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Clinical Advances in Meibomian Gland Dysfunction and Dry Eye Disease

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Ophthalmology".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 20820

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Special Issue Editors

Dr. Motoko Kawashima

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Guest Editor

Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan
Interests: dry eye; meibomian gland; ocular surface; lacrimal gland; eye; eye pain; preventive medicine

Dr. Reiko Arita

E-Mail Website
Guest Editor

1. Itoh Clinic, Saitama 3370042, Japan
2. Lid and Meibomian Gland Working Group, Saitama 3370042, Japan
Interests: dry eye; meibomian glands; ocular surface

Special Issue Information

Dear Colleagues,

Meibomian gland dysfunction (MGD) and dry eye disease (DED) are both quite common. Their ocular symptoms are similar and both reduce quality of life, although the pathogenesis differs somewhat between these diseases. Recent advances in both diagnostic methods, instruments, and treatments of MGD and DED have made tremendous strides.

This Special Issue aims to provide an update regarding diagnostic and therapeutic options in the field of MGD and DED. Therefore, we would like to invite original research and review articles. In particular, we would like to encourage the submission of manuscripts covering important items regarding the topics below.

CO idea: In particular, we would like to encourage the submission of manuscripts covering these leading topics below:

Diagnostic methods of MGD and DED;
Symptoms of MGD and DED;
Treatments of MGD and DED;
Prevention of MGD and DED;
Relationship between MGD and DED

Dr. Reiko Arita
Dr. Motoko Kawashima
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

meibomian gland dysfunction
dry eye disease
eye pain
eye symptoms
diagnosis
treatment
clinical research
preventive medicine

Published Papers (10 papers)

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Research

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9 pages, 883 KiB

Open AccessArticle

The Impact of Probiotics and Prebiotics on Dry Eye Disease Signs and Symptoms

by Azadeh Tavakoli, Maria Markoulli, Eric Papas and Judith Flanagan

J. Clin. Med. 2022, 11(16), 4889; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11164889 - 20 Aug 2022

Cited by 9 | Viewed by 3526

Abstract

Dry eye is considered an inflammatory disease. Gut microbiota are important in the regulation of low-grade chronic inflammation, including in the eye. Probiotics and prebiotics are increasingly used to regulate chronic-disease-associated gut dysbiosis. Therefore, this double-masked, randomized controlled clinical trial aimed to explore the potential of oral probiotics and prebiotics in the management of dry eye disease. In total, 41 participants with dry eye received probiotic and prebiotic supplements (treatment group, n = 23) or respective placebos (control group, n = 18) for 4 months. Dry eye symptoms and signs were evaluated using the Ocular Surface Disease Index (OSDI), Dry Eye Questionnaire 5, osmolarity, non-invasive keratograph break-up time (NIKBUT), ocular surface staining, tear meniscus height (TMH), lipid layer thickness, and conjunctival redness. After 4 months, the average OSDI score of the treatment group was significantly better compared to that of the controls (16.8 ± 5.9 vs. 23.4 ± 7.4; p < 0.001). The NIKBUT and TMH did not change significantly with treatment (p = 0.31 and p = 0.84) but reduced significantly for controls on average by −5.5 ± 1.0 secs (p = 0.03) and 0.2 ± 0.1 mm (p = 0.02). These data suggest that probiotics and prebiotics might be effective in the management of dry eye disease. Full article

(This article belongs to the Special Issue Clinical Advances in Meibomian Gland Dysfunction and Dry Eye Disease)

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10 pages, 249 KiB

Open AccessArticle

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

by Yunhan Lee, Joon Hyuck Jang, Sanghyu Nam, Koeun Lee, Jin Kim, Jae Yong Kim, Hungwon Tchah and Hun Lee

J. Clin. Med. 2022, 11(16), 4724; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11164724 - 12 Aug 2022

Cited by 4 | Viewed by 1655

Abstract

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. Full article

(This article belongs to the Special Issue Clinical Advances in Meibomian Gland Dysfunction and Dry Eye Disease)

12 pages, 1019 KiB

Open AccessArticle

Association of Meibomian Gland Dysfunction with Oral Statin Use

by Sun-Kyoung Park, Ji-Hye Lee, Ho-Sik Hwang, Hyun-Seung Kim, Kyung-Do Han and Kyung-Sun Na

