記述言語：英語   出版者・発行元：Scientific Reports  

Although a positive link between hypertension and intraocular pressure (IOP) has been suggested, the individual effects of systolic and diastolic blood pressure (SBP and DBP, respectively) on IOP remain unclear, particularly among Japanese populations. Here, we conducted a large-scale, cross-sectional study to determine individual and combined effects of SBP/DBP and hypertension on IOP. In total, 6783 Japanese people aged over 40 years underwent systemic and ophthalmological examinations, including measurements of blood pressure and IOP, conducted using non-contact tonometers. After adjusting for a priori known confounding factors, SBP and DBP levels were found to be positively correlated with IOP levels. The multivariable-adjusted odds ratio when comparing the hypertensive and normotensive groups for the prevalence of ocular hypertension was 1.88 (95% confidence interval, 1.14–3.08). When analysing the combined effects of SBP and DBP on ocular hypertension, SBP elevation had a greater effect on ocular hypertension than DBP increase. In conclusion, SBP and DBP levels and the prevalence of systemic hypertension were found to be positively associated with IOP levels and the prevalence of ocular hypertension in an ophthalmologically healthy Japanese population. Our findings suggest that systemic blood pressure control may be key for controlling IOP.

DOI： 10.1038/s41598-022-22301-1

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記述言語：英語   出版者・発行元：Scientific Reports  

Monitoring dynamic changes in near vision is important for early detection of presbyopia. This study assessed the accuracy and reliability of a new smartphone-based application, the Smart Vision Check (SVC), compared with those of a conventional device (AS-28; Kowa, Aichi, Japan), for measuring near functional visual acuity (NFVA). We enrolled 115 healthy volunteers aged ≥ 20 years with bilateral best-corrected visual acuity of ≥ 20/25. The SVC was designed for use on an Apple iPhone SE2 to measure NFVA by tapping on the orientation icon manually. Conventional FVA was measured using the AS-28 with − 2.50 D added to the best distance correction at baseline. There was no significant difference in NFVA-related measurements between the AS-28 and SVC (P > 0.05). The Spearman correlation coefficients of NFVA measurements between the two devices were over 0.60 (P < 0.001). The Bland–Altman plot indicated minimal bias with limits of agreements of ± 0.34 logMAR for NFVA with habitual correction when comparing the AS-28 and SVC. The intraclass correlation coefficient of the repeated SVC-measured NFVA was 0.915 (95% CI 0.800–0.969). In summary, the SVC has the potential to evaluate NFVA in a relatively easy manner. Applied clinically, the SVC can be useful for presbyopia screening.

DOI： 10.1038/s41598-022-27011-2

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記述言語：英語   出版者・発行元：Scientific Reports  

This population-based cross-sectional study was performed to determine the mean corneal endothelial cell density (ECD), coefficient of variation (CV), and hexagonality (HEX), and their associations with myopia in Japanese adults living in Chikusei city. Of 7109 participants with available data, 5713 (2331 male and 3382 female) participants were eligible for analysis. After assessing the relationship between participant characteristics and spherical equivalent refraction (SER), the association of SER with the abnormal value of ECD (< 2000 cells/mm), CV (≥ 0.40), and HEX (≤ 50%) were determined using the logistic regression models adjusting for potential confounders (age, intraocular pressure, keratometric power, height, and antihypertensive drug use). In male participants, there was no statistically significant relationships between SER and endothelial parameters. In female participants, compared to emmetropia, SER ≤ − 6 D had significantly higher odds ratio (OR) of having the abnormal value of CV (OR = 2.07, 95% confidence interval [CI] 1.39–3.10) and HEX (OR = 2.04, 95% CI 1.29–3.23), adjusted for potential confounders, indicating that the high myopia was associated with the abnormal values of CV and HEX. Further adjustment for contact lenses wear partly attenuated these associations. Association between the SER and ECD was not detected.

DOI： 10.1038/s41598-021-85617-4

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記述言語：英語   出版者・発行元：Eye and Contact Lens  

Objective:To investigate the relation between body mass index (BMI) and dry eye disease (DED).Methods:We conducted a cross-sectional questionnaire-based survey in 85,264 Japanese men and women aged 40 to 74 years who participated in the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT Study). Dry eye disease was defined as the presence of severe symptoms or clinical diagnosis. A multivariable logistic regression model was used to estimate the odds ratios (ORs) of DED associated with BMI and their two-sided 95% confidence intervals (CIs). We adjusted for age, cohort area, visual display terminal time, smoking status, alcohol intake, education status, income status, as well as history of hormone replacement therapy for women.Results:Prevalence of DED was 23.4% (n = 19,985; 6,289 men, 13,696 women). Higher BMI was correlated with a lower prevalence of DED in a dose-response fashion, with an adjusted OR of DED (95% CI) per 1 kg/m2increment of BMI of 0.98 (95% CI: 0.97-0.99) for men and 0.97 (95% CI: 0.97-0.98) for women.Conclusions:This large population-based study showed an inverse relationship between BMI and prevalence of DED in a Japanese population. Underestimation of DED is warned, especially for participants with high BMI.

DOI： 10.1097/ICL.0000000000000814

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記述言語：英語   出版者・発行元：Ocular Surface  

Purpose: To investigate whether and how unhealthy sleep habits (i.e., the frequency of difficulty falling or staying asleep, and the frequency of waking up tired) and the duration of sleep are related to the prevalence of dry eye disease (DED) in a general population. Methods: This study included a total of 106,282 subjects aged 40–74 years who participated in a baseline survey of the Japan Public Health Center-based Prospective Study for the Next Generation. DED was defined as the presence of clinically diagnosed DED or severe symptoms. Multivariable-adjusted logistic regression models were used to assess the relationships of various components of sleep status with DED. Results: Higher frequencies of having difficulty falling or staying asleep, and waking up tired were significantly related to increased DED in both sexes (Ptrend<0.001). Compared with those with 8 h/day of sleep, shorter sleepers had an increased prevalence of DED in both sexes, although DED was increased among men who slept ≥10 h/day. By comparing participants with the greatest vs. the least difficulty of falling asleep, the multivariable-adjusted odds ratios (95% confidence interval [CI]) were 2.23 (95% CI, 1.99–2.49) for men and 1.91 (95% CI, 1.76–2.07) for women. When analyzed separately, the magnitude of each relationship was stronger with severe DED symptoms than with clinically diagnosed DED. Conclusions: Sleep deprivation and poor sleep quality were significantly related to DED in a Japanese population.

DOI： 10.1016/j.jtos.2021.04.001

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記述言語：英語   出版者・発行元：Ophthalmology Retina  

Purpose: To determine the relationship of choroidal thickness with the early stages of age-related macular degeneration (AMD) and their disease features in a Japanese population. Design: Cross-sectional survey. Participants: A total of 1293 Japanese persons 65 to 86 years of age residing in the Saku area who underwent eye screening as part of the Japan Public Health Center-based Prospective Study. Methods: Comprehensive ophthalmic assessment included fundus photography, measurement of intraocular pressure, and determination of refractive status. OCT with enhanced depth imaging mode was performed and subfoveal choroidal thickness was assessed. Multinomial logistic regression models were used to assess the relationships of choroidal thickness with the early stages of AMD, namely early AMD and intermediate AMD, and their disease features, after adjustment for potential confounders. Main Outcome Measures: Relationship of choroidal thickness with early AMD, intermediate AMD, and their disease features. Results: Of 1293 potential participants, 901 (mean age, 73.2 years) had choroidal thickness data, fundus photographs of sufficient quality, and no concomitant retinal disease (including 5 with late AMD). Mean choroidal thickness was 246.1 μm, 15.1% had early AMD, and 9.0% had intermediate AMD. After adjustment for age, gender, and refractive status, choroidal thickness was associated positively with presence of intermediate AMD (for each 1- standard deviation [SD] μm increase: odds ratio [OR], 1.43; 95% confidence interval [CI], 1.13–1.81), whereas no significant association was found with presence of early AMD. Among intermediate AMD features, choroidal thickness was associated positively with presence of AMD pigmentary abnormalities (associated with at least medium drusen; for each 1-SD μm increase: OR, 2.21; 95% CI, 1.42–3.42), whereas no significant association was found with presence of large drusen alone. In addition, among large drusen subtypes, choroidal thickness was associated positively with presence of pachydrusen (for each 1-SD μm increase: OR, 1.53; 95% CI, 1.10–2.13). Furthermore, exploratory analysis revealed that choroidal thickness was associated positively with presence of non-AMD pigmentary abnormalities (for each 1-SD μm increase: OR, 1.92; 95% CI, 1.31–2.18). Conclusions: Choroidal thickness seems to be associated with the pathology of intermediate AMD and its features in Asians.

DOI： 10.1016/j.oret.2020.09.001

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記述言語：日本語   出版者・発行元：日本転倒予防学会  

DOI： 10.11335/tentouyobou.7.3_23

CiNii Research

記述言語：英語   出版者・発行元：日本疫学会  

Background: Although the consumption of vegetables and fruits is reported to influence the risk of cataract, no prospective study of this association from Asia has yet appeared. Here, we investigated the association between vegetable and fruit intake and cataract incidence in a large-scale population-based prospective cohort study in Japan. Methods: This study included 32,387 men and 39,333 women aged 45-74 years who had no past history of cataract and had completed a dietary questionnaire of the Japan Public Health Center-based Prospective Cohort Study. The incidence of cataract was evaluated after 5-year follow-up. We used multiple logistic regression analyses to estimate the sex-specific odds ratios (ORs), with adjustment for confounding factors. Results: We identified 1,836 incident cataracts in 594 men and 1,242 women. In men, the OR for cataract was decreased with higher intake of vegetables (ORQ5 vs Q1, 0.77; 95% confidence interval [CI], 0.59-1.01; Ptrend across quartile categories = 0.03) and cruciferous vegetables (ORQ5 vs Q1, 0.74; 95% CI, 0.57-0.96; Ptrend = 0.02). In contrast, the OR for cataract was increased with higher intake of vegetables among women (ORQ5 vs Q1, 1.28; 95% CI, 1.06-1.53; Ptrend = 0.01). Green and yellow vegetable and fruit intake were not associated with cataract in either sex. Conclusions: This study suggests that vegetables may reduce the risk of cataract in men, but not in women.

DOI： 10.2188/jea.je20190116

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記述言語：英語   出版者・発行元：British Journal of Ophthalmology  

Background/aims The aim of our study was to investigate the associations between driving self-regulation and glaucoma severity, and between driving self-regulation and glaucomatous visual field (VF) defect patterns. Methods In 247 patients with primary open-angle glaucoma included in this prospective observational study, a battery of ophthalmic examination was performed, including visual acuity (VA) and VF. Integrated binocular VF was constructed and mean of total deviation (mTD) values in four sectors was calculated (mTDsup-peri, mTDsup-centre, mTDinf-peri and mTDinf-centre). In addition, all participants answered seven questions regarding their avoidance in driving. (1) at night, (2) in rain, (3) in fog, (4) on freeways, (5) lane changing, (6) at high speed and (7) close to the car in front. The associations between these driving behaviours and 10 variables (age, gender, best VA, worst VA, the four sectorial average TD values, years holding a driver's licence and distance driven per week) were analysed using the generalised linear model with binomial distribution, followed by the model section method using the corrected Akaike information criterion. Results As a result of the model selection, it was suggested that deterioration of mTDsup-peri was associated with (1) avoiding driving at night and (2) avoiding driving in rain. On the other hand, mTDsup-centre was related to (3) avoiding driving in fog. Conclusion Damage in visual function was related with driving behaviours in patients with glaucoma.

DOI： 10.1136/bjophthalmol-2019-315187

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記述言語：英語   出版者・発行元：Scientific Reports  

The study subjects were residents of Chikusei city, Japan, aged 40 years or older who attended annual health check-up programs and participated in the JPHC-NEXT Eye Study which performed non-mydriatic fundus photography of both eyes. The relationship of glaucomatous fundus changes such as optic disc cupping (cup to disc ratio ≥ 0.7) and retinal nerve fiber layer defect (NFLD) with the presence of epiretinal membrane (ERM) were examined cross-sectionally. A total of 1990 persons gave consent to participate in this study in 2013. The overall prevalence of ERM was 12.9%. Of these, 1755 had fundus photographs of sufficient quality and no history of intraocular surgery (mean age: 62.3 ± 10.0 years). After adjusting for age, sex and refractive error, NFLD was positively associated with the presence of ERM (odds ratio [OR]: 2.48; 95% confidence interval [CI]: 1.24, 4.96; P = 0.010), but optic disc cupping was not (OR: 1.33; CI: 0.71, 2.48; P = 0.37). The results did not necessarily suggest an association between glaucoma and ERM, but indicated an association between NFLD and ERM.

DOI： 10.1038/s41598-019-57260-7

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記述言語：英語   出版者・発行元：Scientific Reports  

The management of intra-ocular pressure (IOP) is important for glaucoma treatment. IOP is recognized for showing seasonal fluctuation. Glaucoma patients can be at high risk of dry eye disease (DED). We thus evaluated seasonal variation of IOP with and without DED in glaucoma patients. This study enrolled 4,708 patients, with mean age of 55.2 years, who visited our clinics in Japan from Mar 2015 to Feb 2017. We compared the seasonal variation in IOP (mean ± SD) across spring (March–May), summer (June–August), fall (September–November), and winter (December–February). IOP was highest in winter and lowest in summer, at 14.2/13.7 for non-glaucoma without DED group (n = 2,853, P = 0.001), 14.5/13.6 for non-glaucoma with DED group (n = 1,500, P = 0.000), 14.0/13.0 for glaucoma without DED group (n = 240, P = 0.051), and 15.4/12.4 for glaucoma with DED group (n = 115, P = 0.015). Seasonal variation was largest across the seasons in the glaucoma with DED group. IOP was also inversely correlated with corneal staining score (P = 0.000). In conclusion, the seasonal variation was significant in most of study groups and IOP could tend to be low in summer.

DOI： 10.1038/s41598-020-70606-w

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記述言語：英語   出版者・発行元：Scientific Reports  

Although a meta-analysis previously suggested a positive relationship between diabetes and intraocular pressure (IOP), the interrelationships among diabetes, IOP, and other ocular biometric parameters remain unclear. The present study investigated the relationships of diabetes, haemoglobin A1c (HbA1c), and serum glucose with IOP and ocular hypertension (IOP > 21 mmHg) in non-glaucomatous Japanese adults living in Chikusei City. Diabetes was defined as a self-reported history of diabetes, the use of antidiabetic medication, or HbA1c levels ≥6.5%. Among 6,786 enrolled participants aged 40 years and above, 734 were classified as diabetic (10.8%). After adjusting for several confounders, the IOP values were significantly higher in participants with diabetes than in those without diabetes (14.4 ± 0.1 vs. 13.9 ± 0.1 mmHg, P < 0.001) and were also significantly increased in those with elevated HbA1c and serum glucose levels (both P < 0.001). Moreover, diabetes was significantly related to ocular hypertension (multivariable-adjusted odds ratio, 1.75; 95% confidence interval, 1.09–2.81; P < 0.05). The positive influence of diabetes with ocular hypertension was consistent even after adjustment for central corneal thickness. In conclusion, diabetes, elevated HbA1c, and increased serum glucose are significant contributing factors for elevated IOP.

