Search

Abstract We identified characteristics of patients with subretinal fluid (SRF) in macular edema (ME) secondary to branch retinal vein occlusion (BRVO) and determined their clinical outcomes after anti-vascular endothelial growth factor (VEGF) treatment. Fifty-seven eyes of BRVO patients with ME were divided into two groups according to the presence or absence of SRF at diagnosis. We compared the aqueous profiles, ocular and systemic characteristics at baseline, and the clinical outcomes. The SRF group had significantly greater central subfield thickness (CST) values and poorer best-corrected visual acuity (BCVA) at baseline compared to the non-SRF group. The former group had significantly higher aqueous levels of interleukin-8, VEGF, and placental growth factor. CST reduction and BCVA improvement during treatment were significantly greater in the SRF group than in the non-SRF group. Consequently, CST values were significantly lower in the SRF group than in the non-SRF group at 12 months, when BCVA did not differ significantly between the two groups. The SRF group required more frequent anti-VEGF treatment over 12 months and exhibited a higher rate of macular atrophy. Based on the aqueous profiles and the number of treatments required, the presence of SRF in BRVO patients appears to be associated with higher disease activity.

Abstract We assessed the relationship between blood vitamin A levels and the risk of diabetic retinopathy. The study was population-based epidemiological study for 11,727 participants aged 40 or older who participated in the Korean National Health and Nutrition Examination Survey. Vitamin A in the blood was classified into quartiles. Diabetic retinopathy was diagnosed by the Early Treatment for Diabetic Retinopathy Study. After adjusting confounding variables such as age, sex, smoking, cholesterol, diabetes prevalence period, glycated hemoglobin levels, and high blood pressure, the odd ratio (OR) of vitamin A at quartile level 4 for diabetic retinopathy was 0.32 (95% confidence interval [CI], 0.14–0.72, P for trend

Abstract Background We determined the cost-effectiveness of the anti-vascular endothelial growth factor (VEGF) intravitreal injection versus panretinal photocoagulation (PRP) for patients with proliferative diabetic retinopathy (PDR) in South Korea. Methods We simulated four treatment strategies using PRP and the anti-VEGF injection by constructing a Markov model for a hypothetical cohort of 50-year-old PDR patients: (1) PRP only; (2) anti-VEGF injection only; (3) PRP first; and (4) anti-VEGF injection first. Results In this cost-effectiveness analysis, compared with only-PRP, the incremental cost-effectiveness ratio was $95,456 per quality-adjusted life-year (QALY) for PRP first, $34,375 per QALY for anti-VEGF injection first, and $33,405 per QALY for anti-VEGF injection only from a healthcare perspective. From the societal and payer perspective, strategy (2) was more cost-saving and effective than (1). In the probabilistic sensitivity analysis, only-PRP was cost-effective up to the willingness-to-pay (WTP) of about $42,000, while anti-VEGF injection only was cost-effective from a healthcare perspective. From the societal and payer perspectives, regardless of the value of WTP, anti-VEGF injection only was the most cost-effective strategy. Conclusion In our study, the anti-VEGF injection for PDR was cost-effective from the payer and societal perspectives.

Abstract We compared the aqueous profiles, baseline characteristics, and clinical outcomes of 54 eyes with macular edema secondary to major branch retinal vein occlusion (BRVO) and macular BRVO. We also identified the characteristics of poor responders to anti-vascular endothelial growth factor (VEGF) injections. Aqueous inflammatory cytokine and VEGF concentrations were significantly higher in major BRVO. In optical coherence tomography, major BRVO had a higher proportion with subretinal fluid, disorganization of retinal inner layers, and ellipsoid zone disruption. Comparing the clinical outcomes, major BRVO required more intravitreal anti-VEGF injections and had a poorer visual prognosis in the first 12 months. A significantly higher proportion of patients with major BRVO required additional treatments after 6 months compared to macular BRVO. Patients who responded poorly to anti-VEGF had higher aqueous VEGF levels and central subfield thickness (CST) at baseline. In conclusion, major BRVO patients required more and longer treatments, and had worse visual prognoses. BRVO that responds poorly to anti-VEGF had greater CST and higher aqueous VEGF levels at baseline.

