Meibography health score: a simple grading system for isotretinoin-induced meibography alterations on patients with acne vulgaris.

PURPOSE: To develop a simple, subjective, and reliable grading scale for isotretinoin-induced meibography changes. METHODS: After analyzing meibography images obtained from systemic isotretinoin users, a grading scale was proposed and named "meibography health score." The score ranged from 1 to 3, with decreasing gland reflectivity and identifiable margins. A total of 11 medical professionals were asked to grade 10 meibography images obtained from isotretinoin users using the proposed scale and were divided into three groups: (A) ophthalmologists with experience with meibography, (B) ophthalmologists with no experience with meibography, and (C) radiologists. The kappa statistic was determined to test interrater reliability. RESULTS: The overall kappa was approximately 0.64. The kappa scores for Groups A, B, and C were 0.78, 0.59, and 0.90, respectively. Grade 2 had the lowest kappa scores (0.62, 0.35, and 0.82 for A, B, and C, respectively) and grade 3 the highest (0.78, 0.90, and 1.0 for A, B and C, respectively). Furthermore, Group C had the highest kappa scores and Group B the lowest. CONCLUSION: The meibography health score exhibited good interrater reliability, particularly in severe cases.

Classification of dry eye disease subtypes.

PURPOSE: The current subclassifications of dry eye disease (DED) are aqueous deficient (ADDE) and evaporative (EDE) forms, but there lacks consistency in the clinical characteristics used to define each of these. This study used clinical data to inform cut-off values for the subclassification of ADDE and EDE, to allow more consistent study of the epidemiology of both DED subtypes. METHODS: The study enrolled 261 residents from the UK, extracted from a cohort with demographics representing the population (mean 42.4 ± 18.7 years, 56 % females). The TFOS DEWS II diagnostic criteria were used to identify those with DED. Meibomian gland loss/drop-out (from meibography), lipid layer thickness (LLT - from interferometry graded on the Guillon-Keeler scale), and tear meniscus height (TMH - Keratograph 5M) along with tear evaporation (Delfin Vapometer) were used to characterise the subclassification. The Dry Eye Risk Factor Survey was used to assess risk factors associated with each DED subtype. RESULTS: Compared to individuals who were not diagnosed with DED, EDE was characterized by signs of meibomian gland loss of > 28 %, LLT grade < 3 and tear evaporation > 46 g/m2/h. In contrast, ADDE was best characterized by a reduced TMH < 0.2 mm. Based on these criteria, the prevalence of ADDE was 6.2 %, EDE was 64.2 %, and 11.1 % exhibited features of both ADDE and EDE, with 18.5 % unclassified despite having a DED diagnosis. Contact lens wear and computer use were risk factors for ADDE (p < 0.05), whereas age was a positive risk factor for EDE (p < 0.01). Meibomian gland loss (occurring in 27.9 %) was the most commonly observed sign in EDE. CONCLUSIONS: Data driven-classification of DED confirms that the evaporative form is most prevalent and identified that in a generalisable UK population, ADDE alone occurs only in approximately 1 in 16 cases of DED.

Advances in artificial intelligence for meibomian gland evaluation: A comprehensive review.

Meibomian gland dysfunction (MGD) is increasingly recognized as a critical contributor to evaporative dry eye, significantly impacting visual quality. With a global prevalence estimated at 35.8 %, it presents substantial challenges for clinicians. Conventional manual evaluation techniques for MGD face limitations characterized by inefficiencies, high subjectivity, limited big data processing capabilities, and a dearth of quantitative analytical tools. With rapidly advancing artificial intelligence (AI) techniques revolutionizing ophthalmology, studies are now leveraging sophisticated AI methodologies--including computer vision, unsupervised learning, and supervised learning--to facilitate comprehensive analyses of meibomian gland (MG) evaluations. These evaluations employ various techniques, including slit lamp examination, infrared imaging, confocal microscopy, and optical coherence tomography. This paradigm shift promises enhanced accuracy and consistency in disease evaluation and severity classification. While AI has achieved preliminary strides in meibomian gland evaluation, ongoing advancements in system development and clinical validation are imperative. We review the evolution of MG evaluation, juxtapose AI-driven methods with traditional approaches, elucidate the specific roles of diverse AI technologies, and explore their practical applications using various evaluation techniques. Moreover, we delve into critical considerations for the clinical deployment of AI technologies and envisages future prospects, providing novel insights into MG evaluation and fostering technological and clinical progress in this arena.

