Urine metabolomics unravel the effects of short-term dietary interventions on oxidative stress and inflammation: a randomized controlled crossover trial.

Dietary biomarkers in urine remain elusive when evaluating diet-induced oxidative stress and inflammation. In our previous study, we conducted a randomized controlled crossover trial to compare the short-term (4-weeks) effects of the balanced Korean diet (BKD) with Western diets, including the 2010 dietary guidelines for Americans (2010 DGA) and typical American diet (TAD), on various metabolic indices in obese Korean adults. Building on this work, the current research focuses on the impact of these dietary interventions on oxidative stress (d-ROMs and BAP) and inflammation (CRP, TNF-α, IL-6, IL-1ß, MCP-1) biomarkers in serum, and the concurrent urine metabolomes. Each dietary regimen was in silico and experimentally examined for their antioxidant levels using ABTS, DPPH, and FRAP assays, as well as total flavonoid (TFC) and total phenolic (TPC) contents. We assessed post-intervention variations in oxidative stress and inflammation biomarkers in serum, as well as the urine metabolite profiles for the participants (n = 48, average age: 41 years). Antioxidant contents and associated total antioxidant capacity (TAC) were significantly higher for the recommended diets (BKD and 2010 DGA) compared to TAD (p < 0.05). Butanol extracts from recommended diets (BKD and 2010 DGA) showed significantly higher antioxidant activity compared to TAD in ABTS (p < 0.01), DPPH, and FRAP (p < 0.05) assays. Consistent results were observed in total phenolic and flavonoid contents, mirroring their respective antioxidant activities. Following the intervention period, oxidative stress & inflammation markers in serum varied marginally, however, the urine metabolite profiles were clearly demarcated for the BKD and Western dietary groups (PC1 = 5.41%). For BKD group, the pre- and post-intervention urine metabolite profiles were clearly segregated (PLS2 = 2.93%). Compared to TAD, urine extracts from the recommended dietary group showed higher abundance of benzoic acid & phenolic derivatives (VIP > 0.7, p < 0.05). Metabolites associated with oxidative stress were observed higher in the urine samples from Western dietary groups compared to BKD. Urine metabolomics data delineated the post-intervention effects of three dietary interventions which corroborates the respective findings for their effects on metabolic indices.

Clinical Characteristics and Associated Factors to the Development of Glaucoma in Eyes With Myopic Optic Neuropathy.

PURPOSE: To observe the development of glaucoma in myopic eyes with and without myopic optic neuropathy (MON) and analyze associated factors to the development of typical glaucomatous damage. DESIGN: A prospective, observational, cohort study. METHODS: A total of 233 myopic eyes with no definite evidence of glaucomatous damage were included. Myopic patients without any retinal nerve fiber layer (RNFL) or visual field (VF) abnormalities were classified as myopic eyes without MON. Myopic patients with decreased RNFL at the superonasal (SN) or nasal area, and with corresponding VF defects either in the temporal or inferotemporal (IT) region were classified as myopic eyes with MON. Myopic eyes that developed glaucoma were defined by the presence of glaucomatous VF in the SN region including defects in Bjerrum area, or a new localized RNFL defect in the IT region. Disc morphological features and optic nerve head (ONH) parameters of two groups were compared. RESULTS: Myopic eyes with MON had a thinner average peripapillary RNFL thickness (P < 0.001), worse MD of the VF (P = 0.031), a higher percentage of IT VF defects (P < 0.001), smaller torsion degree (P = 0.047), and greater LCD (P = 0.022). Myopic eyes with MON who developed glaucoma had a thinner average peripapillary RNFL thickness (P = 0.009), greater PPA area (P = 0.049), greater LCD (P < 0.001), and thinner LCT (P < 0.001). Thinner baseline temporal RNFL thickness (HR, 0.956; 95% CI, 0.928-0.986; P = 0.004), greater baseline LCD (HR, 1.003; 95% CI, 1.000-1.005; P = 0.022), and greater PPA area (HR, 1.000; 95% CI, 1.000-1.003; P = 0.050) were significantly associated factors with glaucoma development. CONCLUSIONS: Myopic eyes with MON have a greater risk to develop glaucoma compared to myopic eyes without MON. Structural weakness due to myopia, especially at the temporal side of the ONH and the peripapillary sclera, increases the risk of glaucoma in myopic eyes with MON.

