Hidetoshi Yamashita

Yamagata University, Ямагата, Yamagata, Japan

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Publications (171)492.4 Total impact

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    ABSTRACT: A higher plasma aldosterone-renin ratio (ARR) is an established marker for screening for primary aldosteronism (PA). The association between higher ARR and mortality in a general population has not been fully explored. We here examined whether higher ARR is a risk factor for total and cause-specific mortality in a Japanese population.
    Clinical Endocrinology 10/2014; · 3.40 Impact Factor
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    ABSTRACT: Indocyanine green (ICG), an adjuvant used for peeling of the internal limiting membrane (ILM) during vitreous surgery for idiopathic macular hole (MH), has been reported to be toxic, possibly affecting postoperative visual acuity. We compared the long-term outcomes (within 2 years) of brilliant blue G (BBG), ICG, and triamcinolone acetonide (TA).
    Japanese journal of ophthalmology. 09/2014;
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    ABSTRACT: Purpose To determine retinal and systemic risk associations of branch retinal vein occlusion (BRVO) over 5 years in adult population-based cohort in Japan.Methods The Funagata study is a population-based longitudinal cohort study in Yamagata, Japan. In 2000-2, we performed baseline survey including fundus photography and systemic examination. In 2005-7, 5-year follow-up survey was performed and newly developed BRVO cases were determined. There were 954 persons who attended both baseline and 5-year follow-up survey; 878 persons had good quality fundus photographs suitable for grading (right eye only). Using multiple logistic regression models, retinal and systemic risk characteristics were determined.Results Mean age of study participants were 58.9 years old and 57.2% were women. Prevalence of diabetes and hypertension was 4.0% and 32.2%, respectively. There were 12 newly developed BRVO over 5- years (1.37%, right eyes only). In multiple logistic regression models including those significantly associated systemic risks, older age (adjusted odds ratio [OR] 1.15 per 1 year, 95% confidence interval [CI] 1.02-1.31, p=0.026) and waist-to-hip ratio (adjusted OR 6.15 per 0.1, 95%CI 1.50-25.3, p=0.012) remained as significant risk characteristics. Retinal vessel opacification was significantly associated with incident BRVO after adjusting for systemic risk characteristics.Conclusion In addition to older age, larger waist-to-hip ratio was identified as a modifiable systemic risk characteristic of 5-year incident BRVO. Retinal vessel opacification was also identified as a risk characteristic in the retina; there is a potential as a marker to predict BRVO. Commercial interest
    Acta ophthalmologica 09/2014; 92(s253). · 2.44 Impact Factor
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    ABSTRACT: To facilitate personalized health care for multifactorial diseases, risks of genetic and clinical/environmental factors should be assessed together for each individual in an integrated fashion. This approach is possible with the likelihood ratio (LR)-based risk assessment system, as this system can incorporate manifold tests. We examined the usefulness of this system for assessing type 2 diabetes (T2D). Our system employed 29 genetic susceptibility variants, body mass index (BMI), and hypertension as risk factors whose LRs can be estimated from openly available T2D association data for the Japanese population. The pretest probability was set at a sex- and age-appropriate population average of diabetes prevalence. The classification performance of our LR-based risk assessment was compared to that of a non-invasive screening test for diabetes called TOPICS (with score based on age, sex, family history, smoking, BMI, and hypertension) using receiver operating characteristic analysis with a community cohort (n = 1263). The area under the receiver operating characteristic curve (AUC) for the LR-based assessment and TOPICS was 0.707 (95% CI 0.665-0.750) and 0.719 (0.675-0.762), respectively. These AUCs were much higher than that of a genetic risk score constructed using the same genetic susceptibility variants, 0.624 (0.574-0.674). The use of ethnically matched LRs is necessary for proper personal risk assessment. In conclusion, although LR-based integrated risk assessment for T2D still requires additional tests that evaluate other factors, such as risks involved in missing heritability, our results indicate the potential usability of LR-based assessment system and stress the importance of stratified epidemiological investigations in personalized medicine.
    Endocrine Journal 07/2014; 61. · 2.23 Impact Factor
  • Koichi Nishitsuka, Hidetoshi Yamashita
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    ABSTRACT: To evaluate a novel surgical technique for IOL fixation using a newly designed suture thread inserter.