Tear film assessment before and after phacoemulsification in patients with age-related cataracts.

BACKGROUND: The study aims to assess the tear film before and after phacoemulsification in patients with age-related cataracts. METHODS: A prospective observational study of 41 age-related cataract patients undergoing phacoemulsification procedure. Tear Film Break-Up Time (TBUT), Tear Film Meniscus Height (TMH), Meibomian glands (MG), and Lipid Layer Thickness (LLT) were assessed by a non-invasive Dry Eye Diagnostic System. All measurements were taken preoperatively, one week, one month, and three months postoperatively. The Marginal homogeneity and The Cochran Q tests were used in the statistical analysis. RESULTS: The value of Non-Invasive Break-Up Time (NITBUT) was statistically significantly lower at one week (7.15 ± 3.31), one month (7.61 ± 3.41), and three months (7.66 ± 3.36) postoperatively than preoperatively (10.71 ± 2.71), p < 0.001. The Non- Invasive Tear Meniscus Height (NITMH) was significantly lower at one week (0.18 ± 0.0), one month (0.20 ± 0.09), and three months (0.20 ± 0.09) postoperatively than preoperatively (0.30 ± 0.113) p < 0.001. By the first month, both (NITBUT) and (NITMH) improved significantly compared to the first post-operative week. There was no statistically significant difference between one month and three months. The (NITMH) improved to a healthy level of ≥ 0.2 mm by the first month through the third month. Both (NITBUT) and (NITMH) did not reach the baseline by the third month. The meibomian glands and the lipid layer thickness had the same preoperative grade distribution without changes. CONCLUSION: Phacoemulsification surgery can cause post-operative deterioration in the tear film, which starts within a week of the procedure, followed by gradual recovery over the next weeks and months. The phacoemulsification procedure mainly affects the tear break-up time and tear meniscus height. Both the lipid layer and meibomian glands are not affected.

The impact of systemic isotretinoin treatment on the tear film, meibomian glands, and corneal endothelium.

PURPOSE: The study aims to investigate changes in tear function, meibomian glands and corneal endothelium in patients receiving systemic isotretinoin therapy. MATERIALS AND METHODS: This prospective study included 38 eyes from 38 patients (23 females and 15 males) treated with systemic isotretinoin (0.5-1 mg/kg/day) following the diagnosis of acne vulgaris. All patients underwent a comprehensive ophthalmologic examination at baseline, 1st month, and third month of treatment. Subjective complaints were assessed using the Ocular Surface Disease Index (OSDI). Tear functions were evaluated through non-invasive tear break up time (NIBUT) and Schirmer I test. Meibomian gland (MG) changes were examined using meibography. Corneal parameters, including endothelial cell density (ECD), coefficient of variation (CV), the number of cells with a hexagonal shape (6A), average cell area (AVG), and central corneal thickness (CCT) were assessed using non-contact specular microscopy. RESULTS: The mean age of the patients was 19.29 ± 2.83 years. Ocular surface-related discomfort, measured with OSDI scores, significantly worsened at the third month measurements compared to the pre-treatment values (p < 0.001). In the 1st month of treatment, there was a significant decrease in NIBUT (p < 0.05). No statistically significant difference was found in the Schirmer test results at each visit. According to the 1st and third-month analysis, there was a significant increase in MG loss compared to the pre-treatment period (p < 0.001). ECD, CV, 6 A, AVG measurements at the first and third months showed a significant change compared to the pre-treatment values (p < 0.001). No significant difference was observed in the CCT measurements during the treatment. CONCLUSION: Systemic isotretinoin disrupted tear stability, caused MG loss, deterioration in corneal endothelium, and led to symptomatic complaints in patients.

The effect of airborne particulate matter 2.5 (PM2.5) on meibomian gland.

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-1ß, 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-1ß 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.

Lid Margin Microbiome in Stevens-Johnson Syndrome Patients With Lid Margin Keratinization and Severe Dry Eye Disease.

