Joon Young Hyon

Association between Depression and Dry Eye Disease in an Elderly Population

PURPOSE A population-based cross-sectional study to investigate the association between depression and dry eye disease (DED) in a community-dwelling elderly population. METHODS The subjects were 657 Korean elders ≥ 65 years of age randomly selected from an official household registration database in Yongin, Korea. DED symptoms were assessed using the six-item Dry Eye Questionnaire. DED signs were evaluated using the Schirmer test, fluorescein stain score, tear film break-up time (BUT). Depression was assessed using the Korean version of the Short Geriatric Depression Scale (SGDS-K). The association between DED and depression was evaluated using logistic linear analyses. RESULTS The SGDS-K score correlated with the number of positive responses in the Dry Eye Questionnaire (r = 0.229, P < 0.001), but not with tear film break-up time (r = 0.041, P = 0.139) or Schirmer test score (r = 0.048, P = 0.642). In the binary logistic regression model, female sex (P = 0.014), residence in urban areas (P < 0.001), depression (P < 0.001), and Schirmer score of ≤ 5 mm (P = 0.035) were associated with the risk of DED. Depression was associated with the risk of DED (P < 0.001) in the patients with Schirmer score > 5 mm but not in those with Schirmer score ≤ 5 mm (P = 0.290). CONCLUSIONS Depression was associated with DED symptoms in subjects with normal or mildly reduced tear production.

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, Schirmers 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 Schirmers 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.

Management of ocular surface inflammation in Sjögren syndrome.

Purpose: To evaluate the clinical efficacy of anti-inflammatory therapy in the management of primary Sjögren syndrome. Methods: Thirty-eight patients with primary Sjögren syndrome were included in this study. The diagnosis of Sjögren syndrome was made on the basis of the classification criteria of the American-European Consensus Group. Fluorescein staining score, rose-bengal staining score, Schirmer test score, tear film breakup time, and functional parameters including ocular surface disease index (OSDI) and visual analog scale (VAS) score were measured at the first visit. Anti-inflammatory therapy included topical corticosteroids, topical autologous serum, and topical cyclosporin A. The clinical efficacy of anti-inflammatory treatment was evaluated in terms of subjective symptoms and objective signs (including Schirmer-1 test, breakup time, rose-bengal score, and fluorescein score). Results: Patients with Sjögren syndrome had higher rose-bengal scores than patients with non-Sjögren dry eye (P < 0.05). The OSDI score showed better correlation with fluorescein score than with VAS score. Subjective symptoms improved with anti-inflammatory treatment in 70% of patients with primary Sjögren syndrome. Anti-inflammatory treatment provided significant improvement in visual acuity and fluorescein score but did not affect Schirmer score, tear breakup time, or rose-bengal score. Conclusions: Anti-inflammatory therapy in primary Sjögren syndrome significantly improved subjective symptoms and objective ocular signs; however, we did not find evidence that anti-inflammatory treatment increases tear production in patients with Sjögren syndrome.

Cytotoxicity of Voriconazole on Cultured Human Corneal Endothelial Cells

ABSTRACT The purpose of the present study was to evaluate the toxicity of voriconazole on cultured human corneal endothelial cells (HCECs). HCECs were cultured and exposed to various concentrations of voriconazole (5.0 to 1,000 μg/ml). Cell viability was measured using a Cell Counting Kit-8 (CCK-8) and live/dead viability/cytotoxicity assays. Cell damage was assessed using phase-contrast microscopy after 24 h of exposure to voriconazole. To analyze the effect of voriconazole on the intercellular barrier, immunolocalization of zonula occludens 1 (ZO1) was performed. A flow cytometric assay was performed to evaluate the apoptotic and necrotic effects of voriconazole on HCECs. Cytotoxicity tests demonstrated the dose-dependent toxic effect of voriconazole on HCECs. Voriconazole concentrations of ≥100 μg/ml led to a significant reduction in cell viability. The morphological characteristics of HCECs also changed in a dose-dependent manner. Increasing concentrations of voriconazole resulted in fading staining for ZO1. Higher concentrations of voriconazole resulted in an increased number of propidium iodide (PI)-positive cells, indicating activation of the proapoptotic pathway. In conclusion, voriconazole may have a dose-dependent toxic effect on cultured HCECs. The results of this study suggest that although voriconazole concentrations of up to 50 μg/ml do not decrease cell viability, intracameral voriconazole concentrations of ≥100 μg/ml may increase the risk of corneal endothelial damage.

