Search

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 ratiowas $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: Our results on the cost-effectiveness of the anti-VEGF injection for PDR, alone or in combination with PRP treatment, can be used as important evidence when making medical service decisions.

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 belonging 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 PLINK 1.9 version. PRSBM from the selected genetic variants were estimated by generalized multifactor dimensionality reduction (GMDR) after adjusting for 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 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, where 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.

This report provides a detailed description of the methodology for ophthalmic examinations according to the Korea National Health and Nutrition Examination Survey (KNHANES) VII and VIII (from 2017 to 2021). The KNHANES is a nationwide survey which has been performed since 1998 in representatives of whole Korean population. During the KNHANES VII and VIII, in addition to the ophthalmic questionnaire, intraocular pressure measurement, visual field test, auto refractometry, axial length and optical coherence tomography measurements were included. This new survey will provide not only provide normative and pathologic ophthalmic data including intraocular pressure, refractive error, axial length, visual field and precise measurement of anterior segment, macula and optic nerve with optical coherence tomography, but also a more accurate diagnosis for major adult blindness diseases, including age-related macular degeneration, diabetic retinopathy, glaucoma, and other ocular diseases, for the national Korean population.

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.

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.

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.

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.

The current study determined the natural angiogenic molecules using an unbiased metabolomics approach. A chick chorioallantoic membrane (CAM) model was used to examine pro- and antiangiogenic molecules, followed by gas chromatography–mass spectrometry (GCMS) analysis. Vessel formation was analyzed quantitatively using the angiogenic index (p < 0.05). At embryonic day one, a white streak or circle area was observed when vessel formation begins. GCMS analysis and database search demonstrated that angiogenesis may initiate when oleic, cholesterol, and linoleic acids increased in the area of angiogenic reactions. The gain of function study was conducted by the injection of cholesterol and oleic acid into a chick embryo to determine the role of each lipid in angiogenesis. We propose that oleic acid, cholesterol, and linoleic acid are natural molecules that set the platform for the initiation stage of angiogenesis before other proteins including the vascular endothelial growth factor, angiopoietin, angiotensin, and erythropoietin join as the angiome in sprout extension and vessel maturation.

PURPOSE: The current study aims to determine the molecular mechanisms of diabetic retinopathy (DR) using the protein-protein interactome and metabolome map. We examined the protein network of novel biomarkers of DR for direct (physical) and indirect (functional) interactions using clinical target proteins in different models. METHODS: We used proteomic tools including 2-dimensional gel electrophoresis, mass spectrometry analysis, and database search for biomarker identification using in vivo murine and human model of diabetic retinopathy and in vitro model of oxidative stress. For the protein interactome and metabolome mapping, various bioinformatic tools that include STRING and OmicsNet were used. RESULTS: We uncovered new diabetic biomarkers including prohibitin (PHB), dynamin 1, microtubule-actin crosslinking factor 1, Toll-like receptor (TLR 7), complement activation, as well as hypothetical proteins that include a disintegrin and metalloproteinase (ADAM18), vimentin III, and calcium-binding C2 domain-containing phospholipid-binding switch (CAC2PBS) using a proteomic approach. Proteome networks of protein interactions with diabetic biomarkers were established using known DR-related proteome data. DR metabolites were interconnected to establish the metabolome map. Our results showed that mitochondrial protein interactions were changed during hyperglycemic conditions in the streptozotocin-treated murine model and diabetic human tissue. CONCLUSIONS: Our interactome mapping suggests that mitochondrial dysfunction could be tightly linked to various phases of DR pathogenesis including altered visual cycle, cytoskeletal remodeling, altered lipid concentration, inflammation, PHB depletion, tubulin phosphorylation, and altered energy metabolism. The protein-metabolite interactions in the current network demonstrate the etiology of retinal degeneration and suggest the potential therapeutic approach to treat DR. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40200-020-00570-9) contains supplementary material, which is available to authorized users.

