Updated on 2024/03/18

写真a

 
YUKI Kenya
 
Organization
Graduate School of Medicine Program in Integrated Medicine Head and Neck and Sensory Organ Medicine Associate professor
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine Department of Medicine
Title
Associate professor

Degree 1

  1. Doctor (Medicine) ( 2012.3   Keio University ) 

Research Interests 1

  1. Glaucoma

Research Areas 1

  1. Life Science / Ophthalmology  / Glaucoma

Current Research Project and SDGs 1

  1. 難治緑内障に対する緑内障手術成績向上

Professional Memberships 1

  1. 日本眼科学会 緑内障学会 視野画像学会

Awards 1

  1. Suda award

    2017   Japan Glaucoma society  

 

Papers 113

  1. Relation between a history of glaucoma and subjective happiness: the JPHC-Next study

    Yamanishi R., Yotsukura E., Hanyuda A., Uchino M., Yuki K., Negishi K., Yasuda N., Saito I., Kato T., Arima K., Aoyagi K., Tanno K., Yamagishi K., Muraki I., Yamaji T., Iwasaki M., Inoue M., Tsugane S., Sawada N.

    BMJ Open Ophthalmology   Vol. 9 ( 1 )   2024.2

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    Objective This population-based, cross-sectional study was performed to investigate the relationship between a history of glaucoma and subjective happiness. Methods and analysis We conducted a cross-sectional questionnaire-based survey of 92 397 Japanese men and women aged 40–74 who participated in the Japan Public Health Center-based Prospective Study for the Next Generation study. A multivariable logistic regression model was used to estimate the ORs of glaucoma associated with subjective happiness and their two-sided 95% CIs. Results Among 40 727 men and 51 670 women, 1733 participants (635 men, 1098 women) had a history of glaucoma. The odds of unhappiness in male participants with a history of glaucoma were higher (OR 1.26; 95% CI 1.05 to 1.51) than in female participants (OR 1.05; 95% CI 0.90 to 1.23). In a subgroup analysis stratified by age, among participants with a history of glaucoma, males in the younger group (40–59 years) showed the most robust association with unhappiness (OR 1.40; 95% CI 1.04 to 1.88). Conclusions These findings suggest that a history of glaucoma is related with subjective unhappiness, especially in men.

    DOI: 10.1136/bmjophth-2023-001553

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  2. Associations between fatty acid intake and diabetic retinopathy in a Japanese population

    Sasaki M., Yuki K., Hanyuda A., Yamagishi K., Motomura K., Kurihara T., Tomita Y., Mori K., Ozawa N., Ozawa Y., Sawada N., Negishi K., Tsubota K., Tsugane S., Iso H.

    Scientific Reports   Vol. 13 ( 1 ) page: 12903   2023.12

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    Residents of Chikusei City, aged 40–74 years, underwent systemic and ophthalmological screening, and participants with diabetes were included in this analysis. Dietary intake was assessed using a food frequency questionnaire and calculated as a percentage of the total energy. The presence of diabetic retinopathy (DR) was defined as Early Treatment Diabetic Retinopathy Study levels ≥ 20 in either eye. The association between dietary fatty acid intake and DR has been examined in a cross-sectional study. Among the 647 diabetic participants, 100 had DR. The mean total fat and saturated fatty acid (SFA) intakes were 22.0% and 7.3% of the total energy intake, respectively. After adjusting for potential confounders, the highest quartiles of total fat and SFA intake were positively associated with the presence of DR compared with the lowest quartiles (odds ratios (95% confidence intervals), 2.61 (1.07–6.39), p for trend = 0.025, and 2.40 (1.12–5.17), p for trend = 0.013, respectively). No significant associations were found between DR prevalence and monounsaturated or unsaturated fatty acid intake. These results suggest that a high intake of fat and SFA may affect the development of DR, even in individuals whose total fat intake is generally much lower than that of Westerners.

    DOI: 10.1038/s41598-023-39734-x

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  3. Association Between Fatty Acid Intakes and Age-Related Macular Degeneration in a Japanese Population: JPHC-NEXT Eye Study

    Yasukawa T., Sasaki M., Motomura K., Yuki K., Kurihara T., Tomita Y., Mori K., Ozawa N., Ozawa Y., Yamagishi K., Hanyuda A., Sawada N., Tsubota K., Tsugane S., Iso H.

    Translational Vision Science and Technology   Vol. 12 ( 1 ) page: 3   2023.1

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    Purpose: To determine the associations between fatty acid intakes and the prevalence of age-related macular degeneration (AMD) under a population-based cross-sectional study. Methods: Residents of Chikusei City aged ≥40 years underwent systemic and eye screening. AMD was graded according to a modified version of the Age-Related Eye Disease Study classification. Dietary intake was assessed using a food frequency questionnaire and was adjusted for total energy intake. Results: Altogether, 10,788 eyes of 5394 participants, 2116 men (mean [standard devia-tion (SD)] age, 62.4 [9.4] years) and 3278 women (60.6 [9.5] years), were included. The mean daily total fat intakes were 52.8 g and 59.0 g in men and women, respectively. After adjustments for potential confounders, saturated fatty acid (SFA) intake was inversely associated with the prevalence of any AMD in men (for each energy-adjusted 1-SD increase: odds ratio [OR], 0.86; 95% confidence interval [CI], 0.74–1.00). Significant trends were found for decreasing odds ratios of AMD with increasing SFA, monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA) intake (P for trend = 0.02, 0.04, and 0.04, respectively). In women, only a significant association was observed between the second quartile of linolenic acid intake and the prevalence of any AMD (OR, 0.78; 95% CI, 0.62–0.99). Conclusions: We found an inverse association of SFA intake and a weak inverse association of MUFA and PUFA intakes with the prevalence of any AMD in a Japanese popula-tion. Translational Relevance: Adequate fatty acid intake may be necessary to prevent or decelerate AMD.

    DOI: 10.1167/tvst.12.1.3

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  4. Association Between Glycemic Traits and Primary Open-Angle Glaucoma: A Mendelian Randomization Study in the Japanese Population

    Hanyuda A., Goto A., Nakatochi M., Sutoh Y., Narita A., Nakano S., Katagiri R., Wakai K., Takashima N., Koyama T., Arisawa K., Imoto I., Momozawa Y., Tanno K., Shimizu A., Hozawa A., Kinoshita K., Yamaji T., Sawada N., Iwagami M., Yuki K., Tsubota K., Negishi K., Matsuo K., Yamamoto M., Sasaki M., Tsugane S., Iwasaki M.

    American Journal of Ophthalmology   Vol. 245   page: 193 - 201   2023.1

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    PURPOSE: A meta-analysis suggests a relationship between abnormal glucose metabolism and primary open-angle glaucoma (POAG); however, the causal association between them remains controversial. We therefore conducted a Mendelian randomization (MR) study to assess the causal association between genetically predicted glycemic traits and the risk of POAG. DESIGN: Two-sample MR design. METHODS: We examined the genetically predicted measures of fasting glucose, hemoglobin A1c (HbA1c), and fasting C-peptide, in relation to POAG. For the single nucleotide polymorphism (SNP)−exposure analyses, we meta-analyzed the study-level genome-wide associations of fasting glucose levels (n = 17,289; n of SNPs = 34), HbA1c (n = 52,802; n of SNPs = 43), and fasting C-peptide levels (n=1666; n of SNPs = 17) from the Japanese Consortium of Genetic Epidemiology studies. We used summary statistics from the BioBank Japan projects (n = 3980 POAG cases and 18,815 controls) for the SNP−outcome association. RESULTS: We observed no association of genetically predicted HbA1c and fasting C-peptide with POAG. The MR inverse-variance−weighted (IVW) odds ratios (ORs) were 1.44 (95% confidence interval [CI], 0.78-2.65; P = .25) for HbA1c (per 1% increment) and 0.92 (95% CI, 0.56-1.53; P = .76) for fasting C-peptide (per 2-fold increment). A significant association between fasting glucose (per 10 mg/dL−increment) and POAG was observed according to the MR IVW analysis (OR = 1.48 [95% CI, 1.10-1.79, P = .009]); however, sensitivity analyses, including MR−Egger and weighted-median methods, did not support this association (P > .10). CONCLUSIONS: We did not observe strong evidence to support the association between genetically predicted glycemic traits and POAG in the Japanese population.

