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Background: Patients with Diabetes mellitus (DM) are at risk of developing dry eye disease (DED). We investigated routine laboratory parameters in patients with type 2 DM (T2D) and T2D-DED to identify potential inflammatory markers., Methods: A retrospective study of 241 randomly selected patients (30 DED non-diabetic, 120 T2D, and 91 with T2D-DED). The neutrophil-to-lymphocyte ratios (NLR), CRP-to-albumin ratios (CAR), and the glycosylated haemoglobin A1c (HbA1c) results were correlated between groups., Results: The NLR and HbA1c were significantly higher in the T2D-DED group (p≤0.001 and 0.0001, respectively) when compared with T2D and DED non-diabetic groups. CAR was insignificantly high in the three groups (p=0.192). A positive correlation was identified between CAR and NLR in T2D-DED patients (p= 0.008)., Conclusion: In T2D-DED patients, NLR was significantly high and positively correlate with CAR. These results predicate diabetes with dry eye complications, and biomarker-mediated inflammation may have important roles in DED pathogenesis.

Background: Dry eye disease (DED) is a complication of dyslipidemia (DLP) that is caused by metabolic syndrome and increased inflammation. This research aimed to assess leukocyte and systemic inflammation index ratios as potential biomarkers for systemic inflammation in dyslipidemia patients with dry eye disease (DLP-DED)., Methods: Several blood biomarkers were studied in 32 patients with DLP-DED (study group) and 63 patients with DLP-only (control group). The evaluated blood biomarkers included specific systemic inflammation index ratios, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte and platelet ratio (NLPR), and lipid profiles, such as total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglyceride (TG), albumin (ALB), and C-reactive protein (CRP) levels., Results: Lymphocyte levels were significantly greater in the DLP-DED group than in the DLP-only group (P = 0.044). In addition, a significant negative correlation between HDL and the NLPR (P = 0.007; r= -0.428) and a significant negative correlation between the serum ALB concentration and the PLR (P = 0.008; r= -0.420) were identified as potential inflammatory predictors of DLP-DED., Conclusion: The findings of this study suggest that patients with DLP-DED may benefit from routine blood monitoring of their elevated lipid profile and blood inflammatory biomarkers, such as CRP, leukocytes, and systemic inflammation index ratios (NLR, PLR, MLR, and NLPR), to reduce the complications of DLP on ocular health. The correlation data suggest that the NLPR, PLR, serum ALB concentration, and serum HDL concentration may be valuable inflammatory biomarkers in DLP-DED patients. More research is required to ascertain the significance of the NLR, PLR, MLR, and NLPR and the additive role that leukocytes play., (© 2024. The Author(s).)

Introduction: Systemic implications create a critical need for identification of dry eye patients with Sjögren syndrome (SS). Herein, we aimed to determine expressions of type I-III interferons (IFNs) in dry eye patients with or without underlying SS and their differential diagnosis., Methods: A prospective, observational, case-control study was performed on 140 dry eye patients among which 78 patients were diagnosed with SS. Clinical evaluations included ELISA detections of serum type I IFN (IFN-α and IFN-β, type II IFN (IFN-γ), and type III IFN (IFN-λ1/IL-29, IFN-λ2/IL-28, and IFN-λ3/IL-28B), as well as reporter cell assay for serum type I IFN activity., Results: The serum levels of IFN-α and IFN-β were notably higher in dry eye patients with SS than those without underlying SS (p < 0.0001). The functional assay for serum type I IFN activity showed the mean summed scores in dry eye patients with SS were remarkably increased compared to those without underlying SS (p < 0.0001). The serum levels of IFN-γ and IFN-λ1/IL-29 seemed higher in dry eye patients with SS than those without underlying SS (p < 0.0001). The serum levels of type I IFN (IFN-α combined with IFN-β), type II IFN (IFN-γ level), and type III IFN (IFN-λ1/IL-29) used as a test to predict underlying SS among dry eye patients produced an area under the curve of 0.86, 0.73, and 0.94, respectively., Conclusion: Serum levels of type I-III IFNs, especially IFN-α, IFN-β, and IFN-λ1/IL-29, may serve as a useful biomarker for identification of SS dry eye from non-SS dry eye., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Dry eye is often the first presenting manifestation of primary Sjögren's syndrome (pSS). Because of the high prevalence of dry eye disease in normal population, ophthalmologists urgently need a non-invasive and reliable screening test to diagnose dry eye associated SS patients, other than ocular symptoms and signs. Currently, there is no single test available. The correlation of serum IL-14α with pSS has been found in pSS mouse model., Purpose: To evaluate whether IL-14α can serve as a biomarker to stratify dry eye in primary Sjögren's syndrome and its correlation to BAFF in a cohort of patients with non-SS dry eye (NSDE), pSS with dry eye disease, rheumatoid arthritis (RA), and healthy controls (HC)., Methods: Retrospective study based on serum levels of IL-14α (defined by Western Blot) and BAFF (measured by ELISA) were evaluated among pSS with dry eye disease, NSDE, RA, and HC groups. Serum levels of SS related autoantibodies (Ro, La, SP1, PSP, and CA6) were also measured by ELISA., Results: One hundred and eighty patients were included for the current study, patients were separated into four groups as defined by pSS (n=65), NSDE (n=20), RA (n=50) and HC (n=45). The level of serum IL-14α in pSS was significantly higher compared to NSDE, RA, and HC (p=0.0011, p=0.0052 and p<0.0001, respectively). The levels of serum BAFF in pSS was significantly higher than in NSDE and HC (p=0.0148 and p<0.0001, respectively, whereas the levels of serum BAFF in RA was only significantly higher than in HC (p=0.001), but the level of BAFF was no significant difference between pSS and RA. In pSS, there was a decrease in the serum levels of IL-14α associated with a longer duration of the disease. Also, there was a correlation between the serum levels of IL-14α and SS related autoantibodies such as anti-SSA/Ro and anti-SSB/La in pSS patients., Conclusions: This is the first paper to report both IL-14α and BAFF could serve as a critical cytokine biomarker for the stratification of dry eye in primary Sjögren's syndrome. This may help ophthalmologists to develop non-invasive metrics for the diagnosis of dry eye associated pSS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liang, Xian, Fu, Liu, Yao, Jin, Gao, Shen, Shi and He.)

Objectives: To compare hematologic and serological parameters among patients with Sjogren's syndrome (SS), dry eye syndrome (DES) and controls, and validate a novel multiplex-serology method for identifying auto-antibodies in these populations., Methods: In a clinic-based case-control study a total of 422 participants were recruited, including 91 with SS, 120 DES, and 211 controls (age and sex frequency-matched). We measured blood counts, anti-nuclear-antibodies (ANA), anti-SSA/SSB, anti-ribonucleoprotein (RNP), anti-double-stranded-DNA (DS-DNA), and rheumatoid factor (RF) using the "Immunodot" qualitative-ELISA assay. Immunoglobulins, C3 and C4 were measured by immune-fluorescence. Autoantibodies were also quantified with a newly-developed method using glutathione-S-transferase fusion proteins of SSA/Ro 52 and 60kD and SSB/La (multiplex-serology), measuring median fluorescence intensity (MFI)., Results: Among DES patients, only 2% (95%CI: 0.36-6.3) had positive immune serology. SS patients had lower lymphocyte, hemoglobin and C3 levels but higher prevalence of RF, ANA, anti-SSA/B and higher IgG and MFI levels, compared to DES and controls (P<0.001). Presence of anti-SSA/Ro-52kD was associated with SS [odds ratio (OR) = 2.05, 95% confidence interval (CI): 1.46-2.88]. Anti-SSB/La was inversely associated with DES (OR = 0.81, 95%CI: 0.65-1.00) compared to controls. Positivity to RF (adjusted for age, gender and ethnicity OR = 5.03, 95%CI: 1.78-14.21), ANA (OR = 14.75, 95%CI: 4.09-53.17), or combination of anti-SSA/B (OR = 20.97, 95%CI: 4.60-95.54) were more likely in SS compared to DES. The novel multiplex-serology method correctly identified anti-SSA/B autoantibodies by ELISA among SS, DES patients and controls (sensitivity = 1.0, negative-predictive-value = 1.0)., Conclusions: Serologic parameters distinguish SS from DES patients and controls. A newly-developed multiplex-serology technique may be useful to detect autoantibodies in large epidemiologic studies., Competing Interests: The authors have declared that no competing interests exist.

