A novel transillumination meibography device for in vivo imaging of mouse meibomian glands

PurposeWhile mouse models of dry eye disease (DED) have been developed, studies evaluating the role of the meibomian glands limited by the inability to temporally document changes. In this report we describe the development of a novel mouse transillumination meibography device and assess the ability of this device to detect age-related changes in the meibomian glands of young and old mice.MethodsThe mouse meibography device was comprised of a 3 mm wide right angle prism attached to broad spectrum light source by an optical fiber. Eyelids were then pulled over the prism using double tooth forceps and imaged using a stereomicroscope and low light level camera. Meibomian glands from four young and four old male, BALB/c mice were then imaged and analyzed using ImageJ.ResultsIn young mice, meibography documented the presence of 7–8 meibomian glands appearing as black and distinct eyelid structures with the length shorter in the lower eyelid compared to the upper eyelids. Eyelids of old mice showed apparent dropout of meibomian glands along with smaller and more irregularly shaped acini. The mean acini area of one meibomian gland was 0.088 ± 0.025 mm² in young mice and 0.080 ± 0.020 mm² in old mice (p = 0.564), but the Meibomian gland density was significantly lower in older mice (41.7 ± 6.4%, 27.3 ± 4.2%) (p = 0.021).ConclusionWe have developed an in vivo meibography device that may prove useful in sequentially documenting changes during development of meibomian gland dysfunction and following treatment.     

Randomised double-masked placebo-controlled trial of the cumulative treatment efficacy profile of intense pulsed light therapy for meibomian gland dysfunction

PurposeTo assess long-term cumulative treatment effects of intense pulsed light (IPL) therapy in meibomian gland dysfunction (MGD).MethodsEighty-seven symptomatic participants (58 female, mean ± SD age, 53 ± 16 years) with clinical signs of MGD were enrolled in a prospective, double-masked, parallel-group, randomised, placebo-controlled trial. Participants were randomised to receive either four or five homogeneously sequenced light pulses or placebo treatment to both eyes, (E-Eye Intense Regulated Pulsed Light, E-Swin, France). Visual acuity, dry eye symptomology, tear film parameters, and ocular surface characteristics were assessed immediately before treatment on days 0, 15, 45, 75, and four weeks after treatment course completion on day 105. Inflammatory and goblet cell function marker expression, and eyelid swab microbiology cultures were evaluated at baseline and day 105.ResultsSignificant decreases in OSDI, SPEED, and SANDE symptomology scores, and meibomian gland capping, accompanied by increased tear film lipid layer thickness, and inhibited Corynebacterium macginleyi growth were observed in both treatment groups (all p < 0.05). Sustained clinical improvements occurred in both treatment groups from day 75, although significant changes from day 45, in lipid layer quality, meibomian gland capping, OSDI and SANDE symptomology, were limited to the five-flash group (all p < 0.05).ConclusionsIPL therapy effected significant improvements in dry eye symptomology, tear film lipid layer thickness, and meibomian gland capping in MGD patients. Five-flash IPL treatment showed superior clinical efficacy to four-flash, and an initial course of at least four treatments is suggested to allow for establishment of sustained cumulative therapeutic benefits prior to evaluation of overall treatment efficacy.Trial registration numberACTRN12616000667415.     

Association of meibomian gland architecture and body mass index in a pediatric population

