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

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.

Comparison of efficacy and safety of accelerated trans-epithelial crosslinking for keratoconus patients with corneas thicker and thinner than 380µm.

PURPOSE: Accelerated trans-epithelial cross-linking (ATE-CXL), a therapy to halt keratoconus progression, has the merit of widening the indications for thinner corneas (<380 µm). Since a hypotonic solution affects the swollen cornea, corneas of <380 µm thickness at preoperative measurement can be an indication for ATE-CXL. The aim of this retrospective study was to compare the efficacy and safety of ATE-CXL for keratoconus between corneas with thicknesses <380 µm and ≥380 µm. MATERIALS AND METHODS: Thirty-four eyes of 27 patients who underwent ATE-CXL (30 mW/cm2; 3 minutes) with completion of a 24-month follow-up, were enrolled and divided into two groups: Group 1, thinnest corneal thickness (TCT), <380 µm (n = 10) and Group 2, TCT, ≥380 µm (n = 24). A hypotonic solution was administered to Group 1 until the corneal thickness increased by >380 µm before UV-A irradiation. We measured uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), maximum and average keratometric values (Kmax and AveK), central corneal thickness (CCT), TCT by anterior segment optical coherence tomography, and corneal endothelial cell density (ECD) using specular microscopy. The changes from baseline to 24 months postoperatively between the two groups were compared accordingly. RESULTS: The changes in Kmax and AveK from baseline to 24 months in Group 1 (ΔKmax: -7.8 ± 7.7 D, ΔAveK: -4.3 ± 6.1 D) showed significant decreases compared to those in Group 2 (ΔKmax: 0.2 ± 3.0 D, ΔAveK: 0.6 ± 2.7 D) (p = .004 and p = .001), and there were no significant changes from baseline to 24 months postoperatively in UCVA, BCVA, CCT, TCT, and ECD in both groups. CONCLUSION: ATE-CXL is effective and safe for keratoconic corneas in both groups. The effect of reducing keratometric values was greater in the group with thinner corneas.

Assessment of Long-Term Anterior and Posterior Topographic Changes in the Cornea After Ptosis Surgery Using Fourier Harmonic Analysis.

PURPOSE: We aimed to assess the corneal refractive changes induced by ptosis surgery in patients with acquired ptosis using Fourier harmonic analysis. METHODS: This retrospective observational study enrolled consecutive patients who underwent levator aponeurotic surgery for acquired ptosis at the Department of Ophthalmology in the University of Tokyo Hospital from May 2016 to January 2018. Best corrected visual acuity, central corneal thickness, average keratometric corneal power (AvgK), corneal astigmatism, and topographic data using Fourier analysis were analyzed preoperatively and 6 months postoperatively. RESULTS: Thirty-two eyes of 32 patients (age, 72.6 ± 8.5 years) were included in this study. There were no significant differences in best corrected visual acuity and central corneal thickness. However, there were significant decreases in anterior AvgK, anterior corneal astigmatism, and posterior corneal astigmatism 6 months postoperatively (all, P < 0.001). Fourier harmonic analysis showed that the anterior spherical component significantly decreased 6 months postoperatively (P < 0.001). There were no significant differences in other components of the anterior and posterior cornea. There was a significant negative correlation between preoperative posterior AvgK and changes in posterior AvgK (r = -0.891, P < 0.001) and between preoperative posterior corneal astigmatism and changes in posterior corneal astigmatism at 6 months (r = -0.858, P < 0.001). CONCLUSIONS: Anterior and posterior corneal keratometry and posterior corneal astigmatism significantly changed 6 months after ptosis surgery for acquired ptosis.

Relation of Dietary Fatty Acids and Vitamin D to the Prevalence of Meibomian Gland Dysfunction in Japanese Adults: The Hirado-Takushima Study.

