Meibomian Gland Alterations Research Articles

Tear film ocular surface lifestyle report: Lifestyle challenges

This presentation summarizes the findings of the Lifestyle Challenges Subcommittee of the recent Workshop of the Tear Film & Ocular Surface Society, entitled “A Lifestyle Epidemic: Ocular Surface Disease.”Lifestyle includes different societal, physical and mental aspects, which have a deep impact on dry eye disease (DED).Specifically, among societal factors, the use of tobacco is robustly associated with tear film instability, cocaine reduces corneal sensitivity, alcohol promotes DED symptoms and alterations of the tear film. Among physical factors, extensive mask wear or obesity are associated with Meibomian gland alterations. Moreover, depression, anxiety‐associated or sleep disorders, and medications used for their treatment, have been linked with DED symptoms. Finally, diseases associated with chronic pain, including migraine and fybromyalgia, appear to increase the risk of DED. Further studies are needed to better dissect the role of chronic pain in different DED subtypes.

Automatic characterization of Meibomian gland morphology

Aims/Purpose: To characterize the Meibomian gland (MG) morphology in healthy subjects with an automatic software.Methods: An automatic software was developed for image analysis in R code, consisting of 4 stages: (1) selection of the region of interest, (2) image preprocessing to obtain a binary and a skeleton image, (3) modelling of each MG to fit each MG to a piecewise linear model, and (4) quantification of the following MG features: tortuosity, MG shortening, number of MGs, deviation from a vertical line, and MG area. Meibography images of the upper eyelid were acquired using the Easy Tear View+®. A group of 156 healthy subjects were included, with a mean age and confidence interval (CI) of 43.88 (95% CI: 41.38–46.37) years, range 16–76 years. Reference intervals (RI) were calculated for each MG feature to be used as a diagnostic tool to classify a specific value as normal or non‐normal. Generalized Additive Models for Location, Scale and Shape were used to estimate the percentile curve for each morphologic feature of MG, considering the influence of age and sex.Results: Age had an influence on tortuosity, mean = 0.3 (95% CI: 0.3–0.31), RI: 0.19–0.4 <20 years, and 0.24–0.39 at 50–60 years. Age and sex had an influence in the MG shortening, mean = 63% (95% CI: 62–64%), mean RI: 58–74% <20 years; 59–84% >75 years; women RI: 56–71% <20 years; 57–82% >75 years. The rest of the variables were not affected by age or sex: number of MGs = 16.05 (95% CI: 15.28–16.82), RI: 8–27; vertical deviation = 0.37 (95% CI: 0.36–0.38), RI: 0.29–0.45, and MG area = 14% (95% CI: 14–15%), RI: 8.17–19.81%.Conclusions: Tortuosity variability decreases between 45 and 60 years of age. The MG shortening increases with age and is higher in men. These values could be useful to classify a meibography image as normal or non‐normal, helping to diagnose MG alterations in an objective way.

Association of ocular surface and meibomian gland alterations with silicone hydrogel contact lens wear

PurposeTo evaluate silicone hydrogel contact lens (SH-CL) effects on the meibomian glands, corneal structure, and ocular surface parameters. MethodsFifty SH-CL wearers for at least 6 months, and 50 sex and age-matched control subjects were recruited for this cross-sectional study. Visual display terminal (VDT) work and CL wear duration were questioned, ocular surface and tear functions were evaluated using OSDI questionnaire, tear break-up time (TBUT), corneal fluorescein staining, and Schirmer test. Corneal sensitivity was measured with Cochet-Bonnet aesthesiometry. Meibography and in vivo confocal microscopy (IVCM) were performed to evaluate meibomian glands and corneal structure. Intergroup comparisons were made using the Chi-square test, Wilcoxon test, or Kruskal–Wallis test. ResultsIn the CL group, TBUT was shorter (P = 0.01), corneal fluorescein staining (P = 0.04), OSDI scores (P < 0.001), and meiboscores (P < 0.001) were higher than the control group. The biomicroscopic evaluation revealed meibomian gland dysfunction (MGD) in 34 % of the CL group and 20 % of the control group, which was not statistically significant (P > 0.05). IVCM showed that endothelial cell density was lower (P = 0.01) and polymegethism was higher (P < 0.001) in the CL group. Subbasal nerve density and corneal sensitivity measurements were similar in the two groups (P > 0.05). The longer VDT work duration was associated with increased CFS in the CL group (P = 0.05). ConclusionThe results showed that SH-CL wear increased dry eye symptoms and ocular discomfort, especially in longer VDT work duration. Meibography revealed significantly worse results in SH-CL wearers. SH-CL-related ocular discomfort seems to be more associated with MGD rather than neurosensorial alterations.

Evaluation of Corneal Parameters and Meibomian Gland Alterations After Corneal Cross-Linking in Patients With Progressive Keratoconus.