To determine the association of age-related macular degeneration (AMD) with Alzheimer disease (AD) and Parkinson disease (PD).Retrospective cohort study.The study population consisted of 308,340 participants aged 50 years or older from the Korean National Health Insurance Service-Health Screening Cohort. After exclusion of participants with AMD during 2002, participants were detected for AMD during 2003-2005. Starting from January 1, 2006, all participants were followed up for AD and PD until December 31, 2013. Multivariate Cox proportional hazards regression was used to calculate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for AD and PD risk.Compared to non-AMD participants, AMD patients had higher risk for AD (aHR 1.48, 95% CI 1.25-1.74) and PD (aHR 1.46, 95% CI 1.14-1.88). The risk-increasing association of AMD with AD (aHR 2.25, 95% CI 1.39-3.66) and PD (aHR 2.02, 95% CI 1.00-4.08) were preserved among participants who were never-smokers, did not consume alcohol, and exercised regularly. Finally, AMD was associated with higher risk of AD (aHR 1.96, 95% CI 1.46-2.65 for age70 years and aHR 1.53, 95% CI 1.26-1.86 for age ≥70 years) and PD (aHR 1.90, 95% CI 1.29-2.80 for age70 years and aHR 1.47, 95% CI 1.06-2.04 for age ≥70 years) according to subgroups divided by age.Compared to non-AMD participants, AMD patients had higher risk for AD and PD even among those with healthy lifestyle behaviors. Patients with AMD must be closely monitored for possible subsequent development of AD or PD.

This study aimed to analyze medication adherence and persistence among open-angle glaucoma patients in Korea. A retrospective study was conducted using the Korean National Health Insurance (NHI) claims database from 2016 to 2019. Newly diagnosed open-angle glaucoma patients who were prescribed with the intraocular pressure (IOP)-lowering eyedrops were included. Adherence was measured using the medication possession ratio (MPR), and persistence was measured using the duration of therapy during the 24 month follow-up period. During the study period, 14,648 open-angle glaucoma patients were identified, and 3118 (21.3%) and 4481 patients (30.6%) were adherent to and persistent with their glaucoma treatment, respectively. The mean MPR was 48.8%, and the mean duration of therapy was 357.2 days. Logistic regression analysis showed that patients who are older, female, using prostaglandins as the index medication, and visiting secondary or tertiary hospitals were significantly associated with greater rates of adherence (odds ratio (OR) = 1.21, 1.12, 1.27, and 1.73, respectively) and persistence (OR = 1.11, 1.17, 1.16, 1.17, and 1.36, respectively) during the study period. Patients with open-angle glaucoma in Korea had substandard medication adherence and discontinued their treatment. Ophthalmologists should pay more attention to younger, male patients to improve adherence.

Background The prevalence of cataracts is steadily increasing among the middle-aged and elderly worldwide. We hypothesized that adults aged > 50 years with age-related cataracts (ARCs) have an association with metabolic syndrome (MS) and its components, and MS has interactions with different dietary patterns and lifestyles that affect ARC risk. We examined the hypothesis using the Korean Genome and Epidemiology Study (KoGES; a large-scale hospital-based cohort study), which collected data between 2004–2013. Methods Participants ≥ 50 years old were classified as cases (1,972 ARC patients) and controls (38,290 healthy controls) based on a diagnosis of cataract by a physician. MS and its components were defined using WHO definitions for Asians. Dietary consumption was evaluated using a validated semi-quantitative food frequency questionnaire (SQFFQ), which contained 106 foods, and dietary patterns were analyzed by principal component analysis. After adjusting for potential covariates, logistic regression was used to investigate associations between MS and its components and between dietary patterns and a positive cataract history. Results ARC had a positive association with MS after 1.32-fold adjusting for age, sex, residence area, body mass index, and energy intake. Plasma glucose and HbA1c concentrations exhibited an increased ARC risk in the participants with MS by 1.50- and 1.92-fold and without MS by 1.35 and 1.88-fold, respectively. Serum high-density lipoprotein (HDL) concentrations were negatively associated with ARC risk only in the MS patients, but not without MS. However, blood pressure, abdominal obesity, and serum triglyceride concentrations did not associate with ARC risk regardless of MS. High intake of a Korean-balanced diet (KBD) containing fermented food exhibited a negative association with ARC risk (OR = 0.81) only in the MS group. The fat and coffee intake had a negative association with ARC only in the non-MS group. Current- and former-smokers were positively associated with ARC risk. Conclusion Persons who have hyperglycemia and low-HDL-cholesterolemia had increased susceptibility of ARC prevalence. A KBD with a proper amount of fat (≥ 15%) is recommended, and smoking should be prohibited., Graphical Abstract

