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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.

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.

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.

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.

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.

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.