Regional disparities in food security and depression among single-person households in the Republic of Korea.

BACKGROUND: Single-person households constitute over 40% of all households in the Republic of Korea and are more vulnerable to food insecurity and depression than multi-person households. There is a lack of research on examining whether regional characteristics are associated with the degree of food insecurity and depression among single-person households. This study aimed to examine the regional disparities in food security and depression among single-person households in the Republic of Korea. METHODS: A total of 227,873 adults from the 2019 Korean Community Health Survey was included in the analysis. According to population density and poverty rate, the residence of the participants was classified into four regions: metropolitan areas with high population density were classified into areas with low poverty rates (Region 1) and high poverty rates (Region 2), and provinces with low population density were classified into areas with low poverty rates (Region 3) and high poverty rates (Region 4). Using a single item of household food security, those who had experienced a lack of food due to financial difficulties over the past year were classified as food insecure. Depression was measured using the Patient Health Questionnaire-9. Odds ratios and 95% confidence intervals (CI) for the risk of food insecurity and depression according to regional characteristics were calculated after adjusting for potential confounding variables. RESULTS: After adjusting for confounding variables, single-person households in regions with high population density, Regions 1 and 2, had 1.16 times (95% CI = 1.04-1.30) and 1.43 times (95% CI = 1.27-1.61) higher odds of food insecurity, respectively, compared to those in Region 4. Single-person households in regions with low poverty rates, Regions 1 and 3, had 1.54 times (95% CI = 1.34-1.77) and 1.21 times (95% CI = 1.01-1.46) higher odds of depression, respectively, than those in Region 4. Among those who lived alone, the middle-aged, having low income, receiving livelihood benefits, or having a low educational attainment had higher odds of experiencing both food insecurity and depression than their counterparts. CONCLUSIONS: As the risk of food insecurity and depression in single-person households differs according to regional characteristics, local governments need to implement policies for single-person households in consideration of these distinct characteristics.

Effect of a Pericardium Graft Inserted Adjacent to the Endplate in the Ahmed Glaucoma Valve Implantation.

The surface area of encapsulation around the Ahmed glaucoma valve (AGV) endplate is a critical factor in the surgical outcome as it is associated with the degree of IOP reduction. We investigated the surgical outcome of AGV implantation with an additional pericardium graft inserted adjacent to the endplate, with the intent of expanding the surface area of encapsulation. We enrolled 92 patients (92 eyes) who underwent AGV implantation. Of them, 50 patients underwent conventional surgery (termed the without-expansion group), and 42 received an additional an 8 × 6 mm pericardium graft inserted adjacent to the AGV endplate at the sub-Tenon's space (with-expansion). The hypertensive phase was classified as mild (>21 mmHg), moderate (>25 mmHg), and severe (>30 mmHg). Six months post-surgery, the with-expansion group exhibited a lower IOP (14.90 ± 4.27 mmHg) and lower peak IOP (22.29 ± 4.95 mmHg) than the without-expansion group (17.56 ± 4.88 mmHg and 25.06 ± 6.18 mmHg, p = 0.008 and p = 0.021, respectively). The with-expansion group exhibited a relatively low rate of moderate (16.7%) and severe (4.8%) hypertensive phases compared to the without-expansion group (40.0% and 20.0%, with p = 0.014 and p = 0.031, respectively). The additional pericardium graft was associated with a reduced occurrence of moderate hypertensive phase in both univariate and multivariate analysis logistic regression analyses (p = 0.017 and p = 0.038, respectively). Endplate surface area expansion using an additional pericardium graft reduced the occurrence of moderate and severe hypertensive phases, and lower postoperative 6-month IOP could be achieved.

Fluctuation of Intraocular Pressure and Vascular Factors Are Associated With the Development of Epiretinal Membrane in Glaucoma.

