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To assess the relationship between tear inflammatory cytokine ratios (CRs) and signs and symptoms of dry eye disease (DED) to investigate the possible use of tear CRs, which may better address the complexity of cytokine interactions than absolute cytokine levels, as a DED biomarker. Tear concentrations of IL-1b, IL-6, IL-8, IL-10, IL-17A, IFN-g, and TNF-a were measured using standardized procedures, as were DED signs (corneal and conjunctival staining scores, tear break-up time, Schirmer test, Meibomian gland plugging, tear osmolarity, composite sign severity score) and symptoms [Ocular Surface Disease Index (OSDI)]. Ratios between pro-inflammatory (IL-1b, IL-8, IL-17A, IFN-g, and TNF-a) and anti-inflammatory (IL-10) cytokines were calculated. Given its opposing roles in inflammation, IL-6 was tested as both a pro- and anti-inflammatory cytokine. Correlations between CR and DED symptoms and signs were calculated using Spearman correlation coefficients (rho). At baseline, 131 patients, 80.2% female and mean age 54.2 years (SD 14.1, range 20–82), from 10 sites of the Dry Eye Assessment and Management study had sufficient tear volumes ≥4 μL for analysis. IL-6:IL-10, IL-8:IL-10, and TNF-a:IL-10 had some significant correlations, mostly with conjunctival or corneal staining or the composite sign severity score (IL-8:IL-10 and conjunctival staining: rho = 0.19, p = 0.03; IL-6:IL-10 and corneal staining: rho = 0.31, p < 0.001; IL-8:IL-10 and corneal staining: rho = 0.21, p = 0.01; IL-6:IL-10 and composite sign severity score: rho = 0.26, p = 0.003; IL-8:IL-10 and composite sign severity score: rho = 0.26, p = 0.003; TNF-a:IL-10 and corneal staining: rho = 0.29, p < 0.001; TNF-a:IL-10 and Schirmer test: rho = −0.23, p = 0.009). CRs had no significant correlation with DED symptoms. All significant correlations using IL-6 in the denominator (anti-inflammatory) produced counterintuitive results based on clinical understanding of the disease. Pro- to anti-inflammatory CR was weakly correlated with some DED signs and not with symptoms, as measured by OSDI. Future studies in different dry eye populations are needed and should address sampling biases and tear collection techniques. [ABSTRACT FROM AUTHOR]

To evaluate the effect of air pollution on the tear film stability by analyzing the correlation between Air Quality Index (AQI) and Lipid Layer thickness (LLT) in Xuzhou. As a prospective descriptive observational study, 284 patients with meibomian gland dysfunction (MGD), 157 patients with Sjögren's syndrome (SS), and 264 healthy volunteers were included. The tear film lipid layer thickness of the three groups of subjects was measured weekly and compared with the air quality index to analyze the correlation between the two indicators. Logistic regression analysis and linear regression analysis were used to analyze the effect of AQI on the thickness of the tear film lipid layer. The change of LLT with air pollution at different AQI levels was also analyzed. There are obvious seasonal differences in the changes of air pollution index in Xuzhou. Significant differences could be observed in the thickness of the lipid layer of the tear film among the three groups. LLT in the MGD group and SS group decreased with the aggravation of air pollution, while remained unchanged in the control group. There was strong evidence of correlation between LLT of the MGD group (F = 353.494, p < 0.01, adjusted R2 = 0.695) and the SS group (F = 502.404, p < 0.01, adjusted R2 = 0.764) with AQI, while there was minor correlation between LLT with AQI in control group (F = 8.525, p < 0.01, adjusted R2 = 0.046). Air pollution can cause a decrease in the thickness of the tear film lipid layer, thereby affecting tear film stability, leading to the occurrence of dry eye. [ABSTRACT FROM AUTHOR]