The aim of the study was to evaluate the changes in corneal parameters and meibomian gland alterations after corneal cross-linking (CXL) for progressive keratoconus. Thirty nine eyes of 39 keratoconus patients were treated with CXL. Corneal topography, specular microscopy, the Ocular Surface Disease Index© (OSDI), noninvasive tear break-up time (NITBUT), and meibography indices were evaluated preoperatively and at the first, third, and sixth months after CXL. The flattest keratometry (K1) ( P =0.003), steepest keratometry (K2) ( P <0.001), apex, central, and thinnest corneal thicknesses ( P <0.001) showed significant differences after cross-linking, whereas the changes in the maximum keratometry (Kmax) were not significant ( P =0.140). The endothelial cell density, coefficient of variation, and hexagonality were unchanged. The NITBUT values decreased after cross-linking; however, there was no significant change in OSDI index ( P =0.313), meiboscore ( P =0.392), and meibomian gland loss degrees ( P =0.300). No change was detected in the morphology of the meibomian glands after CXL. In eyes with keratoconus, a flattening in keratometry readings and thinning in corneal thickness were observed after CXL. The corneal endothelium is protected by dextran-free riboflavin. Cross-linking procedure causes dry eye by changing the corneal structure without affecting the morphology of the meibomian glands.

Comparative of meibomian gland morphology in patients with evaporative dry eye disease versus non-dry eye disease

Many recent studies have showed that morphological changes are one of the key signs of meibomian gland disease (MGD). These changes can be seen even before symptom onset, potentially underestimating the prevalence of MGD; however, until now, there is no conclusive information about the impact of meibomian gland (MG) morphology in tear film physiology and disease. This study aimed to investigate the prevalence of anatomical and morphological MG alterations between patients with evaporative dry eye disease (DED) and healthy controls. Retrospective chart review of seventy-five patients with evaporative DED and healthy individuals who had dry eye assessments included Ocular Surface Disease Index questionnaire, meibum quality, meibum expressibility, lid margin abnormality, ocular staining, non-invasive tear film break-up time, and meibography. We did not find significant differences in MG alterations in the upper lid between healthy and DED subjects. Patients with evaporative DED presented MG alterations in the lower lid more frequently than healthy subjects (54.8 vs. 30.3%; p = 0.03). The presence of shortened glands was the only MG alteration that was more prevalent in the lower lid in dry-eye patients than in healthy subjects (p < 0.05). Subjects with evaporative DED presented more alterations in the lower lid than healthy subjects.

Ocular Surface, Meibomian Gland Alterations, and In Vivo Confocal Microscopy Characteristics of Corneas in Chronic Cigarette Smokers.

To evaluate the ocular surface, meibomian gland alterations, and in vivo confocal microscopy (IVCM) parameters through correlation with nicotine dependency level (NDL) and duration of smoking (DS) in chronic smokers. This cross-sectional study included 50 eyes of 50 chronic smokers, and 50 eyes of 50 age- and gender-matched healthy nonsmokers. To examine the ocular surface and tear film, corneal sensitivity (CS) measurement with Cochet-Bonnet esthesiometer, tear film break-up time (TBUT), lissamine green (LG) staining, Schirmer I test with anesthesia, and Ocular Surface Disease Index (OSDI) questionnaire were performed consecutively. Basal epithelial cell, keratocyte, and endothelial cell density, the percentage of endothelial polymegethism/pleomorphism, and subbasal nerve plexus were evaluated using IVCM. Meibomian gland density was evaluated with a meibography unit. The Fagerström test was used to measure NDL, and DS was recorded. In the chronic smokers group, the basal epithelial cell density, anterior and posterior keratocytes, endothelial cell density, and long and total subbasal nerve numbers were lower, and LG staining, meiboscore, and OSDI scores were higher, compared with the control group, whereas other parameters were similar. The percentage of polymegethism was higher and the percentage of pleomorphism was lower in the chronic smokers group. In the correlation analysis, no significant relationship was found between the DS, NDL and ocular surface, and IVCM findings. Decreased corneal basal epithelium, anterior and posterior keratocytes, endothelial cell density, meibomian gland density, and subbasal nerve numbers were found in chronic smokers. The results of the study show that smoking has an adverse effect on ocular surface parameters.

Impact of pterygium on the ocular surface and meibomian glands.

