Researchers Database


    ComprehensiveMedicine2 Assistant Professor
Last Updated :2021/12/07

Researcher Information


  • M.D.(1995/03 Jichi Medical University)


Research funding number

  • 00382846


J-Global ID

Research Interests

  • Additive effects   Combined treatment   Orthokeratology   0.01% atropine ophthalmic solution   Low-concentration atropine ophthalmic solution   Slowing axial elongation   Slowing myopia progession   Prevention myopia progression   Myopia   Retinopathy associated with myocardial infarction.   Diabetic retinopathy   Retinal miorocirculation disturvance   

Research Areas

  • Life sciences / Ophthalmology

Academic & Professional Experience

  • 2021/12 - Today  川越西眼科
  • 2012/12 - Today  Saitama Medical Center, Jichi Medical UniversityDepartment of OphthalmologyLecturer
  • 2021/06 - 2021/11  医療法人クラルスはんがい眼科 新宿センタービル院長
  • 2004/05 - 2012/11  Saitama Medical Center, Jichi Medical UniversityDepartment of OphthalmologyResearch associate
  • 2002/05 - 2004/04  公立和田山病院眼科医長
  • 2000/05 - 2002/04  Omiya Medical Center, Jichi Medical University Department of Ophthalmology,OphthalmologySenior resident
  • 1998/05 - 2000/04  公立村岡病院内科医員
  • 1997/05 - 1998/04  美方町国保大谷診療所所長
  • 1995/05 - 1997/04  兵庫県立淡路病院スーパーローテーション前期研修医


  • 1989/04 - 1995/03  Jichi Medical University  School of Medicine  医学科
  • 1986/04 - 1989/03  兵庫県立豊岡高等学校  理数コース

Association Memberships

  • The Society of Orthokeratology and Specialty lens Japan (SOS-J)   Japan myopia Society   Myopia Society Japan   Saitama Ophthalmologists Associasion   Japan Ophthalmologists Associasion   Japanese Ophthalmological Society   American Academy of Ophthalmology   The Association for Research in Vision and Ophthalmology   