PURPOSE: To identify factors associated with the development of epiretinal membranes (ERM) in glaucoma patients. DESIGN: Multicenter, propensity-score matched, case-control study. METHODS: One hundred ninety-two eyes of 192 patients with glaucoma from the Catholic Medical Center Glaucoma Suspect Cohort Study were analyzed. We identified 64 eyes who developed ERM from the cohort, and 128 eyes without ERM were selected by propensity score matching (1:2) according to baseline age and mean deviation (MD) of the visual field (VF). Demographic, systemic, and ocular characteristics were determined at baseline. Intraocular pressure (IOP) was measured, including baseline, mean IOP, and IOP fluctuation. Early-stage ERM, defined as translucent membrane with no underlying retinal distortion, was detected by fundus photography and optical coherence tomography. Central VF progression was considered when new VF defets developed in one either or both hemifields or when there was an increase of 3 or more abnormal points within 12 points of central 10° fixation. Autonomic nervous system status was evaluated by heart rate variability. RESULTS: Patients who developed ERM were more frequently receiving medication for systemic hypertension and had higher systolic blood pressure, greater IOP fluctuation, more frequent disc hemorrhage (DH), worse VF MD, and a higher rate of central VF progression than patients without ERM. Additionally, patients with early glaucoma who developed ERM had higher rate of autonomic imbalance while patients with moderate-to-advanced glaucoma who developed ERM had greater baseline and peak IOP and worse MD of the last follow-up VF (MD < 6.0 dB). Older age (P = .048), medication for systemic hypertension (P < .001), IOP fluctuation (P < .001), presence of DH (P < .001), and worse last MD of VF (P = .033) were significantly associated with ERM in Cox proportional hazard analysis. CONCLUSIONS: Early stage of ERMs in glaucomatous eyes are significantly associated with glaucoma progression, medication of systemic hypertension, presence of DH, and IOP fluctuation. These suggest that glaucoma patients who develop early stage of ERMs should be carefully monitored in terms of IOP fluctuation, vascular factors, and glaucoma progression.

Factors Affecting Visual Acuity and Central Visual Function in Glaucoma Patients With Myopia.

PURPOSE: To investigate associated factors including structural parameters of myopia and vessel density (VD) using optical coherence tomography angiography (OCT-A) to visual acuity (VA) and central visual function in glaucoma patients with myopia. DESIGN: Retrospective cross-sectional study. METHODS: Sixty-five eyes of 60 glaucoma patients with myopia and without media opacity and retinal lesions were included. Both Swedish interactive thresholding algorithm (SITA) 24-2 and 10-2 visual field (VF) testing were performed. Superficial and deep VD in the peripapillary and macular regions were evaluated using OCT-A; retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thicknesses were measured. ß-zone peripapillary atrophy (PPA) area, disc torsion, disc-fovea distance, and peripapillary choroidal thickness were measured. Decreased VA was defined as best-corrected VA <20/25. RESULTS: The worse mean deviation of SITA 24-2, thinner GCIPL thickness, and lower deep peripapillary VD were associated with the presence of central VF damage in glaucoma patients with myopia. Thinner GCIPL thickness, lower deep peripapillary VD, and longer disc-fovea distance were associated with decreased VA in logistic regression analysis. Thinner GCIPL thickness, lower deep peripapillary VD, and larger ß-zone PPA area were associated with lower VA in linear regression analysis. Deep peripapillary VD showed a positive correlation with GCIPL thickness, whereas there was no relationship between deep peripapillary VD and RNFL thickness. CONCLUSION: Decreased VA in glaucoma patients with myopia was associated with lower deep peripapillary VD and papillomacular bundle damage. Lower deep peripapillary VD was independently associated with decreased VA along with thinner GCIPL thickness. Therefore, it could be stated that decreased VA in glaucoma patients is related to the damage location and the status of blood flow in the optic nerve head.

Angiotensin II-Related Activation of Scleral Fibroblasts and Their Role on Retinal Ganglion Cell Death in Glaucoma.

We identify the angiotensin II (AngII)-associated changes in the extracellular matrix (ECM) and the biomechanical properties of the sclera after systemic hypotension. Systemic hypotension was induced by administering oral hydrochlorothiazide. AngII receptor levels and ECM components in the sclera and biomechanical properties were evaluated based on the stress-strain relationship after systemic hypotension. The effect of inhibiting the AngII receptor with losartan was determined in the systemic hypotensive animal model and the cultured scleral fibroblasts from this model. The effect of losartan on retinal ganglion cell (RGC) death was evaluated in the retina. Both AngII receptor type I (AT-1R) and type II (AT-2R) increased in the sclera after systemic hypotension. Proteins related to the activation of fibroblasts (transforming growth factor [TGF]-ß1 and TGF-ß2) indicated that transformation to myofibroblasts (α smooth muscle actin [SMA]), and the major ECM protein (collagen type I) increased in the sclera after systemic hypotension. These changes were associated with stiffening of the sclera in the biomechanical analysis. Administering losartan in the sub-Tenon tissue significantly decreased the expression of AT-1R, αSMA, TGF-ß, and collagen type I in the cultured scleral fibroblasts and the sclera of systemic hypotensive rats. The sclera became less stiff after the losartan treatment. A significant increase in the number of RGCs and decrease in glial cell activation was found in the retina after the losartan treatment. These findings suggest that AngII plays a role in scleral fibrosis after systemic hypotension and that inhibiting AngII could modulate the tissue properties of the sclera, resulting in the protection of RGCs.