    DOI: 10.1016/j.ajo.2022.09.004

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  5. Relationship between blood pressure and intraocular pressure in the JPHC-NEXT eye study

    Yasukawa T., Hanyuda A., Yamagishi K., Yuki K., Uchino M., Ozawa Y., Sasaki M., Tsubota K., Sawada N., Negishi K., Tsugane S., Iso H.

    Scientific Reports   Vol. 12 ( 1 ) page: 17493   2022.12

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    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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  6. Validation of a novel iPhone application for evaluating near functional visual acuity

    Hanyuda A., Kubota M., Kubota S., Masui S., Yuki K., Tsubota K., Negishi K.

    Scientific Reports   Vol. 12 ( 1 ) page: 22342   2022.12

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    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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  7. Agreement of glaucoma progression diagnosis between optic disc and macular retinal structure change in a 3-year prospective observational study

    Shiba Daisuke, Adachi Sayaka, Yuki Kenya, Negishi Kazuno

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE   Vol. 63 ( 7 )   2022.6

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  8. Myopia, corneal endothelial cell density and morphology in a Japanese population-based cross-sectional study: the JPHC-NEXT Eye Study

    Aketa N., Uchino M., Kawashima M., Uchino Y., Yuki K., Ozawa Y., Sasaki M., Yamagishi K., Sawada N., Tsugane S., Tsubota K., Iso H.

    Scientific Reports   Vol. 11 ( 1 ) page: 6366   2021.12

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    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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  9. Relation between Body Mass Index and Dry Eye Disease: The Japan Public Health Center-Based Prospective Study for the Next Generation

    Yamanishi R., Sawada N., Hanyuda A., Uchino M., Kawashima M., Yuki K., Tsubota K., Kato T., Saito I., Arima K., Mizukami S., Tanno K., Sakata K., Yamagishi K., Iso H., Yasuda N., Shimazu T., Yamaji T., Goto A., Inoue M., Iwasaki M., Tsugane S.

    Eye and Contact Lens   Vol. 47 ( 8 ) page: 449 - 455   2021.8

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    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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  10. Relationship between unhealthy sleep status and dry eye symptoms in a Japanese population: The JPHC-NEXT study

    Hanyuda A., Sawada N., Uchino M., Kawashima M., Yuki K., Tsubota K., Tanno K., Sakata K., Yamagishi K., Iso H., Yasuda N., Saito I., Kato T., Abe Y., Arima K., Shimazu T., Yamaji T., Goto A., Inoue M., Iwasaki M., Tsugane S.

    Ocular Surface   Vol. 21   page: 306 - 312   2021.7

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    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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  11. Association of Choroidal Thickness with Intermediate Age-Related Macular Degeneration in a Japanese Population

    Sasaki M., Ito Y., Yamasaki T., Yanagi Y., Gemmy Cheung C.M., Motomura K., Kawakami S., Kinoshita T., Yuki K., Hanyuda A., Mimura M., Sawada N., Tsugane S., Tsubota K.

    Ophthalmology Retina   Vol. 5 ( 6 ) page: 528 - 535   2021.6

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    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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  12. 緑内障と転倒や転倒恐怖感

    結城 賢弥

    日本転倒予防学会誌   Vol. 7 ( 3 ) page: 23 - 26   2021.3

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    DOI: 10.11335/tentouyobou.7.3_23

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  13. Intake of Vegetables and Fruits and the Risk of Cataract Incidence in a Japanese Population: The Japan Public Health Center-Based Prospective Study

    Adachi Sayaka, Sawada Norie, Yuki Kenya, Uchino Miki, Iwasaki Motoki, Tsubota Kazuo, Tsugane Shoichiro

    Journal of Epidemiology   Vol. 31 ( 1 ) page: 21 - 29   2021.1

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    <p><b>Background:</b> 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.</p><p><b>Methods:</b> 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.</p><p><b>Results:</b> 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 (OR<sub>Q5 vs Q1</sub>, 0.77; 95% confidence interval [CI], 0.59–1.01; <i>P</i><sub>trend</sub> across quartile categories = 0.03) and cruciferous vegetables (OR<sub>Q5 vs Q1</sub>, 0.74; 95% CI, 0.57–0.96; <i>P</i><sub>trend</sub> = 0.02). In contrast, the OR for cataract was increased with higher intake of vegetables among women (OR<sub>Q5 vs Q1</sub>, 1.28; 95% CI, 1.06–1.53; <i>P</i><sub>trend</sub> = 0.01). Green and yellow vegetable and fruit intake were not associated with cataract in either sex.</p><p><b>Conclusions:</b> This study suggests that vegetables may reduce the risk of cataract in men, but not in women.</p>

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  14. Binocular superior visual field areas associated with driving self-regulation in patients with primary open-angle glaucoma

    Yamasaki T., Yuki K., Awano-Tanabe S., Ono T., Murata H., Tsubota K., Asaoka R.

    British Journal of Ophthalmology   Vol. 105 ( 1 ) page: 135 - 140   2021.1

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    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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  15. Relationship between nerve fiber layer defect and the presence of epiretinal membrane in a Japanese population: The JPHC-NEXT Eye Study

    Uchida A., Sasaki M., Motomura K., Yuki K., Kurihara T., Tomita Y., Ozawa Y., Yamagishi K., Kawasaki R., Hanyuda A., Sawada N., Tsubota K., Tsugane S., Iso H.

    Scientific Reports   Vol. 10 ( 1 ) page: 779   2020.12

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    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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  16. Seasonal variation of intra-ocular pressure in glaucoma with and without dry eye

    Kuze M., Ayaki M., Yuki K., Kawashima M., Uchino M., Tsubota K., Negishi K.

    Scientific Reports   Vol. 10 ( 1 ) page: 13949   2020.12

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    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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  17. Relationships of diabetes and hyperglycaemia with intraocular pressure in a Japanese population: the JPHC-NEXT Eye Study

    Hanyuda A., Sawada N., Yuki K., Uchino M., Ozawa Y., Sasaki M., Yamagishi K., Iso H., Tsubota K., Tsugane S.

    Scientific Reports   Vol. 10 ( 1 ) page: 5355   2020.12

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    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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  18. Infant with trisomy 13 who developed acute elevation of intraocular pressure and glaucoma.

    Yaginuma M, Sato T, Yuki K, Hasegawa T

    Congenital anomalies   Vol. 60 ( 5 ) page: 151 - 152   2020.9

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  19. 症例報告 自然寛解した原発先天緑内障と考えられた1例

    篠田 達郎, 結城 賢弥, 小野 岳志, 坪田 一男

    眼科   Vol. 62 ( 5 ) page: 519 - 524   2020.5

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  20. Evaluation of fear of falling in patients with primary open-angle glaucoma and the importance of inferior visual field damage

    Yuki K., Asaoka R., Ono T., Awano-Tanabe S., Murata H., Tsubota K.

    Investigative Ophthalmology and Visual Science   Vol. 61 ( 3 ) page: 52   2020.3

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    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.

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  21. Physical inactivity, prolonged sedentary behaviors, and use of visual display terminals as potential risk factors for dry eye disease: JPHC-NEXT study

    Hanyuda A., Sawada N., Uchino M., Kawashima M., Yuki K., Tsubota K., Yamagishi K., Iso H., Yasuda N., Saito I., Kato T., Abe Y., Arima K., Tanno K., Sakata K., Shimazu T., Yamaji T., Goto A., Inoue M., Iwasaki M., Tsugane S.

    Ocular Surface   Vol. 18 ( 1 ) page: 56 - 63   2020.1

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    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.

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  22. Quantitative Assessment of the Retina Using OCT and Associations with Cognitive Function

    Ito Y., Sasaki M., Takahashi H., Nozaki S., Matsuguma S., Motomura K., Ui R., Shikimoto R., Kawasaki R., Yuki K., Sawada N., Mimura M., Tsubota K., Tsugane S.

    Ophthalmology   Vol. 127 ( 1 ) page: 107 - 118   2020.1

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    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.

