Assessment of leukocyte and systemic inflammation index ratios in dyslipidemia patients with dry eye disease: a retrospective case‒control study.

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.

A Metabolome-Wide Study of Dry Eye Disease Reveals Serum Androgens as Biomarkers.

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.

Reviewing primary Sjögren's syndrome: beyond the dryness - From pathophysiology to diagnosis and treatment.

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.

Lower Serum Vitamin D Level Was Associated with Risk of Dry Eye Syndrome.

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.

Analysis of novel Sjogren's syndrome autoantibodies in patients with dry eyes.

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.

Frequency and risk factors of non-retinopathy ocular conditions in people with diabetes: the Singapore Malay Eye Study.

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.

Oral alcohol administration disturbs tear film and ocular surface.

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.

IL-14α as a Putative Biomarker for Stratification of Dry Eye in Primary Sjögren's Syndrome.

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.

Vitamin D deficiency is associated with dry eye syndrome: a systematic review and meta-analysis.

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.

Serological and hematological characteristics of Sjogren's syndrome and dry eye syndrome patients using a novel immune serology technique.

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.

[Blepharospasm, dry eye and extractable nuclear antigen antibodies (French translation of the article)]. / Blépharospasme, sécheresse oculaire et anticorps anti-nucléaires solubles.

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.

Blepharospasm, dry eye and extractable nuclear antigen antibodies.

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.

Association Between Dyslipidemia and Dry Eye Syndrome Among the Korean Middle-Aged Population.

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.

Rheumatoid factor versus anti - cyclic citrullinated peptide antibody as screening tool for rheumatoid arthritis in an ophthalmic clinic.

Patients with moderate to severe dry eyes are often screened at the Dry Eye Clinic to rule out connective tissue diseases. Rheumatoid factor (RF) is one of the screening tools to rule out rheumatoid arthritis (RA). Patients who turn out positive for the RF are often subjected to anti-CCP antibody evaluation for confirmation of disease. This article tries to highlight 3 cases of negative and anti-CCP antibody positive cases which presented to the ophthalmic clinic, unaware of their systemic status. Though RF is the cheapest modality to screen for RA, it is not always a reliable marker. One should order anti-CCP antibody for patients where suspicion is high, despite RF being normal.

Association Between Early Sjögren Markers and Symptoms and Signs of Dry Eye.

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.

The Association of Serum Vitamin D Level With the Severity of Dry Eye Parameters in Primary Sjögren Syndrome.

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.

Association of Dry Eye Disease With Dyslipidemia and Statin Use.

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.

Local Ocular Surface Alterations in Children with Hashimoto's Thyroiditis.

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.

Reduction in the inflammatory markers CD4, IL-1, IL-6 and TNFα in dogs with keratoconjunctivitis sicca treated topically with mesenchymal stem cells.

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 × 106 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.

Increased homocysteine levels in tear fluid of patients with primary open-angle glaucoma.

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.