A systematic review and meta-analysis was conducted to determine the association between the serum vitamin D level and dry eye. A systematic literature search was performed using the PubMed, Embase, Web of Science and Cochrane Library databases to identify clinical studies evaluating the association between vitamin D levels and dry eye. The random-effect model was used to combine the results. Possible sources of heterogeneity across studies were determined by meta-regression and sensitivity analysis. Overall, 10 studies (n = 18 919) were included. Patients with dry eye had a mean serum vitamin D level that was lower than that in healthy controls by 3.99 ng/ml (95% CI -6.57, -1.40; p = 0.002). The mean Ocular Surface Disease Index score was higher (mean difference 10.70, 95% CI 1.55-19.86; p = 0.02) and Schirmer's test without anaesthesia result was lower (mean difference 6.38 mm/5 min, 95% CI -10.48, -2.28; p = 0.002) in patients with vitamin D deficiency than in controls. Tear break-up time was comparable in the vitamin D deficiency and control groups (p = 0.15). Sensitivity analyses indicated that the results obtained were robust. This meta-analysis suggested that vitamin D deficiency is associated with worse subjective symptoms and less tear production in patients with dry eye. Vitamin D deficiency may be a risk factor for dry eye syndrome. Prospective cohort and intervention studies are warranted to determine if vitamin D has a protective role in the development of dry eye., (© 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: The goal of this study is to determine a link between benign essential blepharospasm and Sjogren's syndrome by analyzing the presence of extractable nuclear antigens in this population., Methods: Seventy-two patients with benign essential blepharospasm (BEB) were included in this study. We eliminated patients with hemifacial spasm or blepharospasm secondary to corneal pathology. We collected the values of the Schirmer I test and the results of the anti-SSA and anti-SSB antibodies., Results: Our study included 72 patients (144 eyes) whose 62 women (86.1%). Mean age was 74.3 years±10.73. Average Schirmer I test was 3.14mm±4.00mm. Five women (8% of this female population) had positive anti-SSA and SSB antibodies. Their mean age was 65.66 years±13.24 whereas the negative antibody patients had an average age of 75.42±9.27. There was no significant difference between their Schimer I test and the Schirmer I of negative antibody population., Conclusion: This study illustrates the possible association between the presence of Sjögren's syndrome and the occurrence of a BEB justifying the search for anti-SSA and anti SSB in blepharospasm patients., (Copyright © 2020. Published by Elsevier Masson SAS.)

Purpose: To determine whether an association exists between dry eye disease (DED) and statin use and/or dyslipidemia., Design: Retrospective, case-control study., Methods: Setting: University of North Carolina (UNC)-affiliated healthcare facilities., Study Population: 72,931 patients seen at UNC ophthalmology clinics over a 10-year period., Main Outcome Measures: Odds ratios (ORs) calculated between DED and a history of low, moderate, or high-intensity statin use; and ORs calculated between DED and abnormal lipid panel values., Results: Total of 39,336 individuals (53.9% female) were analyzed after exclusion of individuals with confounding risk factors for DED. Of these, 3,399 patients (8.6%) carried a diagnosis of DED. Low-, moderate-, and high-intensity statin regimens were used by 751 subjects (1.9%), 2,655 subjects (6.8%), and 1,036 subjects (2.6%). Lipid abnormalities were identified as total cholesterol >200 mg/dL, 4,558 subjects (11.6%); high-density lipoprotein (HDL) <40 mg/dL, 2,078 subjects (5.3%); low-density lipoprotein (LDL) >130 mg/dL, 2,756 subjects (7.0%); and triglycerides (TGs) >150 mg/dL, 2,881 subjects (7.3%). The odds ratios (OR) of carrying a diagnosis of DED given the presence of low-, moderate-, and high-intensity statin use were 1.39 (95% confidence interval [CI]: 1.13-1.72); OR 1.47 (95% CI: 1.30-1.65), and OR 1.46 (95% CI: 1.21-1.75), respectively. The OR of carrying a diagnosis of DED given the presence of total cholesterol >200 mg/dL, HDL <40 mg/dL, LDL >130 mg/dL, and TGs >150 mg/dL were 1.66 (95% CI: 1.52-1.82), 1.45 (95% CI: 1.26-1.67), 1.55 (95% CI: 1.39-1.74), and 1.43 (95% CI: 1.27-1.61), respectively., Conclusions: A history of statin use or dyslipidemia is associated with an increased odds of having a DED diagnosis. Further studies are needed to determine whether statin use and/or dyslipidemia increases the risk of DED., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To study whether there is an association between benign essential blepharospasm and Sjögren's syndrome by analyzing the presence of antibodies to extractable nuclear antigens in this population., Methods: Seventy-two patients with benign essential blepharospasm (BEB) were included in this study. We excluded patients with hemifacial spasm or blepharospasm secondary to known corneal pathology. We recorded results of Schirmer I testing as well as levels of anti-SSA/Ro and anti-SSB/La antibodies., Results: Our study included 72 patients (144 eyes), of which 62 (86.1%) were women. The mean age was 74.3±10.73 years. The mean Schirmer I test result was 3.14±4.00mm. Five women (8% of this female population) were found to have positive anti-SSA/Ro and anti-SSB/La antibodies. Their mean age was 65.66±13.24 years, while the mean age of the antibody-negative patients was 75.42±9.27 years. There was no statistically significant difference between the Schirmer I tests of the antibody positive and negative patients., Conclusion: This study demonstrates a possible association between Sjögren's syndrome and benign essential blepharospasm, justifying anti-SSA/Ro and anti-SSB/La testing in these patients., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Purpose: To evaluate the ocular surface characteristics based on Schirmer's test, tear break-up time (TBUT), and conjunctival impression cytology (CIC) in children with Hashimoto's thyroiditis (HT)., Methods: This study included 51 children with HT and 53 control subjects. The ocular surface characteristics of participants were assessed via Schirmer's test, TBUT, and CIC. Conjunctival samples were examined cytologically according to the Nelson grading system., Results: Schirmer's and TBUT results were significantly lower in HT group ( p < .05). All samples in both the study and control groups were evaluated as grade 0 according to the Nelson classification ( p = .841), however, goblet cell density (GCD) was significantly lower in HT group ( p = .001). Schirmer test results were significantly associated with the duration of HT ( p = .025, r = -0.311)., Conclusion: Hashimoto's thyroiditis without any ocular complaints may cause ocular surface changes with TBUT and Schirmer's. Although CIC analysis showed similar grading results, GCD was significantly decreased in HT group.

Purpose: To analyze the relationship between serum 25(OH)D3 level and dry eye parameters in primary Sjögren syndrome (SS)., Methods: This study included 74 eyes of 74 patients diagnosed with primary SS. Dry eye parameters included tear breakup time, Schirmer I value, corneal staining score, conjunctival staining score, and Ocular Surface Disease Index. The serum concentration of 25(OH)D3 was evaluated., Results: The mean serum 25(OH)D3 level was 20.4 ± 8.0 ng/mL. There were strong negative correlations between serum 25(OH)D3 level and corneal staining score (P < 0.001, r = -0.446) and conjunctival staining score (P < 0.001, r = -0.455). The Schirmer I value and tear breakup time showed significant positive correlations with serum 25(OH)D3 level (P = 0.038, r = 0.261 and P = 0.003, r = 0.352, respectively). The Ocular Surface Disease Index did not show any significant correlation with serum 25(OH)D3 level., Conclusions: This study demonstrates that serum 25(OH)D3 level might be associated with dry eye severity in primary SS.