The "fruit and whole-grain" pattern is associated with a low prevalence of hypertriglyceridemia among middle and older-aged Korean adults: Using Korea National Health and Nutrition Examination Survey 2013-2018 data.

Hypertriglyceridemia is a well-known risk factor of various chronic diseases including diabetes mellitus, metabolic syndrome, obesity, and cardiovascular diseases. This study aimed to determine dietary patterns and explore the relationship between dietary patterns and hypertriglyceridemia in the Korean adult population. We utilized a cross-sectional and nationally representative survey, the Korea National Health and Nutrition Examination Survey 2013-2018 database. From 47,217 subjects who participated in the survey between 2013 and 2018, only subjects over 40 years old were included. Subjects lacking 24-h recall data and data on hypertriglyceridemia and body mass index, and who had implausible energy intake were excluded. A total of 19,806 participants' data were analyzed. Dietary data were based on 24-h recall data, and dietary patterns were derived using factor analysis. Triglyceride levels greater than 200 mg/dl were considered hypertriglyceridemia, according to the Korean Society of Lipid and Atherosclerosis. Three dietary patterns- "oil and fats & seasoning", "soybean paste and vegetable", and "fruit and whole-grain"- explained 7.9%, 6.3%, and 5.8% of variation in food intake, respectively. Comparing the lowest and highest dietary pattern score groups after adjusting for potential confounders revealed an inverse relationship between "fruit and whole-grain" dietary pattern and hypertriglyceridemia in men (odds ratio [OR]: 0.61, 95% confidence interval [CI]: 0.45-0.82, p for trend <.0001); which was only marginal in women (OR: 0.78, 95% CI: 0.58-1.07, p for trend: .628). A diet containing high proportions of fruit and whole-grain may have preventive effects on hypertriglyceridemia in middle and older aged Korean adults.

Factors Contributing to the Development of Choroidal Microvasculature Dropout in Glaucoma Suspects and Patients with Glaucoma.

We aimed to characterize and compare the occurrence of peripapillary microvasculature dropout (MvD) between glaucoma suspects and patients with glaucoma. In addition, the factors related to the development of parapapillary MvD in glaucoma suspects and patients with glaucoma were investigated. Of a total 150 eyes, 68 eyes of glaucoma suspects and 82 eyes of glaucoma patients were analyzed in this study. Univariate and multivariate logistic regression analyses were used to identify factors associated with MvD development. The classification of glaucoma patients or glaucoma suspects was not significantly associated with MvD development (beta 1.368, 95% CI, 0.718-2.608, p = 0.341). In the regression analysis of the glaucoma suspect group, greater axial length (beta 1.520, 95% CI, 1.008-2.291, p = 0.046) and baseline cup volume (beta 3.993, 95% CI, 1.292-12.345, p = 0.035) among the baseline factors and the slope of ganglion cell-inner plexiform layer (GCIPL) thickness (beta 0.027, 95% CI, 0.072-0.851, p = 0.027) and central visual field (VF) progression (beta 7.040, 95% CI, 1.781-16.306, p = 0.014) among follow-up factors were significantly associated with MvD development. In the glaucoma group, central VF progression (beta 5.985, 95% CI, 1.474-24.083, p = 0.012) and ONH depression (beta 3.765, 95% CI, 1.301-10.895, p = 0.014) among follow-up elements were observed as significant factors and the baseline factor had little relationship. MvD appears not only as a result of the progression of axonal loss of RGC in glaucoma but may also be developed due to structural changes and mechanical susceptibility of the ONH associated with baseline characteristics. Analyzing the structural susceptibility of the ONH can predict the occurrence of MvD, which can be helpful in predicting the progression of glaucoma.

Intereye structure-function relationship using photopic negative response in patients with glaucoma or glaucoma suspect.

