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Background: To investigate the association of long-term androgen deprivation therapy (ADT) with ocular surface characteristics in prostate cancer patients., Methods: A total of 30 male prostate cancer patients who received ADT were selected. All candidates were scored using the Ocular Surface Disease Index (OSDI) and subsequently divided into two groups containing 9 symptomatic patients (scores >12) and 21 asymptomatic patients (scores ≤ 12). Another 20 healthy age-matched males were selected as the control group. Each candidate was assessed with respect to eyelid margin abnormality, tear film break-up time (NI-BUT), tear meniscus height (TMH), meiboscore, meibum expressibility, and demodex infection., Results: The NI-BUT in the ADT group was significantly shorter than that in the control group. The scores for OSDI, eyelid margin abnormality, meibum expressibility, and meiboscores were significantly higher in the ADT group ( P < 0.05). Moreover, the NI-BUT in the symptomatic ADT group was significantly shorter than that in the asymptomatic ADT group ( P < 0.05). The meiboscores and meibum expressibility score in the symptomatic ADT group were significantly higher than those in the asymptomatic ADT group ( P < 0.05). The presence of demodex in the symptomatic ADT group was also higher than that in the asymptomatic ADT group ( P < 0.05).The length of time that patients had been taking ADT was positively correlated with meiboscores and negatively correlated with NI-BUT., Conclusion: Androgen levels were associated with significant changes in relative meibomian gland function. Subjective symptoms, such as dryness and foreign body sensation, were more obvious in prostate cancer patients receiving ADT, which may be caused by MGD and demodex infection. It's recommended that more attention be paid to the ocular surface in prostate cancer patients taking ADT by performing examination of NI-BUT and meibomian gland morphology and function with a view to providing more comprehensive prevention and treatment protocols., Competing Interests: The authors declare that there is no potential conflict of interest relevant to the publication of this article., (Copyright © 2021 Weina Li et al.)

Patients with Sjӧgren's syndrome (SS) have dry eye associated with meibomian gland dysfunction (MGD). The meibum from donors with dry eye due to MGD but without SS (M MGD ) presents with lower levels of cholesteryl ester, less straight chains, and more ordered hydrocarbon chains compared with meibum from donors without MGD (Mn). The aim of the current study was to compare the composition and hydrocarbon chain conformation of meibum from donors with Sjögren's syndrome (Mss) to Mn and M MGD . Meibum was expressed from patients with SS using an ILUX instrument (Alcon Inc., Fort Worth TX). All of the nine meibum donors with SS were female. Meibum composition was characterized using 1 H-NMR and meibum hydrocarbon chain conformation was measured using fourier transform infrared spectroscopy. Meibum from every donor with SS measured contained a significantly (P < 0.01) higher cholesteryl ester/wax ester ratio and more straight chains compared with donors without SS or dry eye. None of the nine phase transitional parameters were significantly different, P > 0.05, for Mss compared with Mn. Nor was the CH 3 /CH 2 band height ratio used to estimate the number of hydrocarbon CH 3 and CH 2 moieties different, P = 0.22, for Mss compared with Mn. In conclusion, the compositional differences between Mss compared with Mn did not result in differences in any of the nine meibum lipid phase transitional parameters measured. The compositional differences observed between Mss and Mn could be markers for or contribute to SS as the differences could lead to tear film lipid packing differences other than conformational differences., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the clinical effectiveness of expression treatment on meibomian gland disease (MGD)., Methods: Seventeen right eyes of 17 patients with MGD were divided into 3 groups in this randomized prospective clinical study: no expression group: routine treatment with no expression (five patients, five eyes); digital expression group: routine treatment with digital expression (five patients, five eyes); and plate expression group: routine treatment with plate expression (seven patients, seven eyes). All groups received the same routine treatment for 1 month. Tear film break-up time (TBUT), vital staining scores, meibum expressibility, and the dry eye-related quality of life score (DEQS) questionnaire results were assessed before and 1 month after treatment., Results: There was a statistically significant difference of posttreatment TBUT among groups as determined by one-way analysis of variance (P<0.05). A post hoc test revealed that TBUT was statistically significantly higher in plate expression group compared with digital expression group. The fluorescein staining score did not show a statistically significant difference among the groups. Meibum expressibility and the DEQS scores improved in all groups., Conclusion: Plate expression when used as an adjunct to routine medical management of MGD has been found to be a comparatively effective treatment in terms of improvement of tear film stability compared with no expression or digital expression.

Purpose: This study examined whether hyperspectral stimulated Raman scattering (hsSRS) microscopy can detect differences in meibum lipid to protein composition of normal and evaporative dry eye subjects with meibomian gland dysfunction., Methods: Subjects were evaluated for tear breakup time (TBUT), staining, meibum expression and gland dropout. Expressed meibum was analyzed using SRS vibrational signatures in the CH stretching region (2800-3050 cm -1 ). Vertex component analysis and K-means clustering were used to group the spectral signatures into four fractions containing high lipid (G1) to high protein (G4)., Results: Thirty-three subjects could be statistically analyzed using pooled meibum (13 with stable tear films (TBUTs > 10 s) and 20 with unstable tear films (TBUTs ≤ 10 s). Significant differences in meibum from subjects with unstable vs. stable TBUTs were found for the G1 fraction (medians 0.164 and 0.020, respectively; p = 0.012) and the G2 fraction (medians 0.244 and 0.272, respectively; p = 0.045). No differences were observed for the G3 and G4 fractions. Single orifice samples were not significantly different vs. pooled samples from the fellow eye, and eyelid sector samples (nasal, central and temporal) G2:G3 fractional components were not significantly different (p = 0.449). Spearman analysis suggested a significant inverse correlation between G1 fraction and TBUT (R = -0.351; p = 0.045)., Conclusions: hsSRS microscopy allows compositional analysis of expressed meibum from humans which correlated to changes in TBUT. These findings support the hypothesis that hsSRS may be useful in classifying meibum quality and evaluating the effects of therapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Significance: Early diagnosis of clinical markers of contact lens discomfort can help clinicians set realistic expectations and monitor and provide prophylactic management for contact lens wearers., Purpose: The purpose of this study was to evaluate the potential of eyelid- and tear film-related clinical markers to be used as predictive factors for diagnosing discomfort in contact lens wearers., Methods: A cross-sectional study was performed on 30 contact lens wearers (6 male, 24 female) with median age of 23 years (range, 18 to 41 years). Eyelid signs and tear film characteristics were evaluated during a single visit, and subjects completed the Contact Lens Dry Eye Questionnaire to evaluate ocular discomfort. Area under the curve (AUC) statistics and sensitivity and specificity values from receiver operating characteristic curves were analyzed to evaluate the predictive potential of clinical signs in discriminating symptoms of contact lens discomfort., Results: The presence of foam at meibomian gland orifices (AUC, 0.944; P < .05; sensitivity >0.7), meibomian gland secretion volume (AUC, 0.935; P < .05; sensitivity >0.7), quality (AUC, 0.969; P < .05; sensitivity >0.7), and expressibility (AUC, 0.933; P < .05; sensitivity >0.7) were significant and strong predictors of discomfort in lens wear. Tear evaporation rates with (AUC, 0.779; P < .05; sensitivity >0.7) or without contact lenses (AUC, 0.788; P < .05; sensitivity >0.7), palpebral conjunctival roughness (AUC, 0.859; P < .05; sensitivity >0.7), palpebral conjunctival staining (AUC, 0.817; P < .05; sensitivity >0.7), palpebral conjunctival hyperemia (AUC, 0.746; P < .05; sensitivity >0.7), meibomian gland orifice capping (AUC, 0.873; P < .05; sensitivity >0.7), pouting (AUC, 0.891; P < .05; sensitivity >0.7), and lid-parallel conjunctival folds (AUC, 0.770; P < .05; sensitivity >0.7) were other acceptable discriminators of symptoms of discomfort during contact lens wear. An equation was developed to identify symptomatic from asymptomatic lens wearers based on the significant predictors: Symptom discriminant function score = 3.378 (meibomian gland secretion grade) + 0.224 (meibomian gland morphology grade) + 0.61 (tear evaporation rate without contact lenses) + 0.439 (lid-parallel conjunctival folds grade) - 0.346 (palpebral conjunctival health grade) - 4.625., Conclusions: This study demonstrated that clinical signs related to meibomian gland secretions and morphology, tear evaporation, lid-parallel conjunctival folds, and palpebral conjunctival health may successfully predict symptoms of discomfort in contact lens wearers.