Purpose: The current study evaluated the lid margin microbiome of keratinized lid margins of patients with chronic Stevens-Johnson syndrome (SJS) and compared it with healthy controls and historically reported lid margin microbiome of patients with meibomian gland dysfunction (MGD). Methods: Eyelid margin swabs of 20 asymptomatic adults (mean age = 29 ± 12 years) and 10 patients with chronic SJS (mean age = 31.2 ± 14 years) with lid margin keratinization were sequenced using next generation of 16S rDNA V3 to V4 variable region. Within SJS, the keratinized lid margin microbiome was compared with adjacent eyelid skin. Results: All patients had obstructive MGD, and mean Schirmer I value was 2.8 ± 1.9 mm. The phyla were similar in two groups, whereas at the genera level, an increase in the relative abundance of Corynebacterium, Haemophilus, Azotobacter, and Afipia and a decrease of Acinetobacter was noted in SJS compared to healthy lid margins. SJS-associated microbiota displayed lesser diversity and more heterogeneity than healthy controls. The Principal Components Analysis (PCA) plot revealed wide separation in the SJS and the control groups. Correlational network analysis revealed Corynebacterium and Sphingomonas forming a major hub of negative interactions with other bacterial genera in the SJS group. Significant differences exist in the prevalent genera between keratinized lid margins and historically reported meibum microbiome of patients with MGD. In addition, the eyelid skin of patients with SJS had predominant Staphylococcus, whereas Corynebacterium and Pseudomonas were more in the keratinized lid margins compared to the eyelid skin microbiome. Conclusions: Lid margin microbiome is significantly altered in the keratinized lid margins of patients with SJS compared to the eyelid skin of patients with SJS, normal lid margins, and patients with MGD.

Prevalence of Dry Eye Disease in Laser-Assisted In Situ Keratomileusis Candidates.

OBJECTIVE: To evaluate the prevalence of dry eye disease (DED) in laser-assisted in situ keratomileusis (LASIK) candidates. METHODS: A chart review of consecutive LASIK candidates who underwent full ocular surface work-up was performed, including ocular surface disease index (OSDI), noninvasive tests (noninvasive tear breakup time [ni-TBUT], tear meniscus height, lipid layer thickness, and meibography), and invasive tests (Schirmer test I, fluorescein TBUT, corneal staining, and meibomian gland [MG] expressibility). The prevalence of DED was calculated according to the Dry Eye Workshop II (DEWS II), and Japanese and Asia Dry Eye Society (JDES/ADES) criteria. RESULTS: In total, 135 patients (270 eyes) were evaluated. The mean age was 32.6±8.3 years, and 62.9% were women (n=85); 19 patients (15.4%) wore contact lenses, and 31 patients (23.8%) used artificial tears. The mean OSDI was 18.2±16.9, which was abnormal in 54.1% (n=62). Inferior lid MG dropout was the sign with the highest percentage of abnormal results (61.5%; n=83). There were no differences between men and women in any test except for ni-TBUT (6.3±0.3 and 7.2±0.2, respectively; P=0.002). Dry eye disease prevalence was 25.9% and 53.3%, according to JDES/ADES and DEWS II criteria, respectively. The only significant risk factor for DED was artificial tear use for both DEWS II (odds ratio [OR]=3.5, confidence interval [CI] [1.35-9.39]) and JDES/ADES (OR=2.58, CI [1.03-6.48]). CONCLUSIONS: This study found a high prevalence of DED and abnormalities in LASIK candidates and highlights the importance of ocular surface evaluation before photorefractive surgery.

Analysis of Factors Associated with Anterior Location of Marx's Line.