The current study tested the hypothesis of whether specific lipids may control angiogenic reactions. Using the chorioallantoic membrane assay of the chick embryo, new vessel formation was analyzed quantitatively by gas chromatography and mass spectrometry as well as bioinformatics tools including an angiogenesis analyzer. Our biochemical experiments showed that a specific lipid composition and stoichiometry determine the angiogenesis microenvironment to accelerate or inhibit vessel formation. Specific lipids of angiogenesis determinants in the vessel area and the non-vessel area were identified as nitrooleic acid, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), palmitic acid, oleic acid, linoleic acid, linolenic acid, epoxyoleic acid, lysophosphatidylcholine (LPC), cholesterol, 7-ketocholesterol, and docosahexaenoyl lysophosphatidylcholine (DHA-LPC). Vessel formation happens on the surface area of the hydrophilic membrane of the yolk. Our biochemical data demonstrated that angiogenesis was followed in the white lipid complex area to generate more branches, junctions, segments, and extremities. We analyzed lipid fragments in the vessel, non-vessel, and albumen area to show that each area contains a specific lipid composition and stoichiometry. Mass spectrometry data demonstrated that the vessel area has higher concentrations of nitrooleic acid, palmitic acid, stearic acid, LPC, lysophosphatidylethanolamine, cholesterol, oleic acid, linoleic acid, 7-ketocholesterol, and DHA-LPC; however, DHA and EPA were abundant in the hydrophobic non-vessel area. The purpose of vessel formation is to wrap up the yolk area to transport nutrients including specific fatty acids. Besides, angiogenesis requires aqueous albumen shown by distance-dependent vessel formation from albumen and oxygen. Higher concentrations of fatty acids are required for energy and carbon structure from the carbon-carbon bond, membrane building blocks, and amphiphilic detergent to solubilize a hydrophobic environment in the aqueous blood layer. The current study may guide that the uncovered hydrophobic or zwitterionic molecules such as DHA and DHA-LPC may control angiogenesis as antiangiogenic or proangiogenic molecules as potential drug targets for treating uncontrolled angiogenesis-related diseases, including diabetic retinopathy and age-related macular degeneration.

This study provides a population-based report on eyelid skin cancer epidemiology showing trends in its incidence and survival in South Korea.For this population-based epidemiological study, nationwide cancer incidence data were obtained from the Korea Central Cancer Registry, covering the entire population. Age-standardised incidence rates (ASRs) and annual per cent changes (APCs) were calculated according to sex, histological types, stage, and date of diagnosis. The 5-year relative survival rates (RSRs) were estimated for patients diagnosed between 1993 and 2016.The ASR increased from 0.27 per 100,000 population in 1999 to 0.61 in 2016, with an APC of 4.94%. The most common histopathological type was basal cell carcinoma (BCC), accounting for 67.5% of all eyelid skin cancers during 1999-2016, followed by sebaceous gland carcinoma (SGC, 10.7%), and squamous cell carcinoma (SCC, 10.6%). The number of localised cancer diagnoses tended to increase, compared to that of distant cancer. The 5-year RSR was nearly 100% when considering all eyelid skin cancers together. When considering them separately, the 5-year RSR of BCC was nearly 100% throughout, whereas for SGC and SCC, it gradually increased from 94.2% and 87.7% (1993-1995), respectively, to nearly 100% (2011-2016) for both. Melanoma had the lowest survival, although its survival has increased markedly since 1993.Nationwide data used in this study showed an increase in incidence and survival rates of eyelid skin cancers in Korea. BCC was the most predominant type, and its proportion among all eyelid skin cancer cases has increased.

