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PurposeWe sought to evaluate the relationship between blood vitamin A levels and myopia in adults aged ≥20 years in Korea.MethodsWe collected data of 15,899 participants aged ≥20 years from the Korean National Health and Nutrition Examination Survey. Participants underwent refraction tests to identify myopia and high myopia, and their blood pressure and obesity levels were measured. Blood tests were conducted to assess vitamin A, fasting blood glucose, triglyceride, and total cholesterol levels. Blood vitamin A levels were classified into quartiles.ResultsAfter adjusting for confounding variables like age, sex, income, education, hypertension, diabetes, and obesity, the odds ratio (OR) of blood vitamin A in the second quartile for myopia was 0.66, while the OR in the fourth quartile was 0.74 (P for trend < 0.001). Among women, the ORs for myopia in the second and third quartiles of blood vitamin A levels were 0.48 (95% confidence interval [CI], 0.35-0.66) and 0.67 (95% CI, 0.49-0.90), respectively (P for trend < 0.001). In men, the ORs for high myopia in the second, third, and fourth quartiles of blood vitamin A levels were 0.05 (95% CI, 0.004-0.58), 0.15 (95% CI, 0.024-0.91), and 0.05 (95% CI, 0.008-0.364), respectively (P for trend < 0.001).ConclusionAn inverse relationship was observed between higher blood vitamin A levels and the prevalence of myopia. Notably, higher blood vitamin A levels were associated with a lower prevalence of high myopia in men and a lower prevalence of myopia in women.

PURPOSE:The aim of this study was to investigate the association between refractive error and prevalence of age-related macular degeneration (AMD) in Korean adults, based on the sex and age group. METHODS:This was a nationwide population-based cross-sectional study that included 17,676 subjects aged over 40 years who participated in the 2008-2012 Korean National Health and Nutrition Examination Survey. Digital fundus images (45°) were obtained for both eyes under physiologic mydriasis and were graded using the international classification and grading system for age-related macular degeneration. The spherical equivalents of refractive errors were calculated in diopters using auto-refraction data. RESULTS:After adjustment for potential confounders, myopia was associated with lower risk of any age-related macular degeneration [odds ratio (OR), 0.74; 95% Confidence Interval (CI), 0.61-0.91]. In particular, myopia was significantly associated with lower odds of age-related macular degeneration in female participants (any AMD: OR, 0.71; 95% CI, 0.54-0.93; early AMD: OR, 0.70; 95% CI, 0.53-0.93) and in participants younger than 50 years (any AMD: OR, 0.46; 95% CI, 0.24-0.90; early AMD: OR, 0.47; 95% CI, 0.24-0.93). There was no significant association between myopia and age-related macular degeneration in male participants and in participants older than 50 years. CONCLUSIONS:In the Korean adult population, myopia was associated with significantly lower odds of any type of early age-related macular degeneration, particularly in females and in younger age groups.

BACKGROUND:The characteristics of the optic nerve head (ONH) in open angle glaucoma (OAG) patients with diabetes have not been reported. This study aimed to characterize the ONH structures and glaucomatous damage in diabetic OAG patients, using age-matched non-diabetic OAG patients and control subjects. METHODS:The locations of visual field defects of OAG patients were classified and the prelaminar thickness and lamina cribrosa depth were measured in 64 OAG patients with type 2 diabetes (OAG+DM), 68 OAG patients without diabetes (OAG-DM), and 36 controls. All participants were scanned by spectral domain-optical coherence tomography. The anterior prelaminar depth and lamina cribrosa depth were measured at the center of the reference line (the Bruch's membrane opening plane). The prelaminar tissue thickness was obtained by subtracting the anterior prelaminar depth from the anterior lamina cribrosa depth. RESULTS:The visual field defects in the OAG+DM group were more commonly found in the inferior hemifield (P = 0.010), and tended to involve the central visual field compared to the OAG-DM group (P = 0.044). In the comparison of ONH parameters, the prelaminar thickness was highest in the OAG+DM group, followed by the control subjects and the OAG-DM group (P = 0.035). Post-hoc testing showed that prelaminar thickness was significantly greater in the OAG+DM group than in the OAG-DM group (P = 0.033). The lamina cribrosa depth was deepest in the OAG+DM group, followed by the OAG-DM group and the control subjects (P = 0.006). CONCLUSIONS:Diabetic and non-diabetic OAG patients exhibit different characteristics of glaucoma, particularly increased prelaminar thickening in diabetics.