Significance: Meibomian gland dysfunction, but not atrophy, was associated with lower tear lactoferrin concentration, greater dry eye, and allergic symptoms, indicating greater inflammation and discomfort in patients with lower meibomian gland expressibility., Purpose: Meibomian gland dysfunction can potentially damage adjacent palpebral structures, which may induce inflammation in accessory lacrimal glands and affect lactoferrin secretion. This study aimed to examine the relationships between the severity of meibomian gland dysfunction with tear lactoferrin, conjunctival cell morphology, and clinical features of ocular allergy., Methods: Forty subjects were divided into two groups based on the severity of meibomian gland plugging and expressibility and secondarily based on its atrophy. Dry eye and allergy questionnaires; slit-lamp examination, including lid telangiectasia; and meibography were performed. Tear lactoferrin concentration was measured using TearScan 270 MicroAssay. Impression cytology was performed on the upper palpebral conjunctiva, and goblet cell density and epithelial squamous metaplasia were quantified., Results: Twenty-two subjects with meibomian gland dysfunction were categorized into severely obstructed group (case), whereas 19 subjects had minimal/no obstruction (comparison). Lower lactoferrin (1.3 ± 0.4 vs. 1.7 ± 0.4 mg/mL, P = .007), greater dry eye (7 [1 to 10] vs. 2 [0 to 5], P = .03), and allergy symptoms (9 [4 to 23] vs. 6 [0 to 9], P = .05) were found in the cases compared with the comparisons. There were no differences in conjunctival cell morphology between groups. The plugging score was correlated with lactoferrin concentration (ρ = -0.43, P = .006), dry eye (ρ = 0.36, P = .02), and allergic symptoms (ρ = 0.33, P = .04). Greater lid margin telangiectasia was associated with meibomian gland obstruction, but not atrophy., Conclusions: Meibomian gland activity/dysfunction, but not atrophy, may be associated with increased inflammation on the ocular surface. The inflammation may be sufficient to reduce tear lactoferrin production from damage to accessory lacrimal glands and/or meibomian gland and result in increased symptoms.

Purpose: The purpose of this study was to assess the prevalence of meibomian gland dysfunction (MGD) and its association with tear film and ocular surface parameters in an Austrian clinical population of dry eye patients., Methods: The records of 1372 consecutive patients from a dry eye unit were analysed retrospectively. Symptoms and objective tear film and ocular surface parameters were evaluated. Patients were classified into pure MGD, pure aqueous tear deficiency (ATD), MGD combined with ATD, pure anterior blepharitis (AB), Sjogren's syndrome (SS) without MGD and SS together with MGD., Results: Nine-hundred and sixty-five patients, that is 70.3% of the investigated population, mean age 55.4 ± 16.6 years, had signs of MGD. Of these, 684 (70.9%) were female. The intensity of symptoms did not differ between subgroups. Four hundred and ninety (50.8%) MGD patients had Schirmer test values ≤10 mm/5 min. The fluorescein break-up time and Schirmer test values were significantly higher in the pure AB and MGD group. The pure MGD group showed a significantly lower fluorescein staining of the cornea compared to the other groups, except for pure AB. Lissamine green staining of the ocular surface was present in all groups, but was at least pronounced in the pure MGD and AB group., Conclusion: Meibomian gland dysfunction is a major cause of ocular discomfort and could often be found in combination with a reduced aqueous tear secretion. Although the intensity of subjective complaints was similar to all other subgroups, pure MGD exhibited the lowest severity of signs of ocular surface damage and also affected younger people., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Meibomian Gland Dysfunction (MGD) is a leading cause of evaporative Dry Eye Disease (DED). This makes non-invasive meibography an important procedure in the clinical evaluation of DED patients. Our purpose was to conduct a lead-off investigation focused on the practicality of performing meibography in a developing country, with limited access to complex ophthalmic imaging systems, using a custom meibographer, as a step to future comparative studies on meibomian glands and DED in Africa., Methods: Meibomian glands(MG) in 76 upper eyelids (UL) and 49 lower eyelids (LL) in 1 eye each of 125 patients randomly selected from a patient population presenting with subjective DED symptoms at a clinic were photographed using a custom meibographer. Single frames were captured, and the MG area determined by intensity threshold segmentation and area calculation using Image J software. MG loss (MGL) was quantified by outlining its area and expressing it as a percentage of the total MG per Pult's grading scheme. Dry eye measures included Tear Film Break Up - Time (TUBT), Schirmer's test and Ocular Surface Staining (OSS). Symptoms were evaluated using the SPEED II questionnaire. Correlations between MGL and age, ocular signs and symptoms were analyzed by Pearson's. Differences between comparable groups were analyzed by Mann - Whitney test; p < 0.05 was considered significant., Results: Overall mean MGL was 32.10% ± 25.0% (26.25% ± 22.40% for UL and 40.33% ± 26.70% for LL). MGL correlated significantly with age [r = 0.91, p = 0.001], SPEED scores [r = 0.90, p = 0.001], OSS [r = 0.75, p = 0.001] and TBUT [r = - 0.81, p = 0.001]. MGL scores were significantly higher in the UL than LL [U = 1293.5 p = 0.004]., Conclusion: This study for the first time presents data on the status of Meibomian glands in Africa. It furthermore suggests that it is feasible to examine Meibomian glands using a custom meibographer in developing countries with limited access to complex imaging systems. It also demonstrates the benefit and cost-effectiveness of a simple device by the observed significant relations between meibomian gland loss and DED in these patients.

Purpose: To evaluate the effect of meibomian gland dysfunction (MGD) and friction-related disease (FRD) on the severity of dry eye disease (DED)., Design: Cross-sectional observational study., Participants: This study enrolled 449 patients with DED (63 men and 386 women; mean age, 62.6±15.7 years [range, 21-90 years]) for analysis., Methods: Subjective symptoms, the ocular surface, tear function, and the presence of MGD and FRD (superior limbic keratoconjunctivitis, conjunctivochalasis, and lid wiper epitheliopathy) were investigated., Main Outcome Measures: Schirmer value, tear film breakup time (TBUT), and keratoconjunctival score., Results: We classified the participants into aqueous-deficient dry eye (ADDE; n = 231 [51.4%]) and short TBUT dry eye subtype (TBUT-DE; n = 109 [24.3%]) subgroups. The TBUT was shorter in patients with MGD than in those without MGD, whereas other ocular signs showed no difference (TBUT: MGD present, 1.97±1.02 seconds; MGD absent, 2.94±1.63 seconds [P < 0.001]; ADDE/MGD present, 1.94±1.08 seconds; ADDE/MGD absent, 2.77±1.61 seconds [P < 0.001]; short TBUT-DE/MGD present, 2.07±0.97 seconds; short TBUT-DE/MGD absent, 2.94±1.23 seconds [P = 0.01]). The ADDE patients with FRD showed a worse TBUT than ADDE patients without FRD (TBUT: ADDE/FRD present, 2.08±1.39 seconds; ADDE/FRD absent, 2.92±1.54 seconds; P < 0.001)., Conclusions: This study showed associations between MGD, FRD, or both and ocular signs in DED. In the presence of MGD, FRD, or both, TBUT was significantly shortened regardless of the dry eye status or subtype., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: A previous literature review reported tear evaporation rates (TERs) from studies conducted on rabbits and humans between 1941 and 2003. Closer examination of the presented data revealed inaccuracies in the reporting of some values. This paper presents updated tables of TERs using values from the original papers cited in the review, in addition to incorporating new studies published between 2003 and 2016., Methods: A copy of each paper cited in the literature review was obtained and checked against the evaporation rate reported in the review. If the expected value could not be found in the cited paper, other papers by the same author were consulted to see if the value had been reported elsewhere. A PubMed and Scopus database search was conducted to find papers published on tear evaporimetry since 2003., Results: Two new tables of TERs were created, based on the values reported by the original author. To aid in interpretation, the majority of results are expressed in units of x 10 -7  g/cm 2 /sec. Where it was not possible to convert these values, some values are expressed as x 10 -7  g/sec, x 10 -7  g/sec/eye or W/min., Conclusions: Two new tables of TERs have been compiled to provide an accurate representation of the values reported in the original papers. These tables can be used as a point of reference for other researchers to compare their results., (Copyright © 2017 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the manifestation of meibomian gland dysfunction in patients with Sjögren's syndrome (SS), non-Sjögren's syndrome dry eye (non-SS) patients, and non-dry eye controls., Methods: We recruited 31 participants with SS dry eye, 30 participants with non-SS dry eye, and 35 healthy controls without dry eye symptoms. Noninvasive tear breakup time (NITBUT) and meibomian gland dropout score (meiboscore) were measured using the Oculus Keratograph 5 M. Meibomian gland expressibility and secretion quality were evaluated via slit lamp biomicroscopy. The correlation between measurements was analyzed., Results: NITBUT was lower, and the meiboscore, meibomian gland expressibility, and secretion quality scores were significantly higher in the SS and non-SS groups than in the control group (p < 0.001). NITBUT was lower, and the meiboscore and meibomian gland expressibility were higher in the SS group than in the non-SS group. NITBUT correlated negatively with the meiboscore in both SS and non-SS groups and with meibomian gland expressibility in the SS group. A positive correlation was obtained between meiboscore and meibomian gland expressibility in both the SS and the non-SS groups., Conclusion: Patients in both SS and non-SS groups exhibited greater impairment in meibomian gland function than the non-dry eye controls. SS patients had more severe meibomian gland dysfunction with poorer mean meiboscore and meibomian gland expressibility than non-SS patients.

