Polygenic risk score-based phenome-wide association for glaucoma and its impact on disease susceptibility in two large biobanks.

BACKGROUND: Glaucoma is a leading cause of worldwide irreversible blindness. Considerable uncertainty remains regarding the association between a variety of phenotypes and the genetic risk of glaucoma, as well as the impact they exert on the glaucoma development. METHODS: We investigated the associations of genetic liability for primary open angle glaucoma (POAG) with a wide range of potential risk factors and to assess its impact on the risk of incident glaucoma. The phenome-wide association study (PheWAS) approach was applied to determine the association of POAG polygenic risk score (PRS) with a wide range of phenotypes in 377, 852 participants from the UK Biobank study and 43,623 participants from the Penn Medicine Biobank study, all of European ancestry. Participants were stratified into four risk tiers: low, intermediate, high, and very high-risk. Cox proportional hazard models assessed the relationship of POAG PRS and ocular factors with new glaucoma events. RESULTS: In both discovery and replication set in the PheWAS, a higher genetic predisposition to POAG was specifically correlated with ocular disease phenotypes. The POAG PRS exhibited correlations with low corneal hysteresis, refractive error, and ocular hypertension, demonstrating a strong association with the onset of glaucoma. Individuals carrying a high genetic burden exhibited a 9.20-fold, 11.88-fold, and 28.85-fold increase in glaucoma incidence when associated with low corneal hysteresis, high myopia, and elevated intraocular pressure, respectively. CONCLUSION: Genetic susceptibility to POAG primarily influences ocular conditions, with limited systemic associations. Notably, the baseline polygenic risk for POAG robustly associates with new glaucoma events, revealing a large combined effect of genetic and ocular risk factors on glaucoma incidents.

Association Between High Blood Folate Levels and Glaucoma in a Representative Korean Population.

Purpose: This study aimed to investigate the association between folate levels and the prevalence of glaucoma. Methods: This nationwide population-based cross-sectional study included 1790 participants aged ≥40 years. We analyzed data regarding the participants obtained in the 2016-2018 Korean National Health and Nutrition Examination Survey. The diagnosis of glaucoma was defined according to the International Society of Geographical and Epidemiological Ophthalmology criteria. Logistic regression analyses were used to investigate the relationship between blood folate levels and glaucoma. Results: There was a significantly lower prevalence of glaucoma in the highest quartile of blood folate levels than in the lowest quartile, after adjusting for confounding factors such as age, sex, systemic hypertension, diabetes, hypercholesterolemia, and smoking (odds ratio [OR] = 0.470; 95% confidence interval [CI], 0.291-0.759; P for trend = 0.017). There was a significantly lower risk of glaucoma in the highest quartile of blood folate levels than in the lowest quartile among women (OR = 0.188; 95% CI, 0.099-0.357; P for trend <0.001) and younger participants (OR =0.443; 95% CI, 0.229-0.856; P for trend = 0.045). Conclusions: Our findings indicate a strong inverse correlation between blood folate levels and glaucoma.

Association of glaucoma and lifestyle with incident cardiovascular disease: a longitudinal prospective study from UK Biobank.

The shared pathophysiological features of the cerebrovascular disease (CVD) and glaucoma suggest an association between the two diseases. Using the prospective UK Biobank cohort, we examined the associations between glaucoma and incident CVD and assessed the extent to which a healthy lifestyle reduced the CVD risk in subjects with glaucoma, using a scoring system consisting of four factors: current smoking, obesity, regular physical activity, and a healthy diet. During a mean follow-up time of 8.9 years, 22,649 (4.9%) incident CVD cases were documented. Multivariable Cox regression analyses revealed that subjects with glaucoma were significantly more likely to exhibit incident CVD (hazard ratio [HR]:1.19, 95% confidence interval [CI] 1.03-1.37; p = 0.016) than controls. In the further subgroup analyses, glaucoma increased incident CVD risk both in the young (40-55 years) and the old (56-70 years) and in both sexes, with higher risk in the young (HR: 1.33, CI 1.02-1.74) and female subjects (HR: 1.32, CI 1.14-1.52). When we analyze the associations between glaucoma and incident CVD by lifestyle factors, the highest absolute risks were observed in individuals with both glaucoma and an unhealthy lifestyle (HR: 2.66, CI 2.22-3.19). In conclusion, glaucoma was an independent risk factor for incident CVD. A healthy lifestyle was associated with a substantially lower risk for CVD incidence among adults with glaucoma.