We evaluated the intereye structure-function relationship in glaucoma patients using photopic negative response in electroretinogram analysis. Patients with confirmed glaucoma (36 eyes, 36 patients) or suspected glaucoma (19 eyes, 19 patients) were included in this study. Electroretinogram (RETI-scan) was performed with red stimulus on blue background. Intereye comparison for 55 patients was performed between better eyes and worse eyes, which were divided based on average retinal nerve fiber layer (RNFL) thickness measured using spectral-domain optical coherence tomography. In the intereye analysis, PhNR amplitude was lower in worse eyes than in better eyes (P < 0.001). The intereye difference in PhNR amplitude was significantly correlated with intereye difference in average RNFL, as well as average or minimum ganglion cell-inner plexiform layer (GCIPL) thickness (P = 0.006, 0.044, 0.001). In patients with mean deviation ≥ - 6 dB of worse eyes, the intereye difference in PhNR amplitude was significantly associated with intereye difference in average RNFL thickness or minimum GCIPL thickness (P = 0.037, 0.007), but significant correlation was not found between mean sensitivity of visual field tests and structural parameters. In conclusion, PhNR performed well with regard to intereye structure-function association in glaucoma patients, especially at the early stage.

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.

Predicting Visual Field Progression by Optical Coherence Tomography Angiography and Pattern Electroretinography in Glaucoma.

PRCIS: Reduced P50-N95 amplitude on pattern electroretinography (PERG) and the presence of microvasculature dropout (MvD) on optical coherence tomography angiography (OCT-A) at baseline were significant factors associated with visual field (VF) progression in predominantly normal tension glaucoma (NTG) patients. OBJECTIVE: We investigated the baseline demographics and ocular characteristics that predict future progression in glaucoma patients, including PERG and OCT-A parameters. METHODS: One Hundred forty eyes with open angle glaucoma that were prospectively enrolled and followed up for at least 3 years, and underwent at least 5 serial VF tests were included. Baseline PERG was performed, and N35, P50, and N95 latencies and amplitudes were obtained. Superficial vessel density at the macula and complete loss of microvasculature within the deep retinal layer of the parapapillary region (MvD) were evaluated from baseline OCT-A images. Eyes with a glaucomatous VF defect in either both hemifields within 24 points of a central 10 degrees of fixation, and with no VF abnormality in the nasal periphery outside 10 degrees of fixation, were considered to have isolated central scotoma. During follow-up, detected disc hemorrhage (DH) was recorded. Parameters associated with VF progression were determined using linear regression analysis of the mean deviation (MD) values, in combination with an event-based analysis using the Glaucoma Progression Analysis (GPA) software from the Humphrey Field Analyzer. "Likely progression" using GPA was considered to have glaucoma progression. RESULTS: Of the 140 eyes, 107 (76.4%) were NTG and 57 (40.7%) exhibited glaucoma progression as defined by Humphrey VF GPA. The MD slopes were -0.43±1.11 dB/y in the progressors and 0.59±1.27 dB/y in the nonprogressors ( P <0.001). Glaucoma patients with progression showed frequent MvD on OCT-A, isolated central scotoma, frequent DH, and reduced baseline P50-N95 amplitude compared with patients without progression. Age at diagnosis ( P =0.038) and baseline P50-N95 amplitude ( P =0.019) showed significant associations with the MD slope. The presence of MvD on OCT-A ( P <0.001) and baseline P50-N95 amplitude ( P =0.037) were significantly associated with VF progression on GPA. CONCLUSIONS: The presence of MvD and retinal ganglion cell dysfunction by PERG at baseline, DH or central scotoma were significant factors associated with VF progression in predominantly NTG patients. These patients should be monitored more closely.

Comparison between frequency-doubling technology perimetry and standard automated perimetry in early glaucoma.