Intervention studies have shown that n-3 polyunsaturated fatty acid (PUFA) supplementation is effective for the treatment of meibomian gland dysfunction (MGD). Ointment containing an analog of vitamin D has also been found to improve symptoms and signs of MGD. We have now evaluated the relation of MGD prevalence to dietary intake of fatty acids (FAs) and vitamin D among a Japanese population. Subjects comprised 300 adults aged 20 to 92 years residing on Takushima Island. MGD was diagnosed on the basis of subjective symptoms, lid margin abnormalities, and meibomian gland obstruction. Dietary FA and vitamin D intake was estimated with a brief-type self-administered diet history questionnaire. MGD prevalence was 35.3%. Multivariate adjusted odds ratios (95% confidence intervals) between extreme quintiles of intake for MGD prevalence were 0.40 (0.16-0.97) for total fat, 0.40 (0.17-0.97) for saturated FAs, 0.40 (0.17-0.97) for oleic acid, 0.52 (0.23-1.18) for n-3 PUFAs, 0.63 (0.27-1.49) for n-6 PUFAs, 1.32 (0.59-2.95) for the n-6/n-3 PUFA ratio, and 0.38 (0.17-0.87) for vitamin D. Total fat, saturated FA, oleic acid, and vitamin D intake may thus be negatively associated with MGD prevalence in the Japanese.

Association between tear and blood glucose concentrations: Random intercept model adjusted with confounders in tear samples negative for occult blood.

AIMS/INTRODUCTION: To prevent diabetic complications, strict glucose control and frequent monitoring of blood glucose levels with invasive methods are necessary. We considered the monitoring of tear glucose levels might be a possible method for non-invasive glucose monitoring. To develop tear glucose monitoring for clinical application, we investigated the precise correlation between the blood and tear glucose concentrations. MATERIALS AND METHODS: A total of 10 participants and 20 participants with diabetes were admitted, and blood and tear samples were collected. Before statistical analysis, we eliminated tear samples contaminated with blood. We observed the daily blood and tear glucose dynamics, and carried out a random intercept model analysis to examine the association between the blood and tear glucose concentrations. RESULTS: Tear occult blood tests showed that the tear glucose concentrations and their variation increased in both participants with and without diabetes as contamination of blood increased. In both participants with and without diabetes, fluctuations of the plasma glucose concentrations were observed depending on the timing of collection of the samples, and the dynamics of the tear glucose concentrations paralleled those of the plasma glucose concentrations. The random intercept model analysis showed a significant association between the plasma and tear glucose concentrations in participants with diabetes (P < 0.001). This association still existed even after adjusting for the glycated hemoglobin levels and the prandial state (P < 0.001). CONCLUSIONS: It is important to eliminate the tear samples contaminated with blood. Tear glucose monitoring might be a reliable and non-invasive substitute method for monitoring the blood glucose concentrations for diabetes patients, irrespective of glycated hemoglobin levels and timing of sample collection.

Risk factors and evaluation of keratoconus progression after penetrating keratoplasty with anterior segment optical coherence tomography.

To determine the risk factors and unique characteristics of keratoconus (KC) progression after penetrating keratoplasty (PK), anterior segment optical coherence tomography parameters were statistically analyzed in comparison with eyes undergoing PK for other diseases as a control. Ninety-one eyes maintaining clear PK grafts for over 10 years were divided into 2 groups according to the primary indication for PK (KC vs Others groups). Corneal thinning indicators (inferior host thinnest corneal thickness/central corneal thickness [IHT/CCT], inferior graft thinnest corneal thickness/CCT [IGT/CCT]), were smaller whereas anterior chamber depth, and steepest corneal power (Ks), and maximum corneal power (Kmax) were larger in the KC group with statistical significance. Graft size, Kmax and Ks correlated with IHT/CCT and IGT/CCT in the KC group. These correlations were not detected in controls. Graft size and postoperative period were selected by multivariate regression analysis as factors for corneal ectatic changes in the KC group. In conclusion, KC eyes long after PK show inferior graft and host corneal thinning, and corneal protrusion. Corneal power parameters such as Kmax or Ks can be used to monitor KC progression after PK. A small graft might lead to KC progression after PK.

Corneal topography in keratoconus evaluated more than 30 years after penetrating keratoplasty: a Fourier harmonic analysis.