Purpose: To investigate the tear cytokine profile in congenital aniridia, and correlate cytokine levels with ophthalmologic findings., Methods: We examined 35 patients with aniridia and 21 healthy controls. Tear fluid was collected with Schirmer I test and capillary tubes from each eye, and the concentration of 27 inflammatory cytokines determined using multiplex bead assay. Eyes of all participants were examined with tests for dry eye disease, including evaluation of meibomian glands (meibography). Differences in cytokine levels between the two groups were analyzed, and correlations between cytokine concentrations and ophthalmologic findings in the aniridia group investigated., Results: The concentrations of six tear cytokines were significantly higher in aniridia patients than controls in both eyes, and included interleukin 1β (IL-1β), IL-9, IL-17A; eotaxin; basic fibroblast growth factor (bFGF/FGF2); and macrophage inflammatory protein 1α (MIP-1α/CCL3). The ratio between the anti-inflammatory IL-1RA and the proinflammatory IL-1β was significantly lower in patients than controls in both eyes (P = 0.005 right eye and P = 0.001 left eye). Increasing concentration of IL-1β, IL-9, IL-17A, FGF2, and MIP-1α correlated with parameters for meibomian gland dysfunction (MGD) in the aniridia group, including increasing atrophy of meibomian glands, and shorter break-up time of the tear film., Conclusions: A number of pro-inflammatory cytokines are significantly elevated in tear fluid from aniridia patients, and correlate with parameters for MGD in aniridia. Increased inflammation of the ocular surface may be a factor in the development of MGD in aniridia patients, and explain the high prevalence of MGD and dry eye disease in these patients.

Purpose: The aim is discussing the origins of worsening of external eye condition (EEC) and of tear film (TF) instability after wear of silicone-hydrogel contact lenses (CLs) with hydrogen-peroxide (H 2 O 2 ) care system., Methods: EEC and TF stability were evaluated before and after 15days of wear combined with different care systems: (1) H 2 O 2 , (2) detergent solution and H 2 O 2 , (3) multipurpose solution (MPS), (4) H 2 O 2 and artificial tears. In-vitro cell mortality tests were performed after 24h cell incubation with CLs treated with H 2 O 2 . Photon correlation spectroscopy (PCS) was carried out on tears of non-wearers and CL wearers who used MPS or H 2 O 2 solution., Results: Worsening of EEC was observed only for the group using H 2 O 2 (group 1). In-vitro, cell mortality was found higher for worn CL than for unworn CLs. Worsening of TF stability was observed regardless of care system and also PCS results on tears of CL wearers were found different compared to non-wearers regardless of care system. The only observed remedy for tear instability of CL wearers was found to be the administration of artificial tears., Conclusions: Worsening of EEC of CL wearers using H 2 O 2 is attributed to H 2 O 2 scarce cleaning efficacy, which can be solved by adding a CL detergent solution. The origin of TF instability is found to be different. A remedy was found to be the administration of artificial tears, whose effect could be attributed either to the role of specific components or to rinsing and replacement of TF during wear., (Copyright © 2017 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: Contact lens discomfort remains poorly understood, not least due to lack of associations between clinical signs and symptoms. This study aimed to explore the relationships between osmolarity, comfort and lid wiper epitheliopathy in contact lens wear., Methods: Twenty subjects participated in a randomized, cross-over study where comfilcon A and lotrafilcon A lenses were each worn for 10days separated by a 7days washout period. Tear and contact lens osmolarity, ocular symptoms including comfort, tear stability and production, and lid wiper epitheliopathy were measured., Results: Comfort and tear stability decreased and upper lid wiper staining and foreign body sensation increased with lens wear. These were not affected by lens type. A reduction in tear production was seen after 10days of comfilcon A lens wear. High proportions of lid wiper epitheliopathy were observed at the upper (range 65%-85%) and lower (range 90%-100%) lid margins. Tear and contact lens osmolarity were unaffected by lens wear or type. Contact lens osmolarity was associated with comfort (r=0.45, p=0.009). Tear osmolarity moderately correlated with tear stability (r=-0.53, p=0.014) and tear production (r=-0.44, p=0.012) but not with lid wiper staining., Conclusions: A relationship between comfort and contact lens osmolarity and between tear osmolarity and tear stability and production were found, however, this study was unable to demonstrate an association between comfort and tear osmolarity or lid wiper epitheliopathy. Further studies using contact lenses with a wider range of comfort responses are warranted to investigate these associations further., (Copyright © 2017 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: Better understanding of the pathophysiology of meibomian gland dysfunction (MGD) has provided the opportunity to develop treatments which could be tailored for specific presentations of MGD. This study sought to directly compare treatment effectiveness for three current therapies across differing levels of MG dropout., Methods: Subjects (n=81), grouped by infrared meibography dropout proportions, into either no (control), mild, or pronounced MG dropout, were randomised to receive treatment with a latent heat device (n=25), liposomal spray (n=28), or heated warm compress (n=28). A battery of tear film measures was performed, pre- and post-application of treatment, and compared by treatment type and MG severity., Results: Symptoms correlated with MG dropout proportions (r=0.618, p<0.001). Following treatment, non-invasive tear breakup time improved (p=0.010), independent of treatment type (p=0.131). The improvement was significant only in the pronounced MGD group (+4.32 ±1.15s, p=0.008), however, following treatment, the mild group was no longer distinct from the control group (p=0.843). Lipid layer grade (LLG) also improved following treatment (p<0.009), but again was not specific to treatment type (p=0.349). All three severity groups showed an improvement in LLG, with 49.3% of participants showing an improvement of at least one grade, and none showing decreased LLG., Conclusions: Increased LLG across all three treatment groups suggests that all methods increase meibum outflow to the tear film, resulting in a thicker lipid layer after treatment. These results suggest that all three treatments are effective in improving tear film quality, independent of MGD severity based either on symptoms or based on gland dropout., (Copyright © 2017 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Background: The aim was to evaluate the efficacy of periocular intense pulsed light therapy combined with meibomian gland expression for chronic dry eye due to moderate to advanced meibomian gland dysfunction., Methods: This single-institution, open-label prospective study involved 26 participants who received bilateral treatments using a proprietary intense pulsed light device (E > Eye, E-Swin, Paris, France) combined with therapeutic meibomian gland expression at baseline, Week 2 and Week 6. Clinical evaluations performed at baseline, Week 4, Week 8 and Week 12 were symptom scores (Ocular Surface Disease Index [OSDI], Ocular Comfort Index [OCI], daily lubricant use, tear break-up time and ocular surface staining). Tear secretion, tear osmolarity, InflammaDry tear immunoassay, corneal sensation, meibomian secretion quality and expressibility, bulbar conjunctival, limbal and lid margin redness and eyelid margin bacterial swab for cultures and colony counts were performed at baseline and Week 8 only., Results: Significant improvements occurred at Week 8 in meibomian gland expressibility (p = 0.002), meibum quality (p = 0.006), tear break-up time (p = 0.002), corneal staining (p = 0.001), lid margin redness (p = 0.001), bulbar redness (p = 0.05) and limbal redness (p = 0.001). Symptom survey outcomes, eyelid margin bacteria colony counts, Schirmer I test, tear osmolarity, corneal sensitivity and daily lubricant use were unchanged. At Week 12, significant improvements in symptoms (OSDI p = 0.025; OCI p = 0.003), tear break-up time (p = 0.001) and corneal staining (p = 0.001) occurred. Improvement in OSDI score was correlated to the improvement in ocular surface staining (R = 0.43, p = 0.03) and associated with baseline meibomian gland expressibility (Kendall tau: the distributions are ordered the same, p = 0.1). There were no adverse effects of treatment., Conclusions: Serial intense pulsed light therapy combined with meibomian gland expression significantly improved dry eye symptoms and clinical signs, including meibomian gland secretion quality and expressibility and ocular surface inflammation. Treatment effects were cumulative and sustained for at least six weeks after the final treatment., (© 2017 Optometry Australia.)