PURPOSE: The study aimed to investigate the factors associated with anterior location of Marx's line in ocular surface and living habits, especially in tear film. MATERIALS AND METHODS: This cross-sectional study enlisted 483 participants with meibomian gland dysfunction, who were divided into two groups: 160 participants with mild anterior location of Marx's line and 323 participants with moderate-to-severe anterior location. Participants completed a survey of demographic characteristics (sex, age, length of visual terminal use, sleep duration, skin property), and the Ocular Surface Disease Index and Standard Patient Evaluation of Eye Dryness questionnaires. They also underwent slit-lamp examinations of the lids, and measurements of non-invasive tear break up time, tear meniscus height, fluorescein tear break up time, lipid layer thickness, partial blink rate, lid wiper epitheliopathy, and meibomian gland dropout. RESULTS: The tear meniscus height (mild:0.21(0.18-0.25), moderate-to-severe:0.19(0.16-0.23), p = 0.004), fluorescein tear break up time(mild:3(2-4),moderate to severe:2(1-3), p = 0.000), max LLT(mild:87(62-100), moderate-to-severe:99(69-100), p = 0.04), average LLT(mild:64.5(47.5-96.75), moderate-to-severe:74(53-100), p = 0.012), min LLT(mild:52(38-75), moderate-to-severe:59(41-85), p = 0.029) differed significantly between mild and moderate-to-severe anterior location of Marx's line, and associated to the anterior location of Marx's line(r=-0.134, p = 0.03; r=-0.194, p = 0.000; r = 0.093, p = 0.041; r = 0.119, p = 0.009; r = 0.105, p = 0.022) However, no statistical significance was observed in the OSDI, SPEED, partial blink rate, non-invasive tear breakup time, lipid layer thickness, meibomian gland dropout and lid wiper epitheliopathy(p > 0.05). Meanwhile, in the demographic characteristics, statistically significant correlations were associated with skin property(r = 0.154, p = 0.001) and sleep duration(r=-0.124, p = 0.006), but not with age, sex, and the length of visual terminal use (p > 0.05). CONCLUSIONS: Lower TMH and shorter TBUT positively correlated with anterior location of the Marx's line, and were risk factors. Meanwhile, participants with oily skin and shorter sleep duration were more likely to exhibit anterior location of Marx's line.

Current state and future perspectives in the diagnosis of eyelid margin disease: clinical review.

The eyelid margin is vital to ocular surface integrity. Much peer-reviewed literature has been established in eyelid margin inflammation, better known as blepharitis. The purpose was to review and understand the impact of eyelid margin disease. Anterior blepharitis causes inflammation at the eyelash base, ciliary follicles, and the palpebral skin. Posterior blepharitis occurs when there is inflammation with the posterior eyelid margin disease. In common usage, the term "blepharitis" used alone almost always refers to anterior blepharitis. Classification of eyelid margin disease should be based on etiopathogenesis, location, primary vs secondary, and chronicity. Blepharitis has several etiopathologies (infectious, inflammatory, and squamous). Meibomian gland dysfunction (MGD) can refer to the functional and/or structural problems with the meibomian gland. Meibomitis (or meibomianitis) occurs when there is inflammation associated with the MGD. The presence of blepharitis and/or MGD (with or without inflammation) can affect the ocular surface and thereby affect anterior segment and cataract surgeries. This review article evaluates the differential diagnoses of eyelid margin disease, including various forms of blepharitis, MGD, and meibomitis.

HDAC1/2 and HDAC3 play distinct roles in controlling adult Meibomian gland homeostasis.

PURPOSE: To investigate the roles of HDAC1/2 and HDAC3 in adult Meibomian gland (MG) homeostasis. METHODS: HDAC1/2 or HDAC3 were inducibly deleted in MG epithelial cells of adult mice. The morphology of MG was examined. Proliferation, apoptosis, and expression of MG acinus and duct marker genes, meibocyte differentiation genes, and HDAC target genes, were analyzed via immunofluorescence, TUNEL assay, and RNA in situ hybridization. RESULTS: Co-deletion of HDAC1/2 in MG epithelium caused gradual loss of acini and formation of cyst-like structures in the central duct. These phenotypes required homozygous deletion of both HDAC1 and HDAC2, indicating that they function redundantly in the adult MG. Short-term deletion of HDAC1/2 in MG epithelium had little effect on meibocyte maturation but caused decreased proliferation of acinar basal cells, excessive DNA damage, ectopic apoptosis, and increased p53 acetylation and p16 expression in the MG. By contrast, HDAC3 deletion in MG epithelium caused dilation of central duct, atrophy of acini, defective meibocyte maturation, increased acinar basal cell proliferation, and ectopic apoptosis and DNA damage. Levels of p53 acetylation and p21 expression were elevated in HDAC3-deficient MGs, while the expression of the differentiation regulator PPARγ and the differentiation markers PLIN2 and FASN was downregulated. CONCLUSIONS: HDAC1 and HDAC2 function redundantly in adult Meibomian gland epithelial progenitor cells and are essential for their proliferation and survival, but not for acinar differentiation, while HDAC3 is required to limit acinar progenitor cell proliferation and permit differentiation. HDAC1/2 and HDAC3 have partially overlapping roles in maintaining survival of MG cells.