DOI： 10.1038/s41598-020-62135-3

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記述言語：英語  

DOI： 10.1111/cga.12367

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出版者・発行元：金原出版  

DOI： 10.18888/ga.0000001664

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記述言語：英語   出版者・発行元：Investigative Ophthalmology and Visual Science  

PURPOSE. To evaluate fear of falling using the Fall Efficacy Scale-International (FES-I) in glaucoma patients and investigate its association with glaucomatous visual field loss. METHODS. This study included 273 patients (160 men and 113 women, average age 64.2 years) with primary open-angle glaucoma. Participants were requested to answer the FES-I questionnaire, translated into Japanese, in a face-to-face interview. The relationship between total FES-I score and the following variables was analyzed using multivariable linear regression: age, sex, better and worse best corrected visual acuity, total deviation (TD) in four visual field areas, body mass index (BMI), minutes walked per day, history of diabetes mellitus, history of systemic hypertension, number of previous falls. RESULTS. Univariate analysis suggested that total FES-I score increased with age and in woman, whereas other variables were not significantly associated with total FES-I score. However, age (coefficient, 0.23; standard error [SE], 0.04; P < 0.001), sex (coefficient, 1.79 for women; SE, 0.84; P = 0.034), mean TD in the inferior central area (coefficient, 0.92; SE, 0.22; P <0.001), and mean TD in the inferior peripheral area (coefficient, –0.86; SE, 0.21; P < 0.001) were included in the optimal model for total FES-I score. CONCLUSIONS. Inferior peripheral visual field damage and preserved inferior central visual field sensitivity were associated with increased fear of falling assessed with FES-I in glaucoma.

DOI： 10.1167/iovs.61.3.52

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記述言語：英語   出版者・発行元：Ocular Surface  

Purpose: This population-based, cross-sectional study was performed to assess the influence of life-style modalities, including physical activity, sedentary behaviors, and visual display terminal (VDT) use, on the prevalence of dry eye disease (DED). Methods: The study included a total of 102,582 participants aged 40–74 years, from the Japan Public Health Center-based Prospective Study for the Next Generation, a large nationwide prospective ongoing Japanese cohort study. Logistic regression analyses were used to investigate the relationship of total and leisure-time physical activity, duration of sedentary behaviors, and VDT use (hours/day) with DED. Results: Among 47,346 men and 55,236 women, 25,234 (8315 males and 16,919 females) cases of DED were documented. Total physical activity was significantly related to decreased DED in both sexes; for the highest vs. lowest total physical activity quartiles, the multivariable-adjusted odds ratios (ORs) for DED were 0.90 (95% confidence interval [CI], 0.84–0.97; Ptrend<0.03) and 0.91 (95% CI, 0.86–0.95; Ptrend<0.001) for men and women, respectively. Conversely, prolonged sedentary behaviors and VDT use had significantly higher prevalence of DED in both sexes (Ptrend<0.001). Notably, the favorable effect of total physical activity on decreased DED in women was more prevalent with prolonged VDT use (≥2 h/day) (Pinteraction<0.01). In men, the duration of VDT use or sitting was a significant modifier of the inverse relationship between leisure-time physical activity and DED (Pinteraction<0.05). Conclusions: Physical inactivity, prolonged sedentary behaviors, and use of VDT were related to increased susceptibility to DED among middle-aged to older Japanese adults.

DOI： 10.1016/j.jtos.2019.09.007

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記述言語：英語   出版者・発行元：Ophthalmology  

Purpose: To determine the association of retinal thickness with cognitive function in Japanese persons. Design: Cross-sectional, population-based survey. Participants: A total of 1293 Japanese persons aged 65 to 86 years who resided in the Saku area in the Japan Public Health Center–Based Prospective Study participated in the eye and mental health screening. Methods: Participants underwent comprehensive ophthalmic assessment, including fundus photography, measurement of intraocular pressure, and determination of refraction status. We assessed the thickness of the macular retinal nerve fiber layer (mRNFL), ganglion cell-inner plexiform layer (GC-IPL), and ganglion cell complex (GCC, which includes the retinal nerve fiber layer and GC-IPL), and the full thickness in the macula and peripapillary retinal nerve fiber layer (ppRNFL) using spectral-domain (SD) OCT. Cognitive tests consisted of the Mini-Mental State Examination, Wechsler Memory Scale Revised logical memory I/II subtest, clock drawing test, and Clinical Dementia Rating Scale. These were used to designate the participants in the following 3 groups: Normal, those with mild cognitive impairment (MCI), and those with dementia. Multivariable logistic regression models were used to analyze associations between retinal thickness and cognitive function after adjusting potential confounding factors. Main Outcome Measures: Association of retinal thickness with cognitive function. Results: Among the 1293 potential subjects, 114 were excluded for a diagnosis of depression, 64 were excluded for retinal disease, and 140 were excluded for scanning errors or suboptimal OCT images. The remaining 975 participants (mean age, 73.2 years) were included in this analysis. Significant differences were found in the 3 groups in all layers and GCC thickness, but not in ppRNFL thickness. After adjusting for age, sex, educational status, and refraction, full macular thickness and GCC thickness were inversely associated with the presence of dementia, but ppRNFL thickness was not. Furthermore, GC-IPL, GCC, and full macular thicknesses were all associated with the presence of dementia in the inferior sectors. Conclusions: Macular thickness was associated with the presence of dementia, but ppRNFL was not. Our results suggest that OCT measurements of the macula could be superior to those of the ppRNFL in assessing neurodegenerative changes and a potentially useful diagnostic biomarker of cognitive function.

DOI： 10.1016/j.ophtha.2019.05.021

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記述言語：英語   出版者・発行元：Diagnostics  

Purpose: To evaluate seasonal variation in intraocular pressure (IOP) with and without short tear break-up time (SBUT, BUT ≤5 s) since dry eye and IOP are known to have seasonal variation. Methods: This study enrolled 176 patients who visited one of six eye clinics, in Japan, four times for IOP measurement, in every season. The mean patient age was 67.9 years, including 79 males. Participants were divided into four groups based on the presence of glaucoma and/or SBUT and we compared the seasonal variation in IOP (winter and summer) among the four groups. Results: The IOP (mmHg) in winter and summer, respectively, was 12.8 ± 3.7 and 12.8 ± 3.1 for non-glaucoma patients without SBUT (n = 47, p = 0.964), 14.8 ± 3.4 and 13.3 ± 3.4 for non-glaucoma patients with SBUT (n = 57, p < 0.001), 14.3 ± 3.2 and 14.1 ± 3.4 for glaucoma patients without SBUT (n = 36, p = 0.489), and 13.3 ± 3.0 and 11.6 ± 2.9 for glaucoma with SBUT (n = 36, p < 0.001). Seasonal variation was largest across the seasons in the glaucoma with the SBUT group, and the magnitude of seasonal variation correlated with BUT (β = 0.228, p = 0.003). Conclusions: Seasonal variation tended to be larger in patients with SBUT than those without SBUT.

DOI： 10.3390/diagnostics10020124

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記述言語：英語   出版者・発行元：Journal of Clinical Medicine  

The increasing prevalence of high myopia has been noted. We investigated the epidemiological characteristics and the related factors of high myopia in a Japanese adult population. Japan Public Health Center-Based Prospective Study for the Next Generation (JPHC-NEXT) Eye Study was performed in Chikusei-city, a rural area in mid-east Japan, between 2013 and 2015. A cross-sectional observational analysis was conducted to investigate prevalence and related factors of high myopia. A total of 6101 participants aged ≥40 years without a history of ocular surgeries was included. High myopia was defined as a spherical equivalent refraction of ≤−6.00 diopters according to the American Academy of Ophthalmology. Potential high myopia-related factors included intraocular pressure (IOP), corneal structure, corneal endothelial cell density, age, height, body mass index, heart rate, blood pressure, biochemical profile, and current history of systemic and ocular disorders. The odds ratios of high myopia were estimated using the logistic regression models adjusted for the associated factors. The prevalence of high myopia was 3.8% in males and 5.9% in females with a significant difference. Age was inversely associated, IOP was positively associated, and none of other factors were associated with high myopia in both sexes. In conclusion, only age and IOP were associated with high myopia in this community-based sample.

DOI： 10.3390/jcm8111788

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出版者・発行元：金原出版  

DOI： 10.18888/ga.0000001134

CiNii Research

記述言語：英語   出版者・発行元：Ocular Surface  

Purpose: To investigate whether social support and social trust are associated with DED. Methods: Cross-sectional data from the Japan Public Health Center-Based Prospective Study for the Next Generation (JPHC-NEXT) were used. Subjects are 96,227 Japanese men and women aged 40 to 74. Data from respondents included information on DED, social support and social trust. DED was defined as the presence of clinically diagnosed DED or severe symptoms. Social support was measured by emotional support and tangible support. Social trust was measured by level of general trust in others. Multiple logistic regression analysis was conducted to assess the association of social determinants for DED. Results: Individuals with high levels of social support and social trust were less likely to have severe symptoms of DED and clinically diagnosed DED (P for trend < 0.001 in both cases). Those with the highest levels of social support and social trust were least likely to have DED (odds ratios [OR] = 0.64 [0.61–0.67], 95% confidence interval [CI] = 0.63 [0.60–0.67] for severe symptoms of DED; OR = 0.88 [0.83–0.93] and 0.85 [0.80–0.91] for clinically diagnosed DED). Conclusions: High levels of social support and social trust were associated with a lower prevalence of DED.

DOI： 10.1016/j.jtos.2019.01.005

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出版者・発行元：金原出版  

DOI： 10.18888/ga.0000001054

CiNii Research

出版者・発行元：金原出版  

DOI： 10.18888/ga.0000001022

CiNii Research

記述言語：英語   出版者・発行元：PLoS ONE  

Purpose Prostaglandin analogues (PG) reduce intra-ocular pressure by enhancing uveoscleral flow at the ciliary body, which controls accommodation via the ciliary muscle. We investigated the effect of PG on accommodation and presbyopia progression in glaucoma patients. Methods We conducted a clinic-based, retrospective, cross-sectional study. Inclusion criteria were bilateral phakic patients aged 40–69 years with best corrected visual acuity better than 20/ 30. Exclusion criteria were any disease affecting vision other than glaucoma and history of ocular surgery. Subjects with no prescription or vision-affecting disease served as controls (n = 260). The glaucoma patients were prescribed eye drops containing 0.005% latanoprost for more than six months (n = 23). We measured the binocular near add power at a distance of 30 cm in both groups and compared the results using Kaplan-Meier analysis. Results The mean age (± SD) of the control subjects was 51.5 ± 5.2 years and 39% were male. Similarly, the glaucoma patients had a mean age of 51.0 ± 7.2 years and 39% were male. There were no significant differences in age, gender, intra-ocular pressure, spherical equivalent, astigmatism, or anisometropia between groups. Survival analysis indicated that the glaucoma patients in this study reached the endpoint (near add power of +3.00 D) significantly earlier than control patients (P = 0.0001; generalized Wilcoxon test). Conclusions Exacerbation of presbyopia progression in glaucoma patients is a potential side effect of latanoprost eyedrops.

DOI： 10.1371/journal.pone.0211631

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記述言語：日本語   出版者・発行元：公益社団法人 日本リハビリテーション医学会  

<p>白内障，緑内障，加齢黄斑変性などの眼疾患は視機能障害をきたす眼疾患である．白内障は手術により視機能を回復できるものの，加齢黄斑変性では完全に視機能を回復することは難しく，また緑内障の視野障害/視力障害は不可逆性である．安全な歩行や体勢の維持に正常な視機能が不可欠であることは想像しやすい．眼疾患の多くは加齢がリスク要因であり，多くの高齢者が眼疾患による視機能障害とともに日常生活を送っていると思われる．転倒は高齢者の不慮の事故死の第2位の原因であり，眼疾患の予防により転倒予防が可能であるかは大きな問題である．本報告では白内障，緑内障，加齢黄斑変性と転倒の関係について述べた過去の報告を総括したいと考えている．</p>

DOI： 10.2490/jjrmc.55.921

CiNii Research

記述言語：英語   出版者・発行元：BMC Ophthalmology  

Background: The aim of this study, which included a baseline cross-sectional study and a 3-year follow-up prospective study, was to investigate the association between glaucomatous visual field damage and driving cessation in subjects with primary open-angle glaucoma (POAG). Methods: A total of 211 POAG subjects divided into 3 groups according to POAG severity (mild, moderate, or severe) in the better eye were enrolled along with 148 control subjects; subjects were asked about changes in their driving status. In the 3-year follow-up study, 185 of the POAG subjects and 80 of the controls annually reported their driving status. Adjusted odds ratios and 95% confidence intervals for the prevalence and incidence of driving cessation were estimated with a multiple logistic regression model. Results: In the original cross-sectional study, 11/148 (7%) members of the control group reported having given up driving over the previous 5 years; the corresponding figures for the mild POAG, moderate POAG, and severe POAG groups were 9/173 (5%), 0/22 (0%), and 5/16 (31%), respectively (p = 0.001, Fisher's exact test), with severe POAG found to be associated with driving cessation after adjustment for age, gender, systemic hypertension, and diabetes mellitus (odds ratio 11.52 [95% CI 2.87-46.35], ref. control, p = 0.001). In the follow-up study, the proportions of subjects who ceased driving were 1/80 (1.3%) in the control group, 8/152 (5.3%) in the mild POAG group, 5/22 (22.7%) in the moderate POAG group, and 2/11 (18.2%) in the severe POAG group (p = 0.001, Fisher's exact test). Moderate POAG and severe POAG in the better eye were found to be associated with driving cessation after adjustment for age, gender, systemic hypertension, and diabetes mellitus (moderate POAG in the better eye: odds ratio 37.7 [95% CI 3.7-383.8], ref. control, p = 0.002, and severe POAG in the better eye: odds ratio 52.8 [95% CI 3.5-797.0], ref. control, p = 0.004). Conclusion: Moderate and Severe POAG in the better eye is associated with driving cessation.

DOI： 10.1186/s12886-018-0788-0

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PubMed

記述言語：英語   出版者・発行元：BMC Ophthalmology  

Background: To investigate the relationship between clinical risk factors, including visual field (VF) defects and visual acuity, and a fear of falling, among patients with primary open-angle glaucoma (POAG). Methods: All participants answered the following question at a baseline ophthalmic examination: Are you afraid of falling? The same question was then answered every 12 months for 3 years. A binocular integrated visual field was calculated by merging a patient's monocular Humphrey field analyzer VFs, using the 'best sensitivity' method. The means of total deviation values in the whole, superior peripheral, superior central, inferior central, and inferior peripheral VFs were calculated. The relationship between these mean VF measurements, and various clinical factors, against patients' baseline fear of falling and future fear of falling was analyzed using multiple logistic regression. Results: Among 392 POAG subjects, 342 patients (87.2%) responded to the fear of falling question at least twice in the 3 years study period. The optimal regression model for patients' baseline fear of falling included age, gender, mean of total deviation values in the inferior peripheral VF and number of previous falls. The optimal regression equation for future fear of falling included age, gender, mean of total deviation values in the inferior peripheral VF and number of previous falls. Conclusion: Defects in the inferior peripheral VF area are significantly related to the development of a fear of falling.

DOI： 10.1186/s12886-018-0706-5

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記述言語：英語   出版者・発行元：npj Aging and Mechanisms of Disease  

SIRT3 is a key regulator of mitochondrial reactive oxygen species as well as mitochondrial function. The retina is one of the highest energy-demanding tissues, in which the regulation of reactive oxygen species is critical to prevent retinal neurodegeneration. Although previous reports have demonstrated that SIRT3 is highly expressed in the retina and important in neuroprotection, function of SIRT3 in regulating reactive oxygen species in the retina is largely unknown. In this study, we investigated the role of retinal SIRT3 in a light-induced retinal degeneration model using SIRT3 knockout mice. We demonstrate that SIRT3 deficiency causes acute reactive oxygen species accumulation and endoplasmic reticulum stress in the retina after the light exposure, which leads to increased photoreceptor death, retinal thinning, and decreased retinal function. Using a photoreceptor-derived cell line, we revealed that reactive oxygen species were the upstream initiators of endoplasmic reticulum stress. Under SIRT3 knockdown condition, we demonstrated that decreased superoxide dismutase 2 activity led to elevated intracellular reactive oxygen species. These studies have helped to elucidate the critical role of SIRT3 in photoreceptor neuronal survival, and suggest that SIRT3 might be a therapeutic target for oxidative stress-induced retinal disorders.

