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 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.

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.

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.

Serial intravitreal injections in age-related macular degeneration patients from the dry eye disease perspective: a cross-sectional study.

BACKGROUND: To evaluate the effects of serial intravitreal injections (IVI) on the ocular surface and meibomian glands in patients with neovascular age-related macular degeneration (nAMD). METHODS: Patients receiving anti-vascular endothelial growth factor (anti-VEGF) agent injections for unilateral nAMD were included. Untreated fellow eyes served as the control group. All participants followed a pre-IVI asepsis protocol with povidone-iodine (PI). Ocular surface diseases index (OSDI) questionnaire scores, first and average non-invasive tear break-up time (fNITBUT and avgNITBUT), Schirmer-1 test results, corneal staining score (according to Oxford scale), meibomian gland (MG) loss rates of lower and upper eyelids were recorded four weeks after the last IVI. RESULTS: Forty-two nAMD patients with a mean age of 63.3 ± 19.4 were included in the study. The mean OSDI score was 20.3 and the median of IVI number was 9 (6-22). There were no statistically significant difference between treated and untreated fellow eyes regarding fNITBUT (5.6 vs. 4.5, p = 0.872), avgNITBUT (6.2 vs. 7.2, p = 0.968), Shirmer-1 results (7 vs. 7, p = 0.854), corneal staining (0.3 vs. 0.2, p = 0.341), lower and upper MG loss rate (29.3 vs. 28.4, p = 0.162, and 27.1 vs. 26.9, p = 0.476, respectively). Only significant correlation was observed between age with lower and upper MG loss rate (r:0.396, p = 0.042, and r:0.365, p = 0.047). CONCLUSION: The results of the present study demonstrated that serial IVI of anti-VEGF agents with PI asepsis is well tolerated by nAMD patients in terms of ocular surface, MG loss and DED measurements.

Development of a dry eye index as a new biomarker of dry eye disease.

PURPOSE: To evaluate signs and symptoms in patients diagnosed with dry eye disease (DED), divided into dry eye (DE) groups, in order to find a new biomarker that allows an accurate diagnosis, management and classification of DED. METHODS: This cross-sectional, observational study included 71 DED subjects. Subjective symptoms, visual quality and DE signs were assessed using the Ocular Surface Disease Index (OSDI), the Quality of Vision (QoV) questionnaire, best corrected distance visual acuity (VA), functional visual acuity (FVA), contrast sensitivity (CS), high- and low-order corneal aberrations (HOA and LOA, respectively), tear break-up time (TBUT), Meibomian Gland Dysfunction (MGD), Schirmer test, corneal staining, lid wiper epitheliopathy (LWE) and meibography. Participants were classified into three groups based on dryness severity using a cluster analysis, i.e., mild (N = 17, 55.8 ± 15.4 years), moderate (N = 41, 63.5 ± 10.6 years) and severe (N = 13, 65.0 ± 12.0). A new Dry Eye Severity Index (DESI) based on ocular surface signs has been developed and its association with symptoms, visual quality and signs was assessed. Comparisons between groups were made using Kruskal-Wallis and Chi-squared tests. Spearman correlation analysis was also performed. RESULTS: The DESI was based on three tests for DE signs: TBUT, Schirmer test and MGD. The DESI showed significant differences between different pairs of groups: Mild Dryness versus Moderate Dryness (p < 0.001), Mild Dryness versus Severe Dryness (p < 0.001) and Moderate Dryness versus Severe Dryness (p < 0.001). The DESI was significantly correlated with age (rho = -0.30; p = 0.01), OSDI score (rho = -0.32; p = 0.007), QoV score (rho = -0.35; p = 0.003), VA (rho = -0.34; p = 0.003), FVA (rho = -0.38; p = 0.001) and CS (rho = 0.42; p < 0.001) Also, significant differences between the severity groups were found for OSDI and QoV scores, VA, FVA, CS and MGD (p < 0.05). CONCLUSIONS: The DESI has good performance as a biomarker for the diagnosis, classification and management of DED.

Dry eye syndrome symptoms in patients with psoriasis.