    Ophthalmic surgery, lasers & imaging retina. 06/2014;
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    ABSTRACT: The aim of this study was to examine the efficacy and surgical success rates of amniotic membrane (AM) transplantation performed for corneal perforation closure using a novel technique. This study included 6 eyes from 6 patients with corneal perforation who had received AM transplantation between May 2011 and April 2012. The AM was collected from human placenta shortly after cesarean section. In surgery, the AM was folded into pleats and used to plug the wound using 10-0 nylon suture. The wound was then covered with an AM seal. After reepithelialization and AM scarring, sutures were removed. All 6 patients had successful wound closure with 1 surgery. One patient underwent optical keratoplasty later, and 1 patient required combined preserved sclera transplantation. The absolute value of astigmatism decreased to <3.50 diopters (D) 3 months after surgery and to <3.00 D 6 months after surgery in patients with peripheral AM transplants. The visual acuity gradually improved over the first 3 months after surgery, and visual acuity gains were maintained at the 6-month postoperative mark. The AM transplantation procedure may be an effective option for treating corneal perforations when the wound is circular or irregular, except for incised wounds. Our "Pleats Fold" AM transplantation technique can achieve definite closure and effectively repair wounds of various sizes. Postoperative astigmatic values were acceptable. Therefore, we recommend this procedure for repairing lesions <3 mm in diameter that do not involve the central cornea and that are infection free.
    Cornea 04/2014; · 1.75 Impact Factor
  • Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine. 04/2014; 103(4):987-93.
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    ABSTRACT: Compared with the peripheral corneal limbus, the human central cornea lacks blood vessels, which is responsible for its immunologically privileged status and high transparency. Dendritic cells (DCs) are present in the central avascular area of inflamed corneas, but the mechanisms of their migration to this location are poorly understood. Here, we investigated the contribution of vessel formation to DC migration into the central cornea, and analyzed the DC chemotactic factors produced by human corneal epithelial (HCE) cells. Using human eyes obtained from surgical procedures, we then assessed vessel formation, DC distribution, and activin A expression immunohistochemically. The results demonstrated increased numbers of vessels and DCs in the central area of inflamed corneas, and a positive correlation between the number of vessels and DCs. Activin A was expressed in the subepithelial space and the endothelium of newly formed blood vessels in the inflamed cornea. In infected corneas, DCs were present in the central area but no vascularization was observed, suggesting the presence of chemotactic factors that induced DC migration from the limbal vessels. To test this hypothesis, we assessed the migration of monocyte-derived DCs toward HCE cell supernatants with or without lipopolysaccharide (LPS) stimulation of HCE cells and inflammatory cytokines (released by HCE cells). DCs migrated toward tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and activin A, as well as LPS-stimulated HCE cell supernatants. The supernatant contained elevated TNF-α, IL-6, and activin A levels, suggesting that they were produced by HCE cells after LPS stimulation. Therefore, vessels in the central cornea might constitute a DC migration route, and activin A expressed in the endothelium of newly formed vessels might contribute to corneal vascularization. Activin A also functions as a chemotactic factor, similar to HCE-produced TNF-α and IL-6. These findings enhance our understanding of the pathophysiology of corneal inflammation during infection.
    PLoS ONE 01/2014; 9(10):e109859. · 3.53 Impact Factor
  • Koichi Nishitsuka, Hidetoshi Yamashita
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    ABSTRACT: The world's population is aging, and simultaneously, the prevalence of diabetes mellitus worldwide is rapidly increasing. Therefore, the clinical management of diabetic retinopathy and diabetic maculopathy in elderly patients with diabetes is increasingly becoming more important. Therefore, collaboration between ophthalmologists and physicians is mandatory. The international clinical diabetic retinopathy and macular edema disease severity scales are very useful for information sharing between ophthalmologists and diabetologists. This review describes a strategy to assess symptoms of diabetes, including the clinical course of retinopathy and maculopathy, pathological changes, and pathogenesis, as well as details an updated treatment modality. Elderly patients tend to present with multiple complications that should be considered by the management team.
