Meibum Quality Research Articles

Meibomian Gland Assessment in Routine Ophthalmology Practice.

This cross-sectional study aimed to investigate the connection between meibomian gland (MG) excreta quantity and quality after MG expression (MGX), dry eye disease (DED) symptoms, and objective DED signs and to clarify the relationship between dry eye and MG function in DED pathophysiology. The study included 200 subjects, 100 with and 100 without dry eye symptoms. Schein questionnaire was used to determine the severity of dry eye symptoms and self-reported skin type for facial skin dryness self-evaluation. Objective dry eye signs were assessed by monitoring conjunctival hyperemia, lid parallel conjunctival folds (LIPCOF), tear break-up time (TBUT), fluorescein surface staining and digital MGX. Subjects with DED symptoms had significantly lower MG quantity scores than healthy controls (p < 0.001). Meibum quality and quantity scores significantly correlated with female gender (p = 0.002), Schein questionnaire score (p < 0.001), fluorescein corneal staining score (p = 0.019), self-reported skin type (p < 0.001), TBUT (p < 0.001) and LIPCOF (p = 0.041). After adjustment for age and gender in a logistic regression analysis, dry eye was independently and significantly associated with self-reported skin type (OR 0.73, p < 0.001), LIPCOF (OR 1.04, p < 0.001), fluorescein corneal staining (OR 1.05, p = 0.019), TBUT (OR 0.77, p < 0.001) and meibum quantity score (OR 0.59, p < 0.001). Dry eye symptoms and objective signs correlated well in this study. MGX discriminated between the subjects with and without DED symptoms and was associated with other objective DED signs. Results showed a significant association between meibum quality and quantity, MG function, DED and facial skin dryness self-perception. This paper established a correlation between dry eye symptoms caused by MG dysfunction and dry skin, which can help general health practitioners consider dry eye as a cause of chronic eye complaints with patients who report dry skin.

Predicting an unstable tear film through artificial intelligence.

Dry eye disease is one of the most common ophthalmological complaints and is defined by a loss of tear film homeostasis. Establishing a diagnosis can be time-consuming, resource demanding and unpleasant for the patient. In this pilot study, we retrospectively included clinical data from 431 patients with dry eye disease examined in the Norwegian Dry Eye Clinic to evaluate how artificial intelligence algorithms perform on clinical data related to dry eye disease. The data was processed and subjected to numerous machine learning classification algorithms with the aim to predict decreased tear film break-up time. Moreover, feature selection techniques (information gain and information gain ratio) were applied to determine which clinical factors contribute most to an unstable tear film. The applied machine learning algorithms outperformed baseline classifications performed with ZeroR according to included evaluation metrics. Clinical features such as ocular surface staining, meibomian gland expressibility and dropout, blink frequency, osmolarity, meibum quality and symptom score were recognized as important predictors for tear film instability. We identify and discuss potential limitations and pitfalls.

Microbiota in MGD

AbstractMGD is characterized by significant changes in meibum quality that may lead to the changes in the existing ocular surface flora that can contribute to the inflammatory state typical of the condition. Several papers have addressed this aspect. Li and coworkers, dividing the DE group into MGD and non‐MGD patients, found that no statistically significant differences between the two groups. 67 Pseudomonas, Bacillus, Acinetobacter and Corynebacterium were the most represented, although Bacilli showed a higher relative abundance in the MGD group and could be considered typical pathogens of MGD. Watters and colleagues studied patients with several degrees of MGD, among which CL wearers were included. Meibum expression did not modify the bacterial profile. CoNS were the most prevalent organisms isolated, present in two thirds of the population studied, although their presence was not correlated to the severity of MGD. CL wearers showed an increased presence of P. acnes that was correlated to MGD severity. No differences in microbiota were observed related to the severity of anterior blepharitis or CL wear. Dong and coworkers, using 16 S rDNA sequencing, investigated the microbiome of 47 Chinese MGD patients compared with a control group of 42 sex‐ and age‐matched subjects without MGD. They found significant differences at the phyla level, with a significantly higher abundance of Firmicutes (31.7% vs. 19.7%) and Proteobacteria (27.5% vs. 14.7%), and a lower abundance of Actinobacteria (34.2% vs. 57%) in MGD vs control patients. At the genus level, the numbers of Staphylococcus (20.7% vs. 7.9%) and Sphingomonas (5.7% vs. 0.8%) were significantly higher in patients with MGD vs controls, while the numbers of Corynebacterium (20.2% vs. 46.4%) were significantly lower. The meiboscores showed a significant direct correlation with the abundance of Staphylococcus in MGD patients. They concluded that patients with MGD can have bacterial microbiota alterations in the conjunctival sac, with a potential role of Staphylococcus, Corynebacterium and Sphingomonas sp. in MGD pathophysiology. In a previous study carried out on a small group of patients with blepharitis, Lee and coworkers demonstrated that blepharitis might be associated with a change in microbial composition, namely, greater quantities of Streptophyta, Corynebacterium and Enhydrobacter species. It was suggested that cytotoxicity and inflammatory components, triggered by bacterial growth, may contribute to the pathological process of MGD. Zheng et al confirmed the changes of ocular surface flora in MGD patients showing a wide bacterial profile and positive aerobic and anaerobic culture, significantly higher in both meibomian secretion and conjunctiva of MGD patients than in controls. The ocular surface inflammatory condition occurring in MGD and blepharitis could be mediated by the induced expression of acidic mammalian chitinase (AMCase) that is considered an immune response activator and is over expressed in MGD. It can be hypothesized that changes in ocular surface microbial flora can mediate AMCase upregulation.