Abstract We sought to predict whether central serous chorioretinopathy (CSC) will persist after 6 months using multiple optical coherence tomography (OCT) images by deep convolutional neural network (CNN). This was a multicenter, retrospective, cohort study. Multiple OCT images, including B-scan and en face images of retinal thickness (RT), mid-retina, ellipsoid zone (EZ) layer, and choroidal layer, were collected from 832 eyes of 832 CSC patients (593 self-resolving and 239 persistent). Each image set and concatenated set were divided into training (70%), validation (15%), and test (15%) sets. Training and validation were performed using ResNet50 CNN architecture for predicting CSC requiring treatment. Model performance was analyzed using the test set. The accuracy of prediction was 0.8072, 0.9200, 0.6480, and 0.9200 for B-scan, RT, mid-retina, EZ, and choroid modalities, respectively. When image sets with high accuracy were concatenated, the accuracy was 0.9520, 0.8800, and 0.9280 for B-scan + RT, B-scan + EZ, and EZ + RT, respectively. OCT B-scan, RT, and EZ en face images demonstrated good performances for predicting the prognosis of CSC using CNN. The performance improved when these sets were concatenated. The results of this study can serve as a reference for choosing an optimal treatment for CSC patients.

Abstract Despite many studies, optimal treatment sequences or intervals are still questionable in retinal vein occlusion (RVO) macular edema. The aim of this study was to examine the real-world treatment patterns of RVO macular edema. A retrospective analysis of the Observational Medical Outcomes Partnership Common Data Model, a distributed research network, of four large tertiary referral centers (n = 9,202,032) identified 3286 eligible. We visualized treatment pathways (prescription volume and treatment sequence) with sunburst and Sankey diagrams. We calculated the average number of intravitreal injections per patient in the first and second years to evaluate the treatment intensities. Bevacizumab was the most popular first-line drug (80.9%), followed by triamcinolone (15.1%) and dexamethasone (2.28%). Triamcinolone was the most popular drug (8.88%), followed by dexamethasone (6.08%) in patients who began treatment with anti-vascular endothelial growth factor (VEGF) agents. The average number of all intravitreal injections per person decreased in the second year compared with the first year. The average number of injections per person in the first year increased throughout the study. Bevacizumab was the most popular first-line drug and steroids were considered the most common as second-line drugs in patients first treated with anti-VEGF agents. Intensive treatment patterns may cause an increase in intravitreal injections.

Abstract We identified treatment-naïve diabetic macular edema (DME) patients with or without subretinal fluid (SRF). We compared their baseline characteristics: aqueous concentrations of interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, and IL-17, as well as tumor necrosis factor-α, vascular endothelial growth factor (VEGF), and placental growth factor (PlGF). We also compared fundus and optical coherence tomography (OCT) findings, and responsiveness to anti-VEGF treatments. Of 67 DME patients, 18 (26.87%) had SRF. Compared to the no SRF group, the SRF group had significantly higher levels of IL-6, IL-8, VEGF, and PlGF in aqueous humor. After grouping according to diabetic retinopathy stage, non-proliferative diabetic retinopathy (NPDR) patients with SRF had higher aqueous levels of IL-6 and IL-8, compared to NPDR patients without SRF. Moreover, proliferative diabetic retinopathy (PDR) patients with SRF had higher aqueous levels of VEGF and PlGF, compared to PDR patients without SRF. Fundus and OCT analyses revealed that the SRF group had a greater proportion of patients with succinate or patch-shaped hard exudates involving the macula, and greater central subfield thickness (CST) at baseline. After 6 months of anti-VEGF treatments, the SRF group showed better responsiveness in terms of CST; however, visual acuity was not correlated with responsiveness. Considering higher aqueous levels of VEGFs and pro-inflammatory cytokines, SRF could be a biomarker related to diabetic retinopathy activity. DME patients with SRF showed better anatomical responsiveness to anti-VEGF treatments, but did not show better functional improvement on short-term evaluation compared to those of DME patients without SRF.