PurposeTo determine if meibomian gland architecture in a pediatric population is impacted by body mass index (BMI).MethodsProspective evaluation of 175 eyes of 175 pediatric patients from two clinics. Demographic and clinical information were reviewed. Symptoms of dry eye were assessed with the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. Meibography was performed and grading of images was performed by a masked rater using a previously validated 5-point meiboscale (0–4) for gland atrophy and a 3-point score (0–2) for gland tortuosity.Results175 eyes of 175 participants aged 4–17 years (11.6 ± 3.7 years) were imaged. The mean meiboscore was 0.82 ± 0.94 (range 0–4) and the mean gland tortuosity score was 0.53 ± 0.70 (range 0–2). Ninety-six patients (56%) showed evidence of gland atrophy (meiboscore greater than 0) and the majority of patients (n=50, 29%) had a gland tortuosity score of 1. The mean BMI was 20.5 ± 4.86 kg/m² with 39.4% of patients (n = 69) above the 85th percentile. BMI percentile was not found to be a significant predictor of a meiboscore greater than 0 (odds ratio (OR) 1.004 95% confidence interval (CI) (0.99–1.10, p = 0.41). However, BMI percentile was found to be a significant predictor of gland tortuosity score (OR 1.01 95% CI (1.00–1.02), p = 0.02). Patients with BMI percentiles between 41 and 60 were 3.79 times more likely to have a gland tortuosity score of greater than 0 than patients with BMI percentiles between 0 and 20 (OR 3.789 CI (1.17–12.24)). No significant associations were found between age, race, or sex and meiboscore or tortuosity. There was a trend towards reduction in lipid layer thickness with increasing BMI percentile (p = 0.028, r² = 0.04).ConclusionIn this pediatric population, there was an association between meibomian gland tortuosity and higher percentiles of BMI. Future studies are needed to elucidate the pathogenesis of meibomian gland tortuosity and atrophy in pediatric patients.     

Meibomian gland dropout is associated with immunodeficiency at HIV diagnosis: Implications for dry eye disease

AimTo characterize anterior eye health and tear film characteristics in individuals with human immunodeficiency virus (HIV) undergoing anti-retroviral therapy.MethodsThis cross-sectional study involved 35 adults, categorized as healthy controls (n = 18) or as HIV-positive patients (n = 17), with no history of opportunistic infection or current ocular fundus abnormalities. Participants underwent a comprehensive anterior eye assessment. Primary outcome measures were dry eye symptoms (Ocular Surface Disease Index survey), tear film osmolarity, and extent of meibomian gland dropout. Secondary outcomes measures were ocular redness, tear film stability, and ocular surface staining. Levels of 36 cytokines were assayed from basal tears using a multiplex bead array.ResultsThe HIV-positive group showed more extensive meibomian gland dropout relative to controls (mean ± SD, controls: 29.6 ± 5.8 versus 37.0 ± 13.9%, p = 0.045). The extent of meibomian gland dropout was negatively correlated with blood CD4 T-cell count (a marker of immunodeficiency) at diagnosis (r = −0.69, p = 0.006). All other tests of anterior ocular health, including dry eye symptom levels, were not significantly different between the groups. There were no significant inter-group differences for the 36 cytokines assayed in the tear film.ConclusionsWe find greater meibomian gland dropout in HIV-positive individuals that is related to disease severity at diagnosis. Given this feature predisposes to dry eye disease, it suggests the need for long-term studies of anterior eye health in people with HIV.     

Noninvasive ocular surface analyzer as an adjunct in diagnosis and estimating prevalence of meibomian gland dysfunction: Hospital-based comparative study

Purpose:To assess the role of noninvasive ocular surface analyzer (OSA) in workup of meibomian gland dysfunction (MGD) and to estimate hospital-based prevalence of MGD using this objective device.Methods:The study recruited 113 consecutive participants attending the ophthalmology outpatient department of a tertiary care hospital. All participants were administered a symptom questionnaire. Participants underwent a comprehensive ocular examination, including slit-lamp biomicroscopy and meibomian gland expression. Lipid layer thickness (LLT), noninvasive tear breakup time (NIBUT), tear meniscus height (TMH), and meibomian gland loss (MGL) were assessed using OSA. The presence of either or both reduced/absent meibum secretion and cloudy to toothpaste-like secretion was diagnosed as MGD.Results:Prevalence of total MGD was 57.52% (95% confidence interval [95% CI]: 48.3%–66.8%) and that of symptomatic MGD was 42.5% (95% CI: 33.2%–51.7%). Prevalence of total and symptomatic MGD was highest in those aged ≥50 years (P < 0.001 and P = 0.004, respectively). Computer vision syndrome increased the odds of symptomatic MGD (odds ratio [OR]: 4.3). NIBUT and MGL significantly differed in MGD and non-MGD groups (P = 0.023 and P < 0.001, respectively). LLT significantly differed between asymptomatic and symptomatic cases (P = 0.033). MGL >25% increased the odds of having MGD (OR: 19.1). Significant negative correlations were observed between MGL and NIBUT (P = 0.04) and between MGL and LLT (P = 0.02). MGL demonstrated the highest diagnostic accuracy for MGD (AUC = 0.827, sensitivity = 75.4%, specificity = 85.4%, cut-off value: ≥26%).Conclusion:MGD is a common disorder in adults attending the ophthalmology outpatient services of a tertiary eye care hospital. Incorporating noninvasive OSA in clinical practice can aid in rapid and reliable measurements of MGD-related parameters.     