Analysis of Meibomian Glands in Juvenile Systemic Lupus Erythematosus Patients without Dry Eye Symptoms and Signs.

To evaluate meibomian gland loss and its possible association with disease duration and activity in Juvenile Systemic Lupus Erythematosus (JSLE) patients' without dry eye symptoms or signs. Prospective clinical study. Ten eyes of 10 JSLE patients were evaluated using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and 14 eyes of 14 healthy controls were also enrolled. Ocular Surface Disease Index (OSDI) questionnaire and Schirmer I test were performed. Lid margin score, meibum quality and expressibility scores were evaluated. Noninvasive first breakup time (NIF-BUT) and noninvasive average breakup time (NIAvg-BUT), meibomian gland dropout area (MGDA) and meibography scores were evaluated using non-contact meibography (Sirius; CSO). There was no significant difference between the JSLE patients and the healthy controls in the OSDI, NIF-BUT, NIAvg-BUT and Schirmer I tests. Also lid margin score, meibum quality and expressibility scores were not significantly different between the groups. However, JSLE patients had increased upper and lower lid MGDA and increased upper lid, lower lid and total meibography scores compared to the healthy subjects. Furthermore, the duration of JSLE showed a high positive correlation with upper and lower lid MGDA and meibography scores. Meibomian gland loss could be observed in JSLE patients with no clinical signs and symptoms of dry eye. Considering the longer life expectancy of children, the positive correlation of disease duration with the meibomian gland reveals the importance of routine eye examinations from the diagnosis of the disease.

Different Number of Sessions of Intense Pulsed Light and Meibomian Gland Expression Combination Therapy for Meibomian Gland Dysfunction.

To evaluate the effect of the intense pulsed light (IPL) and meibomian gland (MG) expression (MGX) combination therapy according to the total numbers of sessions in the meibomian gland dysfunction (MGD). Ninety patients with MGD were included. Patients had maximal five sessions of IPL (Aqua Cel, Jeisys Medical) and MGX combination therapy at 2-week intervals. The ocular surface disease index (OSDI) questionnaire score, MG profile grades, tear matrix metalloproteinase-9 (MMP-9), tear break-up time (BUT), tear osmolarity, tear secretion, and corneal erosions were evaluated. The number of patients who had a total of one to five sessions (1S to 5S) was 10, 25, 17, 20, and 18, respectively. The time-serial decrease of OSDI scores was significant in patients who had three or more sessions (3S, p = 0.002; 4S, p < 0.001; 5S, p < 0.001). The MG expressibility grade decreased with two or more sessions (2S-5S, p < 0.001), but the meibum quality significantly improved with all sessions (1S, p = 0.012; 2S, p = 0.024; 3S, p = 0.015; 4S, p < 0.001; 5S, p < 0.001). Although tear BUT increased even in patients with one session (1S, p = 0.040; 3S, p = 0.005; 4S, p = 0.006; 5S, p = 0.021), tear MMP-9, osmolarity, Schirmer I, and corneal erosions were not improved in every number of sessions. The female sex was the sole contributor to the final symptomatic improvement (p = 0.042), and the MGD stages were not related to the final OSDI decrease. The OSDI score, MGD grades, and BUT were improved after the IPL and MGX combination therapy in MGD patients. Unlike MGD grades and tear film instability might be improved just after a few sessions, the overall subjective relief was accomplished in three or more sessions.