PurposeTo determine the characteristics of diabetic macular edema (DME) patients refractory to intravitreal bevacizumab (IVB) treatments and an additional dexamethasone implant.MethodsWe classified 119 DME patients according to whether or not they are responsive to 3 consecutive monthly anti-VEGF treatments and/or an additional dexamethasone implant. We compared their concentrations of IL (interleukin)-1β, IL-8, IL-10, IL-17, placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) in the aqueous humor as well as their optical coherence tomography (OCT) findings, and baseline characteristics. We used logistic regression analyses to identify preoperative factors related to refractoriness to treatments.ResultsOf 119 treatment-naïve DME patients, 50 (42.02%) patients showed responsiveness [central subfield thickness (CST) < 300μm] after 3 IVBs, and 59 (49.58%) patients showed responsiveness after an additional dexamethasone implant, but 10 (8.40%) patients showed CST 300 ≥ μm even after both treatments. Refractory DME patients showed significantly higher number of hyperreflective foci (HF) in the OCT and higher average level of aqueous IL-1β at baseline (pConclusionsHigher number of HF in the OCT at the initial visit was associated with poor responses to IVBs and an additional dexamethasone implant.

BackgroundHerpes simplex virus type 1 (HSV-1) is causative for hypertensive anterior uveitis. Trabecular meshwork (TM) cells, which are the key cells regulating intraocular pressure (IOP), is considered to be the site of inflammation. We explored the profiles of genes expressed in human TM primary cells upon HSV-1 infection.MethodsHuman TM cells were infected with HSV-1 and total RNA was isolated. The global transcriptional gene network analyses were performed in mock-infected and HSV-1 infected TM cells. Using ingenuity pathway analysis, we determined the key biological networks upon HSV-1 infection. The results of microarray analyses were validated using quantitative PCR.ResultsTM cells had a high susceptibility to HSV-1 infection. HSV-1 induced transcriptional suppression of many components related to fibrosis in TM cells. The top biological network related to the genes which were significantly altered upon HSV-1 infection was organismal injury and abnormalities involving TGF-β1 and PDGF-BB. The results of PCR analyses for selected molecules were found to be in good agreement with the microarray data. HSV-1-infected TM cells showed an 80-fold increase in the expression of PDGF-BB, which was further increased by treatment with TGF-β1. HSV-1 also induced a 4-fold increase in the expression of the monocyte chemoattractant protein (MCP)-1, the downstream molecules of PDGF-BB.ConclusionsIn human TM cells, HSV-1 induced transcriptional suppression of many components related to fibrosis and enhanced expression of both PDGF-BB and MCP-1. Our study may provide a novel mechanism for the pathogenesis of HSV-1 infection in TM cells.

[This corrects the article DOI: 10.1371/journal.pone.0218471.].