DOI： 10.1038/s41514-017-0017-8

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PubMed

記述言語：英語   出版者・発行元：BMC Ophthalmology  

Background: The aim of the study is to investigate risk factors for future falls in subject with primary open angle glaucoma (POAG). Methods: All participants answered the following question at their baseline ophthalmic examination: Have you had any falls in the last year? (Yes/No). All study participants answered the same question every 12 months for 3 years. The means of total deviation values in the whole, superior peripheral, superior central, inferior central, and inferior peripheral visual fields (VF) were calculated. The relationship between these mean VF measurements, and various clinical factors against patients' future falls was analyzed using multiple linear regression. Results: Two-hundred ninety four POAG patients answered the baseline and follow-up fall questionnaires over a period of three years. Among 294 subjects, 69 patients experienced a fall during the three-year follow-up. History of falls at baseline (coefficient = 1.22), history of fear of falling at baseline (0.53), best corrected visual acuity in the worse eye (7.37), prevalence of diabetes mellitus (0.60), prevalence of systemic hypertension (0.53) were selected in the optimal model. Conclusions: Visual acuity in the worse eye, history of falls, fear of falling, diabetes mellitus, and systemic hypertension are risk factors for falling in subjects with POAG.

DOI： 10.1186/s12886-017-0613-1

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記述言語：英語   出版者・発行元：PLoS ONE  

Purpose: Prior studies suggested that glaucoma patients suffer worse dry eye and mood and sleep disorders than non-glaucoma subjects. Prostaglandin analogues are first-line therapy for glaucoma, inducing few instillation problems and sufficient pressure-reduction effects. This study compared dry eye, sleep quality, and mood status between glaucoma patients receiving prostaglandin monotherapy and non-glaucoma subjects. Methods: This cross-sectional study evaluated 1520 patients (579 males and 941 females) for glaucoma status and dry eye-related symptoms (dryness, eye fatigue, photophobia, pain, blurring) and signs (Schirmer test, tear break-up time, corneal staining scores). Of the total cohort, 93 patients were also evaluated by Pittsburgh sleep quality index (PSQI) and hospital anxiety and depression score (HADS). Inclusion criteria were consecutive patients ≥ 51 years of age and best-corrected visual acuity ≥ 20/25. Glaucoma patients included those treated with prostaglandin or a fixed combination including prostaglandin. Exclusion criteria were history of ocular surgery within one month. Data were analyzed using the chi-square or Mann-Whitney U tests, at 5% significance. Results: There were no significant differences in dry eye-related signs and symptoms between the control (n = 1431, mean age of 66.9 years) and glaucoma groups (n = 89, 67.9 years). The psychiatric sub-analysis of the control (n = 61, 66.2 years) and glaucoma groups (n = 32, 67.3 years) revealed mean scores of 5.02 ± 3.10 and 5.16 ± 3.46 for PSQI (normal range ≤ 5), 9.47 ± 5.61 and 9.42 ± 7.36 for HADS (normal range ≤ 10), 4.84 ± 3.22 and 4.71 ± 3.45 for anxiety (normal range ≤ 5), and 4.63 ± 3.05 and 4.71 ± 4.40 for depression (normal range ≤ 5), respectively, without statistical significance. Conclusions: Our results were comparable between glaucoma patients on prostaglandin monotherapy and non-glaucoma subjects for dry eye-related clinical manifestations, sleep quality, and mood status.

DOI： 10.1371/journal.pone.0188534

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出版者・発行元：三輪書店  

DOI： 10.11477/mf.5001201054

CiNii Research

記述言語：英語   出版者・発行元：Translational Vision Science and Technology  

Purpose: We predict the likelihood of a future motor vehicle collision (MVC) from visual function data, attitudes to driving, and past MVC history using the penalized support vector machine (pSVM) in subjects with primary open-angle glaucoma (POAG). Methods: Patients with POAG were screened prospectively for eligibility and 185 were analyzed in this study. Self-reported MVCs of all participants were recorded for 3 years from the baseline using a survey questionnaire every 12 months. A binocular integrated visual field (IVF) was calculated for each patient by merging a patient’s monocular Humphrey Field Analyzer (HFA) visual fields (VFs). The IVF was divided into six regions, based on eccentricity and the right or left hemifield, and the average of the total deviation (TD) values in each of these six areas was calculated. Then, the future MVCs were predicted using various variables, including age, sex, 63 variables of 52 TD values, mean of the TD values, visual acuities (VAs), six sector average TDs with (predpenSVM_all) and without (predpenSVM_basic) the attitudes in driving, and also past MVC history, using the pSVM method, applying the leave-one-out cross validation. Results: The relationship between predpenSVM_basic and the future MVC approached significance (odds ratio = 1.15, [0.99–1.29], P = 0.064, logistic regression). A significant relationship was observed between predpenSVM_all and the future MVC (odds ratio = 1.21, P = 0.0015). Conclusions: It was useful to predict future MVCs in patients with POAG using visual function metrics, patients’ attitudes to driving, and past MVC history, using the pSVM. Translational Relevance: Careful consideration is needed when predicting future MVCs in POAG patients using visual function, and without driving attitude and MVC history.

DOI： 10.1167/tvst.6.3.14

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記述言語：英語   出版者・発行元：Journal of Glaucoma  

Purpose: We evaluated the association between functional visual acuity (FVA) and visual fields in glaucoma patients. Patients and Methods: Forty-seven patients with glaucoma were enrolled (28 men, 19 women; mean age: 65.2±7.3 y; range: 38 to 82 y), and their 94 eyes were studied. Inclusion criteria were having glaucomatous optic disc abnormalities, visual field loss with glaucoma, and a best-corrected visual acuity in each eye of 1.0 (equivalent to Snellen 20/20) or better. FVA and visual maintenance ratio evaluations were made with an AS-28 FVA measurement system. To assess FVA, Landolt optotypes were displayed sequentially for 2 seconds each, and the size was reduced when the patient gave the correct answer. Humphrey automated perimetry was performed to determine mean deviation (MD) and foveal threshold, and these values were used to evaluate associations between FVA and visual field. Mean and SD was calculated for all parameters for statistical comparisons. Results: The MD values were -10.1±7.3 (range: -29.87 to 1.05) dB, and foveal thresholds were 34.8±2.8 (mean±SD, range: 25 to 41) dB. The logMAR FVA values were 0.14±0.17 (range: -0.14 to 0.73), and the visual maintenance ratios were 0.92±0.06 (range: 0.73 to 1.02). Linear regression analysis of the logMAR FVA values and visual field gave a MD of R=0.26 (P=0.01), and a foveal threshold of R=0.51 (P<0.001). The corresponding figures for the visual maintenance ratio and visual field were MD: R=0.25 (P=0.01) and foveal threshold: R=0.48 (P<0.001). Conclusions: The results of the current study showed that the logMAR FVA and visual maintenance ratio correlated moderately with foveal threshold.

DOI： 10.1097/IJG.0000000000000585

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記述言語：英語   出版者・発行元：Medicine (United States)  

Intravitreal ranibizumab (IVR) has been approved for treating diabetic macular edema (DME), and is used in daily clinical practice. However, the treatment efficacies of IVR monotherapy in real-world clinical settings are not well known. The medical records of 56 eyes from 38 patients who received their first IVR for DME between April 2014 and March 2015, and were retreated with IVR monotherapy as needed with no rescue treatment, such as laser photocoagulation, were retrospectively reviewed. The clinical course, best-corrected visual acuity (BCVA), and fundus findings at baseline, before the initial IVR injection, and at 12 months, were evaluated. Twenty-five eyes from 25 patients (16 men; mean age 68.7±9.8 years) who received IVR in the first eye, or unilaterally, without any other treatments during follow-up were included. After 12 months, mean central retinal thickness (CRT), which includes edema, was reduced (P=.003), although mean BCVA remained unchanged. There was a negative correlation between individual changes in BCVA (r=-.57; P=.003) and CRT (r=-.60; P=.002) at 12 months compared with baseline values. BCVA changes were greater in individuals with a history of pan-retinal photocoagulation at baseline (P=.026). After adjusting for age and sex, CRT improvement >100mm at 12 months was associated with a greater CRT at baseline (OR 0.87 per 10mm [95% CI 0.72-0.97]; P=.018) according to logistic regression analyses; however, better BCVA and CRT at 12 months were associated with a better BCVA (r=0.77; P<.001) and lower CRT (r=0.41; P=.039) at baseline, respectively, according to linear regression analyses. IVR monotherapy suppressed DME, and the effects varied according to baseline conditions. Eyes that had poorer BCVA or greater CRT, or a history of pan-retinal photocoagulation at baseline, demonstrated greater improvement with IVR monotherapy. In contrast, to achieve better outcome values, DME eyes should be treated before the BCVA and CRT deteriorate. These findings advance our understanding of the optimal use of IVR for DME in daily clinical practice, although further study is warranted.

DOI： 10.1097/MD.0000000000006459

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記述言語：英語   出版者・発行元：The Keio Journal of Medicine  

The aim of this study was to evaluate the effects of transcorneal electrical stimulation in subjects with primary open-angle glaucoma. Five eyes of four male subjects with primary open-angle glaucoma (average age: 52.25 ± 14.68 years) were enrolled. The subjects underwent transcorneal electrical stimulation every 3 months according to the following procedure. A Dawson-Trick-Litzkow electrode was placed on the cornea, and biphasic electric current pulses (10 ms, 20 Hz) were delivered using a stimulator (BPG-1, BAK Electronics) and a stimulus isolation unit (BSI-2). A current that evoked a phosphene that the subject perceived in the whole visual area was delivered continuously for 30 min. Humphrey visual field testing was performed after every third transcorneal electrical stimulation treatment. Changes in mean deviation (MD) values were evaluated with a linear regression model. Transcorneal electrical stimulation was performed 18.2 ± 9.4 times over a period of 49.8 ± 23.0 months. The average pretranscorneal electrical stimulation intraocular pressure, best corrected visual acuity, and MD values were 11.8 ± 1.79 mmHg, 0.14 ± 0.19 (logMAR) and −17.28 ± 6.24 dB, respectively. No significant differences were observed in intraocular pressure before and after transcorneal electrical stimulation. However, there was a significant positive linear relationship between changes in MD values and the number of transcorneal electrical stimulation treatments (R2 = 0.176, P = 0.005, Spearman correlation R = 0.294, P = 0.008). Transcorneal electrical stimulation treatment may improve glaucomatous visual field defects in subjects with primary open-angle glaucoma. Large-scale studies are necessary to confirm these preliminary findings.

DOI： 10.2302/kjm.2017-0015-oa

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CiNii Research

記述言語：英語   出版者・発行元：Journal of Ophthalmology  

Purpose. To evaluate efficacy and safety of a trabecular micro-bypass stent system when used as the sole procedure in Japanese patients with medically uncontrolled primary open-angle glaucoma (POAG). Design. Prospective nonrandomized interventional pilot study. Methods. Ten eyes of 10 Japanese patients with medically uncontrolled POAG taking three ocular hypotensive medications were treated using only the implantation of two iStent trabecular micro-bypass stents. Each patient continued to take the same ocular hypotensive medications used preoperatively throughout the study. Intraocular pressure (IOP) and endothelial cell density (ECD) were determined at baseline and at 1, 3, and 6 months postoperatively. Best-corrected visual acuity (BCVA) was measured at baseline and 6 months after surgery. Results. Mean IOP was 22.0±3.0 mmHg at baseline and 16.9±3.6 mmHg at 6 months, which represented a mean reduction of 5.1 mmHg or 23.2%. No significant changes were observed in the ECD and BCVA. Complications that occurred during the early postoperative period included hyphema, peripheral anterior synechiae, and occlusion of the stent by the iris. Conclusion. Implantation of two trabecular micro-bypass stents as the sole procedure in Japanese POAG patients effectively reduced IOP and exhibited a favorable safety profile. Clinical Trials Registration number is UMIN000004002.

DOI： 10.1155/2017/9605461

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記述言語：英語   出版者・発行元：PLoS ONE  

Purpose: To identify the incidence rate of motor vehicle collisions (MVCs) in patients with no ocular pathology other than primary open-angle glaucoma (POAG) and determine the putative risk factors for MVCs in this group of patients. Methods: We designed a prospective cohort study across three centers utilizing a consecutive sampling method to identify all patients with POAG between the ages of 40 and 80 years old. Patients with glaucoma were consecutively screened for eligibility. All study participants answered a questionnaire about motor vehicle collisions at baseline, and answered the questionnaire again every 12 months (± 1 month) after baseline for three years. A binocular integrated visual field was calculated for each patient by merging a patient's monocular Humphrey Field Analyzer (HFA) visual fields (VFs), using the 'best sensitivity' method. Patients with incident MVCs were defined as the "MVC+" group and patients without incident MVCs were defined as the "MVC-" group. Adjusted odds ratios for the incidence of MVCs were estimated with a logistic regression model. Results: One hundred and ninety-one Japanese POAG patients were analyzed in this study. The age of the participants was 63.7 ± 10.2 [mean ± standard deviation]. A total of 28 participants experienced a MVC during the follow up period of three years (4.9% per year). Ten patients (5.2%) experienced a MVC in the first year, 13 patients (6.8%) in the second year, and 11 patients (5.8%) in the third year (some patients experienced multiple MVCs over different years). Best corrected visual acuity in the worst eye was significantly worse in the MVC+ group (0.03 ± 0.01, mean ± standard deviation, LogMar) compared with the MVC-group (0.01 ± 0.003, p = 0.01), and was the only variable identified as a significant predictor of future MVCs in the multiple logistic regression model [odds ratio: 1.2, 95% confidence interval (CI): 1.1 to 1.4]. Conclusion: Deterioration in visual acuity in the worst eye is a risk factor for future MVCs in patients with POAG.

DOI： 10.1371/journal.pone.0166943

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出版者・発行元：Natural Product Communications  

The rhizomes and roots of Valeriana fauriei were extracted with 80% aqueous ethanol. This extract was found to exhibit potent inhibitory effects on fat accumulation in 3T3-L1 murine adipocytes. After several steps of chromatographic purification, we succeeded in identifying monovalerianester A as an inhibitor of fat accumulation. Thus, monovalerianester A and the crude extract of the rhizomes and roots of V. fauriei may have therapeutic potential for the treatment of obesity.

DOI： 10.1177/1934578x1501000801

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記述言語：英語   出版者・発行元：PLoS ONE  

Purpose: To investigate the relationship between visual function and the risks of falling and injurious falls in subjects with primary open angle glaucoma (POAG) Methods: Questionnaires were conducted in 365 POAG patients to assess history of falls and falls with injury and general patient health. Structural equation modeling (SEM) was used to investigate the relationship between visual function, as measured by a patient's binocular integrated visual field and visual acuity (VA), general health and the risks of falling and injurious falls. Results: Among the 365 subjects, 55 subjects experienced falls in the past year. A significant difference was observed in worse-eye VA between the faller and non-faller groups (p = 0.03). SEM of fallers obtained a Root Mean Square Error of Approximation (RMSEA) of 0.035 and a Comparative Fit Index (CFI) of 0.99. The 95% confidence intervals (CI) of regression coefficients from this model suggested better VA and worse VA were significant risk factors for falling. Among the 55 fallers, 22 subjects experienced an associated injury. There was a significant difference in gender between the non-injurious and injurious faller groups (p = 0.002). SEM of injurious fallers obtained a RMSEA of 0.074 and a CFI of 0.97. In this SEM model, the 95% CI of regression coefficients suggested gender and average total deviation values in the lower peripheral visual field were significant risk factors for an injurious fall. Conclusions: This study suggests that worse-eye and better-eye VAs are associated with falls. Furthermore, patients with inferior visual field loss and females were found to be at greater risk of injurious falls.

