Delphi Survey for COVID-19 Vaccination in Korean Children Between 5 and 11 Years Old

Purpose@#During the coronavirus disease 2019 (COVID-19) pandemic, we conducted a Delphi survey that included the experts from the field of COVID-19 immunization in children aged 5–11 years. The aim was to organize collective expert opinions on COVID-19 vaccination in young children in the Republic of Korea, and so thus assist the vaccination policy. @*Methods@#The panels included pediatric infectious disease specialists, preventive medicine experts, infectious disease physicians, and COVID-19 vaccine experts consulting the Ministry of Health and Welfare. The Delphi survey was conducted online using a questionnaire from February 14 to February 27, 2022. @*Results@#The Delphi panels agreed that children were vulnerable to COVID-19, and the severity of illness was modest. Furthermore the panels reported that children with chronic illness were more susceptible to a worsening clinical course. There were generally positive opinions on the effectiveness of COVID-19 vaccination in children aged 5–11 years, and experts gathered a slightly positive opinion that the adverse events of pediatric COVID-19 were not numerous. The benefits of COVID-19 vaccination were evaluated at a level similar to the potential risks in children.Currently, the only approved mRNA platform vaccine in children seemed to be sustainable; however, the recombinant protein platform COVID-19 vaccines were evaluated as better options. @*Conclusions@#Due to the surge of the Omicron variant and an increase in pediatric cases, the COVID-19 vaccination in young children may have to be considered. Panels had neutral opinions regarding the COVID-19 vaccination in children aged 5–11 years. Thus monitoring of the epidemiology and the data about the safety of COVID-19 vaccination should be continued.

External Validation of the Long Short-Term Memory Artificial Neural Network-Based SCaP Survival Calculator for Prediction of Prostate Cancer Survival / Journal of the Korean Cancer Association, 대한암학회지

Decision-making for treatment of newly diagnosed prostate cancer (PCa) is complex due to the multiple initial treatment modalities available. We aimed to externally validate the SCaP (Severance Study Group of Prostate Cancer) Survival Calculator that incorporates a long short-term memory artificial neural network (ANN) model to estimate survival outcomes of PCa according to initial treatment modality. Materials and Methods The validation cohort consisted of clinicopathological data of 4,415 patients diagnosed with biopsy-proven PCa between April 2005 and November 2018 at three institutions. Area under the curves (AUCs) and time-to-event calibration plots were utilized to determine the predictive accuracies of the SCaP Survival Calculator in terms of progression to castration-resistant PCa (CRPC)–free survival, cancer-specific survival (CSS), and overall survival (OS). Results Excellent discrimination was observed for CRPC-free survival, CSS, and OS outcomes, with AUCs of 0.962, 0.944, and 0.884 for 5-year outcomes and 0.959, 0.928, and 0.854 for 10-year outcomes, respectively. The AUC values were higher for all survival endpoints compared to those of the development cohort. Calibration plots showed that predicted probabilities of 5-year survival endpoints had concordance comparable to those of the observed frequencies. However, calibration performances declined for 10-year predictions with an overall underestimation. Conclusion The SCaP Survival Calculator is a reliable and useful tool for determining the optimal initial treatment modality and for guiding survival predictions for patients with newly diagnosed PCa. Further modifications in the ANN model incorporating cases with more extended follow-up periods are warranted to improve the ANN model for long-term predictions.

External Validation of the Long Short-Term Memory Artificial Neural Network-Based SCaP Survival Calculator for Prediction of Prostate Cancer Survival / Journal of the Korean Cancer Association, 대한암학회지

Decision-making for treatment of newly diagnosed prostate cancer (PCa) is complex due to the multiple initial treatment modalities available. We aimed to externally validate the SCaP (Severance Study Group of Prostate Cancer) Survival Calculator that incorporates a long short-term memory artificial neural network (ANN) model to estimate survival outcomes of PCa according to initial treatment modality. Materials and Methods The validation cohort consisted of clinicopathological data of 4,415 patients diagnosed with biopsy-proven PCa between April 2005 and November 2018 at three institutions. Area under the curves (AUCs) and time-to-event calibration plots were utilized to determine the predictive accuracies of the SCaP Survival Calculator in terms of progression to castration-resistant PCa (CRPC)–free survival, cancer-specific survival (CSS), and overall survival (OS). Results Excellent discrimination was observed for CRPC-free survival, CSS, and OS outcomes, with AUCs of 0.962, 0.944, and 0.884 for 5-year outcomes and 0.959, 0.928, and 0.854 for 10-year outcomes, respectively. The AUC values were higher for all survival endpoints compared to those of the development cohort. Calibration plots showed that predicted probabilities of 5-year survival endpoints had concordance comparable to those of the observed frequencies. However, calibration performances declined for 10-year predictions with an overall underestimation. Conclusion The SCaP Survival Calculator is a reliable and useful tool for determining the optimal initial treatment modality and for guiding survival predictions for patients with newly diagnosed PCa. Further modifications in the ANN model incorporating cases with more extended follow-up periods are warranted to improve the ANN model for long-term predictions.