BackgroundHuman cytomegalovirus (CMV) has been emerged as one of the causes of acute recurrent or chronic hypertensive anterior uveitis in immunocompetent. In hypertensive anterior uveitis, human trabecular meshwork (TM) cells are considered a focus of inflammation. We investigated the effects of losartan, a selective angiotensin II receptor antagonist, on CMV infection in human TM cells.MethodsHuman TM cells were infected with CMV AD169. Virus infected and mock-infected cells were treated with losartan or dexamethasone or ganciclovir with or without transforming growth factor (TGF)-β1. Viral DNA accumulation and host cell response were analyzed using real-time PCR. Levels of secreted TGF-β1 were measured by determining its concentration in conditioned medium using a commercially available sandwich enzyme-linked immunosorbent assay (ELISA) kits.ResultsCMV infection significantly increased the concentrations of the secreted TGF-β1 at 3, 5, and 7 day post infection in TM cells. Treatment with dexamethasone or losartan significantly decreased the levels of TGF-β1, whereas treatment with ganciclovir did not affect TGF-β1 levels. TM cells treated with TGF-β1 along with the presence of losartan for 48 hours showed marked decrease in the expression of α-smooth muscle actin (SMA), lysyl oxidase (LOX), connective tissue growth factor (CTGF), fibronectin and collagen-1A, compared with cells treated with TGF-β1 alone. CMV-infected TM cells stimulated by TGF-β1 significantly increased the expression of α-SMA and CTGF, which were attenuated by additional treatment with losartan.ConclusionLosartan inhibited the expression of TGF-β1 and fibrogenic molecules in human TM cells. Thus, losartan has the potential to decrease TM fibrosis in patients with CMV-induced hypertensive anterior uveitis.

[This corrects the article DOI: 10.1371/journal.pone.0203408.].

[This corrects the article DOI: 10.1371/journal.pone.0201399.].

PURPOSE:To determine the prognosis for ocular toxocariasis (OT) according to the location of the granuloma and to identify factors associated with its recurrence within 1 year. METHODS:OT patients were classified according to the granuloma lesion. After grouping the patients as posterior or peripheral, we compared sex, age, intraocular pressure, best corrected visual acuity (BCVA), degree of inflammation, immunoglobulin E, eosinophil profiles, recurrence, and complications in each group. We also identified factors associated with recurrence within 1 year. RESULTS:A total of 29 (61.70%) patients had granuloma at the periphery, and 18 (38.30%) patients had granuloma around the posterior pole. There were no significant differences in ocular or systemic evaluations except the initial BCVA. The mean decimal BCVA of the posterior pole granuloma group was worse than that of the peripheral granuloma group (p = 0.042). After treatment, the mean BCVA of the posterior pole granuloma group improved significantly (p = 0.019), and the final mean BCVA was not significantly different between the groups (p = 0.673). Multiple logistic regression analyses revealed that recurrence within a year was associated with age at diagnosis (p = 0.007). CONCLUSIONS:The initial BCVA of OT patients differed according to the location of the granuloma, but the BCVA after treatment was not significantly different between the groups. Younger age was associated with recurrence within 1 year.

[This corrects the article DOI: 10.1371/journal.pone.0206690.].

OBJECTIVES:Although determining the quality of life among glaucoma patients has important clinical and public health implications, the utility value of glaucoma patients has not yet been determined in Korea. METHODS:The Korean National Health and Nutrition Examination Survey database was used to identify 833 glaucoma patients based on ophthalmologic examinations. The adjusted mean utility values, calculated by EuroQol-5D (EQ-5D-3L), of glaucoma patients according to patient demographics and measures of glaucoma severity were determined using multivariate linear regression analysis. RESULTS:The mean utility value of glaucoma patients was 0.8968. Patients aged 70 years or more had significantly lower utility value (0.86, p value 0.005) compared to those aged less than 50 years (0.96). Patients within the lowest quartile of income had a utility value of 0.87, compared to a utility value of 0.96 for those within the highest quartile (p value 0.001). Patients who were not married had lower utility value (0.87) compared to married patients (0.93). Patients within the lowest quartile of worse eye frequency doubling technology (FDT) score had lower utility value (0.88) compared to those within the highest quartile (0.94). Finally, bilateral vision loss patients had significantly lower utility value (0.83, p value 0.013) compared to patients without vision loss (0.92). CONCLUSION:The present study assessed utility values of Korean glaucoma patients. The quality of life determined by EQ-5D-3L in Korean glaucoma patients was higher compared to those in other countries. Patient demographics as well as measures of disease severity were important factors in determining the quality of life within glaucoma patients.