The EULAR Sjögren’s syndrome patient reported index as an independent determinant of health-related quality of life in primary Sjögren’s syndrome patients: in comparison with non-Sjögren’s sicca patients

OBJECTIVE To investigate the significant determinants of health-related quality of life (HRQOL) and the association of the EULAR Sjögrens syndrome patient reported index (ESSPRI) with clinical parameters including HRQOL in Korean patients with primary Sjögrens syndrome (pSS) compared with non-SS sicca patients. METHODS We prospectively analysed 104 pSS and 42 non-SS sicca patients. Clinical data including Short Form 36 (SF-36) scores, self-assessments for symptoms and ESSPRI were cross-sectionally collected. RESULTS Although most self-assessments and HRQOL statuses were comparable, different association patterns between HRQOL and symptoms were observed in pSS and non-SS sicca patients. pSS patients with low HRQOL had significantly higher ESSPRI scores [P = 7.6 × 10(-6) for physical component summary (PCS) subgroups and P = 0.0015 for mental component summary (MCS) subgroups] and ESSPRI scores showed a significant association with all SF-36 scales in pSS patients (all P ≤ 0.0020). Moreover, in multivariate linear regression analyses, ESSPRI (P = 0.035) and depression (P = 4.1 × 10(-14)) were significantly correlated with the PCS and the MCS, respectively. However, in the non-SS sicca group, xerostomia inventory (XI) scores were higher in the low PCS subgroup (P = 0.031) and this correlated with five SF-36 scales (all P ≤ 0.046). XI scores (P = 0.0039) and anxiety (P = 7.9 × 10(-10)) were the main determinants of the PCS and MCS, respectively. CONCLUSION HRQOL levels were differentially associated with clinical facets in pSS and non-SS sicca patients, although the groups had similar clinical symptoms and HRQOL reduction. Because depression and ESSPRI are major determinants of HRQOL in Korean pSS patients, ESSPRI is suggested to be disease-specific for pSS.

Chemical injury-induced corneal opacity and neovascularization reduced by rapamycin via TGF-β1/ERK pathways regulation.

PURPOSE To investigate the protective effect of rapamycin against alkali burn-induced corneal damage in mice. METHODS BALB/c mice were treated with 0.1 N NaOH to the cornea for 30 seconds. Corneal neovascularization and opacity were clinically evaluated at 1, 2, and 4 weeks after chemical burn injury. Rapamycin was delivered topically to right eyes (1 mg/mL) and injected intraperitoneally (0.2 mg/kg) once a day. Concentrations of interleukin-6 (IL-6) and transforming growth factor-beta1 (TGF-β1) in the cornea were measured by enzyme-linked immunosorbent assay (ELISA). In vitro-cultured human corneal stromal cells were treated with 0 to 500 nM rapamycin for 3 days and then assessed by immunofluorescence staining of vimentin and alpha-smooth muscle actin (α-SMA). Western blotting assays for α-SMA, phosphorylated extracellular signal-regulated kinase (ρ-ERK 1/2), and total ERK 1/2 were also performed. RESULTS Corneal neovascularization and corneal opacity scores measured 4 weeks after the chemical burn corneal injury were lower in the rapamycin group than in the control group. Two weeks after the chemical burn injury, a significant elevation in the corneal IL-6 levels of the positive control group was observed, compared to the levels in the negative control group or the rapamycin group (P < 0.05). Corneal TGF-β1 levels were lower in the rapamycin-treated group than in the control group at 4 weeks after chemical burn injury (P < 0.05). Moreover, rapamycin inhibited TGF-β1-induced α-SMA expression and augmented ERK 1/2 phosphorylation. CONCLUSIONS Rapamycin treatment reduced corneal opacity and corneal neovascularization in BALB/c mice. Rapamycin protected the cornea from chemical damage via reduction of IL-6 and TGF-β1 expression. Rapamycin reduced α-SMA expression through the ERK 1/2 pathway.

Korean Guidelines for the Diagnosis and Management of Dry Eye: Development and Validation of Clinical Efficacy

Purpose To evaluate the clinical efficacy of newly developed guidelines for the diagnosis and management of dry eye. Methods This retrospective, multi-center, non-randomized, observational study included a total of 1,612 patients with dry eye disease who initially visited the clinics from March 2010 to August 2010. Korean guidelines for the diagnosis and management of dry eye were newly developed from concise, expert-consensus recommendations. Severity levels at initial and final visits were determined using the guidelines in patients with 90 ± 7 days of follow-up visits (n = 526). Groups with different clinical outcomes were compared with respect to clinical parameters, treatment modalities, and guideline compliance. Main outcome measures were ocular and visual symptoms, ocular surface disease index, global assessment by patient and physician, tear film break-up time, Schirmer-1 test score, ocular surface staining score at initial and final visits, clinical outcome after three months of treatment, and guideline compliance. Results Severity level was reduced in 47.37% of patients treated as recommended by the guidelines. Younger age (odd ratio [OR], 0.984; p = 0.044), higher severity level at initial visit, compliance to treatment recommendation (OR, 1.832; p = 0.047), and use of topical cyclosporine (OR, 1.838; p = 0.011) were significantly associated with improved clinical outcomes. Conclusions Korean guidelines for the diagnosis and management of dry eye can be used as a valid and effective tool for the treatment of dry eye disease.