J. Clin. Med. 2022, 11(15), 4632; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11154632 - 8 Aug 2022

Cited by 1 | Viewed by 2054

Abstract

This retrospective cross-sectional study aimed to determine the association of oral statin use, dry eye disease (DED), and meibomian gland dysfunction (MGD). A total of 93 subjects were included and divided into two groups: statin users (n = 45) and nonstatin users (n = 47). Significant differences were observed in the total cholesterol (p = 0.013), low-density lipoprotein (LDL) (p = 0.005), and meiboscore (p = 0.000) levels between the two groups. For stratified analysis, the statin group was divided into subgroups according to the type or dose of statin and total duration of statin use. However, there were no differences in clinical features between the subgroups. In multiple regression analysis, meiboscore was significantly associated with age (slope = 0.05, p = 0.00) and statin use (slope = −1.19, p = 0.00), with an R² of 0.44. Thus, older adults and participants who do not use statin appeared to have higher scores. In conclusion, although the mechanism is unclear, statins may exert a protective effect on the meibomian gland. Further lipidomic studies are required to determine the pharmacological effects of statins on the meibomian gland and other meibum components. Full article

(This article belongs to the Special Issue Clinical Advances in Meibomian Gland Dysfunction and Dry Eye Disease)

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7 pages, 498 KiB

Open AccessArticle

Immediate and Quantitative Changes in Tear Film Parameters and Meibomian Gland Structures after Warm Compression and Meibomian Gland Squeezing in Meibomian Gland Dysfunction Patients and Normal Subjects

by Hae Min Park, Won June Lee, Han Woong Lim and Yu Jeong Kim

J. Clin. Med. 2022, 11(15), 4577; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11154577 - 5 Aug 2022

Cited by 1 | Viewed by 1247

Abstract

Meibomian gland dysfunction (MGD), a chronic abnormality of meibomian glands, causes various dry eye symptoms. Principal treatments for MGD are warm compression and mechanical squeezing of the eyelids. In this study, the immediate impact of this treatment on tear film lipid layer thickness (TFLLT) and the meibomian gland (MG) structure in MGD and normal groups was investigated to establish its efficacy and potential side effects. Nineteen MGD patients and seven normal subjects were enrolled. TFLLT and blinking parameters were evaluated before and after warm compression. Morphological changes of MG structures after mechanical squeezing were analyzed using Image J and Fiji. Differential analysis of the MGD and the normal groups of TFLLT changes after warm compression showed a significant increase in the normal group. In normal eyes, the average, maximum, and minimum TFLLT were significantly increased, and in the MGD group, only the minimum TFLLT was improved. Blinking parameters showed no significant change in either group. Morphometric analysis showed no damages of the MG after MG squeezing. A significant increase in MG length was observed in normal eyes. Warm compression immediately increased TFLLT more significantly in the normal group than in the MGD patients. Mechanical expression is a safe therapeutic option without remarkable structural MG damages. Full article

(This article belongs to the Special Issue Clinical Advances in Meibomian Gland Dysfunction and Dry Eye Disease)

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12 pages, 735 KiB

Open AccessArticle

Association between Dry Eye Parameters Depends on Tear Components

by Shu-Wen Chang and Wan-Lin Wu

J. Clin. Med. 2022, 11(11), 3056; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11113056 - 28 May 2022

Cited by 5 | Viewed by 1641

Abstract

How tear components contribute to dry-eye symptoms/signs remains less well-defined. This observational cross-sectional study enrolled 4817 (F/M = 3590/1227) patients. Subjective symptoms were evaluated with the SPEED and OSDI questionnaires. Fluorescein tear breakup time (FTBUT), superficial punctate keratitis (SPK) grading, Schirmer scores, number of expressible meibomian glands (MGE), lipid layer thickness (LLT), blink/partial blink rates and meibography were recorded. Patients were divided into 4 types according to their Schirmer scores and LLT, i.e., Type 1 (N = 1494): Schirmer > 5 mm, LLT > 60 nm; Type 2 (N = 698): Schirmer > 5 mm, LLT ≤ 60 nm; Type 3 (N = 1160): Schirmer ≤ 5 mm, LLT ≤ 60 nm; Type 4 (N = 1465): Schirmer ≤ 5 mm, LLT > 60 nm. Lipid deficiency (LLT ≤ 60 nm) and aqueous deficiency (Schirmer score ≤ 5 mm) were found in 38.6% and 54.5% of patients, respectively. The majority (62.4%) of lipid-deficient patients were also aqueous deficient, while 44.2% of aqueous-deficient patients were also lipid-deficient. Type 3 patients (mixed type) had the highest symptom scores (p = 0.008 and 0.007 for SPEED and OSDI, respectively), more total blinks (p < 0.001) and the shortest FTBUT (p < 0.001). Stepwise multiple regression demonstrated that LLT and Schirmer score were significant contributors to FTBUT in all 4 types. The FTBUT correlated with SPK severity in all 4 types, with Schirmer score in types 1 and 4, and with LLT in type 3 patients. SPK correlated with LLT and MGE in types 1 and 4. Age correlated with dry eye parameters more significantly than sex. Subtyping by aqueous and lipid components facilitates the understanding of dry eye pathophysiology. Full article