DOI： 10.1371/journal.pone.0129316

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記述言語：英語   出版者・発行元：Optometry and Vision Science  

Purpose. To confirm that subjects with primary open-angle glaucoma (POAG) who avoid driving in high-risk situations are less likely to be involved in motor vehicle collisions (MVCs) than those who do not. Methods. This study evaluated 252 consecutive Japanese aged between 40 and 85 years with POAG. All participants were requested to answer a questionnaire on their driving habits, including self-restriction in driving at night, in rain, in fog, on freeways, and lane changing, and history of MVCs. Those who reported restricting their driving in one or more ways constituted the self-restriction group, and those who reported no self-restriction made up the no-restriction group. The prevalence of MVCs and the crash rate (number of MVCs/10,000 km driven) were compared between the two groups. The association between prevalence of MVCs and the number of driving self-restrictions was also evaluated. Results. The association between driving self-restriction and MVCs was observed among the male subjects, not among the female subjects. Among the male subjects, the prevalence of MVCs was significantly higher in the no-restriction group than in the self-restriction group (no-restriction group, 33/107 = 30.8%; self-restriction group, 9/66 = 13.6%, p = 0.01). The crash rate was also significantly higher in the no-restriction group (no-restriction group, 1.4 T 0.8; self-restriction group, 0.4 T 0.3, average T SE, p = 0.01). No restriction was significantly associated with MVCs (multivariable-adjusted odds ratios, 2.43 [95% confidence interval, 1.03 to 5.73]). The number of driving self-restrictions was also associated with MVCs (multivariable- adjusted odds ratios, 0.41 [95% confidence interval, 0.18 to 0.99], per one increment of self-restriction). Conclusions. Driving self-restriction may be associated with a reduced prevalence of MVCs in men with POAG.

DOI： 10.1097/OPX.0000000000000493

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記述言語：英語   出版者・発行元：Journal of Ophthalmology  

Purpose. This study examined the association between the severity of visual field defects and the prevalence of motor vehicle collisions (MVCs) in subjects with primary open-angle glaucoma (POAG). Methods. This is a cross-sectional study. Japanese patients who have had driver's licence between 40 and 85 years of age were screened for eligibility. Participants answered a questionnaire about MVCs experienced during the previous 5 years. Subjects with POAG were classified as having mild, moderate, or severe visual field defect. We evaluated associations between the severity of POAG and the prevalence of MVCs by logistic regression models. Results. The prevalence of MVCs was significantly associated with the severity of POAG categorized by worse eye MD (control: 30/187 = 16.0%; mild POAG: 17/92 = 18.5%; moderate POAG: 14/60 = 23.3%; severe POAG: 14/47 = 29.8%; P = 0.025, Cochran-Armitage trend test). Compared to the control group, the adjusted OR for MVC prevalence in subjects with mild, moderate, or severe POAG in the worse eye was 1.07 (95% CI: 0.55 to 2.10), 1.44 (95% CI: 0.68 to 3.08), and 2.28 (95% CI: 1.07 to 4.88). Conclusions. There is a significant association between the severity of glaucoma in the worse eye MD and the prevalence of MVCs.

DOI： 10.1155/2015/497067

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記述言語：英語   出版者・発行元：PLoS ONE  

Purpose: To investigate the relationship between visual field (VF) damage and history of motor vehicle collisions (MVCs) in subjects with primary open-angle glaucoma (POAG). Methods: MVC history and driving habits were recorded using patient questionnaires in 247 POAG patients. Patients' driving attitudes (carefulness) were estimated using Rasch analysis. The relationship between MVC outcomes and 52 total deviation (TD) values of integrated binocular VF (IVF), better and worse visual acuities (VAs), age and gender was analyzed using principal component analysis and logistic regression. Results: 51 patients had the history of MVCs. Significant difference was observed between patients with and without history of MVCs only for: better VA, a single TD value in the superior-right VF, and the typical distance driven in a week (unpaired t-test, p=0.002, 0.015 and 0.006, respectively). There was not a significant relationship between MVCs and mean deviation (MD) of IVF (p=0.41, logistic regression). None of the principal components were significantly correlated with MVC outcome (p>0.05, polynomial logistic regression analysis). There was a significant relationship between IVF MD and Rasch derived Person parameter (R2=0.023, p=0.0095). There was also a significant positive relationship between MVCs and the distance driven in a week (p=0.005, logistic regression). Conclusions: In this study of POAG patients, MVCs were not related to central binocular VF damage. These results suggest the relationship between visual function and driving is not straightforward, and careful consideration should be given when predicting patients' driving ability using their VF.

DOI： 10.1371/journal.pone.0115572

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記述言語：英語   出版者・発行元：British Journal of Ophthalmology  

Background/aims: To study the initial characteristics and response to intravitreal ranibizumab (IVR) treatment of age-related macular degeneration (AMD). Methods: We reviewed the clinical records of 141 eyes in 141 AMD patients who received monthly IVR for 3 months and thereafter pro re nata (PRN) injections for 9 months as the first treatment for AMD. Patients whose best corrected visual acuity (BCVA) worsened at month 12, and those with increased exudative fundus findings after IVR or an increased central retinal thickness of more than 100 μm at month 12, were considered to be non-responders as judged by BCVA and fundus findings, respectively. Non-responders' initial characteristics were analysed using logistic regression models. Results: 14.9% of eyes were non-responders as judged by BCVA, and 17.0% were non-responders as judged by fundus findings. Initial fibrovascular pigment epithelial detachment (PED) (OR 22.9, 95% CI 2.61 to 201) and serous PED (OR 4.12, 95% CI 1.08 to 15.8) were associated with non-response as judged by BCVA. Initial fibrovascular PED (OR 33.5, 95% CI 2.95 to 381) and type 1 choroidal neovascularization (OR 6.46, 95% CI 1.39 to 30.0) were associated with non-response, as judged by fundus findings. Conclusions: Although most AMD responded to IVR, non-responders had initial clinical characteristics that might be informative for managing their treatment.

DOI： 10.1136/bjophthalmol-2013-304670

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記述言語：英語   出版者・発行元：PLoS ONE  

Purpose: To design a mathematical model that can predict the relationship between the ganglion cell complex (GCC) thickness and visual field sensitivity (VFS) in glaucoma patients. Design: Retrospective cross-sectional case series. Method: Within 3 months from VFS measurements by the Humphrey field analyzer 10-2 program, 83 eyes underwent macular GCC thickness measurements by spectral-domain optical coherence tomography (SD-OCT). Data were used to construct a multiple logistic model that depicted the relationship between the explanatory variables (GCC thickness, age, sex, and spherical equivalent of refractive errors) determined by a regression analysis and the mean VFS corresponding to the SD-OCT scanned area. Analyses were performed in half or 8 segmented local areas as well as in whole scanned areas. A simple logistic model that included GCC thickness as the single explanatory variable was also constructed. The ability of the logistic models to depict the real GCC thickness/VFS in SAP distribution was analyzed by the χ² test of goodness-of-fit. The significance of the model effect was analyzed by analysis of variance (ANOVA). Results: Scatter plots between the GCC thickness and the mean VFS showed sigmoid curves. The χ² test of goodness-of-fit revealed that the multiple logistic models showed a good fit for the real GCC thickness/VFS distribution in all areas except the nasal-inferior-outer area. ANOVA revealed that all of the multiple logistic models significantly predicted the VFS based on the explanatory variables. Although simple logistic models also exhibited significant VFS predictability based on the GCC thickness, the model effect was less than that observed for the multiple logistic models. Conclusions: The currently proposed logistic models are useful methods for depicting relationships between the explanatory variables, including the GCC thickness, and the mean VFS in glaucoma patients. © 2014 Shiba et al.

DOI： 10.1371/journal.pone.0104126

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記述言語：英語   出版者・発行元：Clinical and Experimental Ophthalmology  

Background: To elucidate the biological effects of blocking fluorescent light on the retina using specific blocking materials. Methods: Seven- to 8-week-old BALB/c mice were divided into three groups and placed in one of the three boxes: one blocked ultraviolet and violet wavelengths of light (violet blockade), one blocked ultraviolet, violet, blue and some other visible wavelengths (blue-plus blockade), and one allowed most visible light to pass through (control). They were then exposed to a white fluorescent lamp for 1h at 5.65E-05mW/cm2/s. After treatment, the electroretinogram, retinal outer nuclear layer thickness and retinal outer segment length were measured. In addition, retinal apoptotic cells were quantified by TdT-mediated dUTP nick-end labelling assay and c-Fos messenger RNA, and protein levels were measured by real-time reverse-transcription polymerase chain reaction and immunoblot analyses, respectively. Results: The blue-plus blockade group retained a significantly better electroretinogram response following light exposure than the control or violet blockade groups. The blue-plus blockade group also exhibited greater outer nuclear layer thickness and greater outer-segment length, and fewer apoptotic cells after light exposure than the other groups. The c-Fos messenger RNA and protein levels were substantially reduced in the blue-plus blockade group and reduced to a lesser extent in the violet blockade group. Conclusions: The blockade of blue plus additional visible wavelengths of light was most effective in protecting the retina from light-induced damage. The blockade of violet light alone was also effective in reducing intracellular molecular responses, but these effects were not sufficient for attenuating retinal degeneration. © 2014 Royal Australian and New Zealand College of Ophthalmologists.

DOI： 10.1111/ceo.12253

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PubMed

記述言語：英語   出版者・発行元：PLoS ONE  

Recent progress in molecular analysis has revealed the possible involvement of multiple inflammatory signaling pathways in pathogenesis of retinal degeneration. However, how aberrant signaling pathways cause tissue damage and dysfunction is still being elucidated. Here, we focus on 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK), originally recognized as a key regulator of energy homeostasis. AMPK is also modulated in response to inflammatory signals, although its functions in inflamed tissue are obscure. We investigated the role of activated AMPK in the retinal neural damage and visual function impairment caused by inflammation. For this purpose, we used a mouse model of lipopolysaccharide-induced inflammation in the retina, and examined the effects of an AMPK activator, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR). During inflammation, activated AMPK in the neural retina was decreased, but AICAR treatment prevented this change. Moreover, the electroretinogram (ERG) a-wave response, representing photoreceptor function, showed visual dysfunction in this model that was prevented by AICAR. Consistently, the model showed shortened photoreceptor outer segments (OSs) with reduced levels of rhodopsin, a visual pigment concentrated in the OSs, in a post-transcriptional manner, and these effects were also prevented by AICAR. In parallel, the level of activated NF-κB increased in the retina during inflammation, and this increase was suppressed by AICAR. Treatment with an NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ) preserved the rhodopsin level during inflammation, suppressing NF-κB. These findings indicated that AMPK activation by AICAR and subsequent NF-κB inhibition had a protective effect on visual function, and that AMPK activation played a neuroprotective role during retinal inflammation. © 2014 Kamoshita et al.

DOI： 10.1371/journal.pone.0103013

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PubMed

記述言語：英語   出版者・発行元：Molecular Brain  

Background: Retinitis pigmentosa (RP) is an inherited human retinal disorder that causes progressive photoreceptor cell loss, leading to severe vision impairment or blindness. However, no effective therapy has been established to date. Although genetic mutations have been identified, the available clinical data are not always sufficient to elucidate the roles of these mutations in disease pathogenesis, a situation that is partially due to differences in genetic backgrounds. Results: We generated induced pluripotent stem cells (iPSCs) from an RP patient carrying a rhodopsin mutation (E181K). Using helper-dependent adenoviral vector (HDAdV) gene transfer, the mutation was corrected in the patient's iPSCs and also introduced into control iPSCs. The cells were then subjected to retinal differentiation; the resulting rod photoreceptor cells were labeled with an Nrl promoter-driven enhanced green fluorescent protein (EGFP)-carrying adenovirus and purified using flow cytometry after 5 weeks of culture. Using this approach, we found a reduced survival rate in the photoreceptor cells with the E181K mutation, which was correlated with the increased expression of endoplasmic reticulum (ER) stress and apoptotic markers. The screening of therapeutic reagents showed that rapamycin, PP242, AICAR, NQDI-1, and salubrinal promoted the survival of the patient's iPSC-derived photoreceptor cells, with a concomitant reduction in markers of ER stress and apoptosis. Additionally, autophagy markers were found to be correlated with ER stress, suggesting that autophagy was reduced by suppressing ER stress-induced apoptotic changes. Conclusion: The use of RP patient-derived iPSCs combined with genome editing provided a versatile cellular system with which to define the roles of genetic mutations in isogenic iPSCs with or without mutation and also provided a system that can be used to explore candidate therapeutic approaches. © 2014 Yoshida et al.; licensee BioMed Central Ltd.

DOI： 10.1186/1756-6606-7-45

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PubMed

記述言語：英語   出版者・発行元：東北ジャーナル刊行会  

Dry eye disease (DED) is defined as a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear-film instability, with potential damage to the ocular surface. It is thought to be associated with reduced quality of life (QOL). The aim of the present study was to investigate the effects of DED on health-related QOL in Japanese university sedentary office workers who are daily users of visual display terminal. In this study, 163 university staff (99 male and 64 female), aged 23-69 years, served as study subjects. Subjects were asked to answer the following three questions. (1) How often do your eyes feel dry? (2) How often do your eyes feel irritated? (3) Have you ever been diagnosed by a clinician as having dry eye syndrome? Sixty-eight subjects who answered "constantly," "often", or "sometimes" to both questions 1 and 2 were classified as the DED Group, and the remaining 95 were defined as the Non-DED Group. QOL was assessed by the SF-36 questionnaire, which consisted of 36 items to produce three summary scores, namely, mental, physical, and role/social component summary scores. For males, the DED Group had significantly lower scores than the Non-DED Group for mental component summary (MCS) (P = 0.005). In multiple regression analysis, MCS scores were adversely related to DED in males (P = 0.015). DED was associated with worsened QOL. DED should be regarded as a factor that can lead to deterioration of mental health.

DOI： 10.1620/tjem.233.215

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CiNii Research

記述言語：英語   出版者・発行元：Journal of Neuroscience  

(Pro)renin receptor [(P)RR], also known as Atp6ap2, has attracted growing attention as a key molecule for tissue renin-angiotensin system (RAS). In addition to its role in tissueRASactivation, Atp6ap2/(P)RR was originally identified as an accessory subunit for vacuolar H+-ATPase (v-ATPase), which is a multisubunit proton pump involved in diverse and fundamental cellular physiology. In this study, to elucidate the physiological function of Atp6ap2/(P)RR during retinal development in mammals, we used Cre-LoxP system to generate photoreceptor-specific conditional knock-out (CKO) mice, and revealed a critical role of Atp6ap2/(P)RR in photoreceptor development. Deletion of photoreceptor Atp6ap2/(P)RR did not affect retinal cell differentiation, but led to laminar disorganization around the outer nuclear layer together with severe dysfunction of photoreceptor cells. In the CKO mice, cell adhesion and polarity molecules, some of which were colocalized with Atp6ap2/(P)RR at the apical edge of the wild-type developing retina, were substantially dispersed together with mislocalization of retinal progenitor cells apart from the apical surface. Among theses molecules, coimmunoprecipitation using retinal homogenates and ATP6AP2/(P)RR-transfected cells showed that Atp6ap2/(P)RR interacted with partitioning defective 3 homolog (PAR3) protein, which is known to function in the Par-atypical protein kinase C (aPKC) system. Furthermore, yeast two-hybrid assays demonstrated direct molecular interaction between ATP6AP2/(P)RR and PAR3. Our present data revealed the novel function of Atp6ap2/ (P)RR required for laminar formation during retinal development. We propose that this cellular activity associated with the Par-aPKC system, in addition to the v-ATPase function and tissue RAS activation, is the third biological role of Atp6ap2/(P)RR. © 2013 the authors.

