研究者総覧

髙橋 秀徳 (タカハシ ヒデノリ)

  • 眼科学講座 准教授
Last Updated :2022/01/25

研究者情報

学位

  • 医学博士(東京大学)

ホームページURL

科研費研究者番号

  • 10361479

J-Global ID

プロフィール

  • DeepEyeVision株式会社を設立し、深層学習による眼科画像診断支援を行っています。深層学習以外では超高感度測定法を用いた滲出型加齢黄斑変性や糖尿病網膜症を中心とする眼内新生血管の診断・治療・病態解析・より良い診断法治療法の開発を行っています。

研究キーワード

  • 機械学習   分子生物学   網膜静脈閉塞症   糖尿病網膜症   加齢黄斑変性   血管内皮増殖因子   

研究分野

  • ライフサイエンス / 眼科学

経歴

  • 2017年04月 - 現在  自治医科大学眼科学講座准教授
  • 2012年04月 - 2017年03月  自治医科大学眼科学講座講師
  • 2009年07月 - 2012年03月  JCHO東京新宿メディカルセンター眼科医長
  • 2009年04月 - 2009年06月  JCHO東京新宿メディカルセンター眼科医員
  • 2008年07月 - 2009年03月  東京大学眼科助教
  • 2008年04月 - 2008年06月  東京大学眼科医員
  • 2003年04月 - 2004年03月  東京大学眼科技官
  • 2001年05月 - 2003年03月  東京大学眼科研修医

学歴

  • 2004年04月 - 2008年03月   東京大学大学院   医学系研究科   眼科学
  • 1997年04月 - 2001年03月   東京大学   医学部   医学科
  • 1995年04月 - 1997年03月   東京大学   教養学部
  • 1989年04月 - 1995年03月   栄光学園

研究活動情報

論文

  • Rapid progression of chorioretinal atrophy in punctate inner choroiditis: a case report
    Yuka Kasuya, Yuji Inoue, Satoru Inoda, Yusuke Arai, Hidenori Takahashi, Hidetoshi Kawashima, Yasuo Yanagi
    J Med Case Rep 15 1 2021年12月 [査読有り][通常論文]
  • Cytokine profiles of macular neovascularization in the elderly based on a classification from a pachychoroid/drusen perspective
    Satoru Inoda, Hidenori Takahashi, Yuji Inoue, Xue Tan, Hironobu Tampo, Yusuke Arai, Yasuo Yanagi, Hidetoshi Kawashima
    Graefes Arch Clin Exp Ophthalmol 2021年10月 [査読有り][通常論文]
  • Aqueous humour cytokine profiles after Descemet's membrane endothelial keratoplasty
    Takahiko Hayashi, Hidenori Takahashi, satoru Inoda, Toshiki Shimizu, Akira Kobayashi, Hidetoshi Kawashima, Takefumi Yamaguchi, satoru Yamagami
    scientific reports 11 17064  2021年08月 [査読有り][通常論文]
  • Efficacy of Modified Treat-and-Extend Regimen of Aflibercept for Macular Edema from Branch Retinal Vein Occlusion:2-Year Prospective Study Outcomes
    Yusuke Arai, Hidenori Takahashi, Satoru Inoda, Shinichi Sakamoto, Xue Tan, Yuji Inoue, Satoko Tominaga, Hidetoshi Kawashima, Yasuo Yanagi
    Journal of Clinical Medicine 10 3162  2021年07月 [査読有り][通常論文]
  • Association between visual field damage and corneal structural parameters
    Alexndru Lavrc, Valentin Popa, Hidenori Takahashi, Rossen M.Hazarbassanov, Siamak Yousefi
    Scientific Reports 11 10732  2021年05月 [査読有り][通常論文]
  • ブロルシズマブ切替後内眼炎の投与前前房水中タンパク質濃度プロファイル
    橋本 悠人, 伊野田 悟, 高橋 秀徳, 吉田 花, 高橋 良太, 坂本 晋一, 新井 悠介, 川島 秀俊, 柳 靖雄
    日本眼科学会雑誌 125 臨増 233 - 233 (公財)日本眼科学会 2021年03月
  • ブロルシズマブ投与後内眼炎を来した滲出型加齢黄斑変性6例の背景検討
    吉田 花, 新井 悠介, 高橋 秀徳, 橋本 悠人, 譚 雪, 伊野田 悟, 高橋 良太, 藤野 雄次郎, 川島 秀俊, 柳 靖雄
    日本眼科学会雑誌 125 臨増 264 - 264 (公財)日本眼科学会 2021年03月
  • AIを利用した効率的な糖尿病網膜症健診
    髙橋秀徳
    日本糖尿病合併症学会 35 1 33 - 36 2021年 [査読無し][招待有り]
  • Keratoconus severity detection from elevation, topography and pachymetry raw data using a machine learning approach
    Alexandru Lavric, Liliana Anchidin, Valentin Popa, Ali H. AI-Timemy, Zaid Alyasseri, Hidenori Takahashi, Simak Yousefi, Rossen M.Hazarbassanov
    IEEE Access 9 84344 - 84355 2021年 [査読有り][通常論文]
  • Accidental Corneal Intrastromal Intraocular Lens Implantation with the Wound-Assisted Technique and Clinical Course with Anterior Segment Optical Coherence Tomography
    Jo Moriya, Shinichi Sakamoto, Satoru Inoda, Hidenori Takahashi, Hidetoshi Kawashima
    Case Reports in Ophthalmology 12 283 - 287 2021年 [査読有り][通常論文]
  • 若年者の増殖糖尿病網膜症に対する小切下開硝子体手術の成績
    案浦加奈子, 新井悠介, 伊野田悟, 坂本晋一, 佐野一矢, 井上裕治, 髙橋秀徳, 川島秀俊
    眼科臨床紀要 14 3 135 - 140 2021年 [査読有り][通常論文]
  • コーツ病に伴った黄斑円孔の1例
    橋本 悠人, 新井 悠介, 坂本 晋一, 高橋 秀徳, 井上 裕治, 牧野 伸二, 川島 秀俊
    眼科臨床紀要 13 10 697 - 698 眼科臨床紀要会 2020年10月
  • Takahiko Hayashi, Akira Kobayashi, Hidenori Takahashi, Itaru Oyakawa, Naoko Kato, Takefumi Yamaguchi
    PLoS One 15 10 e0240458  2020年10月 [査読有り][通常論文]
     