Alteration in meibum lipid composition and subjective symptoms due to aging and meibomian gland dysfunction

PurposeTo investigate the alteration in lipid composition of meibum, objective clinical signs, and subjective symptoms associated with aging and meibomian gland (MG) dysfunction (MGD).MethodsIn 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.ResultsIn 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).ConclusionsOur findings revealed that both MGD and aging affect the composition ratio of major meibum lipids, resulting in the appearance of subjective symptoms.     

Human precorneal tear film and lipid layer dynamics in meibomian gland dysfunction

PurposeTo evaluate the precorneal tear film (PCTF) and lipid layer (TFLL) thicknesses and thinning rates in meibomian gland dysfunction (MGD) using a combined ultra-high-resolution optical coherence tomography (OCT) and thickness dependent fringe (TDF) interferometry system.MethodsBased on the Tear Film and Ocular Surface Society (TFOS) International Workshop on Meibomian Gland Dysfunction diagnostic algorithm, the Ocular Surface Disease Index (OSDI) and meibum grade score (MGS) were used to classify subjects into four groups: Normal (OSDI<13 and MGS<10), MGD (OSDI≥13 and MGS≥10), Asymptomatic MGD (OSDI<13 and MGS≥10), and Mixed (OSDI≥13 and MGS<10). The OCT/TDF system was used to capture PCTF and TFLL thicknesses and thinning rates. Kruskal-Wallis was used to compare median PCTF and TFLL thicknesses and thinning rates.ResultsThere were 190 subjects categorized into four groups: Normal (n = 63), MGD (n = 51), Asymptomatic MGD (n = 29), and Mixed (n = 47). The PCTF was significantly thinner in the Mixed group (3.3 [1.2]) than in the Normal (p < 0.001), MGD (p < 0.001) and Asymptomatic MGD (p = 0.009) groups. Relative to the Normal (4.5 [4.5] μm/min) and Mixed (5.0 [2.0] μm/min) groups, the rate of PCTF thinning was faster in the MGD (8.1 [3.0] μm/min, both p < 0.001) and Asymptomatic MGD (6.9 [3.1] μm/min, p = 0.009 and p = 0.04, respectively) groups. The correlation between PCTF thinning rate and TFLL thickness was ρ = −0.46, p < 0.001.ConclusionsSymptomatic and asymptomatic MGD shows rapid PCTF thinning rates (evaporation), while the PCTF thickness was reduced in mixed disease. Thicker lipid layers were associated with slower PCTF thinning.     

Infrared meibography allows detection of dimensional changes in meibomian glands following intranasal neurostimulation

PurposePatients with dry eye disease (DED) may suffer from decreased tear break-up time due to meibomian gland (MG) dysfunction. Infrared meibography (IR Meibography) uses infrared wavelength light to visualize meibomian glands in vivo. We aimed to explore the feasibility of using serial IR Meibography imaging to assess morphological changes in MGs as an indirect measure of functionality, following intranasal neurostimulation (ITN).MethodsFifteen DED subjects were prospectively enrolled in a single-center, single-arm study. Changes in MGs were captured using IR meibography (RTVUE-XR, Optovue, Inc. Fremont, CA, USA) on the lower eyelids before and after 3 min of ITN (TrueTear®, Allergan, Dublin, Ireland) use that delivers a microcurrent to sensory neurons of the nasal cavity. The same MGs were selected pre- and post-stimulation, and MG area and perimeter were analyzed by two masked observers.ResultsMean (±SD) pre- and post-stimulation MG areas were 2,187.60 ± 635.88 μm² and 1,933.20 ± 538.55 μm², respectively. The mean change in area, 254.49 μm², representing an 11.6% reduction following ITN use, was statistically significant (p = 0.001). Mean (±SD) pre- and post-stimulation MG perimeters were 235.9 ± 51.38 μm and 222.2 ± 47.72 μm, respectively. The mean change in perimeter, 13.7 μm, representing a 5.81% reduction following ITN use, was statistically significant (p = 0.012).ConclusionsOur study shows that IR meibography can be used to detect immediate changes in gland area and perimeter, an indirect measure of MG activity following intervention by ITN.     