We analyzed the tear film proteome of patients with dry eye (DE), meibomian gland dysfunction (MGD), and normal volunteers (CT). Tear samples were collected from 70 individuals. Of these, 37 samples were analyzed using spectral-counting-based LC-MS/MS label-free quantitation, and 33 samples were evaluated in the validation of candidate biomarkers employing customized antibody microarray assays. Comparative analysis of tear protein profiles revealed differences in the expression levels of 26 proteins, including protein S100A6, annexin A1, cystatin-S, thioredoxin, phospholipase A2, antileukoproteinase, and lactoperoxidase. Antibody microarray validation of CST4, S100A6, and MMP9 confirmed the accuracy of previously reported ELISA assays, with an area under ROC curve (AUC) of 87.5%. Clinical endpoint analysis showed a good correlation between biomarker concentrations and clinical parameters. In conclusion, different sets of proteins differentiate between the groups. Apolipoprotein D, S100A6, S100A8, and ceruloplasmin discriminate best between the DE and CT groups. The differences between antileukoproteinase, phospholipase A2, and lactoperoxidase levels allow the distinction between MGD and DE, and the changes in the levels of annexin A1, clusterin, and alpha-1-acid glycoprotein 1, between MGD and CT groups. The functional network analysis revealed the main biological processes that should be examined to identify new candidate biomarkers and therapeutic targets.

Purpose: To investigate the change from baseline of inflammatory markers in tears of dry eye disease (DED) subjects owing to meibomian gland dysfunction (MGD) after intense pulsed light (IPL) treatment and meibomian gland expression (MGE) compared to sham treatment, and the correlations with ocular surface parameters., Design: Randomized, double-masked, controlled study., Methods: Those randomized into the active treatment arm received 3 consecutive treatments (14∼16 J/cm 2 ) approximately 4 weeks apart in the periocular region. Control eyes received 3 treatments in the same intervals of 0 J/cm 2 . Tear samples in all eyes were collected and analyzed at baseline, week 12, and/or week 4 for interleukin (IL)-17A, IL-6, and prostaglandin E2 (PGE2). The correlations between cytokines and ocular surface parameters were analyzed before and after IPL treatment., Results: All of the inflammatory markers declined in value compared to baselines. IL-17A and IL-6 showed statistically significant decreases compared to sham treatment at each measured time point. PGE2 showed statistically significant decreases compared to sham at week 12. Results showed that the expressions of IL-17A and IL-6 correlated well with ocular surface parameters of the lower eyelid before IPL. The changed values of IL-6 and PGE2 in tears correlated with the changed values of partial ocular surface parameters after IPL treatment in study eyes, respectively., Conclusions: The study results suggest that IPL can significantly reduce inflammatory markers in tears of patients suffering with DED owing to MGD after IPL treatment. These findings indicate that IL-17A and IL-6 play roles in the pathogenesis of DED owing to MGD, and the reduction of the inflammatory factors is consistent with the improvement of partial clinical symptoms and signs., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

The meibomian gland is the major contributor to the tear film lipid layer. It is generally accepted that meibomian gland secretions, i.e, meibum, play a critical role in the homeostasis of the tear film. Lipid components of meibum and their structure, as well as functions were intensively studied. However, the proteins from meibum have not attracted enough attention. This review summarizes current knowledge about protein components of the meibum, particularly their function on tear film and ocular surface, and changes in the proteins during meibomian gland dysfunction (MGD)., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: To estimate the prevalence of Meibomian gland dysfunction (MGD) and determine the associated factors in the general population in Iran., Methods: This cross-sectional study is based on the data from the second phase of the Shahroud Eye Cohort Study conducted in 2014. Of the 4737 participants of the second phase, data was available for 4700 people; their mean age was 55.9±6.2 years and 2768 (58.9%) were women. Diagnosis of MGD was made based on the classification of the International Workshop on MGD as judged by the examining ophthalmologist. The prevalence of MGD was summarized as percentage and 95% confidence intervals (CI), and related factors were studied through simple and multiple logistic regressions., Results: The diagnosis of MGD in at least one eye was recorded for 1235 (26.3%) participants; the prevalence of unilateral and bilateral MGD was 26.3% (95% CI: 24.5-28.1) and 26.1% (95% CI: 24.3-27.9), respectively. In the multiple logistic regression analyses, MGD significantly correlated with pinguecula [odds ratio (OR)=1.3, 95% CI: 1.12-1.50], hypertension (OR=1.34, 95% CI: 1.11-1.61), high-density lipoprotein (HDL) level (OR=0.0992, 95% CI: 0.986-0.999), diabetes mellitus (OR=0.83, 95% CI: 0.71-0.97), and years of education (OR=0.98, 95% CI: 0.96-0.99)., Conclusions: MGD prevalence in this study was lower than the rates reported in other studies on Asian populations. Besides HDL level, MGD is associated with another ocular surface disorder, namely pinguecula, as well as certain systemic diseases such as hypertension and diabetes mellitus. These associations should be taken into consideration when diagnosing MGD., (Copyright © 2017. Published by Elsevier Ltd.)

Purpose: Obstructive meibomian gland dysfunction is a leading cause of ocular morbidity and its treatment remains a challenge. Meibomian gland probing was initially described in 2010. Here, the authors describe a modified technique, dynamic intraductal meibomian probing, which offers several advantages over the traditional approach including increased magnification, greater eyelid stabilization, enhanced anesthesia, and easier identification of gland orifices through the expression of meibum., Methods: The authors conducted a retrospective chart review of 70 eyelids with treatment-resistant obstructive meibomian gland dysfunction undergoing dynamic intraductal meibomian probing between January 2013 and April 2015., Results: Immediately after the procedure, 91.4% of cases experienced symptomatic improvement, and no complications were noted., Conclusions: Dynamic intraductal meibomian probing is an effective and safe treatment for obstructive meibomian gland dysfunction that is resistant to traditional therapies.

Purpose: We aimed to compare the tear meniscus measurements using strip meniscometry (SM) and Keratograph5M (K5M) between 3 subtypes of dry eye disease patient groups, classified according to the presence of meibomian gland dysfunction (MGD), and normal subjects., Methods: We enrolled 145 eyes from 145 subjects and measured the tear meniscus using SM and K5M, tear film breakup time, ocular surface staining, and ocular surface disease index; the Schirmer test; and examined lid margins and meibomian glands. Correlation of tear meniscus parameters with other parameters and efficacy of the 2 measurements were evaluated., Results: The SM and K5M results were significantly lower in the non-Sjögren syndrome aqueous-deficient dry eye (non-SS ADDE) with and without MGD groups than in the MGD-only group and normal subjects. The SM or K5M results correlated with each other and with other ocular surface parameters. The area under the curve (AUC) of the SM and K5M results was 0.637 (P = 0.012) and 0.610 (P = 0.042), respectively. Except for the MGD group, the AUC of the SM and K5M results were 0.721 (P < 0.001) and 0.694 (P = 0.001), respectively. The AUC of SM and K5M were 0.947 (P < 0.001) and 0.784 (P = 0.002), differentiating non-SS ADDE-only patients from those with normal eyes., Conclusions: Tear meniscus measurements using SM and K5M can compensate for detection of aqueous-deficient components of dry eye. These results should be interpreted according to the presence or absence of MGD.