DOI： 10.1523/JNEUROSCI.1362-13.2013

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記述言語：英語   出版者・発行元：British Journal of Ophthalmology  

Aim: To evaluate the association between the magnitude of relative afferent pupillary defect (RAPD) and the laterality of visual fields in glaucoma patients using pupillography. Methods: Evaluations were made with an RAPDx (Konan Medical USA, Irvine, California, USA), which is designed to analyse pupil responses to multiple colour stimuli (white, red, green, blue, and yellow) at multiple controlled stimulus intensities. Humphrey automated perimetry (SITA standard 30-2) was performed to determine mean deviations (MDs), which were used to evaluate associations between MD differences (better eye MD - worse eye MD) and RAPDx amplitude and latency measurements in pupil response to multiple colour stimuli. Results: 58 glaucoma patients (35 men, 23 women; mean age: 62.6±12.8 years; range 28-88 years) were enrolled. The MD values were -2.00±3.1 (range -9.64 to 2.33) dB in the better eyes and -8.17±7.1 (range -26.33 to 1.07) dB in the worse eyes. The differences in MD values (better eye MD - worse eye MD) were 6.17±6.1 (range 0.05-26.41) dB. The results of linear regression analysis between the log-scaled RAPD amplitudes and differences in MD values were as follows: white: R2=0.45 (p<0.001), red: R2=0.18 (p=0.002), green: R2=0.30 (p<0.001), blue: R2=0.29 (p<0.001), and yellow: R2=0.32 (p<0.001). The log-scaled RAPD latencies and the differences in MD values were: white: R2=0.17 (p=0.001), red: R2=0.03 (p=0.22), green: R2 =0.01 (p=0.52), blue: R2=0.1 (p=0.02), and yellow: R2=0.05 (p=0.11). Conclusions: The log-scaled RAPD amplitudes correlated moderately with the differences in MD values, but the log-scaled RAPD latencies showed a weaker correlation. Stimulation with white light produced the strongest correlation with differences in MD values.

DOI： 10.1136/bjophthalmol-2013-303825

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記述言語：英語   出版者・発行元：Investigative Ophthalmology and Visual Science  

Purpose. To determine if glaucomatous visual field defect severity is associated with fear of falling. Methods. This is a cross-sectional study. A total of 387 consecutive subjects with POAG were enrolled in this study along with 293-ocular disease-free control subjects, who were screened at the same institutions. We defined mild POAG as MD of -6 dB or better, moderate POAG as MD of -6 to -12 dB, and severe POAG as MD of -12 dB or worse in the better eye. All participants were requested to answer a questionnaire on fear of falling. Associations between POAG severity and the prevalence of fear of falling were evaluated with the Cochran-Armitage trend test. Multivariable factors including age-adjusted odds ratios (ORs) for the prevalence of fear of falling and 95% confidence intervals (CIs) were evaluated with logistic regression models. Results. The p revalence of fear of falling was 35/293 (11.9%) in the control group, 38/313 (12.1%) in the mild POAG group, 12/48 (25.0%) in the moderate POAG group, and 6/26 (23.1%) in the severe POAG group, and the trend was statistically significant (P =0.028 Cochran-Armitage trend test). The adjusted ORs for prevalence in the mild, moderate, and severe POAG groups compared with that in the control group were 1.44 (95% CI: 0.83-2.51), 2.33 (95% CI: 1.00-5.44), and 4.06 (95% CI: 1.39-11.90), respectively. Conclusions. Among patients with POAG, the severity of visual field defects is associated with fear of falling. (http://www.umin.ac.jp/ctr/index.htm number, UMIN000005574.). © 2013 The Association for Research in Vision and Ophthalmology, Inc.

DOI： 10.1167/iovs.13-12079

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記述言語：英語   出版者・発行元：Japanese Journal of Ophthalmology  

Purpose: To investigate the long-term effects of postoperative flat anterior chamber (FAC) development on outcomes following trabeculectomy with mitomycin C. Methods: This was a retrospective cohort study. Data on 383 consecutive patients (383 eyes) who underwent trabeculectomy at our institution between 1999 and 2009 were followed up. Patients who developed FAC after trabeculectomy and patients with maintained anterior chamber were evaluated. The primary outcome variable was the success of the initial trabeculectomy, which was defined at 3 different levels by the achievement of the following intraocular pressure (IOP)-related criteria without secondary IOP-lowering surgery: (a) IOP ≤ 12 mmHg and ≤30 % reduction in IOP from the preoperative level; (b) IOP ≤ 16 mmHg and ≤20 % reduction in IOP; and (c) IOP ≤ 21 mmHg. The hazard ratios (HRs) for the failure of trabeculectomy caused by FAC within 5 years of surgery were examined in conjunction with the Cox proportional hazards regression model. Results: FAC was observed in 90 of the 383 eyes examined (23.4 %). Postoperative mild FAC was associated with the long-term success of trabeculectomy when evaluated according to our strictest success criterion, Criterion-A [HR = 0.72 (95 % CI 0.53-0.98); P = 0.04]. In contrast, severe FAC was inversely associated with the long-term success of the surgery when evaluated according to our most lenient criterion, Criterion-C [HR = 1.93 (95 % CI 1.16-3.22); P = 0.01]. Conclusion: Mild postoperative FAC after trabeculectomy is associated with a favorable long-term outcome, whereas severe postoperative FAC leads to an unfavorable prognosis. © 2013 Japanese Ophthalmological Society.

DOI： 10.1007/s10384-013-0274-4

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記述言語：英語   出版者・発行元：Experimental Eye Research  

The N-methyl- d-aspartate (NMDA) receptor-induced apoptosis is implicated in the pathological mechanisms of neural tissues, increasing the release of reactive oxygen species (ROS), resulting in a type of apoptotic cell death called excitotoxicity. Although intrinsic mechanisms to remove ROS, such as antioxidant enzymes, are provided by the tissue, the association between NMDA-induced excitotoxicity and antioxidative enzymes is not well understood. In this study, we focused on superoxide dismutase 1 (SOD1), an antioxidant enzyme, and investigated the role of SOD1 in the NMDA-induced neuronal cell death in the retina. NMDA was intravitreally injected into wild-type (WT) and SOD1 total knock-out (SOD1-deficient) mice. The number of TUNEL-positive cells in the retinal ganglion cell layer (GCL) and inner nuclear layer (INL) counted in the retinal sections and flatmount retinas were significantly higher in the SOD1-deficient mice than the WT mice after NMDA injection. Visual function assessed by dark-adapted electroretinogram (ERG) showed that the amplitudes of a-wave, b-wave, and oscillatory potential 2 were significantly reduced in the NMDA-injected SOD1-deficient mice. The level of ROS in the GCL and INL, measured using dihydroethidium, and the number of positive cells for γ-H2AX, a marker for DNA double strand breaks, and 8-OHdG, a marker for DNA oxidation, in the GCL were significantly increased in the SOD1-deficient mice after NMDA injection. We also measured mRNA and protein levels of SOD1 and SOD2 in the retina of WT mice, to find that mRNA and protein levels of SOD1, but not SOD2, were significantly reduced after NMDA injection. SOD1 deficiency exacerbated NMDA-induced damage to the inner retinal neurons, and NMDA reduced SOD1 levels in the retina of WT mice. Therefore, SOD1 protected retinal neurons against NMDA-induced retinal neurotoxicity, and NMDA-induced SOD1 reduction may be involved in neuronal vulnerability to excitotoxicity. © 2013 Elsevier Ltd.

DOI： 10.1016/j.exer.2013.07.002

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記述言語：英語   出版者・発行元：Current Eye Research  

Purpose: The objective of this study was to investigate the association between systemic oxidative stress and visual field defect progression in normal-tension glaucoma (NTG). Patients and methods: The subjects were 40 consecutive patients with NTG who were admitted to Keio University Hospital for 24-h intraocular pressure (IOP) evaluation; all subjects underwent six or more visual field tests in either eye and were followed up for >5 years. Spot samples of morning urine were collected during admission from all participants to determine the levels of urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) by ELISA kit. A linear regression line was calculated with the least squares method. Those subjects whose regression lines were negative and the p value <0.05 were classified as progressive, while all others were defined as non-progressive. Urinary 8-OHdG/creatinine level was compared between the two groups. Adjusted odds ratio and 95% confidence intervals for the progression were estimated with logistic regression models. Results: Seventeen subjects showed visual field defect progression (age: 59.9±9.5 years, untreated IOP in the right eye: 15.8±2.1mmHg), and 23 subjects showed no progression (age: 57.4±10.4 years, untreated IOP in the right eye: 16.0±2.6mmHg). Urinary 8-OHdG/creatinine level was significantly higher in the progressive group than in the non-progressive group (progressive group: 9.0±2.4ng/mg creatinine, non-progressive group: 7.3±1.8ng/mg creatinine, p=0.02). Multivariable analysis revealed that higher urinary 8-OHdG/creatinine level was a significant risk factor for the progression (odds ratio 1.54, 95% confidence interval 1.03-2.29). Conclusions: Increased urinary 8-OHdG/creatinine was associated with glaucomatous visual field progression in subjects with NTG. © Informa Healthcare USA, Inc.

DOI： 10.3109/02713683.2013.800889

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記述言語：英語   出版者・発行元：Ophthalmologica  

Purpose: To investigate the incidence, risk factors, time course and prognosis of ocular surface complications after trabeculectomy. Procedures: This is a retrospective, case-control study. Data on 399 consecutive patients who underwent trabeculectomy between 1999 and 2009 were evaluated. Cases of postoperative corneal epithelial defects, filamentary keratitis and dellen were evaluated. The risk factors for these ocular surface complications were analyzed with a logistic regression model. Results: Corneal epithelial defects were found in 44 of the 399 patients (11%), filamentary keratitis in 12 patients (3%) and dellen in 7 patients (2%). Dellen required surgical intervention at a statistically significantly higher rate than corneal epithelial defects or filamentary keratitis (p = 0.0001, Fisher's exact test). The significant risk factors for these ocular surface complications were found to be a history of preoperative superficial punctate keratopathy (odds ratio, OR: 2.10, 95% confidence interval, CI: 1.25-3.51, p = 0.005) and a history of diabetes mellitus (OR: 1.69, 95% CI: 1.02-2.81, p = 0.04). Conclusions: Ocular surface complications following trabeculectomy are not rare. The biggest risk factors for these complications were found to be a history of preoperative superficial punctate keratopathy and a history of diabetes mellitus. Surgery is likely to be required for the treatment of dellen. Copyright © 2013 S. Karger AG, Basel.

DOI： 10.1159/000351649

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記述言語：英語   出版者・発行元：Japanese Journal of Ophthalmology  

Purpose: To analyze the influence of oxidative stress on retinal ganglion cells (RGCs) by using a selective culture system of rat RGCs. Methods: Rat RGCs were purified by a two-step immunopanning procedure and cultured either with or without antioxidant (AO) compounds. Reactive oxygen species (ROS) in RGCs were analyzed using dihydroethidium. Expression of angiotensin II, cleaved caspase 3, and netrin-1 was analyzed by immunocytochemistry. Live RGCs were detected by use of calcein-acetoxymethyl ester. The roles of angiotensin II type 1 receptor (AT1R) signaling and netrin-1 were analyzed by use of an AT1R blocker (telmisartan) and an anti-netrin-1 neutralizing antibody, respectively. Results: ROS and angiotensin II were induced in RGCs cultured without AO compounds (AO-). In these cultures, the number of live RGCs decreased and expression of cleaved and activated caspase 3 increased, but these changes were attenuated by addition of the AT1R blocker. Reduction in netrin-1 expression under the AO- condition was also prevented by the AT1R blocker. The AT1R blocker's effects on RGC survival and reduction in cleaved caspase 3-positive cells were cancelled by the anti-netrin-1 neutralizing antibody. Conclusions: Oxidative stress induced cell death through AT1R signaling and netrin-1 reduction in cultured RGCs. © 2012 Japanese Ophthalmological Society.

DOI： 10.1007/s10384-012-0204-x

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記述言語：英語   出版者・発行元：Japanese Journal of Ophthalmology  

Purpose: To investigate the incidence of intraocular pressure (IOP) elevation after Descemet's stripping endothelial keratoplasty (DSEK) and associated clinical findings. Methods: Forty-eight eyes of 46 patients who underwent DSEK were studied in this single-center retrospective study. IOP elevation was defined as the presence of an increase in IOP above 21 mmHg lasting at least two - months, the need to introduce topical/oral antiglaucoma medications for at least two months, and the need for surgical therapy for uncontrolled IOP. Patients with pre-existing glaucoma or patients who were using antiglaucoma drugs before DSEK were excluded according to the protocol of the study. The incidence of post-DSEK IOP elevation was investigated. Results: The incidence of IOP elevation after DSEK was 16.7%. Glaucoma therapy following DSEK was needed in eight eyes of eight patients. IOP elevations were diagnosed from two to ten months after DSEK. There was no statistical difference in the survival probabilities of patients with different preoperative diagnoses. Pre-op IOP was observed to be a risk factor of IOP elevation in this series. Conclusions: IOP elevation appears to be a common postoperative complication of DSEK. Patients without preexisting glaucoma but with higher pre-op IOP need to be followed up carefully after DSEK. © Japanese Ophthalmological Society 2012.

DOI： 10.1007/s10384-012-0149-0

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記述言語：英語   出版者・発行元：Bioscience, Biotechnology and Biochemistry  

An EtOH extract of Valeriana fauriei was found to exhibit potent inhibition of fat accumulation against 3T3-L1 murine adipocytes. After performing several chromatographic steps, we successfully isolated the conjugated linoleic acid derivative, 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE). Synthesized 9-HODE and its analogs showed inhibitory activity against fat accumulation.

DOI： 10.1271/bbb.110994

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PubMed

記述言語：英語   出版者・発行元：Ophthalmologica  

Aims: The objective of this study was to investigate the association between blood pressure (BP) and visual field defect progression in normal-tension glaucoma (NTG). Methods: The subjects were 35 consecutive patients with NTG who were admitted to Keio University Hospital for 24-hour intraocular pressure evaluation; all subjects underwent 6 or more visual field tests in either eye and were followed up for more than 5 years. Systolic and diastolic BPs were measured at 9.00 h. Subjects with negative regression lines and p values of less than 0.05 were classified as progressive; all others were defined as stable. Systolic BP, diastolic BP, and ocular perfusion pressure were compared between the 2 groups. Results: Twelve subjects showed progression in glaucomatous visual field defects (age 55.1 ± 15.1 years). Twenty-three subjects showed no progression (age 57.2 ± 10.9 years). Diastolic BP (stable group: 77.0 ± 12.1 mm Hg; progressive group: 67.7 ± 9.7 mm Hg; p = 0.03) was significantly lower in the progressive group than in the stable group. Multivariable analysis revealed that low diastolic BP is a significant risk factor for progression (OR 0.90; 95% CI 0.82-0.99). Conclusions: Low diastolic BP was associated with glaucomatous visual field progression in subjects with NTG. Copyright © 2012 S. Karger AG, Basel.