Meibomian gland dysfunction is the primary determinant of dry eye symptoms: Analysis of 2346 patients

PurposeTo determine relative contributions of various ocular surface clinical signs and predisposing factors to the magnitude of dry eye symptoms.MethodsClinical audit data were prospectively collected for newly referred dry eye patients. All 2346 patients had an initial visit evaluation of the Ocular Surface Disease Index (OSDI), and a detailed ophthalmic examination including tear breakup time (TBUT), ocular surface fluorescein staining, Schirmer's I test. Among the participants, 1414 had number of liquid meibum expressing glands (NLMEG) evaluated on standard force expression. Other variables collected included history of glaucoma or glaucoma surgery, and history of allergies.ResultsIn patients aged 46.2 ± 14.8 years, 77.4% were women and 87.1% Chinese. The mean ± SD OSDI was 35.2 ± 21.7. On univariate analysis, higher OSDI was associated with glaucoma diagnosis (p = 0.003), glaucoma surgery (p = 0.002), greater temporal corneal staining (p = 0.002), reduced NLMEG (p < 0.001), and higher inferior forniceal papillary grade (p < 0.001). OSDI was not significantly associated with gender, TBUT, Schirmer's I test values, or the use of cyclosporine eyedrops. On multivariate regression, higher OSDI scores were associated with fewer NLMEG (p = 0.002) and increased lower eyelid forniceal papillary grading (p = 0.002). Corneal staining, glaucoma status and glaucoma surgery were not significantly associated with OSDI. Logistic regression showed that severe symptoms (OSDI>32) was associated with <2 NLMEG [OR(95%CI): 1.34(1.08–1.66)], and presence of inferior eyelid forniceal papillae [1.50(1.17–1.91)].ConclusionsMeibomian gland dysfunction (MGD) and lower forniceal papillary reaction had significant contributions to the severity of symptoms, in contrast to traditional dry eye signs. MGD should be objectively assessed and treated to improve symptoms.     

Alterations in corneal nerves in different subtypes of dry eye disease: An in vivo confocal microscopy study

PurposeTo evaluate corneal subbasal nerve alterations in evaporative and aqueous-deficient dry eye disease (DED) as compared to controls.MethodsIn this retrospective, cross-sectional, controlled study, eyes with a tear break-up time of less than 10 s were classified as DED. Those with an anesthetized Schirmer's strip of less than 5 mm were classified as aqueous-deficient DED. Three representative in vivo confocal microscopy images were graded for each subject for total, main, and branch nerve density and numbers.ResultsCompared to 42 healthy subjects (42 eyes), the 70 patients with DED (139 eyes) showed lower total (18,579.0 ± 687.7 μm/mm² vs. 21,014.7 ± 706.5, p = 0.026) and main (7,718.9 ± 273.9 vs. 9,561.4 ± 369.8, p < 0.001) nerve density, as well as lower total (15.5 ± 0.7/frame vs. 20.5 ± 1.3, p = 0.001), main (3.0 ± 0.1 vs. 3.8 ± 0.2, p = 0.001) and branch (12.5 ± 0.7 vs. 16.5 ± 1.2, p = 0.004) nerve numbers. Compared to the evaporative DED group, the aqueous-deficient DED group showed reduced total nerve density (19,969.9 ± 830.7 vs. 15,942.2 ± 1,135.7, p = 0.006), branch nerve density (11,964.9 ± 749.8 vs. 8,765.9 ± 798.5, p = 0.006), total nerves number (16.9 ± 0.8/frame vs. 13.0 ± 1.2, p = 0.002), and branch nerve number (13.8 ± 0.8 vs. 10.2 ± 1.1, p = 0.002).ConclusionsPatients with DED demonstrate compromised corneal subbasal nerves, which is more pronounced in aqueous-deficient DED. This suggests a role for neurosensory abnormalities in the pathophysiology of DED.     