The aim of this observational study was to examine the characteristics of anterior and posterior corneal topography in keratoconic eyes more than 30 years after penetrating keratoplasty (PK). Patients who maintained clear grafts for more than 30 years after PK were included and divided into the keratoconus (KC) group or other diseases (Others) group, based on the primary indication. Twenty-six eyes of 26 patients were included. The KC group and the Others group included 14 eyes and 12 eyes, respectively. The KC group participants were younger at the time of surgery (P = 0.03). No differences were found in best-spectacle-corrected visual acuity, keratometric power, and central-corneal-thickness. Based on corneal topography using Fourier harmonic analyses, regular astigmatism in the anterior cornea was significantly larger (P = 0.047) and the spherical component in the posterior cornea was significantly lower (P = 0.01) in the KC group. The area under the receiver operating characteristic curve of the spherical component, regular astigmatism, asymmetry component, and higher-order irregularity were 66.07%, 63.10%, 57.14%, and 59.23%, respectively, in the anterior cornea and 80.65%, 52.98%, 63.10%, and 63.99%, respectively, in the posterior cornea. Our results suggested that Fourier harmonic analysis of corneal topography could be useful for patients with KC long after PK.

Comparison of 5-Year Clinical Results of Descemet and Non-Descemet Stripping Automated Endothelial Keratoplasty.

PURPOSE: To compare 5-year clinical results of non-Descemet stripping automated endothelial keratoplasty (nDSAEK) and DSAEK. METHODS: A retrospective chart review involving patients with non-Fuchs-type bullous keratoplasty who underwent nDSAEK or DSAEK 5 years before the review was performed on demographics, graft survival rate, endothelial cell density (ECD), best-corrected visual acuity (BCVA), and complications. RESULTS: Fifty eyes (nDSAEK 28, DSAEK 22) were included in this study. Common indications for surgery were bullous keratopathy due to glaucoma, cataract surgeries, or laser iridotomy. The graft survival rates in nDSAEK and DSAEK eyes at 1, 3, and 5 years were 0.75 and 0.86, 0.67 and 0.81, and 0.59 and 0.74, respectively. The mean donor ECDs of nDSAEK and DSAEK eyes were 2638 and 2503 cells/mm, respectively; these decreased to 1654 and 1406, 1503 and 1218, and 1108 and 1020 cells/mm at 1, 3, and 5 years, respectively. The mean preoperative BCVAs of nDSAEK and DSAEK eyes were 1.08 and 1.11 LogMAR, respectively; these improved to 0.238 and 0.190, 0.126 and 0.157, and 0.097 and 0.070 LogMAR at 1, 3, and 5 years, respectively. The most common complication was intraocular pressure elevation. There were no statistically significant differences between nDSAEK and DSAEK in graft survival rates, changes in ECD and BCVA, or the occurrence of postoperative complications, with the exception of the change in ECD at 2 years (1173 and 1193 cells/mm, P = 0.0159). CONCLUSIONS: Our 5-year clinical results of nDSAEK and DSAEK did not show significant differences at almost all points.

Meibomian Gland Dysfunction and Dry Eye Are Similar but Different Based on a Population-Based Study: The Hirado-Takushima Study in Japan.

PURPOSE: To evaluate the prevalence and risk factors of and the relationship between meibomian gland dysfunction (MGD) and dry eye (DE) in Japan. DESIGN: A population-based cross-sectional study. METHODS: Participants filled in questionnaires regarding ocular symptoms, systemic diseases, and lifestyle factors. Meibomian gland-related parameters and tear film-related parameters were evaluated. Risk factors for MGD and DE were analyzed by using univariate and multivariate logistic regression. Age-specific prevalence of MGD and DE was estimated by using a general additive model with degree-3 natural splines. The structural relation between MGD and DE was assessed by factor analysis using the principal components method and promax rotation. RESULTS: A total of 356 residents of Takushima Island (133 males, 223 females) at the mean ± SD age of 55.5 ± 22.4 years (range, 6-96 years) were enrolled. The prevalence of MGD and DE was 32.9% and 33.4%, respectively, with a coexistence rate of 12.9%. The prevalence of MGD was associated with male sex (odds ratio [OR], 2.42), age (OR per decade increment,1.53), and oral intake of lipid-lowering agents (OR, 3.22). The prevalence of DE was associated with female sex (OR, 3.36), contact lens wear (OR, 2.84), conjunctivochalasis (OR, 2.57), and lid margin abnormalities (OR, 3.16). The age-specific prevalence of MGD and DE differed, and factor analysis for 16 parameters showed that MGD and DE had independent hidden sources (interfactor correlation, -0.017). CONCLUSIONS: MGD and DE are common in this population. Although their ocular symptoms are similar, the pathogenesis of MGD differs from that of DE.

Characteristics and risk factors of recurrent keratoconus over the long term after penetrating keratoplasty.

