Ocular surface inflammation impairs structure and function of meibomian gland

Mizoguchi, Shin; Iwanishi, Hiroki; Arita, Reiko; Shirai, Kumi; Sumioka, Takayoshi; Kokado, Masahide; Jester, James V.; Saika, Shizuya

doi:10.1016/j.exer.2017.06.011

Cited by 63 publications

(50 citation statements)

References 34 publications

(41 reference statements)

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“…In an era of decelerated dry eye drug development, inconsistent clinical trial endpoints, and frustration among ophthalmologists and optometrists caring for patients with symptom–sign disparity, there is a growing need for objective, reliable, and clinically relevant measures of detecting, assessing, and monitoring disease severity in patients with ocular surface disease, such as DED or MGD. 35 Since inflammation contributes to the pathogenesis of MGD, 36,37 and given the paucity of quantitative metrics that reproducibly correlate with both symptoms and clinical signs in DED-associated inflammation, we conducted a rigorous analysis of 10 exploratory IVCM-based immune-cellular metrics for the evaluation of inflammation in MGD. Of these 10 metrics, 4 were focused specifically on quantifying inflammation in each layer of the palpebral conjunctiva (EIC, SIC, PGIC) as well as within meibomian glands (IGIC).…”

Section: Discussionmentioning

confidence: 99%

Clinically Relevant Immune-Cellular Metrics of Inflammation in Meibomian Gland Dysfunction

Qazi

Kheirkhah

Blackie

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PurposeTo determine the reliability and clinical relevance of in vivo confocal microscopy (IVCM)-based immune-cellular metrics of palpebral conjunctival inflammation in meibomian gland dysfunction (MGD).MethodsSixteen MGD patients and 13 reference controls included in this cross-sectional, retrospective study, had an ocular surface exam, symptom assessment (Ocular Surface Disease Index questionnaire [OSDI]), and palpebral conjunctival IVCM imaging. Bland-Altman analyses, intraclass correlation coefficient (ICCa), Lin's concordance correlation coefficient (ρc), receiver operating characteristic (ROC) analyses, and correlations were performed. Clinical outcome measures were symptom severity (OSDI scores), tear break-up time (TBUT), and corneal fluorescein staining (CFS grade).ResultsCompared to controls, patients with MGD had variable symptom severity (average OSDI score: 48.3 ± 7.6, P = 0.0008, range: 8.3–85.42), shorter TBUT (6.8 ± 0.9 seconds, P = 0.002), comparable corneal staining (0.31 ± 0.19, P = 0.20), and greater conjunctival inflammation (epithelial immune cells [EIC]: 477.8 ± 54.2 vs. 123.3 ± 17.2 cells/mm2, P < 0.0001; intraglandular immune cells [IGIC]: 41.9 ± 3.3% vs. 20.33 ± 7.3%, P < 0.01). Immune-cellular metrics had high inter- and intraobserver agreement (ρc: 0.86–0.94; ICCa and Cronbach's α: 0.85–0.97, P < 0.0001). EIC correlated positively with OSDI (rs: 0.49, P = 0.03), while both EIC and IGIC correlated inversely with TBUT (rs: −0.47, −0.45, P < 0.05), and had high accuracy in detecting inflammation (ROC area under the curve [AUC]: 0.97 and 0.89, P ≤ 0.001).ConclusionsEIC and IGIC are increased in highly symptomatic patients with MGD that have minimal corneal staining, and correlate with symptoms and clinical signs. EIC and IGIC may provide reliable and clinically relevant metrics of inflammation.

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Section: Discussionmentioning

confidence: 99%

Clinically Relevant Immune-Cellular Metrics of Inflammation in Meibomian Gland Dysfunction

Qazi

Kheirkhah

Blackie

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…However, most animal models that mimic aspects of MGD lack an underlying primary immunological condition to help tackle this problem (30–37). Moreover, only associative data regarding the role of inflammation in MGD have been obtained in the clinical setting (15, 17, 38, 39). Hence, new tools are needed to revisit the important and unresolved question of whether the immune response can contribute etiologically to obstructive MGD (40).…”

Section: Introductionmentioning

confidence: 99%

Neutrophils cause obstruction of eyelid sebaceous glands in inflammatory eye disease in mice

Reyes

Mathew

et al. 2018

Sci. Transl. Med.

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Meibomian glands (MGs) are sebaceous glands of the eyelid margin that secrete lipids needed to avert tear evaporation and to help maintain ocular surface homeostasis. Obstruction of MGs or other forms of MG dysfunction can promote chronic diseases of the ocular surface. Although chronic eyelid inflammation, such as allergic eye disease, is an associated risk factor for obstructive MG dysfunction, it is not clear whether inflammatory processes contribute to the pathophysiology of MG obstruction. We show that polymorphonuclear neutrophils (PMNs) promoted MG obstruction in a chronic inflammatory model of allergic eye disease in mice. Analysis of leukocytes in tears of patients with MG dysfunction showed an increase in PMN numbers compared to healthy subjects. Moreover, PMN numbers in tears positively correlated with clinical severity of MG dysfunction. Our findings point to a role for PMNs in the pathogenesis and progression of MG dysfunction.

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“… 2 Many ocular disorders, including dry eye symptoms, blepharitis, and chalazia can be linked to MGD. 3 – 5 MGD’s high prevalence and its multiple pathologies suggest that it is a multifactorial disease. 6 , 7 If we treat the MGD, we can easily treat the related diseases.…”

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confidence: 99%

A systematic review of the effect of omega-3 supplements on meibomian gland dysfunction

Al-Namaeh

2020

Ophthalmol Eye Dis

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Introduction: Meibomian gland dysfunction (MGD) is the leading cause of dry eye syndrome (DES). Many ocular disorders including DES and blepharitis can be linked to MGD. If we treat MGD, we can treat related diseases easily. Purpose: This systematic review is intended to determine the efficacy of omega-3 supplementation in MGD patients. Methods: This systematic review included an electronic search on PubMed and Clinicaltrials.gov to include all randomized clinical trials (RCTs) using omega-3 as a treatment for MGD. Results: Database search yielded to one RCT and six clinical trials through the MEDLINE of a total of 350 participants for the systematic review and meta-analysis study. The investigated treatment group (omega-3 group) had a positive effect on MGD protection in the invasive sodium fluorescein-tear break up time (NaFl-TBUT) score compared with the placebo group (odd ratio = 8.72, 95% confidence interval: 4.73, 16.09; p < 0.001). These data suggest that the odd ratios of the omega-3 group to control group increased the likelihood of the improved stated outcome tear break up time (TBUT) being achieved in the treatment group. No evidence of publication bias was detected in the funnel plot inspection or the Egger’s statistical test ( p = 0.2944). Conclusions: A moderate daily dose of omega-3 may be a beneficial therapeutic for MGD. Omega-3 has been beneficial in many diseases, such as heart attack prevention and agerelated macular degeneration, and this systematic review emphasizes its protection against MGD. In addition, this review emphasizes the precision of noninvasive TBUT (NITBUT) compared with invasive NaFl-TBUT which may suggest the importance of NITBUT in the clinic.

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Ocular surface inflammation impairs structure and function of meibomian gland

Cited by 63 publications

References 34 publications

Clinically Relevant Immune-Cellular Metrics of Inflammation in Meibomian Gland Dysfunction

Clinically Relevant Immune-Cellular Metrics of Inflammation in Meibomian Gland Dysfunction

Neutrophils cause obstruction of eyelid sebaceous glands in inflammatory eye disease in mice

A systematic review of the effect of omega-3 supplements on meibomian gland dysfunction

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