Rapamycin reduces reactive oxygen species in cultured human corneal endothelial cells.

Purpose: To investigate the protective effect of rapamycin on oxidative stress-induced cell death of human corneal endothelial cells (HCECs). Methods: HCECs were cultured according to previously published methods. With treatment of 0 mM or 5 mM of tert-butyl hydroperoxide (tBHP) with various concentrations (0, 25 and 50 nM) of rapamycin, reactive oxygen species (ROS) production was measured using an oxidation-sensitive fluorescent probe, 2′7′-dichlorofluorescin diacetate (DCFH-DA, USA) methods. Cell viability was assayed by the method of Cell Counting Kit-8 (CCK-8, Wako). The levels of cellular glutathione were also assessed enzymatically with glutathione reductase by using a commercial glutathione (GSH) assay kit (Cayman Chemical, USA). Results: Rapamycin reduced 2′7′-dihydrodichlorofluorescein oxidation and increased GSH in HCECs. Rapamycin significantly inhibited tBHP-induced ROS production. Cells treated with rapamycin showed higher viability compared to control at 5 mM tBHP. Rapamycin effectively protected HCECs from ROS-induced cell death through increasing intracellular GSH. Conclusion: Our data suggest that rapamycin protects HCECs from oxidative injury-mediated cell death via inhibition of ROS production and enhancement of GSH.

Salivary chemokine levels in patients with primary Sjögren’s syndrome

OBJECTIVE The present study aimed to investigate the salivary chemokine levels in patients with primary SS (pSS) and compare them with those in patients with non-SS sicca symptoms or non-sicca controls. METHODS Unstimulated and stimulated whole saliva samples were obtained from pSS patients (n = 30) and age- and gender-matched patients with non-SS sicca (n = 30) and non-sicca healthy controls (n = 25). Salivary CCL2, CCL3, CCL4, CXCL8 and CXCL10 levels were measured using a Luminex bead-based multiplex assay. RESULTS Patients with pSS had significantly different distributions of salivary CCL3 (P = 0.0001 by the Kruskal-Wallis test), CCL4 (P < 0.00001), CXLC8 (P < 0.0001) and CXCL10 (P < 0.05) levels in unstimulated saliva and all chemokine levels in stimulated saliva when compared with non-SS sicca and non-sicca controls. In comparison with chemokine production rate, the CXCL8 and CXCL10 production rates were significantly higher in pSS than in non-SS sicca controls (P < 0.01 by the Mann-Whitney test). Logistic regression analyses revealed that salivary CXCL8 (P < 0.05) and CXCL10 (P < 0.05) were the significant discriminating chemokines between the pSS and non-SS sicca groups. Although CXCL8 and CXCL10 levels were not correlated with the focus scores, CXCL8 and CXCL10 levels were significantly associated with salivary gland dysfunction. CONCLUSION These results support the notion that CXCL8 or CXCL10 chemokine plays a role in the pathogenesis of pSS.

Ultrasound Energy in Phacoemulsification: A Comparative Analysis of Phaco-Chop and Stop-and-Chop Techniques According to the Degree of Nuclear Density

BACKGROUND AND OBJECTIVE To evaluate the amount of ultrasound energy used, corneal endothelial cell loss, and central corneal thickness using the phaco-chop and stop-and-chop techniques for cataracts with different degrees of nuclear density. PATIENTS AND METHODS One hundred two eyes of 51 patients with bilateral senile cataract were included. Each eye was randomly assigned to have either phaco-chop or stop-and-chop nucleofractis during phacoemulsification. The groups were divided into two subgroups according to the nuclear density. The effective phacoemulsification time, endothelial cell density, and central corneal thickness were analyzed. RESULTS The mean effective phacoemulsification time was similar between the groups in moderately dense nuclei (2.17 +/- 1.33 vs 1.33 +/- 1.05 seconds; P = .41). However, the phaco-chop technique required less effective phacoemulsification time than the stop-and-chop technique in dense nuclei (3.86 +/- 4.18 vs 6.70 +/- 5.43 seconds; P = .01). The endothelial cell loss and the central corneal thickness did not vary significantly between the groups. CONCLUSION The phaco-chop technique requires lower ultrasound energy for nuclear management than the stop-and-chop technique in dense cataracts and the resulting endothelial loss was similar in both techniques.