Kyung-Sun Na

Correlations between tear cytokines, chemokines, and soluble receptors and clinical severity of dry eye disease.

PURPOSE To determine cytokine and chemokine concentrations in the tears of patients with dry eye disease (DED) and analyze the possible relationships with the clinical severity of DED. METHODS Patients were examined using the Ocular Surface Disease Index, corneal and conjunctival staining, tear breakup time, and impression cytology. They were divided into four groups according to the Dry Eye Workshop severity classification. Tears were collected from 133 patients with DED and 70 healthy controls. Concentrations of cytokines, chemokines, and soluble receptors in collected tear samples were analyzed using current technology with a Human Cytokine/Chemokine kit, a Human Cytokine/Chemokine Panel, and a Human Soluble Cytokine Receptor Panel. RESULTS The levels of cytokines interleukin (IL)-1β (P < 0.05), IL-6 (P < 0.001), IL-16 (P < 0.001), IL-33 (P < 0.05), G-CSF (P < 0.001), and transforming growth factor (TGF)-α (P < 0.05) were significantly higher in patients with DED, whereas those of cytokines IL-4 (P < 0.001), IL-12 (p40) (P < 0.001), IL-17A (P < 0.05), and interferon-γ (P < 0.001) were significantly lower. The levels of Fractalkine (chemokine [C-X3-C motif] ligand 1; CX3CL1), MCP-1 (chemokine [C-C motif] ligand 2; CCL2), MIP-1δ (chemokine [C-C motif] ligand 15; CCL15), and ENA-78 (chemokine [C-X-C motif] ligand 5; CXCL5) (P < 0.001, respectively) and soluble receptors, sIL-1RI (P < 0.05), soluble glycoprotein (sgp) 130 (P < 0.05), sIL-6R (P < 0.001), soluble epidermal growth factor receptor (P < 0.05), and soluble tumor necrosis factor receptor 2 (P < 0.001), were higher in patients with DED. There were significant correlations between these molecules and the clinical severity of DED. CONCLUSIONS Fifteen molecules were elevated in the tears of patients with DED; four molecules were decreased. Although the levels of sIL-6R, sIL-6R, and sgp130 may be potential indicators of the homeostatic process, an increase in the levels of IL-6 and IL-1 β are the earliest observable changes in patients with DED. Further study on the biomarkers in the pathogenesis of DED and treatment target modalities would be needed.

Visual Field Characteristics in Normal-Tension Glaucoma Patients With Autonomic Dysfunction and Abnormal Peripheral Microcirculation

PURPOSE To elucidate the visual field (VF) characteristics of normal-tension glaucoma (NTG) patients with either autonomic dysfunction or abnormal peripheral microcirculation. DESIGN Prospective, observational study. METHODS participants: Sixty NTG patients. procedures: All subjects underwent a complete ophthalmic examination and were then referred to a rheumatology department, where they were subjected to heart rate variability (HRV) assessment and nailfold capillaroscopy. Subjects with VF defect clusters confined to the central 10 degrees or outside the central 10 degrees (defined as peripheral) in 1 hemifield were selected (n = 60). The central and peripheral regions were divided further into superior and inferior sectors. Patients were classified into low, middle, and high HRV groups using HRV assessment or normal and abnormal capillaroscopy groups using nailfold capillaroscopy findings. The VF characteristics of the groups were compared. main outcome measures: Location of the VF defect, depth of the VF defect, mean deviation, and the pattern standard deviation of the VF. RESULTS The VF defect was more frequent and deepest in the superior central sector in both the low HRV and abnormal capillaroscopy groups. The mean deviation was similar between groups, but the pattern standard deviation was significantly higher in eyes with central defects than in eyes with peripheral defects among those in the low HRV group or abnormal capillaroscopy group. Logistic regression analysis revealed that the group classified by the HRV assessment and the presence of abnormalities in the capillaroscopy were related to the location of the VF defect. CONCLUSIONS NTG patients with low heart rate variability or abnormal nail capillaroscopy may present as central VF defects. Therefore, vascular risk factors need to be considered when NTG patients have central VF defects.