    PURPOSE: To evaluate the corneal characteristics after Descemet membrane endothelial keratoplasty (DMEK) compared with normal corneas. METHODS: Patients who underwent DMEK at Yokohama Minami Kyosai Hospital were included and prospectively evaluated pre-operatively and at postoperative months 1, 3, 6, and 12, and compared to healthy controls. Corneal characteristics evaluated included corneal curvature (keratometric value [KV]; D), central corneal thickness (CCT), peripheral corneal thickness (PCT), and corneal higher-order aberrations [HOAs] at 6.0 mm diameter, calculated by anterior segment optical coherence tomography and logarithm of the minimal angle of resolution [logMAR]. RESULTS: A total of 30 eyes of 30 patients (6 men, 24 women, mean age 73.4 ± 7.4 years) were included and compared with 31 age-matched healthy control eyes (13 men, 18 women; mean age 73.0 ± 6.7 years). LogMAR after DMEK improved from 0.87 ± 0.07 preoperatively to 0.04 ± 0.07 at 12 months postoperatively (p<0.001). Although anterior KVs of DMEK eyes were similar to those of control eyes, posterior KVs were significantly larger (-6.4 ± 0.3 D vs. -6.3 ± 0.2 D; p = 0.02). Total HOAs after DMEK improved from 1.94 ± 1.05 μm preoperatively to 1.05 ± 0.16 μm at 12 months postoperatively (p<0.001), which was significantly higher than that in control eyes (0.63 ± 0.06) (p<0.001). Despite the similar CCTs in the two groups, the PCT was significantly larger in DMEK eyes (704 ± 41 μm vs 669 ± 38 μm, p = 0.002) at 12 months. CONCLUSION: Despite achieving good visual function and excellent corneal clarity, eyes that underwent DMEK showed a steeper posterior KV and higher corneal HOAs than normal eyes even at 12 months after surgery.
  • Detecting Keratoconus from Corneal Imaging Date using Machine Learning
    Alexandru Lavric, Valentin Popa, Hidenori Takahashi, Siamak Yousefi
    IEEE Access 8 149113 - 149121 2020年08月 [査読有り][通常論文]
  • Yusuke Arai, Hidenori Takahashi, Satoru Inoda, Shinichi Sakamoto, Xue Tan, Yuji Inoue, Satoko Tominaga, Hidetoshi Kawashima, Yasuo Yanagi
    Journal of clinical medicine 9 8 2020年07月 [査読有り][通常論文]
     
    PURPOSE: To assess the efficacy and safety of a modified treat-and-extend (mTAE) regimen of aflibercept for macular edema (ME) due to branch retinal vein occlusion (BRVO). METHODS: This prospective multicentre intervention study evaluated 50 eyes of 50 patients enrolled from October 2016 to September 2017. The patients received intravitreal aflibercept (IVA) injections on an mTAE regimen for a total of 12 months. The main outcome measures were best-corrected visual acuity (BCVA) and central subfield thickness (CST) at 12 months. RESULTS: The baseline BCVA and CST were 0.33 (0.27) and 488 (171) µm (mean (standard deviation)), respectively. The BCVA and CST were significantly improved at month 12 (0.067 (0.19) LogMAR and 295 (110) µm; both p < 0.0001, paired t-test). The mean number of clinic visits and IVA injections was 6.71 (1.41) and 4.26 (0.71), respectively. The time to first recurrence from the first injection was most frequently 3 months. CONCLUSION: The mTAE regimen of IVA injections for ME due to BRVO effectively improved BCVA and reduced CST, and thus might be an effective therapy to reduce the number of injections and visits.
  • Galactosialidosis TypeⅡb with Bilateral Macular Cherry-Red Spots but Mild Dysfunction
    Hanon Fukuyo, Yuji Inoue, Hidenori Takahashi, Yu Hatano, Toko Shibuya, Norio Sakai, Hidetoshi Kawashima
    Case Rep Ophthalmol 11 2 2020年07月 [査読有り][通常論文]
  • 高齢者の黄斑部新生血管の視力予後に関与する炎症性サイトカインの検討
    伊野田 悟, 高橋 秀徳, 譚 雪, 新井 悠介, 坂本 晋一, 井上 裕治, 藤野 雄次郎, 川島 秀俊, 柳 靖雄
    眼科臨床紀要 13 6 440 - 440 眼科臨床紀要会 2020年06月
  • Siamak Yousefi, Hidenori Takahashi, Takahiko Hayashi, Hironobu Tampo, Satoru Inoda, Yusuke Arai, Hitoshi Tabuchi, Penny Asbell
    The ocular surface 18 2 320 - 325 2020年04月 [査読有り][通常論文]
     
