Meibomian Gland Dropout Research Articles

The Proportion of Ocular Involvement and Characteristics of Dry Eye Parameters in Primary Sjögren's Syndrome Referred from the Rheumatology Department.

To report the proportion of ocular involvement in primary Sjögren's syndrome (pSS) and to analyze various dry eye indexes and serum titers of markers depending on whether ocular involvement has occurred or not. This retrospective study considered 214 patients referred from the rheumatology department for pSS workup. Symptom questionnaires, ocular surface stain score (OSS), Schirmer test, tear break-up time (TBUT), meibomian gland (MG) dropout, meibum quality, meibum expressibility, lid margin abnormalities, and lipid layer thickness were evaluated. Anti-Ro Ab, anti-La Ab, ANA, RF, ESR, and CRP were included as systemic serum titers of markers. Patients with (Group 1) and without (Group 2) ocular involvement were compared. We conducted a further subgroup analysis of group 1 by dividing it into two groups based on whether or not the cases met all the ocular criteria for pSS diagnosis. Among the 214 referred patients, 118 were diagnosed as pSS: 87 out of 118 (74%) in group 1 and 31 (25%) in group 2. Group 1 showed higher meibum quality scores (p=0.016), meibum expressibility (p=0.01), and lid margin abnormalities on the lower lid (p=0.029) and lower TBUT (p=0.016) than group 2. Among the serum titers of markers, anti-Ro Ab negatively correlated with TBUT (r=-0.211, p=0.028). OSS, TBUT, and the schirmer test statistically differed between the patients who satisfied both ocular criteria (N=46) and those who satisfied only one criterion (N=41) (p=<0.001, 0.041, 0043, respectively). There were no statistical differences in serum titers of markers between the two groups. About half of patients referred from the rheumatology department for diagnosis of pSS were diagnosed with pSS. The proportion of ocular involvement in the pSS patients was 74%, and half of these patients met both ocular criteria. Only anti-Ro Ab negatively correlated with TBUT. Also, OSS, TBUT, and schirmer test were statistically different between the two subgroups.

Meibomian Gland Dysfunction and Dropout in Diabetic Patients with Non-Proliferative Diabetic Retinopathy.

This study aims to compare meibomian gland (MG) dropout and MG dysfunction (MGD) between patients with diabetes mellitus (DM) with moderate-severe non-proliferative diabetic retinopathy (NPDR) and patients with no diabetes (NDM). This prospective, transversal, age, and gender-matched case-control study included 98 DM and 106 NDM eyes. Dry eye disease (DED) and MGD evaluations were performed, including meibography (Keratograph 5M®). The objective MG dropout percentage was obtained by analyzing meibography images with ImageJ software (v. 1.52o, National Institutes of Health, Bethesda, MD, USA) and was subsequently graded with Arita's meiboscore. The DM duration was 18 ± 9 years. The mean meiboscore (3.8 ± 0.8 vs. 3.4 ± 1.0, p = 0.001), meiboscore severity (p = 0.016), and MG dropout (45.1 ± 0.1% vs. 39.0 ± 0.4%, p < 0.001) were greater in DM than in NDM. All patients showed MG dropout (meiboscore > 1). Lower eyelids showed greater MG dropout in both groups. A correlation with age (r = 0.178, p = 0.014) and no correlations with DM duration or gender (p > 0.005) were observed. Patients with diabetes showed greater corneal staining (1.7 ± 1.3 vs. 0.9 ± 1.1; p < 0.001), reduced corneal sensitivity (5.4 ± 1.1 vs. 5.9 ± 0.4; p < 0.001), lower MG expressibility (3. 9 ± 1.6 vs. 4.4 ± 2.1; p = 0.017), and worse meibum quality (1.9 ± 0.8 vs. 1.7 ± 0.5; p = 0.019). Tear breakup time, osmolarity, MMP-9, Schirmer, and the Ocular Surface Disease Index showed no significant differences. In conclusion, patients with DM with NPDR have greater MG dropout and meiboscore, as well as more severe MGD and DED parameters than persons with NDM.

Tear film parameters and meibography in eyes of children with vernal keratoconjunctivitis.