The correlation between Demodex infestation and meibomian gland dysfunction at different ages

BackgroundThis study aimed to explore the associations between Demodex infestation and the ocular surface characteristics of meibomian gland dysfunction (MGD) in different age groups, to further understand the effect of Demodex on MGD.MethodsA total of 202 consecutive MGD patients aged 18 to 70 years were randomly recruited. All patients were divided into two groups based on their age: young patients (18–40 years) and elderly patients (41–70 years). The main observations were the different relationship between Demodex infestation and ocular surface and meibomian gland (MG) parameters in two age groups. We also compared ocular surface and MG parameters between the young and the elderly groups. Demodex infestation was diagnosed based on expert consensus in China.ResultsOur results indicated significant differences among young Demodex-positive, suspicious-positive, and negative patients in MG dropout (P = 0.000), plugging of MG orifices (P = 0.000), lid margin abnormality (P = 0.000), and meibum quality (P = 0.000). In elderly patients, there were significant differences among the Demodex-positive, suspicious-positive, and negative groups in terms of ocular surface disease index (OSDI) (P = 0.037), fluorescein tear film break-up time (FBUT) (P = 0.002), corneal fluorescein staining (CFS) (P = 0.036), MG dropout (P = 0.000), plugging of MG orifices (P = 0.008), lid margin abnormality (P = 0.000), and MG expression (P = 0.037). The mean number of mites in elderly Demodex-positive patients (10.64 ± 7.50) was greater than that of in young patients (7.60 ± 4.71) (P = 0.014). MG dropout (P = 0.000), plugging of MG orifices (P = 0.006), lid margin abnormality (P = 0.000), MG expression(P = 0.001), and meibum quality (P = 0.032) were more severe in elderly Demodex-positive patients. Additionally, FBUT (P = 0.005) was lower and tear film lipid layer thickness (LLT) (P = 0.001) was higher in the elderly.ConclusionThe effect of Demodex infestation on the ocular surface and MG parameters of MGD was different in patients of different ages. It is necessary to pay more attention to the diagnosis and treatment of Demodex infestation in MGD.

Dry eye-related quality of life among type 2 diabetes patients: a hospital-based cross-sectional study

ABSTRACT Background To investigate the impact of dry eye syndrome (DES) on dry eye-related quality of life (QoL) in patients with type 2 diabetes. Research design and methods Evaluation of DES included assessment of meibomian gland function, tear breakup time (TBUT), Schirmer test, fluorescein ocular surface staining, and Ocular Surface Disease Index (OSDI) scores. DES diagnosis was based on OSDI score ≥13, TBUT < 10s, and fluorescein staining. Results After adjusting for age, duration of diabetes, drug usage, and comorbidities, severity of DES symptomatology and signs resulted in poorer QoL of patients when comparing cases and controls. TBUT, meibum quality, and ocular surface staining were the objective clinical tests that significantly correlated with QoL. Poor QoL was also associated with the presence of eyelash and eyelid anomalies (eyelash: aOR = 2.58, CI = 1.49–4.47, p = 0.001; eyelids: aOR = 1.66, CI = 1.01–2.71, p = 0.04). Patients who had been previously diagnosed and treated for DES registered improved QoL measures. Conclusions Symptoms or clinical signs of DES resulted in poorer QoL in a clinical sample of type 2 diabetes patients, stressing the need for clinicians to evaluate such signs and symptoms in order to improve QoL.

Is contact lens discomfort related to meibomian gland morphology?

PurposeTo examine the relationship between contact lens (CL) discomfort and meibomian gland (MG) morphology assessed by a semi-objective software in subjects without an alteration of MG function (meibum quality and expressibility). MethodsNineteen symptomatic (CLDEQ-8 ≥ 12) CL wearers, 19 asymptomatic (CLDEQ-8 < 12) wearers, and 22 non-wearers were recruited. Upper and lower eyelid meibography images were taken and the following parameters were analysed using a semi-objective software in the central 2/3 of each eyelid: number of MG, number of partial MG, percentage of MG loss and percentage of tortuosity. One-way ANOVA or Kruskal-Wallis H test were used for comparisons among groups. The relationships between CLDEQ-8 and MG morphology parameters were analysed using the Spearman correlation coefficient and multivariable linear regression models. ResultsNo significant differences were found among groups in the MG morphology of the upper or lower eyelids. In all CL wearers, a significant correlation with CLDEQ-8 was found in the upper eyelid for the number of MG (rho = 0.47, p = 0.003). In symptomatic wearers, significant correlations with CLDEQ-8 were found in the lower eyelid for the number of partial MG (rho = 0.49, p = 0.03) and the percentage of partial MG (rho = 0.61, p = 0.005). In all CL wearers, multivariable models were fitted to explain CLDEQ-8 score including the number of MG, the number of partial MG and the percentage of MG loss from the lower eyelid (R2 = 0.19; p = 0.007), and the number of MG from the upper eyelid (R2 = 0.19; p = 0.001). In symptomatic wearers, a model was fitted including the percentage of MG loss from the lower eyelid (R2 = 0.30; p = 0.016). ConclusionsAlterations of MG morphology, without clinically apparent alteration of MG function, can be involved in causing CL discomfort and influence the degree of symptoms. The differences in findings between eyelids indicate the need to monitor both eyelids, especially the lower one, in CL wearers.

