelid, where they produce specialized lipids, or meibum, needed to lubricate the eye surface and slow tear film evaporation - functions which are critical to preserving high-resolution vision. MGD results in tear instability, rapid tear evaporation, changes in local microflora, and dry eye disease, amongst other pathological entities. While studies identifying the mechanisms of MGD have generally focused on gland obstruction, we now know that age is a major risk factor for MGD that is associated with abnormal cell differentiation and renewal. It is also now appreciated that immune-inflammatory disorders, such as certain autoimmune diseases and atopy, may trigger MGD, as demonstrated through a T cell-driven neutrophil response. Here, we independently discuss the underlying roles of gland and immune related factors in MGD, as well as the integration of these two distinct mechanisms into a unified perspective that may aid future studies. From this unique standpoint, we propose a revised model in which glandular dysfunction and immunopathogenic pathways are not primary versus secondary contributors in MGD, but are fluid, interactive, and dynamic, which we likened to the Yin and Yang of MGD.

Influential Signs of Dry Eye-Related Ocular Symptoms in Participants With Unstable Tear Film.

PURPOSE: The aim of this study was to investigate the factors influencing dry eye disease (DED)-related ocular symptoms in participants with short fluorescein tear break-up time (FTBUT). METHODS: This cross-sectional study included 82 participants with short FTBUT (<10 seconds). Examinations included Ocular Surface Disease Index (OSDI), FTBUT, average noninvasive tear break-up time (NIBUTave), lid wiper epitheliopathy, lipid layer thickness, blink rate, partial blink, tear meniscus height, and meibomian gland (MG) evaluation which included ratio of residual MG area (RMGA) and MG grade in tarsal plates. One-way analysis of variance was used to detect differences between symptomatic tear film instability group (FTBUT <5 s, OSDI ≥13), asymptomatic tear film instability group (FTBUT <5 s, OSDI <13), and control group (FTBUT ≥5 s, OSDI <13). A bivariate correlation, partial correlation, and multiple linear regression analyses were used to identify major factors. Only the right eye was included. RESULTS: Among the participants with FTBUT <5 seconds, symptomatic group showed less upper RMGA ( P < 0.001) and NIBUTave ( P = 0.010). OSDI was negatively associated with upper RMGA ( r = -0.450, P < 0.001) and NIBUTave ( r = -0.414, P = 0.001), and positively associated with upper MG grade ( r = 0.277, P = 0.027). Linear regression analysis showed that the upper RMGA significantly affected OSDI (B = -41.895, P = 0.001), while not significantly correlated with age, upper MG grade, and NIBUTave. CONCLUSIONS: The upper RMGA might be the main factor affecting DED-related discomfort in participants with unstable tear film, indicating an early ocular change in DED.

Recent advances in age-related meibomian gland dysfunction (ARMGD).

Meibomian glands (MGs), located within the tarsal plate of the eyelid, secrete meibum which is the lipid-rich secretion necessary for stabilizing the tear film and preventing tear evaporation. Changes in the quality and quantity of meibum produced causes MG dysfunction (MGD), the leading cause of evaporative dry eye disease (EDED). MGD is an underdiagnosed disease and it is estimated that, in the US, approximately 70 % of the population over 60 have MGD. Three forms of MGD occur based on their meibum secretion: hyposecretory, obstructive, and hypersecretory MGD. The pathophysiology of MGD remains poorly understood, however aging is the primary risk factor. With age, MGs undergo various age-related changes, including decreased acinar basal cell proliferation, hyperkeratinization, MG atrophy, and eventual MG drop-out, leading to age-related MGD (ARMGD). Additionally, studies have suggested that MGs can suffer inflammatory cell infiltration and changes innervation patterns with aging, which could also contribute towards ARMGD. This review focuses on how the aging process affects the MG, and more importantly, how age-related changes to the MG can lead to MG atrophy and MG drop-out, ultimately leading to ARMGD. This review also highlights the most recent developments in potential therapeutic interventions for ARMGD.