To study tear film parameters and Meibomian glands in pediatric patients with vernal keratoconjunctivitis (VKC). Forty-four eyes of 22 patients with VKC and 44 eyes of 22 age-matched controls were studied in a hospital-based cross-sectional study. Each subject underwent a complete ophthalmological examination including slit-lamp biomicroscopy, non-invasive break-up time (NIBUT), fluorescein break-up time (FBUT), corneal fluorescein staining, and Schirmer's test. Non-contact meibography was performed using a Sirius topographer. All patients had VKC grades between 1 and 3 (Bonini scale). The mean NIBUT for cases was 8.83 ± 4.02 s and in controls, it was 15 ± 2.8 s (P value < 0.001). The mean FBUT for cases was 9.41 ± 3.45 s and in controls, it was 16.7 ± 2.5 s (P value < 0.001). Schirmer's values were 32 ± 3.1 mm in cases and 21.4 ± 4.1 mm in controls, which were significantly higher (P value < 0.001). Also, 22.72% of the cases had corneal fluorescein staining in the form of superficial punctuate keratitis, whereas none of the control groups showed corneal staining. The examination of Meibomian glands using non-contact meibography showed a mean Meibomian gland dropout in the upper lid to be 29.7 ± 14.4% in VKC cases and 10.5 ± 3.2% in controls (P value < 0.001). Meibography of the lower lid showed 25.9 ± 10.2% dropout in cases and 20.5 ± 6.1% in controls (P value = 0.004). Tear film parameters were significantly deranged in children with VKC in the active stage as compared to age-matched controls. Children with VKC also had a higher Meibomian gland dropout.

The effect of type 2 diabetes mellitus on lid wiper epitheliopathy and ocular surface parameters

IntroductionThis cross-sectional study was conducted to investigate the impact of type 2 diabetes mellitus(DM) and its duration on indicators such as lid wiper epitheliopathy(LWE), and to assess the significance of LWE for early diagnosis of dry eye disease(DED) in DM patients. MethodsA total of 137 subjects with ocular surface disease index(OSDI) score ≥13 were divided into the non-DM group, the short-term DM group (duration <5 years), and the mid-to-long-term DM group(duration ≥5 years). Evaluations were conducted for LWE, OSDI, lipid layer thickness (LLT), partial blinking rate (PBR), fluorescein tear breakup time (FTBUT), corneal fluorescein staining score (CFS), eyelid margin score, and meibomian gland dropout (MGd). ResultsThe upper-LWE score and total LWE score in the mid-to-long-term group were higher than those in the non-DM group (p = 0.008 and p = 0.031, respectively). The lower-LWE scores were more severe than upper-LWE scores in the non-DM and short-term groups (p = 0.001 and p = 0.045, respectively).The confirmed diagnosis rate of DEWSII dry eye with LWE as the primary diagnostic indicator was significantly higher than that which utilize FTBUT<5s as the primary diagnostic indicator(p < 0.05). Compared to the non-DM group, the LLT was thinner and the MGd was more severe in the mid-to long-term group. The upper-LWE score was moderately positively correlated with the MGd, and the lower LWE score was moderately negatively correlated with LLT. ConclusionLWE, LLT, and MGd worsen with the progression of diabetes. Additionally, changes in LWE may precede the FTBUT, indicating that LWE could be considered as an important indicator for early diagnosis of DED in diabetic patients.

The effect of intense pulsed light combined with topical 0.05% Cyclosporin A eyedrops in the treatment of Sjögren’s syndrome related dry eye

ABSTRACT Objectives This study aimed to assess the effectiveness and safety of intense pulsed light (IPL) therapy plus topical 0.05% cyclosporine A (CsA) eye drops to treat Sjögren’s Syndrome-related dry eyes (SS-DE). Research design and methods In this prospective, randomized trial included, 60 individuals with SS-DE symptoms were randomized to receive topical eye drops containing either 0.1% sodium hyaluronate (Group S) or 0.05% CsA (Group C) plus IPL therapy. Before the first treatment (baseline), and at 12, 16, and 20 weeks after treatment commencement, we assessed the best corrected visual acuity (BCVA), the Ocular Surface Disease Index (OSDI) score, the Schirmer I test (SIT), noninvasive tear breakup time (NBUT), corneal fluorescein staining (CFS), meibomian gland (MG) dropout, lid margin abnormality, MG expressibility, and meibum quality. Results Both groups showed significant improvements in the OSDI, NBUT, CFS, MG expressibility, and meibum quality (all p < 0.05). Group C showed a greater increase in OSDI, NBUT, MG expressibility, and meibum quality (all p < 0.05). Moreover, SIT and lid margin abnormalities significantly improved in Group C (both p < 0.05), but not in Group S. Conclusion Treatment with 0.05% CsA eyedrops plus IPL therapy could significantly reduce the issues and physical discomfort of patients with SS-DE. Clinical Trial Registered on 20 July 2021, with the registration number ChiCTR2100049059.