Association between atrial fibrillation and the risk of glaucoma development: a 12-year Nationwide cohort study.

OBJECTIVE: To investigate the risk of glaucoma development in patients with atrial fibrillation (A-fib) using Korean National Health Insurance Service data. METHODS: The present study used a National Sample Cohort consisting of approximately one million random subjects who were tracked from 2002 to 2013 (12 years). Newly diagnosed glaucoma and A-fib were included based on the Korean Classification of Disease codes. The A-fib group consisted of patients who received an initial A-fib diagnosis between January 2003 and December 2007 as an index period (n = 8765). The control group (n = 43,352) was selected using a 1:5 propensity-score matching for social and demographic factors. Each subject was followed up until 2013. Multivariate Cox proportional hazard regression analysis was performed to compare the risk of glaucoma development between the A-fib group and the control group. RESULTS: The rate of glaucoma development was 3.54% in the A-fib group and 2.96% in the control group (P < 0.0001). A-fib increased the risk of glaucoma development [hazard ratio = 1.31; 95% confidence interval (CI): 1.15 to 1.48] after adjusting for age, sex, comorbidities, residence, household income, and year of enrollment. In multivariable Cox regression analysis, patients with comorbidity of diabetes mellitus and chronic renal failure and those aged ≥50 years showed significantly higher risk of glaucoma development (all P < 0.001). CONCLUSIONS: A-fib was significantly associated with the development of glaucoma after adjusting for potential confounding factors. Physicians may need to monitor patients with A-fib carefully for possible glaucoma development.

Anti-inflammatory effect of glucagon-like Peptide-1 receptor agonist on the neurosensory retina in an acute optic nerve injury rat model.

PURPOSE: To explore the possibility of using glucagon-like peptide-1 receptor agonist (GLP-1RA) as a new treatment for neuroinflammation, by analyzing retinal pathological changes in an optic nerve crush rat model. METHODS: Eight-week-old male Sprague-Dawley rats were divided into lixisenatide (LIX, n = 10), traumatic control (T-CON, n = 10), and normal control (n = 5) groups. The optic nerves of left eyes in the LIX and T-CON groups were crushed in a standardized manner. The LIX group was treated with subcutaneous injections of lixisenatide (200 µg/kg/day) for 5 days. One week after initiating treatment, quantitative polymerase chain reaction, Western blot, and immunohistochemistry analyses were performed on the retinal tissues of each group to identify inflammatory markers. RESULTS: The LIX group showed significantly lower mRNA levels of interleukin 1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), thioredoxin interacting protein (TXNIP), and glial fibrillary acidic protein (GFAP) than the T-CON group. Also, the LIX group exhibited decreased TXNIP and GFAP expression compared with the T-CON group, and similar expression to the normal control group, according to Western blot analysis. Significantly increased immunohistochemistry staining of Brn3a and decreased TUNEL staining were seen in the LIX group compared with the T-CON group, indicating that lixisenatide contributes to retinal ganglion cell survival in cases of acute optic nerve injury. CONCLUSIONS: Neuroinflammation was significantly reduced in lixisenatide-treated retinas compared with untreated retinas in our acute optic nerve injury rat model. The neuroprotective effect of lixisenatide indicates that it can serve a new treatment option against clinically intractable traumatic optic neuropathy.

Microvasculature Dropout and Development of Normal Tension Glaucoma in Glaucoma Suspects: The Normal Tension Glaucoma Suspect Cohort Study.