DOI： 10.1159/000335978

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記述言語：英語   出版者・発行元：Journal of Nutritional Biochemistry  

Lutein, a xanthophyll of a carotenoid, is anticipated as a therapeutic product to prevent human eye diseases. However, its biological mechanism is still unclear. Here, we show the molecular mechanism of lutein's effect to reduce photodamage of the retina. We analyzed the light-exposed retinas of Balb/c mice given lutein-supplemented or normal diet. Visual function was measured by electroretinogram, and histological changes were observed. Immunohistochemical and immunoblot analyses were performed to analyze molecular mechanism. The reactive oxygen species induced in the retina was evaluated by fluorescent probes. In the mice after light exposure, reduction of a-wave and b-wave amplitudes in electroretinogram, indicating visual impairment, and thinning of the photoreceptor cell layer owing to apoptosis were both attenuated by lutein diet. Interestingly, γ-H2AX, a marker for double-strand breaks (DSBs) in DNA, was up-regulated in the photoreceptor cells after light exposure, but this increase was attenuated by lutein diet, suggesting that DSBs caused by photodamage contributed to the photoreceptor cell death and that this change was suppressed by lutein. Moreover, the expression of eyes absent (EYA), which promotes DNA repair and cell survival, was significantly up-regulated with lutein diet in the light-exposed retina. Therefore, lutein induced EYA for DNA repair, which could suppress DNA damage and photoreceptor cell apoptosis. Lutein reduced light-induced oxidative stress in the retina, which might contribute to promote DNA repair. The lutein-supplemented diet attenuated light-induced visual impairment by protecting the photoreceptor cells' DNA. © 2012 Elsevier Inc.

DOI： 10.1016/j.jnutbio.2011.01.006

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記述言語：英語   出版者・発行元：The Keio Journal of Medicine  

In the wake of the devastating earthquake and tsunami of March 11, our group at Keio University worked diligently to bring the Vision Van, a mobile eye clinic, from Miami, Florida, to disaster areas where medicines, eyeglasses, and indeed all other ophthalmological supplies and services, were nonexistent, thereby assisting many tsunami survivors suffering from eye problems. This act was encouraging not only to the patients and those working in the disaster-hit areas but also to ophthalmologists who wanted to use their medical specialty to assist those in need. © 2012 by The Keio Journal of Medicine.

DOI： 10.2302/kjm.61.10

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CiNii Research

記述言語：英語   出版者・発行元：Experimental Diabetes Research  

Diabetic retinopathy, a vision-threatening disease, has been regarded as a vascular disorder. However, impaired oscillatory potentials (OPs) in the electroretinogram (ERG) and visual dysfunction are recorded before severe vascular lesions appear. Here, we review the molecular mechanisms underlying the retinal neural degeneration observed in the streptozotocin-(STZ-) induced type 1 diabetes model. The renin-angiotensin system (RAS) and reactive oxygen species (ROS) both cause OP impairment and reduced levels of synaptophysin, a synaptic vesicle protein for neurotransmitter release, most likely through excessive protein degradation by the ubiquitin-proteasome system. ROS also decrease brain-derived neurotrophic factor (BDNF) and inner retinal neuronal cells. The influence of both RAS and ROS on synaptophysin suggests that RAS-ROS crosstalk occurs in the diabetic retina. Therefore, suppressors of RAS or ROS, such as angiotensin II type 1 receptor blockers or the antioxidant lutein, respectively, are potential candidates for neuroprotective and preventive therapies to improve the visual prognosis. © 2011 Yoko Ozawa et al.

DOI： 10.1155/2011/108328

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記述言語：英語   出版者・発行元：Investigative Ophthalmology and Visual Science  

Purpose. AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. The purpose of the present study was to elucidate the roles of AMPK in the pathogenesis of diabetic retinopathy using the known AMPK activators resveratrol and AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) in a mouse model. Methods. C57BL/6 mice with streptozotocin-induced diabetes were treated with resveratrol orally at 50 mg/kg for 7 days or with AICAR intraperitoneally at 100 mg/kg 24 hours before death. Retinal protein levels of phosphorylated and total AMPK, phosphorylated nuclear factor (NF)-κB p65, intercellular adhesion molecule (ICAM)-1, and vascular endothelial growth factor (VEGF) were evaluated by Western blot analysis or enzyme-linked immunosorbent assay. Retinal activity of sirtuin (SIRT)1 was measured by deacetylase fluorometric assay. Leukocyte adhesion to the retinal vasculature was examined with a concanavalin A lectin perfusion-labeling technique. Results. Induction of diabetes in mice led to retinal AMPK dephosphorylation, which was significantly reversed by either resveratrol or AICAR. Either resveratrol or AICAR significantly reversed SIRT1 deactivation and NF-κB phosphorylation, both of which were induced in the diabetic retina. Administration of resveratrol to diabetic mice significantly reduced diabetes-induced retinal leukocyte adhesion, together with retinal expression of ICAM-1 and VEGF. Conclusions. The present findings reveal that diabetes-induced retinal inflammation stems from downregulation of the AMPK pathway, leading subsequently to SIRT1 deactivation and NF-κB activation. The data also suggest the potential use of the AMPK activator resveratrol as a therapeutic agent for diabetic retinopathy. © 2011 The Association for Research in Vision and Ophthalmology, Inc.

DOI： 10.1167/iovs.11-8041

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出版者・発行元：株式会社医学書院  

DOI： 10.11477/mf.1410103871

CiNii Research

記述言語：英語   出版者・発行元：American Journal of Medical Genetics, Part A  

DOI： 10.1002/ajmg.a.34042

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記述言語：英語   出版者・発行元：Investigative Ophthalmology and Visual Science  

Purpose. To investigate the influence of deficiency in superoxide dismutase (SOD) 1, a major antioxidative enzyme, on retinal ganglion cells (RGCs). Methods. In the SOD1 total knockout (SOD1-deficient) mice, the level of superoxide anion was measured using dihydroethidium. The number of RGCs was counted in both the retinal sections and the flat-mount retinas after retrograde labeling. Thickness of nerve fiber layer (NFL) was measured in the sections, and the amount of neurofilament protein was measured by immunoblot analysis. Pattern electroretinogram (ERG), which reflects the function of retinal ganglion cells, dark-adapted ERG, and cone ERG were performed. The intraocular pressure (IOP) was measured with an induction-impact tonometer. The levels of SOD-1 and -2 were measured by ELISA, in the serum of 47 newly diagnosed consecutive normal tension glaucoma (NTG) patients and 44 consecutive control subjects. Results. The level of superoxide anion in the RGC layer was significantly higher in 24-week-old SOD1-deficient mice than in wild-type mice. The RGC number was significantly reduced in 24-week-old SOD1-deficient mice, although they were not in 8-week-old mice. The NFL thickness and neurofilament protein were reduced in 24-week-old SOD1-deficient mice. The amplitude of pattern ERG was significantly reduced, although dark-adapted and cone ERGs showed no impairment, in 24-week-old SOD1-deficient mice. The IOP level was not changed in the SOD1-deficient mice. The serum level of SOD1, but not SOD2, was significantly lower in the NTG patients than in the healthy controls. Conclusions. SOD1 deficiency causes RGC vulnerability, which may be involved in the underlying condition of NTG. © 2011 The Association for Research in Vision and Ophthalmology, Inc.

DOI： 10.1167/iovs.10-6294

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PubMed

記述言語：英語   出版者・発行元：Investigative Ophthalmology and Visual Science  

Purpose. To investigate and compare the prevalence of motor vehicle collisions (MVCs) in individuals with or without primary open-angle glaucoma (POAG). Methods. A total of 265 subjects were consecutively enrolled: 121 (79 men, 42 women; age, 62.1 ± 8.0 years) with POAG; and 144 (95 men, 49 women; age, 61.2 ± 7.9 years) who were free of ocular disease. Participants answered a questionnaire on MVC experience during the previous 10 years, past driving experience, and daily driving habits. The POAG group was subdivided into three groups according to disease severity (mild, moderate, or severe), to assess the relationship between POAG severity and MVC. Results. A statistically significant association between POAG severity and MVC frequency was observed; 3.5% of the controls, 0.0% of the mild POAG group, 3.9% of the moderate POAG group, and 25.0% of the severe POAG group had experienced MVCs (P = 0.007, Cochran-Armitage trend test). The severe POAG group had experienced a much higher frequency of MVCs during the surveyed period than had the control group (P < 0.010; Fisher's exact test). Logistic regression analyses to account for confounding factors (age, presence of diabetes mellitus, driving history, time spent driving per day, and best corrected visual acuity in the better or worse eye) produced consistent results. Conclusions. Advanced POAG with marked visual field defects may be a risk factor for MVCs. © 2011 The Association for Research in Vision and Ophthalmology, Inc.

DOI： 10.1167/iovs.10-6264

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PubMed

記述言語：英語   出版者・発行元：Acta Ophthalmologica  

Purpose:- To investigate the amount of systemic oxidative stress-related DNA damage and serum total antioxidant status of patients with normal-tension glaucoma compared with healthy controls. Methods:- Forty-three patients with normal-tension glaucoma selected from 60 consecutive newly diagnosed patients with primary open-angle glaucoma were enrolled. Each patient's intraocular pressure (IOP) was measured seven times over a 24-hour period. Those whose highest IOP was over 21mmHg were excluded. Forty control subjects were recruited. The serum total antioxidant status was assessed colorimetrically by its ability to reduce the generation of the radical cation ABTS (2,2-azinobis-3-ethylbenzthiazoline sulphonate). The urinary 8-hydroxy-2′-deoxyguanosine was measured as a marker of oxidative DNA damage and normalized to creatinine. The results were compared between healthy subjects and patients with normal-tension glaucoma. Results:- The control and normal-tension glaucoma groups did now show significant differences for age, gender, serum fructosamine, cholesterol and triglyceride levels; systolic and diastolic blood pressure, body mass index; and prevalence of hypertension. The serum total antioxidant status was significantly higher (p=0.01) and the urinary 8-hydroxy-2′-deoxyguanosine/creatinine level significantly lower (p=0.03) in the patients with normal-tension glaucoma compared with the controls. Even after we adjusted the data for independent variables, the incidence of normal-tension glaucoma was significantly correlated with high serum total antioxidant levels (p=0.03; odds ratio, 1.007; 95% confidence interval, 1.001-1.013) and low urinary 8-hydroxy-2′-deoxyguanosine/creatinine (p=0.02; odds ratio 0.76; 95% confidence interval, 0.61-0.96). Conclusions:- Increased serum total antioxidant and decreased 8-hydroxy-2′- deoxyguanosine may reflect compensatory alterations in response to increased systemic oxidative stress in patients with normal-tension glaucoma. © 2010 Acta Ophthalmol.

DOI： 10.1111/j.1755-3768.2010.01997.x

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PubMed

記述言語：英語   出版者・発行元：Journal of Glaucoma  

Purpose: To determine if Chlamydia pneumoniae infection is associated with primary open-angle glaucoma (POAG). Patients and Methods: Consecutive patients with newly diagnosed primary POAG attending the Glaucoma clinic of Keio University Hospital between June 2007 and January 2008 were considered for inclusion in this prospective case-control study. Forty consecutive POAG patients and 41 normal healthy individuals as a control population met the inclusion criteria. The exclusion criteria for both groups were; taking steroids or immunosuppressive agents, smoking, and history of any acute or chronic systemic disease including stroke, heart attack, diabetes mellitus, hypertension, asthma, and autoimmune diseases. The serum was analyzed for C. pneumoniae and C. trachomatis immunoglobulin G antibody titers by enzyme-linked immunosorbent assay. Seroactivity to each antigen between case and control groups was evaluated by Mann-Whitney U test. Results: The age, male/female ratio, and intraocular pressure of the cases and control groups were not significantly different. Immunoglobulin G titers for C. pneuemoniae was significantly higher in patients with POAG than in controls (P=0.009). The titers to C. trachomatis were not significantly different between the 2 groups (P=0.99). Conclusion: The results suggest that higher C. pneumoniae titers are associated with POAG. If confirmed, this may indicate either a common factor that causes susceptibilities to both glaucoma and C. pneumoniae infection or that C. pneumoniae may be a causal factor for developing POAG. Copyright © 2010 by Lippincott Williams & Wilkins.

DOI： 10.1097/IJG.0b013e3181ca7868

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PubMed

記述言語：英語   出版者・発行元：American Journal of Pathology  

Light damage to the retina accelerates retinal degeneration in human diseases and rodent models. Recently, the polyphenolic phytoalexin resveratrol has been shown to exert various bioactivities in addition to its classical antioxidant property. In the present study, we investigated the effect of resveratrol on light-induced retinal degeneration together with its underlying molecular mechanisms. BALB/c mice with light exposure (5000-lux white light for 3 hours) were orally pretreated with resveratrol at a dose of 50 mg/kg for 5 days. Retinal damage was evaluated by TdT-mediated dUTP nick-end labeling, outer nuclear layer morphometry, and electroretinography. Administration of resveratrol to mice with light exposure led to a significant suppression of light-induced pathological parameters, including TdT-mediated dUTP nick-end labeling-positive retinal cells, outer nuclear layer thinning, and electroretinography changes. To clarify the underlying molecular mechanisms, the nuclear translocation of activator protein -1 subunit c-fos was evaluated by enzyme-linked immunosorbent assay, and the retinal activity of sirtuin 1 was measured by deacetylase fluorometric assay. Retinal activator protein-1 activation, up-regulated following light exposure, was significantly reduced by application of resveratrol. In parallel, retinal sirtuin 1 activity, reduced in animals with light damage, was significantly augmented by resveratrol treatment. Our data suggest the potential use of resveratrol as a therapeutic agent to prevent retinal degeneration related to light damage. Copyright © American Society for Investigative Pathology.

DOI： 10.2353/ajpath.2010.100098

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PubMed

記述言語：英語   出版者・発行元：Ophthalmic Research  

The process of aging involves the accumulating changes in the microenvironment that lead to cell senescence or apoptosis, and subsequent tissue or organ dysfunction. Multiple extrinsic and intrinsic events that cause DNA instability are associated with aging. Cells containing unstable DNA are biologically vulnerable, and if the DNA damage is too great for the cell to repair, it becomes senescent or dies by apoptosis. Thus, the cell's capacity to repair its DNA determines the progress of aging, at least in part. Here, we focus on the sirtuins, the mammalian homologs of the yeast life-span-extending molecule, Sir2. Among the sirtuin family proteins in mammals, the one most similar to yeast Sir2 is SIRT1, which is involved in multiple pathways, including the repair of DNA double-strand breaks. Although the role of SIRT1 in mammalian longevity is not clear, it is expressed throughout the retina, where it may suppress aging. In fact, a mutant mouse model of retinal degeneration shows an abnormal subcellular localization of SIRT1 protein and accelerated retinal cell apoptosis. Further analyses are required to elucidate the mechanism of DNA damage and repair, including the contributions of the sirtuins, in the aged or diseased retinas, which will help us understand the mechanisms of retinal aging. © 2010 S. Karger AG, Basel.