Purpose: Animal models suggest that early markers of Sjögren syndrome (EMS)-antibodies against salivary protein 1, parotid secretory protein, and carbonic anhydrase 6 (CA6)-are more accurate signals of early Sjögren when compared with classic markers (anti-Ro and anti-La). To further understand the relationship between EMS and dry eye (DE), we compared symptoms and signs of DE in subjects who tested positive versus negative for EMS., Methods: In this cross-sectional study, patients at the Miami Veterans Affairs Eye Clinic who were tested for EMS underwent a standard ocular surface examination. Indications for EMS testing included DE symptoms in combination with dry mouth symptoms, low tear production, corneal staining, or a Sjögren disease-associated autoimmune disease. Statistical tests performed were the χ test, Fisher exact test, independent sample t test, and Spearman correlation., Results: Seventy-three percent of 44 patients tested positive for 1 or more EMS. CA6 IgG was most frequently elevated, followed by CA6 IgM and parotid secretory protein IgG. EMS-positive versus EMS-negative subjects were more likely to escalate DE treatment past artificial tears to topical cyclosporine (n = 32, 100% vs. n = 9, 75%, P = 0.02). There were no demographic or comorbidity differences between EMS-positive and EMS-negative subjects, and marker levels did not correlate with more severe tear film measures., Conclusions: Most of the individuals with DE tested positive for 1 or more EMS antibodies, including men and Hispanics. Future studies will be needed to understand how to incorporate EMS data into the care of an individual with DE.

Purpose: Dry eye syndrome (DES) is a common eye disease caused by tear deficiency or excessive tear evaporation. Because the tear film layers play a major role in the pathogenesis of the evaporative dry eye, some previous articles have suggested the possible mechanism of dyslipidemia and DES. However, the previous results were inconsistent and few studies were conducted to find the independent relationship between dyslipidemia and DES. Therefore, we investigated the association of dyslipidemia with DES in middle-aged Korean adults., Methods: This study was conducted on 2272 participants (854 men and 1418 women) enrolled in the Study Group for Environmental Eye Disease (2013-2017) after excluding people who have taken lipid-lowering medication. Participants with total cholesterol ≥240 mg/dL or high-density lipoprotein cholesterol <40 mg/dL or low-density lipoprotein cholesterol ≥160 mg/dL or triglycerides ≥200 mg/dL are defined as having dyslipidemia. Using the ocular surface disease index, we measured the DES severity and defined DES as an ocular surface disease index score ≥13., Results: Men with dyslipidemia had an odds ratio of 1.29 (95% confidence interval, 0.97-1.71) for DES in an unadjusted model compared with those without DES. After adjusting for age, body mass index, hypertension, diabetes, occupations, smoking and drinking status, exercise, contact lens use, computer use, study cohorts, and calendar year of examinations, the adjusted odds ratio for DES was 1.40 (1.03-1.90) in men. However, there was no significant association between dyslipidemia and DES in women, even after stratifying by menopausal status., Conclusions: Our findings suggest that dyslipidemia may be associated with the prevalence of DES in Korean men, but not in women.

Keratoconjunctivitis sicca (KCS) is of predominantly immune-mediated origin. Dogs are an excellent model for understanding this disease, as the origin of KCS in dogs is like that in humans. The objective of this study was to localize and quantify immunological markers, such as CD4 lymphocytes, interleukin (IL)-1, IL-6 and tumor necrosis factor alpha (TNFα), before and after topical treatment with mesenchymal stem cells (MSCs). Twenty-two dogs positive for KCS were topically treated with 50 μL (1 × 10 6 MSCs) in the conjunctival sac and were evaluated for 6 months. The levels of the markers CD4, IL-6, IL-1 and TNFα were analyzed in conjunctival biopsy and cytology of the third eyelid gland by immunohistochemistry and immunocytochemistry. The results showed that before treatment, there was marked expression of all the markers (CD4, IL-6, IL-1 and TNFα), and after 6 months, there were significant (p < .05) reductions in the expression levels of all the markers. These results demonstrated that topical MSC treatment promotes a significant decrease in the expression levels of these inflammatory markers and could be used as adjuvant therapy in the treatment of KCS in dogs and humans. In addition, these markers can be excellent tools for diagnosing and analyzing the progression of KCS., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Woundhealing disorders characterized by impaired or delayed re-epithelialization are a serious medical problem that is painful and difficult to treat. Gelsolin (GSN), a known actin modulator, supports epithelial cell regeneration and apoptosis. The aim of this study was to estimate the potential of recombinant gelsolin (rhu-pGSN) for ocular surface regeneration to establish a novel therapy for delayed or complicated wound healing. We analyzed the influence of gelsolin on cell proliferation and wound healing in vitro, in vivo/ex vivo and by gene knockdown. Gelsolin is expressed in all tested tissues of the ocular system as shown by molecular analysis. The concentration of GSN is significantly increased in tear fluid samples of patients with dry eye disease. rhu-pGSN induces cell proliferation and faster wound healing in vitro as well as in vivo/ex vivo. TGF-β dependent transcription of SMA is significantly decreased after GSN gene knockdown. Gelsolin is an inherent protein of the ocular system and is secreted into the tear fluid. Our results show a positive effect on corneal cell proliferation and wound healing. Furthermore, GSN regulates the synthesis of SMA in myofibroblasts, which establishes GSN as a key protein of TGF-β dependent cell differentiation.

Purpose: To determine the possible association between serum vitamin D levels and dry eye symptoms, and the impact of an oral vitamin D supplement., Methods: Three linked studies were performed. (i) 29 older adult participants, (ii) 29 dry eyed participants, and (iii) 2-month vitamin D supplementation for 32 dry eyed/low serum vitamin D levelled participants. All participants were assessed by the Ocular Surface Diseases Index (OSDI) to determine dry eye symptoms, and the phenol red thread test (PRT) and/or Schirmer's tear test, tear meniscus height, non-invasive tear break up time, grading ocular surface redness and fluorescein staining of the cornea to detect the tear quality and ocular surface conditions. Blood samples were collected for serum vitamin D analysis and interleukin-6 (IL-6) levels., Results: Among older adult participants, vitamin D levels were negatively correlated with dry eye symptoms, the severity of dry eye, and associated with tired eye symptom. Vitamin D levels of people with dry eye diagnosis were not correlated with OSDI scores and IL-6 levels; while IL-6 levels showed correlation with tear production. In supplement study, vitamin D levels increased by 29mol/l, while dry eye symptoms and grading of corneal staining appeared significant reductions. No significant changes in IL-6 levels., Conclusions: Low vitamin D levels (<50nmol/l) were associated with dry eye symptoms in older individuals but not those diagnosed with dry eye. Vitamin D supplement increased the vitamin D levels, and improved dry eye symptoms, the tear quality and ocular surface conditions., (Copyright © 2017 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) levels in patients with dry eye disease (DED)., Methods: The white blood cell, neutrophil, platelet, and lymphocyte counts were performed in 78 dry eye patients and 60 controls. The NLR was calculated by dividing neutrophil count by lymphocyte count and the PLR was calculated by dividing platelet count by lymphocyte count., Results: The mean age was 53.4 ± 3.8 years in the DED group and 52.7 ± 3.4 years in the control group. The mean NLR was 2.6 ± 1.2 and the mean PLR was 138.4 ± 62.6 in the DED group and the mean NLR was 1.84 ± 0.5 and the mean PLR was 118.5 ± 64.7 in the control group. A significant difference was found in the NLR and PLR between the DED and the controls (p = 0.032 and p = 0.026, respectively)., Conclusion: The NLR and PLR values were found higher in patients with dry eye than in healthy subjects.