    OBJECTIVE: To apply artificial intelligence (AI) for automated identification of corneal condition and prediction of the likelihood of need for future keratoplasty intervention from optical coherence tomography (OCT)-based corneal parameters. DESIGN: Cohort study. PARTICIPANTS: We collected 12,242 corneal OCT images from 3162 subjects using CASIA OCT Imaging Systems (Tomey, Japan). We included 3318 measurements collected at the baseline visit of each patient. A total of 333 eyes had post-operative penetrating keratoplasty (PKP), lamellar keratoplasty (LKP), deep anterior keratoplasty (DALK), descemet's stripping automated endothelial keratoplasty (DSAEK) or descemet's membrane endothelial keratoplasty (DMEK) intervention. METHOD: We developed a pipeline including linear and nonlinear data transformations followed by unsupervised machine learning and applied on corneal parameters from the baseline visit of each patient. Five non-overlapping clusters of eyes were identified. Post hoc analyses revealed that clusters corresponded to different likelihoods of need for future keratoplasty. These clusters on a 2-dimensional map can be used by clinicians and surgeons to identify patients with higher risk of need for future keratoplasty intervention. MAIN OUTCOME MEASURES: The likelihood of the need for future surgery. RESULTS: The mean age of participants was 69.7 (standard deviation; SD = 16.1) and 59% were female. The normalized likelihood of need for future corneal keratoplasty intervention for eyes mapped onto clusters one to five were 2.2%, 1.0%, 33.1%, 32.7%, and 31.0%, respectively. CONCLUSIONS: The AI system can assist the (cornea) surgeon in identifying those patients who may be at higher risk for future keratoplasty using comprehensive corneal shape, thickness, and elevation parameters. Future research utilizing independent datasets is necessary to validate the proposed system.
  • 漿液性網膜剥離を伴う傾斜乳頭症候群における前房中炎症性サイトカイン濃度
    井上 裕治, 高橋 秀徳, 林 あゆみ, 長岡 広祐, 高橋 良太, 伊野田 悟, 坂本 晋一, 新井 悠介, 富永 聡子, 譚 雪, 川島 秀俊, 柳 靖雄
    日本眼科学会雑誌 124 臨増 167 - 167 (公財)日本眼科学会 2020年03月
  • Satoru Inoda, Takahiko Hayashi, Hidenori Takahashi, Itaru Oyakawa, Hideaki Yokogawa, Akira Kobayashi, Naoko Kato, Hidetoshi Kawashima
    PloS one 15 6 e0234202  2020年 [査読有り][通常論文]
     
    PURPOSE: To investigate the factors associated with endothelial survival after Descemet's membrane endothelial keratoplasty (DMEK) in eyes of Asian patients with bullous keratopathy (BK). METHODS: In this retrospective, consecutive interventional case series, 72 eyes of 72 patients who underwent DMEK were evaluated. Best corrected visual acuity (BCVA) and corneal endothelial cell density (ECD) were assessed at 12 months postoperatively. Multiple regression analysis was performed to assess parameters such as age, sex, axial length, preoperative visual acuity, re-bubbling, the ratio of graft to cornea area, iris damage scores, types of filling gases, air or SF6 volume in the anterior chamber (AC) on postoperative day 1, and ECD loss rates at 12 months postoperatively. RESULTS: BCVA improved significantly at 12 months after DMEK (P < .001). The rate of ECD loss at 12 months after DMEK was 54.4 ± 16.1%. Multiple linear regression analysis showed that a larger ratio of graft to corneal area (P = 0.0061) and higher donor ECD (P = 0.042) were the primary factors for a lower ECD loss rate at 12 months after DMEK. CONCLUSION: A relatively larger graft size compared to the host cornea and more donor ECD might help endothelial survival in patients with BK. Moreover, for such patients, the surgeon should attempt to use a relatively larger graft size when performing DMEK, particularly in Asian eyes.
  • Yusuke Arai, Hidenori Takahashi, Satoru Inoda, Xue Tan, Shinichi Sakamoto, Yuji Inoue, Yujiro Fujino, Hidetoshi Kawashima, Yasuo Yanagi
    PloS one 15 3 e0229342  2020年 [査読有り][通常論文]
     
    We aimed to construct a better model for predicting treatment outcomes of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration (nAMD) using the concentrations of aqueous humour proteins at baseline and during treatment. From the data of 48 treatment-naïve nAMD eyes that received intravitreal ranibizumab pro re nata for up to 12 months, we used the aqueous humour concentrations of C-X-C motif chemokine ligand 1 (CXCL1), CXCL12, CXCL13, interferon-γ-induced protein 10, monocyte chemoattractant protein 1 (MCP-1), C-C motif chemokine ligand 11, interleukin 6 (IL-6), IL-10, and matrix metalloproteinase 9 (MMP-9). After stepwise regression, multivariate analysis was performed to identify which predictors were significantly associated with best-corrected visual acuity (BCVA) changes and the number of injections. The results demonstrated that besides male sex (β coefficient = -0.088, P = 0.040) and central retinal thickness (β coefficient = 0.00051 per μm, P = 0.027), MCP-1 (β coefficient = 0.44, P < 0.001) and IL-10 (β coefficient = -0.16, P = 0.033) were significantly correlated with baseline BCVA. Additionally, high MCP-1 at baseline (β coefficient = -0.20, P = 0.015) and low CXCL13 at baseline (β coefficient = 0.10, P = 0.0054) were independently associated with better BCVA change at 12 months. High MMP-9 at the first injection (β coefficient = 0.56, P = 0.01), CXCL12 at the third injection (β coefficient = 0.10, P = 0.0002), and IL-10 at the third injection (β coefficient = 1.3, P = 0.001) were predictor variables associated with the increased number of injections. In conclusion, aqueous humour protein concentrations may have predictive abilities of BCVA change over 12 months and the number of injections in pro re nata treatment of exudative nAMD.
  • Satoru Inoda, Takahiko Hayashi, Hidenori Takahashi, Itaru Oyakawa, Hideaki Yokogawa, Akira Kobayashi, Naoko Kato, Hidetoshi Kawashima
    Cornea 38 12 e58-e59  2019年12月 [査読有り][通常論文]
  • Ichiya Sano, Hidenori Takahashi, Satoru Inoda, Shinichi Sakamoto, Yusuke Arai, Yuji Takahashi, Akira Ohkubo, Hidetoshi Kawashima, Chihiro Mayama
    American journal of ophthalmology 206 11 - 16 2019年10月 [査読有り][通常論文]
     