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.

Quantitative evaluation of morphological and functional changes in meibomian glands and lipid layer thickness in patients with and without keratoconus.

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.

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.

Ocular surface changes in patients who have undergone head and neck radiation therapy.

PURPOSE: Dry eye syndrome (DES) is a familiar sequelae of radiation therapy (RT) for head and neck cancers (HNC). Ocular surface changes such as DES occur due to injury to the conjunctival epithelium, goblet cells, corneal surface, lacrimal glands, and meibomian glands. This study aimed at the evaluation and early detection of changes in ocular surface parameters in patients receiving RT for extraocular HNC. METHODS: Forty-two eyes of 21 patients undergoing HNC RT were evaluated. Radiation technique and dose of radiation to the lens and eye were recorded. Subjects were evaluated for meibomian gland changes by meiboscore grading, ocular surface disease index (OSDI) questionnaire, Schirmer's test, tear film break-up time (TBUT), and slit-lamp examination before RT, immediately post RT, and 6 weeks post RT. A comparison of the ipsilateral eye on the irradiated side to the contralateral eye was done. RESULTS: A significant reduction in TBUT was seen immediately post RT and 6 weeks post RT ( P < 0.001 and 0.008, respectively), with an increase in meiboscore at both visits ( P < 0.001). An OSDI score of >13 was seen in 23.80% of patients post RT, with a significant difference from baseline ( P < 0.001). On comparing ipsilateral and contralateral eye groups, a significant difference from baseline was seen in TBUT ( P < 0.001 and 0.033, respectively) and meiboscore ( P < 0.001 for both eyes). A significant change of >1 second in TBUT and >1.7 in meiboscore was seen with a mean dose of around 8 Gy to the lens. CONCLUSION: All patients undergoing HNC RT should be followed up for ocular surface and meibomian gland changes. The contralateral eye should also be evaluated. Patients receiving lower doses to the ocular structures should also be kept under follow-up.

Noninvasive screening of ocular surface disease in otherwise healthy patients scheduled for cataract surgery.

PURPOSE: To evaluate prevalence and characteristics of pathological ocular surface findings in healthy patients undergoing cataract surgery using a noninvasive ocular surface workup and a validated questionnaire. DESIGN: Prospective single-centre study (sub-analysis clinical trial no. NCT05754437). METHODS: Healthy patients undergoing senile cataract surgery were screened preoperatively by Oculus Keratograph (K5 M; Oculus GmbH, Wetzlar, Germany) for the evaluation of tear meniscus height (TMH), non-invasive keratograph break-up time (NIKBUT), and meibomian gland dropout. Ocular discomfort symptoms were scored by ocular surface disease index (OSDI) questionnaire. RESULTS: 120 eyes of 120 patients (62 females, 58 males; mean age 73.85 years, range 47-91 years) were included. All patients had at least 1 abnormal finding, while 19 (15.8%; 95% CI [0.09-0.22]) had alterations of all parameters. In detail, 39 patients (32.5%; 95% CI [0.24-0.41]) had pathological TMH (mean 0,15 mm [0.03 SD]), 102 (85%; 95% CI [0.79-0.91]) had pathological NIKBUT (mean 3.64 s [2.63 SD]), 117 (97.5%; 95% CI [0.95-1]) had some degree of gland dropout (mean 1.62 [0.70 SD]), 78 patients (65%; 95% CI [0.56-0.74]) had pathological OSDI scores (mean 28.63 [15.08 SD]). Using TFOS DEWS II criteria, 66 patients (55%; 95% CI [0.42-0.60]) resulted affected by dry eye. CONCLUSIONS: This quick noninvasive screening documented the high prevalence of pathological ocular surface parameters in patients without risk factors or previous diagnosis of dry eye who are scheduled for cataract surgery.

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.