Effects of One-dose Varicella Vaccination on Disease Severity in Children during Outbreaks in Seoul, Korea

BACKGROUND: In Korea, the incidence of varicella has increased despite the introduction of a universal one-dose vaccination for children aged 12–15 months in 2005. A previous study demonstrated that the vaccine effectiveness was insufficient to prevent against varicella. We assessed the effect of the varicella vaccination on disease severity. METHODS: Epidemiologic investigation of varicella cases in Seoul metropolitan area from 2015 to 2017 were used. Varicella-related symptoms such as rash were determined by the clinical practitioners. Disease severity of patients was assessed by the number of skin lesions and divided into mild (≤ 50) and moderate (51–249) to severe (≥ 250). Unconditional logistic regression analysis was performed and age was controlled. RESULTS: Among a total of 1,008 varicella cases reported, 869 cases were breakthrough cases and 139 were unvaccinated cases. The risk for occurrence of moderate-to-severe disease in the breakthrough group was 0.57 times less than that of the unvaccinated group. CONCLUSION: These data suggest that national varicella vaccination may have a significant effect on attenuation of disease severity in children.

Normative Data for the Logical Memory Subtest of the Wechsler Memory Scale-IV in Middle-Aged and Elderly Korean People

OBJECTIVE: The purpose of this study is to identify the demographic variables that are affecting performances on the Logical Memory (LM) subtest included in the Korean version of the Wechsler Memory Scale (WMS)-IV and to provide normative data on the LM subtest for the middle-age and elderly Korean people.METHODS: The participants were 435 non-demented adults aging from 50 to 90 and with the educational level ranging from 0 to 21 years.RESULTS: Age and education were found to be significantly associated with performance on the LM subtest, while gender effect was not statistically significant. Therefore, we stratified the norm blocks by age and education. Age was divided into three groups: 50–59, 60–74, and 75–90 years. Education was stratified into three groups: 0–8 years, 9–12 years, and 13 years or more.CONCLUSION: The normative data provided in the current study are expected to be useful in clinical and research settings to detect or define subtle changes in episodic memory in Korean adults and elderly, and can also be used for cross-cultural comparison of verbal episodic memory performance among elderly populations using different languages.

Implementing Expanded Rapid Human Immunodeficiency Virus Testing in Public Health Centers in Seoul, 2015 / 감염과화학요법

In 2015, rapid human immunodeficiency virus (HIV) testing was implemented in all 25 public health centers in Seoul. During March and December 2015, 20,987 rapid HIV tests were performed, of which 116 (0.5%) were positive. Compared to those of the period before application of the rapid HIV test in place of conventional enzyme immunoassay method, the number of HIV tests performed and the number of positive results increased by sevenfold and twofold, respectively. In conclusion, expansion of the provision of rapid HIV tests in public health centers increased the number of voluntary HIV tests.

Implementing Expanded Rapid Human Immunodeficiency Virus Testing in Public Health Centers in Seoul, 2015 / 감염과화학요법

In 2015, rapid human immunodeficiency virus (HIV) testing was implemented in all 25 public health centers in Seoul. During March and December 2015, 20,987 rapid HIV tests were performed, of which 116 (0.5%) were positive. Compared to those of the period before application of the rapid HIV test in place of conventional enzyme immunoassay method, the number of HIV tests performed and the number of positive results increased by sevenfold and twofold, respectively. In conclusion, expansion of the provision of rapid HIV tests in public health centers increased the number of voluntary HIV tests.