PURPOSE: To determine the characteristics and risk factors of recurrent keratoconus (KC) after penetrating keratoplasty (PK). METHODS: We enrolled patients who had maintained clear grafts for at least 10 years after PK based on their medical records. Patients were divided into the KC group or Others group based on the primary indication for PK. Each case was reviewed for clinically observed corneal ectasia. Steepest keratometric power (Ks), cylinder (CYL), and difference between Ks and minimum keratometric power (MinK) were analyzed in patients that underwent corneal topography more than three times after the 5th postoperative year. RESULTS: One hundred one eyes of 82 patients were enrolled. The KC group comprised 50 eyes and the Others group comprised 51 eyes (herpes [n = 22], corneal leukoma [n = 12], and other [n = 17]). The mean period after PK was 27.2 years in the KC group and 26.0 years in the Others group. Recurrent KCs were observed in 18 eyes of 14 patients (36%), all of whom were in the KC group (p = 0.0001). Six of these eyes underwent PK again and all the grafts showed keratoconic changes histopathologically. The mean Ks during the whole observation period was 52.5 diopters (D) in the KC group and 49.2 D in the Others group (p < 0.0001). Logistic regression analysis revealed the risk factors of recurrent KC with positive Ks change and large CYL with significant p values (p = 0.0102, 0.0318, respectively). CONCLUSIONS: KC progresses even after PK over the long term, requiring re-grafting in some cases. Risk factors for recurrent KC after PK are increasing Ks over time and a large CYL.

Descemet Stripping Automated Endothelial Keratoplasty for Failed Penetrating Keratoplasty: Influence of the Graft-Host Junction on the Graft Survival Rate.

PURPOSE: To investigate the clinical results of Descemet stripping automated endothelial keratoplasty (DSAEK) for failed penetrating keratoplasty (PK) and the influence of the graft-host junction (GHJ) on the graft survival rate. METHODS: Data were retrospectively collected on patient demographics, visual outcomes, complications, and graft survival rate for 17 eyes of 16 patients who underwent DSAEK for failed PK. The graft survival rate was compared between the eyes when divided into a bump group and a well-aligned group according to the shape of the GHJ detected on anterior segment optical coherence tomography. RESULTS: The most common indication for initial PK was bullous keratopathy after glaucoma surgery (35.3%). Seven eyes (41.2%) were classified into the bump group and 10 eyes (58.8%) into the well-aligned group. The mean best-ever documented visual acuity (BDVA) after DSAEK was 0.33 logMAR. Postoperatively, almost 70% of eyes achieved a BDVA that was within 0.2 logMAR of their preoperative BDVA. Graft detachment occurred in 29.4% of eyes and primary graft failure in 17.6%. All primary failures occurred in the bump group. The cumulative graft survival rate was 82.3% at 1 year, 73.2% at 2 years, and 58.6% at 3 years. Graft failure was more likely in eyes in the bump group than in those in the well-aligned group (P = 0.037, Wilcoxon test). CONCLUSIONS: DSAEK for failed PK had a favorable outcome in this study. However, the GHJ should be assessed carefully before performing the procedure.

Quantitative Analysis of Changes to Meibomian Gland Morphology Due to S-1 Chemotherapy.

PURPOSE: The aim of this prospective, noncomparative, observational case series was to evaluate changes to meibomian gland morphology in patients undergoing S-1 chemotherapy with the use of noninvasive meibography and analytical software. METHODS: Patients aged ≥20 years and undergoing S-1 chemotherapy were included. Ophthalmologic examinations were performed before S-1 administration (Pre) and at 1, 3, and 6 months afterward (1M, 3M, and 6M, respectively). Meibography images were analyzed using analytical software. The ratio of the total meibomian gland area relative to the whole measurement area (meibomian gland area ratio [MGAR]) and the rate of change to the MGAR (MGAR at Pre, 1M, 3M, or 6M)/(MGAR at Pre) × 100 were calculated. RESULTS: In total, 28 eyelids of seven men (mean age, 68.9 ± 6.3 years) were studied. The mean MGAR of the upper and lower eyelids significantly decreased at 3M (P = 0.0246 and P = 0.00892, respectively) and 6M (P < 0.0001 and P < 0.0001, respectively). There was a significant negative correlation between the cumulative dose of S-1 and the rate of change to the MGAR of the upper (P < 0.0001, r = -0.77) and lower (P < 0.0001, r = -0.785) eyelids. However, there was no other significant difference. CONCLUSIONS: The meibomian gland area decreased after S-1 administration with significant correlations between the rate of change to the MGAR and the mean cumulative dose of S-1. TRANSLATIONAL RELEVANCE: Systemic S-1 administration decreased the MGAR in a dose-dependent manner; thus, clinicians should pay more attention to morphologic changes to the meibomian glands during early treatment with S-1.