Unsupervised Learning Based on Meibography Enables Subtyping of Dry Eye Disease and Reveals Ocular Surface Features.

Purpose: This study aimed to establish an image-based classification that can reveal the clinical characteristics of patients with dry eye using unsupervised learning methods. Methods: In this study, we analyzed 82,236 meibography images from 20,559 subjects. Using the SimCLR neural network, the images were categorized. Data for each patient were averaged and subjected to mini-batch k-means clustering, and validated through consensus clustering. Statistical metrics determined optimal category numbers. Using a UNet model, images were segmented to identify meibomian gland (MG) areas. Clinical features were assessed, including tear breakup time (BUT), tear meniscus height (TMH), and gland atrophy. A thorough ocular surface evaluation was conducted on 280 cooperative patients. Results: SimCLR neural network achieved clustering patients with dry eye into six image-based subtypes. Patients in different subtypes harbored significantly different noninvasive BUT, significantly correlated with TMH. Subtypes 1 and 5 had the most severe MG atrophy. Subtype 2 had the highest corneal fluorescent staining (CFS). Subtype 4 had the lowest TMH, whereas subtype 5 had the highest. Subtypes 3 and 6 had the largest MG areas, and the upper MG areas of a person's bilateral eyes were highly correlated. Image-based subtypes are related to meibum quality, CFS, and morphological characteristics of MG. Conclusions: In this study, we developed an unsupervised neural network model to cluster patients with dry eye into image-based subtypes using meibography images. We annotated these subtypes with functional and morphological clinical characteristics.

Eccrine Ductal Carcinoma of the Eyelid.

The authors present the third example of an eccrine ductal carcinoma of the eyelid. A woman in her early 70s presented with a lesion of the central right lower eyelid margin in the vicinity where an actinic keratosis was diagnosed by biopsy 2.75 years previously. Her dermatologist and ophthalmologist monitored the area of actinic keratosis, and it was stable for 2.5 years until the area became ulcerated and thickened with the loss of eyelashes. A wedge resection disclosed a squamous cell carcinoma in situ and a separate eccrine ductal carcinoma. The eccrine ductal carcinoma had in situ tumor thickening, an eccrine duct component, and an invasive tumor infiltrating the tarsal plate and replacing the normal meibomian glands. The invasive eccrine ductal carcinoma only mildly thickened the tarsal plate and was most likely an incidental finding in a biopsy prompted by the squamous cell carcinoma in situ. The 5-year relative survival rate for malignant apocrine-eccrine tumors is approximately 97%, and our patient is alive and without evidence of local or distant tumor recurrence 5.5 years following the excision of her eyelid tumor.

Meibomian gland stem/progenitor cells: The hunt for gland renewal.

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.

Study of pathological processes of meibomian gland dysfunction by in vitro culture airlifting conditions.

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.

Evaluation of post-operative dry eye in upper and lower eyelid reconstruction: A cross-sectional study.

Purpose: In cases of eyelid malignancies requiring full thickness excisional biopsy followed by reconstruction of the created defect, the Meibomian glands are lost. Post-operative varying degrees of dry eye disease (DED) are expected in such patients. The aim was to evaluate the objective and subjective statuses of DED in cases of full thickness eyelid reconstruction following excisional biopsy because of malignancies. Methods: This was a cross-sectional pilot study. Objective and subjective dry eye parameters are assessed in cases of full thickness eyelid reconstruction following excisional biopsy because of malignancies in 37 eyes at 6 months post-operative follow-up. Analysis of variance and Chi square test were used for statistical analysis. Results: When compared with fellow eye, all the parameters were found to be statistically significant (P < 0.0). Subjective assessment of dry eye by ocular surface disease index (OSDI) scoring did not corroborate with the objective data (p 0.00). Lower eyelid reconstruction showed a minimum number of dry eye cases (P > 0.05). Conclusion: Prevalence of post-operative dry eye is more with increasing percentage of full thickness upper eyelid reconstruction. Disparity was found between objective and subjective parameters of dry eye in patients requiring varying percentages of upper eyelid reconstruction because of malignancies.