Cost-Effectiveness of Voluntary HIV Testing Strategies in a Very Low-Prevalence Country, the Republic of Korea

BACKGROUND: The Republic of Korea has a very low prevalence of human immunodeficiency virus (HIV) infection, but the number of new HIV diagnoses has steadily risen, strongly indicating a large number of undetected HIV infections. Thus, it is important for Korean public health authorities to adopt and encourage cost-effective HIV detection tools, such as rapid HIV screening tests. In this study, we aimed to evaluate the cost-effectiveness of enzyme-linked immunosorbent assays (ELISA) and rapid tests in a public health center (PHC) setting. METHODS: We developed a decision analytic model to assess the per-examinee cost and the cost-effectiveness of identifying HIV patients in a PHC setting using two HIV testing strategies: conventional HIV screening by ELISA versus rapid HIV testing. Analysis was performed in two scenarios: HIV testing in an average-risk population and in a high-risk population. RESULTS: Compared to the ELISA, the rapid test was cost-saving and cost-effective. The per-examinee cost was USD 1.61 with rapid testing versus USD 3.38 with ELISA in an average-risk population, and USD 4.77 with rapid testing versus USD 7.62 with ELISA in a high-risk population. The cost of identifying a previously undiagnosed HIV case was USD 26,974 with rapid testing versus USD 42,237 with ELISA in an average-risk population, and USD 153 with rapid testing versus USD 183 with ELISA in a high-risk population. CONCLUSION: Rapid testing would be more cost-effective than using conventional ELISA testing for identifying previously undiagnosed HIV-infected cases in Korea, a country with extremely low HIV prevalence.

Effectiveness of Varicella Vaccination Program in Preventing Laboratory-Confirmed Cases in Children in Seoul, Korea

A universal one-dose varicella vaccination program was introduced in 2005 in Republic of Korea. However, the incidence of varicella in Korea has tripled over the last decade. We conducted a community based 1:1 matched case-control study to assess the effectiveness of one MAV strain-based vaccine and three Oka strain-based vaccines licensed for use in Korea. All cases were children in Seoul, Korea with varicella who were reported to the National Notifiable Disease Surveillance System in Seoul during 2013. The controls were age-matched children with mumps or scarlet fever but no history of varicella. We included 537 cases and 537 controls. The overall effectiveness of one dose of varicella vaccination was 13% (95% confidence interval [CI], −17.3–35.6). Of the four licensed varicella vaccines, only one was highly effective (88.9%; 95% CI, 52.1–97.4). The vaccine effectiveness for the other vaccines were 71.4% (95% CI, −37.5–94.1), −5% (95% CI, −61.9–31.9), and −100% (95% CI, −700–50.0). The overall effectiveness of vaccination was 75.8% (95% CI, 22.8–92.4) in the first year after vaccination and decreased thereafter; the effectiveness became −7.2% (95% CI, −130.9–59.2) in the fourth year after vaccination. Further studies are warranted to investigate reduced effectiveness of varicella vaccines in Korea.

Patients Presenting with Advanced Human Immunodeficiency Virus Disease: Epidemiological Features by Age Group

We explored factors influencing presentation with advanced human immunodeficiency virus (HIV) disease by age group. Data were derived from a city-wide cross-sectional survey of 759 HIV-infected adults living in Seoul, Korea. The significance of each observed factor was assessed via multivariate logistic regression. Of subjects aged 20-34 years, lower educational level had a positive influence on presentation with advanced HIV disease (adjusted odds ratio [aOR], 2.43; 95% confidence interval [CI], 1.36-4.34); those recently diagnosed with HIV were more likely to be presented with advanced HIV disease (aOR, 3.17; 95% CI, 0.99-10.2). Of the subjects aged 35-49 years, those w ith advanced HIV disease were more likely to have been diagnosed during health check-ups (aOR, 2.91; 95% CI, 1.15-7.32) or via clinical manifestations (aOR, 3.61; 95% CI, 1.39-9.36). Of the subjects aged > or = 50 years, presentation with advanced HIV disease was significantly more common in older subjects (aOR per increment of 5 years, 2.06; 95% CI, 1.32-3.23) and less common among individuals diagnosed with HIV in 2000-2006 (aOR, 0.18; 95% CI, 0.04-0.83). In conclusion, a lower educational level in younger subjects and more advanced age in older subjects positively influence the presentation of advanced HIV disease.