Changes in meibomian gland morphology and ocular higher-order aberrations in eyes with chalazion.

PURPOSE: To examine the changes in meibomian gland morphology and ocular higher-order aberrations (HOAs) in eyes with chalazion and its excision. METHODS: Seven male patients with previous history of chalazion excision and seven control male subjects were enrolled. Changes in meibomian gland morphology (meiboscores, gland dropout, and shortening) were evaluated by using meibography equipped in a wavefront analyzer KR-1W and in a slit-lamp device BG-4M. Ocular HOAs were measured sequentially with KR-1W. The tear film breakup time (BUT) was measured. RESULTS: Both KR-1W and BG-4M visualized meibomian gland as clear similar images. The tear film BUT (mean ± SD, 5.6±3.0 vs 9.4±2.3 seconds, P=0.025), the total meiboscore (median [interquartile range], 2 (2-3) vs 0 (0-1), P=0.007) as well as the meibomian gland dropout rate (86% vs 14%, P=0.008) and shortening rate (100% vs 29%, P=0.031) differed significantly between the patient and control groups. The first total ocular HOAs (0.142±0.063 vs 0.130±0.015, P=0.80) were similar in both groups, whereas the stability index of the total HOAs over time (0.0041±0.0048 vs -0.0012±0.0020, P=0.030) differed significantly between the patient and control groups. CONCLUSIONS: Chalazion and its excision were associated with dropout and shortening rate of meibomian glands. The morphological changes of meibomian glands in chalazion may be associated to instability of the tear film, which was suggested by the tear film BUT and the stability of ocular HOAs.

Ocular surface alkali injury damages meibomian glands in mice.

PURPOSE: To examine effects of alkali injury of the ocular surface on meibomian gland pathology in mice. METHODS: Three µL of 1 N NaOH were applied under general anesthesia to the right eye of 10-week-old BALB/c (n = 54) mice to produce a total ocular surface alkali burn. The meibomian gland morphology was examined at days 1, 2, 5, 10, and 20 by stereomicroscopy and non-contact infrared meibography. Mice were then sacrificed and eyelids processed for histology with hematoxylin-eosin and immunohistochemistry for ELOVL4, PPARγ, myeloperoxidase (a neutrophil marker) and F4/80 macrophage antigen, as well as TUNEL staining. Another set of specimens was processed for cryosectioning and Oil red O staining. RESULTS: Alkali injury to the ocular surface produced cellular apoptosis, infiltration of neutrophils and macrophages, degeneration of the meibomian gland, and ductal dilation. Inflammation in and destruction of acunal stricture seemed more prominent in the lower eyelid, while duct dilation was more frequently observed in the upper eyelid during healing. Surviving acinar cells were labeled for ELOVL4 and PPARγ. Oil red O staining showed that the substance in the dilated duct contained predominantly neutral lipid. CONCLUSIONS: Alkali injury to the ocular surface results in damage and destruction of the eyelid meibomian glands. The pattern of the tissue damage differs between glands of the upper and lower eyelids.

Morphological changes in the meibomian glands of patients with phlyctenular keratitis: a multicenter cross-sectional study.

BACKGROUND: Phlyctenular keratitis is a hypersensitivity reaction of the cornea, and a complication of eyelid margin disease in children and young adults. In this study, we compared the morphology of the meibomian glands in eyelids between phlyctenular keratitis patients and healthy young adults, using noncontact meibography. METHODS: The study included 16 eyes of 13 patients diagnosed with phlyctenular keratitis and 17 eyes of 17 healthy volunteers. Slit-lamp observations of the cornea and eyelid were performed on all subjects. The morphology of the meibomian glands was scored using non-contact meibography (meiboscore). The meiboscore in worse eye was used in bilateral phlyctenular keratitis. RESULTS: All eyes with phlyctenular keratitis, but not normal controls, showed corneal nodules, neovascularization, and superficial punctate keratopathy. The mean meiboscore in phlyctenular keratitis patients (upper lid: 2.9 ± 0.3, lower lid: 2.7 ± 0.5) was significantly higher than in controls (upper lid: 0.4 ± 0.6, lower lid: 0.1 ± 0.3). CONCLUSIONS: Noncontact meibography enabled visualization of meibomian gland loss in phlyctenular keratitis patients, suggesting a relationship between abnormalities of the meibomian glands in young individuals and the pathogenesis of phlyctenular keratitis.