PURPOSE: To investigate the contribution of vessel parameters to identify normal tension glaucoma (NTG) suspects at risk of NTG development. DESIGN: Multicenter prospective cohort study. SUBJECTS: A total of 307 eyes of 307 NTG suspects having intraocular pressure within the normal range; a suspicious optic disc, but without definite localized retinal nerve fiber layer (RNFL) defects; and a normal visual field (VF). METHODS: To measure laminar vessel density (VD), the VD was measured in the intradisc region from images of the deep vascular layers of optical coherence tomography angiography (OCT-A). Conversion to NTG was defined either by a new localized RNFL defect in the superotemporal or inferotemporal region, or the presence of a glaucomatous VF defect on 2 consecutive tests according to the pattern deviation plots. MAIN OUTCOME MEASURE: Conversion to NTG. RESULTS: In total, 73 (23.8%) of the 307 NTG suspects converted to NTG during the follow-up period of 59.84 ± 12.44 months. Detection rate of microvasculature dropout (MvD) was significantly higher in NTG suspects who progressed to NTG (50.7%) than in those who did not (6.4%; P < .001). The macular deep VD (P = .006) and laminar deep VD (P = .004) were significantly lower in NTG suspects who progressed to NTG. The presence of MvD (P < .001) and lower laminar deep VD (P = .006) were significantly associated with NTG conversion. CONCLUSIONS: NTG suspects with baseline MvD or a lower laminar deep VD on OCT-A had a higher risk of conversion.

Increased Complement-Associated Inflammation in Cytomegalovirus-Positive Hypertensive Anterior Uveitis Patients Based on the Aqueous Humor Proteomics Analysis.

Herpetic anterior uveitis-associated ocular inflammation is commonly manifested with ocular hypertension and glaucoma. Relative to other viruses, cytomegalovirus (CMV) positive hypertensive anterior uveitis is associated with high recurrences of uveitis, as well as with uncontrolled intraocular pressure (IOP) and a subsequent higher requirement for future glaucoma surgery. To gain novel insights into the pathogenesis of ocular hypertension in these patients, we investigated the proteome changes of the aqueous humor (AH) derived from the CMV hypertensive anterior uveitis (CMV-HAU; n = 10) patients and non-glaucoma (cataract; n = 10) patients using liquid chromatography with tandem mass spectrometry. Among a total of 562 proteins identified, fifty and fifteen proteins were significantly elevated and decreased, respectively, in the AH of CMV-HAU patients compared to the control subjects by ≥2 fold. Gene ontology (GO) enrichment and network analyses of elevated proteins revealed that the enrichment of protein was involved in the complement activation, the humoral immune response mediated by the circulating immunoglobulins, proteolysis, and platelet degranulation. In the AH of CMV-HAU, GDF (growth/differentiation factor)-15, the inflammatory marker belonging to the TGF-ß superfamily proteins, was significantly increased, while vasorin, an anti-TGF-ß protein, levels were decreased. The trabecular meshwork cells infected with CMV exhibited a significantly increased expression of inflammatory markers. Collectively, these data indicate increased complement factor associated inflammation and humoral immunity in CMV-HAU associated ocular hypertension.

Ocular Dominance in Open-angle Glaucoma: The Shifting Trend Depending on Stage of the Disease.

PURPOSE: To investigate the characteristics and distribution of ocular dominance in primary open-angle glaucoma eyes. In addition, we tried to catch any trend of ocular dominance according to the stage of disease. METHODS: Two hundred participants with bilateral open-angle glaucoma underwent ocular dominant testing by "the hole-ina-card" test. Using optical coherence tomography, macular ganglion cell-inner plexiform layer, as well as circumpapillary retinal nerve fiber layer thickness were measured and compared according to ocular dominance. Of the two eyes of one subject, the eye with less glaucomatous damage based on mean deviation was considered to be the "better eye" in our study. RESULTS: Ocular dominance was in the right eye in 66% of the population and ocular dominance was positioned in the better eye in 70% of the population (p = 0.001 and p = 0.002, respectively). In conditional logistic regression analyses, right eye and better mean deviation were significantly associated with ocular dominance (p = 0.001 and p = 0.002, respectively). Ocular dominance tends to be present in the better eye and this trend was more apparent as the severity of glaucoma increased. Intereye comparison of visual field indices and retinal nerve fiber layer thickness between dominant versus nondominant eye become apparent in moderate and advanced glaucoma whereas it was not as apparent in early glaucoma. CONCLUSIONS: In glaucomatous eyes, laterality and severity of glaucoma determined ocular dominance. Intereye difference between nondominant and dominant eyes increased with the severity of glaucoma. Our findings suggest the existence of potential reciprocal interactions between ocular dominance and glaucoma.