Prevalence of dry eye in people over 50 years old in Beichen district, Tianjin city: a cross-sectional population-based survey

BackgroundA cross-sectional population-based survey in the Beichen district of Tianjin was conducted to estimate the prevalence of dry eye disease (DED) among the population over 50 years old with Dry Eye Workshop (DEWS) II and Chinese expert consensus (CEC) criteria.MethodsA total of 5791 subjects over 50 years old were enrolled. Ocular surface disease index (OSDI) questionnaire, lipid layer thickness (LLT), partial blink ratio (PBR), fluorescein tear film breakup time (FBUT), Schirmer I test (SIT), fluorescein staining, meibomian gland dropout, meibomian gland expression scores (MES) and quantity scores (MQS) was assessed. Additionally, basic information, weight, disease history, living habits, anxiety, and depression condition were collected.ResultsAccording to the CEC, the prevalence of DED was 39.0%, whereas 44.0% based on DEWS II. The prevalence of DED increased with age and was substantially greater among women (41.1%, 95% CI, 39.5-42.6%) than males (35.1%, 95% CI, 33.1 -37.2%) (p < 0.001). Furthermore, the severity of DED was more severe in women (p = 0.006). The associated risk factors were age, female, depression, smoking, insomnia, and glaucoma. On the other hand, 53.6% of these populations were diagnosed as asymptomatic DED, and the morbidity was higher in males (p = 0.007).ConclusionsThe prevalence of DED in China was relatively high, which was associated with aging, female(sex), depression, smoking and sleep problems. Hence, it is crucial for clinicians and caregivers to be aware of the existence of asymptomatic DED within the susceptible population.

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-1β, 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-1β 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.

Topical glaucoma medications - Possible implications on the meibomian glands.

One of the most common causes of blindness on a global scale is glaucoma. There is a strong association between glaucoma and increased intraocular pressure (IOP). Because of this, adequate IOP-lowering is the most important treatment strategy, mostly through topical eyedrops. Well-functioning meibomian glands are paramount for maintaining a stable tear film, and their dysfunction is the most common cause of dry eye disease. There is a growing concern that both topical glaucoma medications themselves and their added preservatives damage the meibomian glands, and consequently, the ocular surface. Preserved topical glaucoma medications appear to cause dysfunction and atrophy of the meibomian glands. Upon comparison, preserved formulations caused more symptoms of dry eye, tear film instability, inflammatory changes and meibomian gland dropout than the preservative-free counterpart. However, although seemingly less detrimental, unpreserved alternatives may diminish glandular efficacy, and, depending on the active ingredient, lead to glandular death. This negatively impacts quality of life, adherence to treatment regimens and prognosis. In this review, we explore the available evidence regarding the effects of IOP-lowering eye drops on the meibomian glands.

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.

Is Meibomian Gland Dysfunction One Disease? Heterogeneity Among Phenotypes.

The purpose of this study was to examine ocular surface symptoms, tear metrics, and tear cytokines by Meibomian gland dysfunction (MGD) features. Symptom questionnaires and an ocular surface evaluation were performed on 40 individuals with varied MGD signs (Meibomian gland [MG] plugging, eyelid vascularity, meibum quality, and MG dropout). Tear proteins were extracted off Schirmer strips and analyzed for 23 human inflammation-related proteins. Statistical analysis was performed to examine associations between dry eye metrics inflammatory proteins and MGD features. The study involved 40 South Florida veterans with a mean age of 61 ± 13 years; most individuals were male (95%), White (31%), and non-Hispanic (85%). MGD features differentially related to dry eye signs. Eyelid vascularity, meibum quality, and MG dropout, but not MG plugging, correlated with higher corneal staining and lower tear production. MGD features also differentially related to tear cytokines. Eyelid vascularity most closely related to inflammation with significant correlations for interferon-gamma-γ (r = 0.36, P = 0.02), interleukin-4 (IL-4) (r = 0.43, P = 0.006), IL-17A (r = 0.42, P = 0.007), matrix metalloproteinase-2 (r = 0.39, P = 0.01), C-X-C motif chemokine ligand 5 (Regulated upon Activation, Normal T-Cell Expressed and presumably Secreted [RANTES]) (r = 0.32, P = 0.04), and tumor necrosis factor α (r = 0.36, P = 0.02). The other 3 MGD signs were less related to inflammation. Multivariable models revealed IL-4 to be most closely related to eyelid vascularity (standardized β = 0.39, P < 0.0001). Eyelid vascularity was the MGD sign most closely related to inflammatory cytokines, suggesting that different MGD features may be driven by different pathophysiological mechanisms.