Published Papers

  • Nozomi Kinoshita, Yasuhiro Konno, Naoki Hamada, Yoshinobu Kanda, Machiko Shimmura-Tomita, Toshikatu Kaburaki, Akihiro Kakehashi
    Scientific Reports Nature Publishing Group 10 (1) 12750 - 12750 2020/07 [Refereed][Not invited]
    Eighty Japanese children, aged 8-12 years, with a spherical equivalent refraction (SER) of - 1.00 to - 6.00 dioptres (D) were randomly allocated into two groups to receive either a combination of orthokeratology (OK) and 0.01% atropine solution (combination group) or monotherapy with OK (monotherapy group). Seventy-three subjects completed the 2-year study. Over the 2 years, axial length increased by 0.29 ± 0.20 mm (n = 38) and 0.40 ± 0.23 mm (n = 35) in the combination and monotherapy groups, respectively (P = 0.03). Interactions between combination treatment and age or SER did not reach significance level (age, P = 0.18; SER, P = 0.06). In the subgroup of subjects with an initial SER of - 1.00 to - 3.00 D, axial length increased by 0.30 ± 0.22 mm (n = 27) and 0.48 ± 0.22 mm (n = 23) in the combination and monotherapy groups, respectively (P = 0.005). In the - 3.01 to - 6.00 D subgroup, axial length increased by 0.27 ± 0.15 mm (n = 11) and 0.25 ± 0.17 mm (n = 12) in the combination and monotherapy groups, respectively (P = 0.74). The combination therapy may be effective for slowing axial elongation, especially in children with low initial myopia.
  • Yoshiaki Tanaka, Rina Takagi, Takeshi Ohta, Tomohiko Sasase, Mina Kobayashi, Fumihiko Toyoda, Machiko Shimmura, Nozomi Kinoshita, Hiroko Takano, Akihiro Kakehashi
    Journal of diabetes research 2019 8724818 - 8724818 2019 [Refereed][Not invited]
    Objective: The Spontaneously Diabetic Torii (SDT) fatty rat, established by introducing the fa allele (obesity gene) of the Zucker fatty rat into the SDT rat genome, is a new model of obese type 2 diabetes. We studied the pathologic features of diabetic retinopathy (DR) in this animal. Methods: The eyes of SDT fatty, SDT (controls), and Sprague Dawley (SD) rats (normal controls) were enucleated at 8, 16, 24, 32, and 40 weeks of age (n = 5-6 for each rat type at each age). The retinal thicknesses, numbers of retinal folds, and choroidal thicknesses were evaluated. Immunostaining for glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) was performed. Quantitative analyses of the immunopositive regions were performed using a cell-counting algorithm. Results: The retinas tended to be thicker in the SDT fatty rats and SDT rats than in the SD rats; the choroids tended to be thicker in the SDT fatty rats than in the SD rats. The retinal folds in the SDT fatty rats developed earlier and were more severe than in the SDT rats. Quantitative analyses showed that the GFAP- and VEGF-positive regions in the retinas of the SDT fatty rats were significantly larger than those of the SDT rats. Conclusions: SDT fatty rats developed more severe DR earlier than the SDT rats. The SDT fatty rats might be useful as a type 2 diabetes animal model to study DR.
  • Nozomi Kinoshita, Yasuhiro Konno, Naoki Hamada, Yoshinobu Kanda, Machiko Shimmura-Tomita, Akihiro Kakehashi
    Japanese Journal of Ophthalmology Springer Japan 62 (5) 544 - 553 0021-5155 2018/07 [Refereed][Not invited]
    Purpose: To investigate the additive effects of orthokeratology (OK) and atropine 0.01% ophthalmic solution, both of which are effective procedures to slow axial elongation in children with myopia. Study design: Prospective randomized clinical trial. Methods: Japanese children aged 8-12 years with a spherical equivalent refractive error of - 1.00 to - 6.00 diopters were included. A total of 41 participants who had been wearing the OK lenses successfully for 3 months were randomly allocated into two groups to receive either the combination of OK and atropine 0.01% ophthalmic solution (combination group) or monotherapy with OK (monotherapy group). Subjects in the combination group started to use atropine 0.01% ophthalmic solution once nightly from 3 months after the start of OK. Axial length was measured every 3 months using non-contact laser interferometry (IOLMaster), and the axial length measurement at month 3 of OK therapy was used as the baseline value in both groups. The increase in axial length over 1 year was compared between the two groups. Results: A total of 40 consecutive subjects (20 subjects in the combination group and 20 in the monotherapy group) were followed for 1 year. The increase in axial length over 1 year was 0.09 ± 0.12 mm in the combination group and 0.19 ± 0.15 mm in the monotherapy group (P = 0.0356, unpaired t test). Conclusion: During the 1-year follow-up, the combination of OK and atropine 0.01% ophthalmic solution was more effective in slowing axial elongation than OK monotherapy in children with myopia.
  • Yoshiaki Tanaka, Fumihiko Toyoda, Machiko Shimmura-Tomita, Nozomi Kinoshita, Hiroko Takano, Yoh Dobashi, Shigeki Yamada, Hiroto Obata, Akihiro Kakehashi
    Clinical ophthalmology (Auckland, N.Z.) 12 1949 - 1957 2018 [Refereed][Not invited]
    Purpose: The aim of this case series was to clarify the clinicopathological features of epiretinal membranes (ERMs) that developed in eyes after silicone oil (SO) tamponade to treat rhegmatog-enous retinal detachments (RRDs). Patients and methods: In the Department of Ophthalmology, Saitama Medical Center, Jichi Medical University, patients with idiopathic ERMs (23 eyes) and ERMs in eyes filled with SO (SO ERMs) after vitreous surgery to treat RRDs (nine eyes) were enrolled from July 2012 to March 2014. ERM tissues obtained intraoperatively were examined histopathologically. Besides the main outcome measure of the pathological findings of the ERM tissues, other outcome measures included the preoperative findings on optical coherence tomography (OCT) images and the surgical findings. Results: Eight (89%) of nine eyes with SO ERMs had bilayered membranes composed of a firm layer on the retinal side with glial cells and extracellular matrix and a fragile sponge-like layer on the vitreous side. The sponge-like layer was composed of emulsified SO surrounded by macrophages. Quantitative analysis showed that the areas with cluster of differentiation 68 (CD68)-positive macrophages identified by immunohistochemistry in eyes with SO ERMs were significantly (P<0.001) larger than those in eyes with idiopathic ERMs. The findings on OCT images were consistent with the pathological features of the SO ERMs. Surgical removal of the SO ERMs was difficult because the sponge-like layer was fragile, and the underlying retina was also fragile due to inflammation. Conclusion: SO ERMs are bilayered membranes. Long-standing emulsified SO formed a sponge-like layer and SO (foreign body)-induced granulation and caused retinal inflammation in these eyes, making surgical removal difficult. A preoperative OCT examination is necessary to identify SO ERMs.
  • Machiko Shimmura-Tomita, Hiroko Takano, Nozomi Kinoshita, Fumihiko Toyoda, Yoshiaki Tanaka, Rina Takagi, Mina Kobayashi, Akihiro Kakehashi