PURPOSE:Age-related macular degeneration (AMD) is one of the most important causes of blindness globally and may lead to decreased quality of life. Utility values for AMD patients according to sociodemographic and clinical characteristics have been little-studied, particularly among Asian populations. METHODS:A total of 1,283 AMD patients were identified from the Korean National Health and Nutrition Examination Survey from 2008 to 2012. A 45-degree digital retinal image for each eye was used to identify AMD patients. The utility values, calculated by the three level version of EuroQol-5D, of AMD patients according to sociodemographic and clinical characteristics were determined. The Kruskal-Wallis test was used to identify factors associated with reduced utility values among AMD patients. RESULTS:The mean utility value for AMD patients was 0.8765. Patients who were older (mean utility value 0.8339), were women (0.8488), had lower education levels (0.8287), were not employed (0.8467), and had lower household income (0.8022) had lower utility values (all p values

PURPOSE:To determine aqueous cytokines association with response to intravitreal bevacizumab (IVB) injection in diabetic macular edema (DME). METHOD:We compared the concentrations of IL (interleukin)-1β, IL-2, IL-8, IL-10, IL-17, placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) in the aqueous humor of 64 naïve DME patients with those of 13 cataract patients. Factors associated with central subfield thickness (CST) in DME patients were identified. DME patients were then subgrouped in terms of responsiveness to three IVB injections; cytokine concentrations were compared, and factors associated with responsiveness were identified. RESULTS:Levels of IL-2, IL-8, PlGF, and VEGF were significantly elevated in DME patients (p = 0.007, p < 0.001, p < 0.001, and p = 0.004 respectively). Regression analysis showed that the preoperative CST was associated with the preoperative best-corrected visual acuity and the aqueous IL-10 level (p < 0.001, p = 0.006, respectively). Of the 64 DME patients, 28 (43.75%) exhibited either CST < 300 μm or reduction in CST ≥ 50 μm after three consecutive IVB injections. On sub-group analysis, the mean IL-8 concentration was higher in the refractory group than in the responsive group, and multivariate logistic regression analysis showed that the IL-8 was the only factor associated with responsiveness (OR = 0.95, p = 0.017). CONCLUSIONS:The IL-8 concentration in the aqueous humor was associated with responsiveness to IVB in DME patients.

[This corrects the article DOI: 10.1371/journal.pone.0202904.].

BACKGROUND:Interventions that can facilitate early diagnosis of age-related macular degeneration (AMD) will facilitate early treatment and improve clinical outcomes but there has been concerns about additional medical costs to the health care system. An examination through a retina fundus photography by a non-specialist has been suggested as a potential cost-effective alternative to a direct examination by a specialist, but limited scientific data exists on the cost-effectiveness of screening strategies for AMD. Our objective is to conduct an economic evaluation of various population-wide screening strategies for AMD among the South Korean population. METHODS AND FINDINGS:Using a Markov cohort model, we evaluated the cost-effectiveness of four AMD screening strategies (opportunistic examination, opportunistic treatment, systematic photography, and systematic examination) in comparison with status quo (no screening) for South Korean adults. We projected a life time horizon to study a hypothetical cohort of 100,00 persons of age 40 with and without AMD at baseline. The outcome measures were quality-adjusted life-years (QALYs) gained, cost from the societal perspective, and the incremental cost-effectiveness ratio (ICER) of each strategy. Interventions were evaluated at a willingness-to-pay (WTP) threshold of 30,000,000 KRW ($27,538) per QALY gained. Deterministic and probabilistic sensitivity analyses were conducted to address the model uncertainty. Opportunistic examination was strongly dominated because it generated fewer expected QALYs but incurred greater expected cost than the other screening strategies. The mean lifetime expected costs were 289,013 KRW, 363,692 KRW, 9,351,964 KRW, and 12,309,783 KRW, and the mean QALYs gained were 37.73, 37.75, 40.47, 40.68, for no screening, opportunistic treatment, systematic photography, and systematic examination, respectively. The results were most sensitive to the utility weight of mild AMD, the probability of complication from treatment, the cost of being in mild AMD, and the probability of recovery from complication. After eliminating the two weakly dominated strategies, systematic photography was cost-effective at the ICER of 3,310,448 KRW per QALY in comparison to status quo. CONCLUSIONS:Under the WTP threshold of 30,000,000 KRW per QALY, systematic photography is cost-effective for screening AMD in South Korean adults. Systematic examination by ophthalmologists generates more expected QALY and cost compared to systematic photography.