Patients Presenting with Advanced Human Immunodeficiency Virus Disease: Epidemiological Features by Age Group

We explored factors influencing presentation with advanced human immunodeficiency virus (HIV) disease by age group. Data were derived from a city-wide cross-sectional survey of 759 HIV-infected adults living in Seoul, Korea. The significance of each observed factor was assessed via multivariate logistic regression. Of subjects aged 20-34 years, lower educational level had a positive influence on presentation with advanced HIV disease (adjusted odds ratio [aOR], 2.43; 95% confidence interval [CI], 1.36-4.34); those recently diagnosed with HIV were more likely to be presented with advanced HIV disease (aOR, 3.17; 95% CI, 0.99-10.2). Of the subjects aged 35-49 years, those w ith advanced HIV disease were more likely to have been diagnosed during health check-ups (aOR, 2.91; 95% CI, 1.15-7.32) or via clinical manifestations (aOR, 3.61; 95% CI, 1.39-9.36). Of the subjects aged > or = 50 years, presentation with advanced HIV disease was significantly more common in older subjects (aOR per increment of 5 years, 2.06; 95% CI, 1.32-3.23) and less common among individuals diagnosed with HIV in 2000-2006 (aOR, 0.18; 95% CI, 0.04-0.83). In conclusion, a lower educational level in younger subjects and more advanced age in older subjects positively influence the presentation of advanced HIV disease.

Implementing the Use of Rapid HIV Tests in Public Health Centers in Seoul: Results of a Pilot Project, 2014

To determine whether rapid HIV tests in public health centers might encourage voluntary HIV testing, a pilot project was conducted in four selected public health centers in Seoul, 2014. During the period April 10 to November 28 of pilot project, 3,356 rapid tests were performed, and 38 were confirmed as positive. The monthly average numbers of voluntary HIV tests and HIV-positive cases were up to nine-fold and six-fold larger, respectively, than those of the period before application of the rapid HIV test. Among 2,051 examinees that completed questionnaires, 90.3% were satisfied. In conclusion, the use of rapid HIV tests in public health centers promoted voluntary HIV testing and was satisfactory for examinees.

Korean Pharmacological Treatment Guideline for Child-Adolescent Depression: The Efficacy and Choice of Antidepressant / 대한정신약물학회지

OBJECTIVE: The purpose of this guideline was to suggest recommendations for appropriate use of antidepressants in the child-adolescent depression. The differences of efficacy among antidepressants were evaluated. METHODS: Four kinds of reliable guidelines for the treatments of child-adolescent depression had been selected, and evidences and recommendations were extracted by the executive committee under the peer review. All the process was applied to the Manual for Guideline Adaptation version 2.0 by National Evidence-based Healthcare Collaborating Agency. RESULTS: Selective serotonin reuptake inhibitor (SSRI) could be considered for the treatments of moderate to severe child-adolescent depression. Among SSRIs, fluoxetine, sertraline, and escitalopram were recommended as having antidepressant efficacy compared with placebo, while paroxetine, venlafaxine, and tricyclic antidepressant were not recommended owing to lack of evidence. Another recommendation was to use combined treatment with cognitive behavioral therapy. CONCLUSION: This guideline, which was made through former and strict process of guideline adaptation, would contribute toward improving the quality of child-adolescent depression treatment by providing useful recommendations for the choice of antidepressant.

Cost-Effectiveness of Liver Cancer Screening in Adults at High Risk for Liver Cancer in the Republic of Korea / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was conducted in order to determine the most cost-effective strategy, in terms of interval and age range, for liver cancer screening in the high-risk population of Korea. MATERIALS AND METHODS: A stochastic model was used to simulate the cost-effectiveness of liver cancer screening by combined ultrasonography and alpha-fetoprotein testing when varying both screening intervals and age ranges. The effectiveness of these screening strategies in the high-risk population was defined as the probability of detecting preclinical liver cancer, and cost was based on the direct cost of the screening and confirmative tests. Optimal cost-effectiveness was determined using the incremental cost-effectiveness ratio. RESULTS: Among the 36 alternative strategies, one-year or two-year interval screening for men aged between 50 and 80 years, six-month or one-year interval screening for men aged between 40 and 80 years, and six-month interval screening for men aged between 30 and 80 years were identified as non-dominated strategies. For women, identified non-dominated strategies were: one-year interval screening between age 50 and 65 years, one-year or six-month interval screening between age 50 and 80 years, six-month interval screening between age 40 and 80 years, and six-month interval screening between age 30 and 80 years. CONCLUSION: In Korea, a one-year screening interval for men aged 50 to 80 years would be marginally cost-effective. Further studies should be conducted in order to evaluate effectiveness of liver cancer screening, and compare the cost effectiveness of different liver cancer screening programs with a final outcome indicator such as quality-adjusted life-years or disability-adjusted life-years.