Assessment of Laser Parameters to Improve Lid Tension-A Proof of Concept towards Lasercanthoplasty.

BACKGROUND: Preliminary clinical work indicates that increasing eyelid tension improves the function of the meibomian glands. The aim of this study was to optimize laser parameters for a minimally invasive laser treatment to increase eyelid tension by coagulation of the lateral tarsal plate and canthus. METHODS: Experiments were performed on a total of 24 porcine lower lids post mortem, with six lids in each group. Three groups were irradiated with an infrared B radiation laser. Laser-induced lower eyelid shortening was measured and the increase in eyelid tension was assessed with a force sensor. A histology was performed to evaluate coagulation size and laser-induced tissue damage. RESULTS: In all three groups, a significant shortening of the eyelids after irradiation was noticed (p < 0.0001). The strongest effect was seen with 1940 nm/1 W/5 s, showing -15.1 ± 3.7% and -2.5 ± 0.6 mm lid shortening. The largest significant increase in eyelid tension was seen after placing the third coagulation. CONCLUSION: Laser coagulation leads to lower eyelid shortening and an increase in lower eyelid tension. The strongest effect with the least tissue damage was shown for laser parameters of 1470 nm/2.5 W/2 s. In vivo studies of this effect have to confirm the efficacy of this concept prior to clinical application.

Blepharitis and Neoplasms of the Canine Eyelid Margin and Skin.

Canine eyelid masses (tumors) should include the differential clinical diagnoses of neoplasia and blepharitis. They have many common clinical signs including tumor, alopecia, and hyperemia. Biopsy and histologic examination remains the most effective diagnostic test to establish a confirmed diagnosis and appropriate treatment. Neoplasms are typically benign (tarsal gland adenomas, melanocytomas, and so forth) with the exception of lymphosarcoma. Blepharitis is noted in 2 age groups including dogs aged less than 1.5 years and middle aged to older dogs. Most blepharitis cases will respond to specific therapy once an accurate diagnosis is established.

Prevalence of Meibomian Gland Atrophy in Patients Undergoing Cataract Surgery.

PURPOSE: The aim of this study was to determine the prevalence of meibomian gland (MG) atrophy in a US-based population of patients presenting for cataract surgery. METHODS: In this retrospective study, case records of 391 patients aged 50 years or older, who had undergone a preoperative cataract surgery workup with meibography, were included. The amount of atrophy in the lower eyelid was graded as described by Arita et al (grade 0 = no atrophy, grade 1 = 1%-33% atrophy, grade 2 = 34%-66% atrophy, and grade 3 = >66% atrophy), and the prevalence of MG atrophy was determined. Associations between MG atrophy and demography, comorbidities, and risk factors were evaluated. RESULTS: Overall, 95.1% of patients (372/391) had MG atrophy ≥grade 1, with 50.4% (197/391) having grade 1, 25.8% (101/391) grade 2, and 18.9% (74/391) grade 3. MG atrophy had a statistically significant correlation with MG expressibility (R = 0.22; P = 0.001), but not with meibum grade (R = 0.103; P = 0.123) and telangiectasia (R = 0.014; P = 0.787). The prevalence of MG atrophy (≥grade 1) was comparable among patients who had previously been diagnosed with dry eye disease (DED) versus those who had not; however, the severity of MG atrophy was higher in patients with previous DED diagnosis (grade 2/3: 59% vs. 30.9%). Among patients with no previous history of DED, 18% (35/194) had moderate and 13% (25/194) had severe MG atrophy. CONCLUSIONS: MG atrophy is common in patients presenting for cataract surgery evaluation, indicating potential underdiagnosis. Routine use of meibography during preoperative screening in cataract surgery patients may facilitate more timely and effective diagnosis and treatment.