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  23. Tear break-up time and seasonal variation in intraocular pressure in a Japanese population

    Ayaki M., Negishi K., Yuki K., Kawashima M., Uchino M., Tsubota K.

    Diagnostics   Vol. 10 ( 2 )   2020

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    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.

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  24. High myopia and its associated factors in JPHC-NEXT eye study: A cross-sectional observational study

    Mori K., Kurihara T., Uchino M., Torii H., Kawashima M., Sasaki M., Ozawa Y., Yamagishi K., Iso H., Sawada N., Tsugane S., Yuki K., Tsubota K.

    Journal of Clinical Medicine   Vol. 8 ( 11 )   2019.11

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    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.

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  25. 臨床報告 マイトマイシンCを併用したシュレム管外壁開放術併用線維柱帯切開術後に両眼に濾過胞感染を繰り返した1例

    太田 友香, 結城 賢弥, 安達 さやか, 小野 岳志, 芝 大介, 坪田 一男

    眼科   Vol. 61 ( 4 ) page: 421 - 426   2019.4

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  26. Lack of social support and social trust as potential risk factors for dry eye disease: JPHC-NEXT study

    Viet Vu C.H., Uchino M., Kawashima M., Yuki K., Tsubota K., Nishi A., German C.A., Sakata K., Tanno K., Iso H., Yamagishi K., Yasuda N., Saito I., Kato T., Arima K., Tomita Y., Shimazu T., Yamaji T., Goto A., Inoue M., Iwasaki M., Sawada N., Tsugane S.

    Ocular Surface   Vol. 17 ( 2 ) page: 278 - 284   2019.4

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    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.

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  27. 私の経験 緑内障チューブシャント手術後の眼内炎の1例

    藤岡 俊平, 結城 賢弥, 内田 敦郎, 尾関 直毅, 坪田 一男, 芝 大介

    眼科   Vol. 61 ( 2 ) page: 205 - 208   2019.2

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  28. 臨床報告 エクスプレスが無効であった難治性緑内障を合併した虹彩角膜内皮症候群に対してアーメド緑内障バルブが奏効した1例

    矢島 潤一郎, 結城 賢弥, 小野 岳志, 坪田 一男

    眼科   Vol. 61 ( 1 ) page: 91 - 95   2019.1

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    DOI: 10.18888/ga.0000001022

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  29. Latanoprost could exacerbate the progression of presbyopia

    Ayaki M., Tsuneyoshi Y., Yuki K., Tsubota K., Negishi K.

    PLoS ONE   Vol. 14 ( 1 ) page: e0211631   2019.1

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    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.

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  30. Vision Impairment in Elderly and Fall

    Yuki Kenya, Asaoka Ryo

    The Japanese Journal of Rehabilitation Medicine   Vol. 55 ( 11 ) page: 921 - 926   2018.11

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    DOI: 10.2490/jjrmc.55.921

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  31. Association between glaucoma severity and driving cessation in subjects with primary open-angle glaucoma

    Takahashi A., Yuki K., Awano-Tanabe S., Ono T., Shiba D., Tsubota K.

    BMC Ophthalmology   Vol. 18 ( 1 ) page: 122   2018.5

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    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.

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  32. Factors associated with developing a fear of falling in subjects with primary open-angle glaucoma

    Adachi S., Yuki K., Awano-Tanabe S., Ono T., Shiba D., Murata H., Asaoka R., Tsubota K.

    BMC Ophthalmology   Vol. 18 ( 1 ) page: 39   2018.2

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    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.

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  33. Neuroprotective role of retinal SIRT3 against acute photo-stress

    Ban N., Ozawa Y., Osada H., Lin J.B., Toda E., Watanabe M., Yuki K., Kubota S., Apte R.S., Tsubota K.

    npj Aging and Mechanisms of Disease   Vol. 3 ( 1 ) page: 19   2017.12

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    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.

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  34. Factors associated with the occurrence of a fall in subjects with primary open-angle glaucoma

    Adachi S., Yuki K., Awano-Tanabe S., Ono T., Murata H., Asaoka R., Tsubota K.

    BMC Ophthalmology   Vol. 17 ( 1 ) page: 213   2017.11

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    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.

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  35. Dry eye, sleep quality, and mood status in glaucoma patients receiving prostaglandin monotherapy were comparable with those in non-glaucoma subjects

    Ra S., Ayaki M., Yuki K., Tsubota K., Negishi K.

    PLoS ONE   Vol. 12 ( 11 ) page: e0188534   2017.11

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    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.

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  36. 特集 高齢者の自動車運転を支援する 眼疾患と運転適性

    結城 賢弥

    作業療法ジャーナル   Vol. 51 ( 10 ) page: 995 - 999   2017.9

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  37. Predicting future self-reported motor vehicle collisions in subjects with primary open-angle glaucoma using the penalized support vector machine method

    Yuki K., Asaoka R., Awano-Tanabe S., Ono T., Shiba D., Murata H., Tsubota K.

    Translational Vision Science and Technology   Vol. 6 ( 3 ) page: 14   2017.5

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    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.

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  38. Evaluation of functional visual acuity in glaucoma patients

    Ozeki N., Yuki K., Shiba D., Tsubota K.

    Journal of Glaucoma   Vol. 26 ( 3 ) page: 223 - 226   2017

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    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.

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  39. Safety and Efficacy of Two Trabecular Micro-Bypass Stents as the Sole Procedure in Japanese Patients with Medically Uncontrolled Primary Open-Angle Glaucoma: A Pilot Case Series

    Shiba D., Hosoda S., Yaguchi S., Ozeki N., Yuki K., Tsubota K.

    Journal of Ophthalmology   Vol. 2017   page: 9605461   2017

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    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.

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  40. Predictive factors of better outcomes by monotherapy of an antivascular endothelial growth factor drug, ranibizumab, for diabetic macular edema in clinical practice

    Sato S., Shinoda H., Nagai N., Suzuki M., Uchida A., Kurihara T., Kamoshita M., Tomita Y., Iyama C., Minami S., Yuki K., Tsubota K., Ozawa Y.

    Medicine (United States)   Vol. 96 ( 16 ) page: e6459   2017

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    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.

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  41. The Efficacy of Transcorneal Electrical Stimulation for the Treatment of Primary Open-angle Glaucoma: A Pilot Study

    Ota Yuka, Ozeki Naoki, Yuki Kenya, Shiba Daisuke, Kimura Itaru, Tsunoda Kazushige, Shinoda Kei, Ohde Hisao, Tsubota Kazuo

    The Keio Journal of Medicine   Vol. 67 ( 3 ) page: 45 - 53   2017

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    <p>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 (R<sup>2</sup> = 0.176, <i>P</i> = 0.005, Spearman correlation R =0.294, <i>P</i> = 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. </p>

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  42. Risk factors for motor vehicle collisions in patients with primary open-angle glaucoma: A multicenter prospective cohort study

    Yuki K., Awano-Tanabe S., Ono T., Shiba D., Murata H., Asaoka R., Tsubota K.

    PLoS ONE   Vol. 11 ( 11 ) page: e0166943   2016.11

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    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.

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  43. Isolation of monovalerianester a, an inhibitor of fat accumulation, from valeriana fauriei

    Yuki K., Ikeda M., Yoshida S., Ohno O., Suenaga K., Yamada K., Uemura D., Miyamoto K.

    Natural Product Communications   Vol. 10 ( 8 ) page: 1333 - 1334   2015.8

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    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.

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  44. Investigating the influence of visual function and systemic risk factors on falls and injurious falls in glaucoma using the structural equation modeling

    Yuki K., Asaoka R., Tsubota K.

    PLoS ONE   Vol. 10 ( 6 ) page: e0129316   2015.6

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    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.

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  45. Driving self-restriction and motor vehicle collision occurrence in glaucoma

    Ono T., Yuki K., Awano-Tanabe S., Fukagawa K., Shimoyama M., Ozawa Y., Ozeki N., Shiba D., Tsubota K.

    Optometry and Vision Science   Vol. 92 ( 3 ) page: 357 - 364   2015.3

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    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.