To assess the concentrations of matrix metalloproteinase (MMP)-1 and MMP-9 in the aqueous humor of diabetic macular edema (DME) patients.The concentrations of MMP-1 and MMP-9 in the aqueous humors of 15 cataract patients and 25 DME patients were compared. DME patients were analyzed according to the diabetic retinopathy (DR) stage, diabetes mellitus (DM) duration, pan-retinal photocoagulation (PRP) treatment, recurrence within 3 months, HbA1C (glycated hemoglobin) level, and axial length.The concentrations of MMP-1 and MMP-9 of the DME groups were higher than those of the control group (p = 0.005 and p = 0.002, respectively). There was a significant difference in MMP-1 concentration between the mild non-proliferative diabetic retinopathy (NPDR) group and the proliferative diabetic retinopathy (PDR) group (p = 0.012). MMP-1 concentrations were elevated in PRP-treated patients (p = 0.005). There was a significant difference in MMP-9 concentrations between the mild NPDR group and the PDR group (p < 0.001), and between the moderate and severe NPDR group and the PDR group (p < 0.001). The MMP-9 concentrations in PRP treated patients, DM patients with diabetes ≥ 10 years and recurrent DME within 3months were elevated (p = 0.023, p = 0.011, and p = 0.027, respectively). In correlation analyses, the MMP-1 level showed a significant correlation with age (r = -0.48, p = 0.01,), and the MMP-9 level showed significant correlations with axial length (r = -0.59, p < 0.01) and DM duration (r = 049, p = 0.01).Concentrations of MMP-1 and MMP-9 were higher in the DME groups than in the control group. MMP-9 concentrations also differed depending on DR staging, DM duration, PRP treatment, and degree of axial myopia. MMP-9 may be more important than MMP-1 in the induction of DM complications in eyes.

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.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.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.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.

To investigate the association between blood 25-hydroxyvitamin D levels and pterygium.Korean National Health and Nutrition Examination Survey 2008-2011 were used for the present epidemiologic study. A total of 19,178 participants aged ≥ 30 years were evaluated for blood 25-hydroxyvitamin D levels and performed ophthalmic slit lamp examinations. Pterygium was considered as a growth of fibrovascular tissue over the cornea.The average blood 25-hydroxyvitamin D levels were 18.6 ng/mL, and prevalence of pterygium was 6.5%. The odds of pterygium significantly increased across blood 25-hydroxyvitamin D quintiles after controlling sun exposure time as well as other confounders such as sex, age, smoking, diabetes, hypertension (P < 0.001). The odds ratios (OR) for pterygium was 1.51 (95% Confidence Interval[95%CI]; 1.19-1.92) in the highest blood vitamin D quintile. Stratified analysis by sex showed a positive association between blood 25-hydroxyvitamin D levels and pterygium in both men (quintile 5 versus 1, OR; 1.68, 95%CI; 1.19-2.37) and women (quintile 5 versus 1, OR; 1.37, 95% CI; 1.00-1.88).Even after controlling sun light exposure time, we found a positive association between blood 25-hydroxyvitamin D levels and pterygium in a representative Korean population. The mechanism underlying this association is unknown.