PurposeTo analyze how ocular surface parameters correlate to presence of pterygium and investigate the possible impact of pterygia on tear film findings and meibomian glands findings.MethodsWe investigated objective parameters of the ocular surface such as conjunctival hyperemia, tear film stability and volume, meibomian gland dysfunction, dry eye disease, corneal topography comparing healthy individuals and correlating with the pterygium clinical presentation.ResultsA total of 83 patients were included. Corneal astigmatism induction was 2.65 ± 2.52 D (0.4–11.8). The impact of pterygium on the ocular surface parameters compared to matched controls was seen in: conjunctival hyperemia (control 1.55±0.39/pterygium 2.14±0.69; p = 0.0001), tear meniscus height (control 0.24±0.05 mm/pterygium 0.36±0.14mm; p 0.0002), meiboscore lower eyelid (control 0.29±0.64/pterygium 1.38±0.95; p 0.0001) and meiboscore upper eyelid (control 0.53±0.62/pterygium 0.98±0.75; p = 0.0083). We found a high number of pterygium patients (88%) presented meibomian gland alterations. Interestingly, meibomian gland loss was coincident to the localization of the pterygium in 54% of the upper and 77% lower lids.ConclusionPterygium greatly impacts on ocular surface by inducing direct alterations in the pattern of meibomian glands besides corneal irregularities, conjunctival hyperemia and lacrimal film alterations, inducing significant symptoms and potential signs of dysfunction.

Ocular surface assessment and morphological alterations in meibomian glands with meibography in obstructive sleep apnea Syndrome

PurposeTo evaluate ocular surface and Meibomian glands morphology of patients with obstructive sleep apnea syndrome (OSAS). Materials and methodsBased on polysomnography, 36 eyes of 36 patients with severe OSAS (Group 1, apnea-hypopnea index (AHI) ≥30/h) and 24 eyes of 24 patients with primary snoring or mild OSAS (Group 2, AHI<15/h) were enrolled. Detailed eye examination along with ocular surface staining (fluorescein, 2%) according to Oxford scale, tear film break-up time (t-BUT), Schirmer 1 test, ocular surface disease index (OSDI) scoring, and evaluation of upper and lower eyelid Meibomian glands using infrared filter of slit-lamp biomicroscope were performed. In addition to grading Meibomian gland drop-out, the presence morphologic alterations such as Meibomian gland duct distortion, thinning and dilatation were also assessed. ResultsThe mean ages were 50.8 ± 8.3 (range, 35–68) and 47.9 ± 10.5 (range, 27–69) in Group 1 and Group 2, respectively (p = 0.616). Best-corrected visual acuity, Schirmer 1 test, Oxford scale and OSDI scores, and lower meiboscores did not differ significantly between groups. In Group 1, average t-BUT was lower (p = 0.003), upper and total (upper + lower) meiboscores were higher as compared to Group 2 (p < 0.05). The frequency of Meibomian gland duct distortion, thinning and dilatation were also significantly greater in Group 1 (p < 0.05). ConclusionMorphological changes, in addition to Meibomian glands dropout were significant in severe OSAS patients as demonstrated objectively with meibography. Schirmer 1 and t-BUT tests were in favor of evaporative type dry eye syndrome, which also support Meibomian gland alterations in severe OSAS patients.

In vivo confocal microscopy evaluation of ocular and cutaneous alterations in patients with rosacea.

The physiopathology of rosacea and the correlation between ocular and cutaneous rosacea remains unclear. This study analysed ocular and cutaneous rosacea with in vivo confocal microscopy (IVCM). Thirty-four eyes of 34 patients with confirmed rosacea-associated meibomian gland dysfunction-related evaporative dry eye were enrolled in the study. The ophthalmological investigations included dry eye ocular surface disease index (OSDI), the Schirmer test, tear osmolarity, tear break up time, the Oxford score, infrared meibography for meibomian gland (MG) analysis and IVCM investigation for cornea, MG and skin analysis (cheek, hand). Presences of Demodex in the MG and in the cheek were also investigated. We established scores for quantifying the MG alterations in the MG (IVCM-MG) and cheek (IVCM-Cheek), and scores for Demodex quantification in the MG and cheek (IVCM-MG-Dex and IVCM-Cheek-Dex). IVCM was relevant for analysing the cornea and MG structures and was also suitable for cutaneous analysis. Exposed skin explorations presented the epidermal and dermal layers clearly. In patients with rosacea, the IVCM-MG alteration scores were correlated with IVCM-Cheek (R2=0.27 and p=0.0006) and IVCM-MG-Dex was correlated with IVCM-Cheek-Dex (R2=0.70 and p<0.0001). However, no correlation was found between the IVCM-MG or IVCM-Cheek and the break up time, Schirmer, Oxford and osmolarity evaluations. IVCM could be a safe, effective and reliable tool to quantify alterations of the cornea, MG and cheek glands in patients with rosacea combined with quantification of Demodex infections. As a valuable tool for investigating the pathophysiology of the disease, it could be used to assess the effectiveness of therapy.