To describe tear concentrations of IL-1β, Il-6, IL-8, IL-10, IL-17A, IFNγ and TNFα in tears, collected by microcapillaries, and their correlation with symptoms and signs in subjects with dry eye disease (DED) in the DREAM Study. Cytokine levels of patients with moderate to severe DED were determined using a magnetic bead assay. Scores for Ocular Surface Disease Index, corneal and conjunctival staining, tear break-up time (TBUT), and Schirmer's test were obtained using standardized procedures. Associations of cytokines with each other and signs/symptoms were assessed with Spearman correlation coefficients (r). Assay results from 131 patient samples from 10 sites with tear volumes ≥ 4 ul were analyzed. Cytokine concentrations did not correlate with each other in a generally acknowledged pro-inflammatory/anti-inflammatory pattern, such as proinflammatory IL-17A and IFNγ were not inversely correlated to anti-inflammatory cytokine IL-10, and cytokines did not correlate with DED symptoms. Lower corneal staining was correlated with higher concentrations of IL-17A (r= −0.24, p = 0.006), IL-10 (r= −0.25, p = 0.005) and IFNγ (r= −0.33, p = 0.0001). Higher concentrations of IFNγ were associated with lower conjunctival staining (r= −0.18, p = 0.03). Higher concentrations of IL-17A were associated with higher TBUT scores (r = 0.19 p = 0.02). Cytokines IL-10, IL-17A and IFNγ were highly correlated with each other but weakly correlated with some DED signs. No key cytokines or definitive expression patterns were identified in this study of moderate to severe DED patients. Further studies addressing various biases, including methodological and sampling biases, and standardization of methodology for inter-laboratory consistency are needed to confirm and establish pathological and clinical relevance of tear cytokines in DED. [ABSTRACT FROM AUTHOR]

To determine the metabolic activity, and cytokine expression over time from immortalized human corneal epithelial cells (HCECs) exposed to hyperosmotic stress. HCECs were cultured and expanded in DMEM/F-12 with 10% FBS. The cells were exposed to either normal media (295 mmol/kg) or hyperosmolar media (500 mmol/kg) for 0.25, 3, 6, and 12 hours. After each exposure duration, metabolic activity was quantified using alamarBlue, and a panel of pro-inflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α, IFN-γ, and IL-17A) was quantified using multiplexed electrochemiluminescence (Meso Scale Diagnostics, Rockville, MD). Metabolic activity of the HCEC exposed to hyperosmolar conditions was significantly reduced at the 3-, 6-, and 12-hour mark compared to the control (all p < 0.01). There was no significant difference in cytokine expression between the hyperosmolar media and control at the 0.25- and 3-hour mark for all cytokines (all p ≥ 0.28). The difference in cytokine expression between the hyperosmolar media and the control was significant for IL-1β, IL-4, IL-6, IL-8, IL-12p70, IL-13, and TNF-α at the 6-hour mark (all p ≤ 0.02). No significant change in cytokine expression between the hyperosmolar media and control was noted for IL-2, IL-10, IL-17A, and IFN-γ (all p ≥ 0.74) at the 6-hour mark. Hyperosmolar stress reduced cell metabolic activity and increased expression of IL-1β, IL-4, IL6, IL8, IL-12p70, IL-13, and TNF-α over a 6-hour period in an immortalized HCEC line. [ABSTRACT FROM AUTHOR]

Dry eye (DE) disease is a multifactorial disease in which uncontrolled inflammation can lead to corneal epithelium lesions and symptoms of discomfort. The aim of the present study was to evaluate the efficacy of two cyclosporine emulsions in a mouse model of DE with corneal epithelium lesions. Six- to 9-week-old female C57BL/6 N mice were housed in a controlled-environment room to induce DE. Following DE development, mice were instilled with: QD 0.1%CsA cationic emulsion (CaEm), BID 0.05%CsA anionic emulsion (AEm), or left untreated. Aqueous tear production and corneal epithelium lesions were assessed throughout the experiment. At the end of the treatment period, left eyes were sampled, fixed, and stained for histology, while the cornea, conjunctiva, and lacrimal gland of right eyes were sampled for transcriptomic analysis. Corneal lesion scores were reduced by 10.4%, 18.4%, and 10.9% at day 6, 10, and 14, respectively, with CaEm (QD), and by 2.6%, 3.0%, and 5.5% at day 6, 10, and 14, respectively, with AEm (BID). Histology demonstrated that 7 out of 10 DE mice presented moderate to severe ocular lesions, while only 2 and 5 out of 10 mice presented slight to moderate ocular lesions when treated with the CaEm (QD) and AEm (BID), respectively. The transcriptomic profile analysis suggests that a different set of inflammatory genes are modulated in the cornea, conjunctiva, and lacrimal gland upon DE development. In addition, the two emulsions distinctively modulate the gene expression profile. This study demonstrates that both emulsions were effective at reducing corneal lesions, with the CaEm (QD) being slightly better than the AEm (BID). Interestingly, this study suggests that ocular tissues may not respond similarly to a dry environment and that a different set of genes is modulated by the two formulations in the ocular tissues. [ABSTRACT FROM AUTHOR]