Sex and age differences in symptoms and signs of dry eye disease in a Norwegian cohort of patients

PurposeTo investigate sex and age differences in symptoms and signs in a Norwegian clinic-based cohort of patients with dry eye disease (DED).MethodsVisitors at the Norwegian Dry Eye Clinic were examined using Ocular Surface Disease Index (OSDI) questionnaire score, tear osmolarity, tear break-up time (TFBUT), ocular surface staining, corneal sensitivity, Schirmer I test, and meibum expressibility (ME) and quality (MQ). A diagnosis of DED was made by an ophthalmologist based on symptoms and signs, and only DED patients were enrolled in the study: 1823 patients (338 males; mean age 51.2 ± 16.2 years; 1485 females; mean age 52.5 ± 16.0 years). The patients were divided into age subgroups: 20–39 years, 40–59 years and ≥60 years. Sex differences in the aforementioned tests were analyzed. Values were reported as mean ± standard deviation (SD), and intergroup comparisons were performed using Mann-Whitney U test. Multiple regression was used to analyze sex and age influences on symptoms and signs.ResultsWhen patients of all ages were analyzed, females had increased osmolarity, shorter TFBUT, reduced MQ and ME and higher corneal sensitivity. OSDI, Schirmer I test, ocular surface staining and corneal staining were not significantly different between the sexes. Only with TFBUT and ME were the sex difference present in all age subgroups. Multiple regression showed that all parameters were influenced by either sex or age, but only TFBUT and ME were influenced by both sex and age. (all p < 0.05).ConclusionsSex and age differences in dry eye were most consistent in TFBUT and ME, that indicate differences in meibomian gland functionality. Sex and age subgroup stratification is important in future studies investigating DED in other populations.     

Morphological characteristics of Meibomian Glands and their Influence on Dry Eye disease in contact lens wearers

PurposeMeibomian glands (MG) are now easily imaged via clinical meibography machines. The purpose of this work was to explore the utility of the known MG morphology metrics for predicting dry eye disease (DED) in contact lens (CL) wearers.MethodsSuccessful and previous CL wearers were recruited. DED was diagnosed if the participant's worst eye had a reduced tear meniscus height (TMH) of <0.2 mm or non-invasive tear break-up time (NITBUT) of <10 s and a Standardized Patient Evaluation of Eye Dryness (SPEED) score >5.0. Meibography was performed and images were subjectively graded by two examiners for the following MG characteristics: distorted, tortuous, hooked, abnormal gap, overlapping, fluffy areas, tadpoling, thinned, thickened, ghost, no extension to lid margin, shortened and dropout (atrophy). DED diagnostic ability of each metric was determined with receiver operating characteristic (ROC) analysis.ResultsA total of 112 participants were recruited, with 18.8% having DED and 60.7% being female. The only MG morphology metrics that were marginally predictive of DED were thickened upper eyelid MGs (p = 0.046), thickened mean upper plus lower eyelid MGs (p = 0.007), and atrophy of upper eyelid MGs (p = 0.043); however, none of these metrics reached a meaningful area under the curve in ROC analysis (all <0.70).ConclusionWhile abnormal MG morphology is likely suggestive of DED in CL wearers, none of the MG morphology metrics evaluated alone in this study had clinically meaningful predictive value for detecting DED in this group of current and previous CL wearers.     

Systemic risk factors of dry eye disease subtypes: A New Zealand cross-sectional study

PurposeTo evaluate systemic risk factors of dry eye disease, aqueous tear deficiency, and meibomian gland dysfunction.MethodsThree hundred and seventy-two community residents (222 females, 150 males; mean ± SD age, 39 ± 22 years) were recruited in a cross-sectional study. Past medical history, dry eye symptomology, ocular surface characteristics, and tear film quality were evaluated for each participant within a single clinical session. The diagnosis of dry eye disease, aqueous tear deficiency, and meibomian gland dysfunction were based on the global consensus recommendations of the Tear Film and Ocular Surface Society's Dry Eye Workshop II (TFOS DEWS II) and International Workshop on Meibomian Gland Dysfunction.ResultsOverall, 109 (29%) participants fulfilled the TFOS DEWS II criteria for dry eye disease, 42 (11%) had aqueous tear deficiency, and 95 (26%) had meibomian gland dysfunction. Multivariate logistic regression analysis demonstrated that systemic rheumatologic disease and antidepressant medication were independently associated with aqueous tear deficiency (both p < 0.05). Significant risk factors for meibomian gland dysfunction included age, East Asian ethnicity, migraine headaches, thyroid disease, and oral contraceptive therapy (all p ≤ 0.01).ConclusionsBoth etiological subtypes of dry eye disease were associated with a number of systemic risk factors. These findings would support routine systemic inquiry of dry eye disease and associated systemic conditions and medications, in order to facilitate opportunistic screening and timely inter-disciplinary referral where necessary.     