DOI： 10.1159/000316484

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PubMed

記述言語：英語   出版者・発行元：British Journal of Ophthalmology  

DOI： 10.1136/bjo.2009.168229

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PubMed

記述言語：英語  

DOI： 10.2147/opth.s10297

PubMed

記述言語：英語   出版者・発行元：Diabetologia  

Aims/hypothesis: Diabetic retinopathy is a progressive neurodegenerative disease, but the underlying mechanism is still obscure. Here, we focused on oxidative stress in the retina, and analysed its influence on retinal neurodegeneration, using an antioxidant, lutein. Methods: C57BL/6 mice with streptozotocin-induced diabetes were constantly fed either a lutein-supplemented diet or a control diet from the onset of diabetes, and their metabolic data were recorded. In 1-month-diabetic mice, reactive oxygen species (ROS) in the retina were measured using dihydroethidium and visual function was evaluated by electroretinograms. Levels of activated extracellular signal-regulated kinase (ERK), synaptophysin and brain-derived neurotrophic factor (BDNF) were also measured by immunoblotting in the retina of 1-month-diabetic mice. In the retinal sections of 4-month-diabetic mice, histological changes, cleaved caspase-3 and TUNEL staining were analysed. Results: Lutein did not affect the metabolic status of the diabetic mice, but it prevented ROS generation in the retina and the visual impairment induced by diabetes. ERK activation, the subsequent synaptophysin reduction, and the BDNF depletion in the diabetic retina were all prevented by lutein. Later, in 4-month-diabetic mice, a decrease in the thickness of the inner plexiform and nuclear layers, and ganglion cell number, together with increase in cleaved caspase-3- and TUNEL-positive cells, were avoided in the retina of lutein-fed mice. Conclusions/interpretation: The results indicated that local oxidative stress that has a neurodegenerative influence in the diabetic retina is prevented by constant intake of a lutein-supplemented diet. The antioxidant, lutein may be a potential therapeutic approach to protect visual function in diabetes. © 2010 Springer-Verlag.

DOI： 10.1007/s00125-009-1655-6

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PubMed

出版者・発行元：Clinical Ophthalmology  

Purpose: To report on the efficacy of selective laser trabeculoplasty (SLT) for elevated intraocular pressure (IOP) following subtenon injection of triamcinolone acetonide. Method: SLT was performed on four of 148 eyes in which IOP was elevated after a subtenon injection of triamcinolone acetonide and could not be maintained within normal limits by conventional medications. Postoperative IOP and relative reduction of IOP were evaluated. Results: IOP was reduced in three eyes to within the normal range without any medications six months after SLT alone, but trabeculotomy was performed on one eye. Percentage reduction in IOP after SLT was 21.6% at one month, 45.0% at three months, and 52.7% at nine months. Conclusion: SLT may be effective in reducing elevated IOP following subtenon injection of triamcinolone acetonide and should be considered before glaucoma surgery. © 2010 Yuki et al, publisher and licensee Dove Medical Press Ltd.

Scopus

出版者・発行元：Clinical Ophthalmology  

Purpose: To determine the free fatty acid levels in the sera of patients with normal-tension glaucoma and compare it with that of normal controls. Methods: Forty-four consecutive patients with newly diagnosed normal-tension glaucoma and forty-four age and gender matched controls were evaluated. The type and level of fatty acids in the sera were measured by gas chromatography (Model GC17A; Shimazu, Kyoto, Japan). Twenty-four fatty acids were identified from 12:0 to 24:1. The values were compared between the normal-tension glaucoma and control groups by Mann-Whitney U tests. Results: No statistically significant difference was found in the levels of any free fatty acids between the normal-tension glaucoma group and control group. Conclusion: No significant association was found in the serum free fatty acids levels including docosahexaenoic acid and eicosapentaenoic acid between normal-tension glaucoma patients and controls. © 2010 Yuki et al, publisher and licensee Dove Medical Press Ltd.

Scopus

記述言語：英語   出版者・発行元：Graefe's Archive for Clinical and Experimental Ophthalmology  

Background: Vitamin A, B9, C, E, and uric acid are well-known antioxidants and may prevent age-related eye disorders. The aim of the present study was to investigate the levels of antioxidant vitamins, A, B9, C, E, and antioxidative substance, uric acid in the serum of Japanese patients with normal-tension glaucoma and compare the results with normal controls. Methods: All subjects with suspicion of primary open-angle glaucoma who came to the glaucoma subspeciality clinic of Keio University Hospital were enrolled in this study. Sixty patients (28 males, 32 females; mean age ± standard deviation: 59.9 ± 9.8 years) with newly diagnosed primary open-angle glaucoma patients were consecutively enrolled in this study. After the diagnosis of primary open-angle glaucoma, the patients underwent 24-h IOP measurements. Forty-seven newly diagnosed consecutive normal-tension glaucoma patients (18 males, 29 females; mean age ± standard deviation: 59.5 ± 10.2 years) were enrolled in this study. The control subjects were recruited from subjects who came to the clinic for annual refractive check-up. The 44 consecutive control subjects of the current study, (16 males, 28 females; 62.7 ± 14.8 years) did not have any ocular diseases. The serum levels of vitamins A, B9, C, E, and uric acid were measured. The values were compared between the normal-tension glaucoma and control groups by the Mann-Whitney U test. Results: Serum levels of vitamin C were significantly lower in normal-tension glaucoma patients than in normal healthy controls (P = 0.04; normal-tension glaucoma; 4.6 ± 4.0 μg/ml control; 6.3 ± 3.9 μg/ml). Uric acid level was significantly higher in normal-tension glaucoma patients than in controls (P = 0.01; normal-tension glaucoma; 5.8 ± 1.5 mg/dl control; 4.9 ± 1.4 mg/dl). No statistically significant difference was seen in vitamin A (P = 0.41; normal-tension glaucoma; 82.1 ± 26.7 μg/dl control; 77.1 ± 30.1 μg/dl), B9 (P = 0.37; normal-tension glaucoma; 8.7 ± 4.3 ng/ml control; 8.0 ± 3.1 ng/ml)and E (P = 0.83; normal-tension glaucoma; 1.5 ± 0.6 control; 1.5 ± 0.6) levels between normal-tension glaucoma and control groups. Conclusion: Normal-tension glaucoma patients had lower serum levels of vitamin C and increased levels of uric acid. These observations may pave the way for possible alternative treatment for normal-tension glaucoma. © 2009 Springer-Verlag.

DOI： 10.1007/s00417-009-1183-6

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PubMed

記述言語：英語   出版者・発行元：American Journal of Ophthalmology  

Purpose: To investigate the efficacy of intraoperative sub-Tenon injection of triamcinolone acetonide (TA) in increasing the success rate of trabeculectomy for the treatment of secondary glaucoma. Design: Prospective randomized controlled clinical trial. Methods: Fifty-three consecutive eyes scheduled for trabeculectomy were randomly allocated in an institutional setting. In the study group (n = 26), TA was injected in the sub-Tenon at the conclusion of the surgery. In the control group (n = 27) surgery was completed without TA injection. Surgical success was defined as a complete success if the intraocular pressure (IOP) was 21 mm Hg or less with an IOP reduction of greater than or equal to 20% without any antiglaucoma medication. Success rates in both groups were compared using Kaplan-Meier survival curves and the log-rank test. The morphologic characteristics of the filtering blebs were evaluated using the Indiana Bleb Appearance Grading Scale. Results: Fifty-three eyes completed the study (26 in the study group and 27 in the control group), with a follow-up of 12 months. Complete success rates were 65.4% for the study group and 63.0% for the control group (P = .77) at 12 months. The morphologic characteristics of the filtering blebs and postoperative complications were similar in the study and the control eyes (P > .40). IOP measurements in both groups were similar at all visits (P > .05). Conclusions: Trabeculectomy with intraoperative sub-Tenon injection of TA for the treatment of secondary glaucoma neither increased the intermediate-term success rate nor decreased postoperative complications. © 2009 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ajo.2009.01.007

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PubMed

記述言語：英語   出版者・発行元：Japanese Journal of Ophthalmology  

DOI： 10.1007/s10384-008-0605-z

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PubMed

記述言語：英語   出版者・発行元：Biological Trace Element Research  

We evaluated the association between hair lead concentrations and primary open-angle glaucoma. Ninety-eight Japanese patients (40 males, 58 females; average age 57.6±10.8 years) with primary open-angle glaucoma and control subjects (131 males, 114 females; average age 56.0±12.8 years) were recruited in this study. Hair lead levels were measured by inductively coupled plasma mass spectrometry. Hair lead concentrations between primary open-angle glaucoma and control groups were compared using Mann-Whitney U test. As a subgroup analysis, we compared hair lead concentrations between low-tension glaucoma, high-tension glaucoma, and control groups using one-factor analysis of variance. Lead accumulation levels were significantly higher in the female subjects with primary open-angle glaucoma compared to the control group (P=0.03). Lead accumulation levels were significantly higher in female patients with low intraocular pressure compared to control group 2 (P=0.02). A higher hair lead level, which reflects the total body burden of lead, was observed to be associated with primary open-angle glaucoma in females especially with low-tension glaucoma. Accumulation of lead may be an unrecognized risk factor of non-pressure-dependent glaucomatous optic neuropathy. © 2009 Humana Press Inc.

DOI： 10.1007/s12011-009-8376-z

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PubMed

出版者・発行元：株式会社医学書院  

DOI： 10.11477/mf.1410102428

CiNii Research

出版者・発行元：British Journal of Ophthalmology  

DOI： 10.1136/bjo.2008.144766

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記述言語：英語   出版者・発行元：Journal of Cataract and Refractive Surgery  

Purpose: To evaluate anterior chamber angle alterations after phakic intraocular lens (pIOL) implantation using the Pentacam rotating Scheimpflug camera (Oculus) and the effect on intraocular pressure (IOP) and anterior chamber inflammation. Setting: Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan. Methods: Twenty eyes of 11 patients with high myopia who had implantation of pIOLs (Artisan/Verisyse, model 204, Ophtec BV) were included. All pIOLs were fixated on the iris near the 3 o'clock and 9 o'clock positions. Angles at the 2, 3, 4, 8, 9, and 10 o'clock positions, IOP, and postoperative flare were evaluated retrospectively. Results: The mean angle degree at 2, 3, 4, 8, 9, and 10 o'clock was 40.3 degrees ± 3.3 (SD) preoperatively and 36.5 ± 5.8 degrees postoperatively; the postoperative angles were significantly narrower than the preoperative angles (P<.001). The mean angles at 3 o'clock and 9 o'clock were 39.8 ± 3.7 degrees and 40.6 ± 3.5 degrees, respectively, preoperatively and 32.7 ± 6.0 degrees and 31.3 ± 5.4 degrees, respectively, postoperatively. The postoperative angles at 3 o'clock and 9 o'clock were narrower than the preoperative angles (P<.001). There was no significant difference between preoperative IOP and postoperative IOP (P = .22). The flare at 1 month (r = 0.573, P = .0071) and 1 year (r = 0.700, P = .004) was significantly correlated with the angle change. Conclusion: Partial localized narrowing of anterior chamber angles that occurred after pIOL implantation induced acute and chronic anterior chamber inflammation in patients with large angle alterations. © 2008 ASCRS and ESCRS.

DOI： 10.1016/j.jcrs.2008.04.033

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PubMed

記述言語：英語   出版者・発行元：Journal of Refractive Surgery  

PURPOSE: To report steroid-induced glaucoma after photorefractive keratectomy (PRK). METHODS: A 50-year-old Japanese woman was referred for end-stage glaucoma 9 months after PRK. Topical fluorometholone 0.1% was administered for corneal subepithelial haze in both eyes for 9 months after PRK. Pneumatic non-contact tonometry values of intraocular pressure (IOP) remained normal (range: 11 to 17 mmHg), until she was diagnosed with end-stage steroid-induced glaucoma with extensive restriction in visual fields. At the patient's initial examination in our hospital, IOP measured by Goldmann applanation tonometry was 34 mmHg in the right eye and 32 mmHg in the left eye, but the estimated IOP as corrected by central corneal thickness measurement was >40 mmHg in both eyes. RESULTS: The patient underwent uneventful bilateral trabeculectomies, resulting in reduction of IOP to <10 mmHg in both eyes. CONCLUSIONS: The underestimation of IOP after PRK led to advanced visual field loss. Careful evaluation of IOP, optic disc, and visual field tests are indispensable to avoid such a devastating outcome after PRK.

DOI： 10.3928/1081597x-20080401-17

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出版者・発行元：金原出版  

DOI： 10.18888/ga.0000003053

CiNii Research

記述言語：英語   出版者・発行元：American Journal of Ophthalmology Case Reports  

Purpose: Implantation of presbyopia-correcting intraocular lenses (IOLs) has not been advised for glaucomatous eyes because of the risk of decreased contrast sensitivity with progress of glaucoma. Extended depth-of-focus (EDF) IOLs have been reported to provide comparable postoperative visual function and influence on the visual field to monofocal IOLs. Methods: This case series was a retrospective medical record review of 16 eyes of 10 patients who had normal tension glaucoma (NTG) with no central visual field defects and underwent cataract surgery with implantation of diffractive EDF IOLs. At 3 months postoperatively, distance-corrected visual acuities (DCVAs) at distances of 5, 1, and 0.5 m and photopic contrast sensitivity were examined. Automated perimetry using the 30-2 Swedish interactive threshold algorithm was also performed, and the mean variance (MD) values, mean deviation values at the central four points (central MD), and foveal threshold were recorded. Results: The mean age of the patients (5 men, 5 women) was 66.5 years. Over 80% of eyes obtained DCVAs of 20/20, 20/20, and 20/25 at 5 m, 1 m, and 0.5 m, respectively. Whereas 5 of 16 eyes were categorized as severe by the Hodapp-Parrish-Anderson classification, postoperative contrast sensitivity was within the normal range, except for 4 eyes at 18 cycles per degree. Conclusions and importance: In this case series, the postoperative visual functions of NTG patients with EDF IOLs were almost comparable to those of normal eyes with the same IOLs, which demonstrated that the use of EDF IOLs for controlled NTG eyes would be permissible. While careful patient selection and follow-up for NTG progress are important, further investigations are necessary for confirming the safety and exploring the selection criteria.

DOI： 10.1016/j.ajoc.2022.101792

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PubMed

出版者・発行元：金原出版  

DOI： 10.18888/ga.0000002661

CiNii Research

出版者・発行元：Ophthalmology  

Purpose: To evaluate ethnic variations, ocular and systemic determinants of retinal nerve fiber layer (RNFL) thickness, and neuroretinal rim area among Asians using a large consortium of population-based eye studies. Design: Cross-sectional pooled analysis. Participants: Twenty-two thousand four hundred thirty-six participants (22 436 eyes) from 10 population-based studies (in China, Hong Kong, India, Japan, Russia, and Singapore) of the Asian Eye Epidemiology Consortium. Methods: Participants 40 years of age or older without glaucoma were included. All participants underwent spectral-domain OCT imaging and systemic and ocular examinations. Data were pooled from each study. Multivariable regression was performed to evaluate interethnic differences, intermachine variations, and ocular and systemic factors associated with RNFL thickness and rim area, adjusting for age, gender, diabetes, intraocular pressure (IOP), spherical equivalent (SE), ethnicity, OCT model, and study group. When evaluating body mass index, smoking, and hypertension as exposures, these factors were additionally adjusted for in the model. Main Outcome Measures: Average RNFL thickness (in micrometers) and rim area (in square millimeters). Results: Indian and Japanese eyes have thinner RNFLs than those of other Asian ethnicities (β values range, 7.31–12.76 μm; P < 0.001 for all pairwise comparisons). Compared with measurements by Cirrus HD-OCT (Carl Zeiss Meditec, Inc), RNFL on average was 7.29 μm thicker when measured by Spectralis (Heidelberg Engineering), 12.85 μm thicker when measured by RS-3000 (NIDEK Co, Ltd), and 17.48 μm thicker when measured by iVue/RTVue (Optovue, Inc) devices (all P < 0.001). Additionally, older age (per decade, β = –2.70), diabetes (β = –0.72), higher IOP (per 1 mmHg, β = –0.07), more myopic SE (per diopter, β = –1.13), cardiovascular disease (β = –0.94), and hypertension (β = –0.68) were associated with thinner RNFL (all P ≤ 0.003). Similarly, older age (β = –0.019), higher IOP (β = –0.010), and more myopic SE (β = –0.025) were associated with smaller rim area (all P < 0.001). Conclusions: In this large pooled analysis of Asian population studies, Indian and Japanese eyes were observed to have thinner RNFL profiles. These findings suggest the need for an ethnic-specific normative database to improve glaucoma detection.