Purpose: To investigate whether blood glucose regulation in patients with diabetes mellitus (DM) has an influence on the ocular surface disease index (OSDI) score and tear function tests such as tear film osmolarity (TFO), tear break-up time (TBUT) and Schirmer tests., Methods: Fifty diabetic patients with a fasting blood glucose (FBG) level greater than 200mg/dL and HbA1c level greater than 10% were recruited for this prospective study. All of the patients underwent a detailed ophthalmic examination including OSDI questionnaire, TFO test, TBUT test and Schirmer test initially. All tests were repeated after obtaining regulation of patients' blood sugar (approximately 6 weeks later)., Results: The mean age of the diabetic patients in the study was 54.96±12.48 years. Initially, the mean FBG, postprandial blood glucose (PBG) and HbA1c levels were 301.40±79.11mg/dL, 431.06±74.47mg/dL and 12.31±1.67%, respectively. After blood glucose regulation; the levels of all parameters (153.78±59.32mg/dL, 252.32±88.34mg/dL and 9.67±1.60%, respectively) statistically significantly decreased (P<0.001). The mean levels of OSDI score, TFO measurement, TBUT test and Schirmer test were 28.38±16.46 points, 349.66±13.09 mOsm/L, 6.44±1.91s and 8.66±3.57mm initially, and 17.82±11.70 points, 314.14±12.80 mOsm/L, 6.62±2.03s and 9.02±3.68mm after blood glucose regulation, respectively. Although the improvements in TBUT and Schirmer test values were not statistically significant (P>0.05), statistically significant reduction was obtained in OSDI scores and TFO levels (P<0.001, for each)., Conclusion: DM, which is a hyperosmolar disorder, appears to cause elevation in OSDI score and increase in TFO level, especially if blood glucose is poorly regulated., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

BACKGROUND To determine the association between serum 25(OH)D and dry eye syndrome (DES) incidence. This study was also designed to determine whether serum 25(OH)D levels were associated with ocular parameter of DES patients. MATERIAL AND METHODS This is a case-control study with 70 DES cases and 70 healthy controls. Clinical data included body mass index (BMI, kg/m²), smoking history, diabetes, and blood pressure. Serum 25(OH)D was chosen as the main parameter and reflected the level of vitamin D. The DES parameters included ocular surface disease index (OSDI) scales, tear film breakup time (TBUT) and Schirmer test I. The differences in each parameter between case and control groups were detected and the association of serum 25(OH)D and DES parameter were detected. RESULTS It was shown that 25(OH)D levels were lower in patients with DES than in healthy controls. When the 25(OH)D levels was stratified, vitamin D deficiency was more common in the DES cases. In advanced studies, it was found that there were statistically significant associations between serum 25(OH) D levels and the Schimer test, TBUT, and OSDI scales. CONCLUSIONS A significant association between serum 25(OH)D level and DES incidence was detected in this study. Considering the relatively small sample size of this study, larger studies are needed in the future.

Purpose: To test the association between serum metabolites and dry eye disease (DED) using a hypothesis-free metabolomics approach., Design: Cross-sectional association study., Participants: A total of 2819 subjects from the population-representative TwinsUK cohort in the United Kingdom, with a mean age of 57 years (range, 17-82 years)., Methods: We tested associations between 222 known serum metabolites and DED. All subjects underwent nontargeted metabolomic analysis of plasma samples using gas and liquid chromatography in combination with mass spectrometry (Metabolon Inc., Durham, NC). Dry eye disease was defined from the validated Short Questionnaire for Dry Eye Syndrome (SQDES) as a previous diagnosis of DED by a clinician or "often" or "constant" symptoms of dryness and irritation. Analyses were performed with linear mixed effect models that included age, BMI, and sex as covariates, corrected for multiple testing., Main Outcome Measures: Primary outcome was DED as defined by the SQDES, and secondary outcomes were symptom score of DED and a clinical diagnosis of DED., Results: Prevalence of DED as defined by the SQDES was 15.5% (n = 436). A strong and metabolome-wide significant association with DED was found with decreased levels of the metabolites androsterone sulfate (P = 0.00030) and epiandrosterone sulfate (P = 0.00036). Three other metabolites involved in androgen metabolism, 4-androsten-3beta,17beta-diol disulfate 1 and 2, and dehydroepiandrosterone sulfate, were the next most strongly associated of the 222 metabolites, but did not reach metabolome-wide significance. Dryness and irritation symptoms, as opposed to a clinical diagnosis, were particularly strongly associated with decreased androgen steroid metabolites, with all reaching metabolome-wide significance (androsterone sulfate, P = 0.000000029; epiandrosterone sulfate, P = 0.0000040; 4-androsten-3beta,17beta-diol disulfate 1, P = 0.000016; 4-androsten-3beta,17beta-diol disulfate 2, P = 0.000064; and dehydroepiandrosterone sulfate, P = 0.00011). Of these 5 androgens, epiandrosterone sulfate (P = 0.0076) was most associated with 2-year incidence of clinician-diagnosed DED. In addition, we found decreased glycerophosphocholines to be associated with DED, although not at metabolome-wide significance., Conclusions: This hypothesis-free metabolomic approach found decreased serum androgens to be highly associated with DED and adds important evidence to the growing body of research that links androgens to ocular surface disease and DED., (Copyright © 2017 American Academy of Ophthalmology. All rights reserved.)

Background: Dry eye is a common problem in Ophthalmology and may occur for many reasons including Sjogren's syndrome (SS). Recent studies have identified autoantibodies, anti-salivary gland protein 1 (SP1), anti-carbonic anhydrase 6 (CA6) and anti-parotid secretory protein (PSP), which occur early in the course of SS. The current studies were designed to evaluate how many patients with idiopathic dry eye and no evidence of systemic diseases from a dry eye practice have these autoantibodies., Methods: Patients from a dry eye clinic and normal controls were assessed by Schirmer's test for tear flow. Sera were assessed for autoantibodies using ELISA assays. Statistics was performed with Prism 7 software and student's unpaired t test., Results: In this study 60% of the dry eye patients expressed one of these autoantibodies. Only 30% expressed one of the autoantibodies associated with long-standing SS, which are included in the diagnostic criteria for SS, anti-Ro and anti-La. Patients with disease for less than 2 years and mild dry eyes did not express anti-Ro or anti-La, while 25% expressed anti-SP1. Similar observations, with smaller numbers, were made when patients had not only dry eye but also dry mouth., Conclusions: Antibodies to SP1, CA6 and PSP occur in some patients with idiopathic dry eyes. Further studies will be needed to determine how many of these patients go on to develop systemic manifestations of SS. Testing for these autoantibodies may allow early recognition of patients with SS. This will lead to improved management of the patients and the development of new strategies to maintain normal lacrimal and salivary gland function in patients with SS.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease, characterized by lymphocytic infiltration of the secretory glands. This process leads to sicca syndrome, which is the combination of dryness of the eyes, oral cavity, pharynx, larynx and/or vagina. Extraglandular manifestations may also be prevalent in patients with pSS, including cutaneous, musculoskeletal, pulmonary, renal, hematological and neurological involvement. The pathogenesis of pSS is currently not well understood, but increased activation of B cells followed by immune complex formation and autoantibody production are thought to play important roles. pSS is diagnosed using the American-European consensus group (AECG) classification criteria which include subjective symptoms and objective tests such as histopathology and serology. The treatment of pSS warrants an organ based approach, for which local treatment (teardrops, moistures) and systemic therapy (including non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease-modifying antirheumatic drugs (DMARDS) and biologicals) can be considered. Biologicals used in the treatment of pSS mainly affect the total numbers of B cells (B cell depletion (Rituximab)) or target proteins required for B cell proliferation and/or activation (e.g. B cell activating factor (BAFF)) resulting in decreased B cell activity. The aim of this review is to provide physicians a general overview concerning the pathogenesis, diagnosis and management of pSS patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Aim: To explore the relationship between serum concentration of sex hormones and dry eye symptoms and signs in postmenopausal women., Methods: A cross-sectional analysis was undertaken. Subjects were 46 postmenopausal women with dry eye (mean age 64.4±5.2 years, 13.7±6.4 years since menopause; not undergoing hormone replacement therapy). Ocular symptoms (Ocular Surface Disease Index (OSDI) and Ocular Comfort Index (OCI)), tear function (tear osmolarity, non-invasive tear break-up time, tear secretion), corneal and conjunctival staining, and meibomian gland (MG) appearance, were recorded. Venous blood was collected and serum concentrations of 17β-oestradiol (E2), 3-α-androstanediol-glucuronide (3α-diol-G), and dehydroepiandrosterone sulfate (DHEA-S) were determined using ELISA. Multiple linear regression analysis was used to examine predictors of dry eye symptoms and signs., Results: Mean serum concentration of E2, 3α-diol-G and DHEA-S was 9.02±13.40 pg/mL, 1.59±1.02 ng/mL and 0.74±0.53 μg/mL, respectively. Ocular symptoms were elevated (mean scores 27.0±18.1 (OSDI) and 40.3±8.4 (OCI)) but signs were within normal ranges. Higher serum E2 concentration along with capped glands, lid telangiectasia and older age was a significant predictor of worse MG secretion quality (p<0.001, R 2 adj=0.75). Serum hormones were not significant predictors of ocular symptoms in multivariate analysis (p>0.05)., Conclusion: Serum oestrogen appears to be a key factor in MG signs. Although serum hormone levels did not contribute significantly to dry eye symptoms in this study, it is possible that oestrogen plays a role through its effect on meibum secretion. These findings suggest that MG dysfunction underpins dry eye symptoms in non-Sjögren's dry eye in postmenopausal women., Trial Registration Number: ACTRN12612000281897., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