    PURPOSE: To investigate changes in the interpupillary distance (IPD) after continual instillation of topical prostaglandin analogs (PGAs) in glaucoma patients as an objective indicator of prostaglandin-associated periorbitopathy (PAP). DESIGN: Retrospective, comparative case series. METHODS: A total of 152 institutional patients with glaucoma were enrolled in this study. Inclusion criteria were visual acuities exceeding 10/20 bilaterally and no intraocular surgery during observation. Intervention/observation procedures: First-time bilateral instillation of bimatoprost, travoprost, latanoprost, or tafluprost and IPDs measured by automatic refractometry. IPDs, intraocular pressures (IOPs), and refractive errors were measured before and after continual drug administration (treatment, 2-24 months). MAIN OUTCOME MEASUREMENTS: Post-treatment changes in IPDs. A total of 61 untreated patients served as controls. RESULTS: The IPDs shortened significantly (P < 0.001) after treatment (-0.80 ± 2.1 mm); the IPDs of control subjects remained unchanged (0.05 ± 0.96 mm; P = 0.69). The IPD change after bimatoprost instillation (-2.20 ± 0.97 mm) was significantly (P < 0.001) greater than with other PGAs (-0.65 ± 2.09 mm). The IOPs decreased significantly (P < 0.001) (-3.7 ± 4.3 mm Hg); the refractive errors did not change significantly (P < 0.099) (-0.07 ± 0.69 diopter) post-treatment. The percentages of subjects with 2-mm or greater decreases in IPD after bimatoprost, travoprost, latanoprost, or tafluprost were 85.7%, 20.0%, 18.2%, and 17.2%, respectively, and with 3-mm or greater decreases in IPD 35.7%, 12.0%, 14.5%, and 12.1%, respectively. The specificities were 93.4% and 100% in the control group, respectively, with IPD threshold changes of 2 and 3 mm or more, respectively. CONCLUSIONS: The IPD decreased significantly after topical PGAs within 24 months. The effect was significantly greater with bimatoprost than with other PGAs. The noninvasive, immediate automatic refractometry measurement may be an objective numerical indicator of PAP.
  • 近藤 由佳, 新井 悠介, 高橋 秀徳, 坂本 晋一, 伊野田 悟, 佐野 一矢, 井上 裕治, 川島 秀俊
    臨床眼科 73 8 1039 - 1044 (株)医学書院 2019年08月 
    <文献概要>目的:網膜静脈分枝閉塞症(BRVO)発症後の硝子体出血に対し硝子体手術を行った症例から,手術成績と網膜光凝固(PC)の必要性について検討した。対象と方法:対象は2013年4月〜2018年3月に自治医科大学眼科でBRVO発症後に硝子体出血を生じた眼に対し硝子体手術を施行した46例46眼。術前PCの有無,術前・術後視力,術後視力と術前PCの有無,無血管野の部位と術後視力,術中・術後合併症について後ろ向きに検討した。結果:硝子体手術前に31例(67%)でPCが施行されていた。術後視力1.0以上は29例(63%)で得られた。術前PCの有無と術後視力との間には関連はなく,網膜血管アーケード内に無血管野があるものでは術後視力が不良であった。術中・術後合併症は10例にみられた。結論:術前にPCが施行された症例が多かったが,術後視力は良好であった。術前PCの有無は術後視力に影響はなかった。PCの必要性についてはさらに検討が必要と考えられた。
  • Inoda S, Hayashi T, Takahashi H, Oyakawa I, Yokogawa H, Kobayashi A, Kato N, Kawashima H
    Cornea 38 7 820 - 824 2019年07月 [査読有り][通常論文]
     