Dyslipidemia and its association with meibomian gland dysfunction

Abnormal serum lipid levels significantly increase the risk for cardiovascular disease. Furthermore, abnormal compositions of cholesterol in glandular secretions have been hypothesized as an etiology for meibomian gland dysfunction, yet this relationship has not been well studied in clinical settings. The primary purpose of this study was to determine if there is an association between dyslipidemia and meibomian gland dysfunction (MGD). The secondary purpose was to identify the factors, if any, that play a role in this association. A case–control study was performed between October 2013 and February 2015 which recruited 109 patients with MGD and 115 control patients without MGD. All participants were of Indian descent and had no history of dyslipidemia. Basic demographic information was collected as well as fasting levels of serum glucose, creatinine, triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). To calculate differences between groups, Z test or Student t test were used. A stepwise logistic regression model was used to calculate the estimates of odds ratios (ORs), where MGD was the dependent variable, making the independent variables consist of sex, age, body mass index (BMI), triglycerides ≥150 mg/dL, total cholesterol ≥200 mg/dL, LDL ≥130 mg/dL, or HDL ≤40 mg/dL, serum glucose, and serum creatinine. Dyslipidemia, defined by either a fasting total cholesterol level of ≥ 200 mg/dL, triglycerides ≥150 mg/dL, LDL ≥130 mg/dL, or HDL ≤40 mg/dL, was detected in 70 cases (64 %) and 21 controls (18 %), P < 0.001. Mean levels of triglycerides, total cholesterol, LDL, and HDL were 98.5 ± 42.1, 203.1 ± 13.2, 126.1 ± 10.2, and 53.3 ± 4.2 mg/dL, respectively, in cases and 82.3 ± 36.5, 156.6 ± 14.5, 92.2 ± 12.4, 45.8 ± 2.6 mg/dL, respectively, in controls. All differences were statistically significant (P < 0.05). MGD was significantly associated with age >65 years (OR 2.1; 95 % CI 1.2–3.2, P = 0.04), serum triglyceride concentration ≥150 mg/dL (OR 3.2; 95 % CI 1.9–4.4; P = 0.03), total cholesterol ≥200 mg/dL (OR 14.3; 95 % CI 8.2–20.7, P < 0.01), and LDL ≥130 mg/dL (OR 9.1; 95 % CI 6.6–13.2, P < 0.01). Adults from northern rural India with MGD are more likely to have abnormal serum lipid levels compared to age- and sex-matched adults without MGD. Eye care providers may have a role in discovering undiagnosed dyslipidemia, an important risk factor for cardiovascular illness.     

睑板腺功能障碍相关干眼的诊疗进展

近年来随着电子产品终端使用频率的增加,干眼的发病率也逐年攀升,严重影响人们的工作与生活。干眼是最常见的眼表疾病,通常由多种因素引起,其中睑板腺功能障碍是引起干眼的主要因素之一。睑板腺分泌异常或导管阻塞均会引起蒸发过强型干眼的发生。本综述通过总结相关文献,对睑板腺功能障碍相关干眼的病因、病理、诊断、相关治疗进行阐述。     

Comparable meibomian gland changes in patients with and without ocular graft-versus-host disease after hematopoietic stem cell transplantation