Role of vasorin, an anti-apoptotic, anti-TGF-ß and hypoxia-induced glycoprotein in the trabecular meshwork cells and glaucoma.

Glaucoma, one of the leading causes of irreversible blindness, is commonly associated with elevated intraocular pressure due to impaired aqueous humour (AH) drainage through the trabecular meshwork. The aetiological mechanisms contributing to impaired AH outflow, however, are poorly understood. Here, we identified the secreted form of vasorin, a transmembrane glycoprotein, as a common constituent of human AH by mass spectrometry and immunoblotting analysis. ELISA assay revealed a significant but marginal decrease in vasorin levels in the AH of primary open-angle glaucoma patients compared to non-glaucoma cataract patients. Human trabecular meshwork (HTM) cells were confirmed to express vasorin, which has been shown to possess anti-apoptotic and anti-TGF-ß activities. Treatment of HTM cells with vasorin induced actin stress fibres and focal adhesions and suppressed TGF-ß2-induced SMAD2/3 activation in HTM cells. Additionally, cobalt chloride-induced hypoxia stimulated a robust elevation in vasorin expression, and vasorin suppressed TNF-α-induced cell death in HTM cells. Taken together, these findings reveal the importance of vasorin in maintenance of cell survival, inhibition of TGF-ß induced biological responses in TM cells, and the decreasing trend in vasorin levels in the AH of glaucoma patients suggests a plausible role for vasorin in the pathobiology of ocular hypertension and glaucoma.

Structure-Function Relationship and Vision-Related Quality of Life in Glaucoma Secondary to Anterior Uveitis: Comparison with Open Angle Glaucoma.

PURPOSE: The aim of this study is to investigate the structure-function characteristics and vision-related quality of life (VR-QoL) in uveitic glaucoma (UG) compared with open-angle glaucoma (OAG). METHOD: The study included 69 patients with UG and 138 patients with primary open angle glaucoma, normal-tension glaucoma. A 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) was used to evaluate the patients' VR-QoL. The retinal nerve fiber layer thickness (RNFLT) was measured using optical coherence tomography, and the integrated visual field (IVF) was determined using the best location method. RESULTS: There were no significant differences in the binocular IVF and mean deviation (MD) of the affected eye between the OAG and UG group, whereas the average RNFLT was significant thinner in the OAG group (p = 0.008). The patients with UG showed a significantly lower composite score and five subscales of the VFQ-25, compared with those with OAG (p < 0.05, for all, general linear model). Multivariate linear regression analyses showed that the composite score showed the strongest associations with the whole IVF (ß = 1.240, p < 0.001) in the OAG group, whereas in the UG group, a significant association was seen only with the inferior VF of the affected eye (ß = 0.596, p = 0.038). CONCLUSIONS: The eyes with UG exhibited distinctive structure-function characteristics and worse VR-QoL that differentiated them from OAG eyes.

Cytokine profile and cytoskeletal changes after herpes simplex virus type 1 infection in human trabecular meshwork cells.