The Efficacy and Safety of New-Generation Intense Pulsed Light in the Treatment of Meibomian Gland Dysfunction-Related Dry Eye: A Multicenter, Randomized, Patients-Blind, Parallel-Control, Non-Inferiority Clinical Trial.

IntroductionThis study aimed to evaluate the efficacy and safety of a new-generation intense pulsed light (IPL) device in improving the symptoms and signs of meibomian gland dysfunction (MGD)-related dry eye, and compare it with a traditional IPL device.MethodsThis multicenter randomized controlled trial enrolled 132 patients with MGD-related dry eye from two centers. Patients were randomly assigned into the new-generation IPL (Eyesis) group or traditional IPL (E-Eye) group, and then blinded to receive treatment on days 0 and 7. Ocular Surface Disease Index (OSDI), tear meniscus height (TMH), tear breakup time (TBUT), corneal fluorescein staining (CFS), Schirmer test, and meibomian gland signs were evaluated on days 0, 7, and 14. The primary outcome was defined as the effective rate of treating MGD at day 14. Any adverse events were recorded for safety assessment. Intergroup comparisons and non-inferiority analysis were performed. p values less than 0.05 were considered statistically significant.ResultsBasic information showed no significant difference between treatment groups. The intergroup difference of the effective rate was − 1.7% in the left eye and 1.6% in right eye, verifying the non-inferiority of the Eyesis device (p = 0.927). Significant improvements in OSDI, TBUT, Schirmer test, TMH, CFS, and meibomian gland signs were observed in Eyesis group on days 7 and 14 (all p < 0.05). Compared to the E-Eye group, the Eyesis group achieved more significant improvements in OSDI, TBUT, Schirmer test, TMH, and meibum quality (all p < 0.05). There was no significant difference in the incidences of adverse events between groups (p = 1.000).ConclusionsThe new-generation IPL was effective and safe in relieving the symptoms and signs of MGD-related dry eye, exhibiting a non-inferior effective rate compared to the traditional IPL. Additionally, Eyesis showed more clinical benefits over E-Eye in alleviating symptoms, increasing tear film stability and improving meibomian gland function.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40123-022-00556-1.

Investigation of Prognostic Factors for Intense Pulsed Light Treatment with a Vascular Filter in Patients with Moderate or Severe Meibomian Gland Dysfunction.

We aimed to investigate the prognostic factors for, and treatment efficacy of, intense pulsed light (IPL) treatment with a vascular filter in patients with moderate or severe meibomian gland dysfunction (MGD). In this retrospective observational study, 58 moderate or severe MGD patients who underwent IPL treatment with a vascular filter were enrolled. IPL treatment was administered to the upper and lower eyelids four times at two-week intervals. At baseline, and four weeks after IPL, we evaluated the matrix metalloproteinase (MMP)-9 expression levels, tear break-up times (TBUT), ocular surface staining scores, lid margin telangiectasias, and meibomian gland characteristics. The subjective symptoms and adverse effects were reviewed and recorded. Regression analyses were performed to explore the prognostic factors affecting clinical outcomes. IPL treatment using a vascular filter led to improvements in the TBUT, ocular surface staining score, meibomian gland grade, meibum quality and consistency, lid margin telangiectasia, and symptom score (all p < 0.001). Furthermore, the positivity rate (90.2% to 70.6%, p = 0.013) and expression levels (1.92 ± 1.18 to 1.24 ± 1.18, p < 0.001) of tear MMP-9 improved after the IPL treatment. In multivariate logistic regression analysis, a young age (odds ratio = 0.867, p = 0.007) and a toothpaste-like consistency in the upper lid (odds ratio = 8.449, p = 0.046) were associated with improvements in the meibomian gland grade. No adverse effects were detected. IPL with a vascular filter is a safe and effective treatment for moderate and severe MGD. Age and the meibum consistency in the upper lid are important prognostic factors.

Skin temperature change in patients with meibomian gland dysfunction following intense pulsed light treatment.