BACKGROUND: Psoriasis is one of the most common dermatoses associated with a variety of comorbidities. There have been some reports on its possible association with ocular disorders however dry eye syndrome (DES) in such patients has been poorly investigated. OBJECTIVES: To investigate the frequency of DES symptoms in psoriatic patients, also regarding psoriasis severity in PASI, manifestation and therapy. METHODS: 40 patients with psoriasis and 40 volunteers without dermatoses were enrolled in the study. They completed Ocular Surface Disease Index (OSDI) questionnaire and were objectively examined by IDRA® device to perform automatic interferometry, automatic meibography of lower eyelid glands, non-invasive break-up time (NIBUT), blink quality and tear meniscus height. RESULTS: Patients with psoriasis had statistically significantly thicker lipid layer (p = 0.0042 left eye, p = 0.0313 right eye) and greater loss of Meibomian glands compared to controls (p = 0.0128 left eye, p = 0.048 right eye). The patients had lower, although insignificantly, eye blink quality and tear meniscus height than the control group, as well as shorter NIBUT and higher score in OSDI. After the division of patients into two groups-with or without nails involvement/psoriatic arthritis/systemic treatment- we did not observe any significant differences between the groups. PASI did not correlate with any DES parameter. CONCLUSIONS: This is the first study of DES symptoms with an objective IDRA® analyzer. We managed to observe that patients with psoriasis have thicker lipid layer and higher Meibomian glands' loss in lower eyelids. Based on all assessed objective and subjective parameters psoriatics do not seem to have an increased risk of DES. The presence of psoriatic arthritis or nail involvement does not seem to be a predisposing factor for DES development. PASI probably cannot be a prognostic factor for any of the DES-associated parameters. Nevertheless, DES in psoriasis requires further research on bigger samples to establish reliable recommendations.

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.

Correlation between meibomian gland dysfunction and sebaceous adenitis in dogs.

BACKGROUND: Sebaceous adenitis (SA) is an immune-mediated disease targeting the sebaceous glands. Meibomian gland dysfunction is a disease affecting meibomian glands with inflammatory features. Sebaceous and meibomian glands share anatomical, physiological and embryological similarities. The involvement of meibomian glands in dogs with SA is currently unknown. OBJECTIVES: To evaluate meibomian glands in dogs affected by SA and compare them with healthy dogs. ANIMALS: Eighteen dogs were enrolled. Nine dogs with SA were retrospectively identified from clinical records and represented the case group. Nine healthy, breed- and age-matched dogs were prospectively enrolled in the control group. MATERIALS AND METHODS: Both groups underwent dermatological examination, Schirmer tear test-1 (STT-1), tear meniscus height (TMH), slit-lamp biomicroscopy, interferometry (INT) and noncontact infrared meibography (NIM). RESULTS: One third of SA dogs presented subepithelial crystalline opacities. No significant difference between groups was observed in TMH (p = 0.944) and STT-1 values (p = 0.066). INT (p = 0.016) and NIM grades (p = 0.010) were significantly higher and lower in the SA group compared to the control group, respectively. INT values decreased with age (η = 0.930), while NIM scores (η = 0.935) increased. CONCLUSIONS: Clinical Relevance: Subepithelial crystalline opacities in SA dogs might reflect a reduced tear film quality. In the absence of standardised methods, INT and NIM proved to be noninvasive and useful methods to examine meibomian glands. Dogs with SA showed a thinner lacrimal lipid layer and more severe meibomian gland abnormalities than control dogs, which seemed to progress with age.

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.

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.

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.

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.

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.

Safety and efficacy of a low-level radiofrequency thermal treatment in an animal model of obstructive meibomian gland dysfunction.

This study aimed to evaluate the safety and efficacy of a low-level radiofrequency thermal treatment in an obstructive MGD rabbit model. Meibomian gland orifices of the central two-thirds of the upper and lower eyelid margins were coagulated twice at 2-week intervals using a 5-MHz high-frequency electrosurgical unit. Sixteen eyes of eight rabbits were treated with one session of radiofrequency thermal treatment (radiofrequency group) and eight eyes of four rabbits were followed up without treatment (control group). Lid margin abnormality and corneal staining scores, histologic examination of the eyelids and meibombian gland, and meibography imaging were evaluated just before and 4 weeks after meibomian gland orifice closure and 4 weeks after radiofrequency thermal treatment. Lid margin abnormality score improved significantly for the upper and lower eyelids after radiofrequency thermal treatment (P < 0.001 for both eyelids). Corneal staining score remained unchanged in the radiofrequency group; however, the control group saw an increase at final follow-up. There was a significant improvement to almost baseline levels in the mean area of secretory acini in the radiofrequency group (P = 0.004). Additionally, meibography indicated an improvement in meibomian gland loss rate in the radiofrequency group. Low-level radiofrequency thermal treatment heating the inner and outer eyelid surfaces is safe and effective to treat obstructive MGD in a rabbit animal model of MGD.