Uveitis caused by herpes simplex virus (HSV)-1 is characterized by increased intraocular pressure (IOP) in the presence of anterior chamber inflammation. Despite their clinical significance, the pathogenic changes associated with HSV-1 infection in trabecular meshwork (TM) cells, the key cell type regulating IOP, have not been completely elucidated. In this study, cytokine array analyses showed a significant stepwise increase in monocyte chemoattractant protein (MCP)-1 expression upon HSV-1 infection in TM cells (p < 0.05). HSV-1 infection led to downregulation of fibrogenic molecules (fibronectin, α-smooth muscle actin, connective tissue growth factor and TGF-ß1). Notably, HSV-1 infection caused a significant increase in actin stress fibres, with a twofold increase in active RhoA, which was enhanced by treatment with TGF-ß1 and inhibited by treatment with the Rho-kinase inhibitor, Y-27632. TM cells treated with MCP-1 exhibited a dose-dependent increase in actin stress fibres compared to untreated TM cells. Our study suggests that HSV-1 infection in TM cells increases cell contractile activity rather than fibrotic changes in the extracellular matrix (ECM) components. Taken together, these observations demonstrate the enhanced expression of MCP-1 and TM cell contractile activity upon HSV-1 infection and events with potential implications for the pathobiology of abrupt IOP elevation in HSV-1 anterior uveitis.

Predicting the development of normal tension glaucoma and related risk factors in normal tension glaucoma suspects.

This study investigated the predicted risk factors for the development of normal-tension glaucoma (NTG) in NTG suspects. A total of 684 eyes of 379 NTG suspects who were followed-up for at least 5 years were included in the study. NTG suspects were those having (1) intraocular pressure within normal range, (2) suspicious optic disc (neuroretinal rim thinning) or enlarged cup-to-disc ratio (≥ 0.6), but without definite localized retinal nerve fiber layer (RNFL) defects on red-free disc/fundus photographs, and (3) normal visual field (VF). Demographic, systemic, and ocular characteristics were determined at the time of the first visit via detailed history-taking and examination of past medical records. Various ocular parameters were assess using spectral-domain optical coherence tomography and Heidelberg retinal tomography. Conversion to NTG was defined either by the presence of a new localized RNFL defect at the superotemporal or inferotemporal region on disc/fundus red-free photographs, or presence of a glaucomatous VF defect on pattern standard deviation plots on two consecutive tests. Hazard ratios were calculated with the Cox proportional hazard model. In total, 86 (12.6%) of the 684 NTG suspects converted to NTG during the follow-up period of 69.39 ± 7.77 months. Significant (P < 0.05, Cox regression) risk factors included medication for systemic hypertension, longer axial length, worse baseline VF parameters, thinner baseline peripapillary RNFL, greater disc torsion, and lamina cribrosa (LC) thickness < 180.5 µm (using a cut-off value obtained by regression analysis). Significant (P < 0.05, Cox regression) risk factors in the non-myopic NTG suspects included medication for systemic hypertension and a LC thinner than the cut-off value. Significant (P < 0.05, Cox regression) risk factors in the myopic NTG suspects included greater disc torsion. The results indicated that 12.6% of NTG suspects converted to NTG during the 5-6-year follow-up period. NTG suspects taking medication for systemic hypertension, disc torsion of the optic disc in the inferotemporal direction, and thinner LC of the optic nerve head at baseline were at greater risk of NTG conversion. Related baseline risk factors were different between myopic and non-myopic NTG suspects.

The Enhanced Inhibitory Effect of Estrogen on PD-L1 Expression Following Nrf2 Deficiency in the AOM/DSS Model of Colitis-Associated Cancer.

Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a dual role in carcinogenesis. We previously reported that Nrf2 deficiency enhances the anti-tumorigenic effect of 17ß-estradiol (E2) in an azoxymethane (AOM)/dextran sodium sulfate (DSS) model of colitis-associated cancer (CAC). Herein, we aimed to determine a possible explanation for our recent work and investigated the immune microenvironment represented by programmed death-ligand 1 (PD-L1) expression. One week after the AOM injection, mice were administered with DSS in drinking water for seven days; daily E2 injections were intraperitoneally administered during this period. The mice were sacrificed 16 weeks after AOM injection and analyzed for PD-L1 expression in the distal colon tissues using Western blotting and immunohistochemistry (IHC). Based on Western blotting results, PD-L1 expression was reduced in Nrf2 knockout (KO) female and E2-treated male mice when compared with their wild-type counterparts, following AOM/DSS treatment; this supports the association of PD-L1 expression with tumor progression. Additionally, this finding was in good agreement with the IHC results for PD-L1. Furthermore, we observed that PD-L1 is predominantly expressed in stromal cells rather than on epithelial cells in the colon. Western blotting revealed that PD-L1 expression in the colon positively correlates with expressions of inducible nitric oxide synthase (iNOS) (male, P = 0.002; female, P <0.001) and cyclooxygenase-2 (COX-2) (male, P <0.001; female, P <0.001). Collectively, our findings indicate that estrogen ameliorates the immune microenvironment represented by PD-L1 expression and enhances its effect in the absence of Nrf2.