Red filter meibography by smartphones in patients with meibomian gland dysfunction: a validity and reliability study

ObjectiveThe objective of this study is to determine the validity and reliability of the red filter meibography by smartphone compared with infrared in assessing meibomian gland drop-out.Methods and analysisAn analytical...

Ocular surface and meibomian gland evaluation in euthyroid Graves’ ophthalmopathy

PurposeEuthyroid Graves’ ophthalmology (EGO) refers to the subgroup of thyroid eye disease patients with distinct clinical presentations. This study evaluated the ocular surface and meibomian gland changes in EGO patients.MethodsA cross-sectional study was conducted at The Chinese University of Hong Kong including 34 EGO patients and 34 age-and sex- matched healthy controls. Outcome measures include anterior segment examination, keratographic and meibographic imaging.ResultsBetween 34 EGO patients and 34 age and sex-matched healthy controls, EGO was associated with a higher ocular surface disease index (P < 0.01), higher severity of meibomian gland dropout (upper: P < 0.001, lower: P < 0.00001) and higher percentage of partial blinking (P = 0.0036). The worse affected eyes of the EGO patients were associated with corneal staining (P = 0.0019), eyelid telangiectasia (P = 0.0009), eyelid thickening (P = 0.0013), eyelid irregularity (P = 0.0054), meibomian gland plugging (P < 0.00001), expressibility (P < 0.00001), and meibum quality (P < 0.00001). When the two eyes of the same EGO patient were compared, the degree of meibomian gland dropout was higher among the worse affected eyes (upper: P < 0.00001, and lower: P < 0.00001). Tear meniscus height, lipid layer thickness, and noninvasive break-up time were comparable between the two eyes of EGO patients and also between EGO patients and healthy controls. TMH was positively correlated with the degree of exophthalmos (r = 0.383, P < 0.05).ConclusionEGO patients have more ocular surface complications and meibomian gland dropouts than healthy controls. Almost 60% of them had dry eye symptoms, but aqueous deficiency was not apparent. Further studies are warranted to clarify the mechanism of dry eye in EGO.(249 words).

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

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. Prospective single-centre study (sub-analysis clinical trial no. NCT05754437). 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. 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. 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.

Meibomian gland dropout of upper eyelids as a novel biomarker for early diagnosis of primary Sjögren's syndrome: a pilot study.

Early diagnosis of primary Sjögren's syndrome (pSS) remains difficult due to its insidious onset. To identify whether meibomian gland dropout (MGD) is a sensitive and noninvasive predictor of pSS by studying its association with histopathology in labial salivary gland biopsy in patients with clinically suspected pSS. Prospective, randomized, multicenter, comparative effectiveness study. The study was conducted from July 2022 to July 2023. In all, 56 eligible participants with clinically suspected pSS were recruited from three combined ophthalmology medicine/rheumatology SS clinics. All participants with suspected pSS were evaluated and diagnosed by ophthalmology and rheumatology consultants and underwent infrared imaging of the meibomian glands using Keratograph 5M and histopathological evaluation of labial salivary gland biopsies. The length, width, and tortuosity of the meibomian glands were measured; the dropout rate in the nasal, temporal, and total eyelids was analyzed; and the dropout score was calculated using meibography grading scales. Among the 56 participants, 34 were identified with pSS, and 22 were diagnosed with non-SS dry eye (NSSDE) and served as the control group. We recorded significant differences in the temporal and total MGD rates of the upper eyelids between the pSS and NSSDE groups (all p < 0.01). Improved prediction accuracy was achieved with the temporal and total MGD rates in the upper eyelids, with area under the curve values of 0.94 and 0.91, and optimal cutoff points of 0.78 and 0.75, respectively. MGD in the upper eyelids, especially in the temporal portion, is strongly associated with the histopathological outcome of labial salivary gland biopsy in pSS and is proposed as a highly predictive and noninvasive biomarker for the early diagnosis of pSS. ClinicalTrials.gov identifier: ChiCTR2000038911.