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

AbstractPurpose To evaluate the effect of hormone replacement therapy (HRT) on lens opacity as measured by Scheimpflug densitometry, serum inflammatory cytokines, and antioxidant levels.Methods A total of 264 women who were at least five years beyond menopause were included. The control group of 128 patients (Group 1) did not use HRT at any time after menopause. The treatment group of 136 patients (Group 2) used HRT for5 years or more after menopause. Cortical, nuclear, and posterior subcapsular density; pentacam nucleus staging (PNS); pentacam densitometry of zone (PDZ) as measured using a Scheimpflug imaging system (Pentacam); and antioxidant and inflammatory cytokines activities in serum using multiplex bead analysiswere examined.Results Uncorrected visual acuity (logMAR) of group1 was significantly worse than those of group 2 (p

Purpose: We performed this study to determine the association between serum 25-hydroxyvitamin D [25(OH) D] level and myopia in adults. Methods: A total of 25,199 subjects aged ≥20 years were included from the National Health and Nutrition Examination Survey 2008–2012. Blood 25(OH)D levels were evaluated from blood samples. Refractive error was measured without cycloplegia. Myopia and high myopia were defined as ≥-0.50 diopters (D) and ≥-6.0 D, respectively. Other covariates such as education, physical activity, and economic status were obtained from interviews. Results: Linear regression analysis showed that as 25(OH) D level increased by 1 ng/mL, myopic refractive error significantly decreased by 0.01 D (P < 0.001) after adjusting for potential confounders including sex, age, height, education level, economic status, physical activity, and sunlight exposure time. The odds ratios for myopia was 0.75 (95% Confidence interval [CI]; 0.67–0.84, P < 0.001) in the highest 25(OH) D quintile compared to the lowest quintile. The odds ratios for high myopia was 0.63 (95% CI; 0.47–0.85, P < 0.001) in the highest 25(OH)D quintile compared to the lowest quintile. Conclusion: Serum 25(OH)D level was inversely associated with myopia in Korean adults.

Objective To examine healthcare resource utilisation (HRU) and direct medical costs for patients with diabetic macular oedema (DME) treated with antivascular endothelial growth factor (anti-VEGF) in Korea by comparing with those for (1) patients with diabetes mellitus (DM) without retinopathy and (2) patients with neovascular age-related macular degeneration (nAMD) treated with anti-VEGF.Design Retrospective cohort study.Setting The Korean National Health Insurance (NHI) database from 1 January 2014 to 31 December 2016.Participants We identified 1398 patients older than 30 years of age who received anti-VEGF treatment for DME in 2015 after excluding patients who had a diagnosis of nAMD in 2015 and any cancer in the preceding year.Main outcome measures One-year healthcare resource use and direct medical costs of patients with DME treated with anti-VEGF.Results In total, 1398 patients with DME receiving anti-VEGF, 12 813 patients with DM without retinopathy and 12 222 patients with nAMD receiving anti-VEGF were identified. Hospital admissions and outpatient visits were highest in patients with DME, while the number of licensed anti-VEGF injections in those with DME was about half that of those with nAMD (2.1 vs 3.9 per patient per year). Mean 1-year medical costs were also higher in patients with DME (US$6723) than in those with DM without retinopathy (US$2687) and nAMD (US$4980). In a multivariable analysis with matched cohorts, DME was associated with 66% higher medical costs for comorbid diseases (adjusted OR (aOR), 1.66; 95% CI 1.45 to 1.90) and 50% lower anti-VEGF injections (aOR, 0.50; 95% CI 0.46 to 0.54) compared with nAMD.Conclusions The overall HRU and economic burden for DME treated with anti-VEGF were higher than for DM without retinopathy or for nAMD treated with anti-VEGF. Meanwhile, the lower number of licensed anti-VEGF injections compared with nAMD may reflect a potential lack of ophthalmological treatment for DME supported by the NHI in Korea.

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.