This study investigated the effect of vitamin D supplementation in patients with dry eye syndrome (DES) refractory to conventional treatment with vitamin D deficiency. A total of 105 patients with DES refractory to conventional treatment and vitamin D deficiency that was treated with an intramuscular injection of cholecalciferol (200,000 IU). Serum 25-hydroxyvitamin D (25(OH)D) levels were measured. Eye discomfort was assessed using ocular surface disease index (OSDI) and visual analogue pain score (VAS). Tear break-up time (TBUT), fluorescein staining score (FSS), eyelid margin hyperemia, and tear secretion test were measured before treatment, and 2, 6, and 10 weeks after vitamin D supplementation. Mean serum 25(OH)D level was 10.52 ± 4.61 ng/mL. TBUT, and tear secretion test showed an improvement at 2 and 6 weeks after vitamin D supplementation compared to pretreatment values (p < 0.05 for all, paired t-test). Eyelid margin hyperemia and the severity of symptoms showed improvement at 2, 6, and 10 weeks after vitamin D supplementation (p < 0.05 for all). Compared to pre-treatment values, FSS, OSDI and VAS were decreased at 2 weeks (p < 0.05 for all). In conclusion, vitamin D supplementation is effective and useful in the treatment of patients with DES refractory to conventional treatment and with vitamin D deficiency.

Purpose: To assess the neutrophil-to-lymphocyte ratio (NLR) as an indicator of inflammation in patients with non-Sjögren dry eye disease., Methods: Serum NLR and C-reactive protein values were determined in 33 patients with dry eye and in 32 controls. The NLR was calculated by dividing the neutrophil count by the lymphocyte count., Results: Characteristics of the dry eye and control groups were similar. The mean NLR value was 2.8 ± 1.4 (range: 1.1-6.1) in the dry eye group and 1.6 ± 0.7 (range: 0.8-2.8) in the control group (P = 0.002, t test). The mean C-reactive protein value was 0.6 ± 0.7 mg/dL (range: 0-2.3 mg/dL) in the dry eye group and 0.5 ± 0.6 mg/dL (range: 0-1.9 mg/dL) in the control group (P = 0.307, t test)., Conclusions: The NLR values were found to be higher in patients with non-Sjögren dry eye than in controls. This result suggests that non-Sjögren dry eye disease may be associated with systemic inflammation or the NLR values may increase in local inflammatory ocular diseases.

Objectives: The purpose of this study was to investigate whether blood mercury concentrations associated with the presence of dry eye symptoms in a nationally representative Korean population., Methods: Population-based prospective cross-sectional study using the heavy metal data set of the 2010-2012 Korean National Health and Nutrition Examination Survey (KNHANES). A total of 4761 adult Koreans were the eligible population in this study. Of the 7162 survey participants, 2401 were excluded because they were <19 years of age, there were missing data in the heavy metal data set, or they had diabetes, rheumatoid arthritis, thyroid disease, asthma, depression and/or under-the-eye surgery. Blood mercury levels were measured on the day the participants completed a questionnaire regarding the presence of dry eye symptoms (persistent dryness or eye irritation). The population was divided into low and high groups by median level (4.26 and 2.89 µg/L for males and females, respectively)., Results: Self-reported dry eye symptoms were present in 13.0% of the cohort. Participants with dry eye symptoms were significantly more likely to have blood mercury levels exceeding the median than those without dry eye symptoms (45.7% vs 51.7%, p=0.021). Logistic regression analysis showed that, after adjusting for age, gender, education, total household income, smoking status, heavy alcohol use, sleep time, perceived stress status, total cholesterol levels and atopy history, dry eye symptoms were significantly associated with blood mercury levels that exceeded the median (reference: lower mercury group; OR, 1.324; 95% CI 1.059 to 1.655; p<0.05)., Conclusions: High blood mercury levels were associated with dry eye symptoms in a nationally representative Korean population., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Purpose: To investigate associations between serum 25-hydroxyvitamin D levels and dry eye syndrome (DES), and to evaluate the differential effect of vitamin D on ocular diseases including age-related macular disease (AMD), diabetic retinopathy (DR), cataract, and DES., Methods: A total of 16,396 participants aged >19 years were randomly selected from the Korean National Health and Nutrition Examination Survey. All participants participated in standardized interviews, blood 25-hydroxyvitamin D level evaluations, and comprehensive ophthalmic examinations. DES was defined by a history of clinical diagnosis of dry eyes by a physician. The association between vitamin D and DES was compared to the associations between vitamin D and AMD, DR, cataract, and DES from our previous studies., Results: The odds of DES non-significantly decreased as the quintiles of serum 25-hydroxyvitamin D levels increased (quintile 5 versus 1, OR = 0.85, 95%CI: 0.55-1.30, P for trend = 0.076) after adjusting for potential confounders including age, sex, hypertension, diabetes, smoking status, and sunlight exposure times. The relative odds of DES (OR = 0.70, 95% CI: 0.30-1.64) and cataract (OR = 0.76, 95% CI: 0.59-0.99) were relatively high, while those of DR (OR = 0.37, 95% CI: 0.18-0.76) and late AMD (OR = 0.32, 95% CI: 0.12-0.81) were lower in men., Conclusions: The present study does not support an association between serum 25-hydroxyvitamin D levels and DES. The preventive effect of serum 25-hydroxyvitamin D may be more effective for DR and late AMD than it is for cataract and DES.

Purpose: The aims of this analysis were to determine if there is an association between serum levels of testosterone and estradiol with meibomian gland (MG) morphology and lipid layer thickness., Methods: The data used for this analysis were collected from postmenopausal women with and without dry eye disease. Meibography was used to assess MG dropout on the central two-thirds of the eyelid and biomicroscopy was used for assessing MG expressibility and meibum quality. Venous blood samples were drawn for serum hormone level analysis. The Kruskal-Wallis test and Spearman correlations were used for statistical analysis., Results: One hundred ninety-eight postmenopausal women with an average age of 61.2 (± 9.1) years were included in this analysis. Testosterone levels showed significant differences between MG dropout grades 1 and 4 (P = 0.002) and grades 2 and 4 (P = 0.01), whereas estradiol levels were different based on MG dropout (P = 0.53). No significant correlations were found between testosterone (r = 0.10, P = 0.17) or estradiol (r = 0.05, P = 0.45) and lipid layer thickness., Conclusions: Testosterone levels were increased with MG dropout, which was significant between the mild and severe dropout groups, whereas no significant differences were found with estradiol and any MG assessment. Although the literature suggests an association of serum hormone levels and pathogenesis of dry eye disease in postmenopausal women, analysis of active sex steroid precursors and local tissue hormone levels may prove more useful.