This study was performed to investigate the association between oral health and sleep duration in South Korean subjects using 2010-2015 data from the Korean National Health and Nutrition Examination Survey (KNHANES).Cross-sectional data on 35,599 adults over the age of 19 years who completed KNHANES were analyzed. All participants reported subjective oral health status and their daily average sleep duration using a self-reported questionnaire. Sleep duration and oral health status were divided into 3 categories: ≤5, 6-8, ≥9 h/day and good, fair, poor, respectively.The overall prevalence of poor oral health status was 43.8%. Univariate analysis demonstrated that poor oral health status was significantly associated with age, smoking, alcohol, diabetes, education, income, depression, marital status, and sleep duration. After adjusting for covariates (age, sex, diabetes mellitus, hypertension, obesity, smoking, income, education, marital status), sleep durations of ≤5 hours (OR = 1.42; 95% CI, 1.26-1.60) and ≥9 hours (OR = 1.21; 95% CI, 1.04-1.40) were significantly associated with poor oral health, compared to a sleep duration of 6-8 hours. Short or long sleep duration was more likely to have an impact on the development of poor oral health status in men than in women. A significant relationship between sleep duration and oral health status was found in participants younger than 60 years.This is the first report that both short and long sleep durations are significantly associated with the development of poor oral health status. The effect of short or long sleep duration on poor oral health was more significant in younger subjects and in men.

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.

Purpose To determine the relationship between the sighting eye choice and functional and structural asymmetries in open-angle glaucoma (OAG). Methods Two hundred patients with bilateral OAG underwent dominant eye testing using a hole-in-a-card test. The paired eyes were divided into worse and better eyes according to the mean deviation (MD) of visual field (VF) results. Based on the results, patients whose sighting eyes corresponded to eyes with a better VF were designated as group 1, and those whose sighting eyes corresponded to eyes with a worse VF as group 2. Results The sighting eye corresponded predominantly to eyes with better VFs (P < 0.001). The MD of the worse eye was significantly lower (P = 0.008), and the intereye difference in MD was significantly larger in group 1 than in group 2 (P < 0.001). In a comparison of regional VF threshold values and corresponding retinal nerve fiber layer thickness (RNFLT), the superior and inferior VF threshold values were consistently more deteriorated in the nonsighting worse eyes in group 1 (P = 0.009 and 0.003), compared with the sighting worse eyes in group 2, whereas the corresponding RNFLT was not significantly different between the groups. Multiple linear regression analysis showed that the sighting eye choice (P = 0.047), higher vertical cup-to disc ratio (P = 0.042), older age (P = 0.044), thinner average RNFLT (P = 0.007), and average ganglion cell-inner plexiform layer thickness of worse eyes (P < 0.001) were significantly associated with the MD of the worse eyes. Conclusions The sighting eye choice was associated with functional asymmetry between eyes with glaucoma. The functional deterioration was evident in nonsighting eyes with worse VFs.

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

In this study, we explored the presence and elevation of glucose-regulated protein 78 (GRP78) in aqueous humor of patients with diabetic macular edema (DME). After comparing DME patients with the controls, we analyzed GRP78 and vascular endothelial growth factor (VEGF) levels in DME patients. We examined factors associated with GRP78 levels in DME patients. GRP78 was detected in aqueous humor with elevated levels in DME patients. Stepwise backward regression analysis showed that GRP78 levels were associated with the VEGF levels and the duration of diabetes (P

Lipoprotein(a) [Lp(a)] has mainly been considered to be a predictor of the incidence of cardiovascular disease. In addition, previous studies have shown potential linkage between Lp(a) and diabetic microvascular complications.We investigated the incidence and risk factors for the development of diabetic retinopathy (DR) in patients with type 2 diabetes.A total of 787 patients with type 2 diabetes without DR were consecutively enrolled and followed up prospectively. Retinopathy evaluation was annually performed by ophthalmologists. The main outcome was new onset of DR.The median follow-up time was 11.1 years. Patients in the DR group had a longer duration of diabetes (P.001), higher baseline HbA1c (P.001), higher albuminuria level (P = .033), and higher level of Lp(a) (P = .005). After adjusting for sex, age, diabetes duration, presence of hypertension, renal function, LDL cholesterol, mean HbA1c, and medications, the development of DR was significantly associated with the serum Lp(a) level (HR 1.57, 95% confidence interval [1.11-2.24]; P = .012, comparing the 4th vs 1st quartile of Lp(a)). The patient group with the highest quartile range of Lp(a) and mean HbA1c levels ≥7.0% had an HR of 5.09 (95% confidence interval [2.63-9.84]; P.001) for developing DR compared with patients with lower levels of both factors.In this prospective cohort study, we demonstrated that the DR was independently associated with the serum Lp(a) level in patients with type 2 diabetes.