Impact of Home-Based Exercise Training with Wireless Monitoring on Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

Recent studies have suggested a favorable effect of cardiac rehabilitation (CR) on patients with cardiovascular disease. This study aimed to evaluate the impact of home-based exercise training with wireless monitoring on acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). A total of 55 ACS patients undergoing PCI were randomly divided into home based exercise training with wireless monitoring cardiac rehabilitation (CR, n = 26) and usual care (UC, n = 29). Exercise capacity and quality of life (QOL) were evaluated at baseline and after 12 weeks. Change of metabolic equivalent of the tasks, maximal exercise time and QOL were significantly increased (+2.47 vs +1.43, P = 0.021; +169.68 vs +88.31 sec, P = 0.012; and +4.81 vs +0.89, P = 0.022, respectively), and the change of submaximal rate pressure product, and of submaximal rate of perceived exertion were significantly decreased (-28.24 vs -16.21, P = 0.013; and -1.92 vs -1.62, P = 0.018, respectively) in the CR group compared to the UC group after 12 weeks. CR using home-based exercise training with wireless monitoring led to improvement of exercise capacity and QOL relative to conventional care in ACS patients undergoing PCI. Our findings suggest that early scheduled CR may be considered in ACS patients undergoing PCI.

Current status of the National Cancer Screening Program for cervical cancer in Korea, 2009 / 부인종양

OBJECTIVE: The National Cancer Screening Program (NCSP) began in 1999. In this report, we evaluate the results of the NCSP for cervical cancer in 2009 and provide participation rates in an organized cervical cancer screening program in Korea. METHODS: Using data obtained from the National Cancer Screening Information System, cervical cancer screening participation rates were calculated. Recall rates, defined as the proportion of abnormal cases among women screened, were also estimated with 95% confidence intervals. RESULTS: The target population of cervical cancer screening in 2009 included 4,577,200 Korean women aged 30 and over, 1,349,668 of whom underwent the Papanicolaou smear test (29.5% participation rate). Compared with the participation rate of women covered by the National Health Insurance Program (31.3%), the participation rate of women covered by the Medical Aid Program was lower (18.4%). Participation rates also varied in different age groups (the highest of 39.3% in women aged 50 to 59 and the lowest of 14.4% in those aged 70 and older), and different areas (the highest of 34.1% in Busan and the lowest of 21.5% in Chungnam). The overall recall rate for cervical cancer screening was 0.41% (95% confidence interval, 0.40 to 0.42). CONCLUSION: According to our study, efforts to facilitate participation and reduce disparities in cervical cancer screening among Korean women are needed.

Comparison of Cytokine Gene Induction in RAW 264.7 Cells by Porphyromonas gingivalis and Escherichia coli Lipopolysaccharide

Porphyromonas gingivalis lipopolysaccharide (Pg LPS) is an important virulence factor in chronic periodontitis. The aim of this study was to compare the expression of inflammatory cytokine genes in Escherichia coli LPS (Ec LPS) and Pg LPS-stimulated mouse macrophage RAW 264.7 cells. Cells were treated with Ec LPS and Pg LPS for 18 hours, and the cytokine gene expression profile was assessed using microarrays and confirmed by real-time PCR. Microarray analysis showed that both types of LPS induced a significant increase in the expression of IL-17beta, IL-2, Ccl4, Cxcl2 and TNFalpha compared with the control. However, LT-b was up-regulated by Pg LPS but not by Ec LPS. Real-time PCR analysis of these genes showed similar results for LT-b, Ccl4, Cxcl2, and TNF-alpha but found that IL-17beta and IL-2 were upregulated by Pg LPS but not by Ec LPS. These data indicate that Pg LPS stimulates the transcription of IL-17beta, IL-2, Ccl4, Cxcl2, LT-b, and TNFalpha, all of which may be involved in the pathogenesis of chronic periodontitis.