PurposeWe investigated the change in skin temperature of treated areas during intense pulsed light (IPL) treatment in patients who have meibomian gland dysfunction (MGD) to determine whether there is superficial telangiectatic blood vessel ablation.MethodsThe medical records of 90 patients (90 eyes) with MGD who underwent IPL treatment were reviewed. The patients had undergone IPL treatment four times every 4 weeks. Ocular Surface Disease Index (OSDI) scores, dry eye (DE), and MGD parameters were obtained before the first and after the fourth IPL treatments. The skin temperatures of the upper and lower lids were measured before every IPL treatment.ResultsThe skin temperatures of the lower lids were 31.89 ± 0.72°C at the first IPL (IPL#1), 30.89 ± 0.63°C at the second IPL (IPL#2), 30.14 ± 0.95°C at the third IPL (IPL#3), and 29.74 ± 0.87°C at the fourth IPL (IPL#4) treatments. The skin temperatures of upper lids were 32.01 ± 0.69°C at IPL#1, 31.13 ± 0.75°C at IPL#2, 30.34 ± 1.07°C at IPL#3, and 29.91 ± 0.76°C at IPL#4. The skin temperature of the upper and lower lids significantly decreased with every IPL treatment. Schirmer 1 test (ST) result was 12.97 ± 10.22 mm before IPL#1 and 14.45 ± 9.99 mm after IPL#4. Tear break-up time (TBUT) was 3.15 ± 1.38 s before IPL#1 and 5.53 ± 2.34 s after IPL#4. Corneal staining scores (CFS) was 1.61 ± 3.09 before IPL#1 and 0.50 ± 0.78 after IPL#4. Lipid layer thickness (LLT) was 71.88 ± 26.34 nm before IPL#1 and 68.38 ± 24.16 nm after IPL#4. Lid margin abnormality score (LAS) was 1.96 ± 0.62 before IPL#1 and 0.86 ± 0.67 after IPL#4. Meibum expressibility (ME) was 1.67 ± 0.87 before IPL#1 and 1.03 ± 1.67 after IPL#4. Meibum quality (MQ) was 18.18 ± 6.34 before IPL#1 and 10.16 ± 5.48 after IPL#4. OSDI was 35.38 ± 19.97 before IPL#1 and 15.48 ± 34.32 after IPL#4. OSDI scores, DE, and MGD parameters significantly improved after the fourth IPL treatment but not ST and LLT.ConclusionOur study showed that the occurrence of superficial telangiectatic vessels were indirectly reduced by the decrease in skin temperature accompanying IPL treatments in patients with MGD.

Ocular surface disease index questionnaire as a sensitive test for primary screening of chronic ocular graft-versus-host disease.

BackgroundAfter allogeneic hematopoietic stem cell transplantation (allo-HSCT), patients are followed up by transplant clinicians. Finding an effective primary screening method that transplant clinicians or patients can master is essential in the early referral of suspected chronic ocular graft-versus-host disease (coGVHD) to an ophthalmologist. This study investigated if the ocular surface disease index (OSDI) questionnaire could be used for coGVHD primary screening.MethodsThis case-controlled, cross-sectional study enrolled 161 allo-HSCT patients. All participants completed an OSDI questionnaire and underwent a silt-lamp examination. Bulbar conjunctival injection (BCI) was assessed using torchlight, while tear volume was measured via the Schirmer test (ST). The receiver operating characteristic curve was used to evaluate the sensitivity, specificity, and cutoff values of OSDI, ST, and BCI grading. Performance comparisons of the 3 tests applied in isolation, parallel, and series were made.ResultsThere were 84 patients with and 77 patients without coGVHD. Compared to those without coGVHD, patients with coGVHD had significantly higher median values of OSDI, corneal fluorescein staining, conjunctival injection, conjunctival fibrosis, and meibum quality, but lower ST scores (All P values <0.001). The cutoff values for OSDI, ST, and BCI grade in the diagnosis of coGVHD were 19.4 points, 7 mm, and grade 0, respectively. The sensitivity and specificity of the tests based on the cutoff values were, respectively, 89.3% and 89.6% for OSDI, 91.7% and 59.7% for ST, and 78.6% and 70.1% for BCI. The area under the curve (AUC) value of OSDI was significantly higher than that of ST (0.931 vs. 0.826; P=0.010) and BCI grade (0.931 vs. 0.781; P<0.001). The AUC values of the combinations were lower than that of OSDI alone.ConclusionsThe OSDI questionnaire can be used as a simple screening test for coGVHD as demonstrated by its high sensitivity and specificity in the transplant clinic and patients’ self-monitoring. An OSDI greater than 19.4 could be considered an ophthalmology referral criterion.

Uneven Index: A Digital Biomarker to Prompt Demodex Blepharitis Based on Deep Learning.

Purpose: To evaluate ocular surface manifestations and morphological changes in meibomian glands (MGs) based on artificial intelligence (AI) analysis in patients with Demodex blepharitis. Methods: In this retrospective study, 115 subjects were enrolled, including 64 subjects with Demodex blepharitis and 51 subjects without Demodex blepharitis as control group. Morphological indexes were evaluated for height, width, tortuosity, MG density, total variation, and the three types of corrected total variation as Uneven indexes. Results: There were no statistically significant differences in all MGs’ average tortuosity and width between the two groups. The average height of all MGs and MG density were significantly lower in the Demodex blepharitis group than control group. The total variation and two types of Uneven indexes were significantly higher in the Demodex blepharitis group than in the control group. Especially the Uneven Index of total variation/MG density had an AUC of 0.822. And the sensitivity and specificity were 59.4% and 92.2%, respectively, at a cut-off value of 3971.667. In addition, Demodex blepharitis was associated with significantly lower meibum quality and expressibility, severe atrophy of MGs, a higher ocular surface disease index (OSDI), and more instability of the tear film. Conclusion: Demodex mites are strongly associated with morphological changes in the MGs and may cause uneven gland atrophy. Therefore, the novel characteristic parameter, the Uneven index, may serve as a digital biomarker to evaluate uneven atrophy of MGs and prompt Demodex blepharitis.