Autonomic dysfunction in normal tension glaucoma: the short-term heart rate variability analysis.

IntroductionThe purpose of this study was to investigate the dysfunction of autonomic control that may be a contributing factor in normal tension glaucoma (NTG) by showing the short-term heart rate variability in NTG patients. Materials and MethodsNewly diagnosed NTG patients and an age-matched normal control group were enrolled in this prospective study. Blood pressure was obtained and the electrocardiogram was monitored for 5 minutes after 30-minute rest in a supine position. Electrocardiographic signals were transferred to a heart rate analyzer. The time and frequency domain parameters of heart rate variability were analyzed between two groups. ResultIn all, 77 NTG patients and 30 healthy controls were included in the study. There were no significant differences between NTG and controls with respect to age, sex, and a hypertensive history, heart rate, systolic pressure, and diastolic pressure. NTG patients showed a significant reduction in the standard deviation of the mean of qualified normal-to-normal intervals in comparison with controls (27.64±10.90 vs. 36.22±10.21, P=0.041). Low-frequency values in NTG patients were statistically lower than in healthy controls (P=0.001) and the low-frequency/high-frequency ratio was significantly higher in the NTG group (P=0.000). DiscussionOur study results showed that the dysfunction of an autonomic control is associated with NTG patients.

Depression, Stress, Quality of Life, and Dry Eye Disease in Korean Women: A Population-Based Study.

Purpose: To determine the relationship between dry eye disease (DED) and depressive symptoms in a nationally representative sample of Korean women. Methods: This population-based cross-sectional study comprised 6655 women (aged 19 years or older) participating in the fifth annual Korea National Health and Nutrition Examination Survey from 2010 to 2011. Psychological problems associated with clinically diagnosed DED by ophthalmologists and symptoms of DED were assessed using questionnaires and surveys. Data were analyzed using logistic regression to determine the association of depression with allergic disease while controlling for age, lifestyle factors, and medical factors. Results: Among the participants, the prevalence of clinically diagnosed DED and its symptoms was 12.3% and 20.0%, respectively. Subjects with the diagnosis had a higher likelihood of experiencing severe psychological stress [odds ratio (OR), 2.5; 95% confidential interval (CI), 1.6–4.0], depressive mood (OR, 1.5; 95% CI, 1.1–2.0), anxiety/depression problems (OR, 1.5; 95% CI, 1.1–2.0) and tended to have a history of psychological counseling (OR, 1.8; 95% CI, 1.0–3.1). Subjects with symptoms of DED showed similar patterns. Conclusions: There is a close association between depression, stress, and DED in women who have been clinically diagnosed with it or those presenting with its symptoms.

Total cholesterol and lipoprotein composition are associated with dry eye disease in Korean women

BackgroundThis study aimed to determine the relationship between dyslipidemia and dry eye disease (DED) in a Korean population.MethodsThis population-based study enrolled 5,627 adults (aged >19 years) who were participating in the first year of the fifth annual Korea National Health and Nutrition Examination Survey from 2010 to 2011. Clinically diagnosed DED and its symptoms were surveyed, and biochemical blood analysis data were collected. Dyslipidemia was defined as any of the following: hypercholesterolemia (total cholesterol > 200 mg/dL), hypertriglyceridemia (triglyceride > 150 mg/dL), low levels of high-density lipoprotein (<40 mg/dL), or high levels of low-density lipoprotein (>100 mg/dL).ResultsAfter adjusting for demographics (age and body mass index), lifestyle (smoking, drinking, exercise, and residential district), and medical factors (diabetes, hypertension, previous ophthalmic surgery, menopause, and rheumatologic disease), elevated serum cholesterol level was found to be associated with increased likelihood of DED (odds ratio, 1.77; 95% confidence interval, 1.127–2.78) in women.ConclusionsDED in a Korean population was found to be associated with high serum cholesterol levelsThe results of this study highlight the significance of eye examinations and independent lipid profile monitoring in patients with dyslipidemia because of its possible correlation with DED progression.