    PURPOSE: To investigate factors associated with cystoid macular edema (CME) after Descemet membrane endothelial keratoplasty (DMEK) in Asian eyes. METHODS: In this retrospective, interventional, consecutive case series, 77 eyes of 65 patients who underwent DMEK were evaluated; in 53 eyes, cataract surgery was performed 1 month before DMEK (staged DMEK), and 24 eyes underwent DMEK alone (simple DMEK). Central retinal thickness, incidence of CME, postoperative best-corrected visual acuity, central corneal thickness, and corneal endothelial cell density were assessed at 1, 3, and 6 months after surgery. Multiple regression analysis and stepwise variable selection were performed for parameters such as type of surgery, iris damage scores, age, sex, axial length, preoperative visual acuity, rebubbling, air volume in the anterior chamber on postoperative day 1, history of diabetes, and endothelial cell density loss rates at 6 months after surgery. RESULTS: CME occurred in 12 (15.6%) of 77 eyes. There was no significant difference in best-corrected visual acuity between eyes with and without CME (P = 0.27). Multivariable analysis revealed that the difference in iris damage scores between before and after DMEK (P < 0.001), air volume in the anterior chamber (P = 0.012), simple DMEK (P = 0.020), and rebubbling (P = 0.036) were significantly associated with CME. Stepwise variable selection indicated that iris damage (P < 0.001) was the most important risk factor for CME. CONCLUSIONS: Iris damage due to DMEK might be a possible risk and aggravating factor for the development of CME after DMEK. Surgeons should attempt to minimize damage to the iris.
  • Nagaoka K, Inoda S, Takahashi H, Arai Y, Inoue Y, Takizawa Y, Fujioka S, Kawashima H
    Case Rep Ophthalmol 10 195 - 199 2019年06月 [査読有り][通常論文]
  • Yuda K, Kato N, Takahashi H, Shimizu T, Oyakawa I, Matsuzawa A, Yuda K, Hayashi T
    Cornea 2019年05月 [査読有り][通常論文]
  • Satoru Inoda, Hidenori Takahashi, Yuji Inoue, Hironobu Tampo, Shinichi Sakamoto, Yusuke Arai, Hidetoshi Kawashima, Yasuo Yanagi
    Clinical ophthalmology (Auckland, N.Z.) 13 959 - 968 2019年 [査読有り][通常論文]
     
    Purpose: To investigate the efficacy of half-dose photodynamic therapy (PDT) for treating symptomatic serous non-neovascular pigment epithelial detachment (PED) and to identify factors associated with treatment outcome. Patients and methods: This is a single-institute retrospective case series involving 12 eyes of 12 consecutive patients with serous non-neovascular PED who received half-dose PDT. We investigated the temporal change in best-corrected visual acuity (BCVA), the anatomic outcomes of PED, including recurrence, central choroidal thickness (CCT), and also choroidal thickness as a possible factor associated with treatment outcome. Results: At baseline, mean logMAR BCVA was 0.06 (range Snellen equivalent 6/20 to 24/20); 24 months later, it was 0.01 (Snellen equivalent 6/20 to 24/20; P=0.3). At 3 months, PED had completely flattened in 8, decreased in height in 2, and remained unchanged in 2. The CCT in eyes with PED was 410 µm and thicker than that in fellow eyes (290 µm, P<0.0001). Recurrence was noted in 2 within 12 months after treatment. Eyes in which the choroidal thickness with a baseline CCT >350μm or a 100 µm difference in CCT responded favorably to half-dose PDT (P=0.02). Conclusion: Half-dose PDT is effective in patients with non-neovascular PED. Thicker choroid and some difference in CCT between affected and fellow eye might be a good index for predicting the efficacy of this treatment.
  • Oyakawa I, Hayashi T, Kobashigawa Y, Matsuzawa A, Takahashi H, Kato N
    Cornea 37 11 1360 - 1365 2018年11月 [査読有り][通常論文]
  • Shimizu T, Hayashi T, Kentaro Yuda K, Takahashi H, Oyakawa I, Yamazaki K, Mizuki N, Kato N
    Cornea 37 11 1355 - 1359 2018年11月 [査読有り][通常論文]
     
    PURPOSE: To evaluate the frequency and severity of iris posterior synechiae after Descemet membrane endothelial keratoplasty (DMEK) and to investigate possible causes of iris posterior synechiae. METHODS: Twenty-three eyes were investigated in 20 Asian patients who underwent DMEK 1 month after phacoemulsification and intraocular lens implantation surgery. A preexisting iris damage score was defined by iris damage and classified into 5 grades. Six months after DMEK, the iris posterior synechiae severity score was evaluated based on the extent of posterior synechiae, according to every 45 degrees of the pupillary rim (posterior synechiae score, 0-8). Correlations were analyzed between the posterior synechiae score and preexisting factors (preexisting iris damage score, axial length [AXL], anterior chamber depth, and anterior chamber volume, both before and after cataract surgery). RESULTS: Iris posterior synechiae appeared in 20 of 23 eyes (87.0%). Best spectacle-corrected visual acuity significantly improved at 6 months after DMEK (P < 0.001). Endothelial cell density was 1596 ± 530 cells/mm (P < 0.001); loss of cell density was 37.8 ± 19.9% at 6 months. Single regression analysis showed that the onset of iris posterior synechiae was correlated with the preexisting iris damage score (P = 0.006, r = 0.55), AXL (P < 0.001, r = -0.71), anterior chamber depth (P < 0.001, r = -0.70), and anterior chamber volume before cataract surgery (P < 0.001, r = -0.79). CONCLUSIONS: Iris posterior synechiae after DMEK frequently appeared in Asian eyes with shorter AXLs or a damaged iris.
  • Takahashi H, Yanagi Y
    Investigative ophthalmology & visual science 59 10 4107  2018年08月 [査読有り][通常論文]
  • Yamada N, Hayashi T, Yuda K, Shimizu T, Oyakawa I, Takahashi H, Kato N
    Journal of Ophthalmology 2018 2018 7  2018年 [査読有り][通常論文]
  • Shinichi Sakamoto, Hidenori Takahashi, Yuji Inoue, Yusuke Arai, Satoru Inoda, Natsuko Kakinuma, Yujiro Fujino, Tatsuro Tanabe, Hidetoshi Kawashima, Yasuo Yanagi
    Clinical ophthalmology (Auckland, N.Z.) 12 1137 - 1147 2018年 [査読有り][通常論文]
     