Role of MCP-1 and IL-8 in viral anterior uveitis, and contractility and fibrogenic activity of trabecular meshwork cells.

The inflammatory chemokines, monocyte chemoattractant protein (MCP)-1 and IL-8, are produced by normal trabecular meshwork cells (TM) and elevated in the aqueous humor of primary open angle glaucoma (POAG) and hypertensive anterior uveitis associated with viral infection. However, their role in TM cells and aqueous humor outflow remains unclear. Here, we explored the possible involvement of MCP-1 and IL-8 in the physiology of TM cells in the context of aqueous outflow, and the viral anterior uveitis. We found that the stimulation of human TM cells with MCP-1 and IL-8 induced significant increase in the formation of actin stress fibers and focal adhesions, myosin light chain phosphorylation, and the contraction of TM cells. MCP-1 and IL-8 also demonstrated elevation of extracellular matrix proteins, and the migration of TM cells. When TM cells were infected with HSV-1 and CMV virus, there was a significant increase in cytoskeletal contraction and Rho-GTPase activation. Viral infection of TM cells revealed significantly increased expression of MCP-1 and IL-8. Taken together, these results indicate that MCP-1 and IL-8 induce TM cell contractibility, fibrogenic activity, and plasticity, which are presumed to increase resistance to aqueous outflow in viral anterior uveitis and POAG.

Long-term prognosis for glaucoma in patients with Posner-Schlossman syndrome.

BACKGROUND: The aim of this study is to investigate the long-term prognosis for glaucoma in patients with Posner-Schlossman syndrome (PSS). METHODS: In this retrospective case series study, a total of 98 patients with PSS from January 2014 to February 2019 were included in this study. Initial presentations and follow-up data were obtained from medical records. Vision-related quality of life (VR-QoL) was assessed using the 25-item National Eye Institute Visual Functioning Questionnaire. RESULTS: Of the 98 patients included in the study, 66 (67%) presented with glaucoma, and among them, 21 (32%) required glaucoma surgery. The mean follow-up time was 50.1 months (range 1-263 months). Iris involvement was noted in 46 (46.9%) eyes; 26 (26.5%) had sectoral iris changes and 20 (20.4%) showed diffuse iris changes. Eyes with iris involvement had a significantly higher number of acute attacks of uveitis than those without (p = 0.010). The 5-year glaucoma surgery-free interval was 77.8% according to Kaplan-Meier analysis. Significant predictors of glaucoma surgery included iris involvement (hazard ratio [HR] = 5.215; confidence interval [CI] = 1.387-19.610), highest number of anti-glaucoma agents (HR = 5.069; CI = 1.848-13.905), baseline average retinal nerve fiber layer thickness (RNFLT) thickness (HR = 0.949; CI = 0.917-0.982), and disease duration (HR = 0.977; CI = 0.957-0.996). Overall complete surgical success and qualified success at 2 years was 35.3% and 75.5%, respectively. Patients with iris involvement, glaucoma surgery, and thinner average RNFLT had significantly poorer VR-QoL (all, p < 0.05). CONCLUSIONS: Patients with PSS and glaucoma required glaucoma surgery in a high rate. Iris involvement increased the probability of surgical treatment and lowered the VR-QoL of PSS patients.

Association Between Chronic Renal Disease and the Risk of Glaucoma Development: A 12-year Nationwide Cohort Study.