Purpose: To investigate automated values from an advanced corneal topographer with a built-in real keratometer, color camera, and ocular surface interferometer for the evaluation of non-Sjögren dry eye syndrome (NSDES) with meibomian gland dysfunction (MGD)., Methods: Sixty-four patients (64 eyes) diagnosed with NSDES with MGD were enrolled. All eyes were evaluated using the Ocular Surface Disease Index (OSDI), fluorescence staining score, tear film breakup time (TBUT), Schirmer test, and MGD grade. Noninvasive Keratograph average tear film breakup time (NIKBUTav), tear meniscus height (TMHk), meibomian gland (MG) dropout grade, and lipid layer thickness (LLT) using interferometry were measured., Results: Among automated indexes, NIKBUTav (mean 7.68 ± 4.07 s) and the MG dropout grade (mean 1.0 ± 0.5) significantly correlated with the OSDI (mean 40.6 ± 22.9) (r = -0.337, P = 0.006; and r = 0.201, P = 0.023, respectively), as did all conventional indicators, except the Schirmer score (mean 9.1 ± 5.9 mm). TMHk (mean 0.21 ± 0.18 mm) had significant correlation with the Schirmer score, the staining score (mean 1.2 ± 0.7), TBUT (mean 3.8 ± 1.8 s), and NIKBUTav (r = 0.298, P = 0.007; r = -0.268, P = 0.016; r = 0.459, P < 0.001; and r = 0.439, P < 0.001, respectively), but not any MGD indicator, even the MG dropout grade. NIKBUTav showed significant correlations with all clinical parameters and other automated values, except the Schirmer score and LLT (mean 83.94 ± 20.82 nm) (all (Equation is included in full-text article.)≥ 0.25 and P < 0.01). The MG dropout grade highly correlated with all indexes except TMHk (all (Equation is included in full-text article.)≥ 0.25 and P < 0.05). LLT was significantly associated with TBUT, MGD grade (mean 2.0 ± 0.7), and MG dropout grade (r = 0.219, P = 0.047; r = -0.221, P = 0.039; and r = 0.433, P < 0.001, respectively), although it was not related to patient symptoms., Conclusions: Automated noninvasive measurements using an advanced corneal topographer and LLT measured with an ocular surface interferometer can be alternatives to conventional methods to evaluate tear conditions on the ocular surface; the former device can provide information about conformational MG changes in NSDES with MGD.

Background: To investigate the possible mechanisms by which cataract surgery aggravates meibomian gland dysfunction (MGD), we evaluated the changes in tear cytokines and ocular surface parameters after cataract surgery according to the preoperative MGD grade., Design: Prospective, observational case series., Participants: A total of 50 eyes from 50 patients who underwent cataract surgery were included., Methods: Patients were classified into two groups: Group I had no or minimal MGD, and group II had grades 2-4 MGD. Ocular surface parameters were measured, including tear film break-up time, Schirmer I test, ocular surface staining and Ocular Surface Disease Index, and tear cytokine levels were measured., Main Outcome Measures: The main outcomes were changes in ocular surface parameters and inflammatory tear cytokine concentrations., Results: In group II, preoperative MGD grade, ocular surface staining, tear film break-up time and Ocular Surface Disease Index were worse, and mean interleukin (IL)-2, IL-6 and TNF-α levels were higher than those of group I. MGD and ocular surface parameters were worsened to a greater degree after surgery in group II than in group I (P < 0.050). In group II, IL-6 and TNF-α levels significantly increased at postoperative 1 month, and there were significant correlations between changes in ocular surface parameters and tear cytokines (IL-2, IL-6 and TNF-α; P < 0.050)., Conclusions: The extent to which the MGD grade was aggravated following cataract surgery differed based on preoperative MGD grade. Preoperative MGD and ocular surface status should be carefully evaluated., (© 2016 Royal Australian and New Zealand College of Ophthalmologists.)

Introduction: Lagophthalmos can be characterized as the dysfunction of the eye aperture and in some cases even by the disruption of tear production. Dry eye syndrome can consequently develop. Instability of the tear film, hyperosmolarity and inflammatory reaction are considered as the key mechanisms of dry eye syndrome. In our report we monitored the tear osmolarity of patients with postsurgical unilateral lagophthalmos. Results were compared with tear osmolarity of the non-lagophthalmic eyes., Methods: We examined 10 patients (6 women, 4 men) with postsurgical facial nerve palsy and lagophthalmos complicating management of either cerebellopontine (8 patients) or salivary gland tumors (2 patients). Only patients without severe corneal defects enrolled the study. The tear osmolarity was measured in lower tear meniscus by TearLab Osmolarity System device. The lagophthalmic eye was always examined first. The results are presented as mean plus/minus the standard deviation. The paired t-test was used for statistical data processing. The p-value 0,05 was considered as statistically significant., Results: The mean tear osmolarity of the lagophthalmic eyes was 296 ± 15,0 mosmol/l (275-315 mosmol/l). In case of healthy eyes the mean osmolarity was 310 ± 12 mosmol/l (292-336 mosmol/l). The tear osmolarity in case of lagophthalmos was significantly lower than in the healthy eyes (p = 0,05)., Conclusion: In contrary to the studies demonstrating higher tear osmolarity under the scenario of dry eye syndrome, we found lower tear osmolarity in the lagophthalmic eyes than in the healthy eyes. The possible reason could be the changes in tear dynamics of the lagophthalmic eye due to disturbance of eye lid function. Our results also stress the need of evaluation of the actual tear osmolarity in the view of complex clinical eye findings. The place of tear collection should also be considered.Key words: lagophthalmos, dry eye syndrom, tear osmolarity.

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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

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., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess tear cytokine levels and clinical outcomes in moderate and severe meibomian gland dysfunction (MGD) after 2 months of treatment with topical loteprednol etabonate and eyelid scrubs with warm compresses vs eyelid scrubs with warm compresses alone., Design: Randomized controlled trial., Methods: Patients with moderate and severe MGD were randomized into 2 groups: topical loteprednol etabonate and eyelid scrubs with warm compresses (Group I, 34 eyes) or eyelid scrubs with warm compresses (Group II, 36 eyes). We evaluated cytokine levels, tear film break-up time (TBUT), corneal and conjunctival fluorescein staining, biomicroscopic examination of lid margins and meibomian glands, and the Ocular Surface Disease Index before initiating treatment and 1 month and 2 months after treatment., Results: There were significant decreases in the levels of interleukin (IL)-6, IL-8, and IL-1β in Group I, and IL-6 and IL-8 in Group II. Moreover, the observed decreases of these cytokines in Group I were attributed to a remarkable decrease between treatment and 1 month after treatment. In Group I, there were improvements in all of the clinical outcomes, with prominent improvement in TBUT, corneal and conjunctival fluorescein staining, and meibum quality after 1 month of treatment, compared with Group II. An improvement in meibomian gland expressibility and MGD stage reduction were more remarkable in Group I., Conclusions: Topical loteprednol etabonate and eyelid scrubs with warm compresses were tolerated and efficacious for the treatment of moderate and severe MGD. We suggest that such beneficial effects could manifest after 1 month., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Nutrition disorders and their correlates such as obesity are increasingly prevalent worldwide. A number of studies to date have suggested numerous potential associations between diet and tear film health; this paper will provide a summary of the available literature. The tear film is characterized through its protein and lipid content and through clinical measurements of characteristics such as osmolarity, volume and stability. Malnutrition, protein and vitamin-A deficiencies are extremely deleterious to tear film health and supplementation with oral vitamin A in this setting is of clear benefit. The relative impact of diet on tear film within what would be considered normal ranges of consumption is less clear. A number of population studies have suggested that hyperlipidemia and a diet low in omega-3 fatty acids are risks factor for dry eye disease. Numerous studies have investigated the effectiveness of oral supplementation with antioxidants, omega-3 (e.g. fish oil and linseed oil) and omega-6 (e.g. evening primrose oil) fatty acids in the last 10 years. Taken together, these suggest a small benefit of oral supplementation on tear film volume, stability and decreased ocular symptoms in patients previously diagnosed with diseases involving the ocular surface (e.g. Sjögren's syndrome, meibomian gland dysfunction, dry eye disease) and contact lens wearers suffering from dry eye. More research is required to determine the exact composition, dosage and indications for their use and to fully characterize how these nutraceuticals modulate the tear film., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: To compare serum and tear inflammatory and anti-inflammatory cytokine levels of rosacea patients with the healthy controls and evaluate the correlation of tear cytokine levels with tear function parameters., Methods: Tear and serum interleukin (IL)-1α, IL-6, IL-8, IL-10, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF) levels were measured using multiplex bead (Luminex) technology in 12 rosacea patients without ocular involvement (group 1), 20 rosacea patients with ocular involvement (group 2), and 22 healthy subjects (group 3). The correlation of the cytokines with tear function parameters was analyzed using Spearman correlation test., Results: Tear IL-10 and VEGF levels were significantly lower in group 1 (median: 35.78 pg/mL and 427.29, respectively) and group 2 (median: 26.25 pg/mL and 348.31, respectively) than in group 3 (median: 75.96 pg/mL and 480.12, respectively) (p < 0.05). Mean serum IL-8 level was significantly lower in group 2 (median = 0) compared to group 3 (median = 3.98) (p = 0.02). Tear breakup time was found to be positively correlated with IL-10 (r = 0.46, p = 0.013) and inversely correlated with MCP-1 (r = -0.52, p = 0.004)., Conclusions: Tear and serum levels of cytokines and growth factors measured with Luminex technology showed a large variation in rosacea and healthy subjects. Decreased levels of tear IL-10, an anti-inflammatory cytokine, may lead to an inflammatory ocular surface environment, exacerbate ocular surface inflammation, and deteriorate tear function tests. A bigger sample size, including rosacea patients with corneal involvement, is needed to confirm the role of cytokines in the pathogenesis of rosacea-associated ocular inflammation.