This study aimed to find out the significance of the difference between frequency-doubling technology perimetry (FDT) and standard automated perimetry (SAP) in terms of the detected visual field (VF) damage, and evaluate associated factors to SAP-FDT difference in early glaucoma. Glaucoma patients in early stage (MD better than - 6.0 decibel, 96 eyes) were included in this cross-sectional study. We subtracted mean deviation (MD) and pattern standard deviation (PSD) of FDT from those of SAP, respectively. Additionally, we counted significantly depressed points of P < 5% and P < 1% on the pattern deviation probability plot of both FDT and SAP and defined eyes with significant SAP-FDT difference when the number of abnormal points were greater than 4 points on FDT. We measured lamina cribrosa depth (LCD) and lamina cribrosa curvature index (LCCI) for structural parameters of the optic nerve head from images using enhanced depth imaging of the optical coherence tomography (OCT). Peripapillary vessel density (VD) and presence of microvasculature dropout (MvD), the complete loss of choriocapillaris in localized regions of parapapillary atrophy, was evaluated using deep layer map of OCT angiography (OCT-A) for vascular parameters. Peripheral nasal step (PNS) group had an isolated glaucomatous VF defect within nasal periphery outside 10° of fixation. Parafoveal scotoma (PFS) group had an isolated glaucomatous VF defect within 12 points of a central 10˚ radius. Eyes with significant SAP-FDT difference showed higher detection of MvD on deep layer map of OCT-A, greater LCD, and greater LCCI (all P < 0.05, respectively). In logistic regression analysis, frequent presence of MvD, less presence of disc hemorrhage, and greater LCD were significantly associated with significant SAP-FDT difference. Sub-analysis was performed in eyes with PNS (50 eyes) and PFS (46 eyes). SAP-FDT difference of MD value showed positive association with peripapillary VD on deep layer of OCT-A, which was significant in eyes with PFS compared to eyes with PNS. SAP-FDT difference of PSD value showed negative association with LCCI and LCD, which was significant in eyes with PNS compared to eyes with PFS. Glaucomatous eyes classified by the difference of the detected VF damage on FDT versus SAP showed different clinical features. Greater SAP-FDT difference was significantly associated with structural parameters such as LCD and LCCI. Less SAP-FDT difference was associated with presence of disc hemorrhage and lower deep layer peripepillary VD. There is possibility to use the difference of SAP and FDT to identify associated risk factors in glaucoma patients.

Ocular and Hemodynamic Factors Contributing to the Central Visual Function in Glaucoma Patients With Myopia.

Purpose: The purpose of this study was to investigate the ocular and hemodynamic factors contributing to the central visual function in glaucoma patients with myopia. Methods: This study was a prospective observational study, which included 236 eyes of 140 patients with normal-tension glaucoma (NTG), which includes 114 eyes with mild myopia (axial length ≥24 and <26 mm) and 122 eyes with moderate-to-severe myopia (axial length ≥26 mm). Ocular characteristics were axial length and posterior pole profiles, including peripapillary atrophy (PPA) to disc area ratio, disc tilt ratio, disc torsion, and disc-foveal angle. Hemodynamic factors included standard deviation of the mean of qualified normal-to-normal intervals (SDNN) of a heart rate variability (HRV) test and vessel density (VD) parameters from optical coherence tomography angiography (OCTA). The root mean square error was estimated as a measure of the VD fluctuation. Association between ocular characteristics and VD parameters of the OCTA with the central sensitivity of the 10-degree visual field or the presence of central scotoma were analyzed. Results: Deep layer VD of the peripapillary and macular areas showed significant differences between mild and moderate-to-severe myopia (P = 0.034 and P = 0.045, respectively). Structural parameters, especially PPA to disc area ratio, had significant correlation with peripapillary VD parameters in myopic eyes. Lower SDNN value (ß = 0.924, P = 0.011), lower deep VD of the macular area (ß = 0.845, P = 0.001), and greater fluctuation of deep VD in the peripapillary area (ß = 1.517, P = 0.005) were associated with the presence of central scotoma in patients with glaucoma with myopia in multivariate logistic regression analysis. Conclusions: The structural changes by myopia, especially in the peripapillary region, affected VD parameters in myopic eyes. Lower deep VD and greater VD fluctuation in the peripapillary region showed association with central scotoma in patients with glaucoma with myopia, suggesting both structural and vascular changes by myopia may be related to central visual function in glaucoma patients with myopia.

Parapapillary Choroidal Microvasculature Dropout in Branched Retinal Vein Occlusion and Glaucoma.