Purpose: The purpose of this study was to present the results of our investigation into the risk of glaucoma development in patients with chronic renal disease (CRD). Methods: The present retrospective cohort study used the Korean National Health Insurance Service data, which consisted of 1,025,340 random subjects who were tracked from 2002 to 2013. Newly diagnosed glaucoma and CRD were included on the basis of the Korean Classification of Disease codes. The CRD group consisted of patients who received an initial CRD diagnosis between January 2003 and December 2007 as an index period (n = 3640). The control group (n = 17,971) was selected using 1:5 propensity-score matching using social and demographic factors, along with the year of enrollment. Each group subject was followed until 2013. We used multivariate Cox proportional hazard regression analysis to compare the risk of glaucoma development between the two groups. Results: Glaucoma consecutively developed in 4.3% in the CRD group and 2.8% in the control group (P < 0.0001). CRD increased the risk of glaucoma development (hazard ratio [HR] = 1.63, 95% confidence interval [CI] = 1.34-1.98] after adjusting for age, sex, comorbidities, residence, household income, and the year of enrollment. In multivariate Cox regression analysis, patients with comorbidity of hypertension, diabetes mellitus, or aged ≥ 50 years showed a significantly higher risk of glaucoma development (all P < 0.008). Conclusions: A significant association between CRD and following development of glaucoma was revealed after adjusting the potential confounding factors.

Fasting plasma glucose level and the risk of open angle glaucoma: Nationwide population-based cohort study in Korea.

BACKGROUND: The level of fasting plasma glucose (FPG) is positively associated with intraocular pressure. Diabetes causes early structural changes of retina, especially on ganglion cell layer. In this regard, the FPG level itself may also show an independent association with open angle glaucoma (OAG) development in general population. Herein, we investigate the association of the FPG level with the incidence of OAG. METHODS: Using nationally representative data from the Korean National Health Insurance System, 374,376 subjects ≥40 years of age without OAG who underwent health examinations from 2009 to 2013 were enrolled and followed to the end of 2014. Incident cases of OAG using the International Classification of Diseases 10 codes and medication information were analyzed based on the levels of FPG. RESULTS: Subjects with the highest FPG level (≥160 mg/dL), compared with the lowest level (<80 mg/dL), showed a higher hazard ratio (HR) [2.189; 95% confidence interval (CI): 1.779-2.695; P for trend < 0.001] for OAG after adjustments for age and sex. This result persisted after further adjustments for the presence of type 2 diabetes, current smoking, drinking, and exercise habits, diastolic blood pressure, body mass index (BMI), and total cholesterol level (HR: 1.588; 95% CI: 1.268-1.989; P for trend < 0.001). The positive association between the FPG level and the incidence of OAG was distinct in subjects 40-64 years of age, those with a BMI <25 kg/m2, and those without hypertension (HR 2.022; 95% CI: 1.494-2.736; P for trend <0.001: HR 1.817; 95% CI: 1.372-2.407; P for trend < 0.001: HR 1.706; 95% CI: 1.180-2.467; P for trend <0.001, respectively). CONCLUSIONS: This nationwide population-based cohort study showed that the fasting glucose was associated with an increased risk of OAG. These findings suggest that subjects with high FPG levels require special attention when screening for glaucoma.

Cardiac rehabilitation and 5-year mortality after acute myocardial infarction. Report from 11 tertiary hospitals in Korea (ETHIK Study).