Purpose: To evaluate the correlation between tear film lipid layer thickness and other objective measurements such as tear film break-up time (TBUT), upper and lower meibomian gland losses, and Schirmer 1 test in patients with obstructive meibomian gland dysfunction (MGD) and normal controls., Design: Cross-sectional study., Methods: Thirty eyes of 30 patients with obstructive MGD and 25 eyes of 25 normal controls were enrolled. Lipid layer thickness was measured using an interferometer. Tear film stability and tear production were evaluated by TBUT and Schirmer 1 test. Upper and lower meibomian gland losses were evaluated using noncontact meibography. The correlations among variables were evaluated in the obstructive MGD group and the control group., Results: TBUT was significantly shorter in the obstructive MGD group than in the control group (P < .001). Upper and lower meibomian gland losses were higher in the obstructive MGD group than in the control group (P < .001 and P < .001, respectively), and lipid layer thickness was significantly thicker in the control group than in the obstructive MGD group (P = .028). Lipid layer thickness was significantly negatively correlated with upper and lower meibomian gland losses in both groups., Conclusions: Lipid layer thickness objectively measured with the interferometer was significantly thicker in the control group than in the obstructive MGD group. Lipid layer thickness was negatively correlated with upper and lower meibomian gland losses in the control group as well as in the obstructive MGD group., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aim: To analyse repeatability of subjective grading and objective assessment in non-contact infra-red meibography., Methods: Meibography photographs of 24 subjects (female 14; mean age=46; range=19-69 years, upper-lid images=12, lower-lid images=12) were classified in two sessions by three experienced observers (OI, OII, OIII). Relative area or portion affected by meibomian glands (MG) loss was classified applying three different grading scales in randomized order: a four-grade scale (4S) (degree 0=no partial glands; 1=<25% partial glands; 3=25-75% partial glands; 3=>75% partial glands), a pictorial five-grade scale (5S) (degree 0=no meibomian gland loss (MGL); 1=<25% MGL; 3=26-50% MGL; 3=51-75%; 4=>75% MGL) and objectively by a 100-grade scale (DA) applying ImageJ software., Results: Observed MG loss ranged from 0% to 69%. Intra-observer agreement of the 5S (OI: κ=0.80, p<0.001; OII: κ=0.40, p=0.009; OIII κ=0.81, p<0.001) was better than of the 4S (OI: κ=0.79, p<0.001; OII: κ=0.15, p=0.342; OIII κ=0.50, p=0.0071). Intra-observer agreement of OI and OIII (±0.88 (95% confidence interval), ±1.305) was better than of OII (±2.21) in 4S and 5S (±0.99, ±2.00 and ±0.91; OI, OII and OIII, respectively) while it was relatively similar in DA (±18, ±17 and ±17). Inter-observer agreement was better in DA (OI-OII: ±13, OI-OII: ±19, OII-OIII: ±26) than in 4S (OI-OII: ±1.76; OI-OIII: ±1.29 and OII-OIII: ±1.31) or 5S (OI-OII: ±1.49; OI-OIII: ±0.91 and OII-OIII: ±1.20)., Conclusion: Intra-observer and inter-observer agreement was better in computerized grading followed by the subjective five-grade scale and four-grade scale., (Copyright © 2012 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: To assess clinical outcomes and tear cytokine levels in patients with moderate and severe meibomian gland dysfunction (MGD) after treatment with oral minocycline and artificial tears versus artificial tears only., Design: Prospective, randomized clinical trial., Methods: Sixty eyes of 60 patients with stage 3 or 4 meibomian gland dysfunction were enrolled. We evaluated the tear film break-up time, Schirmer test results, corneal and conjunctival fluorescein staining results, biomicroscopic examination results of lid margins and meibomian glands, and tear cytokine levels before and after 1 month and 2 months of oral minocycline and artificial tears (group 1) or artificial tears only (group 2). Tear samples were collected and analyzed using a BD Cytometric Bead Array (BD Bioscience, San Jose, California, USA) for detection of interleukin (IL)-1β, IL-6, IL-7, IL-8, IL-12p70, IL-17α, interferon-γ, tumor necrosis factor-α, and monocyte chemotactic protein-1. The Wilcoxon signed-rank test, Mann-Whitney U test, generalized linear model, and linear mixed model were performed., Results: Patients in group 1 showed statistically significant improvement in all clinical signs and symptoms after 1 month and 2 months of treatment. Patients of group 1 showed more significant improvement compared with those in group 2. Patients in group 1 also showed statistically significant reductions in IL-6, IL-1β, IL-17α, tumor necrosis factor-α, and IL-12p70 after 2 months of treatment., Conclusions: Oral minocycline can provide clinical benefits in treating moderate and severe meibomian gland dysfunction by reducing inflammatory cytokine levels., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: We evaluated the ocular surface and tear function in patients with periocular vitiligo in this prospective, case-control study., Methods: Sixty eyes of 30 vitiligo patients with periocular involvement and 100 eyes of 50 control subjects were included in the study. Patients and control subjects were compared for Schirmer test and tear film break-up time (BUT) results and impression cytology findings graded according to Nelson's classification., Results: The mean BUT value was 9.5 ± 4.1 seconds in patients with periocular vitiligo and 13.1 ± 4.2 seconds in the control group. The difference was statistically significant (p=0.005). Thirty-seven eyes (61.7%) in the vitiligo group and 28 eyes (28.0%) in the control group had BUT values less than 10 seconds (p<0.001). The mean Schirmer test value was 14.6 ± 4.3 mm in patients with periocular vitiligo and 15.1 ± 4.4 mm in the control group (p>0.05). Nineteen eyes (31.7%) in patients with periocular vitiligo and 8 eyes (8.0%) in the control group had grade 2-3 changes according to Nelson's classification (p<0.001). Three eyes (5.0%) in the periocular vitiligo group and none of the eyes in the control group had inflammation signs in the impression cytology analysis., Conclusions: In patients with periocular vitiligo, ocular surface and tear function alterations may occur. Further studies on ocular surface involvement in periocular vitiligo patients may help to increase understanding of the pathophysiology of vitiligo.

Purpose: We evaluated inter-examiner reliability in grading of clinical variables associated with meibomian gland dysfunction (MGD) in real-time examination versus a graded digital image., Methods: Meibography grading of meibomian gland atrophy and acini appearance, and slit-lamp grading of lid debris and telangiectasias were conducted on 410 post-menopausal women. Meibography and slit-lamp photos were captured digitally and saved for analysis by a masked examiner. Gland atrophy was graded as a proportion of partial glands in the lower lid, and acini appearance by the presence/absence of grape-like clusters. Lid debris and telangiectasias were graded based on severity and quantity from the same image, respectively. Observed agreement and weighted kappas (κ(w)) with 95% confidence intervals (CI) determined the degree of inter-examiner reliability between grading of these clinical variables in real-time examination and digital photographs using a multiple-point categorical scale., Results: Observed agreement was determined for telangiectasias (40.6%), lid debris (50.9%), gland dropout (42.8%), and acini appearance (54.5%). Inter-examiner reliability for the four clinical outcomes ranged from fair agreement for acini appearance (κ(w) = 0.23, 95% CI = 0.14-0.32) and lid debris (κ(w) = 0.24, 0.16-0.32) to moderate agreement for gland dropout (κ(w) = 0.50, 0.40-0.59) and telangiectasias (κ(w) = 0.47, 0.39-0.55). Conclusions. Gland dropout and potentially lid telangiectasia grading from a photograph are more representative of grading in a real-time examination compared to acini appearance and lid debris. Alternative grading scales and/or clinical variables associated with MGD should be addressed in future studies.