Background: We evaluated the protective effect of ALS-L1023, an extract of Melissa officinalis L. (Labiatae; lemon balm) against oxidative stress-induced apoptosis in human retinal pigment epithelial cells (ARPE-19 cells). Methods: ARPE-19 cells were incubated with ALS-L1023 for 24 h and then treated with hydrogen peroxide (H2O2). Oxidative stress-induced apoptosis and intracellular generation of reactive oxygen species (ROS) were assessed by flow cytometry. Caspase-3/7 activation and cleaved poly ADP-ribose polymerase (PARP) were measured to investigate the protective role of ALS-L1023 against apoptosis. The protective effect of ALS-L1023 against oxidative stress through activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) was evaluated by Western blot analysis. Results: ALS-L1023 clearly reduced H2O2-induced cell apoptosis and intracellular production of ROS. H2O2-induced oxidative stress increased caspase-3/7 activity and apoptotic PARP cleavage, which were significantly inhibited by ALS-L1023. Activation of the PI3K/Akt pathway was associated with the protective effect of ALS-L1023 on ARPE-19 cells. Conclusions: ALS-L1023 protected human RPE cells against oxidative damage. This suggests that ALS-L1023 has therapeutic potential for the prevention of dry age-related macular degeneration.

Background The effect of ALS-L1023, an extract of Melissa officinalis L. (Labiatae; lemon balm) leaves, on experimental choroidal neovascularization (CNV) in mice was evaluated. Methods C57BL/6 mice were given either vehicle or ALS-L1023 daily via oral gavage for 3 weeks (days 0–21). CNV was induced by rupturing Bruch's membrane using laser photocoagulation (day 7). Two weeks after laser injury (day 21), the CNV lesions were evaluated by an examination of choroidal flat mounts using fluorescein-labelled dextran, immunofluorescence staining with isolectin B4 and fluorescence angiography. The effects of ALS-L1023 on endothelial cell tube formation and the expression of phosphorylated extracellular signal-regulated kinase 1/2 were evaluated using human umbilical vein endothelial cells. Results The extent of CNV was reduced by ALS-L1023. Mice treated with 100 and 200 mg/kg/day of the material exhibited 44.3 and 68.1% reductions in the extent of CNV lesions, respectively, compared to the vehicle group (P

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.

To determine characteristics of diabetic macular edema patients with serous retinal detachment (SRD). We classified naïve diabetic macular edema (DME) patients with or without SRD, and compared their baseline characteristics; intravitreal bevacizumab (IVB) responsiveness; aqueous concentrations of IL (interleukin)-1β, -2, -8, -10, -17, placental growth factor (PlGF), and vascular endothelial growth factor (VEGF). In addition, factors associated with the existence of SRD were identified. Of the 64 DME patients, 14 had SRD. The average levels of aqueous VEGF and PlGF were significantly higher in the SRD group than in the control group (P = .022 and P = .041, respectively). The best-corrected visual acuity (BCVA) and central subfield thickness (CST) did not differ significantly between the 2 groups at baseline or after 3 consecutive monthly IVBs. In multivariate logistic regression analysis, the level of aqueous VEGF was the only factor associated with the existence of SRD (odds ratio: 1.03; P = .038). Rather than aqueous inflammatory cytokines, levels of aqueous VEGFs were associated with the occurrence of SRD in DME patients. In terms of prognosis, the existence of SRD was not related with BCVA or CST changes.

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.

We hypothesized that the ocular dominance associated with brain asymmetry would influence macular structure. We assessed the structural asymmetry of the macula by ocular dominance.A total of 144 patients with no ophthalmic abnormalities were examined. After classifying eyes as dominant or non-dominant using the hole-in-a-card test, the macular ganglion cell inner plexiform layer and the macular thickness were measured in both groups using spectral domain optical coherence tomography, and we sought associations between ocular dominance and retinal thickness.Ocular dominance was more frequently found in right eyes than in left eyes (68.75% vs 31.25%, respectively; p0.001). Using conditioned logistic regression, the right eye and the temporal-to-nasal retinal thickness ratio of the macular ganglion cell inner plexiform layer were selected as a final model for the determination of ocular dominance (p0.001, p = 0.013 respectively).Macular vertical asymmetry was associated with ocular dominance. The macular structure and ocular dominance associated with visual cortex lateralization have functional and structural relationships.