(This article belongs to the Special Issue Clinical Advances in Meibomian Gland Dysfunction and Dry Eye Disease)

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11 pages, 753 KiB

Open AccessArticle

Exploratory Search for Characteristic Symptoms to Distinguish Meibomian Gland Dysfunction from Dry Eye in a Population-Based Study in Japan

by Reiko Arita, Takanori Mizoguchi, Motoko Kawashima, Shima Fukuoka, Shizuka Koh, Rika Shirakawa, Takashi Suzuki and Naoyuki Morishige

J. Clin. Med. 2022, 11(6), 1715; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11061715 - 19 Mar 2022

Cited by 1 | Viewed by 1720

Abstract

Symptom overlap between meibomian gland dysfunction (MGD) and dry eye (DE) makes it difficult to distinguish between these two conditions on the basis of symptoms alone. We searched for characteristic symptoms that might help to distinguish MGD from DE on the basis of a population-based study. Subjects comprised 311 residents of Takushima island (18 to 96 years), including 117 individuals with MGD and 114 with DE. Responses to a symptom-related questionnaire (19 items) were subjected to factor analysis, and univariate regression analysis was performed to identify ocular surface parameters associated with characteristic symptoms of MGD. Factor analysis revealed aggregation of symptoms according to three factors: Factor 1 related to Symptom Score, Factor 2 to DE, and Factor 3 to MGD. Symptoms associated with DE included 11 items, whereas the only item related to MGD was tearing sensation. Pearson’s correlation analysis revealed that tearing sensation was associated with tear meniscus height (TMH), noninvasive tear-film breakup time, fluorescein staining score, meiboscore, meibum grade, and Schirmer value. Subjects with MGD experienced significantly more tearing and had a larger TMH than did those without MGD (p = 0.0334). Tearing sensation may thus be a characteristic symptom of MGD. Physicians should suspect MGD who complain of tearing sensation. Full article

(This article belongs to the Special Issue Clinical Advances in Meibomian Gland Dysfunction and Dry Eye Disease)

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9 pages, 508 KiB

Open AccessArticle

How Long to Continue Eyelid Hygiene to Treat Meibomian Gland Dysfunction

by Hyunmin Ahn, Bo Yi Kim, Jinyoung Kim, Yong Woo Ji, Ikhyun Jun, Tae-im Kim, Hyung Keun Lee and Kyoung Yul Seo

J. Clin. Med. 2022, 11(3), 529; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11030529 - 20 Jan 2022

Cited by 4 | Viewed by 1712

Abstract

To determine the efficacy duration of eyelid hygiene for meibomian gland dysfunction (MGD) treatment, a total of 1015 participants with primary MGD, followed for at least 6 months, were enrolled. The participants were classified into the eyelid hygiene group and the control group. The participants who had stopped eyelid hygiene at any point in the observation period after the initial 2 months were classified into the withdrawal group. Analysis was conducted with a generalized linear mixed model. Treatment group, age, sex, ocular surface inflammation, anti-inflammatory treatments, and baseline MGD subtype were considered as fixed effects, and the individual factor was considered as a random effect. The MGD stage decreased significantly for the observational period in the eyelid hygiene group (p < 0.001). Approximately 40.1% of the participants continuously maintained eyelid hygiene throughout the observational period. The MGD stage in the eyelid hygiene group continued to decrease for 6 months and was maintained thereafter. After 4 months of stopping eyelid hygiene, the MGD stage in the withdrawal group was worse than in the eyelid hygiene group (p < 0.001) and similar to that in the control group (p = 0.762). Maintaining eyelid hygiene was significantly effective in MGD treatment. Efficacy increased with treatment for 6 months, and the efficacy duration was maintained for 4 months even after stopping eyelid hygiene. Therefore, we recommend that patients with MGD maintain eyelid hygiene, and compliance should be checked continuously. Full article

(This article belongs to the Special Issue Clinical Advances in Meibomian Gland Dysfunction and Dry Eye Disease)