Purpose: To evaluate the effect of excess meibum on tear evaporation rate in patients with and without dry eye., Methods: Eleven healthy subjects and 16 patients with dry eye were tested. The dry eye group was divided into 2 subgroups: classic keratoconjunctivitis sicca (KCS) with clear and easily expressed meibum and KCS with meibomian gland dysfunction (MGD) with turbid secretions and difficult-to-express meibum. Evaporative measurements were performed at baseline and after digital expression of meibomian glands at 12, 24, 36, and 48 minutes. Two ranges of relative humidity were used, 25% to 35% and 35% to 45%. The data were expressed as microliters per square centimeter per minute., Results: An increase in the evaporation rate of the tear film was noted for all measurements at both relative humidities in the classic KCS and KCS with MGD groups compared with healthy subjects (P < 0.05). The average evaporation rates at relative humidities of 25% to 35% and 35% to 45% were 0.056 ± 0.016 and 0.040 ± 0.008 for the classic KCS group; 0.055 ± 0.026 and 0.037 ± 0.019 for the KCS with MGD group and 0.033 ± 0.012 and 0.023 ± 0.008 for the healthy group. Also, a decrease in the evaporation rate was observed in the healthy and KCS with MGD groups between baseline and the first measurement after digital expression for both relative humidities (P < 0.05). The classic KCS group did not show any changes after expression., Conclusions: Classic KCS and KCS with MGD groups showed an increase in tear evaporation rates compared with the healthy group. Aqueous tear evaporation diminished in the healthy and KCS with MGD groups after expression of meibomian glands. However, this effect was transient and negligible after the second measurement.

Purpose: Instability of the tear film with rapid tear break-up time is a common feature of aqueous-deficient and evaporative dry eye diseases, suggesting that there may be a shared structural abnormality of the tear film that is responsible for the instability. It may be that a change in the normal meibum lipid composition and conformation causes this abnormality. Principle component analyses of infrared spectra of human meibum indicate that human meibum collected from normal donors (Mn) is less ordered than meibum from donors with meibomian gland dysfunction (Md). In this study the conformation of Md was quantified to test this finding., Methods: Changes in lipid conformation with temperature were measured by infrared spectroscopy. There were two phases to our study. In phase 1, the phase transitions of human samples, Mn and Md, were measured. In phase 2, the phase transitions of model lipid standards composed of different waxes and cholesterol esters were measured., Results: The phase-transition temperature was significantly higher (4°C) for the Md compared with the Mn of age-matched donors with no history of dry-eye symptoms. Most (82%) of the phase-transition temperatures measured for Md were above the values for Mn. The small change in the transition temperature was amplified in the average lipid order (stiffness) at 33.4°C. The average lipid order at 33.4°C for Md was significantly higher (30%, P = 0.004) than for Mn. The strength of lipid-lipid interactions was 72% higher for Md than for Mn. The ability of one lipid to influence the melting of adjacent lipids is termed cooperativity. There were no significant differences between Mn and Md in phase-transition cooperativity, nor was there a difference between Mn and Md in the minimum order or maximum order that Mn and Md achieved at very low and very high temperatures, respectively. The model wax studies showed that the phase transition of complex mixtures of natural lipids was set by the level of unsaturation. A double bond decreased the phase-transition temperature by approximately 40°C. The addition of a second CH CH moiety decreased the phase-transition temperature by approximately 19°C. Unsaturated waxes were miscible with saturated waxes. When a saturated wax was mixed with an unsaturated one, the saturated wax disproportionately increased the phase transition of the mixture by approximately 30°C compared with the saturated wax alone. Cholesterol ester had little effect on the phase-transition temperature of the waxes. Model studies indicated that changes in the amount of lipid saturation, rather than the amount of cholesterol esters, could be a factor in the observed conformational changes., Conclusions: Meibum lipid compositional changes with meibomian gland dysfunction reflect changes in hydrocarbon chain conformation and lipid-lipid interaction strength. Spectroscopic techniques are useful in studying the lipid-lipid interactions and conformation of lipid from individual patients. (ClinicalTrials.gov number, NCT00803452.).

We have hypothesized previously that evaporation from the tears generates a solute gradient across the tear meniscus, which delivers hyperosmolar stress to the mucocutaneous junction (MCJ) of the lid margin. This is proposed as the basis for Marx's line, a line of staining with topically applied dyes that lies directly behind the MCJ. In this article, we consider the implications of this hypothesis for progressive damage to the lid margin as an age-related phenomenon, its amplification in dry eye states, and its possible role in the etiology of meibomian gland dysfunction (MGD). It is suggested that a hyperosmolar or related stimulus, acting behind the MCJ over a lifetime, promotes the anterior migration of the MCJ, which is a feature of the aging lid margin. This mechanism would be amplified in dry eye states, not only by reason of increased tear molarity at the meniscus apex but also by raising the concentration of inflammatory peptides at this site. This could explain the increased width and irregularity of Marx's line in dry eye. While the presence of stem cells at the lid margin may equip this region to respond to such stress, their depletion could be the basis of irreversible lid margin damage. It is further proposed, given the proximity of the MCJ to the meibomian gland orifices, that the solute gradient mechanism could play a role in the initiation of MGD by delivering hyperosmolar and inflammatory stresses to the terminal ducts and orifices of the glands. By the same token, the presence of a zone of increased epithelial permeability in this region may provide a back door route for the delivery of drugs in the treatment of MGD.

Purpose: To evaluate tear film stability in patients with tear dysfunction and an asymptomatic control group by using the novel, noninvasive Tear Stability Analysis System (TSAS)., Methods: In this prospective case-control study, 45 patients with dysfunctional tear syndrome (DTS) were stratified into three groups (1, 2, and 3/4) based on clinical severity, with higher scores indicating more severe symptoms; 25 asymptomatic control subjects were evaluated. TSAS measurements were performed with the RT-7000 Auto Refractor-Keratometer (Tomey Corporation, Nagoya, Japan). Images of ring mires projected onto the cornea every second for 6 seconds were captured and analyzed. Focal changes in brightness were calculated as numerical ring breakup (RBU) values, and the elapsed time when the cumulative values (RBU sum) exceeded a threshold was defined as the ring breakup time (RBUT)., Results: RBUTs in the DTS groups were all significantly lower than those in the control subjects, with the lowest values found in DTS 3/4. RBUT was significantly shorter in DTS 3/4 than in DTS 1 (P<0.001). The change in RBU sum over a 6-second period in the DTS groups combined or between the individual groups was statistically significant (P<0.001), as was the difference between the 1- and 6-second values. For distinguishing between asymptomatic controls and DTS, the sensitivity and specificity of a 5.0-second RBUT cutoff were 82.0% and 60.0%, respectively., Conclusions: The TSAS may be a useful, noninvasive instrument for evaluating tear stability and for classifying DTS severity.

Purpose: To compare tear epidermal growth factor (EGF) concentration in dry eye (DE) conditions and determine correlations between EGF levels and severity of symptoms and ocular surface signs., Methods: In this prospective case-control study, 35 patients with DE, including subgroups with meibomian gland disease (MGD), Sjögren's syndrome (SS) aqueous tear deficiency, or neurotrophic keratopathy (NK), and 17 asymptomatic control subjects were evaluated. Symptoms, Schirmer test, fluorescein clearance test (FCT), EGF concentration, dye staining, and the presence of corneal subepithelial fibrosis and meibomian gland (MG) orifice metaplasia were recorded. Tear EGF and the severity of irritation and ocular surface signs were correlated., Results: Tear EGF was higher in MGD than in the control (P = 0.03) and was lower in SS than in the control (P < 0.0001; MGD (P < 0.05) and NK (P < 0.01) groups. The DE subgroup with results in the FCT > 3 and Schirmer 1 >or= 8 had higher EGF levels than the group with FCT > 3 and Schirmer 1 < 8 and both groups with good tear clearance (P < 0.01). Tear EGF levels correlated inversely with conjunctival (r = -0.49, P = 0.0032) and corneal (r = -0.39, P = 0.022) dye staining and positively with MG orifice metaplasia (r = 0.36, P = 0.03) and corneal subepithelial fibrosis (r = 0.5, P = 0.0006)., Conclusions: Tear EGF concentration was increased in eyes with MGD, corneal subepithelial fibrosis, and MG orifice metaplasia. Elevated tear EGF may promote development of corneal subepithelial fibrosis and lid margin changes.