Meibomian Gland Alteration in Patients with Primary Chronic Dacryocystitis: An In vivo Confocal Microscopy Study

Purpose: To evaluate meibomian gland (MG) alterations in patients with primary chronic dacryocystitis (PCD) by in vivo confocal microscopy (IVCM), and to correlate the finding with clinical presentation.Methods: Twenty-eight eyes with the diagnosis of PCD and their contralateral unaffected eyes were studied and compared with 27 normal controls. All subjects completed an Ocular Surface Disease Index questionnaire (OSDI) and underwent slit-lamp biomicroscopy examination, tear break-up time (BUT) measurements, fluorescein staining, Schirmer test I, and an IVCM examination of the MG. IVCM parameters, including the MG acinar unit density (MGAUD), periglandular inflammatory cell density (ICD), MG acinar unit longest diameter (MGALD), and MG acinar unit shortest diameter (MGASD) and their correlation with clinical data were analyzed.Results: The mean MG expressibility scores, BUT values, and staining scores were significantly worse in eyes with PCD compared with the contralateral clinically unaffected eyes and controls (p < 0.05). A significant decrease in MGAUD was observed in PCD eyes compared with the controls and the contralateral clinically unaffected eyes. Conversely, the mean ICD and MGASD values were significantly higher in the PCD eyes. There were no significant differences in mean MGALD value between the PCD eyes and the contralateral clinically unaffected eyes. In addition, there were significant changes in the IVCM parameters in the contralateral unaffected eyes compared with the controls, including MGAUD, ICD, MGALD, and MGASD. All IVCM parameters showed a strong, significant correlation with MG dropout grades, MG expressibility, fluorescein staining scores, and OSDI values (all p < 0.05).Conclusions: Patients with unilateral PCD demonstrated significant changes in MG as compared with the contralateral clinically unaffected eyes and controls. The MG function should be closely observed in these patients.

Oxidative stress induced age dependent meibomian gland dysfunction in Cu, Zn-superoxide dismutase-1 (Sod1) knockout mice.

PurposeThe purpose of our study was to investigate alterations in the meibomian gland (MG) in Cu, Zn-Superoxide Dismutase-1 knockout (Sod1 −/−) mouse.MethodsTear function tests [Break up time (BUT) and cotton thread] and ocular vital staining test were performed on Sod1 −/− male mice (n = 24) aged 10 and 50 weeks, and age and sex matched wild–type (+/+) mice (n = 25). Tear and serum samples were collected at sacrifice for inflammatory cytokine assays. MG specimens underwent Hematoxylin and Eosin staining, Mallory staining for fibrosis, Oil Red O lipid staining, TUNEL staining, immunohistochemistry stainings for 4HNE, 8-OHdG and CD45. Transmission electron microscopic examination (TEM) was also performed.ResultsCorneal vital staining scores in the Sod1 −/− mice were significantly higher compared with the wild type mice throughout the follow-up. Tear and serum IL-6 and TNF-α levels also showed significant elevations in the 10 to 50 week Sod1 −/− mice. Oil Red O staining showed an accumulation of large lipid droplets in the Sod1 −/− mice at 50 weeks. Immunohistochemistry revealed both increased TUNEL and oxidative stress marker stainings of the MG acinar epithelium in the Sod1 −/− mice compared to the wild type mice. Immunohistochemistry staining for CD45 showed increasing inflammatory cell infiltrates from 10 to 50 weeks in the Sod1 −/− mice compared to the wild type mice. TEM revealed prominent mitochondrial changes in 50 week Sod1 −/− mice.ConclusionsOur results suggest that reactive oxygen species might play a vital role in the pathogensis of meibomian gland dysfunction. The Sod1 −/− mouse appears to be a promising model for the study of reactive oxygen species associated MG alterations.

Is complete androgen insensitivity syndrome associated with alterations in the meibomian gland and ocular surface?

This study's purpose was to determine whether complete androgen insensitivity syndrome (CAIS) is associated with alterations in the meibomian gland and ocular surface. Individuals with CAIS, as well as age-matched female and male controls, completed questionnaires which assessed dry eye symptoms and underwent slit lamp evaluations of the tear film, tear meniscus, lids and lid margins and conjunctiva. The quality of meibomian gland secretions was also analyzed. Our results demonstrate that CAIS is associated with meibomian gland alterations and a significant increase in dry eye signs and symptoms. Clinical assessment revealed that CAIS women, as compared to controls, had a significant increase in telangiectasia, keratinization, lid erythema and orifice metaplasia of the meibomian glands, and a significant decrease in the tear meniscus and quality of meibomian gland secretions. Questionnaire results showed that dry eye symptoms were increased over twofold in CAIS individuals, as compared to controls, including a significant increase in the sensations of dryness, pain and light sensitivity. Our results suggest that androgen insensitivity may promote meibomian gland dysfunction and an increase in the signs and symptoms of dry eye.