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  46. Glaucomatous visual field defect severity and the prevalence of motor vehicle collisions in Japanese: A hospital/clinic-based cross-sectional study

    Ono T., Yuki K., Asaoka R., Kouyama K., Abe T., Tanabe S., Fukagawa K., Uchino M., Shimoyama M., Ozawa Y., Ozeki N., Shiba D., Tsubota K.

    Journal of Ophthalmology   Vol. 2015   page: 497067   2015

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    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.

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  47. The relationship between central visual field damage and motor vehicle collisions in primary open-angle glaucoma patients

    Yuki K., Asaoka R., Tsubota K.

    PLoS ONE   Vol. 9 ( 12 ) page: e115572   2014.12

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    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.

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  48. Predictive factors for non-response to intravitreal ranibizumab treatment in age-related macular degeneration

    Suzuki M., Nagai N., Izumi-Nagai K., Shinoda H., Koto T., Uchida A., Mochimaru H., Yuki K., Sasaki M., Tsubota K., Ozawa Y.

    British Journal of Ophthalmology   Vol. 98 ( 9 ) page: 1186 - 1191   2014.9

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    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.

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  49. Multivariable logistic regression model: A novel mathematical model that predicts visual field sensitivity from macular ganglion cell complex thickness in glaucoma

    Shiba D., Hatou S., Ono T., Hosoda S., Tanabe S., Ozeki N., Yuki K., Shimoyama M., Fukagawa K., Shimmura S., Tsubota K.

    PLoS ONE   Vol. 9 ( 8 ) page: e104126   2014.8

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    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 χ<sup>2</sup> 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 χ<sup>2</sup> 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.

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  50. Biological effects of blocking blue and other visible light on the mouse retina

    Narimatsu T., Ozawa Y., Miyake S., Kubota S., Yuki K., Nagai N., Tsubota K.

    Clinical and Experimental Ophthalmology   Vol. 42 ( 6 ) page: 555 - 563   2014.8

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    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.

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  51. AMPK-NF-κB axis in the photoreceptor disorder during retinal inflammation

    Kamoshita M., Ozawa Y., Kubota S., Miyake S., Tsuda C., Nagai N., Yuki K., Shimmura S., Umezawa K., Tsubota K.

    PLoS ONE   Vol. 9 ( 7 ) page: e103013   2014.7

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    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.

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  52. The use of induced pluripotent stem cells to reveal pathogenic gene mutations and explore treatments for retinitis pigmentosa

    Yoshida T., Ozawa Y., Suzuki K., Yuki K., Ohyama M., Akamatsu W., Matsuzaki Y., Shimmura S., Mitani K., Tsubota K., Okano H.

    Molecular Brain   Vol. 7 ( 1 ) page: 45   2014.6

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    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.

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  53. Dry Eye Disease Is Associated with Deterioration of Mental Health in Male Japanese University Staff

    Tounaka Kaoru, Yuki Kenya, Kouyama Keisuke, Abe Takayuki, Tsubota Kazuo, Kawabe Hiroshi, Yokoyama Kazuhito

    The Tohoku Journal of Experimental Medicine   Vol. 233 ( 3 ) page: 215 - 220   2014

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    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) (<i>P</i> = 0.005). In multiple regression analysis, MCS scores were adversely related to DED in males (<i>P</i> = 0.015). DED was associated with worsened QOL. DED should be regarded as a factor that can lead to deterioration of mental health.

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  54. Atp6ap2/(Pro)renin receptor interacts with Par3 as a cell polarity determinant required for laminar formation during retinal development in mice

    Kanda A., Noda K., Yuki K., Ozawa Y., Furukawa T., Ichihara A., Ishida S.

    Journal of Neuroscience   Vol. 33 ( 49 ) page: 19341 - 19351   2013.12

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    (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.

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  55. Pupillographic evaluation of relative afferent pupillary defect in glaucoma patients

    Ozeki N., Yuki K., Shiba D., Tsubota K.

    British Journal of Ophthalmology   Vol. 97 ( 12 ) page: 1538 - 1542   2013.12

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    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.

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  56. The association between visual field defect severity and fear of falling in primary open-angle glaucoma

    Yuki K., Tanabe S., Kouyama K., Fukagawa K., Uchino M., Shimoyama M., Ozeki N., Shiba D., Ozawa Y., Abe T., Tsubota K.

    Investigative Ophthalmology and Visual Science   Vol. 54 ( 12 ) page: 7739 - 7745   2013.11

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    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.

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  57. Postoperative flat anterior chamber: Incidence, risk factors, and effect on the long-term success of trabeculectomy

    Ono T., Yuki K., Shiba D., Abe T., Kouyama K., Tsubota K.

    Japanese Journal of Ophthalmology   Vol. 57 ( 6 ) page: 520 - 528   2013.11

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    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.

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  58. Neuroprotective role of superoxide dismutase 1 in retinal ganglioncells and inner nuclear layer cells against N-methyl-d-aspartate-induced cytotoxicity

    Yuki K., Yoshida T., Miyake S., Tsubota K., Ozawa Y.

    Experimental Eye Research   Vol. 115   page: 230 - 238   2013.10

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    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.

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  59. Increased urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG)/creatinine level is associated with the progression of normal-tension glaucoma

    Yuki K., Tsubota K.

    Current Eye Research   Vol. 38 ( 9 ) page: 983 - 988   2013.9

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    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.

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  60. Ocular surface complications after trabeculectomy: Incidence, risk factors, time course and prognosis

    Ono T., Yuki K., Ozeki N., Shiba D., Tsubota K.

    Ophthalmologica   Vol. 230 ( 2 ) page: 93 - 99   2013.8

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    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.

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  61. Renin-angiotensin system involvement in the oxidative stress-induced neurodegeneration of cultured retinal ganglion cells

    Ozawa Y., Yuki K., Yamagishi R., Tsubota K., Aihara M.

    Japanese Journal of Ophthalmology   Vol. 57 ( 1 ) page: 126 - 132   2013.1

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    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.

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  62. Intraocular pressure elevation after Descemet's stripping endothelial keratoplasty

    Ozeki N., Yuki K., Shiba D., Shimmura S., Murat D., Tsubota K.

    Japanese Journal of Ophthalmology   Vol. 56 ( 4 ) page: 307 - 311   2012.7

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    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.

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  63. Isolation of 9-hydroxy-10E,12Z-octadecadienoic acid, an inhibitor of fat accumulation from Valeriana fauriei

    Yuki K., Ikeda M., Miyamoto K., Ohno O., Yamada K., Uemura D.

    Bioscience, Biotechnology and Biochemistry   Vol. 76 ( 6 ) page: 1233 - 1235   2012.6

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    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.

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  64. Low diastolic blood pressure is associated with the progression of normal-tension glaucoma

    Okumura Y., Yuki K., Tsubota K.

    Ophthalmologica   Vol. 228 ( 1 ) page: 36 - 41   2012.6

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    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.

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  65. Biological role of lutein in the light-induced retinal degeneration

    Sasaki M., Yuki K., Kurihara T., Miyake S., Noda K., Kobayashi S., Ishida S., Tsubota K., Ozawa Y.

    Journal of Nutritional Biochemistry   Vol. 23 ( 5 ) page: 423 - 429   2012.5

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    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.

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  66. The Vision Van, a Mobile Eye Clinic, Aids Relief Efforts in Tsunami-stricken Areas

    Oshima Catherine Ross, Yuki Kenya, Uchida Atsuro, Dogru Murat, Koto Takashi, Ozawa Yoko, Tsubota Kazuo

    The Keio Journal of Medicine   Vol. 61 ( 1 ) page: 10 - 14   2012

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    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.

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  67. Neural degeneration in the retina of the streptozotocin-induced type 1 diabetes model

    Ozawa Y., Kurihara T., Sasaki M., Ban N., Yuki K., Kubota S., Tsubota K.

    Experimental Diabetes Research   Vol. 2011   page: 108328   2011.12

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    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.

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  68. Roles of AMP-activated protein kinase in diabetes-induced retinal inflammation

    Kubota S., Ozawa Y., Kurihara T., Sasaki M., Yuki K., Miyake S., Noda K., Ishida S., Tsubota K.

    Investigative Ophthalmology and Visual Science   Vol. 52 ( 12 ) page: 9142 - 9148   2011.11

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    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.