    Clinical ophthalmology (Auckland, N.Z.) 12 2567 - 2573 2018 [Refereed][Not invited]
    Purpose: To determine risk factors and clinical signs for severe Acanthamoeba keratitis (AK) by comparing severe cases with mild cases with good prognosis. Patients and methods: We reviewed medical records of ten cases of AK (five males and five females) referred to our hospital and classified cases into two groups. One eye that required therapeutic keratoplasty and three eyes with a poor visual acuity (<0.2) on last visit were included in the severe group. Six eyes that had good prognosis with a visual acuity of 1.2 on last visit were classified as mild group. We compared patients' age, the time required for diagnosis, visual acuity on first visit, the history of steroid eye drops use, and other clinical findings. Results: The average age of the severe group was older than the mild group (P=0.04). The duration between onset and diagnosis of AK and visual acuity on first visit was not statistically different. A history of steroid eye drop use was found in four eyes of the severe group (100%) and four eyes of the mild group (67%). Keratoprecipitates were found in all severe group eyes and one mild group eye during follow-up (P=0.01). One case in the severe group was diagnosed with diabetes mellitus at initial examination. We detected Staphylococcus epidermis by palpebral conjunctival culture in one case of the severe group. Conclusion: Aging may be a possible risk factor for severe AK. The presence of keratoprecipitates is a possible sign of severe AK. Attention is also required in patients with comorbidities such as diabetes mellitus and bacterial infection.
  • Fumihiko Toyoda, Yoshiaki Tanaka, Machiko Shimmura, Nozomi Kinoshita, Hiroko Takano, Akihiro Kakehashi
    Journal of diabetes research 2016 2345141  2314-6745 2016 [Refereed][Not invited]
    We evaluated the features of diabetic retinal and choroidal edema in Spontaneously Diabetic Torii (SDT) rats. We measured the retinal and choroidal thicknesses in normal Sprague-Dawley (SD) rats (n = 9) and SDT rats (n = 8). The eyes were enucleated 40 weeks later after they were diagnosed with diabetes, and 4-micron sections were cut for conventional histopathologic studies. The mean retinal and choroidal thicknesses were significantly thicker in the SDT rats than in the normal SD rats. The choroidal thickness was correlated strongly with the retinal thickness in both rat models. Diabetic retinopathy (DR) and diabetic choroidopathy appeared as edema in the SDT rats. The retinal thickness was correlated strongly with the choroidal thickness in the SDT rats, which is an ideal animal model of both DR and choroidopathy.
  • Ayumi Ota, Yoshiaki Tanaka, Fumihiko Toyoda, Machiko Shimmura, Nozomi Kinoshita, Hiroko Takano, Akihiro Kakehashi
    Clinical ophthalmology (Auckland, N.Z.) 10 7 - 11 1177-5483 2015/12 [Refereed][Not invited]
    Purpose: To clarify the relationship between variations in posterior vitreous detachments (PVDs) and visual prognoses in idiopathic epiretinal membranes (ERMs). Methods: In this retrospective, observational, and consecutive case series, we observed variations in PVDs in 37 patients (mean age, 65.7±11.0 years) with ERMs and followed them for 2 years. Three PVD types were found biomicroscopically: no PVD, complete PVD with collapse (C-PVD with collapse), and partial PVD without shrinkage, with persistent vitreous attachment to the macula through the premacular hole of the posterior hyaloid membrane (P-PVD without shrinkage [M]). The best-corrected visual acuity (BCVA) was measured and converted to the logarithm of the minimum angle of resolution (logMAR) BCVA at the first visit and 2 years later. Results: No PVD was observed in 16 of the 37 eyes (mean age, 61.3±11.3 years), C-PVD with collapse in 11 of the 37 eyes (mean age, 69.1±9.9 years), and P-PVD without shrinkage (M) in 10 of the 37 eyes (mean age, 69.3±10.9 years). The logMAR BCVA at the first visit was the worst in the P-PVD without shrinkage (M) group (0.22±0.35) compared with the no-PVD group (−0.019±0.07 P< 0.01) and the C-PVD group (0.029±0.08 P< 0.05). The logMAR BCVA 2 years later was also worst in the P-PVD without shrinkage (M) group (0.39±0.35) compared with the no-PVD group (0.04±0.13) and the C-PVD with collapse group (0.03±0.09 P< 0.05 for both comparisons). The change in the logMAR BCVA over the 2-year follow-up period was worst in the P-PVD without shrinkage (M) group (0.17±0.23) compared with the no-PVD group (0.06±0.14) and the C-PVD with collapse group (0.0009±0.09 P< 0.05 for both comparisons). Conclusion: Cases with an ERM with a P-PVD without shrinkage (M) had a worse visual prognosis than those with an ERM with no PVD and C-PVD with collapse.
  • Kenshiro Arao, Asuka Kuribara, Hiroyuki Jinnouchi, Mitsunari Matsumoto, Takayuki Fujiwara, Nozomi Kinoshita, Akihiro Kakehashi, Junya Ako, Shin-ichi Momomura
    Ophthalmology 121 (11) 2261 - 2267 0161-6420 2014/11 [Refereed][Not invited]
    Purpose: To explore the occurrence of transient retinopathy and its prognostic importance in patients with acute aortic dissection (AAD). Design: Prospective, observational study. Participants: Sixty-four patients with Stanford type B AAD were treated with conservative medical therapy. Methods: Retinopathy findings, such as cotton-wool spots and hemorrhage, were examined. Fundus photography was performed on hospital days 9 to 14 and after 2 or 3 months. The association between the appearance of retinopathy and the subsequent cardio-cerebrovascular events was investigated. Main Outcome Measures: The primary outcomes included the incidence of retinopathy and subsequent adverse cardio-cerebrovascular events. Results: Retinopathy was detected in 55% (35 of 64) of patients (cotton-wool spots alone, n = 31; dot hemorrhage alone, n = 1; and both, n = 3). These findings disappeared in all 12 patients who underwent follow-up fundus examinations. In the multivariate analysis, a history of hypertension and higher peak C-reactive protein level were independently associated with retinopathy. At a median follow-up of 911 days, adverse cardiocerebrovascular events were reported in 11 patients, of whom those with retinopathy experienced adverse events significantly more frequently than those without retinopathy (P = 0.045). Conclusions: Retinopathy occurred frequently in patients with AAD. This retinopathy was associated with a history of hypertension and higher peak C-reactive protein levels and was an important predictive factor for adverse cardio-cerebrovascular outcomes. (C) 2014 by the American Academy of Ophthalmology.
  • Fumihiko Toyoda, Yoshiaki Tanaka, Ayumi Ota, Machiko Shimmura, Nozomi Kinoshita, Hiroko Takano, Takafumi Matsumoto, Junichi Tsuji, Akihiro Kakehashi
    Journal of diabetes research 2014 672590  2314-6745 2014 [Refereed][Not invited]
