Analysis of tear inflammatory molecules and clinical correlations in evaporative dry eye disease caused by meibomian gland dysfunction

Abstract Purpose To compare the levels of inflammatory molecules in tear samples between patients with meibomian gland dysfunction (MGD)-related evaporative dry eye (EDE) and healthy subjects and to analyze the correlations between the levels of tear inflammatory molecules and ocular surface parameters. Methods A total of 30 MGD-related EDE patients (48 eyes) and ten healthy volunteers (15 eyes) were enrolled. Dry eye-related examinations and questionnaires were obtained from all participants. The levels of nine inflammatory molecules were determined through multiplex bead analysis. Results Inflammatory molecules including ICAM-1, IFN-γ, CXCL8/IL-8, IL-6, TNF-α and IL-12p70 were detected in 100% of the patients, while IL-1α, IL-1β and IL-10 were detected in 56.25%, 13.60% and 45.83% of the patients, respectively. Moreover, ICAM-1, IL-8, IL-6, TNF-α, IL-12p70 and IFN-γ were detected in 86.67–100% of the healthy subjects, and the detection rates of IL-10, IL-1α and IL-1β were below 50%. The levels of IL-8, IL-6, IFN-γ and ICAM-1 were significantly higher in the patient group compared with the control group. In addition, IL-8 and IL-6 were negatively correlated with Schirmer I test. Besides, IFN-γ was negatively correlated with tear film breakup time. Furthermore, ICAM-1 and IL-6 were positively correlated with meibography score. Conclusions Collectively, patients with MGD-related EDE had higher levels of inflammatory molecules in their tears, and some molecules were correlated with ocular surface parameters. These findings suggested that inflammation played an important role in MGD-related EDE, and several inflammatory molecules could be used in the diagnosis and the treatment of MGD-related EDE.

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Effects of intense pulsed light treatment on tear cytokines and clinical outcomes in meibomian gland dysfunction

PLoS ONE ◽

10.1371/journal.pone.0256533 ◽

2021 ◽

Vol 16 (8) ◽

pp. e0256533

Author(s):

Qian Li ◽

Junxiu Liu ◽

Cheng Liu ◽

Junfeng Piao ◽

Wei Yang ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Ocular Surface ◽

Signs And Symptoms ◽

Meibomian Gland ◽

Intense Pulsed Light ◽

Tissue Inhibitor Of Metalloproteinase ◽

Meibomian Gland Dysfunction ◽

Pulsed Light ◽

Tnf Α ◽

Ifn Γ

Meibomian gland dysfunction (MGD) has become a prevalent ocular surface disorder. Its pathogenesis is regarded as a self-perpetuating inflammatory vicious circle. Intense Pulsed Light (IPL) treatment was recently applied to improve the meibomian gland function and reduce symptoms of MGD. However, studies investigating the change of specific inflammatory cytokines during IPL treatment remained sparse. To further figure out how IPL treatment modulates the inflammatory cytokines in tears of MGD, we therefore performed a cross-sectional study and enrolled 32 patients from March 2019 to December 2020. The patients received 3 sessions of IPL treatment (10 to 16 J/cm2) at 4-week interval. The signs and symptoms of MGD were evaluated by ocular surface disease index (OSDI), tear film breakup time (TBUT), and meibomian gland yield secretion score (MGYSS). The clinical evaluators and tear samples were analyzed at baseline and at each IPL treatment session. Concentrations of (chemokine ligand) CXCL1, (C-C motif chemokine) CCL11, (tumor necrosis factor) TNF-α, (interferon) IFN-γ, (interleukin) IL-2, IL-6 and (tissue inhibitor of metalloproteinase) TIMP-1were measured by Quantibody Human Dry Eye Disease Array1. OSDI significantly decreased after IPL treatment compared with baseline. TBUT and MGYSS increased consecutively during treatment. CXCL1, CCL11, TNF-α, IFN-γ, IL-2, IL-6 presented significantly decrease and TIMP-1 showed significantly increase from the pretreatment baseline. The changed concentrations of TNF-α, IFN-γ, IL-2, TIMP-1 correlated with TBUT, the changed values of CXCL1, TNF-α, IFN-γ, CCL11, IL-2, IL-6, TIMP-1 correlated with MGYSS, and the changed concentrations of CXCL1, IFN-γ, CCL11, IL-2, IL-6 correlated with TIMP-1. The data supported IPL treatment could significantly relieve both signs and symptoms of MGD. The therapeutic effect of IPL treatment may originate from regulation of inflammatory cytokines including CXCL1, TNF-α, IFN-γ, CCL11, IL-2, IL-6, and TIMP-1.

