Meibomian gland dysfunction (MGD) is one of the primary causes of evaporative dry eye. Stagnation of meibum induces an unstable tear film, thus resulting in shortened tear film breakup time and superficial punctate keratopathy (SPK) in the lower cornea and punctate staining of lower bulbar conjunctiva. MGD is sometimes accompanied with inflammation (termed “meibomitis”) via the proliferation of bacteria in the meibomian gland and eyelash area. Meibomitis is strongly related to ocular surface inflammation such as corneal cellular infiltrates and neovascularization, SPK, and conjunctivitis. It is difficult to differentiate SPK caused by dry eye from that caused by meibomitis. When clinicians are unaware of the existence of meibomitis, and only aware of SPK on the cornea, they often try to treat SPK as it is caused by dry eye using dry eye–specific eyedrops or even using punctual plugs when conservative therapy is ineffective. However, even when intensive dry eye therapy is applied, it may be unsuccessful until SPK caused by meibomitis is recognized and treated with systemic antimicrobial agents. Hence, the tear secreting glands, including the meibomian glands, and the ocular surface should be clinically considered as one unit (i.e., the meibomian gland and ocular surface [MOS]) when considering the pathophysiology and treatment of ocular surface inflammatory diseases (i.e., corneal epithelial damage). Following this clinical pathway, a treatment focusing on meibomian gland inflammation may be a more reasonable approach for meibomitis-related or associated keratoconjunctivitis to more effectively treat this ocular surface disease.

Purpose: The purpose of this study was to investigate the microbiome in the meibum, conjunctival sac, and eyelid skin in young and elderly healthy subjects, and analyze the effect that age, sex, and region have on microbiome composition. Methods: This study involved 36 healthy subjects (young-age subjects: 9 men/9 women, age range: 20–35 years; elderly age subjects: 9 men/9 women, age range: 60–70 years). In all subjects, lower-eyelid meibum, lower conjunctival sac, and lower-eyelid skin specimens were collected from one eye, and then stored at –20°C. Taxonomic composition of the microbiome was obtained via 16S rRNA gene sequencing, and then analyzed. Results: The meibum microbiome showed a high α-diversity (within-community diversity), particularly in the young subjects. However, in approximately 30% of the elderly subjects, a low-diversity microbiome dominated by Corynebacterium sp. or Neisseriaceae was observed. In the young subjects, the microbiome of the meibum resembled that of the conjunctival-sac, yet in the elderly subjects, the microbiome of the conjunctival-sac became more similar to that of the eyelid skin. The eyelid-skin microbiome was relatively simple, and was typically dominated by Propionibacterium acnes in the young subjects, or by Corynebacterium sp. or Neisseriaceae in the elderly subjects. In both age groups, no significant difference was seen between the men and women in regard to the meibum, conjunctival-sac, and eyelid-skin microbiome. Conclusions: Our findings confirmed that the meibum of healthy adult-age subjects harbors highly diverse microbiota, and revealed that the meibum microbiome, especially the decrease of its diversity, alters with aging and may affect the homeostasis of the ocular surface.

Meibomian gland inflammation, "meibomitis," is associated with ocular surface inflammatory diseases. However, these diseases are poorly defined clinically, making effective treatment difficult. Herein, we propose a new disease subset, termed meibomitis-related keratoconjunctivitis (MRKC). The ocular surface features of MRKC include: meibomitis with redness and swelling of the eyelid margin and palpebral conjunctiva; superficial vascularization and granulomatous nodules in the cornea; and conjunctival hyperemia, similar or identical to that observed in phlyctenular keratitis. The characteristics of MRKC patients include a significantly higher prevalence in women, multiple history of chalazia, close association with meibomitis, the presence of specific human leukocyte antigen association, high Propionibacterium acnes detection rates in meibum culture, and the effectiveness of systemic antimicrobial therapy targeting P. acnes. MRKC may share many clinical features with ocular rosacea, especially during childhood. The clinical effectiveness of systemic antimicrobial agents in treating both diseases suggests the importance of focusing on the elimination of bacteria such as P. acnes.

To investigate the alteration in lipid composition of meibum, objective clinical signs, and subjective symptoms associated with aging and meibomian gland (MG) dysfunction (MGD). In 10 MGD patients [4 males/6 females, mean age: 65.6 ± 7.9 years (range: 50-79 years)] and 24 healthy volunteer subjects [young subjects: 6 males/6 females, mean age: 25.7 ± 3.8 years (range: 20-35 years), elderly subjects: 6 males/6 females, mean age: 58.4 ± 7.5 years (range: 50-79 years)], three objective clinical signs were evaluated: MG orifice obstruction, meibum score, and tear film lipid layer interference pattern. Subjective symptoms were analyzed via a 15-item questionnaire. After careful collection of meibum samples, comprehensive lipid analysis was performed via liquid chromatography-mass spectrometry. Data was analyzed via JMP® ver. 13 (SAS Institute, Inc., Cary, NC) statistical analysis software. In the MGD patients and elderly subjects, there was a significant decrease in non-polar lipids such as cholesterol esters (ChEs), while a significant increase in polar lipids [cholesterol (Ch), (O-acyl)-ω-hydroxy fatty acid (OAHFA), and free fatty acid (FA)] in total lipids (Tukey-Kramer test: p < 0.05). Triglyceride was significantly increased only in MGD patients (p < 0.05). Symptom scores representative of vision quality (i.e., blurred vision/haziness) were significantly negatively-correlated with the ratio of the non-polar lipid ChE, while significantly positively correlated with the polar lipids Ch, OAHFA, and FA (Spearman's rank correlation coefficient: p < 0.05). Our findings revealed that both MGD and aging affect the composition ratio of major meibum lipids, resulting in the appearance of subjective symptoms.

Dry eye is a multifactorial and common age-related ocular surface disease. Dyslipidemia has been reported to be involved in meibomian gland dysfunction (MGD). However, it has not been clearly identified which lipid abnormality is responsible for MGD. In this systematic review and meta-analysis, we discuss how lipid profile changes with aging is responsible for MGD development. Methods. An article search was performed in PubMed, EMBASE, and Web of Science. Eleven studies involving dyslipidemia in patients with MGD were identified. Five out of eleven studies were further analyzed with meta-analysis. The preferred reporting items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were followed. Study-specific estimates (prevalence of dyslipidemia in MGD patients) were combined using one-group meta-analysis in a random-effects model. Results. Meta-analysis revealed that high total cholesterol (TC) and high triglycerides (TG) were significantly associated with MGD prevalence, with odds ratios of 5.245 (95% confidence interval [CI]: 1.582–17.389; p < 0.001) and 3.264 (95% CI: 1.047–10.181; p < 0.001), respectively, but high low-density lipoprotein (LDL) and low high-density lipoprotein (HDL) were not identified. Systematic review found that the percentage of MGD patients with TC ≥ 200 mg/dL ranged from 20.0–77.6%, TG ≥ 150 mg/dL ranged from 8.3–89.7%, whereas, in the aged-match-adjusted controls, TC range of 200 mg/dL or higher and TG range of 150 mg/dL was 6.1–45.1% and 1.1–47.8%, respectively. The severity of MGD was higher with dyslipidemia. Conclusion. Dyslipidemia and higher TC and TG are significant risk factors for MGD.