Upregulated MYC expression and p53 mutations may contribute to the oncogenesis of canine Meibomian gland carcinomas.

Sebaceous carcinomas of the human ocular adnexa commonly exhibit pagetoid spread, mutations in tumor-suppressor genes, and protooncogene copy number gain. Sebaceous carcinomas are rarely reported in other species, and while the Meibomian gland (MG) represents the most common ocular adnexal structure of the canine eyelid to develop neoplasia, most are clinically and histologically benign. The objective of this study was to compare molecular features of canine MG carcinomas and adenomas. Two retrospectively identified MG carcinomas were subject to immunohistochemistry and qPCR. When compared with normal glands, MYC was upregulated in benign and malignant MG neoplasms. Aberrant p53 expression was restricted to the nuclei of intraepithelial neoplastic cells in MG carcinomas. Adipophilin expression was diminished in MG neoplasms compared with the normal MG. Our findings, if confirmed in a larger cohort of cases, could suggest that MG oncogenesis in a dog may exhibit similar molecular features as their human counterparts.

Morphological variants of meibomian glands: correlation of meibography features with histopathology findings.

PURPOSE: This study describes the histopathological features of different morphological variants of human meibomian glands (MGs) seen on infrared imaging. METHODS: Tarsal plates dissected from seven cadaveric upper eyelids were imaged using infrared meibography, and then studied histopathologically using H&E, peroxisome proliferator-activated receptor gamma (PPARγ, meibocyte differentiation marker) and Ki-67 (cellular proliferation marker) antibody staining. The different morphological characteristics (varying size and shape) of MGs on meibography were correlated with histopathology findings using image analysis software. RESULTS: Of the total 127 glands, the morphological variants observed on meibography based on size were: normal (n=62), short (n=18), severely short (n=6) and dropout (n=12) glands, and on shape were: hooked (n=2), tortuous (n=5), overlapping (n=1), thick (n=15) and fluffy (n=6) glands. Short, hooked, tortuous and overlapping glands had similar acinar and ductal histology as seen in normal glands whereas thick, and fluffy glands had increased acinar diameter. All glands except the severely short type demonstrated normal signs of holocrine secretory activity and normal nuclear and cytoplasmic PPARγ expression. Severely short glands had nil while short glands had reduced Ki-67 proliferation index (3%±1%) as compared with normal and other variants (8%±5.2%). Gland dropout areas showed no evidence of any glandular tissue on histology. CONCLUSION: Hooked, tortuous and overlapping glands had completely normal glandular histology, whereas severely short glands showed atrophic changes with loss of meibocyte differentiation and cellular proliferation. Dropout areas showed total loss of glandular elements. Further studies are needed to validate and to explore the clinical implications of these findings.

Is Corneal Subbasal Nerve Loss Associated With Meibomian Gland Loss in Inactive Mild and Moderate-to-Severe Graves' Ophthalmopathy?

PURPOSE: To evaluate meibomian gland and subbasal nerve plexus parameters in Graves' Ophthalmopathy (GO) and association of meibomian gland loss with corneal subbasal nerve plexus loss. METHODS: Fifty-two eyes of 52 mild and moderate-to-severe GO patients and 32 eyes of 32 healthy controls were enrolled. The meibomian gland dropout area (MGDA) and meibography scores were evaluated using noncontact meibography. In vivo confocal microscopy of corneal subbasal nerve plexus were conducted. ACCMetrics was used to obtain corneal parameters. RESULTS: Compared with healthy subjects, GO patients had worse upper and lower eyelid MGDA ( p < 0.001, for all) and upper, lower and total meibography scores ( p < 0.001, p = 0.001, and p < 0.001, respectively). Eyelid margin scores were worse in the GO group ( p < 0.001) and showed correlation with all noncontact meibography parameters ( p < 0.001 for all). All corneal subbasal nerve parameters were significantly lower in the GO group compared with the controls ( p < 0.05 for all). Subbasal nerve parameters of GO patients did not reveal a correlation with MGDA and meibography scores but showed correlations with ocular surface disease index score and Schirmer I test (r = -0.304; p = 0.042 and r = 0.336; p = 0.021, respectively). CONCLUSION: Meibomian gland and corneal nerve loss could be observed even in the inactive phase and mild GO. The lack of a correlation between meibomian gland loss and subbasal nerve loss suggests that meibomian gland loss is not a significant additional component in the pathogenesis of subbasal nerve damage in GO. Furthermore, our study revealed new evidence regarding the use of eyelid margin score to represent meibomian gland loss in GO.