    Purpose. To evaluate the effect of ranirestat, a new aldose reductase inhibitor (ARI), on diabetic retinopathy (DR) in Spontaneously Diabetic Torii (SDT) rats. Methods. The animals were divided into six groups, normal Sprague-Dawley rats (n = 8), untreated SDT rats (n = 9), ranirestat-treated SDT rats (0.1, 1.0, and 10 mg/kg/day, n = 7,8, and 6, resp.), and epalrestat-treated SDT rats (100mg/kg/day, n = 7). Treated rats received oral ranirestat or epalrestat once daily for 40 weeks after the onset of diabetes. After the eyes were enucleated, the retinal thickness and the area of stained glial fibrillary acidic protein (GFAP) were measured. Results. The retinas in the untreated group were significantly thicker than those in the normal and ranirestat-treated (0.1, 1.0, and 10mg/kg/day) groups. The immunostained area of GFAP in the untreated group was significantly larger than that in the normal and ranirestat-treated (1.0 and 10mg/kg/day) groups. There were no significant differences between the untreated group and epalrestat-treated group in the retinal thickness and the area of stained GFAP. Conclusion. Ranirestat reduced the retinal thickness and the area of stained GFAP in SDT rats and might suppress DR and have a neuroprotective effect on diabetic retinas.
  • Ayumi Ota, Akihiro Kakehashi, Fumihiko Toyoda, Nozomi Kinoshita, Machiko Shinmura, Hiroko Takano, Hiroto Obata, Takafumi Matsumoto, Junichi Tsuji, Yoh Dobashi, Wilfred Y. Fujimoto, Masanobu Kawakami, Yasunori Kanazawa
    Journal of diabetes research 2013 175901  2314-6745 2013 [Refereed][Not invited]
    We evaluated ranirestat, an aldose reductase inhibitor, in diabetic cataract and neuropathy (DN) in spontaneously diabetic Torii (SDT) rats compared with epalrestat, the positive control. Animals were divided into groups and treated once daily with oral ranirestat (0.1, 1.0, 10 mg/kg) or epalrestat (100 mg/kg) for 40 weeks, normal Sprague-Dawley rats, and untreated SDT rats. Lens opacification was scored from 0 (normal) to 3 (mature cataract). The combined scores (0-6) from both lenses represented the total for each animal. DN was assessed by measuring the motor nerve conduction velocity (MNCV) in the sciatic nerve. Sorbitol and fructose levels were measured in the lens and sciatic nerve 40 weeks after diabetes onset. Cataracts developed more in untreated rats than normal rats (P < 0.01). Ranirestat significantly (P < 0.01) inhibited rapid cataract development; epalrestat did not. Ranirestat significantly reversed the MNCV decrease (40.7 +/- 0.6 m/s) in SDT rats dose-dependently (P < 0.01). Epalrestat also reversed the prevented MNCV decrease (P < 0.05). Sorbitol levels in the sciatic nerve increased significantly in SDT rats (2.05 +/- 0.10 nmol/g), which ranirestat significantly suppressed dose-dependently, (P < 0.05, < 0.01, and < 0.01); epalrestat did not. Ranirestat prevents DN and cataract; epalrestat prevents DN only.
  • Nozomi Kinoshita, Ayumi Ota, Fumihiko Toyoda, Hiroko Yamagami, Akihiro Kakehashi
    Clinical ophthalmology (Auckland, N.Z.) Dove Medical Press 6 (1) 915 - 918 1177-5467 2012/06 [Refereed][Not invited]
    Purpose: To report a new technique of blunt needle revision with viscoelastic materials via the anterior chamber for the treatment of early failed filtering blebs and elevated intraocular pressure after trabeculectomy, in which digital ocular massage and laser suture lysis have been ineffective methods: A 27-gauge blunt needle attached to a syringe containing viscoelastic material was inserted into the anterior chamber from the inferior paracentesis. The needle tip was inserted into the subscleral flap space from the filtering fistula at the anterior chamber side, and the scleral flap was lifted bluntly. The needle tip was then inserted into the subconjunctival space where the viscoelastic agent was injected and the adhesion between the sclera and conjunctiva was separated bluntly. Blunt needle revision via the anterior chamber was performed 14 times in six eyes of six patients at Saitama Medical Center, Jichi Medical University from January 2007 to May 2009. All procedures were performed within 1 month after trabeculectomy results: The intraocular pressure remained 21 mmHg or lower for more than 6 months in three of six eyes. Slight bleeding from the iris occurred in one of the 14 procedures, and hypotony (intraocular pressure below 5 mmHg) occurred in one of the 14 procedures. No serious complications eveloped.Conclusion: Blunt needle revision via the anterior chamber for early failed filtering blebs is a new, simple, and safe procedure. © 2012 Kinoshita et al, publisher and licensee Dove Medical Press Ltd.
  • Nozomi Kinoshita, Ayumi Ota, Fumihiko Toyoda, Hiroko Yamagami, Akihiro Kakehashi
    Clinical ophthalmology (Auckland, N.Z.) Dove Medical Press 5 (1) 1777 - 1781 1177-5467 2011/12 [Refereed][Not invited]
    Purpose: To report on pars plana vitrectomy (PPV) combined with pars plana lensectomy (PPL) with a preserved anterior capsule, panretinal endophotocoagulation (EPC) throughout the pars plana, and silicon oil (SO) tamponade (PPV + PPL + EPC + SO tamponade) for neovascular glaucoma (NVG). Methods: Thirteen eyes with NVG were treated. Ten eyes also underwent SO removal and intraocular lens (IOL) implantation (SO removal + IOL). Intraocular pressure (IOP), number of medications, and visual acuity were evaluated at the first visit, immediately before and 3 months after the procedure, 3 months after SO removal + IOL, and 1 year after the procedure. Results: At the first visit, immediately before and 3 months after the procedure, 3 months after SO removal + IOL, and 1 year after the procedure, the IOPs were 29 ± 19, 23 ± 12, 13 ± 5, 17 ± 10, and 17 ± 6 mmHg numbers of medications, 0.7 ± 1.4, 2.1 ± 2.0, 0.6 ± 0.7, 1.2 ± 1.2, and 1.6 ± 1.6 and best-corrected visual acuities converted to logarithm of the minimum angle of resolution (BCVA logMAR), 0.96 ± 0.96, 1.27 ± 0.80, 1.67 ± 0.91, 1.37 ± 0.89, and 1.90 ± 1.44, respectively. No severe hypotony or phthisis bulbi developed within 1 year after the procedure. The success rates (IOP ≤ 21 mmHg and sustained light perception) were 92.3% after 3 months and 69.2% after 1 year. Conclusion: PPV + PPL + EPC + SO tamponade might have prevented acute increases of vascular endothelial growth factor and inflammatory cytokine production postoperatively and resulted in good vision in patients with NVG. © 2011 Kinoshita et al, publisher and licensee Dove Medical Press Ltd.
  • Nozomi Kinoshita, Akihiro Kakehashi, Yoh Dobashi, Ryuichiro Ono, Fumihiko Toyoda, Chiho Kambara, Hiroko Yamagami, Yusuke Kitazume, Eiji Kobayashi, Yasuhiro Osakabe, Motoshige Kudo, Masanobu Kawakami, Yasunori Kanazawa
    Open Diabetes Journal 4 (1) 114 - 118 1876-5246 2011/03 [Refereed][Not invited]