Relationship between meibomian gland loss in infrared meibography and meibum quality in dry eye patients

BackgroundIn the present study, we evaluated the correlation between meibomian gland dropout and meibum quality in the same central 8 meibomian glands of the eyelid.MethodsNinety-nine eyes of 91 patients with dry eye were included in the study. Dropout of the 8 central meibomian glands of the eyelids was graded as 0, 1, 2, or 3, according to the dropout area. The meibum quality was graded as follows: grade 0, no secretion; 1, inspissated/toothpaste consistency; 2, cloudy liquid secretion; and 3, clear liquid secretion. For 68 eyes of 68 patients, correlation analysis between dropout and meibum quality was performed. To precisely analyze the direct correlation between meibomian gland dropout in meibography and meibum quality, we evaluated 31 eyes of 23 patients with focal dropout in meibography.ResultsThe median (interquartile range) meiboscore was 1.0 (2.0) in the upper eyelids and 0.0 (1.0) in the lower eyelids. The median (interquartile range) meibum quality grade was 3.0 (1.0) in the upper eyelids and 1.0 (1.0) in the lower eyelids. No significant correlation between the meiboscore and meibum quality grade was detected in the upper (p =0.746) or lower (p =0.551) eyelids. Analysis of the direct correlation between meibomian gland dropout in meibography and meibum quality in patients with focal dropout (loss of 1 or 2 adjacent meibomian glands), however, indicated that meibomian glands with dropout secreted little to no meibum.ConclusionsOverall analysis revealed no relationship between meibomian gland dropout and meibum quality, but more detailed investigation of each meibomian gland alone revealed that meibomian glands with dropout secrete little to no meibum.

Effect of Thermoelectric Warming Therapy for the Treatment of Meibomian Gland Dysfunction

To evaluate the efficacy of thermoelectric warming therapy (MiBoFlo) in improving patient symptoms with standardized questionnaires and objective signs of meibomian gland dysfunction (MGD), which is an important underlying treatable factor in dry eye disease (DED), such as ocular surface staining, tear quality, and meibomian gland morphology. Multivariate analysis to identify predictors for the improvement in Ocular Surface Disease Index (OSDI) was also performed. Retrospective before-and-after study. A total of 203 eyes of 102 patients with DED were treated with MiBoFlo at the dry eye center. The OSDI and Standard Patient Evaluation of Eye Dryness (SPEED) questionnaires, best-corrected visual acuity, tear osmolarity, tear film breakup time (TBUT), corneal and conjunctival staining, meibography, number of glands expressing liquid, and quality of the improved meibum were assessed before and 6 months after MiBoFlo. Exclusion criteria included active ocular inflammation. Dry eye symptoms improved in the population, with both SPEED and OSDI lowering of dry eye symptoms by approximately 35% (P < .001) at month 6. Significant improvements in lissamine green conjunctival staining, corneal fluorescein staining, TBUT, osmolarity, and secreting meibomian glands and meibum quality were also seen. Improvement was seen across all domains of the questionnaires and across all baseline parameters. Eyes with blepharitis and autoimmune disease improved less than average. No complications or adverse events occurred. MiBoFlo treatments produced clinical and statistically significant improvements in the signs and symptoms of MGD, irrespective of underlying ocular conditions. This improvement was sustained for the 6-month period of observation after initiating the treatment.

Intense pulsed light improves signs and symptoms of dry eye disease due to meibomian gland dysfunction: A randomized controlled study.