Purpose: To investigate parapapillary choroidal microvasculature dropout (MvD) in branch retinal vein occlusion (BRVO) patients and compare them with open-angle glaucoma (OAG) patients using optical coherence tomography angiography (OCT-A). Methods: In total, 85 eyes of BRVO patients and 85 eyes of OAG patients, matched by age, spherical equivalent, and baseline mean deviation (MD) of the visual field (VF), were assessed. MvD was defined as complete loss of microvasculature within the choroidal layer on OCT-A. Linear regression analysis was used to obtain the slope of the MD change of the VF. Results: The presence of MvD on OCT-A was significantly more frequent in OAG eyes (63.1%) compared to BRVO eyes (31.8%). BRVO eyes with MvD showed worse baseline MD of the VF than BRVO eyes without MvD (-10.19 ± 8.50 and -7.77 ± 6.46 dB, respectively; P = 0.045). The presence of MvD was the only factor significantly associated with MD change of the VF in OAG eyes. Lower baseline average RNFL thickness, greater MvD angle, and lower macular superficial vessel density were significantly associated with MD change of the VF in BRVO eyes. Conclusions: OCT-A of the parapapillary area showed choroidal microvasculature impairment in both BRVO and OAG patients. However, the frequency was higher in glaucoma patients with similar degrees of VF damage, which suggests that the glaucomatous process contributes to MvD development. The effect of MvD on VF change was different between BRVO and OAG, suggesting that the underlying pathogenesis may also be different.

Mitochondrial Reactive Oxygen Species Elicit Acute and Chronic Itch via Transient Receptor Potential Canonical 3 Activation in Mice.

Mitochondrial reactive oxygen species (mROS) that are overproduced by mitochondrial dysfunction are linked to pathological conditions including sensory abnormalities. Here, we explored whether mROS overproduction induces itch through transient receptor potential canonical 3 (TRPC3), which is sensitive to ROS. Intradermal injection of antimycin A (AA), a selective inhibitor of mitochondrial electron transport chain complex III for mROS overproduction, produced robust scratching behavior in naïve mice, which was suppressed by MitoTEMPO, a mitochondria-selective ROS scavenger, and Pyr10, a TRPC3-specific blocker, but not by blockers of TRPA1 or TRPV1. AA activated subsets of trigeminal ganglion neurons and also induced inward currents, which were blocked by MitoTEMPO and Pyr10. Besides, dry skin-induced chronic scratching was relieved by MitoTEMPO and Pyr10, and also by resveratrol, an antioxidant. Taken together, our results suggest that mROS elicit itch through TRPC3, which may underlie chronic itch, representing a potential therapeutic target for chronic itch.

Metabolically healthy obesity and the risk of all-cause and cardiovascular disease mortality in a Korean population: a prospective cohort study.

OBJECTIVES: This study aimed to examine the association between metabolically healthy obesity and all-cause and cardiovascular disease (CVD) mortality in a Korean population. DESIGN: A prospective study. SETTING: This study used data from the Korean Genome and Epidemiology Study. PARTICIPANTS: A total of 140 137 participants were followed up over a median period of 9.2 years. Participants were categorised into four groups according to obesity (obese: body mass index ≥25 kg/m2 or non-obese) and metabolic health (metabolically unhealthy: two or more metabolic abnormalities or metabolically healthy). PRIMARY AND SECONDARY OUTCOME MEASURES: All-cause and CVD mortality of the participants until 31 December 2018 were ascertained by the National Health Insurance Service of beneficiary status of Korea. RESULTS: Metabolically unhealthy non-obese participants were at elevated risk of all-cause mortality (HR, 1.12; 95% CI, 1.04 to 1.21; p=0.0019) and CVD mortality (HR, 1.39; 95% CI, 1.17 to 1.65; p=0.0002), particularly mortality from ischaemic heart disease (IHD) (HR, 1.54; 95% CI, 1.10 to 2.14; p=0.0116) compared with metabolically healthy non-obese participants. Surprisingly, metabolically healthy obese participants were at reduced risk of all-cause mortality (HR, 0.89; 95% CI, 0.81 to 0.98; p=0.0197). Metabolically unhealthy obese participants were at elevated risk of CVD mortality (HR, 1.51; 95% CI, 1.26 to 1.81; p<0.0001) and IHD mortality (HR, 1.88; 95% CI, 1.35 to 2.63; p=0.0002) compared with metabolically healthy non-obese participants. CONCLUSIONS: In a Korean population, metabolically healthy obese participants had reduced risk of all-cause mortality compared with their non-obese counterparts, whereas metabolically unhealthy participants had elevated risk of CVD mortality, in particular mortality from IHD regardless of obesity.