The Ocular Benefits of Estrogen Replacement Therapy: A Population-Based Study in Postmenopausal Korean Women

Purpose To elucidate the prevalence of cataract, glaucoma, pterygia, and diabetic retinopathy among Korean postmenopausal women with or without estrogen replacement therapy (ERT). Methods A cross-sectional, nationally representative sample from the 4th Korea National Health and Nutrition Examination Survey (KNHANES IV) (2007–2009) was used. Participants were interviewed for the determination of socioeconomic and gynecologic factors. Each woman also underwent an ophthalmologic examination and provided a blood sample for risk factor assessment. Results Of 3968 postmenopausal women enrolled, 3390 had never received estrogen, and 578 were undergoing estrogen treatment. After adjusting for age, diabetes, hypertension, high cholesterol levels, and high low-density lipoprotein levels, the prevalence of anterior polar cataract, retinal nerve fiber layer (RNFL) defect, and flesh pterygium was higher in the non-ERT group (OR, 3.24; 95% CI, 1.12–9.35, OR 1.70; 95% CI, 1.04–2.78, OR 3.725; 95% CI, 1.21–11.45, respectively). Further, the prevalence of atrophic pterygium was lower in the non-ERT group compared to that in the ERT group (OR, 0.21, 95% CI, 0.07–0.63). Conclusions These data suggest that ERT has a protective effect against the development of anterior polar cataract, flesh pterygium, and RNFL defect.

Tear Osmolarity and Ocular Surface Parameters as Diagnostic Markers of Ocular Graft-Versus-Host Disease.

PURPOSE To evaluate the diagnostic value of tear osmolarity and several ocular surface parameters in screening for ocular surface alterations in ocular graft-vs-host disease (GVHD) patients. DESIGN Case-control study. METHODS Sixty-three patients with ocular GVHD and 74 healthy participants were screened for ocular surface changes using the Ocular Surface Disease Index (OSDI), tear osmolarity, Schirmer test, tear break-up time (TBUT), and fluorescein corneal staining. The severity of ocular GVHD was diagnosed according to the National Institutes of Health (NIH) grading system. The diagnostic sensitivity and specificity and cutoff values were determined for each ocular parameter using a receiver operating characteristic (ROC) curve and area under the curve (AUC) analysis. Significance was defined at P < .05. RESULTS The tear osmolarity, corneal staining score, and OSDI score gradually increased as the severity of ocular GVHD increased, and Schirmer value gradually decreased as the GVHD grade increased in severity. The Schirmer test showed greatest diagnostic sensitivity and specificity for ocular GVHD (92.1% sensitivity, 85.7% specificity, cutoff = 9 mm), followed by the TBUT (87.3% sensitivity, 75.0% specificity, cutoff = 6 s), tear osmolarity (98.4% sensitivity, 60.7% specificity, cutoff = 311 mOsm/L), corneal staining score (66.7% sensitivity, 82.1% specificity, cutoff = 2), and OSDI score (77.8% sensitivity, 66.1% specificity, cutoff = 20.8). CONCLUSIONS Multiple diagnostic modalities should be used to detect ocular surface changes in GVHD patients. The severity of ocular GVHD can be effectively monitored using tear osmolarity; however, additional studies are required.

Comparison of LASIK and surface ablation by using propensity score analysis: a multicenter study in Korea.