    Nippon rinsho. Japanese journal of clinical medicine 11/2013; 71(11):2005-9.
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    ABSTRACT: To report the findings of fine folds on the retina obtained by spectral-domain optical coherence tomography (OCT). A retrospective non-comparative case series; 26 eyes of diabetic macular edema (DME) patients who underwent vitrectomy were observed using three-dimensional (3D) images of OCT preoperatively and postoperatively. The specimens were investigated immunohistochemically. Using only tomography, non-tractional vitreoretinal interfaces were observed in 15 eyes and tractional vitreoretinal interfaces in the other 11 eyes. Using 3D imaging, we observed fine folds in 11 eyes among 15 cases showing non-tractional interfaces. Based on these findings, the state of the vitreoretinal interface was classified into 3 patterns. Group 1, both tomography and 3D imaging showed smooth retinal surfaces. Group 2, tomography showed a smooth retinal surface, but 3D imaging showed fine folds on the retina. Group 3, both tomography and 3D imaging showed a tractional vitreoretinal interface with an obvious epiretinal membrane and/or taut posterior vitreous cortex. The fine folds in group 2 disappeared and macular edema improved after inner limiting membrane (ILM) peeling, and the CRT of groups 2 and 3 reduced significantly. The fine folds were confirmed to involve the ILM because type IV collagen expression was detected in the surgically obtained specimens. We observed tangential fine folds of the ILM. These were detected by using only 3D imaging, and might be useful for investigating the optimal indication of vitrectomy for DME.
    Japanese Journal of Ophthalmology 10/2013; · 1.27 Impact Factor
  • International Journal of Epidemiology 08/2013; · 6.98 Impact Factor
  • Journal of Human Genetics 06/2013; · 2.53 Impact Factor
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    ABSTRACT: The impact of cryptic relatedness (CR) on genomic association studies is well studied and known to inflate false-positive rates as reported by several groups. In contrast, conventional epidemiological studies for environmental risks, the confounding effect of CR is still uninvestigated. In this study, we investigated the confounding effect of unadjusted CR among a rural cohort in the relationship between environmental risk factors (body mass index, smoking status, alcohol consumption) and systolic blood pressure. We applied the methods of population-based whole-genome association studies for the analysis of the genome-wide single nucleotide polymorphism data in 1622 subjects, and detected 20.2% CR in this cohort population. In the case of the sample size, approximately 1000, the ratio of CR to the population was 20.2%, the population prevalence 25%, the prevalence in the CR 26%, heritability for liability 14.3% and prevalence in the subpopulation without CR 26%, the difference of estimated regression coefficient between samples with and without CR was not significant (P-value = 0.55). On the other hand, in another case with approximately >20% heritability for liability, we showed that confounding due to CR biased the estimation of exposure effects.
    Molecular genetics & genomic medicine. 05/2013; 1(1):45-53.
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    ABSTRACT: OBJECTIVE To develop and validate a risk engine that calculates the risks of macro- and microvascular complications in type 2 diabetes.RESEARCH DESIGN AND METHODS We analyzed pooled data from two clinical trials on 1,748 Japanese type 2 diabetic patients without diabetes complications other than mild diabetic retinopathy with a median follow-up of 7.2 years. End points were coronary heart disease (CHD), stroke, noncardiovascular mortality, overt nephropathy defined by persistent proteinuria, and progression of retinopathy. We fit a multistate Cox regression model to derive an algorithm for prediction. The predictive accuracy of the calculated 5-year risks was cross-validated.RESULTSSex, age, HbA(1c), years after diagnosis, BMI, systolic blood pressure, non-HDL cholesterol, albumin-to-creatinine ratio, atrial fibrillation, current smoker, and leisure-time physical activity were risk factors for macro- and microvascular complications and were incorporated into the risk engine. The observed-to-predicted (O/P) ratios for each event were between 0.93 and 1.08, and Hosmer-Lemeshow tests showed no significant deviations between observed and predicted events. In contrast, the UK Prospective Diabetes Study (UKPDS) risk engine overestimated CHD risk (O/P ratios: 0.30 for CHD and 0.72 for stroke). C statistics in our Japanese patients were high for CHD, noncardiovascular mortality, and overt nephropathy (0.725, 0.696, and 0.767) but moderate for stroke and progression of retinopathy (0.636 and 0.614). By combining macro- and microvascular risks, the classification of low- and high-risk patients was improved by a net reclassification improvement of 5.7% (P = 0.02).CONCLUSIONS The risk engine accurately predicts macro- and microvascular complications and would provide helpful information in risk classification and health economic simulations.