Development of Definitive and Reliable Grading Scales for Meibomian Gland Dysfunction.

PURPOSE: To develop and validate grading scales for meibomian gland dysfunction (MGD) that allow consistent diagnosis of MGD and are suitable for clinical studies. DESIGN: Development and validation study of grading scales. METHODS: Lid margin and meibomian gland photographs were taken in the multicenter, prospective cross-sectional study for MGD and control subjects. New grading scales for MGD signs (abnormal lid margin findings of vascularity, plugging of gland orifices, lid margin irregularity, lid margin thickening, partial glands, and gland dropout) in both upper and lower eyelids were developed. Three MGD experts, 3 general ophthalmologists, and 3 non-physicians independently tested the scales by evaluating photographs. The levels of interrater and intrarater agreement for each grading scale were estimated with the use of kappa statistics. RESULTS: Thirty-eight patients with MGD and 20 control subjects were enrolled and photographed. New grading scales were developed using a total of 226 photographs. The interrater kappa values for MGD experts and for general ophthalmologists and non-physicians with reference to an MGD expert ranged from 0.36 to 0.87 (median of 0.66), 0.41 to 0.73 (0.60), and 0.30 to 0.77 (0.59), respectively. Those for intrarater reliability for 2 MGD experts ranged from 0.49 to 0.93 (0.82). CONCLUSIONS: New grading scales for MGD signs were developed and found to have appropriate inter- and intrarater reliabilities for grading MGD. These grading scales are suitable for MGD diagnosis and application to multicenter trials.

Linoleic acid content of human meibum is associated with telangiectasia and plugging of gland orifices in meibomian gland dysfunction.

To examine the relation between changes in the free fatty acid (FFA) composition of human meibum and both objective signs and subjective symptoms of meibomian gland dysfunction (MGD), we analyzed the FFA content of meibum collected from both MGD patients and control subjects. Thirty-eight patients with MGD (13 men and 25 women; mean age ± SD, 66.9 ± 15.0 years) were evaluated. Various objective signs and subjective symptoms of MGD were assessed. Meibum was analyzed by liquid chromatography-Fourier transform mass spectrometry, and the relation between the FFA composition of meibum and each objective sign and subjective symptom was examined by principal component analysis (PCA). No relation was apparent between the FFA composition of meibum and individual subjective symptoms or objective signs of MGD. However, a PCA score plot for meibum samples grouped on the basis of the severity of both telangiectasia and plugging of meibomian gland orifices revealed clear separation of mild and severe groups. This separation of the two groups was largely due to a significantly increased linoleic acid content in meibum of the severe group (3.56%, versus 0.70% of total FFAs in the mild group). The relative amount of linoleic acid in meibum was thus associated with the severity of telangiectasia and plugging of gland orifices in MGD, suggesting that this FFA might contribute to the pathogenesis of these signs.

Meibum Color and Free Fatty Acid Composition in Patients With Meibomian Gland Dysfunction.

PURPOSE: We measured the components of meibum in patients with meibomian gland dysfunction (MGD) and control subjects and then examined the relation between meibum composition and clinical parameters. METHODS: Thirty-eight patients with MGD (13 men and 25 women; mean age ± SD, 66.9 ± 15.0 years) and 20 control subjects (8 men and 12 women; 64.5 ± 6.7 years) were enrolled. Ocular symptom score, keratoconjunctival staining score, tear film breakup time, and Schirmer's test value were determined. Lid margin abnormalities and meibomian gland morphology were assessed for upper and lower eyelids, and meibum properties were evaluated at temporal, central, and nasal sites of each lid. Free fatty acid (FFA) composition of meibum was analyzed by liquid chromatography-Fourier transform mass spectrometry. RESULTS: Upper meibum color score was significantly correlated with epiphora and sticky sensation in MGD patients. Meibum grade, color, or viscosity did not differ significantly among the sites evaluated. A total of 103 species of FFA--including very long chain (such as C36 and C37) and odd-numbered chain (such as C17, C19, and C21) FFAs--were detected in meibum. Free fatty acid composition differed between clear and colored (cloudy or yellow) meibum, with unsaturated FFAs tending to be more abundant in colored meibum. CONCLUSIONS: Free fatty acid composition of human meibum correlates with meibum color as determined with a slit-lamp microscope. This finding may provide insight into the pathogenesis of MGD.