Background: Dry eye syndrome (DES) is a common tear film and ocular surface disease that results in discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. Systemic diseases associated with DES include diabetes mellitus, rheumatoid arthritis, depression, anxiety, thyroid disease, allergic diseases, irritable bowel syndrome, chronic pain syndrome, and hyperlipidemia. Interestingly, it has been found that most of these are associated with low levels of serum 25-hydroxyvitamin D (25(OH)D) or inadequate sunlight exposure., Methods: In this cross-sectional data analysis, noninstitutionalized adults aged ≥19 years (N = 17,542) who participated in Korean National Health and Nutrition Examination Survey 2010-2012 were included. Information regarding duration of sunlight exposure was collected from the survey participants. Serum 25(OH)D and zinc levels were measured. The confounding variables were age, gender, sunlight exposure time, region of residence, obesity, serum 25(OH)D level, diabetes mellitus, rheumatoid arthritis, depression, thyroid disorder, atopic dermatitis, history of ocular surgery, regular exercise, and walking exercise., Results: Mean serum 25(OH)D levels of subjects with and without DES were 16.90 ± 6.0 and 17.52 ± 6.07 (p<0.001). Inadequate sunlight exposure time (odds ratio [OR], 1.554; 95% confidence interval [CI], 1.307-1.848), urban residence (OR, 1.669; 95% CI, 1.456-1.913), indoor occupation (OR, 1.578; 95% CI, 1.389-1.814), and low serum 25(OH)D level (OR, 1.158; 95% CI, 1.026-1.308) were the risk factors for DES. After adjusting for age, sex, obesity, diabetes mellitus, rheumatoid arthritis, depression, thyroid disorder, atopic dermatitis, history of ocular surgery, regular exercise, and occupation, low serum 25(OH)D level (OR, 1.178; 95% CI, 1.010-1.372) and deficient sunlight exposure time (OR, 1.383; 95% CI, 1.094-1.749) were the risk factors for diagnosed DES., Conclusion: Low serum 25(OH)D levels and inadequate sunlight exposure are associated with DES in Korean adults. These results suggest that sufficient sunlight exposure or vitamin D supplementation may be useful in DES treatment.

Dry eye disease (DED) has evolved into a major public health concern with ocular discomfort and pain being responsible for significant morbidity associated with DED. However, the etiopathological factors contributing to ocular pain associated with DED are not well understood. The current IVCM based study investigated the association between corneal dendritic cell density (DCD), corneal subbasal nerve plexus (SBNP) features, and serum vitamin D and symptoms of evaporative dry eye (EDE). The study included age and sex matched 52 EDE patients and 43 heathy controls. A significant increase in the OSDI scores (discomfort subscale) was observed between EDE (median, 20.8) and control (median, 4.2) cohorts (P < 0.001). Similarly, an increase in DCD was observed between EDE (median, 48.1 cells/mm(2)) patients and controls (median, 5.6 cells/mm(2)) (P < 0.001). A significant decrease in SBNP features (corneal nerve fiber length, fiber density, fiber width, total branch density, nerve branch density, and fiber area) was observed in EDE patients with OSDI score >23 (P < 0.05). A positive correlation was observed between DCD and OSDI discomfort subscale (r = 0.348; P < 0.0003) and SBNP features. An inverse correlation was observed between vitamin D and OSDI scores (r = -0.332; P = 0.0095) and DCD with dendritic processes (r = -0.322; P = 0.0122). The findings implicate DCD, SBNP features, and vitamin D with EDE symptoms.

Purpose: Dry eye is one of the suggested extrahepatic complications associated with hepatitis C virus (HCV) infection. HCV RNA has been detected from the tear fluid of patients with chronic HCV. There has been no literature evidence on the presence of HCV RNA in the tear fluid of patients with dry eye without HCV infection. In this study, tear fluid of patients with dry eye with no HCV infection was screened for the presence of HCV RNA., Methods: Tear fluid was collected from patients with dry eye (n = 36) and healthy controls (n = 20). Real-time polymerase chain reaction was performed to detect HCV RNA in the tear fluid. Anti-HCV enzyme-linked immunosorbent assay, alkaline phosphatase, and alanine aminotransferase tests were performed in the serum samples collected from 15 patients with dry eye., Results: Viral RNA was detected in 58.3% of the patients. Serum samples collected from 15 patients with dry eye were negative for anti-HCV. Alkaline phosphatase levels were elevated in 12 of 15 patients. Alanine aminotransferase levels were normal in all 15 patients. The odds ratio for the presence of HCV RNA in patients with dry eye was 22.4., Conclusions: These results indicate a direct correlation between dry eye and HCV in non-HCV patients.

Purpose: The aim of this study was to evaluate the association between a Mediterranean dietary pattern (MeDi) and Vitamin D levels on dry eye syndrome (DES)., Methods: This was a cross-sectional study. Male patients seen in the Miami Veterans Affairs eye clinic with normal eyelid, corneal, and conjunctival anatomy were recruited to participate in the study. The patients filled out the 2005 Block Food Frequency Questionnaire and the Dry Eye Questionnaire 5 and underwent measurement of tear film parameters. The serum level of 25-hydroxy vitamin D was also measured. The main outcome measures included the association among MeDi, Vitamin D levels, and DES., Results: Two hundred forty-seven men underwent DES testing. The mean patient age was 69 years (range, 55-95). Using latent class analysis to categorize the presence or absence of disease and quantify its severity, we found that adherence to the MeDi was positively associated with the risk of having DES (odd ratio 1.25, 95% confidence interval, 1.06-1.47, P = 0.007) and with increasing disease severity. Vitamin D levels were not significantly associated with the presence or severity of disease. However, higher levels of vitamin D were associated with decreased DES symptoms, with a -1.24 decrease in median Dry Eye Questionnaire 5 score for every 10-U increase in Vitamin D levels (P = 0.01)., Conclusions: Adherence to the MeDi was not associated with a beneficial effect on DES. Higher vitamin D levels had a small but favorable effect on DES symptoms.

Aims: To evaluate the role of 17-β-oestradiol, oestrone and total testosterone (TT) deficiency in the pathogenesis of severe evaporative dry eye syndrome (DES), investigating the relationship between tear osmolarity, tear film break-up time (TF-BUT), Schirmer test and serum sex hormones in postmenopausal women., Methods: 44 postmenopausal women were recruited for a case-control study: 22 women with severe evaporative DES (Group A) and 22 without DES (Group B). The tests performed included laboratory blood analysis: fasting plasma profile (17-β-oestradiol, oestrone and TT), glucose level and lipid profile. Detailed eye examinations, including corneal and conjunctival staining, tear osmolarity measurement, tear volume and TF-BUT, were performed. The Ocular Surface Disease Index Questionnaire was also administered., Results: Values of Schirmer test and TF-BUT in Group A were significantly lower in comparison with Group B (p<0.001). Serum levels of 17-β-oestradiol, oestrone and TT were significantly lower in Group A compared with Group B (p<0.05). In women with severe evaporative DES, the levels of 17-β-oestradiol, oestrone and TT were inversely correlated with the tear film osmolarity (r=-0.7, -0.88, -0.81, respectively)., Conclusions: In postmenopausal women with severe evaporative DES, sex hormone levels are lower than control and that tear osmolarity is negatively correlated with sex hormone levels.

Purpose: To compare plasma homocysteine levels between patients with dry eye disease and normal control subjects., Methods: Plasma homocysteine (enzyme immunoassay), vitamin B12, and folate levels were determined in 38 patients with dry eye and in 38 controls., Results: Characteristics of the dry eye and control groups were similar. The mean plasma homocysteine level was 16.38 ± 6.98 μmol/L in the dry eye group and 14.39 ± 5.11 μmol/L in the control group (P = 0.10, t test). Hyperhomocysteinemia was present in the 43.9% of the dry eye patients and 33.3% of the controls (P = 0.43, χ test). There were no statistical differences between dry eye and control groups regarding plasma vitamin B12 and folate levels (P = 0.72 and P = 0.69, respectively, t test)., Conclusions: Plasma homocysteine levels in dry eye patients may be inadequate to give homocysteine a role in pathogenesis. However, in ocular diseases like glaucoma, plasma homocysteine levels are significantly higher, and associated dry eye disease may cause an additional increase in plasma homocysteine levels.