PurposeTo compare the presentation and severity of meibomian gland dysfunction (MGD) in patients with and without chronic ocular graft-versus-host disease (coGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).MethodsThis prospective cross-sectional study included 79 patients (47 with coGVHD and 32 without) after allo-HSCT. All participants completed ocular surface disease index questionnaire, and received slit lamp, ocular surface interferometer, meibography and confocal microscopy examination. The prevalence and severity of MGD were compared between two groups and related factors were analyzed. Main outcome measures were lipid layer thickness (LLT) and meiboscore.ResultsSimilarly high prevalence of MGD was detected in coGVHD and non-coGVHD groups (87.2% vs 84.4%, P = 0.977). Among those with MGD, although patients without coGVHD had longer noninvasive break-up time [5.54 (2.87, 9.37) vs 2.29 (0.00, 3.82) s, P < 0.001], patients in two groups presented similarly decreased LLT (53.5 ± 22.3 vs 47.1 ± 25.2 nm, P = 0.286), increased meiboscore (2.7 ± 1.5 vs 3.5 ± 1.8, P = 0.060) and enlarged acinar unit area (1647.7 ± 942.9 vs 1808.8 ± 1211.5 μm², P = 0.592). Meibomian gland inflammation and fibrosis were observed in both groups, but more predominant in coGVHD group. Results were consistent when patients within a comparable post-HSCT time interval were compared. Regression analysis revealed neither LLT nor meiboscore was associated with coGVHD severity. LLT was positively correlated with systemic immunosuppressant use (β = 12.0, P = 0.044), while meiboscore was positively correlated with lymphoma (β = 1.78, P = 0.040) and matched unrelated donor (β = 1.59,P = 0.008).ConclusionsMGD was common and evident in patients after allo-HSCT. MGD is not different between coGVHD and non-coGVHD patients except more inflammation and fibrosis in the former.     

Association of meibomian gland morphology with symptoms and signs of dry eye disease in the Dry Eye Assessment and Management (DREAM) study

PurposeTo describe associations between symptoms and signs of dry eye disease (DED) and meibomian gland (MG) morphology.MethodsCross-sectional study utilizing data from the Dry Eye Assessment and Management (DREAM) Study. Readers graded MG features in the middle third of upper and lower lids on infrared meibography images. Associations with signs and symptoms of DED were evaluated with adjustment for age and sex.ResultsAmong 268 patients, no MG features were associated with symptom scores (p > 0.08). Among 394 upper eyelids, better tear break-up times (<2, >2- <3.2and ≥ 3.2 s) were associated with more tortuous glands (mean (SD) 0.58(0.95), 0.83(1.2) and 1.14 (1.4), p = 0.01) and with higher scores on a composite score of MG features (21.90 (9.76), 23.29 (9.50), 26.26 (10.27); p = 0.02). Longer Schirmer test wetting lengths (0–5, >5–10, and >10 mm) were associated with increasing composite scores (22.02 (9.29), 23.80 (10.34), 24.96 (9.96), p = 0.03). Patients with Sjogren syndrome compared to other patients had fewer distorted MGs (mean 3.4 (2.3) vs 4.3 (2.3), p = 0.03) and fewer ghost glands (mean 0.33 (0.88) vs 0.89 (1.8), p = 0.006) in the upper lid.ConclusionIn the DREAM study, most MG morphologic features were not associated with the severity of DED symptoms or signs. Tortuous glands and a higher composite score for MG features were associated with longer tear break-up times and longer Schirmer test length in the upper eyelid only. Patients with Sjogren syndrome had fewer distorted and ghost glands.     

Visualization of microneuromas by using in vivo confocal microscopy: An objective biomarker for the diagnosis of neuropathic corneal pain?

PurposeThe diagnosis of neuropathic corneal pain (NCP) is challenging, as it is often difficult to differentiate it from conventional dry eye disease (DED). In addition to eye pain, NCP can present with similar signs and symptoms of DED. The purpose of this study is to find an objective diagnostic sign to identify patients with NCP, using in vivo confocal microscopy (IVCM).MethodsThis was a comparative, retrospective, case-control study. Patients with clinical diagnosis of NCP (n = 25), DED (n = 30), and age- and sex-matched healthy controls (n = 16), who underwent corneal imaging with IVCM (HRT3/RCM) were included. Central corneal IVCM scans were analyzed by 2 masked observers for nerve density and number, presence of microneuromas (terminal enlargements of subbasal corneal nerve) and/or nerve beading (bead-like formation along the nerves), and dendritiform cell (DC) density.ResultsThere was a decrease in total nerve density in both NCP (14.14 ± 1.03 mm/mm²) and DED patients (12.86 ± 1.04 mm/mm²), as compared to normal controls (23.90 ± 0.92 mm/mm²; p < 0.001). However, total nerve density was not statistically different between NCP and DED patients (p = 0.63). Presence of nerve beading was not significantly different between patients and normal controls (p = 0.15). Interestingly, microneuromas were observed in all patients with NCP, while they were not present in any of the patients with conventional DED (sensitivity and specificity of 100%). DC density was significantly increased in both NCP (71.89 ± 16.91 cells/mm²) and DED patients (111.5 ± 23.86 cells/mm²), as compared to normal controls (24.81 ± 4.48 cells/mm² (p < 0.05). However, there was no significant difference in DC density between DED and NCP patients (p = 0.31).ConclusionIVCM may be used as an adjunct diagnostic tool for the diagnosis of NCP in the presence of neuropathic symptoms. Microneuromas may serve as a sensitive and specific biomarker for the diagnosis of NCP.     