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  69. Acute angle-closure glaucoma in a case each of cicatricial retinopathy of prematurity and persistent hyperplastic primary vitreous

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  70. Reproductive success in patients with Hallermann-Streiff syndrome

    Numabe H., Sawai H., Yamagata Z., Muto K., Kosaki R., Yuki K., Kosaki K.

    American Journal of Medical Genetics, Part A   Vol. 155 ( 9 ) page: 2311 - 2313   2011.9

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  71. Retinal ganglion cell loss in superoxide dismutase 1 deficiency

    Yuki K., Ozawa Y., Yoshida T., Kurihara T., Hirasawa M., Ozeki N., Shiba D., Noda K., Ishida S., Tsubota K.

    Investigative Ophthalmology and Visual Science   Vol. 52 ( 7 ) page: 4143 - 4150   2011.6

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    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.

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  72. The association between primary open-angle glaucoma and motor vehicle collisions

    Tanabe S., Yuki K., Ozeki N., Shiba D., Abe T., Kouyama K., Tsubota K.

    Investigative Ophthalmology and Visual Science   Vol. 52 ( 7 ) page: 4177 - 4181   2011.6

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    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.

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  73. Increased serum total antioxidant status and decreased urinary 8-hydroxy-2′-deoxyguanosine levels in patients with normal-tension glaucoma

    Yuki K., Murat D., Kimura I., Tsubota K.

    Acta Ophthalmologica   Vol. 88 ( 7 ) page: e259 - 64   2010.11

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    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.

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  74. Elevated serum immunoglobulin G titers against chlamydia pneumoniae in primary open-angle glaucoma patients without systemic disease

    Yuki K., Kimura I., Shiba D., Imamura Y., Tsubota K.

    Journal of Glaucoma   Vol. 19 ( 8 ) page: 535 - 539   2010.10

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    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.

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  75. Resveratrol prevents light-induced retinal degeneration via suppressing activator protein-1 activation

    Kubota S., Kurihara T., Ebinuma M., Kubota M., Yuki K., Sasaki M., Noda K., Ozawa Y., Oike Y., Ishida S., Tsubota K.

    American Journal of Pathology   Vol. 177 ( 4 ) page: 1725 - 1731   2010.10

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    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.

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  76. Retinal aging and sirtuins

    Ozawa Y., Kubota S., Narimatsu T., Yuki K., Koto T., Sasaki M., Tsubota K.

    Ophthalmic Research   Vol. 44 ( 3 ) page: 199 - 203   2010.9

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    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.

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  77. A new method to prevent loss of mitomycin C soaked sponges under the conjunctiva during trabeculectomy

    Yuki K., Shiba D., Ota Y., Ozeki N., Murat D., Tsubota K.

    British Journal of Ophthalmology   Vol. 94 ( 8 ) page: 1111 - 1112   2010.8

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  78. Neurodegenerative influence of oxidative stress in the retina of a murine model of diabetes

    Sasaki M., Ozawa Y., Kurihara T., Kubota S., Yuki K., Noda K., Kobayashi S., Ishida S., Tsubota K.

    Diabetologia   Vol. 53 ( 5 ) page: 971 - 979   2010.5

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    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.

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  79. Selective laser trabeculoplasty for elevated intraocular pressure following subtenon injection of triamcinolone acetonide

    Yuki K., Inoue M., Shiba D., Kawamura R., Ishida S., Ohtake Y.

    Clinical Ophthalmology   Vol. 4 ( 1 ) page: 247 - 249   2010.4

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    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.

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  80. Serum free fatty acids levels not associated with normal tension glaucoma

    Yuki K., Kimura I., Tsubota K.

    Clinical Ophthalmology   Vol. 4 ( 1 ) page: 91 - 94   2010.4

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    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.

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  81. Reduced-serum vitamin C and increased uric acid levels in normal-tension glaucoma

    Yuki K., Murat D., Kimura I., Ohtake Y., Tsubota K.

    Graefe's Archive for Clinical and Experimental Ophthalmology   Vol. 248 ( 2 ) page: 243 - 248   2010

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    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.

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  82. Trabeculectomy With or Without Intraoperative Sub-Tenon Injection of Triamcinolone Acetonide in Treating Secondary Glaucoma

    Yuki K., Shiba D., Kimura I., Ohtake Y., Tsubota K.

    American Journal of Ophthalmology   Vol. 147 ( 6 ) page: 1055 - 60, 1060.e1   2009.6

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    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.

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  83. End-stage glaucoma in Stevens-Johnson syndrome

    Yuki K., Shimmura S., Shiba D., Tsubota K.

    Japanese Journal of Ophthalmology   Vol. 53 ( 1 ) page: 68 - 70   2009.1

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  84. Lead accumulation as possible risk factor for primary open-angle glaucoma

    Yuki K., Dogru M., Imamura Y., Kimura I., Ohtake Y., Tsubota K.

    Biological Trace Element Research   Vol. 132 ( 1-3 ) page: 1 - 8   2009.1

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    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.

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  85. Fuchs heterochromic iridocyclitis in a case of keratoconus

      Vol. 62 ( 10 ) page: 1687 - 1691   2008.10

  86. Trabeculotomy for the treatment of glaucoma after descemet stripping endothelial keratoplasty

    Yuki K., Shimmura S., Shiba D., Tsubota K.

    British Journal of Ophthalmology   Vol. 92 ( 9 ) page: 1299 - 1300   2008.9

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    DOI: 10.1136/bjo.2008.144766

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  87. Alterations in the anterior chamber angle after implantation of iris-fixated phakic intraocular lenses

    Yamaguchi T., Negishi K., Yuki K., Saiki M., Nishimura R., Kawaguchi N., Tsubota K.

    Journal of Cataract and Refractive Surgery   Vol. 34 ( 8 ) page: 1300 - 1305   2008.8

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    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.

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  88. Diagnosis of steroid-induced glaucoma after photorefractive keratectomy

    Yamaguchi T., Murat D., Kimura I., Negishi K., Yuki K., Tsubota K., Ohtake Y.

    Journal of Refractive Surgery   Vol. 24 ( 4 ) page: 413 - 415   2008.4

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    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.

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  89. 特集 超高齢化社会における緑内障マネージメント 2 加齢変化と視野,運転

    結城 賢弥

    眼科   Vol. 65 ( 3 ) page: 227 - 234   2023.3

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    DOI: 10.18888/ga.0000003053

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  90. Implantation of diffractive extended depth-of-focus intraocular lenses in normal tension glaucoma eyes: A case series

    Bissen-Miyajima H., Ota Y., Yuki K., Minami K.

    American Journal of Ophthalmology Case Reports   Vol. 29   page: 101792   2023.3

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    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.

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  91. 症例報告 ヘッドマウント型視野計が診断に有用であった心因性視覚障害が疑われた1例

    長谷川 岳史, 結城 賢弥, 大出 尚郎

    眼科   Vol. 64 ( 6 ) page: 567 - 573   2022.6

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  92. Retinal Nerve Fiber Layer Thickness and Rim Area Profiles in Asians: Pooled Analysis from the Asian Eye Epidemiology Consortium

    Majithia S., Tham Y.C., Chong C.C.Y., Yu M., Cheung C.Y., Bikbov M.M., Kazakbaeva G.M., Wang N., Hao J., Cao K., Wang Y.X., Sasaki M., Ito Y., Wong I.Y., Cheuk-Hung Chan J., Khanna R.C., Marmamula S., Nakano E., Mori Y., Aung T., Wong T.Y., Jonas J.B., Miyake M., Cheng C.Y., Banerjee S., Chee M.L., Gilmanshin T.R., Iakupova E.M., Matsuda F., Mettla A.L., Pang C.P., Rim T., Soh Z.D., Tham C.C., Tsubota K., Tsujikawa A., Bin Wei W., Wu J., Xu J., Yuki K.

    Ophthalmology   Vol. 129 ( 5 ) page: 552 - 561   2022.5

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    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.

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  93. Retinal Ganglion Cell Axon Regeneration Requires Complement and Myeloid Cell Activity within the Optic Nerve.