PurposeTo compare the safety and efficacy of intense pulsed light (IPL) followed by meibomian gland expression (MGX), against monotherapy of MGX.MethodsPatients with moderate to severe meibomian gland dysfunction (MGD) were 1:1 randomized to 4 sessions of intense pulse light + MGX at 2-week intervals, or 4 sessions of Sham + MGX at 2-week intervals. Both patients and examiners were blinded to the allocation. Outcome measures, evaluated at the baseline (BL) and at a follow-up (FU) conducted 4 weeks after the last IPL session, included fluorescein tear breakup time (TBUT) as the primary outcome measure, OSDI (Ocular Surface Disease Index) questionnaire, Eye Dryness Score (EDS, a visual analog scale (VAS)-based questionnaire), Meibomian gland score (MGS, a score of meibum expressibility and quality in 15 glands on the lower eyelid), daily use of artificial tears, and daily use of warm compresses. In addition, during each treatment session, the number of expressible glands was counted in both eyelids, the predominant quality of meibum was estimated in both eyelids, and the level of pain/discomfort due to MGX and IPL was recorded.ResultsTBUT increased from 3.8±0.2 (μ±standard error of mean (SEM)) to 4.5±0.3 seconds in the control arm, and from 4.0±0.2 to 6.0±0.3 in the study arm. The difference between arms was statistically significant (P < .01). Other signs/symptoms which improved in both arms but were greater in the study arm included MGS (P < .001), EDS (P < .01), the number of expressible glands in the lower eyelids (P < .0001) and upper eyelid (P < .0001), the predominant meibum quality in the lower eyelid (P < .0001) and upper eyelid (P < .0001), and the level of pain due to MGX (P < .0001). Outcome measures which improved in both arms with no significant differences between the two were OSDI (P = .9984), and the daily use of artificial tears (P = .8216). Meibography, daily use of warm compresses, and severity of skin rosacea did not show statistically significant changes in either arm. No serious adverse events were observed. There was a slight tendency for more adverse events in the control group (P = 0.06).ConclusionsThe results of this study suggest that, in patients with moderate to severe symptoms, combination therapy of intense pulse light (IPL) and meibomian gland expression (MGX) could be a safe and useful approach for improving signs of dry eye disease (DED) due to meibomian gland dysfunction (MGD). Future studies are needed to elucidate if and how such improvements can be generalized to different severity levels of MGD.

Relationships between ocular surface sphingomyelinases, Meibum and Tear Sphingolipids, and clinical parameters of meibomian gland dysfunction

PurposeSphingolipids (SPL) are a class of lipid molecules that play important functional and structural roles in our body and are a component of meibum. Sphingomyelinases (SMases) are key enzymes in sphingolipid metabolism that hydrolyze sphingomyelin (SM) and generate ceramide (Cer). The purpose of this study was to examine relationships between ocular surface SMases, SPL composition, and parameters of Meibomian gland dysfunction (MGD). MethodsIndividuals were grouped by meibum quality (n = 25 with poor-quality, MGD, and n = 25 with good-quality, control). Meibum and tears were analyzed with LC-MS to quantify SPL classes: Cer, Hexosyl-Ceramide (Hex-Cer), SM, Sphingosine (Sph), and sphingosine 1-phosphate (S1P). SMase activity in tears were quantified using a commercially available ‘SMase assay’. Statistical analysis included multiple linear regression analyses to assess the impact of SMase activity on lipid composition, as well as ocular surface symptoms and signs of MGD. ResultsDemographic characteristics were similar between the two groups. nSMase and aSMase levels were lower in the poor vs good quality group. aSMase activity in tears negatively correlated with SM in meibum and tears and positively with Sph in meibum and S1P in tears. Lower SMase activity were associated with signs of MGD, most notably Meibomian gland dropout. ConclusionThis study suggests that individuals with MGD have reduced enzymatic activity of SMases in tears. Specifically, individuals with poor vs good meibum quality were noted to have alterations in SMase activity and SPL composition of meibum and tears which may reflect deviations from normal lipid metabolism in individuals with MGD.

Bevacizumab Eye Drops Vs. Intra-meibomian Gland Injection of Bevacizumab for Meibomian Gland Dysfunction-Associated Posterior Blepharitis.

AimsThis study aimed to evaluate the efficacy and safety of bevacizumab eye drops compared with those of an intra-meibomian gland (MG) injection of bevacizumab when performed in conjunction with standard lid hygiene in patients with meibomian gland dysfunction (MGD)-associated posterior blepharitis.MethodsThis prospective, open-label, observer-blinded randomized controlled trial included 60 eyes of 30 patients with MGD-associated posterior blepharitis who exhibited lid margin telangiectasia, treated at the Chula Refractive Surgery Center of King Chulalongkorn Memorial Hospital. Patients were randomized to receive lid hygiene plus 0.05% bevacizumab eye drops or a single intra-MG injection of 2.5% bevacizumab. All patients were instructed to perform routine lid hygiene care as demonstrated in an instructional video. Primary outcomes included telangiectasia grading and the lid margin neovascularized area (LMNA). Secondary outcomes included the Ocular Surface Disease Index (OSDI) score, corneal staining, meibum quality, meiboscore, conjunctival redness, fluorescein break-up time (FBUT), lipid layer thickness, treatment compliance, and adverse events. All parameters were evaluated before and 3 months after treatment.ResultsAfter treatment, there were no significant differences in telangiectasia grade and LMNA between groups (mean difference, −0.14, 95% CI −0.42 to 0.15, p = 0.338, −0.1, 95% CI −1.1 to 0.8, p = 0.761, respectively); however, the injection group exhibited significant improvements in both telangiectasia grade and LMNA, while, in the eye drop group, only telangiectasia grade showed a significant improvement relative to baseline. The injection group also exhibited significant improvements in corneal staining (mean difference, −0.78, 95% CI −1.29 to −0.27, p = 0.003), meiboscores (mean difference, −0.37, 95% CI −0.52 to −0.21, p <0.001), and FBUT (mean difference, 1.25, 95% CI 0.21–2.29, p = 0.019) compared to the eye drop group. OSDI scores, corneal staining, meibum quality, meiboscores, and conjunctival redness significantly improved relative to baseline in both groups. No local and systemic adverse event was observed at month 3 in both groups.ConclusionWhen performed with regular lid hygiene, intra-MG injection and topical application of bevacizumab are safe and effective for improving lid margin telangiectasia and the signs and symptoms of MGD-associated posterior blepharitis. This therapy may represent an alternative or adjunctive treatment for patients with MGD-associated posterior blepharitis.