    We tested the effect of topical nipradilol, an antiglaucoma drug with α- and β-blocker and nitric oxide (NO) donor activities, on the early retinal changes using electron microscopy in Spontaneously Diabetic Torii (SDT) rats. In seven young male SDT rats (17 to 18 weeks old), nipradilol solution was instilled in the right eyes and nipradilol-free base solution in the left eyes three times daily for 3 months. All rats were sacrificed and both eyes were enucleated for electron microscopy at the end of the experiments. All rats had blood glucose levels exceeding 350 mg/dl within 2 weeks after the beginning of the experiment (mean final blood glucose level, 558±100.2 mg/dl). In untreated eyes of young SDT rats, the overall pathological features were almost comparable to those in older SDT rats, although the pinocytotic vesicles and free ribosomes were not as remarkable in the latter. In contrast, in nipradilol-treated eyes of SDT rats, although the basement membrane was thickened, microvilli were seen, and a larger number of electron-dense mitochondria were in the wide cytoplasm. Lipofuscin-like electron-dense granules and lamellated myelin figures also were identified. Nipradilol reduced the early morphologic changes in the endothelial cells, which reflects the metabolically active state of diabetic retinopathy in SDT rats through its action as a NO donor. © Kinoshita et al.
  • Akihiro Kakehashi, Mikiko Takezawa, Fumihiko Toyoda, Nozomi Kinoshita, Chiho Kambara, Hiroko Yamagami, Noriaki Kato, San-e Ishikawa, Masanobu Kawakami, Yasunori Kanazawa
    Open Diabetes Journal 4 (1) 101 - 107 1876-5246 2011 [Refereed][Not invited]
    We evaluated the effect of an aldose reductase inhibitor, fidarestat, on diabetic retinopathy (DR) and cataract in spontaneously diabetic Torii (SDT) rats. Four rat groups were included: untreated, low- and high-dose (8 and 32 mg/kg/day) fidarestat-treated SDT rats, and nondiabetic control Sprague-Dawley rats. DR and cataract were evaluated and retinal and lens sorbitol, reduced glutathione (GSH), ocular fluid vascular endothelial growth factor (VEGF), and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was measured. The incidence rates of DR and cataract were significantly lower in the low- and high-dose fidarestat groups vs the untreated group (p< 0.001/p< 0.001). Retinal and lens sorbitol levels were lower in the control (1.1±0.1/3.1±0.2 nmol/mg protein) (p< 0.05/p< 0.01) and low- (2.7±1.1/30.0±3.3 nmol/mg protein) (p< 0.01/p< 0.01) and high-dose groups (0.7±0.2/5.9±0.6 nmol/mg protein) (p< 0.001/p< 0.001) vs the untreated group (23.2±4.7/123.9±29.6 nmol/mg protein). Retinal and lens GSH levels were higher in the nondiabetic control (52.2±5.8/29.0±2.7 μmol/mg protein) (p< 0.01/p< 0.001) and the low- (46.8±8.2/24.7±2.8 μmol/mg protein) (not significant (NS)/p< 0.001) and high-dose groups (63.3±14.6/26.9±3.6 umol/mg protein) (p< 0.05/p< 0.001) vs the untreated group (30.3±2.0/1.6±0.4 μmol/mg protein). VEGF levels were lower in the nondiabetic control (40.4±10.0 pg/ml) (p< 0.01) and low- (65.3±4.5 pg/ml) (p< 0.05) and high-dose groups (47.7±10 pg/ml) (p< 0.001) vs the untreated group (324.7±76.4 pg/ml). 8-OHdG levels were lower in the nondiabetic control (0.73±0.11 ng/mg creatinine) (p< 0.01) and low-(4.57±0.42 ng/mg creatinine) (NS) and high-dose groups (3.58±0.70 ng/mg creatinine) (NS) vs the untreated group (6.04±1.28 ng/ml). Fidarestat inhibited activation of the polyol pathway, reduced oxidative stress and VEGF, and prevented DR and cataract in SDT rats. © Kakehashi et al.
  • Fumihiko Toyoda, Akihiro Kakehashi, Ayumi Ota, Nozomi Kinoshita, Chiho Kambara, Hiroko Yamagami, Hiroyuki Tamemoto, Hiroto Ueba, Yoh Dobashi, San-e Ishikawa, Masanobu Kawakami, Yasunori Kanazawa
    Open Diabetes Journal 4 (1) 108 - 113 1876-5246 2011 [Refereed][Not invited]
    Advanced glycation end products (AGEs) play important roles in the development of ocular complications in diabetes mellitus. Spontaneously Diabetic Torii (SDT) rats have marked hyperglycemia and severe ocular complications. We evaluated the effect of anti-AGE agents, aminoguanidine and pyridoxamine, and an antioxidant, probucol, on the development of diabetic retinopathy (DR) and cataract in SDT rats. Experiment 1 included five SDT rats treated with aminoguanidine, four SDT rats treated with probucol, and four untreated control SDT rats. After age 55 weeks, we evaluated DR by fluorescein angiomicroscopy and pathological study and cataract by biomicroscopy. Experiment 2 included six SDT rats treated with pyridoxamine, and six SDT rats and 10 non-diabetic normal Sprague-Dawley (SD) rats not treated with pyridoxamine. Retinopathy and cataract were evaluated as in experiment 1. Urinary pentosidine and Maillard reaction product X (MRX) levels were measured for 40 weeks in each group. Experiment 1: Mature cataracts and DR developed in all untreated SDT rats aminoguanidine prevented cataracts and DR (p< 0.05, vs untreated SDT rats). Probucol had no effect. Experiment 2: Mature cataracts developed in all untreated SDT rats (p< 0.001 vs normal SD rats [0/10]) and DR developed in 67% (p< 0.01, vs normal SD rats [0/10, 0%]). Pyridoxamine did not prevent cataracts (6/6, 100%) or DR (4/6, 37%) (nonsignificant vs untreated SDT rats) in SDT rats. Urinary pentosidine levels were higher in untreated (0.12±0.07 μg/mg-Cre) and pyridoxamine-treated (0.12±0.05 μg/mg-Cre) SDT rats than normal SD rats (0.069±0.019 μg/mg-Cre), but not significantly so. Urinary MRX levels were significantly (p< 0.01) lower in normal SD rats (17.5±9.6 μg/mg-Cre) compared with untreated SDT rats (163.0±107.0 μg/mg-Cre) pyridoxamine had no effect (149.0±66.5 μg/mg-Cre) (nonsignificant vs untreated SDT rats). Aminoguanidine but not pyridoxamine and probucol prevents DR and cataracts in SDT rats. © Toyoda et al.
  • Fumihiko Toyoda, Akihiro Kakehashi, Kana Hashimoto, Nozomi Kinoshita, Chiho Kanbara, Hiroko Yamagami, Hiroyuki Tamemoto, San-e Ishikawa, Yoh Dobashi, Masanobu Kawakami, Yasunori Kanazawa
    Open Diabetes Journal 4 (1) 41 - 44 1876-5246 2011 [Refereed][Not invited]
    Background/Aims: The Spontaneously Diabetic Torii (SDT) rat develops advanced diabetic retinopathy (DR). The aim of this study was to identify advanced glycation end products (AGEs) related to vascular endothelial growth factor (VEGF) expression, a cause of DR in SDT rats. Methods: One eye was obtained from six SDT rats (blood glucose, > 250 mg/dl) and 10 nondiabetic normal Sprague-Dawley (SD) rats and prepared for immunohistochemical study of VEGF and AGEs (pyrraline, pentosidine, carboxy methyl lysine [CML]). Immunostaining was described as minimal, moderate, and severe. Results: In diabetic rats, for CML, five eyes had severe and one moderate immunostaining. For pyrraline, one eye had moderate and five eyes minimal immunostaining. For pentosidine, one eye had moderate and five eyes minimal immunostaining. For VEGF, three eyes each had moderate and severe immunostaining. In nondiabetic rats, for CML one eye had minimal, seven had moderate, and two had severe immunostaining. For pyrraline, four eyes had moderate and six eyes minimal immunostaining. For pentosidine, 10 eyes had minimal immunostaining. For VEGF, one eye had moderate and nine had minimal immunostaining. The prevalence rates of CML and VEGF were significantly (P< 0.05, P< 0.001, respectively) greater in diabetic than in nondiabetic rats. The prevalence rates of pyrraline and pentosidine were not significantly (P=0.35, P=0.38) different between diabetic and nondiabetic rats. Conclusion: CML coexists with VEGF and may be involved in the pathogenesis of severe ocular complications in SDT rats. © Toyoda et al. .