Purpose To investigate associations between serum 25-hydroxyvitamin D levels and age-related cataracts. Setting Department of Ophthalmology, College of Medicine, Catholic University of Korea, South Korea. Design Observational cross-sectional study. Methods Participants aged 40 years or older in the fourth (2008 to 2009) and fifth (2010 to 2012) Korea National Health and Nutrition Examination Survey (KNHANES) had evaluation of their serum 25-hydroxyvitamin D levels and ophthalmic slitlamp examinations to identify cataract. An age-related cataract was defined as the presence of a cortical, nuclear, anterior subcapsular, posterior subcapsular, or mixed cataract or a history of cataract surgery. Results The study evaluated eyes of 18 804 patients. The mean levels of serum 25-hydroxyvitamin D were 20.0 ng/mL in men and 17.5 ng/mL in women. In men, but not in women, the odds ratio (OR) for age-related cataracts decreased statistically significantly when the serum 25-hydroxyvitamin D levels were in the highest quintile than when they were in the lowest quintile (OR, 0.76; 95% confidence interval, 0.59-0.99) after adjusting for potentially confounding factors including age, sex, smoking status, diabetes, hypertension, and sunlight exposure. However, trend analysis did not show a significant declining trend in the cataract risk associated with higher serum 25-hydroxyvitamin D quintiles (P = .084). In women, serum 25-hydroxyvitamin D levels were not associated with age-related cataracts. Conclusions The age-related cataract risk decreased in men with higher serum 25-hydroxyvitamin D levels than in those with lower serum 25-hydroxyvitamin D levels after adjusting for potential confounding factors. In light of previous research indicating an antioxidative effect of vitamin D, the connection between vitamin D and age-related cataract warrants further study. Financial Disclosure Neither author has a financial or proprietary interest in any material or method mentioned.

Purposes To investigate the association between sleep duration and myopia. Methods This population-based, cross-sectional study using a nationwide, systemic, stratified, multistage, clustered sampling method included a total of 3625 subjects aged 12–19 years who participated in the Korean National Health and Nutrition Examination Survey 2008–2012. All participants underwent ophthalmic examination and a standardized interview including average sleep duration (hr/day), education, physical activity and economic status (annual household income). Refractive error was measured by autorefraction without cycloplegia. Myopia and high myopia were defined as ≤−0.50 dioptres (D) and ≤−6.0 D, respectively. Sleep durations were classified into 5 categories: 9 hr. Results The overall prevalence of myopia and high myopia were 77.8% and 9.4%, respectively, and the overall sleep duration was 7.1 hr/day. The refractive error increased by 0.10 D per 1 hr increase in sleep after adjusting for potential confounders including sex, age, height, education level, economic status and physical activity. The adjusted odds ratio (OR) for refractive error was 0.90 (95% confidence interval [CI], 0.83–0.97) per 1 hr increase in sleep. The adjusted OR for myopia was decreased in those with >9 hr of sleep (OR, 0.59; 95% CI, 0.38–0.93; p for trend = 0.006) than in those with

There are concerns about arterial thromboembolic event after intravitreal injection of bevacizumab or ranibizumab. Motivated by the fact that D-dimer was a sensitive biomarker for thromboembolism, we evaluated serum D-dimer levels in patients with age-related macular degeneration (AMD) after intravitreal injection of bevacizumab and ranibizumab.In this prospective, nonrandomized, uncontrolled study, 122 patients (122 eyes) with AMD were enrolled. Sixty-two eyes received intravitreal injections of bevacizumab and 60 eyes received intravitreal injections of ranibizumab monthly for 3 months. Serum D-dimer levels were measured in patients before intravitreal injection and 1 day, 1 week, 1 month, and 3 months thereafter.Serum D-dimer levels were not significantly altered following injection of either bevacizumab or ranibizumab. Subgroup analysis for patients at risk for thromboembolic events revealed that serum D-dimer levels showed no significant change after injection of ranibizumab. However, D-dimer levels significantly increased at 1 day (P=0.041) and 1 week (P=0.022) after injection of bevacizumab.Serum D-dimer levels were not changed after injection with either bevacizumab or ranibizumab. In subgroup analysis, bevacizumab injection in patients at risk of thromboembolism increased serum D-dimer levels.