Purpose/aim: To assess the effectiveness of polytetrafluoroethylene (PTFE) tubes in the collection of human tears and meibum. Materials and methods: This was a prospective study that enrolled 10 healthy human subjects. Both the tear film and meibum were sampled using PTFE tubes in the right eye of all subjects. In the left eyes, either 5-µL or 1-µL glass microcapillary tubes were used to collect tears, and 0.5-µL glass microcapillary tubes were used to collect meibum. The lipids from the samples were extracted and analyzed using mass spectrometry (SCIEX TripleTOF 5600, Framingham, MA, USA). The absolute peak intensities of the omega-acyl hydroxy fatty acids (OAHFA), cholesterol esters (CE), and wax esters (WE) obtained for both methods were summed and compared between collection methods. Results: A total of 10 subjects completed the study (five female, mean age: 35.7 ± 7.9 years). Using the mass spectrometer output, the median (first quartile, third quartile) summed intensity units of OAHFA, CE, and WE collected associated with tears using PTFE were 516 (125, 1315), 7946 (2571, 19,915), and 38,892 (139,630, 174,082), all of which were significantly higher (all p ≤ 0.04) than those collected from glass microcapillaries (91 (41, 408), 2463 (1389, 6042), and 11,109 (7465, 37,371), respectively). The median summed intensity units of OAHFA, CE, and WE associated with meibum (1958 (1417, 3502), 11,726 (8434, 87,691), and 84,771 (52,657, 206,050), respectively) using PTFE were not significantly different (all p ≥ 0.13) than those associated with glass microcapillaries (1502 (699, 4407), 10,781 (3287, 38,205), and 77,381 (26,590, 178,213), respectively). Conclusions: PTFE tubes, which are thought to be lipophilic, were associated with more measurable lipids from the tear film than glass microcapillaries. There was no difference between collection methods in lipid profiles when used with meibum. [ABSTRACT FROM AUTHOR]

Purpose: To investigate Nerve Growth Factor (NGF) and nitric oxide synthase (iNOS) levels in tears obtained from Video Display Terminal (VDT) workers and correlate their expression with ocular signs and symptoms. Methods: A total of 120 VDT workers (62M/58F; 31-63 years old) and 40 age/sex matched no-VDT volunteers (19M/21F; 30-60 years old) were enrolled in the study. Participants completed the OSDI questionnaire and were subjected to clinical assessment of ocular surface status, including ocular symptoms and tear film parameters. NGF and iNOS levels were quantified in tear samples and their expressions correlated with OSDI, ocular symptoms and tear film parameters. Results: 59.17% of the studied population was symptomatic based on OSDI scores. Women were more commonly affected. The most frequent symptom was asthenopia and except for dryness, no differences were found between genders regarding other symptoms. A statistically significant decrease in NGF levels was found between normal and moderate (p < 0.05) and between mild and moderate (p < 0.05) OSDI grading. iNOS expression was increased in moderate OSDI grading compared to normals (p < 0.05). A negative correlation was found between NGF and respectively OSDI results, dryness and blurry vision (p < 0.05). No correlations were found among NGF, iNOS and ocular surface parameters (Schirmer, BUT, ocular surface staining). Conclusion: Our data suggest that NGF and iNOS levels contribute to VDT ocular discomfort. Further studies are required to better understand the relationship between NGF and iNOS in VDT ocular surface. [ABSTRACT FROM AUTHOR]

Dry eye (DE) is a multifactorial disorder of the ocular surface unit that results in eye discomfort, visual disturbance and ocular surface damage. It is one of the most common complaints in daily ophthalmic practice. The risk of DE increases with age in both sexes, while its incidence is higher among females. In addition, the condition of menopause in aging women may also contribute to DE onset or worsening as a consequence of an overall hormonal imbalance. Sex hormones play a key role in ocular surface physiology and they impact differently on ocular surface tissues. Reduced estrogen levels were historically thought to be responsible in age-related DE onset but more recent investigations have reconsidered the role of androgens that are present and exert a protective function on the ocular surface. Hormone levels themselves, withdrawal changes in hormone levels, and the changes in hormone-receptor responsiveness are all important factors but it remains to be fully elucidated how estrogen or androgen insufficiency act alone or together in a combined imbalance or interplay to raise the risk of disease. The purpose of this review is to briefly outline current scientific evidence on the influence of androgens and estrogens, on the Lachrymal and Meibomian glands and on ocular surface epithelia including conjunctival goblet cells during reproductive and menopausal periods. The role of sex steroids is also discussed in relation to the pathogenesis of different forms of DE and Sjogren's syndrome (SS). The impact of systemic hormone therapy (HT) in DE post-menopausal women still appears as a controversial issue, despite the many clinical studies. Finally, the outcomes of topical applications of steroid-based products are summarized, underlying the need for potential (tear) biomarker(s) in the rationale of DE-targeted therapy. [ABSTRACT FROM AUTHOR]