Categorization of Meibomian Gland Dysfunction Using Lipid Layer Thickness and Meibomian Gland Dropout in Dry Eye Patients: A Retrospective Study.

In the present study, we determined the prevalence of obstructive meibomian gland dysfunction (MGD), hyposecretory MGD, grossly normal MG, and hypersecretory MGD in patients with dry eye syndrome using lipid layer thickness (LLT) and MG dropout. Eighty-eight patients with dry eye syndrome were included in the study. Patients were categorized into four groups according to the LLT and weighted total meiboscore. The proportion of patients in each group was calculated. The age, sex, Ocular Surface Disease Index, LLT, Schirmer, tear film breakup time, cornea stain, weighted total meiboscore, expressibility, and quality of meibum were compared between the four groups. Fifteen eyes (17.0%) had obstructive MGD, two eyes (2.3%) had hyposecretory MGD, 40 eyes (45.5%) had grossly normal MG, and 17 eyes (19.3%) had hypersecretory MGD. The obstructive MGD group was younger than the grossly normal MG group. In obstructive MGD, the ratio of men to women was higher than that of the other groups. However, Ocular Surface Disease Index, Schirmer, tear film breakup time, and corneal stain did not show statistically significant differences between the four groups. The meibum expressibility of the hyposecretoy MGD group was worse than those of the other groups. The meibum expressibility of the hyposecretoy MGD group was poor than those of the obstructive and hypersecretory MGD group. This categorization was expected to help determine the best treatment method for dry eye syndrome, according to the MG status.

Age related changes in hyaluronan expression leads to Meibomian gland dysfunction

The prevalence of dry eye disease (DED) ranges from ∼5 to 50 % and its associated symptoms decrease productivity and reduce the quality of life. Approximately 85 % of all DED cases are caused by Meibomian gland dysfunction (MGD). As humans and mice age, their Meibomian glands (MGs) undergo age-related changes resulting in age related-MGD (ARMGD). The precise cause of ARMGD remains elusive, which makes developing therapies extremely challenging. We previously demonstrated that a hyaluronan (HA)-rich matrix exists surrounding the MG, regulating MG morphogenesis and homeostasis. Herein, we investigated whether changes to the HA matrix in the MG throughout life contributes towards ARMGD, and whether altering this HA matrix can prevent ARMGD. For such, HA synthase (Has) knockout mice were aged and compared to age matched wild type (wt) mice. MG morphology, lipid production, PPARγ expression, basal cell proliferation, stem cells, presence of atrophic glands and MG dropout were analyzed at 8 weeks, 6 months, 1 year and 2 years of age and correlated with the composition of the HA matrix. We found that as mice age, there is a loss of HA expression in and surrounding the MGs of wt mice, while, in contrast, Has1−/−Has3−/− mice present a significant increase in HA expression through Has2 upregulation. At 1 year, Has1−/−Has3−/− mice present significantly enlarged MGs, compared to age-matched wt mice and compared to all adult mice. Thus, Has1−/−Has3−/− mice continue to develop new glandular tissue as they age, instead of suffering MG atrophy. At 2 years, Has1−/−Has3−/− mice continue to present significantly larger MGs compared to age-matched wt mice. Has1−/−Has3−/− mice present increased lipid production, increased PPARγ expression and an increase in the number of proliferating cells when compared to wt mice at all-time points analyzed. Taken together, our data shows that a loss of the HA matrix surrounding the MG as mice age contributes towards ARMGD, and increasing Has2 expression, and consequently HA levels, prevents ARMGD in mice.

Risk Factors for Meibomian Gland Disease Assessed by Meibography.