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The prevalence of meibomian gland dysfunction, tear film and ocular surface parameters in an Austrian dry eye clinic population

Acta Ophthalmologica ◽

10.1111/aos.13732 ◽

2018 ◽

Vol 96 (6) ◽

Cited By ~ 9

Author(s):

Dieter Franz Rabensteiner ◽

Haleh Aminfar ◽

Ingrid Boldin ◽

Gerold Schwantzer ◽

Jutta Horwath‐Winter

Keyword(s):

Dry Eye ◽

Ocular Surface ◽

Tear Film ◽

Meibomian Gland ◽

Meibomian Gland Dysfunction ◽

Surface Parameters ◽

Clinic Population ◽

Eye Clinic

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A novel noninvasive ocular surface analyzer for the assessment of dry eye with Meibomian gland dysfunction

Experimental and Therapeutic Medicine ◽

10.3892/etm.2017.4364 ◽

2017 ◽

Vol 13 (6) ◽

pp. 2983-2988 ◽

Cited By ~ 9

Author(s):

Yuanyuan Qi ◽

Chen Zhang ◽

Shaozhen Zhao ◽

Yue Huang ◽

Ruibo Yang

Keyword(s):

Dry Eye ◽

Ocular Surface ◽

Meibomian Gland ◽

Meibomian Gland Dysfunction

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The Deterioration of Meibomian Gland Over the Duration of Sjögren Syndrome

10.21203/rs.3.rs-273620/v1 ◽

2021 ◽

Author(s):

Mi Yeon Song ◽

Sung Rae Noh ◽

Kook Young Kim ◽

Kyu Yeon Hwang ◽

Young A Kwon ◽

...

Keyword(s):

Dry Eye ◽

Ocular Surface ◽

Meibomian Gland ◽

Sjögren Syndrome ◽

Sjogren Syndrome ◽

Strong Positive Correlation ◽

Surface Parameters ◽

Standard Patient ◽

Average Maximum ◽

Positive Correlations

Abstract Purpose: To investigate the correlation between Sjögren syndrome (SS) duration and ocular surface parameters in patients with SS-related dry eye. Methods: We analyzed 108 eyes of 108 female patients with primary SS-related dry eye. Meibomian gland (MG) dysfunction, MG dropout, lipid layer thickness (LLT), partial and total blinking, and partial blinking rate (PBR) were measured using a LipiView® II ocular surface interferometer (TearScience, Morrisville, NC, USA). All patients underwent rheumatoid serologic tests and ocular surface assessments. The ocular surface assessment included the Standard Patient Evaluation of Eye Dryness (SPEED), Schirmer’s I test, non-invasive tear break-up time, and grading of corneal/conjunctival staining. The correlations between SS duration and MG dropout rates as well as other ocular surface parameters were determined. Results: The mean SS duration was 54.1±41.3 months. There was a strong positive correlation between SS duration and MG dropout (r = 0.766, p < 0.001). The average, maximum, and minimum LLTs showed a weak negative correlation with SS duration (r = -0.310, -0.211, and - 0.304, respectively, p = 0.014, 0.028, and 0.022, respectively) and MG dropout (r = -0.191, -0.326, and -0.299, respectively, p = 0.049, 0.002, and 0.009, respectively). Significant positive correlations were also observed between the SPEED scores and SS duration (r = 0.303, p = 0.042) and MG dropout (r = 0.450, p = 0.029). Conclusions: Longer durations of primary SS-related dry eye were associated with worse MG dysfunction.

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A study to assess the efficacy of topical cyclosporine A 0.05% in the management of dry eye with meibomiam gland dysfunction

Indian Journal of Clinical and Experimental Ophthalmology ◽

10.18231/j.ijceo.2021.134 ◽

2022 ◽

Vol 7 (4) ◽

pp. 667-671

Author(s):

Prajwalli Reddy ◽

Wajeeha Umam

Keyword(s):