  • Takuji Katayama, Takanori Yasu, Nozomi Kinoshita, Akihiro Kakehashi, Norifumi Kubo, Muneyasu Saito, Shin-ichi Momomura, Masanobu Kawakami
    Circulation Journal 73 (7) 1278 - 1282 1346-9843 2009/07 [Refereed][Not invited]
    Background: A unique transient retinopathy characterized by soft exudates around the optic disc after percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) has been reported, so in the present study the risk factors for retinopathy associated with AMI (RAMI) were investigated. Methods and Results: The study group comprised 62 patients with their first AMI who underwent successful PCI within 24h of onset (48 men, 14 women; age 63 +/- 10 years). The fundus of each eye was assessed on days 3-5, and again at 4 weeks after AMI onset. New soft exudates developed in 29 patients (47%) at 4 weeks. The frequency of diabetes mellitus (DM), and the hemoglobin A(1c) and peak creatine kinase concentrations were higher in patients with than in those without RAMI (55% vs 21%, P=0.008; 7.0 +/- 2.0% vs 5.9 +/- 1.4%, P=0.013; and 3,428 +/- 2,210 IU/L vs 2,352 +/- 1,652 IU/L, P=0.036, respectively). Multivariate analysis identified DM as an independent predictive factor for the occurrence of RAMI (odds ratio, 6.60-, 95% confidence interval, 1.68-25.90; P=0.007). Conclusions: DM might be a risk factor for RAMI. (Circ J 2009; 73: 1278-1282)
  • 急性特発性盲点拡大と考えられた1例
    木下 望, 牧野 伸二
    眼科臨床紀要 眼科臨床紀要会 2 (4) 380 - 381 1882-5176 2009/04
  • Nozomi Kinoshita
    Jichi Medical University 自治医科大学 2006/12 [Refereed][Not invited]
    1. 研究目的 網膜の循環障害を起こす疾患は、主幹動静脈での閉塞と毛細血管での閉塞の二つに大きく分けられる。本論文では、毛細血管での閉塞、すなわち、網膜微小循環障害に起因する網膜症を研究対象とした。 糖尿病網膜症の初期の病態として、網膜における白血球の停留が起こりその結果、網膜毛細血管の灌流障害と血液網膜関門破綻を引き起こすと考えられている。経口血糖降下剤であるグリクラジドが高濃度ブドウ糖下で白血球の培養血管内皮細胞への接着を抑制することが報告され、網膜における白血球の停留を抑制する可能性が示唆された。本論文前半では、糖尿病ラット網膜における白血球停留の亢進を再確認するとともに、グリクラジドの網膜における白血球停留に対する抑制作用をin vivoで定量的に評価した。 また経皮的冠動脈インターベンション(PCI)による再灌流療法を施行された急性心筋梗塞(AMI)後、血栓などによる網膜動静脈の血管閉塞なしに、網膜に綿花様白斑が多発する症例を経験した。これまでにAMIに対するPCI後の網膜動脈塞栓の症例報告はあるが、その合併なしにAMIにより綿花様白斑が出現することは一般に知られていない。本論文後半では、この未知のAMIとPCIに関連する網膜症を確立するために、新規発症AMI患者に眼底検査、蛍光眼底造影検査、血液検査を施行し、その発症率、時間経過および危険因子につき前向きに検討した。 2. 糖尿病ラット網膜における白血球停留の亢進に対するグリクラジドの抑制効果 (1)研究方法: ストレプトゾトシン(STZ)誘発糖尿病ラットを無治療糖尿病群(n=8)、グリクラジド投与糖尿病群(n=8;150mg/kg/日×3週間)、グリベンクラミド投与糖尿病群(n=8;8.6mg/kg/日×3週間)の3群に分け、非糖尿病ラットをコントロール群(n=8)とした。糖尿病発症3週間後、経静脈的に投与したアクリジンオレンジにより生体内で白血球を染色し、走査レーザー検眼鏡を用いて網膜内に存在する白血球を観察した(Acridine Orange Leukocyte Fluorography)。視神経乳頭を中心に半径3乳頭径内の網膜に停留した白血球数を算定した。 (2)研究成績: 無治療糖尿病群、グリクラジド投与糖尿病群、グリベンクラミド投与糖尿病群のSTZ注射48時間後と3週間後の血糖値は、コントロール群に比較して有意に高く、コントロール群以外の3群間には血糖値に有意差はなかった。無治療糖尿病群(36.9±5.1個)では、コントロール群(21.9±2.9個)と比較して網膜に停留した白血球数が有意に増加した(p=0.0007)。グリクラジド投与糖尿病群(23.5±4.0個)では、無治療糖尿病群と比較して停留した白血球数が有意に減少した(p=0.0008)。一方、グリベンクラミド投与糖尿病群(37.8±5.8個)では、無治療糖尿病群と比較して停留した白血球数に有意差はなかった(p=0.7923)。 (3)考察: グリクラジドが実験的糖尿病ラットの網膜における白血球の停留を血糖値に関わらず抑制することが明らかになった。このことは、グリクラジドが血糖降下作用以外に糖尿病初期にみられる網膜内の白血球停留を抑制する作用を有し、糖尿病網膜症の発症、進展を予防する可能性を示唆する。 3. 急性心筋梗塞の再灌流療法後に出現する網膜症の検討 (1)研究方法: AMI発症24時間以内にPCIを施行された連続30症例(男23例、女7例、年齢39~85才、平均59才)に対して、PCI施行後3日以内、2週間後、1ヵ月後、2ヵ月後、3ヵ月後に、コントロールとして安定狭心症でPCIを受けた連続10症例(男8例、女2例、年齢57~75才、平均69才)に対して、PCI施行後3日以内と1ヶ月後に眼科的検査(視力検査および眼底検査)を施行した。網膜微小循環の変化を評価するためにフルオレセイン蛍光眼底造影検査を網膜症の出現した3症例に施行した。網膜症出現群、網膜症非出現群間で、臨床的背景因子、血液検査データを比較し危険因子について検討した。 (2)研究成績: 検査の開始時にすでに既知の網膜症が認められた症例は除外した。AMI群ではPCI施行後3ヶ月の期間中、30例中17例(57%)に綿花様白斑が出現し、その17例中7例(41%)は表層性出血も併発した。17例中12例(71%)は両側性に網膜症を認めた。網膜症を認めた17例中4例(24%)でPCIを受けた後、霧視や変視の自覚を訴えたが、全例で視力低下は認めなかった。3症例に施行したフルオレセイン蛍光眼底造影検査では、網膜動静脈の閉塞はなく綿花様白斑の部位に一致して網膜毛細血管の無灌流野を認めた。安定狭心症群では、PCI施行後3日以内、1ヶ月後ともに網膜症はみられなかった。AMI群で出現した網膜変化は、特別な治療なしに比較的短期間のうちに消退する傾向があった。しかし、網膜症が出現した17例中6例は3ヶ月以上網膜症が遷延し、そのうち5例は糖尿病を有していた。網膜症出現群の59%は糖尿病を有していたが、網膜症非出現群では糖尿病合併は23%であった(p=0.0542)。 (3)考察: 綿花様白斑を主所見するAMIとPCIに関連する新しい網膜症の病態が明らかになった。この網膜症の原因として、心臓の虚血再灌流障害よる激しい炎症反応が遠隔臓器である眼球にも影響を及ぼし、網膜微小循環障害を引き起こした可能性があると考えられる。糖尿病患者ではこの網膜症が出現しやすく遷延する傾向があり、注意深い経過観察が必要である。 4. 結論 網膜微小循環障害に起因する網膜症を対象とした動物実験研究と臨床研究について報告した。動物実験研究では、グリクラジドが実験的糖尿病ラットの網膜における白血球停留の亢進を血糖値に関わらず抑制することをin vivoで初めて明確に示した。また臨床研究では、AMIに対するPCIによる再灌流療法後に出現する新しい疾患概念の網膜症を発見した。 今後、糖尿病網膜症や今回発見した心筋梗塞再灌流後の網膜症などの網膜微小循環障害に起因する網膜症の発症機序解明および治療薬についてさらに研究を進める予定である。
  • Ryuichiro Ono, Akihiro Kakehashi, Hiroko Yamagami, Norito Sugi, Nozomi Kinoshita, Takako Saito, Hiroyuki Tamemoto, Masatoshi Kuroki, San-E. lshikawa, Masanobu Kawakami
    International Ophthalmology 26 (1-2) 15 - 19 0165-5701 2005/04 [Refereed][Not invited]
    Purpose: To study the relation between posterior vitreous detachment (PVD) and progression of diabetic retinopathy (DR), based on our observation that proliferative DR is rare in patients with complete PVD. Methods: The medical records of 403 patients with diabetes were reviewed for the relation between progressive DR and the status of PVD and HbA1c over 3 years. PVD was classified into none, complete PVD with collapse, complete PVD without collapse, partial PVD with a thickened posterior vitreous cortex, and partial PVD without a thickened posterior vitreous cortex. DR was classified into none, simple, preproliferative, or proliferative. When it became more extensive or when laser treatment or vitreous surgery was performed, the DR was considered progressive. Results: Progression of DR over 3 years occurred in 128/292 (43.8%) eyes with no PVD, 0/14 (0%) eyes with complete PVD with collapse, 2/8 (25%) eyes with complete PVD without collapse, 15/15 (100%) eyes with partial PVD with a thickened posterior vitreous cortex, and 19/74 (25.7%) eyes with partial PVD without a thickened posterior vitreous cortex. Progression of DR occurred significantly more frequently in eyes with partial PVD with a thickened posterior vitreous cortex compared to eyes with complete PVD with collapse (p < 0.0001). HbA1c, did not differ significantly between these two groups (6.9 ± 0.9% and 7.5 ± 0.9%, respectively p = 0.14), although HbA1c was significantly higher (p = 0.04) in patients with progressive DR (78 ± 1.8%) than in patients without progressive DR (7.5 ± 1.5%). Conclusion: Complete PVD is a strong negative risk factor for DR. The PVD status in patients with diabetes should be evaluated. © Springer 2006.
  • 杉 紀人, 梯 彰弘, 斉藤 由香, 大野 隆一郎, 木下 望, 牧野 伸二, 安 隆則, 黒木 昌寿, 加園 恵三, 川上 正舒
    Therapeutic Research ライフサイエンス出版(株) 26 (3) 364 - 365 0289-8020 2005/03 
    網膜症発症,進行のメカニズムに沿った薬剤の開発のために,ATP-K+チャネル開口とNO供与により心血管保護作用を示し,心筋梗塞後の虚血再灌流障害の治療に用いられているニコランジルに注目した.このニコランジルの血管保護作用が糖尿病初期の網膜微小循環に改善効果を示すか,STZ誘発糖尿病モデルラットを用いてretinal leukostasisに対するニコランジルの作用を検討した.ニコランジル治療群では,未治療群に比べ網膜微小循環で有意にretinal leukostasisが抑制された.ニコランジルは初期糖尿病網膜症の治療に有効である可能性が示唆された
  • K Kasono, T Yasu, A Kakehashi, N Kinoshita, H Tamemoto, K Namai, R Ohn, H Ueba, M Kuroki, S Ishikawa, M Kawakami
    European Journal of Endocrinology 151 (2) 277 - 285 0804-4643 2004/08 [Refereed][Not invited]