    Purpose: We report the 2-year outcomes of intravitreal aflibercept (IVA) for exudative age-related macular degeneration (AMD) with good visual acuity (VA) and examine the baseline factors associated with good visual outcome. Materials and methods: This multicenter, prospective study evaluated 39 eyes (39 AMD patients) enrolled from August 2013 to August 2014 at 12 and 24 months. Only patients with initial best-corrected VA (BCVA) >0.3 logarithm of the minimum angle of resolution (20/40 Snellen) were eligible. Three consecutive monthly IVA injections were followed by 2 monthly injections for 12 months. Thereafter, patients received injections on a treat- and-extend regimen for up to 24 months. Outcome measures included BCVA and central macular thickness (CMT) at 12 and 24 months. Post hoc analysis, BCVA, and CMT were evaluated by AMD types (typical AMD [tAMD], type 1, and type 2 polypoidal choroidal vasculopathy [PCV]). Baseline characteristics and BCVA associations were evaluated with linear regression analysis and Student's t-test. Results: Mean age was 69 years and 26 of 39 eyes were male. tAMD, type 1 and type 2 PCV occurred in 18, 12, and 9 eyes, respectively. Baseline mean BCVA was 0.097 logarithm of the minimum angle of resolution (20/25 Snellen) and showed significant improvement to 0.058 (20/22 Snellen, P=0.03) at 12 months and 0.066 (20/23) at 24 months. CMT improved significantly from 320 (99) µm (mean [SD]) to 250 (93) µm (P=0.002) at 12 months and 240 (93) µm (P=0.0005) at 24 months. BCVA and CMT were not significantly different among the three groups. Only subretinal hemorrhage (SRH) was significantly associated with improved BCVA. BCVA change from baseline was -0.12 with SRH and -0.011 without SRH (P=0.017) at 12 months. Conclusion: IVA showed good efficacy for exudative AMD with good VA at 24 months. tAMD and type 1 and 2 PCV showed similar prognosis. Baseline SRH predicted favorable long-term vision in AMD with good VA.
  • Takahashi H, Inoue Y, Tan X, Inoda S, Sakamoto S, Arai Y, Yanagi Y, Fujino Y, Kawashima H
    Clin Ophthalmol 12 369 - 375 2018年 [査読有り][通常論文]
     
    Purpose: To investigate the correlation between visual acuity and central macular thickness (CMT) and choroidal thickness (CCT) in patients with wet age-related macular degeneration (AMD). Methods: In this retrospective analysis, 14 eyes that received >10 ranibizumab injections (based on pro re nata [PRN] regimen) and maintained initial visual acuity gain were analyzed. The following 5 parameters were measured at the foveal center: CMT (distance from the inner limiting membrane [ILM] to Bruch's membrane); central retinal thickness (CRT; distance from the ILM to the inner limit of the retinal pigment epithelium or subretinal fluid [SRF]); SRF thickness (SRFT); pigment epithelium detachment thickness (PEDT); and CCT. The correlation between the logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) and the 5 parameters was examined with generalized estimating equations. Results: CMT, CRT, and CCT were negatively correlated with logMAR BCVA (P=0.031, 0.023, and 0.036, respectively) when only CMT values less than the thickness that maximized visual acuity for each eye were used for the analysis. Each 100-μm reduction in CMT, CRT, or CCT improved logMAR BCVA by -0.1, -0.08, or -0.07, respectively. SRFT and PEDT were not correlated with BCVA. The median CMT that maximized the visual acuity was 230 μm. Conclusion: Dry macula with CMT <230 μm was associated with temporary decrease in visual acuity in AMD patients whose visual acuity was maintained with PRN regimen.
  • Shinichi Sakamoto, Hidenori Takahashi, Xue Tan, Yuji Inoue, Yoko Nomura, Yusuke Arai, Yujiro Fujino, Hidetoshi Kawashima, Yasuo Yanagi
    British Journal of Ophthalmology 102 4 448 - 454 2018年 [査読有り][通常論文]
     
    PURPOSE: To determine changes in multiple cytokine concentrations in the anterior chamber during the induction phase of ranibizumab treatment in patients with neovascular age-related macular degeneration (AMD). METHODS: This prospective study included 48 treatment-naïve neovascular AMD eyes of 48 patients who received three consecutive monthly injections of ranibizumab at the Japan Community Health Care Organization Tokyo Shinjuku Medical Center between November 2010 and August 2012. We collected ~0.2 mL aqueous humour before the first and third (2 months later) injections. Controls were 80 eyes with cataracts without retinal disease. The cytokines C-X-C motif chemokine ligand 1 (CXCL1), interferon-γ-induced protein 10 (IP-10), C-X-C motif chemokine ligand 12 (CXCL12), C-X-C motif chemokine ligand 13 (CXCL13), monocyte chemoattractant protein 1 (MCP-1), CCL11, C-C motif chemokine ligand 11 (CCL11), interleukin-6 (IL-6), interleukin-10 (IL-10) and matrix metalloproteinase 9 (MMP-9) were analysed using multiplex cytokine assays. RESULTS: Mean ages of the patients with AMD and controls were 73 and 75 years, respectively, and 31 (65%) and 37 (46%) subjects were men, respectively. Polypoidal choroidal vasculopathy was found in 27 eyes (56%). Mean concentrations of cytokines in aqueous humour in patients with neovascular AMD before the first and third ranibizumab injections were as follows (in pg/mL): CXCL1, 8.4 and 3.3; IP-10, 110 and 55; CXCL12, 480 and 240; CXCL13, 9.2 and 2.6; MCP-1, 620 and 220; CCL11, 7.1 and 2.8; IL-6, 5.9 and 1.6; IL-10, 0.15 and 0.015 (all p<0.0001), and MMP-9, 0.92 and 1.5 (p=0.0216), respectively. Concentrations of all cytokines decreased significantly after two consecutive ranibizumab injections, except for MMP-9, which increased significantly. CONCLUSIONS: After two monthly consecutive antivascular endothelial growth factor injections, inflammatory cytokine levels in the aqueous humour of the eyes with AMD were strongly suppressed, while MMP-9 levels increased.
  • Siamak Yousefi, Ebrahim Yousefi, Hidenori Takahashi, Takahiko Hayashi, Hironobu Tampo, Satoru Inoda, Yusuke Arai, Penny Asbell
    PloS one 13 11 e0205998  2018年 [査読有り][通常論文]
     