    Peterson SL, Li Y, Sun CJ, Wong KA, Leung KS, de Lima S, Hanovice NJ, Yuki K, Stevens B, Benowitz LI

    The Journal of neuroscience : the official journal of the Society for Neuroscience   Vol. 41 ( 41 ) page: 8508 - 8531   2021.10

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    DOI: 10.1523/JNEUROSCI.0555-21.2021

    PubMed

  94. 症例報告 レーザー虹彩切開術が有効であった逆瞳孔ブロックの2例

    上原 朋子, 結城 賢弥, 小野 岳志, 坪田 一男

    眼科   Vol. 63 ( 9 ) page: 899 - 903   2021.9

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    DOI: 10.18888/ga.0000002263

    CiNii Research

  95. 症例報告 エクスプレスTM挿入術後早期に濾過胞感染をきたした1例

    加藤 諒, 結城 賢弥, 小野 岳志, 秋野 邦彦, 坪田 一男

    眼科   Vol. 63 ( 9 ) page: 893 - 898   2021.9

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    DOI: 10.18888/ga.0000002262

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  96. 原著 原発開放隅角緑内障と歩行時間の関係

    守谷 元宏, 小野 岳志, 粟野-田辺 佐智子, 結城 賢弥, 坪田 一男

    眼科   Vol. 61 ( 2 ) page: 185 - 191   2019.2

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    DOI: 10.18888/ga.0000001051

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  97. Quantitative magnetic resonance angiography as a potential predictor for cerebral hyperperfusion syndrome: a preliminary study.

    Andereggen L, Amin-Hanjani S, El-Koussy M, Verma RK, Yuki K, Schoeni D, Hsieh K, Gralla J, Schroth G, Beck J, Raabe A, Arnold M, Reinert M, Andres RH

    Journal of neurosurgery   Vol. 128 ( 4 ) page: 1006 - 1014   2018.4

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    DOI: 10.3171/2016.11.JNS161033

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  98. Lenticular Findings in Emergency Workers at Tokyo Electric Power Fukushima Nuclear Power Plant at 3-5 Years Post-exposure

    Hatsusaka Natsuko, Yuki Kenya, Uchino Miki, Tsubota Kazuo, Sasaki Hiroshi

    The Journal of The Japanese Society for Cataract Research   Vol. 30 ( 1 ) page: 57 - 60   2018

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    DOI: 10.14938/cataract.10-010

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  99. Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration.

    Li Y, Andereggen L, Yuki K, Omura K, Yin Y, Gilbert HY, Erdogan B, Asdourian MS, Shrock C, de Lima S, Apfel UP, Zhuo Y, Hershfinkel M, Lippard SJ, Rosenberg PA, Benowitz L

    Proceedings of the National Academy of Sciences of the United States of America   Vol. 114 ( 2 ) page: E209 - E218   2017.1

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    DOI: 10.1073/pnas.1616811114

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  100. Effects of laser in situ keratomileusis on mental health-related quality of life

    Tounaka-Fujii K., Yuki K., Negishi K., Toda I., Abe T., Kouyama K., Tsubota K.

    Clinical Ophthalmology   Vol. 10   page: 1859 - 1864   2016.9

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    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

  101. Evaluation of surgical outcomes for ptosis surgery by face recognition software

    Ideta S., Ota Y., Yuki K., Noda M., Inoue M., Tsubota K.

    Asia-Pacific Journal of Ophthalmology   Vol. 4 ( 1 ) page: 14 - 18   2015

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    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

  102. Role of the Vision Van, a mobile ophthalmic outpatient clinic, in the Great East Japan Earthquake

    Yuki K., Nakazawa T., Kurosaka D., Yoshida T., Alfonso E.C., Lee R.K., Takano S., Tsubota K.

    Clinical Ophthalmology   Vol. 8   page: 691 - 696   2014.4

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    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

  103. Ophthalmic viscoelastic device injection for the treatment of flat anterior chamber after trabeculectomy: A case series study

    Hosoda S., Yuki K., Ono T., Tsubota K.

    Clinical Ophthalmology   Vol. 7   page: 1781 - 1785   2013.9

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    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

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  104. The association between primary open-angle glaucoma and fall: An observational study

    Tanabe S., Yuki K., Ozeki N., Shiba D., Tsubota K.

    Clinical Ophthalmology   Vol. 6 ( 1 ) page: 327 - 331   2012.3

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    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

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  105. Transpupillary thermotherapy for atypical central serous chorioretinopathy

    Kawamura R., Ideta H., Hori H., Yuki K., Uno T., Tanabe T., Tsubota K., Kawasaki T.

    Clinical Ophthalmology   Vol. 6 ( 1 ) page: 175 - 179   2012.2

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    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

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  106. A gene therapy for a gene mutation in human iPS cell using helper-dependent adenoviral vector

    Yoshida T., Koizumi H., Yuki K., Kubota S., Hirabayashi Y., Suzuki K., Mitani K., Kobayashi T., Ohyama M., Amagai M., Okada Y., Akamatsu W., Tsubota K., Shimmura S., Ozawa Y., Okano H.

    DIFFERENTIATION   Vol. 80   page: S42 - S42   2010.11

  107. Alternative approach to treating malignant glaucoma after trabeculectomy with unplanned zonulectomy

    Ozeki N., Yuki K., Kimura I.

    Clinical Ophthalmology   Vol. 4 ( 1 ) page: 383 - 385   2010.5

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    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.

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  108. Alternative approach to treating malignant glaucoma after trabeculectomy with unplanned zonulectomy.

    Ozeki N, Yuki K, Kimura I

    Clinical ophthalmology (Auckland, N.Z.)   Vol. 4   page: 383 - 5   2010.5

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    DOI: 10.2147/opth.s10297

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  109. Selective laser trabeculoplasty for elevated intraocular pressure following subtenon injection of triamcinolone acetonide.

    Yuki K, Inoue M, Shiba D, Kawamura R, Ishida S, Ohtake Y

    Clinical ophthalmology (Auckland, N.Z.)   Vol. 4   page: 247 - 9   2010.4

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    DOI: 10.2147/opth.s9318

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  110. Serum free fatty acids levels not associated with normal tension glaucoma.

    Yuki K, Kimura I, Tsubota K

    Clinical ophthalmology (Auckland, N.Z.)   Vol. 4   page: 91 - 4   2010.2

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    DOI: 10.2147/opth.s9418

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  111. Thickness of central cornea measured by Pentacam(R),ultrasonography and specular microscopy in eyes with primary open-angle glaucoma

      Vol. 63 ( 12 ) page: 1777 - 1781   2009.11

  112. Thickness of central cornea measured by Pentacam®, ultrasonography and specular microscopy in eyes with primary open-angle glaucoma Reviewed

    Hosoda S., Yuki K., Saeki M., Funayama T., Shiba D., Ohtake Y., Kimura I., Tsubota K.

    Japanese Journal of Clinical Ophthalmology   Vol. 63 ( 12 ) page: 1777 - 1781   2009.11

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    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.

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  113. Fuchs heterochromic iridocyclitis in a case of keratoconus Reviewed

    Yaguchi S., Yuki K., Shiba D., Kimura I., Matsumoto Y., Ohtake Y., Tsubota K.

    Japanese Journal of Clinical Ophthalmology   Vol. 62 ( 10 ) page: 1687 - 1691   2008.11

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    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.

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Books 1

  1. Antioxidative treatment for neuroprotection in glaucoma

    Yuki K.

    Neuroprotection and Neuroregeneration for Retinal Diseases  2014.5  ( ISBN:9784431549642

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    Glaucoma is a neurodegenerative disease with progressive retinal ganglion cell apoptosis. IOP elevation is a modifiable proven risk factor for glaucoma. Although a lot of new medicines and surgeries for lowering IOP have come in, glaucoma is still a leading cause of blindness in the world, motivating us to search IOP-independent treatment. Accumulating evidences point to an association between oxidative stress and glaucoma. Increased level of oxidative DNA damage, lipid peroxidation, and protein oxidation and reduced antioxidative status were observed in serum, trabecular meshwork, and aqueous humor of human glaucoma subjects. Antioxidants protect retinal ganglion cell apoptosis from IOP elevation, optic nerve injury, inflammation, and impaired ocular blood flow in vivo and in vitro. Some population-based epidemiological studies showed that higher antioxidant intake reduced risk of glaucoma. This review focused on the present evidence that support the possibility of antioxidant neuroprotective treatment for glaucoma.