Introduction: Cataracts are associated with the accumulation of galactose and galactitol in the lens. We determined the polygenetic risk scores for the best model(PRSBM) associated with age-related cataract(ARC) risk and their interaction with diets and lifestyles in 40,262 Korean adults aged over 50 years belonged to a hospital-based city cohort. Methods: The genetic variants for ARC risk were selected in lactose and galactose metabolism-related genes with multivariate logistic regression using the PLINK 1.9 version. PRSBM from the selected genetic variants was estimated by generalized multifactor dimensionality reduction (GMDR) after adjusting covariates. The interactions between the PRSBM and each lifestyle factor were determined to modulate ARC risk. Results: The genetic variants for ARC risk related to lactose- and galactose metabolism were SLC2A1_rs3729548, ST3GAL3_rs3791047, LCT_rs2304371, GALNT5_rs6728956, ST6GAL1_rs2268536, GALNT17_rs17058752, CSGALNACT1_rs1994788, GALNTL4_rs10831608, B4GALT6_rs1667288, and A4GALT_ rs9623659. In GMDR, the best model included all ten genetic variants. The highest odds ratio (OR) for a single SNP in the PRSBM was 1.26. However, subjects with a high-PRSBM had a higher ARC risk by 2.1-fold than a low-PRSBM after adjusting for covariates. Carbohydrate, dairy products, kimchi, and alcohol intake interacted with PRSBM for ARC risk: the participants with high-PRSBM had a much higher ARC risk than those with low-PRSBM when consuming diets with high carbohydrate and low dairy product and kimchi intake. However, only with low alcohol intake, the participants with high-PRSBM had a higher ARC risk than those with low-PRSBM. Conclusion: Adults aged >50 years having high-PRSBM may modulate dietary habits to reduce ARC risk.

We aimed to evaluate the anatomical and functional outcomes of pars-plana vitrectomy (PPV) with or without autologous platelet concentrate (APC) injection in patients with recurrent macular holes (MHs), large MHs, or MHs with high myopia. This multicenter, prospective, interventional randomized controlled trial was conducted from March 2017 to April 2020. Participants were randomly allocated to a PPV group or a PPV+APC group. All participants underwent standard 25-gauge PPV, and eyes in the PPV+APC group underwent PPV with intravitreal APC injection before air-gas exchange. A total of 117 patients were enrolled (PPV group: n = 59, PPV+APC group: n = 58). Hole closure was achieved in 47 participants (79.7%) in the PPV group and 52 participants (89.7%) in the PPV+APC group. There were no between-group differences in the anatomical closure rate or functional outcomes including best-corrected visual acuity, metamorphopsia, pattern-reversal visual evoked potential, or Visual Function Questionnaire-25 score. The use of APC injection does not improve the anatomical and functional outcomes of surgery for large MHs, recurrent MHs, or MHs with high myopia. The adjunctive use of APC can be considered in selected cases because it is not inferior to conventional MH surgery, is relatively simple to perform, and is not affected by the surgeon’s skill.

BackgroundWe investigated clinical course and risk factors for diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).MethodsA total of 759 patients with T2DM without DR were included from January 2001 to December 2004. Retinopathy evaluation was performed at least annually by ophthalmologists. The severity of the DR was classified into five categories according to the International Clinical Diabetic Retinopathy Severity Scales.ResultsOf the 759 patients, 523 patients (68.9%) completed the follow-up evaluation. During the follow-up period, 235 patients (44.9%) developed DR, and 32 patients (13.6%) progressed to severe nonproliferative DR (NPDR) or proliferative DR (PDR). The mean duration of diabetes at the first diagnosis of mild NPDR, moderate NPDR, and severe NPDR or PDR were 14.8, 16.7, and 17.3 years, respectively. After adjusting multiple confounding factors, the significant risk factors for the incidence of DR risk in patients with T2DM were old age, longer duration of diabetes, higher mean glycosylated hemoglobin (HbA1c), and albuminuria. Even in the patients who had been diagnosed with diabetes for longer than 10 years at baseline, a decrease in HbA1c led to a significant reduction in the risk of developing DR (hazard ratio, 0.73 per 1% HbA1c decrement; 95% confidence interval, 0.58 to 0.91; P=0.005).ConclusionThis prospective cohort study demonstrates that glycemic control, diabetes duration, age, and albuminuria are important risk factors for the development of DR. More aggressive retinal screening for T2DM patients diagnosed with DR should be required in order to not miss rapid progression of DR.

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.

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.

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.].