Effects of Eyelid Warming Devices on Tear Film Parameters in Normal Subjects and Patients with Meibomian Gland Dysfunction.

PURPOSE: To evaluate the effects of commercially available eyelid warming devices on ocular temperatures, tear film function, and meibomian glands in normal subjects and patients with meibomian gland dysfunction (MGD). METHODS: Ten healthy volunteers were enrolled to evaluate the effects of a single warming and of repeated warming for 2 weeks. Ten MGD patients were enrolled for evaluation of repeated warming over 1 month. Two non-wet (Azuki no Chikara, Eye Hot R) and three wet (hot towel, Hot Eye Mask, Memoto Este) devices were compared in a masked manner. Visual analog scale (VAS) score for ocular symptoms, tear film breakup time (TFBUT), meibum grade, temperatures (eyelid skin, tarsal conjunctiva, central cornea), Schirmer test value, and meibomian gland area were measured before and after warming application. RESULTS: The single application of the five warming devices improved the VAS score, TFBUT, and ocular temperatures. In the repeated warming application, Azuki no Chikara as a representative non-wet warming device induced a stable and significant improvement in TFBUT and increased the tarsal conjunctival temperature and meibomian gland area in both normal subjects and MGD patients. It also improved meibum grade in MGD patients. CONCLUSION: Our results suggest that repeated eyelid warming with a non-wet device improves tear film function in normal individuals and may have beneficial effects on both tear film and meibomian gland function in MGD patients.

Increased Tear Fluid Production as a Compensatory Response to Meibomian Gland Loss: A Multicenter Cross-sectional Study.

PURPOSE: To compare tear film parameters as well as meibomian gland morphologic features and function among patients with meibomian gland dysfunction (MGD), those with non-Sjögren syndrome aqueous-deficient dry eye (non-SS ADDE), those with non-SS ADDE and MGD, and normal subjects. DESIGN: Multicenter, cross-sectional, observational case series. PARTICIPANTS: Forty-one eyes of 41 patients (all women; mean age ± standard deviation, 62.1±9.9 years) with non-SS ADDE, 70 eyes of 70 patients (all women; 66.0±8.7 years) with MGD, 17 eyes of 17 patients (all women; 72.4±7.8 years) with non-SS ADDE and MGD, and 70 eyes of 70 normal control subjects (all women; 65.0±7.1 years). METHODS: Ocular symptoms were scored from 0 to 14 and lid margin abnormalities from 0 to 4 according to their respective number. Meibomian gland changes were scored from 0 to 6 (meiboscore) on the basis of noncontact meibography findings, and meibum was graded from 0 to 3 depending on its volume and quality. Conjunctival and corneal epithelial damage were scored from 0 to 9 (fluorescein score). Tear film break-up time (TBUT) was measured as an index of tear film stability, and tear fluid production was evaluated with Schirmer's test. MAIN OUTCOME MEASURES: Ocular symptom score, lid margin abnormality score, meiboscore, meibum grade, fluorescein score, TBUT, and Schirmer's test value. RESULTS: The ocular symptom score did not differ significantly between the MGD and non-SS ADDE groups (P = 0.762). The lid margin abnormality score, meiboscore, and meibum grade were significantly higher in the MGD group than in the non-SS ADDE group (P = 0.0012, P < 0.0001, and P < 0.0001, respectively). The fluorescein score, TBUT, and Schirmer's test value were significantly worse in the non-SS ADDE group than in the MGD group (P < 0.0001, P = 0.0061, and P < 0.0001, respectively). The meiboscore correlated significantly with Schirmer's test value only in the MGD group (ρ = 0.508, P = 8.3×10(-6)). CONCLUSIONS: An increase in tear fluid production likely compensates for loss of meibomian glands in individuals with MGD.