    DOI: 10.1007/978-4-431-54965-9_4

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MISC 10

  1. Glaucoma Q & A 悪性緑内障とはどんな病気ですか?診断や治療法についても教えてください.

    結城 賢弥

    Frontiers in Glaucoma   Vol. 1 ( 62 ) page: 64 - 67   2021.9

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    Publisher:メディカルレビュー社  

    DOI: 10.34449/j0024.01.62_0064-0067

    CiNii Research

  2. 緑内障と転倒や転倒恐怖感

    結城 賢弥

    日本転倒予防学会誌   Vol. 7 ( 3 ) page: 23 - 26   2021.3

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    Language:Japanese   Publisher:日本転倒予防学会  

    DOI: 10.11335/tentouyobou.7.3_23

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  3. 綜説 緑内障の生活リスク

    結城 賢弥

    眼科   Vol. 63 ( 1 ) page: 57 - 64   2021.1

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    Publisher:金原出版  

    DOI: 10.18888/ga.0000001998

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  4. Vision Impairment in Elderly and Fall

    Yuki Kenya, Asaoka Ryo

    The Japanese Journal of Rehabilitation Medicine   Vol. 55 ( 11 ) page: 921 - 926   2018.11

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    Language:Japanese   Publisher:The Japanese Association of Rehabilitation Medicine  

    DOI: 10.2490/jjrmc.55.921

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  5. 増刊号 7年前の常識は現在の非常識!-眼科診療の最新標準 3.緑内障 3)治療 線維柱帯切開術の基本手技とその術後管理

    結城 賢弥

    臨床眼科   Vol. 72 ( 11 ) page: 183 - 187   2018.10

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    Publisher:株式会社医学書院  

    DOI: 10.11477/mf.1410212902

    CiNii Research

  6. 特集 高齢者の自動車運転を支援する 眼疾患と運転適性

    結城 賢弥

    作業療法ジャーナル   Vol. 51 ( 10 ) page: 995 - 999   2017.9

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    Publisher:三輪書店  

    DOI: 10.11477/mf.5001201054

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  7. 特集 緑内障の非眼圧的要素 3.抗酸化物質と緑内障進行予防との関連

    結城 賢弥

    眼科   Vol. 59 ( 6 ) page: 589 - 594   2017.6

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    Publisher:金原出版  

    DOI: 10.18888/ga.0000000053

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  8. 増刊号 緑内障なんでも質問箱-エキスパートに聞いたら最新エビデンスをもとにズバリと答えてくれた! III.治療編 【臨床研究】 41.緑内障の進行は生活習慣と関連がありますか?

    結城 賢弥

    臨床眼科   Vol. 69 ( 11 ) page: 213 - 216   2015.10

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    Publisher:株式会社医学書院  

    DOI: 10.11477/mf.1410211578

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  9. A New Method to Prevent MMC Soaked Sponge Lost under the Conjunctiva during Trabeculectomy

    YUKI Kenya

      Vol. 23 ( 1 ) page: 86 - 87   2010.1

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  10. 緑内障における前房容積 : ペンタカム^【○!R】による解析

    結城 賢弥, 大竹 雄一郎

    あたらしい眼科 = Journal of the eye   Vol. 23 ( 2 ) page: 191 - 192   2006.2

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Presentations 29

  1. Acute angle-closure glaucoma in a case each of cicatricial retinopathy of prematurity and persistent hyperplastic primary vitreous

    2011.10.15 

  2. Association between driving avoidance at night and the severity of primary-open angle glaucoma in a Japanese population International conference

    Hanyuda Akiko, Yuki Kenya, Tanabe-Awano Sachiko, Ono Takeshi, Shiba Daisuke, Tsubota Kazuo

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2019.7 

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  3. Association between glaucoma severity and driving cessation in subjects with primary open-angle glaucoma.

    Yuki Kenya, Tanabe-Awano Sachiko, Ono Takeshi, Takahashi Aya, Shiba Daisuke, Tsubota Kazuo

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2018.7 

  4. Baseline characteristics and response to intravitreal ranibizumab therapy for age-related macular degeneration

    Suzuki Misa, Nagai Norihiro, Izumi-Nagai Kanako, Shinoda Hajime, Koto Takashi, Uchida Atsuro, Mochimaru HIroshi, Yuki Kenya, Tsubota Kazuo, Ozawa Yoko

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2013.6 

  5. Comparison of reproducibility in glaucoma severity staging by structural measurement and functional test

    Shiba Daisuke, Hirano Eri, Adachi Sayaka, Yuki Kenya, Tsubota Kazuo

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2017.6 

  6. Comparison of reproducibility in quantitative evaluation of glaucoma between structure and function

    Shiba Daisuke, Hirano Eri, Adachi Sayaka, Ono Takeshi, Yuki Kenya, Tsubota Kazuo

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2016.9 

  7. Corneal Endothelial Cell Density and Associated Factors in a Cross Sectional, Population-Based Study in Japan: The Chikusei Eye Study

    Nakayama Naohiko, Kawashima Motoko, Yuki Kenya, Sasaki Mariko, Ozawa Yoko, Yamagishi Kazumasa, Sawada Norie, Tsugane Shoichiro, Iso Hiroyasu, Tsubota Kazuo

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2016.9 

  8. Driving habits and graucomatous visual field loss in Japanese population

    Hanyuda Akiko, Yuki Kenya, Tanabe-Awano Sachiko, Ono Takeshi, Shiba Daisuke, Tsubota Kazuo

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2018.7 

  9. Effect of LASIK on mental health-related quality of life

    Yajima Junichiro, Yuki Kenya, Tounaka-Fujii Kaoru, Negishi Kazuno, Toda Ikuko, Ide Takeshi, Fukumoto Teruki, Miki Emiko, Tsubota Kazuo

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2016.9 

  10. Enhanced repeatability by B-scan averaging in measurement of macular ganglion cell complex with spectral-domain optical coherence tomography in glaucomatous eye.

    Adachi Sayaka, Shiba Daisuke, Hirano Eri, Ono Takeshi, Yuki Kenya, Tsubota Kazuo

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2016.9 

  11. Functional analysis of (pro)renin receptor in mouse retinal development

    Kanda Atsuhiro, Noda Kousuke, Yuki Kenya, Ozawa Yoko, Furukawa Takahisa, Ichihara Atsuhiro, Ishida Susumu

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2013.6 

  12. Histological Examination of Filtering Blebs With in vivo Confocal Microscope

    Shiba D., Murat D., Sato E. Adan, Ozeki N., Yuki K., Tsubota K.

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2010.4 

  13. Impact of Cataract on Repeatability of Measurements of Macular Inner Retinal Thickness with Spectral-domain Optical Coherence Tomography in Glaucoma eye

    Shiba Daisuke, Adachi Sayaka, Hirano Eri, Ota Yuka, Ono Takeshi, Yuki Kenya, Tsubota Kazuo

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2019.7 

  14. Intraocular Pressure Reduction of Modified 360-degree Suture Trabeculotomy in Intent-to-treat Eyes

    Shiba Daisuke, Ono Takeshi, Ozeki Naoki, Yuki Kenya, Tsubota Kazuo

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2013.6 

  15. Neuroprotective Effect of an Anti-Oxidant, Lutein, on Light-Induced Retinal Degeneration

    Sasaki M., Ozawa Y., Kurihara T., Kubota S., Yuki K., Noda K., Kobayashi S., Ishida S., Tubota K.

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2010.4 

  16. Potential Role of Superoxide Dismutase I in Normal-Tension Glaucoma

    Yuki K., Yoshida T., Kurihara T., Kubota S., Sasaki M., Noda K., Ishida S., Ozawa Y., Tsubota K.

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2010.4 

  17. Prevalence of diabetic retinopathy by the glycemic and blood pressure levels in an adult Japanese population: the Chikusei Eye Study

    Sasaki Mariko, Motomura Kaoru, Ozawa Yoko, Yuki Kenya, Kawasaki Ryo, Yamagishi Kazumasa, Sawada Norie, Tsugane Shoichiro, Iso Hiroyasu, Tsubota Kazuo

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2016.9 

  18. Purification of Human iPS Cells From Feeder Cells to Analyze DNA Sequence

    Yoshida T., Koizumi H., Yuki K., Tsubota K., Ozawa Y., Okano H.