Ageing and the natural history of dry eye disease: A prospective registry-based cross-sectional study

PurposeTo investigate the impact of ageing on ocular surface parameters, and empirically determine optimal prognostic cut-off ages for clinical markers of dry eye disease, aqueous tear deficiency, and meibomian gland dysfunction.MethodsA total of 1331 community residents (785 females, 546 males; mean ± SD age, 38 ± 19 years) were recruited in a prospective registry-based cross-sectional study. Dry eye symptomology, ocular surface characteristics, and tear film quality were evaluated for each participant within a single clinical session, in accordance with the global consensus recommendations of the TFOS DEWS II reports.ResultsMultivariate regression analysis demonstrated positive associations between ageing and clinical markers of dry eye disease (all p ≤ 0.001). The Youden-optimal prognostic cut-off ages for signs of meibomian gland dysfunction occurred during the third decade of life (24–29 years); the optimal predictive ages for lid wiper epitheliopathy, tear film instability, hyperosmolarity, and dry eye symptoms occurred during the fourth decade of life (31–38 years); while the optimal prognostic thresholds for signs of aqueous tear deficiency and ocular surface staining occurred in the fifth and sixth decades of life (46–52 years).ConclusionsAdvancing age is a significant risk factor for dry eye disease, which represents a growing public health concern with the ageing population worldwide. Signs of meibomian gland dysfunction appeared earlier in the natural history of disease progression, and the brief delay prior to the development of other clinical dry eye signs might represent a window of opportunity for preventative interventions in the young adult age group.     

DryEyeRhythm: A reliable and valid smartphone application for the diagnosis assistance of dry eye

PurposeUndiagnosed or inadequately treated dry eye disease (DED) decreases the quality of life. We aimed to investigate the reliability, validity, and feasibility of the DryEyeRhythm smartphone application (app) for the diagnosis assistance of DED.MethodsThis prospective, cross-sectional, observational, single-center study recruited 82 participants (42 with DED) aged ≥20 years (July 2020–May 2021). Patients with a history of eyelid disorder, ptosis, mental disease, Parkinson's disease, or any other disease affecting blinking were excluded. Participants underwent DED examinations, including the Japanese version of the Ocular Surface Disease Index (J-OSDI) and maximum blink interval (MBI). We analyzed their app-based J-OSDI and MBI results. Internal consistency reliability and concurrent validity were evaluated using Cronbach's alpha coefficients and Pearson's test, respectively. The discriminant validity of the app-based DED diagnosis was assessed by comparing the results of the clinical-based J-OSDI and MBI. The app feasibility and screening performance were evaluated using the precision rate and receiver operating characteristic curve analysis.ResultsThe app-based J-OSDI showed good internal consistency (Cronbach's α = 0.874). The app-based J-OSDI and MBI were positively correlated with their clinical-based counterparts (r = 0.891 and r = 0.329, respectively). Discriminant validity of the app-based J-OSDI and MBI yielded significantly higher total scores for the DED cohort (8.6 ± 9.3 vs. 28.4 ± 14.9, P < 0.001; 19.0 ± 11.1 vs. 13.2 ± 9.3, P < 0.001). The app's positive and negative predictive values were 91.3% and 69.1%, respectively. The area under the curve (95% confidence interval) was 0.910 (0.846–0.973) with concurrent use of the app-based J-OSDI and MBI.ConclusionsDryEyeRhythm app is a novel, non-invasive, reliable, and valid instrument for assessing DED.