The Eyelid Meibomian Gland Deficiency in Fucosyltransferase 1 Knockout Mice.

To investigate the effect of fucosyltransferase (FUT) 1-mediated fucosylation on meibomian glands (MG), we first confirmed that FUT1 and its fucosylated products were expressed in the eyelid, conjunctiva and skin in wild-type (WT) mice, whereas their mRNA and protein levels were downregulated in Fut1 knock-out (KO) mice. We then evaluated age-dependent changes in the total and acinar areas of MG, meibocyte differentiation, lipid synthesis, and eyelid inflammation and oxidative stress in Fut1 KO and WT mice. Results show that both the total and acinar areas of MG were smaller in Fut1 KO mice than in WT mice in all evaluated age groups. Meibocyte differentiation, lipid-producing capacities and the enzyme levels responsible for lipid synthesis were reduced in Fut1 KO mice, compared to WT controls. The levels of pro-inflammatory cytokines and oxidative-stress-related markers were elevated in the eyelids and MG of FUT1 KO mice. These findings demonstrate the physiologic function of FUT1-mediated fucosylation in MG development and function, and indicate its potential role in ocular surface homeostasis.

Sex Hormones and Their Effects on Ocular Disorders and Pathophysiology: Current Aspects and Our Experience.

Sex hormones are molecules produced by the gonads and to a small extent by the adrenal gland, which not only determine the primary and secondary sexual characteristics of an individual, differentiating man from woman, but also participate in the functioning of the various systems of the body. The evidence that many eye diseases differ in terms of prevalence between men and women has allowed us, in recent years, to carry out several studies that have investigated the association between sex hormones and the pathophysiology of eye tissues. Specific receptors for sex hormones have been found on the lacrimal and meibomian glands, conjunctiva, cornea, lens, retina, and choroid. This work summarizes the current knowledge on the role that sex hormones play in the pathogenesis of the most common ocular disorders and indicates our clinical experience in these situations. The aim is to stimulate an interdisciplinary approach between endocrinology, neurology, molecular biology, and ophthalmology to improve the management of these diseases and to lay the foundations for new therapeutic strategies.

Meibomian gland atrophy with duration of Sjogren's syndrome in adult females.

BACKGROUND: To investigate the correlation between the duration of Sjögren syndrome (SS) and ocular surface parameters in patients with SS-related dry eye. METHODS: We analyzed 108 eyes of 108 female patients with primary SS-related dry eye. All patients underwent rheumatoid serologic tests and ocular surface assessments. The ocular surface assessment included the Standard Patient Evaluation of Eye Dryness (SPEED) score, meibomian gland (MG) atrophy, lipid layer thickness (LLT), partial and total blinking, partial blinking rate, Schirmer's I test, non-invasive tear break-up time, and ocular surface staining score. Correlations between the duration of SS and ocular surface assessments were calculated. RESULTS: The average age and SS duration of the participants were 56.7 ± 10.2 (range 21-78) years and 54.15 ± 41.10 (range 1-134) months, respectively. There was a strong positive correlation between SS duration and MG atrophy (r = 0.766, p < 0.001). The correlation between SS duration and MG atrophy rate remained significant after controlling for age (r = 0.559, p < 0.001). Average, maximum, and minimum LLTs showed weak negative correlations with SS duration (r = - 0.310, - 0.211, and-0.304, respectively, p = 0.014, 0.028, and 0.022, respectively) and MG atrophy (r = - 0.191, - 0.326, and - 0.299, respectively, p = 0.049, 0.002, and 0.009, respectively). SPEED score showed a weak positive correlation to SS duration (r = 0.303, p = 0.042) and a moderate positive correlation to MG atrophy (r = 0.450, p = 0.029). CONCLUSIONS: Longer duration of primary SS was related to more severe MG atrophy. Therefore, it is necessary to perform meibography in SS patients to verify MG atrophy status. A comparative study with non-SS dry eye patients is required to validate this study.