Aim: To investigate the frequency and risk factors of non-retinopathy ocular conditions in persons with diabetes., Methods: A population-based cross-sectional study of 3176 Malay persons aged between 40 and 79 years in Singapore was conducted. Cataract, glaucoma, refractive errors, age-related macular degeneration, dry eye, epiretinal membrane, ocular hypertension and retinal conditions were assessed based on standardized interviews, clinical examinations and laboratory investigations., Results: A total of 768 participants (24.2%) had diabetes. People with diabetes were more likely to have cortical cataract (52.1 vs. 37.3%, P < 0.001), ocular hypertension (10.9 vs. 7.4%, P = 0.002) and epiretinal membrane (17.2 vs. 10.1%, P < 0.001) compared with those without diabetes. The odds of having cortical cataract (odds ratio 1.63, 95% CI 1.20-2.20) and epiretinal membrane (among those with previous cataract surgery: odds ratio 1.63, 95% CI 1.20-2.20) were significantly higher in people with diabetes compared with those without. The population attributable risks for cortical cataract and epiretinal membrane because of diabetes were 8.7 and 9.0%, respectively. In persons with diabetes, hypertension and high cholesterol were the major risk factors associated with non-retinopathy eye complications such as ocular hypertension (odds ratio 1.18, 95% CI 1.04-1.33) and retinal emboli (odds ratio 1.99, 95% CI 1.05-3.80)., Conclusion: Our results allow clinicians to better inform patients with diabetes that they are more likely to have cortical cataract and epiretinal membranes (those with previous cataract surgery) in addition to diabetic retinopathy. Two modifiable risk factors-blood pressure and cholesterol associated with ocular hypertension and retinal emboli, respectively-are also risk factors for non-retinopathy ocular conditions in persons with diabetes., (© 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.)

Objective: To evaluate the correlation between tear osmolarity and blood levels of 17-β estradiol, estrone, and testosterone in postmenopausal women with dry eye syndrome, and to assess the efficacy and safety of oral supplementation with phytoestrogens, lipoic acid, and eicosapentaenoic acid in this population., Design: Cross-sectional study including 66 postmenopausal women with dry eye syndrome., Methods: Sixty-six postmenopausal women with dry eye syndrome were enrolled in a randomized, double-blind, placebo-controlled, crossover study. Patients were divided into 2 groups (groups A and B) and treated, respectively, with phytoestrogen (Bioos, Montegiorgio, Italy) tablets or placebo tablets for 30 days. The 2 treatment periods were separated by a 30-day washout. Patients were examined on days 0 and 30 of each period. Assessments included blood levels of sex hormones, the Schirmer test for tear production, and measurement of tear osmolarity and tear film break-up time., Results: At baseline, all patients had low sex hormone levels, which were correlated with high tear film osmolarity values (r = -0.59,-0.61,-0.58, respectively). After 30 days of therapy, the group treated with Lacrisek® (Bioos) had significantly decreased tear osmolarity (P<0.005) and significantly increased tear production evaluated with the Schirmer test and tear film break-up time values (P<0.001) compared with the placebo-treated group., Conclusions: Our study confirms that steroid hormones play an important role in ocular surface equilibrium and functions. Consequently, reduced blood levels of these hormones can produce changes at the ocular surface. Phytoestrogen supplementation can significantly improve the signs and symptoms of dry eye syndrome in postmenopausal women., (Copyright © 2012 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate whether ethanol administration disturbs the tear film and ocular surface., Design: Case-control study., Participants: Twenty healthy male subjects were recruited. Ethanol was administered to 10 subjects and another 10 subjects served as controls., Methods: Twenty healthy male subjects with no ocular disease were recruited. Ethanol (0.75 g/kg) was administered orally at 8 pm for 2 hours to 10 subjects., Main Outcome Measures: The tear film and ocular surface were evaluated at 6 pm before drinking, at midnight, and immediately (6 am) and 2 hours (8 am) after waking the next morning. Tear osmolarity, ethanol concentration in tears and serum, Schirmer's test results, tear film break-up time (TBUT), corneal punctuate erosion, and corneal sensitivity were measured., Results: Ethanol was detected in tears and serum at midnight, but it was not detected the next morning. The mean tear osmolarity level increased in the alcohol group at midnight compared with that in the control group (P<0.001). The alcohol group showed a significantly shorter TBUT compared with the control group after drinking alcohol (P<0.001 at 12 am, P<0.001 at 6 am, and P = 0.002 at 8 am). There were significantly higher fluorescein staining scores in the alcohol group compared with those in the control group at 6 am and 8 am (P = 0.001 and P<0.001, respectively). No significant change was shown in corneal sensitivity or Schirmer's test results in either group., Conclusions: Orally administered ethanol was secreted into the tears. Ethanol in tears induced tear hyperosmolarity and shortened TBUT and triggered the development of ocular surface diseases. Similar changes could exacerbate signs and symptoms in patients with ocular surface disease., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the association between dry eye syndrome (DE) and serum levels of interleukin (IL)-17 in patients with systemic immune-mediated diseases., Methods: IL-17 and IL-23 levels were measured in the sera of patients whose tear production was <5 mm on the Schirmer test. Subjects included patients with chronic graft-versus-host disease (GVHD), rheumatoid arthritis (RA), Sjogren's syndrome (SS), systemic lupus erythematosus (SLE), and no systemic disease. Corneal/conjunctival fluorescein staining was scored and the correlation between the score and the IL-17 level was evaluated., Results: A strong correlation existed between IL-17 level and the type of systemic disease. IL-17 was significantly elevated in patients with chronic GVHD compared to those with RA and SS. IL-17 was not detectable in patients with SLE or in those without systemic disease. IL-23 was not detected in any of the subjects. IL-17 was significantly increased in patients with high fluorescein staining scores., Conclusions: Our data suggest that IL-17 is involved in the pathogenesis of DE in patients with systemic immune-mediated diseases., (© 2011 The Korean Ophthalmological Society)

Background: To perform a comprehensive serum growth factor analysis in dry eye syndrome patients and to compare this with matched controls., Methods: Six female dry eye syndrome patients and six age- and gender-matched controls were recruited. Whole blood was collected, allowed to clot and then centrifuged. Serum was extracted by using sterile technique. Enzyme-linked immunosorbent assays were performed to quantify serum growth factor levels., Results: Levels of transforming growth factor-beta 1 and 2 (TGF-beta1 and beta2), nerve growth factor (NGF), insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), acidic and basic fibroblast growth factor (FGF), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor-AA, AB and BB (PDGF-AA, AB and BB), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and glial cell line-derived neurotrophic factor (GDNF) were quantified, and statistical analysis was performed by using the Mann-Whitney U-test with the Bonferroni correction., Conclusions: No significant difference was found between serum growth factor levels in dry eye syndrome patients versus controls. Our study provides comprehensive analysis of serum growth factor levels in autologous serum eye drops produced from ocular surface disease patients. A knowledge of growth factor levels in serum may be important because of the increasing use of autologous serum eye drops in refractory ocular surface diseases and for an understanding of how topical serum may provide benefit.