To investigate the clinical characteristics and treatment results of adult patients with ocular toxocariasis.A total of 54 consecutive patients who were clinically and serologically diagnosed with ocular toxocariasis were retrospectively reviewed.Among patients, 66.7 and 77.3% showed increases in eosinophil cationic protein (ECP) and total Ig E in serum, respectively. Four eyes (7.2%) initially presented as neuroretinitis with subsequent motile retinal lesion. The recurrence rates in the combination treatment group with albendazole and corticosteroids were significantly lower than those in the steroid-alone group during the mean follow-up of 27.6 months (p = 0.001).The adjunctive test of serum total IgE level may be helpful for the diagnosis of ocular toxocariasis. Ocular toxocariasis should be considered in the differential diagnosis of unilateral neuroretinitis with subsequent motile retinal lesion. Combined treatment with albendazole and corticosteroids appeared to be effective for reducing the recurrence of intraocular inflammation.

To evaluate the prevalence of and risk factors for age-related macular degeneration (AMD) in a representative Korean population.A nationwide population-based cross-sectional study was conducted among the civilian, noninstitutionalized Korean population aged 40 and older (mean age, 55.7 years; 95% confidence interval [CI], 55.4-56.0). A total of 16,109 older (≥40 years of age) subjects participated in the Korean National Health and Nutrition Survey 2008-2011. All participants underwent standardized interviews and comprehensive ophthalmic examinations. Using physiologic mydriasis, a 45° digital fundus photograph was taken of both eyes of each participant. All fundus photographs were graded according to an international classification and grading system. Main outcome measures consisted of prevalence of early- and late-AMD.Of the 16,109 subjects, fundus photographs were gradable for 14,352 (89.1%). The prevalence of early- and late-AMD in the Korean population was 6.0 and 0.6%, respectively. The prevalence of early-AMD increased from 1.5% in those aged 40-49 years to 16.2% in those aged ≥70 years. After adjusting for confounders, the prevalence of early-AMD increased with increasing age (odds ratio [OR], 1.08; CI, 1.06-1.09). For late-AMD, old age (OR, 1.09; CI, 1.04-1.14), male gender (OR, 2.45; CI, 1.11-5.37), high systolic blood pressure (OR, 1.03; CI, 1.00-1.06) and high fasting glucose level (OR, 0.97; CI, 0.94-0.99) were significant risk factors. Smoking was not associated with either early- or late-AMD in this Korean population.The present study provides the first population-based data on the prevalence of and risk factors for AMD in a representative Korean population. The prevalences of early- and late-AMD in this population were 6.0 and 0.6%, respectively. The prevalence of AMD in Koreans is higher than for those in other Asian countries and similar to that of Caucasians in Western countries.

PURPOSE: The aim of this study was to determine the normal range of interocular peripapillary retinal nerve fiber layer (RNFL) thickness symmetry value in young adults. Factors affecting interocular RNFL thickness symmetry were also investigated. MATERIALS AND METHODS: Both eyes of 241 ophthalmologically and neurologically normal subjects were scanned using optical coherence tomography (200×200 optic disc cube protocol). The effect of ocular cyclotorsion on interocular RNFL thickness symmetry was determined and mathematically accounted for. Symmetry value between the right and left RNFL thickness values was calculated. Linear regression analyses were used to identify correlations between the corrected interocular symmetry value and interocular differences in refractive error, axial length, superior and inferior temporal retinal artery and vein location, and optical coherence tomography signal strength. RESULTS: The mean interocular RNFL thickness symmetry value before and after correction of ocular cyclotorsion was 0.8791±0.0665 and 0.9044±0.0571 (P

Human 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.Human 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.CMV 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.Losartan 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.

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.