    Objective: N-(2-hydroxyethyl)-nicotinamide nitrate (nicorandil) is a unique anti-anginal agent, reported to act as both an ATP-sensitive K+ channel opener (PCO) and a nitric oxide donor. It also has an anti-oxidant action. We examined the effects of nicorandil on streptozotocin (STZ)-induced islet beta-cell damage both in vivo and in vitro. Design and methods: STZ-induced diabetic Brown Norway rats (STZ-DM) were fed with nicorandil-containing chow from day 2 (STZ-DM-N48). 3 (STZ-DM-N72), and 4 (STZ-DM-N96) to day 30. Body weight, blood glucose, and plasma insulin were measured every week. For the in vitro assay, neonatal rat islet-rich cultures were performed and cells were treated with nicorandil from 1 h before to 2 h after exposure to STZ for 30 min. Insulin secretion from islet cells was assayed after an additional 24 h of culture. We also observed the effect of nicorandil on the generation of reactive oxygen species (ROS) from rat inslinoma cells (RINm5F). Results: Body weight loss and blood glucose levels of STZ-DM-N48 rats were significantly lower than those of STZ-DM rats. Immunohistochemical staining of insulin showed preservation of insulin-secreting islet beta-cells in STZ-DM-N48 rats. Nicorandil also dose-dependently recovered the insulin release from neonatal rat islet cells treated with STZ in in vitro experiments. Nicorandil did not act as a PCO on neonatal rat islet beta-cells or RINm5F cells, and did not show an inhibitory effect on poly( ADP-ribose) polymerase-1. However, the drug inhibited the production of ROS stimulated by high glucose (22.0 mmol/l) in RINm5F cells. Conclusions: These results suggested that nicorandil improves diabetes and rat islet beta-cell damage induced by STZ in vivo and in vitro. It protects islet beta-cells, at least partly, via a radical scavenging effect.
  • STZ誘発糖尿病ラットの初期糖尿病網膜症におけるニコランジルの影響
    杉 紀人, 梯 彰弘, 斉藤 由香, 大野 隆一郎, 木下 望, 牧野 伸二, 安 隆則, 黒木 昌寿, 加園 恵三, 川上 正舒
    糖尿病 (一社)日本糖尿病学会 47 (Suppl.1) S173 - S173 0021-437X 2004/04
  • Nozomi Kinoshita, Akihio Kakehashi, Takanori Yasu, Takuji Katayama, Masatoshi Kuroki, Yutaka Tsurimaki, Ryuichiro Ono, Hiroko Yamagami, Muneyasu Saito, Masanobu Kawakami
    British Journal of Ophthalmology 88 (4) 494 - 496 0007-1161 2004/03 [Refereed][Not invited]
    Aim: To report a new form of retinopathy that was observed in patients who had undergone percutaneous coronary intervention (PCI) following acute myocardial infarction (AMI). Methods: Serial ophthalmological examinations were conducted in 40 patients who underwent PCI. Thirty patients were diagnosed with AMI, and another 10 had stable angina pectoris. Results: Cotton wool spots developed in 17 (57%) patients from the group with AMI undergoing PCI (n = 30) within 2 months. Of these, 41% ( seven patients) also developed superficial haemorrhages. Retinopathy was most prominent 1 - 2 months after AMI and then tended to become quiescent afterwards, without treatment. Conclusion: We have identified a new form of retinopathy in patients with AMI that spontaneously subsides without treatment.
  • Takuji Katayama, Takanori Yasu, Nozomi Kinoshita, Akihiro Kakehashi, Hiroto Ueba, Shigemasa Hashimoto, Nobuhiko Kobayashi, Yoshio Tsuruya, Norifumi Kubo, Mikihisa Fujii, Masatoshi Kuroki, Masanobu Kawakami, Muneyasu Saito
    Journal of Cardiology 42 (1) 23 - 28 0914-5087 2003/07 [Refereed][Not invited]
    Objectives. The severe inflammatory reaction caused by acute myocardial infarction and reperfusion affects both the heart and other remote organs. The occurrence of retinopathy was evaluated in patients with acute myocardial infarction who underwent reperfusion therapy. Methods. We investigated 29 patients with first acute myocardial infarction who underwent successful reperfusion therapy within 24 hr of the onset. Ophthalmic examinations including visual acuity test and ocular fundoscopy were performed within 3 days, 2 weeks, and then monthly up to 3 months after the onset of acute myocardial infarction. Plasma levels of intercellular adhesion molecule-1 (ICAM-1), interleukin-6 and high sensitivity C-reactive protein were measured on admission. Results. Soft exudates around the optic disc appeared in 17 (58.6%) of the 29 patients, among whom 5 also developed superficial hemorrhages (17.2%). The retinopathy became most remarkable between 1 to 2 months after the onset of acute myocardial infarction and then faded away without any specific treatment. None of the patients had impairment of visual acuity, although 4 of the 17 patients with retinopathy complained of either blurred vision or metamorphopsia. Hypertension and/or diabetes mellitus tended to be more common in the retinopathy group than in the non-retinopathy group(59% vs 33%, p = 0.096). Plasma ICAM-1 levels were significantly higher than in the non-retinopathy group than in the retinopathy group (p = 0.017). There was no significant difference in plasma levels of interleukin-6 and high sensitivity C-reactive protein between the two groups. Conclusions. Retinopathy may occur after reperfusion for acute myocardial infarction. The dominant manifestation is transient soft exudates reflecting spotty retinal ischemia, probably due to microvascular obstruction.
  • Nozomi Kinoshita, Akihiro Kakehashi, Sigeru Inoda, Yuka Itou, Masatoshi Kuroki, Takanori Yasu, Masanobu Kawakami, Y Kanazawa
    Diabetologia Springer-Verlag 45 (5) 735 - 739 0012-186X 2002/04 [Refereed][Not invited]
    Aims/hypothesis. Early stage leukocyte entrapment in the retinal microcirculation (retinal leukostasis) is considered to be one of the important pathogenetic events in diabetic retinopathy. Gliclazide, a sulphonylurea, was reported to reduce leukocyte adhesion to endothelial cells in hyperglycaemia in vitro, thus suggesting possible selective efficacy of this sulphonylurea in preventing leukostasis in diabetic patients. This study evaluated the effectiveness and selectivity of gliclazide treatment on retinal leukostasis of diabetic rats in vivo. Methods. Streptozotocin (STZ) (65 mg/kg)-induced diabetic rats were divided into three groups (n = 8 each): an untreated diabetic group, a gliclazide-treated diabetic group, and a glibenclamide-treated diabetic group. Gliclazide or glibenclamide was administered orally during a 3-week period. Non-diabetic rats were used as a control (n = 8). Retinal leukostasis was quantitatively evaluated in vivo by acridine orange T leukocyte fluorography using a scanning laser ophthalmoscope. Results. The number of leukocytes trapped in the area around the optic disc in the untreated diabetic group (36.9 +/- 5.1 cells) increased significantly compared with the non-diabetic control group (21.9 +/- 2.9 cells; p = 0.0007). The number of leukocytes trapped in the gliclazide-treated diabetic group (23.5 +/- 4.0 cells) decreased significantly compared with untreated diabetic group (p = 0.0008). In contrast, no reduction of retinal leukostasis was found in the glibenclamide-treated diabetic group (37.8 +/- 5.8 cells; p = 0.7923). Conclusion/interpretation. This suggests that gliclazide could directly improve abnormalities in the retinal microcirculation independent of blood glucose control and possibly have selective therapeutic benefits in preventing early, critical events in diabetic retinopathy compared with other sulphonylurea drugs.