Purpose. To determine the characteristics of diabetic macular edema (DME) patients with cotton-wool spots (CWS). Methods. We classified 80 treatment-naïve DME patients according to whether or not they had CWS involving macula and then compared the concentrations of interleukin- (IL-) 1β, IL-6, IL-8, IL-10, IL-17, placental growth factor, vascular endothelial growth factor (VEGF), and intercellular adhesion molecule (ICAM)-1 in the aqueous humor between the groups, as well as optical coherence tomography (OCT) findings, baseline characteristics, and intravitreal bevacizumab responsiveness. Results. Aqueous levels of ICAM-1 and VEGF in the group with CWS were significantly higher than those in the non-CWS (control) group (p

Age-related cataract (ARC) development is associated with loss of crystalline lens transparency related to interactions between genetic and environmental factors. We hypothesized that polygenetic risk scores (PRS) of the selected genetic variants among the ARC-related genes might reveal significant genetic impacts on ARC risk, and the PRS might have gene–gene and gene–lifestyle interactions. We examined the hypothesis in 1972 and 39,095 subjects aged ≥50 years with and without ARC, respectively, in a large-scale hospital-based cohort study conducted from 2004 to 2013. Single nucleotide polymorphisms (SNPs) of the genes related to ARC risk were identified, and polygenetic risk scores (PRS) were generated based on the results of a generalized multifactor dimensionality reduction analysis. Lifestyle interactions with PRS were evaluated. The PRS derived from the best model included the following six SNPs related to crystallin metabolism: ULK4_rs1417380362, CRYAB_rs2070894, ACCN1_rs55785344, SSTR2_rs879419608, PTN_rs322348, and ICA1_rs200053781. The risk of ARC in the high-PRS group was 2.47-fold higher than in the low-PRS group after adjusting for confounders. Age, blood pressure, and glycemia interacted with PRS to influence the risk of ARC: the incidence of ARC was much higher in the elderly (≥65 years) and individuals with hypertension or hyperglycemia. The impact of PRS on ARC risk was greatest in middle-aged individuals with hypertension or hyperglycemia. Na, coffee, and a Western-style diet intake also interacted with PRS to influence ARC risk. ARC risk was higher in the high-PRS group than in the low-PRS group, and high Na intake, Western-style diet, and low coffee intake elevated its risk. In conclusion, ARC risk had a positive association with PRS related to crystallin metabolism. The genetic impact was greatest among those with high Na intake or hypertension. These results can be applied to precision nutrition interventions to prevent ARC.

Glaucoma, a leading cause of blindness, has multifactorial causes, including environmental and genetic factors. We evaluated genetic risk factors of glaucoma with gene-gene interaction and explored modifications of genetic risk with gene-lifestyles interaction in adults >40 years. The present study included 377 subjects with glaucoma and 47,820 subjects without glaucoma in a large-scale hospital-based cohort study from 2004 to 2013. The presence of glaucoma was evaluated by a diagnostic questionnaire evaluated by a doctor. The genome-wide association study was performed to identify genetic variants associated with glaucoma risk. Food intake was assessed using a semiquantitative food frequency questionnaire. We performed generalized multifactor dimensionality reduction analysis to construct polygenetic-risk score (PRS) and explored gene × nutrient interaction. PRS of the best model included LIM-domain binding protein-2 (LDB2) rs3763969, cyclin-dependent kinase inhibitor 2B (CDKN2B) rs523096, ABO rs2073823, phosphodiesterase-3A (PDE3A) rs12314390, and cadherin 13 (CDH13) rs12449180. Glaucoma risk in the high-PRS group was 3.02 times that in the low-PRS group after adjusting for confounding variables. For those with low serum glucose levels (

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

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

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.

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.

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

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

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.

[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.

AIM: To examine the refractive prediction error in high myopic eyes after phacovitrectomy. METHODS: This retrospective comparative case series included 91 eyes (18 high myopic eyes and 73 non-high myopic eyes) of 91 patients who underwent successful phacovitrectomy (phacoemulsification, intraocular lens implantation, and pars plana vitrectomy). The high myopic eyes were defined as the eye with more than 26.0 mm of axial length. The postoperative prediction error of mean error and mean absolute error were evaluated at 4mo postoperatively. Axial length and keratometry measurement were performed preoperatively and 4mo postoperatively using the IOL Master. RESULTS: The refractive outcome after phacovitrectomy showed significantly greater myopic shift in the high myopic eyes [-1.08±0.87 diopters (D)] than that in the non-high myopic eyes (-0.43±0.63 D, P=0.004). Axial length and keratometric value in the high myopic eyes were significantly increased (P=0.043, 0.037 respectively), whereas those in the non-high myopic group were not significantly increased (P=0.135, 0.347 respectively). The change of the axial length in the myopic eye (0.46±0.28 mm) was greater than that in the non-high myopic eye (0.11 ± 0.34 mm; P

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.