BACKGROUND: The participation rate for cardiac rehabilitation (CR) remains low in some Europe and Asia including Korea. AIM: To investigate effects of CR on prognosis improvements in terms of recurrence, readmission, revascularization, and mortality rates in patients with acute myocardial infarction (AMI) in Korea. DESIGN: A retrospective cohort study. SETTING: Eleven Tertiary Hospitals In Korea (ETHIK Study). POPULATION: Data from a total of 7299 patients between January 2012 and December 2015 were collected, of which data from 7136 patients were linked to insurance claims data. In the final analysis, 6743 patients were included. METHODS: Patients who participated in the CR program while receiving outpatient treatment were classified into CR group. Those who did not participate in CR programs were classified into the non-CR group. RESULTS: Kaplan-Meier survival analyses showed five-year survival rate of 96.9% in the CR group and 93.3% in the non-CR group. The hazard ratio (HR) for total 5-year mortality in the CR group was approximately 0.41 (95% CI: 0.27-0.63) times that of the non-CR group, indicating a reduction in the risk of mortality by approximately 59% in propensity score weighted cohort of 1878 patients. The HR for major adverse cardiac events (MACE) with respect to 5-year mortality, MI recurrence, revascularization, and readmission due to cardiovascular disease in CR group was 0.96 times that of non-CR group (95% CI: 0.83-1.12), without significant difference between the two groups. CONCLUSIONS: In this study, 5-year mortality decreased by 59% in patients with AMI who had participated in CR compared to those who did not. CLINICAL REHABILITATION IMPACT: This finding should be very helpful in emphasizing the need for CR in a country like Korea where CR has not yet been actively implemented.

Enhancing Personalized Ads Using Interest Category Classification of SNS Users Based on Deep Neural Networks.

The classification and recommendation system for identifying social networking site (SNS) users' interests plays a critical role in various industries, particularly advertising. Personalized advertisements help brands stand out from the clutter of online advertisements while enhancing relevance to consumers to generate favorable responses. Although most user interest classification studies have focused on textual data, the combined analysis of images and texts on user-generated posts can more precisely predict a consumer's interests. Therefore, this research classifies SNS users' interests by utilizing both texts and images. Consumers' interests were defined using the Curlie directory, and various convolutional neural network (CNN)-based models and recurrent neural network (RNN)-based models were tested for our user interest classification system. In our hybrid neural network (NN) model, CNN-based classification models were used to classify images from users' SNS postings while RNN-based classification models were used to classify textual data. The results of our extensive experiments show that the classification of users' interests performed best when using texts and images together, at 96.55%, versus texts only, 41.38%, or images only, 93.1%. Our proposed system provides insights into personalized SNS advertising research and informs marketers on making (1) interest-based recommendations, (2) ranked-order recommendations, and (3) real-time recommendations.

Risk stratification of non-obstructive coronary artery disease for guidance of preventive medical therapy.

BACKGROUND AND AIMS: Given the potential benefit of medical therapy in patients with non-obstructive coronary artery disease (CAD), there is a need for risk stratification and treatment strategy for these patients. We aimed to develop a risk prediction model for non-obstructive CAD patients for risk stratification and guidance of statin and aspirin therapy. METHODS: From a cohort of consecutive patients who underwent coronary computed tomography angiography (CCTA) (n = 25,087), we identified patients with non-obstructive CAD of 1-49% diameter-stenosis (n = 6243) and developed a risk prediction model for 5-year occurrence of a composite of all-cause mortality, myocardial infarction, and late coronary revascularization using a derivation cohort (n = 4391). RESULTS: Age, sex, hypertension, diabetes, anemia, C-reactive protein, and the extent of non-obstructive CAD were incorporated in the prediction model (risk score 0-13, C-index = 0.716). Patients were categorized into 4 groups; risk score of 0-3 (low-risk), 4-6 (intermediate-risk), 7-9 (high-risk), and ≥10 (very high-risk). Patients with very high-risk demonstrated unfavorable outcome comparable to patients with obstructive CAD. The low-risk group exhibited favorable outcome similar to those with no CAD. While statin therapy was associated with better outcomes in high- or very high-risk group (hazard ratio, 0.62; 95% confidence interval, 0.39-0.96; p = 0.033), aspirin use was associated with an increased risk in low-risk group (hazard ratio, 2.57; 95% confidence interval, 1.34-4.90; p = 0.004). CONCLUSIONS: A dedicated risk scoring system for non-obstructive CAD using clinical factors and CCTA findings accurately predicted prognosis. According to our risk prediction model, statin therapy can be beneficial for high-risk patients, whereas aspirin can be harmful for low-risk patients.