Meibomian Gland Dysfunction: A Route of Ocular Graft-Versus-Host Disease Progression That Drives a Vicious Cycle of Ocular Surface Inflammatory Damage.

PURPOSE: To investigate the role of aggressive meibomian gland dysfunction (MGD) in the immune pathogenesis of ocular graft-vs-host disease (GVHD). METHODS: In mice, an allogeneic GVHD model was established by transferring bone marrow (BM) and purified splenic T cells from C57BL/6J mice into irradiated C3-SW.H2b mice (BM+T). Control groups received BM only. Mice were scored clinically across the post-transplantation period. MGD severity was categorized using the degree of atrophy on harvested lids. Immune disease was analyzed using flow cytometry of tissues along with fluorescent tracking of BM cells onto the ocular surface. In humans, parameters from 57 patients with ocular GVHD presenting to the Duke Eye Center were retrospectively reviewed. MGD was categorized using the degree of atrophy on meibographs. Immune analysis was done using high-parameter flow cytometry on tear samples. RESULTS: Compared with BM only, BM+T mice had higher systemic disease scores that correlated with tear fluid loss and eyelid edema. BM+T had higher immune cell infiltration in the ocular tissues and higher CD4+-cell cytokine expression in draining lymph nodes. BM+T mice with worse MGD scores had significantly worse corneal staining. In patients with ocular GVHD, 96% had other organs affected. Patients with ocular GVHD had abnormal parameters on dry eye testing, high matrix metalloproteinase-9 positivity (92%), and abundance of immune cells in tear samples. Ocular surface disease signs were worse in patients with higher MGD severity scores. CONCLUSIONS: Ocular GVHD is driven by a systemic, T-cell-dependent process that causes meibomian gland damage and induces a robust form of ocular surface disease that correlates with MGD severity. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Clinical association between trace elements of tear and dry eye metrics.

Trace elements exposure is proposed to play a role in the pathogenesis of the systemic disease. Emerging studies have suggested that trace metal exposure may contribute to dry eye disease. Our study primarily aimed to investigate the association between trace metal exposure in tear samples and the presence of dry eye metrics in the shipyard industry. Overall, 84 eligible participants from the shipyard industry were included in this cross-sectional study. The parameters for identifying dry eye symptoms included O.S.D.I., SPEED, N.I.B.U.T., and ocular surface conditions, such as tear meniscus height, eye blinking, and meibomian gland area were performed by S.B.M. sistemi ocular surface analyzer. The concentration of tear trace elements was detected by inductively coupled plasma mass spectroscopy (ICP-MS). The association between tear trace elements and dry eye parameters was investigated using regression models. Participants in the exposure group had significantly higher levels of tear Pb than the control group. In the exposure group, tear Pb was significantly associated with increased SPEED and O.S.D.I. score with beta coefficients of 0.144 (95% CI 0.092, 0.197), 0.121 (95% CI 0.049, 0.194), respectively, and decreased lower and upper meibomian gland area with beta coefficients of - 0.158 (- 0.283, - 0.033) and - 0.228 (- 0.396, - 0.061), respectively. Tear trace elements exposure is considered to impact the appearance of dry eye metrics. Improving the occupational environment and monitoring the ocular surface health may benefit workers under exposure to trace elements.