PURPOSE We compared the 3-year outcomes with regard to efficacy, stability, and safety of LASIK and surface ablation performed at multiple centers in Korea. METHODS The charts of 5109 eyes that underwent LASIK or surface ablation, including LASEK, epi-LASIK, and photorefractive keratectomy (PRK), at multiple centers between 2002 and 2005 were reviewed. Of these, 577 LASIK-treated eyes and 577 propensity score-matched surface-ablated eyes were included in this cohort study. A standardized case report form (CRF) was completed based on a review of the 3-year follow-up chart. The CRF included the preoperative, surgical, and postoperative data for the refractive error, uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), IOP, corneal thickness, keratometry, corneal topography, Schirmer test, and tear breakup time (TBUT). RESULTS The efficacy index calculated after 3 years and the postoperative spherical equivalents measured at 3 months or 3 years did not differ between the LASIK and surface ablation groups. Although myopic regression was observed in the surface ablation group through postoperative years 1 and 2, this difference did not affect the visual acuity significantly. Surface ablation did carry a higher cumulative incidence of corneal haze. CONCLUSIONS LASIK and surface ablation produced similar postoperative visual efficacy after corneal healing. The outcome predictability did not differ between the 2 groups, but myopic regression was observed more frequently in the surface ablation group. Corneal haze after surface ablation is much more common than reported previously.

Examination of Gland Dropout Detected on Infrared Meibography by Using Optical Coherence Tomography Meibography

PURPOSE To elucidate the anatomic details of gland dropout detected on two-dimensional infrared (IR) meibography in cases of dry eye associated with meibomian gland dysfunction (MGD) by using three-dimensional optical coherence tomography (OCT) meibography. METHODS In this cross-sectional, observational case series, we enrolled gland dropout detected on IR meibography; the condition was then examined using a real-time swept-source OCT system. Accordingly, a series of 500 raster B-scan OCT images, with the gland dropout site (observed on IR imaging) at the center, were obtained and rendered as three-dimensional volume images. The OCT images were classified based on the anatomic details, including acini and ducts, at the meibomian glands (Group I, constricted acini; II, atrophic acini; III, no acini). RESULTS The percentage of disagreement between IR and OCT images for dropout detected on IR imaging was 49.45% (43 and 93 cases in group I and II, respectively). Loss of the meibomian glands on both IR and OCT imaging (Group III) was observed in 50.55% cases (133 and 6 cases of gland dropout at the partial and whole eyelid on IR imaging, respectively). The proportion of disagreement between IR and OCT images (Group I and II) was higher in the middle area (63/119, 53.39%), as compared to that in the nasal (34/73, 46.58%) or temporal areas of the eyelid (26/65, 40%). CONCLUSIONS The loss of the meibomian glands, as observed on IR imaging, should be carefully interpreted, and OCT images may be useful to confirm the anatomic details of the meibomian glands.

The Influence of Overnight Orthokeratology on Ocular Surface and Meibomian Glands in Children and Adolescents.

Purpose: The aim of this study was to investigate the influence of overnight orthokeratology (OOK) on ocular surface and meibomian glands in children and adolescents. Methods: Prospective, noncomparative study included the ocular surface disease index (OSDI), tear osmolarity, corneal and conjunctival fluorescein staining, tear film breakup time (TBUT), the Schirmer I test, and meiboscore using noncontact meibography. Immunofluorescence confocal microscopy of interleukin-1&bgr; (IL1&bgr;), interleukin-6 (IL6), epidermal growth factor (EGF), and matrix metalloproteinase (MMP)-9 using impression cytology filter paper was performed. The tests were performed before and at 6, 12, 24, and 36 months after OOK wear. Results: Fifty-eight subjects using OOK were observed. Significant increases in OSDI score (P=0.0009) and corneal and conjunctival staining score (P<0.0001) were observed compared with baseline values at 36 and 24 months, respectively. Ocular surface and meibomian changes were noted in 2 patients (3.5%). One patient exhibited an increase in OSDI score, concurrent with a decrease in TBUT at 36 months and minor loss of the meibomian gland at the distal portion of the lower lid at 24 months. The other patients exhibited the development of papillary hypertrophy and meibomian gland distortion at 24 months. No significant changes were detected in IL1&bgr;, IL6, EGF, or MMP expression after OOK use. Conclusion: Based on the findings, OOK was a relatively safe modality. However, given the potential changes in the meibomian gland and tear film stability, special attention must be paid to children with baseline meibomian gland distortions or a history of allergic conditions.