To investigate the association between blood lead levels and prevalence of age-related macular degeneration (AMD).A nationwide population-based cross-sectional study included 4,933 subjects aged over 40 years who participated in the 2008-2012 Korean National Health and Nutrition Examination Survey, and for whom fundus photographs were available. All participants underwent a standardized interview, evaluation of blood lead concentration, and a comprehensive ophthalmic examination. Digital fundus photographs (45°) were taken of both eyes under physiological mydriasis. All fundus photographs were graded using an international classification and grading system.Mean blood lead levels were 3.15 μg/dL in men and 2.27 μg/dL in women (P < 0.001). After adjusting for potential confounders including age, gender, smoking status, total cholesterol levels, triglyceride levels, heart problems and strokes, the adjusted odds ratio (OR) in women for any AMD was 1.86 (95% Confidence Interval [CI], 1.03-3.36) and for early AMD was 1.92 (95% CI, 1.06-3.48), for those in the highest quintile of lead level compared with the lowest quintile. In men, however, blood lead level was not significantly associated with AMD.Blood lead levels were higher in men, but were only associated with AMD in women. Increased levels of blood lead may be involved in the pathogenesis of AMD development in women.

To investigate the association between 25-hydroxyvitamin D and diabetic retinopathy (DR).A population-based cross-sectional study using a nation-wide, systemically stratified, multistage, clustered sampling method included a total of 18,363 subjects aged ≥ 40 years who participated in the Korean National Health and Nutrition Examination Survey during 2008-2012. All participants participated in standardized interviews, blood 25-hydroxyvitamin D level evaluations, and comprehensive ophthalmic examinations. Seven standard retinal fundus photographs were obtained from both eyes after pupil dilatation. DR was graded according to the modified Airlie House classification system.The blood 25-hydroxyvitamin D levels were 19.2 ng/mL in men and 17.9 ng/mL in women. After adjusting for potential confounders, including age, sex, diabetes duration, hemoglobin A1c levels, and hypertension, the odds ratios (OR) for any DR and proliferative DR among men decreased significantly in the highest blood 25-hydroxyvitamin D level quintile relative to the lowest quintile (OR, 0.37; 95% confidence interval [CI], 0.18-0.76; P for trend = 0.004 and OR, 0.15; 95% CI, 0.03-0.83; P for trend = 0.043).This study provides the first epidemiologic findings of the inverse relationships of blood 25-hydroxyvitamin D levels with any DR and proliferative DR only in men. Considering anti-angiogenic and anti-fibrotic action of vitamin D, further studies including longitudinal and interventional analysis are warranted.

PURPOSE: To examine the prevalence and risk factors of refractive errors in a representative Korean population aged 20 years old or older. METHODS: A total of 23,392 people aged 20+ years were selected for the Korean National Health and Nutrition Survey 2008-2011, using stratified, multistage, clustered sampling. Refractive error was measured by autorefraction without cycloplegia, and interviews were performed regarding associated risk factors including gender, age, height, education level, parent's education level, economic status, light exposure time, and current smoking history. RESULTS: Of 23,392 participants, refractive errors were examined in 22,562 persons, including 21,356 subjects with phakic eyes. The overall prevalences of myopia (< -0.5 D), high myopia (< -6.0 D), and hyperopia (> 0.5 D) were 48.1% (95% confidence interval [CI], 47.4-48.8), 4.0% (CI, 3.7-4.3), and 24.2% (CI, 23.6-24.8), respectively. The prevalence of myopia sharply decreased from 78.9% (CI, 77.4-80.4) in 20-29 year olds to 16.1% (CI, 14.9-17.3) in 60-69 year olds. In multivariable logistic regression analyses restricted to subjects aged 40+ years, myopia was associated with younger age (odds ratio [OR], 0.94; 95% Confidence Interval [CI], 0.93-0.94, p < 0.001), education level of university or higher (OR, 2.31; CI, 1.97-2.71, p < 0.001), and shorter sunlight exposure time (OR, 0.84; CI, 0.76-0.93, p = 0.002). CONCLUSIONS: This study provides the first representative population-based data on refractive error for Korean adults. The prevalence of myopia in Korean adults in 40+ years (34.7%) was comparable to that in other Asian countries. These results show that the younger generations in Korea are much more myopic than previous generations, and that important factors associated with this increase are increased education levels and reduced sunlight exposures.