To elucidate risk factors for meibomian gland disease (MGD) and understand associated changes in meibography and in relation to ocular surface disease. As part of the standard workup for ocular surface disease at a tertiary academic center, 203 patients received an ocular history and lifestyle questionnaire. The questionnaire included detailed inquiries about ocular health and lifestyle, including makeup use, cosmetic eyelid procedures, screen time, and contact lens habits. Subjects also took the standardized patient evaluation of eye dryness (SPEED) II questionnaire. Meibomian gland (MG) dropout and structural changes were evaluated on meibography and scored by three independent graders using meiboscores. Statistical analysis was conducted to identify significant risk factors associated with MG loss. This retrospective, cross-sectional studyincluded 189 patients (378 eyes) with high-quality images for grading, and the average age was 67 years (77% female). Patients older than 45 years had significantly more dropout than younger patients (p < 0.01). Self-reported eye makeup use did not significantly impact MG loss. Patients with a history of blepharoplasty trended toward higher meiboscores, but the difference was not statistically significant. Self-reported screen time did not affect meiboscores. Contact lens use over 20 years was associated with significant MG loss (p < 0.05). SPEED II scores had no relationship to meiboscores (p = 0.75). Older age is a significant risk factor for MG loss. Any contact lens use over 20 years also impacted MG dropout. Highlighting the incongruence of symptoms to signs, SPEED II scores showed no relationship to the structural integrity of MGs.

Outcomes of the addition of oral administration of curcumin-phospholipid to hyaluronic acid-based tear substitute for the treatment of dry eye disease.

The aim of this study is to report the clinical outcomes of oral supplementation with curcumin-phospholipid in addition to hyaluronic acid-based tear substitute for the management of dry eye disease (DED). Patients with a diagnosis of DED confirmed by pathological values of both NIKBUT <10 s. and OSDI Questionnaire score > 12 were included. Patients were randomized to receive 2 different treatments: 0.25% hyaluronic acid-based tear substitute 3 time daily (Group 1) or as above plus curcumin-phosphatidylcholine complex tablets once a day (Group 2). Patients were evaluated at baseline (T0) and after 90 days of treatment (T1) by means of Keratograph for the measurement of NIKBUT, TMH, meibomian gland dropout and bulbar redness. Overall, data from 90 eyes of 45 patients were included. Group 1 consisted of 48 eyes of 24 patients, while group 2 included 42 eyes of 21 patients. When comparing median values of both groups at T0, no statistically significant differences were found for all parameters; instead for T1, statistically significant differences were found for redness and OSDI compared to Group 1. In group 1, a statistically significant reduction after the treatment was detected for Nikbut average and OSDI questionnaire; while in group 2, a statistically significant reduction after treatment was recorded for Nikbut average, bulbar redness and OSDI questionnaire. The addition of an oral supplement containing curcumin-phospholipid may help in a greater improvement of bulbar redness and subjective ocular symptoms compared to the treatment with tear substitutes alone for the management of 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.

Anterior segment optical coherence tomography meibography compared with keratograph meibography.

The aim of this study was to determine the feasibility of using readily accessible technology, anterior segment optical coherence tomography (AS-OCT), to detect and grade meibomian gland dropout and examine its interchangeability with the Oculus Keratograph 5M (K5M). A total of 30 participants (30 eyes) with a median age of 21 (range = 19-28 years) were recruited. Meibography was performed using two commercially available imaging devices to look at the structure of the meibomian glands and grade them subjectively in real time, and image analysis was used to quantify meibomian gland loss objectively. Gland loss as imaged by the two techniques was graded using the meiboscore grading schema. Test-retest reliability was determined with intraclass correlation coefficients (ICCs). Weighted kappa was used to evaluate agreement between the two imaging devices and four methods of image analysis. Spearman and Pearson correlation coefficients were used to determine the association of structural measurements between each of the techniques. The agreement between the two imaging techniques was determined with the Bland-Altman analysis. Reliability of subjective grading was strong for AS-OCT (ICC: 0.92, 95% CI: 0.83-0.96, p < 0.001) and K5M (ICC: 0.96, 95% CI: 0.96-0.91, p = 0.001). Image analysis with ImageJ reliability was strong between the imaging devices (ICC: 0.84, 95% CI: 0.55-0.94, p < 0.001). Agreement between each subjective technique was fair, κ = 0.45 (95% CI: 0.17-0.73, p < 0.001) and a positive Spearman correlation was also observed (r = 0.52, p < 0.001). There was no significant difference between the mean meibomian gland loss measured with ImageJ between AS-OCT and K5M (0.92 ± 6.28, p = 0.26). The 95% limits of agreement were -12.45% to +14.04%. These findings suggest subjective real-time grading of meibomian gland loss could be performed using readily available AS-OCT technology and that this method was interchangeable with the K5M.