    We developed an unsupervised machine learning algorithm and applied it to big corneal parameters to identify and monitor keratoconus stages. A big dataset of corneal swept source optical coherence tomography (OCT) images of 12,242 eyes acquired from SS-1000 CASIA OCT Imaging Systems in multiple centers across Japan was assembled. A total of 3,156 eyes with valid Ectasia Status Index (ESI) between zero and 100% were selected for the downstream analysis. Four hundred and twenty corneal topography, elevation, and pachymetry parameters (excluding ESI Keratoconus indices) were selected. The algorithm included three major steps. 1) Principal component analysis (PCA) was used to linearly reduce the dimensionality of the input data from 420 to eight significant principal components. 2) Manifold learning was used to further reducing the selected principal components nonlinearly to two eigen-parameters. 3) Finally, a density-based clustering was applied to the eigen-parameters to identify eyes with keratoconus. Visualization of clusters in 2-D space was used to validate the quality of learning subjectively and ESI was used to assess the accuracy of the identified clusters objectively. The proposed method identified four clusters; I: a cluster composed of mostly normal eyes (224 eyes with ESI equal to zero, 23 eyes with ESI between five and 29, and nine eyes with ESI greater than 29), II: a cluster composed of mostly healthy eyes and eyes with forme fruste keratoconus (1772 eyes with ESI equal to zero, 698 eyes with ESI between five and 29, and 117 eyes with ESI greater than 29), III: a cluster composed of mostly eyes with mild keratoconus stage (184 eyes with ESI greater than 29, 74 eyes with ESI between five and 29, and 6 eyes with ESI equal to zero), and IV: a cluster composed of eyes with mostly advanced keratoconus stage (80 eyes had ESI greater than 29 and 1 eye had ESI between five and 29). We found that keratoconus status and severity can be well identified using unsupervised machine learning algorithms along with linear and non-linear corneal data transformation. The proposed method can better identify and visualize the keratoconus stages.
  • Hidenori Takahashi, Suguru Nakagawa, Yaqiong Wu, Yukari Kawabata, Atsushi Numabe, Yasuo Yanagi, Yasuhiro Tamaki, Yoshio Uehara, Makoto Araie
    HYPERTENSION RESEARCH 40 11 945 - 945 2017年11月 [査読有り][通常論文]
  • Hidenori Takahashi, Suguru Nakagawa, Yaqiong Wu, Yukari Kawabata, Atsushi Numabe, Yasuo Yanagi, Yasuhiro Tamaki, Yoshio Uehara, Makoto Araie
    HYPERTENSION RESEARCH 40 11 912 - 920 2017年11月 [査読有り][通常論文]
     
    Salt-sensitive hypertension is associated with severe organ damage. Generating oxygen radicals is an integral component of salt-induced kidney damage, and activated leukocytes are important in oxygen radical biosynthesis. We hypothesized that a high-salt diet causes the upregulation of immune-related mechanisms, thereby contributing to the susceptibility of Dahl salt-sensitive rats to hypertensive kidney damage. For verifying the hypothesis, we investigated leukocytes adhering to retinal vessels when Dahl salt-sensitive rats were challenged with a high-salt (8% NaCl) diet using acridine orange fluoroscopy and a scanning laser ophthalmoscope. The high-salt diet increased leukocyte adhesion after 3 days and was associated with a significant increase in mRNA biosynthesis of monocyte chemotactic protein-1 and intercellular adhesion molecule-1 (ICAM-1) -related molecules in the kidney. Losartan treatment did not affect increased leukocyte adhesion during the early, pre-hypertensive phase of high salt loading; however, losartan attenuated the adhesion of leukocytes during the hypertensive stage. Moreover, the inhibition of leukocyte adhesion in the pre-hypertensive stage by anti-CD18 antibodies decreased tethering of leukocytes and was associated with the attenuation of functional and morphological kidney damage without affecting blood pressure elevation. In conclusion, a high-salt challenge rapidly increased leukocyte adhesion through the over-expression of ICAM-1. Increased leukocyte adhesion in the pre-hypertensive stage is responsible for subsequent kidney damage in Dahl salt-sensitive rats. Immune system involvement may be a key component that initiates kidney damage in a genetic model of salt-induced hypertension.
  • 深層学習によるカラー眼底写真からの脈絡膜厚推測
    反保 宏信, 高橋 秀徳, 添田 めぐみ, 高橋 良太, 伊野田 悟, 坂本 晋一, 新井 悠介, 井上 裕治, 川島 秀俊, 柳 靖雄
    眼科臨床紀要 10 10 873 - 873 眼科臨床紀要会 2017年10月
  • Kenji Yamashiro, Keisuke Mori, Shigeru Honda, Mariko Kano, Yasuo Yanagi, Akira Obana, Yoichi Sakurada, Taku Sato, Yoshimi Nagai, Taiichi Hikichi, Yasushi Kataoka, Chikako Hara, Yasurou Koyama, Hideki Koizumi, Munemitsu Yoshikawa, Masahiro Miyake, Isao Nakata, Takashi Tsuchihashi, Kuniko Horie-Inoue, Wataru Matsumiya, Masashi Ogasawara, Ryo Obata, Seigo Yoneyama, Hidetaka Matsumoto, Masayuki Ohnaka, Hirokuni Kitamei, Kaori Sayanagi, Sotaro Ooto, Hiroshi Tamura, Akio Oishi, Sho Kabasawa, Kazuhiro Ueyama, Akiko Miki, Naoshi Kondo, Hiroaki Bessho, Masaaki Saito, Hidenori Takahashi, Xue Tan, Keiko Azuma, Wataru Kikushima, Ryo Mukai, Akihiro Ohira, Fumi Gomi, Kazunori Miyata, Kanji Takahashi, Shoji Kishi, Hiroyuki Iijima, Tetsuju Sekiryu, Tomohiro Iida, Takuya Awata, Satoshi Inoue, Ryo Yamada, Fumihiko Matsuda, Akitaka Tsujikawa, Akira Negi, Shin Yoneya, Takeshi Iwata, Nagahisa Yoshimura
    SCIENTIFIC REPORTS 7 1 9196  2017年08月 [査読有り][通常論文]
     