Books etc

  • Nozomi Kinoshita (Single work)
    IOL&RS Vol.35 No.4 / Kyorinsya 2021/12
  • Nozomi Kinoshita (Single work)
    GENTOSHA INC. 2021/07 9784344935310 172
  • Nozomi Kinoshita (ContributorHow effective can the combination therapy be?)
    Bunkodo Co., Ltd. 2021/05 9784830656071 232 p.138-142 
    Essence ・オルソケラトロジー+0.01%アトロピン点眼併用療法は,2年間で28%の相加効果 ・同併用療法の2年間の近視進行抑制率は,単焦点眼鏡と比べて59%に相当 ・同併用療法は,特に弱度近視の1年目においてより効果的
  • Nozomi Kinoshita (ContributorLow-concentration atropine)
    Ganka Vol. 63, No. 1 / Kanehara & Co., Ltd. 2021/01 5 p.23-31 
    近年のIOLマスター®(カールツァイスメディテック社)など非接触式眼軸長計測機器の進歩は,児童の眼軸長測定を簡便かつ精確なものとし,児童の近視発症・進行の主原因が眼軸長の伸展であることを明らかにした.近視の進行が止まらず強度近視になると眼軸伸長によって網膜が引き伸ばされ菲薄化することにより,近視性黄斑変性,網膜剥離,緑内障などの失明に繋がる眼疾患の発症リスクが高まる.そのため,近視進行抑制効果を評価する際に,以前は屈折値変化量で比較されていたが,近年では眼軸長変化量での比較がより重要視されるようになった.また近視は発症年齢が低いほど進行が速く将来強度近視になる可能性が高いので,幼少期からの治療が必要である. 近視進行抑制治療は,ムスカリン受容体拮抗点眼液による薬物的治療とオルソケラトロジー(オルソK)・多焦点ソフトコンタクトレンズ(SCL)・特殊眼鏡による光学的治療に大別される.ムスカリン受容体拮抗点眼液による薬物的治療は,オルソK・多焦点SCLによる光学的治療と比較して,簡便で角膜感染症のリスクが少ないため年少者に使用し易く,経済的な負担も軽いといったメリットがある.しかしながら一方で,高濃度の強力な点眼液を使用すると散瞳による羞明, 調節麻痺による近見障害,全身的な副作用が問題となり,さらに裸眼での遠見視力が改善するわけではないため患者満足度が低く,中等度まで近視が進行すると,眼鏡,コンタクトレンズ,オルソKなどの近視を矯正する手段との併用が必要になる弱点がある.
  • Nozomi Kinoshita (Contributorオルソケラトロジーと低濃度アトロピン点眼液の併用による近視進行予防)
    Visual Science Vol. 40, No. 4 / The Japanese Society of Ophthalmological Optics 2019/12 4 p.95-98 
    Many studies from around the world have reported the efficacy of orthokeratology in slowing myopia progression since 2005, which has been supported by a meta-analysis. Orthokeratology (OK) is now recognized as the most reliable treatment to slow myopia progression. Atropine 0.01% ophthalmic solution has recently been attracting attention, since the report of its efficacy in 2012. It is generally considered that atropine can slow the progression of myopia by a pharmaceutical mechanism, and that OK can slow the progression by an optical mechanism. We conducted a prospective clinical study to confirm the effectiveness of the combined treatment and reported that additive effects were achieved.
  • Nozomi Kinoshita (ContributorPrevent myopia progression with eye drops)
    Ganka Graphic Vol. 8 No. 6 / Medicus Shuppan,Publishers Co., Ltd. 2019/11 9784840468381 5 p.651-655 
    近年,IOLマスター®(カールツァイスメディテック)などの非接触式眼軸長計測機器の進歩により簡便かつ精確な眼軸長の測定が可能となり,子供の近視進行の原因は軽度のものも含めてほとんどが眼軸長の伸展であることが明らかになった.近視の進行が止まらず強度近視になると眼軸伸長によって網膜が引き伸ばされ菲薄化することにより,網脈絡膜萎縮,黄斑変性,緑内障,網膜剥離の発症リスクが高まり失明に繋がる.近視は発症年齢が低いほど進行しやすいので,強度近視への進行を予防するためには幼少期からの治療が必要である. 近視進行抑制治療は,ムスカリン受容体拮抗点眼液による薬物的治療とオルソケラトロジー・多焦点コンタクトレンズなどの光学的治療に大別される.点眼液による薬物的治療は,コンタクトレンズによる光学的治療と比較して,簡便で角膜感染症のリスクが少ないため年少者に使用し易く,経済的な負担も軽いといったメリットがある反面,散瞳作用による羞明, 調節麻痺作用による近見障害などの副作用が問題となり,遠見視力を改善しないため別の近視矯正手段が必要となるデメリットがある.これまでに近視治療に用いられてきた点眼液について,古いものから順番に解説する.

Conference Activities & Talks


Awards & Honors

  • 2019/10 American Academy of Ophthalmology AAO Best Poster Award
     PO349-2019 Additive Effects of Orthokeratology and Atropine 0.01% Ophthalmic Solution for Slowing Axial Elongation 
    受賞者: Nozomi Kinoshita;Yasuhiro Konno, Naoki;Hamada;Machiko Shimmura-Tomita;Akihiro Kakehashi
  • 2013/05 Saitama Ophthalmologist Association 2012 Saitama Ophthalmologist Association Award
     Blunt needle revision with viscoelastic materials via the anterior chamber for early failed filtering blebs after trabeculectomy. 
    受賞者: Nozomi Kinoshita;Ayumi Ota;Fumihiko Toyoda;Hiroko Yamagami;Akihiro Kakehashi
  • 2002/05 Japanese Ophthalmological Society 106th Annual Meeting of the Japanese Ophthalmological Society Excellent Presentation Award
     A study on novel retinopathy that developed after acute myocardial infarction 
    受賞者: Nozomi Knoshita;Akihiro Kakehashi;Takuji Katayama;Takanori Yasu;Masatoshi Kuroki;Yuzuru Tsurimaki;Ryuichiro Ono;Hiroko Yamagami;Muneyasu Saito;Masanobu Kawakami

Research Grants & Projects

Teaching Experience

  • OphthalmologyOphthalmology Jichi Medical University

Media Coverage


  • 2021/04 - Today 身体障害者福祉法第15条指定医
  • 2021/04 - Today The Society of Orthokeratology and Specialty lens Japan (SOS-J), caretaker
    The Society of Orthokeratology and Specialty lens Japan
  • 2021/02 - Today ボトックス講習修了医
  • 2020/12 - Today Refractive Surgery Course Completed Doctor
  • 2020/01 - Today 難病指定医
  • 2013/04 - Today Orthokeratology Course Completed Doctor
    Japanese Ophthalmological Society
  • 2005/10 - Today 眼科専門医
  • 2014/10 -2020/09 眼科指導医
  • 2014/07 -2019/07 トラベクトーム認定医

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