In vivo confocal microscopy assessment of meibomian glands microstructure in patients with Graves' orbitopathy.

BACKGROUND: To evaluate microstructural changes in the meibomian glands (MGs) in patients with active and inactive Graves' orbitopathy (GO), using in vivo confocal microscopy (IVCM), and to investigate the correlations between clinical and confocal findings. METHODS: Forty patients (80 eyes) with GO (34 eyes with active GO, 46 eyes with inactive GO), and 31 age- and sex-matched control participants (62 eyes) were enrolled consecutively. A researcher recorded the clinical activity score (CAS) for each patient. A complete ophthalmic examination was then performed, including external eye, ocular surface and MGs. IVCM of the MGs was performed to determine the MG acinar density (MAD), MG longest and shortest diameters (MALD and MASD), MG orifice area (MOA), MG acinar irregularity (MAI), meibum secretion reflectivity (MSR), acinar wall inhomogeneity (AWI), acinar periglandular interstices inhomogeneity (API), and severity of MG fibrosis (MF). RESULTS: All confocal microscopy assessments of MGs significantly differed among groups (all P = 0.000). Compared to controls, GO groups showed lower MOA (1985.82 ± 1325.30 µm2 in active GO and 2021.59 ± 1367.45 µm2 in inactive GO vs. 3896.63 ± 891.90 µm2 in controls, all P = 0.000) and MAD (87.21 ± 32.69 /mm2 in active GO and 80.72 ± 35.54 /mm2 in inactive GO vs. 114.69 ± 34.90 /mm2 in controls, P = 0.001 and 0.000, respectively); greater MALD (118.11 ± 30.23 µm in active GO and 120.58 ± 27.64 µm in inactive GO vs. 58.68 ± 20.28 µm in controls, all P = 0.000) and MASD (44.77 ± 19.16 µm in active GO and 46.02 ± 20.70 µm in inactive GO vs. 27.80 ± 9.90 µm in controls, all P = 0.000); and higher degrees of MAI, MSR, and MF (all P<0.05). Eyes with active GO had higher degrees of MAI (P = 0.015), AWI (P = 0.000), and API (P = 0.000), while eyes with inactive GO had higher degrees of MSR (P = 0.000) and MF (P = 0.017). In GO groups, AWI and API were positively correlated with CAS (r = 0.640, P = 0.000; r = 0.683, P = 0.000, respectively), and MF was negatively correlated with CAS (r = - 0.228, P = 0.042). CONCLUSIONS: IVCM effectively revealed microstructural changes of MGs in eyes with GO and provided strong in vivo evidence for the roles of obstruction and inflammation in the ocular surface disease process. Furthermore, it revealed discernible patterns of MG abnormalities in eyes with active GO and inactive GO, which are not easily distinguishable by typical clinical examinations.

Depletion of Cholesteryl Esters Causes Meibomian Gland Dysfunction-Like Symptoms in a Soat1-Null Mouse Model.

Previous studies on ablation of several key genes of meibogenesis related to fatty acid elongation, omega oxidation, and esterification into wax esters have demonstrated that inactivation of any of them led to predicted changes in the meibum lipid profiles and caused severe abnormalities in the ocular surface and Meibomian gland (MG) physiology and morphology. In this study, we evaluated the effects of Soat1 ablation that were expected to cause depletion of the second largest class of Meibomian lipids (ML)-cholesteryl esters (CE)-in a mouse model. ML of the Soat1-null mice were examined using liquid chromatography high-resolution mass spectrometry and compared with those of Soat1+/- and wild-type mice. Complete suppression of CE biosynthesis and simultaneous accumulation of free cholesterol (Chl) were observed in Soat1-null mice, while Soat1+/- mutants had normal Chl and CE profiles. The total arrest of the CE biosynthesis in response to Soat1 ablation transformed Chl into the dominant lipid in meibum accounting for at least 30% of all ML. The Soat1-null mice had clear manifestations of dry eye and MG dysfunction. Enrichment of meibum with Chl and depletion of CE caused plugging of MG orifices, increased meibum rigidity and melting temperature, and led to a massive accumulation of lipid deposits around the eyes of Soat1-null mice. These findings illustrate the role of Soat1/SOAT1 in the lipid homeostasis and pathophysiology of MG.