    Diabetes care 02/2013; · 7.74 Impact Factor
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    ABSTRACT: BACKGROUND:: Antioxidants and dietary fiber are postulated to have preventive effects on diabetic retinopathy, but evidence is lacking. We investigated this association in a cohort with type 2 diabetes 40-70 years of age with hemoglobin (Hb)A1C ≥6.5%, originally part of the Japan Diabetes Complications Study. METHODS:: After excluding people who did not respond to a dietary survey and patients with diabetic retinopathy or a major ocular disease at baseline, we analyzed 978 patients. Baseline dietary intake was assessed by a food frequency questionnaire based on food groups and 24-hour dietary records. Primary outcome was incident diabetic retinopathy determined using international severity scales. RESULTS:: Mean fruit intake in quartiles ranged from 23 to 253 g/day, with increasing trends across quartiles of fruit intake for vitamin C, vitamin E, carotene, retinol equivalent, dietary fiber, potassium, and sodium. Mean energy intake ranged from 1644 to 1863 kcal/day, and fat intake was approximately 25%. HbA1C, body mass index, triglycerides, and systolic blood pressure were well controlled. During the 8-year follow-up, the numbers of incident cases of diabetic retinopathy from the first through the fourth quartiles of fruit intake were 83, 74, 69, and 59. Multivariate-adjusted hazard ratios for the second, third, and fourth quartiles of fruit intake compared with the first quartile were 0.66 (95% confidence interval = 0.46-0.92), 0.59 (0.41-0.85), and 0.48 (0.32-0.71) (test for trend, P < 0.01). There was no substantial effect modification by age, sex, HbA1C, diabetes duration, overweight, smoking, and hypertension. Risk for diabetic retinopathy declined with increased intake of fruits and vegetables, vitamin C, and carotene. CONCLUSION:: Increased fruit intake in ranges commonly consumed was associated with reduced incident diabetic retinopathy among patients adhering to a low-fat energy-restricted diet.
    Epidemiology (Cambridge, Mass.) 01/2013; · 5.51 Impact Factor
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    ABSTRACT: Previously, I* parameter has been proposed to diagnose noninvasively the progressive degree of atherosclerosis which is considered to concern the discrimination of the progressive degree of visco elasticity of blood vessel wall. However, the detailed physical meaning of this parameter has not yet been clarified. In this paper, the theoretical analysis and experiments were conducted and the detailed physical meaning of I* parameter was clarified. The following results were obtained. I* parameter was found to well correlate with the progressive degree of visco elasticity of blood vessel wall characterized by the Ith* parameter derived based on the analysis of visco elasticity in this paper. That is, I* was found to have the physical meaning of representing the progressive degree of visco elasticity of blood vessel wall. On the basis of this results, using clinical data, two dimensional representation between the progressive degree of visco elasticity of blood vessel wall by I* and the decrease in the rigidity of blood vessel wall by PWV was found to be useful to conduct much more detailed diagnosis of atherosclerosis.