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12 pages, 901 KiB

Open AccessArticle

Morphology of Meibomian Glands in a 65-Year-Old Norwegian Population without Dry Eye Disease

by Xiangjun Chen, Reza A. Badian, Håvard Hynne, Behzod Tashbayev, Lene Hystad Hove, Janicke Liaaen Jensen and Tor Paaske Utheim

J. Clin. Med. 2022, 11(3), 527; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11030527 - 20 Jan 2022

Cited by 2 | Viewed by 2445

Abstract

Analyses of meibography may help in the diagnosis, prevention, and management of meibomian gland dysfunction (MGD). However, there is currently a paucity of data regarding meibography analyses in the young elderly populations in the Nordic countries. In the current study, meibography of the upper and lower eyelids of 117 65-year-old residents in Oslo, Norway, who did not fulfil the diagnosis of dry eye disease (DED) were analysed. Meibomian gland (MG) dropout and tarsal areas were measured semi-automatically using ImageJ software. The relationship between morphological features of the MGs and clinical dry eye tests was examined. The median percent MG dropout was 26.1% and 40.7% in the upper and lower eyelids, respectively. There was no significant difference between males and females. None of the MG morphological parameters demonstrated significant values in discriminating abnormal dry eye symptom loads or MGD diagnosis from the normal loads. We therefore concluded that moderate MG atrophy was common among the Norwegian population of 65-year-olds without DED and showed no sexual differences. Meibography alone cannot discriminate MGD from non-MGD; thus, both morphological and functional MG tests are necessary when screening for MGD. Full article

(This article belongs to the Special Issue Clinical Advances in Meibomian Gland Dysfunction and Dry Eye Disease)

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Review

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13 pages, 976 KiB

Open AccessReview

Association of Serum Lipid Level with Meibum Biosynthesis and Meibomian Gland Dysfunction: A Review

by Young-Sik Yoo, Sun-Kyoung Park, Ho-Sik Hwang, Hyun-Seung Kim, Reiko Arita and Kyung-Sun Na

J. Clin. Med. 2022, 11(14), 4010; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11144010 - 11 Jul 2022

Cited by 5 | Viewed by 1492

Abstract

The primary role of meibomian glands (MGs) is to actively synthesize and secret lipids and proteins spread onto the tear film, and the glandular lipids promote tear stability, prevent evaporation, and reduce friction. Meibomian gland dysfunction (MGD) is the leading cause of dry eye disease and one of the most common ophthalmic problems worldwide. MGs are densely innervated and regulated by hormones and growth factors. However, since the polar and nonpolar lipids are produced through processes in MGs that are not completely understood, a relevant question has been raised: Would the altered systemic lipids metabolism affect the physiology and structure of MGs? This review introduces the recent update regarding the relationships between serum lipid and MGD in clinical and basic research while providing answers to this question. A causal relationship remains to be established; however, serum lipid level or dyslipidemia may be related to MGD directly or indirectly, or both. Further studies are warranted to establish the role of serum lipid level and meibocyte differentiation/maturation and lipid synthesis. Full article

(This article belongs to the Special Issue Clinical Advances in Meibomian Gland Dysfunction and Dry Eye Disease)

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34 pages, 723 KiB

Open AccessReview

In Vivo Confocal Microscopy in Different Types of Dry Eye and Meibomian Gland Dysfunction

by Ralene Sim, Kenneth Yong, Yu-Chi Liu and Louis Tong

J. Clin. Med. 2022, 11(9), 2349; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11092349 - 22 Apr 2022

Cited by 8 | Viewed by 2104

Abstract

In vivo confocal microscopy (IVCM) imaging is increasingly popular in ocular surface disease diagnosis and management. We conducted a systematic review to update the use of IVCM in the diagnosis and treatment of dry eye and meibomian gland dysfunction (MGD). A literature review was conducted on IVCM studies in MGD, dry eye disease, systemic disease causing dry eye, dry eye in glaucoma patients, contact lens-associated ocular conditions, graft-versus-host disease, and Sjogren’s syndrome-related dry eye. The articles were identified through PubMed and a total number of 63 eligible publications were analyzed in detail. All primary research studies on confocal microscopy on dry eye and related conditions from 2017 onwards were included. The reports were reviewed for their contribution to the existing literature as well as potential biases and drawbacks. Despite limitations such as small field of view, lack of population-based norms, and lack of standardization of image acquisition, interpretation, and quantification, IVCM is useful as a complementary technique for clinical diagnosis in various ocular surface disorders related to dry eye. With advances in hardware and software in the near future, it has the potential for further practical impact. Full article

(This article belongs to the Special Issue Clinical Advances in Meibomian Gland Dysfunction and Dry Eye Disease)

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