The Association Between Coffee Consumption and Nonalcoholic Fatty Liver Disease in the South Korean General Population.

SCOPE: To identify the cross-sectional and prospective association between coffee consumption and nonalcoholic fatty liver disease (NAFLD) among South Korean adults. METHODS AND RESULTS: Participants are selected from the Health Examinees study. NAFLD is defined using three non-invasive indexes: fatty liver index (FLI), hepatic steatosis index, and fibrosis-4 calculator (FIB-4). In the cross-sectional analysis, higher habitual coffee consumption is associated with a lower risk for NAFLD, define using the FLI, (men, odds ratio [OR] 0.702; women, OR 0.810) compared with non-consumers. Participants who consumed coffee with sugar and creamer also have a lower risk for NAFLD, defined using the FIB-4, compared with non-coffee-consumers (men, OR 0.739; women, OR 0.807). A prospective analysis indicated that higher coffee consumption is associated with a lower incidence of NAFLD, defined using the FLI, in men (hazard ratio, 0.706). In both men and women, a lower FIB-4 index score is associated with higher coffee consumption regardless of coffee type (all p-value <0.05). CONCLUSIONS: Coffee consumption of >3 cups per day has a protective effect against the development of NAFLD to a certain extent, and a negative association is found between coffee consumed with sugar and creamer and the FIB-4 index score in South Korean adults.

Red meat and processed meat consumption and the risk of dyslipidemia in Korean adults: A prospective cohort study based on the Health Examinees (HEXA) study.

BACKGROUND AND AIMS: There has been conflicting results on the effect of red meat and processed meat intake on the dyslipidemia risk. Moreover, studies in Asian population with lower meat intake than the Western population are lacking. In this study, we aimed to investigate the association between red and processed meat consumption and the dyslipidemia risk by sex among Koreans. METHODS AND RESULTS: A total of 20,407 participants from a prospective cohort were divided into quintiles according to their red meat consumption and tertiles according to their processed meat consumption based on the validated semi-quantitative food frequency questionnaire. The Cox proportional hazards regression analysis was used to estimate the relative risk and 95% confidence interval of dyslipidemia according to red and processed meat consumption. Higher red meat consumption was associated with a 34% and 10% increased risk of hypercholesterolemia in both men and women, and further, a 58% and 17% increased risk of hyper-low-density lipoprotein cholesterolemia and dyslipidemia, in men, compared to the lowest consumption group. Higher processed meat consumption was associated with a 38% and 9% increased risk of hypercholesterolemia, 29% and 18% increased risk of hypertriglyceridemia, and 32% and 10% increased risk of dyslipidemia in both men and women, respectively, compared to the lowest consumption group. CONCLUSION: The results of the present study can provide compelling evidence on Asian population that red and processed meat consumption can lead to a higher risk of dyslipidemia.

Association of Coffee Consumption and Its Types According to Addition of Sugar and Creamer with Metabolic Syndrome Incidence in a Korean Population from the Health Examinees (HEXA) Study.

Coffee is widely consumed worldwide, and numerous studies indicate that coffee consumption may potentially affect the development of chronic diseases. Metabolic syndrome (MetS) may constitute a risk factor for chronic diseases. We aimed to prospectively evaluate the association between coffee consumption and MetS incidence. All participants were selected from the Health Examinees study. MetS was defined by the Adult Treatment Panel III criteria of the National Cholesterol Education Program. A multivariate Cox proportional hazards regression model was used to assess the relationship between coffee consumption and MetS incidence. In comparison with non-consumers, male moderate consumers (≤3 cups/day) showed a lower risk for low high-density lipoprotein cholesterol (HDL-C) (≤1 cup/day, hazard ratio (HR): 0.445, 95% confidence interval (CI): 0.254-0.780; 1-3 cups/day, HR: 0.507, 95% CI: 0.299-0.859) and high fasting blood glucose (FPG) (≤1 cup/day, HR: 0.694, 95% CI: 0.538-0.895; 1-3 cups/day, HR: 0.763, 95% CI: 0.598-0.972). Male 3-in-1 coffee (coffee with sugar and creamer) consumers also showed a lower risk for low HDL-C (HR: 0.423, 95% CI: 0.218-0.824) and high FPG (HR: 0.659, 95% CI: 0.497-0.874). These findings indicate a negative association between moderate coffee consumption and low HDL-C and high FPG among Korean male adults.