    Bio-medical materials and engineering 01/2013; 23(1):75-91. · 1.09 Impact Factor
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    ABSTRACT: OBJECTIVE To examine the interactive relationship between diabetic retinopathy (DR) and diabetic nephropathy (DN) in type 2 diabetic patients, and to elucidate the role of DR and microalbuminuria on the onset of macroalbuminuria and renal function decline.RESEARCH DESIGN AND METHODS We explored the effects of DR and microalbuminuria on the progression of DN from normoalbuminuria and low microalbuminuria (<150 mg/gCr) to macroalbuminuria or renal function decline in the Japan Diabetes Complications Study (JDCS), which is a nationwide randomized controlled study of type 2 diabetic patients focusing on lifestyle modification. Patients were divided into four groups according to presence or absence of DR and MA: normoalbuminuria without DR [NA(DR-)] (n = 773), normoalbuminuria with DR [NA(DR+)] (n = 279), microalbuminuria without DR [MA(DR-)] (n = 277), and microalbuminuria with DR [MA(DR+)] (n = 146). Basal urinary albumin-to-creatinine ratio and DR status were determined at baseline and followed for a median of 8.0 years.RESULTSAnnual incidence rates of macroalbuminuria were 1.6/1,000 person-years (9 incidences), 3.9/1,000 person-years (8 incidences), 18.4/1,000 person-years (34 incidences), and 22.1/1,000 person-years (22 incidences) in the four groups, respectively. Multivariate-adjusted hazard ratios of the progression to macroalbuminuria were 2.48 (95% CI 0.94-6.50; P = 0.07), 10.40 (4.91-22.03; P < 0.01), and 11.55 (5.24-25.45; P < 0.01) in NA(DR+), MA(DR-), and MA(DR+), respectively, in comparison with NA(DR-). Decline in estimated glomerular filtration rate (GFR) per year was two to three times faster in MA(DR+) (-1.92 mL/min/1.73 m(2)/year) than in the other groups.CONCLUSIONS In normo- and low microalbuminuric Japanese type 2 diabetic patients, presence of microalbuminuria at baseline was associated with higher risk of macroalbuminuria in 8 years. Patients with microalbuminuria and DR showed the fastest GFR decline. Albuminuria and DR should be considered as risk factors of renal prognosis in type 2 diabetic patients. An open sharing of information will benefit both ophthalmologists and diabetologists.
    Diabetes Care 01/2013; · 7.74 Impact Factor
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    ABSTRACT: To describe the pathophysiological findings of a patient with pemphigus vulgaris (PV) showing giant conjunctival papillae. A 64-year-old man who had mucosal-dominant PV with giant conjunctival papillae, resembling those of vernal keratoconjunctivitis (VKC), underwent an ophthalmological workup. The clinical and pathological findings were investigated. Ophthalmic interventions were unable to provide the desired beneficial effects, and multiple excisions were necessary to remove the proliferative conjunctival lesions. Histopathological investigations of the excised tissues demonstrated acantholysis and a subconjunctival infiltration with numerous inflammatory cells such as lymphocytes, plasma cells, and neutrophils. However, in contrast to typical VKC, mast cells and eosinophils were rarely found in the subconjunctival tissues. Direct immunofluorescent staining showed a significant deposition of immunoglobulin G and complement component 3 in the epithelial intercellular substance, consistent with mucosal-dominant PV. Then, the patient was hospitalized because of oral erosion exacerbation and malnutrition. Because of the patient's declining general condition, we administered an increasing dose of a systemic steroid with an intravenous immunoglobulin, after which his ocular lesions and symptoms improved. The histological conjunctival papilla findings were quite different from those of VKC papillae. If PV causes a lesion in a patient, systemic immunosuppression might be more effective than topical ophthalmic treatment because of overall immunological involvement.
    Case reports in ophthalmology. 01/2013; 4(3):114-21.