Dry Eye ◽

Cyclosporine A ◽

Ocular Surface ◽

Tear Film ◽

Meibomian Gland ◽

Meibomian Gland Dysfunction ◽

Control Group ◽

Dry Eyes ◽

Group A ◽

Group B

: Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface. Meibomian Gland Dysfunction (MGD) is an abnormality of the meibomian gland that blocks the secretion of lipids. Without sufficient lipid production, tears evaporate quickly causing Dry Eye.MGD is associated with multiple pathological mechanisms including inflammation, microbial factors and lipid deficiencies. Topical Cyclosporine A (CsA) 0.05% is a calcineurin inhibitor that reduces inflammation by specifically inhibiting T‑cell activity, which reduces ocular surface inflammation and improves tear film dynamics. This was a prospective observational study done on 100 patients at the Department of Ophthalmology Basaveshwar teaching and general hospital, on patients of dry eyes due to meibomian gland dysfunction. Patients who were diagnosed with dry eyes due to meibomian gland dysfunction were invited to take part in the study. Patients were divided randomly into two groups of 50 patients each. This study, was explained in detail to them. An informed consent was obtained. Patients fulfilling the inclusion criteria were listed.All OSDI scores (symptom intensity, frequency and aggravation) revealed decreasing patterns throughout the observation period in both the groups. In single analysis, the cyclosporine A 0.05% group showed a significant improvement for each score at 3 months (p < 0.01, p = 0.01, p = 0.02, respectively). The mean TBUT after treatment in the group A (cyclosporine A group) increased to 12.36± 3.58(p<0.001) seconds, and in the group B (Control group) the TBUT score increased to 11.01±3.06 seconds. After 3 Months, there was statistically significant improvement in the mean Schirmer’s scores in both the treatment groups, however improvement was significantly greater in Cyclosporine A group. Prior to the treatment in group A (Cyclosporine A) mean Lissamine staining score was 2.73±0.15 and post treatment it reduced to 1.32±0.15 which was statistically significant (P<0.001). In group B (Control group) score before treatment was 2.46±0.15 and after treatment it reduced to 2.39±0.27 (p=0.11), not much difference was seen. : Findings from our study showed that there were significant improvements in the dry eye conditions due to defect in meibomian gland by treatment of topical Cyclosporine A 0.05% and sodium hyaluronate 0.1%.

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Focused ultrasound stimulation on meibomian glands for the treatment of evaporative dry eye

Experimental Biology and Medicine ◽

10.1177/15353702211052035 ◽

2021 ◽

pp. 153537022110520

Author(s):

Gengxi Lu ◽

Sumanth Gollapudi ◽

Runze Li ◽

Margaret L Pfeiffer ◽

Preeya Mehta ◽

...

Keyword(s):

Layer Thickness ◽

Dry Eye ◽

Focused Ultrasound ◽

Meibomian Gland ◽

Meibomian Gland Dysfunction ◽

Lipid Layer ◽

Mean Values ◽

Ultrasound Stimulation ◽

Evaporative Dry Eye ◽

Meibomian Glands

Current treatments for meibomian gland dysfunction have several limitations, creating a necessity for other advanced treatment options. The purpose of this study is to determine the effectiveness of focused ultrasound stimulation for the treatment of dry eye disease caused by meibomian gland dysfunction. An in vivo study of nine Dutch Belted rabbits was conducted with focused ultrasound stimulation of the meibomian glands. A customized line-focused ultrasonic transducer was designed for treatment. Fluorescein imaging, Schirmer’s test, and Lipiview II ocular interferometer were used to quantify outcomes from three aspects: safety, tear production, and lipid layer thickness. Both tear secretion and lipid layer thickness improved following ultrasound treatment. Five to 10 min after the ultrasound treatment, the mean values of lipid layer thickness increased from 55.33 ± 11.15 nm to 95.67 ± 22.77 nm ( p < 0.05), while the mean values measured with the Schirmer’s test increased from 2.0 ± 2.3 to 7.2 ± 4.3 ( p < 0.05). Positive effects lasted more than three weeks. Adverse events such as redness, swelling, and mild burn, occurred in two rabbits in preliminary experiments when the eyelids sustained a temperature higher than 42°C. No serious adverse events were found. The results suggest that ultrasound stimulation of meibomian glands can improve both tear production and lipid secretion. Ultimately, ultrasound stimulation has the potential to be an option for the treatment of evaporative dry eye disease caused by meibomian gland dysfunction.