Objectives: Open-angle glaucoma (OAG) imposes high disease burden in South Korea. Although various effective interventions are available to manage the progression of OAG, there is limited data on the cost-effectiveness of these treatment strategies in South Korea. Methods: Using a Markov cohort model, we evaluated the cost-effectiveness of 3 major treatment strategies (medication, laser trabeculoplasty, and trabeculectomy) for South Korean patients with OAG. We projected a 25-year time horizon to study a hypothetical cohort of 10,000 patients of age 40 with mild OAG. The outcome measures were quality-adjusted life-years (QALYs) gained, cost from the societal perspective, and the incremental cost-effectiveness ratio (ICER) of medication, laser trabeculoplasty, and trabeculectomy. Interventions were evaluated at a willingness-to-pay (WTP) threshold of 30,000,000 KRW ($29,152) per QALY gained. Deterministic and probabilistic sensitivity analyses were conducted to address the model uncertainty. Results: The mean costs for medication, laser trabeculoplasty, and trabeculectomy were 29,661,740 KRW, 17,34,1342 KRW, and 22,275,438 KRW, respectively. The mean QALYs gained were 15.7, 15.3, and 14.8 for medication, laser trabeculoplasty, and trabeculectomy, respectively. Surgery was strongly dominated because it generated fewer expected QALYs but incurred greater expected cost than laser. The ICER was 30,885,179 KRW per QALY for medication versus laser trabeculoplasty. Laser was cost-effective, however, at a lower WTP threshold of 21,000,000 KRW per QALY gained or below. The results were most sensitive to the progression rates from mild to moderate glaucoma under laser treatment. Conclusion: Under the WTP threshold of 30,000,000 KRW per QALY, medication was cost-effective compared with laser trabeculoplasty and trabeculectomy for treating mild OAG in South Korean population. Laser, however, can be a cost-effective alternative in more resource-limited settings.

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.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.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).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 of the study The purpose of study was to measure the diagnostic utility of interocular retinal nerve fiber layer (RNFL) symmetry and interocular RNFL thickness comparison. Methods Both eyes of 103 normal subjects and 106 glaucoma patients (31 patients with early glaucoma and 75 patients with moderate to severe glaucoma) received comprehensive ophthalmologic evaluation including visual field testing and optic disc scanning using optical coherence tomography. RNFL thickness values for 256 measurement points were rearranged according to a new reference line connecting the optic disc center and the foveola. The interocular RNFL thickness symmetry value and absolute and fractional interocular difference in RNFL thickness were calculated and compared between groups. Area under the receiver operating characteristic curves (AUROCs) were calculated and compared. Result Among the parameters reflecting whole RNFL status, the corrected interocular RNFL thickness symmetry exhibited the largest AUROCs at all glaucoma stages. RNFL thickness and absolute and fractional interocular difference in RNFL thickness exhibited largest AUROC in the inferotemporal area, regardless of glaucoma stage. In the early glaucoma group, absolute and fractional interocular RNFL thickness differences in the temporal and superotemporal areas exhibited equal to or larger AUROCs than RNFL thickness. The AUROCs for RNFL thickness were greater than those for absolute and fractional interocular RNFL thickness differences in the moderate to severe glaucoma group except in the nasal and temporal area. Conclusions The corrected interocular RNFL thickness symmetry value is an effective diagnostic tool for glaucoma. Interocular comparison of RNFL thickness has good diagnostic performance and gives information about the RNFL beyond just the RNFL thickness itself.

Background: To examine the effectiveness of prolonged oral acyclovir treatment in patients with acute retinal necrosis (ARN).Methods: Fifty-five ARN patients (62 eyes) who had been treated with short-term or long-term oral acyclovir were identified in this retrospective study: one group treated with prolonged oral acyclovir (≥14 weeks) and the other group treated with a shorter duration of oral acyclovir (

Purpose To evaluate the effect of the Honan intraocular pressure reducer (HIPR) on vitreous reflux during intravitreal (IVT) injection. Methods Prospective, comparative, controlled, investigator-blinded, randomized clinical study. Sixty eyes of 60 patients who underwent IVT injection were allocated into 2 groups with or without using the HIPR. Vitreous reflux was estimated by measuring largest diameter of the conjunctival bleb formed after IVT injection. Preoperative intraocular pressure (IOP) before and after application of the HIPR and IOP immediately postoperatively and 3 and 10 minutes postoperatively were evaluated. Results The mean amount of vitreous reflux was significantly less with the HIPR than without the HIPR (1.46±1.04 mm vs 2.61±1.37 mm; pConclusions The HIPR prevents vitreous reflux after IVT through a reduction in the preoperative IOP. However, the HIPR appears not to affect the postoperative course of transient IOP elevation.