Induction of Signal Transduction Pathway Genes in Dendritic Cells by Lipopolysaccharides from Porphyromonas gingivalis and Escherichia coli

Porphyromonas (P.) gingivalis lipopolysaccharide (Pg LPS) is the major pathogenic component of periodontal disease. In this study, we have attempted to determine the expression profiles of the signal transduction pathway genes induced by Pg LPS in comparison with Escherichia (E.) coli LPS (Ec LPS). DC2.4 cells were treated for two hours with 1 microg/ml of Pg LPS or 0.5 microg/ml of Ec LPS. The total RNA from these cells was then isolated and reverse-transcribed. Gene expression profiles were then analyzed with a signal transduction pathway finder GEArray Q series kit and significant changes in expression were confirmed by real-time PCR. The microarray results indicated that several genes, including Tnfrsf10b, Vcam1, Scyb9, Trim25, Klk6, and Stra6 were up-regulated in the DC2.4 cells in response to Pg LPS treatment, but were downregulated or unaffected by Ec LPS. Real-time PCR revealed that the expression of Trim25, Scyb9 and Tnfrsf10b was increased over the untreated control. Notably, Trim25 and Tnfrsf10b were more strongly induced by Pg LPS than by Ec LPS. These results provide greater insight into the signal transduction pathways that are altered by P. gingivalis LPS.

Relationships of Serum Leptin Levels with Bone Metabolism in the Childhood Obesity / 대한소아소화기영양학회지

PURPOSE: The aim of this study was to evaluate the influence of leptin on biochemical markers of bone metabolism in childhood obesity. METHODS: A total of 50 male children (25 obese and 25 controls) were recruited from the pediatric outpatient clinic at the Chosun University Hospital from November 1st 2005 to May 30th 2006. BMI, body fat percentage, serum leptin, bone-specific alkaline phosphatase (B-ALP), C-terminal propeptide of type 1 collagen (CICP), total deoxypyridinoline crosslinks (total DPD) were measured. The correlations of leptin with BMI, body fat percentage, B-ALP, CICP, total DPD were analyzed by Pearson's correlation. In a multiple stepwise regression analysis, leptin after correction for body weight was evaluated if there was a correlation with biochemical markers of bone formation and resorption respectively. RESULTS: The leptin levels of the obese group were significantly higher than those of the control group (p=0.012). In the obese group, the leptin level was significantly positively correlated with the BMI (r=0.551, p=0.01) and the percentage of body fat (r=0.584, p=0.018). In the obese group, of bone markers, B-ALP (r=-0.613, p=0.026) and CICP (r=-0.583, p=0.037) were negatively correlated with leptin. B-ALP (r=-0.728, p=0.007) and CICP (r=-0.684, p=0.014) were negatively correlated with leptin when corrected for body weight. In the control group, bone markers were not correlated with leptin. In the multiple stepwise regression analyses, there was a negative correlation between the leptin and B-ALP (Y=-39.653X+356.341, p=0.026), CICP (Y=-13.437X+116.013, p=0.037) respectively in the obese group. CONCLUSION: Leptin was a significant factor in the bone formation but not in bone resorption in childhood obesity.

Angiogenesis according to Expressive Change of Angiogenic Related Factor in Human RPE under Oxidative Stress

PURPOSE: To elucidate the mechanism of neoangiogenesis in human retinal pigment epithelium under oxidative stress. METHODS: Paraquat was added to cultured human retinal pigment epithelium (HRPE) for 72 hours to induce oxidative stress milieu. Expression and production of angiogenic factors, including vascular endothelial growth factor (VEGF) and pigment epithelial derived factor (PEDF), was checked by RT-PCR and Western blot, respectively. The induction of neoangiogenesis was monitored by both tube formation in ECV 304 cell and migration assay of human fetal dermal microvascular endothelial cells. RESULTS: Competitive RT-PCR showed that PEDF gene in paraquat-treated HRPE was expressed at a significantly lower level than in non-treated HRPE. However, Western blot showed a significant increase of VEGF production (p<0.05) and a decrease of PEDF production (p<0.05). Moreover, angiogenesis was dose-dependently increased when the various concentrations of paraquat were added to HRPE. CONCLUSIONS: Taken together, oxidative stress by addition of paraquat caused HRPE to produce more VEGF and less PEDF, thereby leading to neoangiogenesis, and suggesting that the neovascularization in age-related macular degeneration (AMD) is caused by destroying the balance of angiogenic factors in HRPE such as VEGF and PEDF; that is, in oxidative stressed HRPE, more VEGF is released and less PEDF, as compared to normal HRPE.