DOI： 10.1016/j.ophtha.2021.11.022

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記述言語：英語  

DOI： 10.1523/JNEUROSCI.0555-21.2021

PubMed

出版者・発行元：金原出版  

DOI： 10.18888/ga.0000002263

CiNii Research

出版者・発行元：金原出版  

DOI： 10.18888/ga.0000002262

CiNii Research

記述言語：日本語   出版者・発行元：金原出版  

DOI： 10.18888/ga.0000001051

CiNii Research

記述言語：英語  

DOI： 10.3171/2016.11.JNS161033

PubMed

記述言語：日本語   出版者・発行元：日本白内障学会  

DOI： 10.14938/cataract.10-010

CiNii Research

記述言語：英語  

DOI： 10.1073/pnas.1616811114

PubMed

記述言語：英語   出版者・発行元：Clinical Ophthalmology  

Purpose: The aims of our study were to investigate whether laser in situ keratomileusis (LASIK) improves health-related quality of life (HRQoL) and to identify factors that affect postoperative HRQoL. Materials and methods: A total of 213 Japanese patients who underwent primary LASIK were analyzed in this study. The average age of patients was 35.0±9.4 years. The subjects were asked to answer questions regarding subjective quality of vision, satisfaction, and quality of life (using the Japanese version of 36-Item Short Form Health Survey Version 2) at three time points: before LASIK, 1 month after LASIK, and 6 months after LASIK. Longitudinal changes over 6 months in the outputs of mental component summary (MCS) score and the physical component summary (PCS) score from the 36-Item Short Form Health Survey Version 2 questionnaire were compared between time points using a linear mixed-effects model. Delta MCS and PCS were calculated by subtracting the postoperative score (1 month after LASIK) from the preoperative score. Preoperative and postoperative factors associated with a change in the MCS score or PCS score were evaluated via a linear regression model. Results: The preoperative MCS score was 51.0±9.4 and increased to 52.0±9.8 and 51.5±9.6 at 1 month and 6 months after LASIK, respectively, and the trend for the change from baseline in MCS through 6 months was significant (P=0.03). PCS score did not change following LASIK. Delta MCS was significantly negatively associated with preoperative spherical equivalent, axial length, and postoperative quality of vision, after adjusting for potential confounding factors. Conclusion: Mental HRQoL is not lost with LASIK, and LASIK may improve mental HRQoL. Preoperative axial length may predict postoperative mental HRQoL.

DOI： 10.2147/OPTH.S118545

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PubMed

記述言語：英語   出版者・発行元：Asia-Pacific Journal of Ophthalmology  

Purpose: This study was aimed to use the age estimation segment of face recognition software to determine whether patients appeared younger after surgery for aponeurotic ptosis and dermatochalasis. Design: This is a prospective interventional case series. Methods: Face recognition software was used to estimate the age of 12 Japanese patients who had surgery to repair aponeurotic ptosis or dermatochalasis. Photographs of the faces before and 1 month after the surgery were taken and uploaded to the face recognition software to estimate the age of the subjects. Results: The preoperative estimated age significantly correlated with the actual age (r = 0.647, P = 0.023), and the postoperative estimated age also significantly correlated with the actual age (r = 0.727, P = 0.007). The scores of the palpebral fissure width of the right eyes (P = 0.003) and left eyes (P = 0.002) significantly improved postoperatively. However, the postoperative estimated age was not significantly younger than the preoperative estimated age (P = 0.173). Conclusions: The face recognition software may not be influenced by the lid plastic surgery. Many factors other than the width of the palpebral fissure influence the estimation of age by the face recognition software.

DOI： 10.1097/APO.0000000000000045

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PubMed

記述言語：日本語   出版者・発行元：Clinical Ophthalmology  

Purpose: The Great East Japan Earthquake of March 11, 2011 triggered powerful tsunami waves off the northeastern Pacific coast of Japan that destroyed almost all of the built-up areas along the coast. The study reported here examined the role played by the Vision Van, a mobile outpatient ophthalmological clinic, in providing eye care to disaster evacuees. Methods: This was a retrospective case-series study of 2,070 victims (male: 732, female: 1,338) who visited the Vision Van. The subjects' medical records were examined retrospectively and analyzed in terms of age, sex, and date of visit to the Vision Van. Information regarding each patient's chief complaint, diagnosis, medication(s) prescribed, and eyeglasses and contact lenses provided, was also examined.Results: The Vision Van was used to conduct medical examinations on 39 days between April 23 and June 29, 2011. The average number of subjects visiting the Vision Van each day was 53±31 (range: 7-135), with examinations carried out in Miyagi Prefecture and Iwate Prefecture. The most frequent complaint was a need for eye drops (871/2,070 [42.1%]). The second and third most frequent complaints, respectively, were the need for contact lenses (294/2,070 [14.2%]) and eyeglasses (280/2,070 [13.5%]). The most frequent ocular disease diagnosis was cataract (497/2,070 [24.0%]). Eye drops were prescribed to 74.1% of the subjects.Conclusion: Mobile clinics such as the Vision Van provide valuable care, in this case, particularly to individuals who lost or left behind eyeglasses or contact lenses while escaping a natural disaster, and to subjects with chronic eye disease. © 2014 Yuki et al. This work is published by Dove Medical Press Limited.

DOI： 10.2147/OPTH.S58887

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PubMed

記述言語：英語   出版者・発行元：Clinical Ophthalmology  

Purpose: Flat anterior chamber (FAC) in association with overfiltration is a complication after trabeculectomy. The aim of the current study was to investigate the efficacy of injection of an ophthalmic viscoelastic device (OVD) to treat FAC after trabeculectomy in a retrospective consecutive case series study. Materials and methods: Twenty-five consecutive patients who underwent injection of OVD for the treatment of FAC after trabeculectomy were analyzed. The primary outcome variable was the qualified success of trabeculectomy, which was defined at three different levels by the achievement of one of three IOP-related criteria with or without glaucoma medication. Kaplan-Meier plots were generated to estimate survival functions for trabeculectomy with OVD injection. Results: Twenty-one patients (21/25 = 84.0%) recovered from FAC by one OVD injection. The postoperative intraocular pressure (IOP) measured at 12 months, 24 months, 36 months, 48 months, and 60 months was 14.7 ± 3.6 mmHg, 15.6 ± 7.0 mmHg, 14.2 ± 2.8 mmHg, 14.2 ± 3.8 mmHg, and 14.6 ± 2.7 mmHg, respectively. All postoperative IOP measurements were significantly lower than the preoperative IOP (P < 0.001). The probabilities of qualified success for 5 years after trabeculectomy with OVD injection were as follows: 24.4% (IOP ≦ 21 mmHg and ≧20% reduction of preoperative IOP), 16.5% (IOP ≦ 16 mmHg and ≧20% reduction) and 6.3% (IOP ≦ 12 mmHg and ≧30% reduction). One patient, who had undergone deep lamellar keratoplasty, experienced a complication associated with the injection of the viscoelastic material, Descemet's membrane detachment. Conclusion: Injection of OVD may be effective for the treatment of FAC; however, the longterm success rate was relatively low. © 2013 Hosoda et al.

DOI： 10.2147/OPTH.S51165

Scopus

PubMed

記述言語：英語   出版者・発行元：Clinical Ophthalmology  

Purpose: Falls are among the most serious public health concerns for the elderly. Information conveyed via the visual sense is relevant to postural balance and movement, and proper visual function is essential to avoid falls. Here we investigated the prevalence of injurious falls among patients with primary open-angle glaucoma (POAG) who were more than 45 years old, compared with comparably aged healthy subjects. Methods: This is a cross-sectional study. Consecutive patients who visited the Tanabe Eye Clinic, Yamanashi, Japan between January 1 and March 30, 2009 were screened for eligibility by ophthalmic examination. A total of 117 control subjects (77 men, 40 women; aged 60.2 ± 7.5 years) who were free of ocular disease and 101 POAG patients (58 men, 43 women; aged 62.3 ± 8.7 years) were consecutively enrolled. Participants answered a questionnaire on injurious fall experience during the previous 10 years. The prevalence of injurious fall in subjects with POAG versus healthy controls was examined with Fisher's exact test. Adjusted odds ratios and 95% confidence intervals were estimated with logistic regression models for the subjects with POAG (factors: age, gender, mean deviation in the better eye or worse eye). Results: The self-reported prevalence of injurious fall was 0.9% (1/117) in the control group and 6.9% (7/101) in the POAG group. The association between injurious fall and POAG was statistically significant (P = 0.026, Fisher's exact test). Within the POAG patients, the group reporting falls was significantly older and had a lower BMI, worse BCVA, and worse mean deviation in both the better and worse eye than the group reporting no falls. Worse mean deviation in the eye with the better visual field (odds ratios 0.75; 95% confidence intervals: 0.57 to 0.99; P = 0.036) was a significant risk factor for injurious falls in subjects with POAG. Conclusions: POAG was significantly associated with injurious falls. © 2012 Tanabe et al, publisher and licensee Dove Medical Press Ltd.

DOI： 10.2147/OPTH.S28281

Scopus

PubMed

記述言語：英語   出版者・発行元：Clinical Ophthalmology  

Background: Central serous chorioretinopathy (CSC) has been traditionally treated with laser photocoagulation. We thought that transpupillary thermotherapy (TTT) utilizing a lower temperature than that of conventional laser photocoagulation might minimize permanent retinal and choroidal damage. Studies suggest that undesirable effects on vision due to TTT are minimal even if it is applied to foveal and/or parafoveal lesions when TTT requires a larger irradiation spot. The aim of this study was to evaluate the efficacy of TTT in the management of atypical CSC. Methods: We defined atypical CSC as bullous retinal detachment with diffuse or several leakages, severe leakage with fibrin formation under serous retinal detachment, or leakage within a pigment epithelium detachment. Eight consecutive patients with atypical CSC underwent visual acuity testing, ophthalmic examination, color photography, fluorescein angiography, and optical coherence tomography to evaluate the results of transpupillary thermotherapy. Retreatment of atypical CSC was based on ophthalmic examination, optical coherence tomography, and fluorescein angiography. TTT was performed on the leaking spots shown in fluorescein angiography, with a power of 50-250 mW, spot size of 500-1200 μm, and exposure time of 13-60 seconds to minimize retinal damage. Results: In five of eight affected eyes, serous detachments completely resolved within 1 month after the initial TTT. One eye had persistent subretinal fluid and required a second TTT treatment. Two eyes showed no resolution of CSC and were treated by conventional photocoagulation. Initial best-corrected visual acuity (BCVA) ranged from 20/600 to 20/20 (mean, 20/40; median, 20/30). Final BCVA ranged from 20/200 to 20/20 (mean, 20/25; median, 20/20). BCVA improved in all cases. Only two eyes with persistent subretinal fibrin and existing retinal pigment epithelial alternations in macular area showed limited improvement of BCVA despite the absence of subretinal exudation. The presence of retinal attachment was confirmed by optical coherence tomography in six eyes (75%). Conclusions: TTT seems to be effective for the treatment of atypical CSC in the short term. Additional studies are necessary to evaluate the long-term effectiveness and safety. © 2012 Kawamura et al, publisher and licensee Dove Medical Press Ltd.

DOI： 10.2147/OPTH.S28239

Scopus

PubMed

DOI： 10.1016/j.diff.2010.09.081

Web of Science

出版者・発行元：Clinical Ophthalmology  

Purpose: To report the role of Healon5™ injection combined with medications in patient with malignant glaucoma after trabeculectomy with unplanned zonulectomy. Methods: Two days after trabeculectomy with unplanned zonulectomy for neovascular glaucoma in an eye with diabetic retinopathy, a patient developed malignant glaucoma due to the ciliovitreal block caused by the vitreous herniation through the peripheral iridectomy to the limbal incision with flat bleb and anterior chamber, and the intraocular pressure was elevated to 33 mmHg. The medications for the management of malignant glaucoma failed to relieve the malignant mechanism, and Healon5™, a viscoadaptive, viscoelastic, and ophthalmic viscosurgical device, was injected through a paracentesis until the anterior chamber became deep enough to block the vitreous herniation to the limbal incision. Results: After Healon5™ injection, the intraocular pressure was reduced enough that the bleb was re-formed, and the anterior chamber remained deep, even without medication. Conclusions: In patients presenting with malignant glaucoma after trabeculectomy with unplanned zonulectomy, Healon5™ injection, combined with medications, may be a safe and effective approach before performing vitrectomy. © 2010 Ozeki et al, publisher and licensee Dove Medical Press Ltd.

Scopus

記述言語：英語  

DOI： 10.2147/opth.s9318

PubMed

記述言語：英語  

DOI： 10.2147/opth.s9418

PubMed

出版者・発行元：株式会社医学書院  

DOI： 10.11477/mf.1410103018

CiNii Research

記述言語：日本語   出版者・発行元：Japanese Journal of Clinical Ophthalmology  

Purpose : To evaluate the reliability of Pentacam® in the measurement of central corneal thickness. Cases and Method : This prospective study was made on 116 eyes of 116 patients with primary open-angle glaucoma. The age ranged from 35 to 82 years, average 61 years. Thickness of central cornea was measured by Pentacam®, ultrasonography and noncontact specular microscopy. Results : Central corneal thickness averaged 534.3±35.6μm by Pentacam®, 526.5±33.9μm by ultrasonography, and 512.7± 38.7 μm by specular microscopy. These three values were significantly correlated. No significant difference was present between values by Pentacam® and ultrasonography (p=0.30). Values by Pentacam® and specular microscopy were significantly different (p<0.00l). Conclusion : Pentacam® shows same values for central corneal thickness as ultrasonography in eyes with open-angle glaucoma.

Scopus

記述言語：日本語   出版者・発行元：Japanese Journal of Clinical Ophthalmology  

Purpose: To report a case of keratoconus associated with Fuchs heterochromic iridocyclitis. Case = A 28-year-old male presented with ocular hypertension with blurring in his right eye. He had been treated for iridocyclitis in the same eye since one month before. He had been diagnosed with bilateral keratoconus and been using hard contact lens. Findings = His visual acuity was 10 cm counting fingers right and 0.7 left when corrected by -30 diopters. Intraocular pressure (IOP) was 30mmHg right and 14 mmHg left. Both eyes showed typical features of keratoconus. The right eye showed iris atrophy and signs of inflammation in the anterior chamber, leading to the diagnosis of heterochromic iritis. Steroid glaucoma was ruled out. IOP in the right eye normalized after trabeculectomy with corrected visual acuity of 0.07. Conclusion ?' This case illustrates that keratoconus may be associated with heterochromic iritis. The association may be due to common embryological origin of iris and corneal stroma in the neural crest.

Scopus

出版者・発行元：三輪書店  

DOI： 10.11477/mf.5001201054

CiNii Research

出版者・発行元：金原出版  

DOI： 10.18888/ga.0000000053

CiNii Research

出版者・発行元：株式会社医学書院  

DOI： 10.11477/mf.1410211578

CiNii Research

記述言語：日本語  

CiNii Research

記述言語：日本語  

CiNii Research

記述言語：英語