Conventional treatment of dry eye mainly consists of the use of preservative-free artificial eye drops and punctal occlusion. None of the commercially available artificial tear preparations include essential tear components such as epidermal growth factor, hepatocyte growth factor, fibronectin, neurotrophic growth factor, and vitamin A-all of which have been shown to play important roles in the maintenance of a healthy ocular surface epithelial milieu. We reported previously that autologous serum (AS) eye drops contain these essential factors and that AS eye drops are beneficial in the treatment of ocular surface diseases such as persistent epithelial defects, superior limbic keratoconjunctivitis, keratoconjunctivitis sicca, and neurotrophic keratopathy. However, there is some controversy regarding the efficacy of AS treatment. We demonstrated that this modality is more effective than artificial tears in a randomized control study. In in vivo and in vitro experiments, AS eye drops showed marked suppression of apoptosis in the conjunctival and corneal epithelium. Albumin, the major protein in serum, improved ocular surface damage in vivo and rescued apoptosis after serum deprivation in vitro. The biological background of AS eye drops and previous clinical studies of these medications for the treatment of dry eye are discussed.

Aims: We assessed homocysteine (Hcy) levels in tear fluid and plasma of patients with primary open-angle glaucoma (POAG). We determined the association between Hcy levels, dry eye syndrome and B vitamin status., Methods: This prospective case-control study included 36 patients with POAG and 36 controls. Hcy concentrations were measured by high-performance liquid chromatography., Results: Patients with POAG had significantly higher mean Hcy levels both in tear fluid (205 +/- 84 nmol/l; p < 0.001, t test) and in plasma (13.43 +/- 3.53 micromol/l; p = 0.001, t test) than control subjects (130 +/- 53 nmol/l and 10.50 +/- 3.33 micromol/l, respectively). Hcy in tear fluid was significantly correlated with plasma Hcy in POAG patients (r = 0.459; p = 0.005, Pearson's correlation), but not in controls (r = 0.068; p = 0.695). POAG patients with dry eye disease had significantly higher Hcy levels both in tear fluid and plasma than POAG patients without dry eye disease. There was no association between Hcy levels and B vitamin status in subjects with POAG., Conclusions: The study suggests increased Hcy levels in tear fluid and plasma of patients with POAG. Elevated Hcy levels might be a risk factor for POAG and dry eye syndrome in subjects with glaucoma., (Copyright 2008 S. Karger AG, Basel.)

Purpose: The purpose of this study was to compare total testosterone blood level among three groups of postmenopausal women: control, mild to moderate dry eye and severe dry eye., Methods: Twenty-nine postmenopausal women were selected. The exclusion criteria were: hormone replacement therapy in the last 8 weeks, mechanical palpebral abnormalities, pterygium, lacrimal obstructions, intraocular inflammation or contact lens use. A blood sample was collected for total testosterone level determination, and the patients were submitted to an ophthalmologic examination (emphasizing on dry eye detection) and answered the OSDI (Ocular Surface Disease Index) questionnaire. Five patients were excluded. Postmenopausal women were divided into three groups according to OSDI score and the ophthalmic examination., Results: Five patients were classified in the no dry eye group (control), fifteen in the mild to moderate dry eye group and four in the severe dry eye group. There were no statistically significant differences regarding mean age (p=0.3915); instruction level (p=0.9333); number of comorbidities (p=0.2551); medication taken (p=0.2844) and total testosterone level among those groups (p=0.1275)., Conclusion: Further research with a greater bigger sample is necessary to establish the relation of androgen levels in dry eye patients.

Purpose: To investigate the efficacy of umbilical cord serum eyedrops for the treatment of severe dry eye syndrome., Methods: Fifty-five eyes of 31 patients with severe dry eye syndrome were treated with umbilical cord serum eyedrops. Symptom scoring, tear film break-up time (BUT), Schirmer test, corneal sensitivity test, and corneal fluorescein staining were performed before and 1 and 2 months after treatment, and conjunctival impression cytology was performed before and 2 months after treatment. The concentrations of epidermal growth factor (EGF), vitamin A, and transforming growth factor-beta (TGF-beta) in umbilical cord serum and normal peripheral blood serum were measured., Results: Two months after treatment, significant improvement was observed in symptom score (from 3.07 +/- 0.54 to 0.96 +/- 0. 58), BUT (from 3.96 +/- 1.56 to 5.45 +/- 2.54 seconds), and keratoepitheliopathy score (from 4.87 +/- 3.22 to 1.71 +/- 1.84) (P < 0.01). There was no statistically significant change in Schirmer and corneal sensitivity tests. In impression cytology, the grade of squamous metaplasia (from 2.35 +/- 0.72 to 1.44 +/- 0.69) and goblet cell density (from 80.91 +/- 31.53 to 154.68 +/- 43.06 cell/mm) improved significantly (P < 0.01). The mean concentrations of EGF, TGF-beta, and vitamin A were 0.48 +/- 0.09, 57.14 +/- 18.98, and 230.85 +/- 13.39 ng/mL in umbilical cord serum and 0.14 +/- 0.03, 31.30 +/- 12.86, and 372.34 +/- 22.32 ng/mL in peripheral blood serum, respectively., Conclusion: Umbilical cord serum contains essential tear components, and umbilical cord serum eyedrops are effective and safe for the treatment of severe dry eye syndrome.

Purpose: To evaluate androgen levels of patients diagnosed with nonautoimmune dry eye, either with meibomian gland dysfunction (MGD) or without MGD (non-MGD), and normal control subjects. This is a prospective, comparative, case-control study., Methods: Sixty-four (32 men and 32 women) subjects were enrolled for each of the three diagnostic groups. All dry eye patients were symptom positive. Nonfasting testosterone (T), sex hormone-binding globulin, serum albumin, dehydroepiandrosterone (DHEA), and DHEA sulphate levels of all study participants were determined using either automated immunoenzymatic assay, or standard radioimmunoassay. Analysis of variance was used to compare androgen levels among the three diagnostic groups in a gender-based design, followed by post-hoc multiple comparisons with the Tukey honestly significant difference test., Results: Mean T levels in men and women of the three diagnostic groups were not significantly different (p = 0.808, p = 0.156, respectively; ANOVA). Statistical analyses of the three diagnostic groups revealed a significant difference for men and women in bioavailable T levels (p = 0.002, p = 0.014, respectively; ANOVA), DHEA levels (p = 0.009, p = 0.004, respectively; ANOVA), and DHEA sulphate levels (p = 0.001, p = 0.001, respectively; ANOVA), whereas there was no statistically significant difference between non-MGD dry eye patients and controls for any of the measured androgen levels according to the post-hoc tests., Conclusion: This study demonstrates that the androgen pool of nonautoimmune dry eye patients with MGD is significantly depleted compared with that of non-MGD and control cases., (Copyright (c) 2006 S. Karger AG, Basel.)

Purpose: To examine the changes in tear volume, sodium concentration, and osmolarity in BALB/c and C57BL/6J mice in response to experimental dry eye (EDE)., Methods: Tear volumes were determined at baseline and after 2 days of EDE using phenol red-impregnated cotton thread. Tear fluid was collected by instilling 1 microl of distilled water into the conjunctival sac and collecting the diluted tear fluid in a 0.5-microL glass capillary tube. CoroNa Red in dimethyl sulfoxide DMSO was added, and the fluorescent intensity was measured, which was compared to a standard curve of sodium concentrations. The resulting concentration was then corrected by the proper dilution factor. The tear osmolarity owing to sodium was calculated by comparing the calculated tear sodium concentration to a standard curve established by a vapor pressure osmometer. Serum osmolarity was also determined using a vapor pressure osmometer., Results: After 2 days of EDE, tear volume significantly decreased from 0.093 microL to 0.028 microL in BALB/c mice and from 0.066 microL to 0.026 microL in C57BL/6J mice. There was a concomitant significant increase in tear osmolarity from 177 mOsm/L to 300 mOsm/L in C57BL/6J mice. Tear osmolarity nearly doubled from 285 mOsm/L to 559 mOsm/L in BALB/C mice with EDE, approaching statistical significance (P=0.12). No change in the serum osmolarity was observed in either mouse strain., Conclusions: These experiments show the ability of these new techniques for determining tear volume and estimating tear osmolarity in mice. By mimicking the findings of human dry eye disease, these findings validate the relevance of the mouse model for studying the pathogenesis of human keratoconjunctivitis sicca.