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A Systematic Approach to Dry Eye using LipiFlow Treatment

US Ophthalmic Review ◽

10.17925/usor.2014.07.02.104 ◽

2014 ◽

Vol 07 (02) ◽

pp. 104 ◽

Cited By ~ 1

Author(s):

Mitchell A Jackson ◽

Keyword(s):

Dry Eye ◽

Ocular Surface ◽

Inflammatory Markers ◽

Systematic Approach ◽

Tear Film ◽

Meibomian Gland ◽

Diagnostic Methods ◽

Therapeutic Options ◽

Eye Disease ◽

Evaporative Dry Eye

The complex strategy to understanding dry eye syndrome has led to a widespread change in approaching this condition as an ocular surface disease, stratified as evaporative dry eye, aqueous deficient dry eye, and ocular allergy. The diagnostic armamentarium has vastly expanded to include tear osmolarity and inflammatory markers as redefined by the new International Dry Eye WorkShop (DEWS) in 2007. The Tear Film & Ocular Surface Society (TFOS) panel on meibomian gland dysfunction (MGD) further expanded the interpretation of evaporative dry eye and its therapeutic options, including the newest US Food and Drug Administration (FDA)-approved device known as LipiFlow Thermal Pulsation System. This paper will give an overview on understanding dry eye disease, its etiology, diagnostic methods, and current therapeutic options.

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

Scientific Reports ◽

10.1038/s41598-021-00122-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ricaurte Ramiro Crespo-Treviño ◽

Anna Karen Salinas-Sánchez ◽

Francisco Amparo ◽

Manuel Garza-Leon

Keyword(s):

Dry Eye ◽

Healthy Subjects ◽

Morphological Changes ◽

Tear Film ◽

Meibomian Gland ◽

Dry Eye Disease ◽

Eye Disease ◽

Ocular Surface Disease Index ◽

Evaporative Dry Eye ◽

The Impact

AbstractMany 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.

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Meibomian Gland Dysfunction

Pakistan Journal of Ophthalmology ◽

10.36351/pjo.v35i1.866 ◽

2019 ◽

Vol 35 (1) ◽

Author(s):

Sameera Irfan

Keyword(s):

Dry Eye ◽

Ocular Surface ◽

Treatment Strategies ◽

Tear Film ◽

Meibomian Gland ◽

Dry Eye Disease ◽

Meibomian Gland Dysfunction ◽

Eye Disease ◽

Treatment Protocols ◽

Dry Eyes

Dry eyes is a common, chronic condition that has a prevalence of about 5- 50%.1 According to the Dry Eye Workshop II report (DEWS II report), published in 2017, the updated definition of Dry Eye Disease is, “a multifactorial disease of the ocular surface characterised by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyper-osmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.” The Tear Film & Ocular Surface Society (TFOS) released their report on the international work on Meibomian Gland Dysfunction (MGD)2 in 2011, which defined MGD, classified it and considered it as the primary cause of dry eye disease worldwide. Previously dry eye disease was considered as an aqueous deficiency problem, but after this report by TFOS, there is a paradigm shift towards “not producing enough lipids to retain the tears that are being produced”. This has led to a huge impact on the treatment protocols which were previously focused on managing the sequelae and symptoms of dry eyes rather than targeting directly on the underlying cause, the MGD. It has now been accepted worldwide that dry eye occurs when the ocular surface system cannot adequately protect itself from the desiccating stress due to the lack of a healthy meibomian gland secretion. This article is mainly focussed on the Meibomian Gland Dysfunction, discussing the normal anatomy of the glands, how they are affected by disease, its implications on the ocular surface and finally, the various treatment strategies. Key words: Blepharitis, Dry eyes, Meibomian gland dysfunction, blepharospasm.

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Comparative of Meibomian Gland Morphology in Patients With Evaporative Dry Eye Versus Non-Dry Eye

10.21203/rs.3.rs-343591/v1 ◽

2021 ◽

Author(s):

Ricaurte Ramiro Crespo-Treviño ◽

Anna Karen Salinas-Sánchez ◽

Francisco Amparo ◽

Manuel Garza-Leon

Keyword(s):

Dry Eye ◽

Healthy Subjects ◽

Morphological Changes ◽

Tear Film ◽

Retrospective Chart Review ◽

Meibomian Gland ◽

Ocular Surface Disease Index ◽

Non Invasive ◽

Evaporative Dry Eye ◽

The Impact

Abstract Many recent studies have demonstrated 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 MG morphology in tear film physiology and disease. This study aimed to investigate the prevalence of anatomical and morphological MG alterations between patients with evapo-rative DED and healthy controls. Retrospective chart review of Seventy-five patients with evaporative dry eye and healthy individuals who had dry eye assesments 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 dry-eye subjects. Patients with evaporative dry eye 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 dry eye presented more alterations in the lower lid than healthy subjects.

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