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2010.4 

  19. Relationship Between Relative Afferent Pupillary Defect with Pupillography and Ganglion Cell Complex Thickness by Optical Coherence Tomography in Asymmetric Glaucoma

    Ozeki Naoki, Yuki Kenya, Shiba Daisuke, Tsubota Kazuo

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2013.6 

  20. Relationship Between Within-eye Asymmetry of Relative Afferent Pupillary Defect with Pupillography and Ganglion Cell Complex Thickness by Optical Coherence Tomography in Asymmetric Glaucoma

    Ono Takeshi, Ozeki Naoki, Shiba Daisuke, Yuki Kenya, Tsubota Kazuo

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2014.4 

  21. Risk factors for incident motor vehicle collisions in patients with primary open-angle glaucoma: a prospective study.

    Yuki Kenya, Awano-Tanabe Sachiko, Ono Takeshi, Ozeki Naoki, Shimoyama Masaru, Asaoka Ryo, Shiba Daisuke, Tsubota Kazuo

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2016.9 

  22. Risk of Motor Vehicle Collisions in Glaucoma

    Tanabe S., Yuki K., Ozeki N., Shiba D., Tsubota K.

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2010.4 

  23. Seasonal variation of intra-ocular pressure in glaucoma with and without short tear break-up time

    Ayaki Masahiko, Kuze Manami, Yuki Kenya, Kawashima Motoko, Uchino Miki, Tsubota Kazuo, Negishi Kazuno

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2019.7 

  24. Surgical effect of modified 360-degree suture trabeculotomy compared to trabeculotomy

    Ono Takeshi, Shiba Daisuke, Adachi Sayaka, Ui Rihito, Ozeki Naoki, Yuki Kenya, Tsubota Kazuo

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2015.6 

  25. The association between the presence of epiretinal membrane and nerve fiber layer defect in an adult Japanese population : The Chikusei Eye Study

    Uchida Atsuro, Sasaki Mariko, Ozawa Yoko, Motomura Kaoru, Yuki Kenya, Yamagishi Kazumasa, Sawada Norie, Tsugane Shoichiro, Iso Hiroyasu, Tsubota Kazuo

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2016.9 

  26. The change of macular ganglion cell complex thickness in preperimetric glaucoma and normal eyes

    Shiba Daisuke, Ono Takeshi, Ozeki Naoki, Yuki Kenya, Tsubota Kazuo

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2014.4 

  27. Transcorneal electrical stimulation in patients with primary open-angle glaucoma: A prospective long-term, case-series study

    Ota Yuka, Ozeki Naoki, Yuki Kenya, Shiba Daisuke, Kimura Itaru, Tsunoda Kazushige, Shinoda Kei, Ohde Hisao, Tsubota Kazuo

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2016.9 

  28. Fuchs heterochromic iridocyclitis in a case of keratoconus

    2008.10.15 

  29. AMPK-NF-kappa B axis modulates visual function during inflammation

    Kamoshita Mamoru, Kubota Shunsuke, Yuki Kenya, Miyake Seiji, Nagai Norihiro, Umezawa Kazuo, Tsubota Kazuo, Ozawa Yoko

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  2013.6 

▼display all

KAKENHI (Grants-in-Aid for Scientific Research) 4

  1. 深層学習、光干渉断層計測定結果を用いた変分近似ベイズ視野進行予測モデルの拡張

    Grant number:18KK0253  2018.10 - 2024.3

    科学研究費助成事業  国際共同研究加速基金(国際共同研究強化(B))

    朝岡 亮, 結城 賢弥, 松浦 将人, 藤野 友里, 村田 博史, 谷戸 正樹, 平澤 一法

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    Authorship:Coinvestigator(s) 

    2616眼の緑内障眼の視野を用いて、光干渉断層計の計測結果から視野感度を推測するタスクと、時系列視野進行を推測するタスクをジョイントさせたマルチテスク学習モデルを構築した。このモデルでは早期と進行期での推測を別個に行う改善が図られている。この結果予測精度は既存のモデルに比べて有意に改善していた。この結果については論文投稿中である(Under Review)。
    <BR>
    また、研究分担者の平澤一法が英国Moorfields Eye Hospitalに滞在し、United Kingdom Glaucoma Treatmaent Studyのデータを取得し、解析を行っている。
    Guided Progression Analysis定義について解析が進んだため。United Kingdom Glaucoma Treatmaent Studyのデータを利用し、解析を行っているが、コロナ禍の影響でこちらはやや進行が当初計画より遅れている。
    United Kingdom Glaucoma Treatmaent Studyのデータを取得し、また国内外の関連データをさらに拡充させ解析を行っていく。

  2. Analytical epidemiological study for investigating risk factor of ophthalmic diseases including age-related macular degeneration, and glaucoma.

    Grant number:16K11271  2016.4 - 2021.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    YUKI Kenya

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    Authorship:Principal investigator 

    Grant amount:\4550000 ( Direct Cost: \3500000 、 Indirect Cost:\1050000 )

    This study is an ophthalmic epidemiological study conducted in Chikusei City, Ibaraki Prefecture. About 10,000 residents of Chikusei City participated in this study. In this study, the refractive index measurement, intraocular pressure measurement, corneal endothelial cell number measurement, anterior chamber depth and axial length measurement, retinal thickness measurement and ophthalmic disease screening using optical coherence tomography, and fundus photography. As a result, we have revelated that there is a significant increase in corneal endothelium malformation in myopia, high intraocular pressure in diabetic patients, high rate of association between epiretinal membrane and retinal nerve fiber bundle defect, and association between intraocular pressure and high myopia.

  3. Establishment of efficient differentiation method of retinal ganglion cells from human iPS cells.

    Grant number:22791689  2010 - 2011

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)

    YUKI Kenya

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    Authorship:Principal investigator 

    Grant amount:\3900000 ( Direct Cost: \3000000 、 Indirect Cost:\900000 )

    [Purpose] To investigate the efficient way collecting Rx-positive Retinal progenitor cell by FACS.
    [Method] We used mouse iPS(miPS) cells which was inserted Nanog-GFP-IRES-Puro reporter construct. The GFP was negative when the iPS cell when it was induced differentiation.(Okita, Yamanaka et al. Nature 2007). A Bacterial artificial chromosome(BAC) clone containing the mouse Rax gene in its center was isolated. By using the recombination technique, we inserted a DsRed-Neo cassette into the 5` UTR of the mouse Rax gene. We introduced the modified BAC into miPS cells by electroporation. Mice iPS cells were dissociated to single cells, and 5×10^4 cells per 1 ml differentiation medium(see ref) were seeded into bacterial-grade dishes(10ml). miPS aggregates were generated spontaneuously in a suspension culture within 1d. Medium was changed on day 3. Dkk1(100 ng/ml) LeftyA(500 ng/ml), 5% FBS and activin-A were added to the differentiation medium.(Osakada, Takahashi et al et al Nature Protocol)
    [Results] Rx-DsRED positive cells were observed in embryoid body after 9 day in the SFEB/DLFA culture. Rx-DsRed+mouse iPS cells are selected by flow cytometry. After flow cytometry, RxDsRed positive cells were observed only in the Ds-Red section by Imager.
    [Conclsion] By using flowcytometry, we obtain Rx-DsRed positive cells, which are thought to be retinal progenitor cells.

  4. Primary culture of mice non-pigmented ciliary epithelium and establishment of the screening system of anti-glaucoma medications by using mice non-pigmented ciliary epithelium in vitro.

    Grant number:20791273  2008 - 2009

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)

    YUKI Kenya

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    Authorship:Principal investigator 

    Grant amount:\4030000 ( Direct Cost: \3100000 、 Indirect Cost:\930000 )

    We tried to cultivate non-pigmented ciliary epithelial cells by explant of ciliary body. However, only pigmented ciliary cells were obtained. In the experiment, we observed sphere formation of GFP-positive cells from ciliary body of P0cre-GFP mice. This showed that neural stem cell from neural crest presents in the ciliary body of mice.