Purpose: To compare tear cytokine and chemokine concentrations in asymptomatic control and Dysfunctional Tear syndrome (DTS) patients and determine the correlations between tear inflammatory mediators and clinical severity., Design: Prospective observational cohort study., Methods: Concentrations of epidermal growth factor (EGF), interleukin (IL)-1 alpha (1alpha), 1 beta (1beta), 6, 10, 12, and 13, interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and chemokines: IL-8 (CXC); macrophage inflammatory protein-1 alpha (MIP-1alpha) (CCL3); and regulated upon activation, normal T-cell expressed and secreted (RANTES CCL5) were measured by a multiplex immunobead assay in an asymptomatic control group and DTS patients with and without meibomian gland disease (MGD). Spearman correlations between tear cytokines and severity of irritation symptoms and ocular surface signs were calculated., Results: Tear concentrations of IL-6, IL-8 and TNF-alpha were significantly higher in DTS with and without MGD and EGF was significantly reduced in the DTS without MGD group compared with the control group. MIP-1alpha was greater in entire DTS and DTS without MGD groups than the control group and RANTES was greater in DTS with MGD than the control and DTS without MGD groups. IL-12 was significantly higher in the DTS with MGD than the DTS without MGD subgroup. Significant correlations were observed between IL-6 and irritation symptoms and between a number of cytokines and chemokines and clinical parameters., Conclusions: As predicted, patients with DTS have higher levels of inflammatory mediators in their tears that show correlation with clinical disease parameters. Furthermore, different tear cytokine/chemokine profiles were observed in DTS patients with and without MGD groups.

Purpose: To determine the impact of evaporation on preocular aqueous tear (AT) loss in normal subjects (controls) and patients with keratoconjunctivitis sicca (KCS)., Methods: Eighteen patients (32 eyes) with KCS with or without associated meibomian gland dysfunction (MGD) and 11 sex-matched controls had AT evaporation determined between relative humidity (RH) of 20% and 45% using an evaporometer. AT volume, flow, and turnover were determined with a fluorophotometer., Results: Evaporative rates increased significantly when the RH was changed from 40%-45% to 20%-25% (P < .001). This change was similar in all groups and on average accounted for a 99.43% increase. There were no statistically significant differences in evaporative rate between controls, the KCS alone group, and the KCS/MGD group. Dry eye patients exhibited a decreased tear turnover when compared to controls. Evaporative contribution to tear loss at 40%-45% RH was 23.47% for controls, 30.99% for "classic" KCS patients, and 25.44% for KCS/MGD patients. At 20%-25% RH, the evaporative contribution was 41.66% for controls, 57.67% for classic KCS patients, and 50.28% for KCS/MGD patients., Conclusions: RH significantly impacts evaporation regardless of the presence of dry eye disease and probably accounts for the increased dry eye symptoms in people (controls and dry eye patients) in conditions of low RH (eg, deserts, airplane cabins, cold dry seasons). Contribution of evaporation to tear loss tends to be higher than previously described. The percent contribution is dependent on environmental conditions such as RH. There was a trend toward increased contribution to AT loss in dry eye patients vs controls, but statistical significance was not reached.

Objective: Parkinson's disease (PD) has both motor and nonmotor features. Parkinson's disease patients are prone to dry eye due to both autonomic dysfunction and motor symptoms affecting blinking. This study was conducted to investigate the changes in tear functions in PD patients., Design: Nonrandomized, prospective, clinical study., Participants: Fifty-six eyes of 56 consecutive patients with PD were studied. Thirty-six eyes of age-matched non-PD patients without pathology affecting tear tests were examined as control subjects., Intervention: Modified Hoehn-Yahr (H-Y) scale, blink rate (BR), and tear tests were examined., Main Outcome Measures: Modified H-Y scale, BR, dry eye assessment questionnaire, meibomian gland evaluation, tear meniscus height, tear breakup time, fluorescein stain, rose bengal stain, Schirmer's test, and phenol red thread test., Results: Overall tear function abnormalities were significantly more common in PD patients (P = 0.001, Mann-Whitney U test). Each test was found to be significantly disturbed in PD patients relative to controls (P<0.05, Mann-Whitney U test). Each PD patient had at least 1 abnormal test. Overall tear function abnormalities as assessed by the total abnormal test count correlated with the H-Y score (P<0.001, Spearman rho correlation). Parkinson's disease patients' mean BR (12.7+/-7.42 per minute) was significantly less than the controls' (21.8+/-7.37) (P<0.01, Student's t test). The abnormality in each tear test, except those for meibomian gland function and tear meniscus height, was significantly related to the H-Y scores (P<0.05, chi2 linear-by-linear association)., Conclusion: The results of this study indicate that PD is associated with disturbances in tear function. With the exception of meibomian gland disease and tear meniscus height, the tests were found to have a linear association with the H-Y scale, which may be attributed to associated dysfunctions of PD.

Background/aim: Recent studies have demonstrated that tear lipocalin (TL) and phospholipids have a crucial role in maintaining tear film stability. The level of TL in patients with meibomian gland dysfunction (MGD) was examined and these data were correlated with the severity of their clinical disorder., Methods: 12 patients with obstructive MGD, 12 patients with seborrhoeic MGD, and 12 age matched normal control subjects participated in this study. 3 mul of unstimulated tears were collected with a micropipette from the inferior tear meniscus in the right eye of all subjects. Tear samples were fractionated by high performance liquid chromatography, and TL concentrations were assayed with a bicinchoninic acid technique., Results: The mean concentration of TL in patients with obstructive and seborrhoeic MGD was significantly lower than in normal controls. TL concentration correlated positively with tear film break up time and negatively with fluorescein staining scores., Conclusion: These results suggest that TL deficiency may be a predisposing factor for the manifestation of symptoms in MGD.

Purpose: Floppy eyelid syndrome (FES) presents nonspecific ocular surface irritation. The hypothesis for the current study was that one contributing factor is the abnormality in tear film dynamics., Methods: Sixteen patients with FES were consecutively examined. Tear film dynamics were evaluated by kinetic tear interference images, infrared thermometry, water evaporation rate, tear break-up time, and fluorescein clearance test. Data showing evaporation rate and thermometry were compared with those of 10 normal subjects., Results: There was a high correlation between the eye with the worse symptoms and the eyes with the more severe floppy lids (P < 0.01) and with ocular surface evaporation rate (P = 0.02). Except for one patient, all others showed abnormal tear film, with an average tear break-up time of 2.9 +/- 3.7 seconds. Kinetic analysis of tear interference images revealed that lipid spread in a vertical or mixed pattern in 18 eyes (75%) with a delayed spread time (P = 0.0007), indicating that most of the patients had lipid tear deficiency. The ocular skin temperature and water evaporation rate were higher in the FES group (P = 0.0003 and 0.026, respectively). Nearly all patients with FES showed eyelid hyperpigmentation. The ocular surface evaporation rate in the FES group was also higher than that of the normal subjects (P < 0.0001). Multiple regression analysis showed that a vertical pattern of lipid spread had a significant influence on ocular surface evaporation rate (P = 0.003)., Conclusions: Tear film abnormality is prevalent in patients with FES and is characterized by lipid tear deficiency, leading to rapid tear evaporation. The FES lid skin is also characterized by high temperature, high water evaporation rate, and hyperpigmentation. Studies directed to investigating the linkage of lid changes and meibomian gland dysfunction may shed new lights on the pathogenesis of FES.

Purpose: To review the literature on lipid supplementation therapy for dry eye and on image analysis using tear interference images from the specific tear lipid layer interference camera DR-1., Methods: Systematic literature review of lipid supplementation therapy for lipid tear deficiency dry eye, kinetic analysis of tear interference images using DR-1 camera, and computer-synthesized interference color chart for DR-1 camera., Conclusion: To establish lipid supplementation therapy, a quantification system of tear lipid layer is required. Tear lipid thickness could be quantified using a computer-synthesized interference color chart system.