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    ABSTRACT: OBJECTIVE: Diabetic retinopathy (DR) is linked to cardiovascular risk in diabetic patients. This study examined whether mild-stage DR is associated with risk of coronary heart disease (CHD) and stroke in type 2 diabetic patients of the Japan Diabetes Complications Study (JDCS). DESIGN: Prospective cohort study. PARTICIPANTS: In the JDCS, there were 2033 Japanese persons with type 2 diabetes free of cardiovascular diseases at baseline. METHODS: Diabetic retinopathy was ascertained from clinical and photographic grading (70%) following the international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Incident CHD and stroke were followed up prospectively annually up to 8 years. MAIN OUTCOME MEASURES: Eight-year incidence of CHD and stroke compared between persons with or without DR. RESULTS: After adjusting for traditional cardiovascular risk factors, persons with mild to moderate nonproliferative DR had a higher risk of CHD (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.17-2.97) and stroke (HR, 2.69; 95% CI, 1.03-4.86). Presence of retinal hemorrhages or microaneurysms was associated with risk of CHD (HR, 1.63; 95% CI, 1.04-2.56) but was not associated with stroke (P = 0.06). Presence of cotton-wool spots was associated with risk of incident stroke (HR, 2.39; 95% CI, 1.35-4.24) but was not associated with CHD (P = 0.66). When information about DR was added in the prediction models for CHD and stroke based on traditional cardiovascular risk factors, the area under the receiver operating curve improved from 0.682 to 0.692 and 0.640 to 0.677, and 9% and 13% of persons were reclassified correctly for CHD and stroke, respectively. CONCLUSIONS: Type 2 diabetic patients with even a mild stage of DR, such as dot hemorrhages, are already at higher risk of CHD and stroke independent of traditional risk factors. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
    Ophthalmology 11/2012; · 5.56 Impact Factor
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    ABSTRACT: Hyperhomocysteinaemia is associated with chronic obstructive pulmonary disease (COPD). However, the relationship between plasma homocysteine (Hcy) levels and spirometric measures has not been investigated in a general population. We aimed to determine whether Hcy levels are predictive for a rapid decline in lung function among healthy current smokers.Blood sampling and spirometry were performed on subjects (n=3,257), participating in a community-based annual health check in Takahata, Japan, from 2004 to 2006. Spirometry was re-evaluated in 147 male current smokers in 2009.On initial assessment, percent predicted forced vital capacity (%FVC) and forced expiratory volume in 1 s (%FEV1) correlated inversely with Hcy levels, and were predictive for Hcy levels, independent of various clinical factors. Hcy levels were higher in subjects with restrictive, obstructive, or mixed ventilatory disorders. Additionally, Hcy levels were higher in subjects with mixed ventilatory disorders, compared with restrictive or obstructive disorders. On follow-up, subjects showing a decline in FEV1 had higher Hcy levels than those who did not. Logistic regression analysis indicated that Hcy levels were predictive for a decline in FEV1.%FVC and % FEV1 were significantly associated with Hcy levels, and hyperhomocysteinaemia predicted the annual rate of decline in FEV1 among male smokers.
    European Respiratory Journal 11/2012; · 6.36 Impact Factor

Publication Stats

5k Citations
492.40 Total Impact Points

Institutions

  • 2001–2014
    • Yamagata University
      • • Department of Ophthalmology and Visual Sciences
      • • School of Medicine
      Ямагата, Yamagata, Japan
    • The Jikei University School of Medicine
      • Department of Ophthalmology
      Tokyo, Tokyo-to, Japan
  • 2013
    • Tohoku University
      • Graduate School of Engineering
      Sendai, Kagoshima-ken, Japan
  • 2012
    • Royal Victorian Eye and Ear Hospital
      Melbourne, Victoria, Australia
  • 2011
    • Japan Society for the Promotion of Science
      Edo, Tōkyō, Japan
    • Kagoshima University
      • Department of Ophthalmology
      Kagosima, Kagoshima, Japan
  • 2010
    • Yamagata Prefectural Central Hospital
      Ямагата, Yamagata, Japan
    • University of Melbourne
      • Centre for Eye Research Australia
      Melbourne, Victoria, Australia
  • 2001–2010
    • Tokyo Women's Medical University
      • Department of Ophthalmology
      Tokyo, Tokyo-to, Japan
  • 1993–2010
    • Ludwig Institute for Cancer Research Sweden
      Uppsala, Uppsala, Sweden
  • 2009
    • University of the Ryukyus
      • Department of Ophthalmology
      Okinawa, Okinawa-ken, Japan
  • 2003–2006
    • Hiroshima University
      • Department of Ophthalmology and Visual Science
      Hiroshima-shi, Hiroshima-ken, Japan
    • Tokyo Medical University
      • Department of Ophthalmology
      Edo, Tōkyō, Japan
  • 2005
    • Uppsala University
      Uppsala, Uppsala, Sweden
  • 2004
    • Universidade Federal de São Paulo
      San Paulo, São Paulo, Brazil
  • 1996–2003
    • The University of Tokyo
      • Faculty & Graduate School of Medicine
      Tōkyō, Japan
  • 1998
    • Japanese Foundation for Cancer Research
      Edo, Tōkyō, Japan