Compliance with Lid Hygiene in Patients with Meibomian Gland Dysfunction.

PurposeTo evaluate the level and predictor of compliance with lid hygiene of the patients with meibomian gland dysfunction (MGD) by a specially designed and validated questionnaire.Patients and MethodsA cross-sectional, descriptive study was conducted among patients with symptomatic meibomian gland dysfunction visiting at Ramathibodi Hospital from April 2019 to December 2020. Dry eye symptom, fluorescein tear breakup time (TBUT), ocular surface staining, lid morphology, meibum quality, and meibum expressibility were evaluated. All patients were instructed to perform lid hygiene two times daily. Eight weeks after receiving the instruction, the patients were asked to complete a newly developed seven-item questionnaire to assess compliance. The associated factors limiting treatment adherence were evaluated. Proper statistical analyses were used to determine the relationships between compliance and non-compliance and a group of relevant baseline variables. P < 0.05 was considered to be statistically significant.ResultsA total of 77 patients were recruited into the study. Sixty-three patients (81.8%) were female. The mean age was 66.71 ± 8.17 years old (42–87 years). Good compliance with lid hygiene was reported by 42 patients (54.6%). Patient demographic factors or the number of concurrent systemic or ophthalmic drugs were not significantly different between the compliance and non-compliance groups. Some clinical signs, including the higher scores of meibomian gland expressibility and moderate to severe ocular surface staining, were significantly positively associated with lid hygiene compliance (χ2 = 10.13, P = 0.001 and χ2 = 10.48, P = 0.001, respectively). A lack of time was the most notable reason for non-compliance.ConclusionApproximately half of the patients with symptomatic MGD had good compliance with lid hygiene by the specific questionnaire. Appropriate patient education and optimization methods of lid hygiene may promote patient compliance.

Structural and Functional Evaluation of Meibomian Glands and Its Correlation With Dry Eye Parameters in Stevens-Johnson Syndrome

To evaluate the structural and functional changes of the meibomian gland and correlate with subjective and other objective dry eye parameters in Stevens-Johnson syndrome (SJS) patients. Prospective cross-sectional study. This study recruited 60 patients (120 eyes) with SJS and chronic ocular sequelae. All patients underwent evaluation with a Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire, tear osmolarity, Keratograph 5M, LipiView, Schirmer's 1, corneal staining, Meibum Expression score (MES, 0-3), and Meibum Quality score (MQS, 0-3). The meibomian gland dropout area (meiboscore) was calculated for both lids and graded on a 4-point scale from 0 to 3. The mean age of patients (n=60) was 31.08 ± 12.94 years; 25 were males. The commonest cause for SJS, in 51 patients (85%), was drug reaction. The mean tear osmolarity, lipid layer thickness (LLT), Schirmer's test-1, and tear break-up time was 322.70 ± 17.82 mOsm/L, 53.07 ± 27.0 nm, 6.62 ± 5.74 mm, 3.38 ± 1.90 seconds, respectively. Out of 240 eyelids (both upper and lower), 160 (65%) eyelids revealed severe meibomian gland loss. The mean upper and lower lid gland loss was 77.36 ± 28.82% and 76.65 ± 29.33%, respectively, Seventy-four eyelids (61%) had no expressible glands. Meiboscore showed positive correlation with SPEED (P < .001), corneal staining scores (P < .001), MES (P < .001), and MQS (P < .001). The LLT negatively correlation with SPEED (P < .01), meiboscore (P < .001), MES (P < .01), and MQS (P < .001). Significant alterations in anatomical and functional aspects of the meibomian gland are seen in SJS. The high meiboscore, MES, MQS, and decreased LLT contributed to the worsening dry eye state, as seen by their correlation with other dry eye parameters. This study highlights the need to evaluate meibomian gland structure and function in patients with chronic ocular sequelae of SJS.