    We conducted a genome-wide association study (GWAS) on the outcome of anti-VEGF treatment for exudative age-related macular degeneration (AMD) in a prospective cohort. Four hundred and sixtyone treatment-naive AMD patients were recruited at 13 clinical centers and all patients were treated with 3 monthly injections of ranibizumab followed by pro re nata regimen treatment for one year. Genomic DNA was collected from all patients for a 2-stage GWAS on achieving dry macula after the initial treatment, the requirement for an additional treatment, and visual acuity changes during the 12-month observation period. In addition, we evaluated 9 single-nucleotide polymorphisms (SNPs) in 8 previously reported AMD-related genes for their associations with treatment outcome. The discovery stage with 256 patients evaluated 8,480,849 SNPs, but no SNPs showed genome-wide level significance in association with treatment outcomes. Although SNPs with P-values of < 5 x 10(-6) were evaluated in replication samples of 205 patients, no SNP was significantly associated with treatment outcomes. Among AMD-susceptibility genes, rs10490924 in ARMS2/HTRA1 was significantly associated with additional treatment requirement in the discovery stage (P = 0.0023), and pooled analysis with the replication stage further confirmed this association (P = 0.0013). ARMS2/HTRA1 polymorphism might be able to predict the frequency of injection after initial ranibizumab treatment.
  • Hidenori Takahashi, Hironobu Tampo, Yusuke Arai, Yuji Inoue, Hidetoshi Kawashima
    PLOS ONE 12 6 2017年06月 [査読有り][通常論文]
     
    Purpose Disease staging involves the assessment of disease severity or progression and is used for treatment selection. In diabetic retinopathy, disease staging using a wide area is more desirable than that using a limited area. We investigated if deep learning artificial intelligence (AI) could be used to grade diabetic retinopathy and determine treatment and prognosis. Methods The retrospective study analyzed 9,939 posterior pole photographs of 2,740 patients with diabetes. Nonmydriatic 45 degrees field color fundus photographs were taken of four fields in each eye annually at Jichi Medical University between May 2011 and June 2015. A modified fully randomly initialized GoogLeNet deep learning neural network was trained on 95% of the photographs using manual modified Davis grading of three additional adjacent photographs. We graded 4,709 of the 9,939 posterior pole fundus photographs using real prognoses. In addition, 95% of the photographs were learned by the modified GoogLeNet. Main outcome measures were prevalence and bias-adjusted Fleiss' kappa (PABAK) of AI staging of the remaining 5% of the photographs. Results The PABAK to modified Davis grading was 0.64 (accuracy, 81%; correct answer in 402 of 496 photographs). The PABAK to real prognosis grading was 0.37 (accuracy, 96%). Conclusions We propose a novel AI disease-staging system for grading diabetic retinopathy that involves a retinal area not typically visualized on fundoscopy and another AI that directly suggests treatments and determines prognoses.
  • Yukiko Tsubota, Hidenori Takahashi, Kenji Sugisaki, Tatsuro Tanabe, Yujiro Fujino
    Case Reports in Ophthalmology 8 1 49 - 54 2017年01月 [査読有り][通常論文]
     
    Purpose: We present an atypical case of submacular fluid leading to serous macular detachment. Method/Patient: A 69-year-old man was evaluated for metamorphopsia in the left eye. Results: Best-corrected visual acuity was 20/25 in both eyes. He had undergone cataract surgeries in both eyes 12 years ago. The axial length was 25.93 mm (OD) and 24.12 mm (OS). Optical coherence tomography showed posterior staphylomas and subretinal fluid on the superior border of the staphylomas in both eyes in the left eye, submacular fluid was noted extending up to the macula. Fundus fluorescein angiography revealed leakage from the superior border of the staphylomas in both eyes. The fluid persisted for 4 months. Four consecutive, monthly injections of bevacizumab (1.25 mg/0.05 mL) were administered in the left eye subsequently, the subretinal fluid gradually dissipated from the macula and became localized at the superior border of the staphyloma. This localization persisted for 12 months. Conclusions: We have detailed a case of submacular fluid that spread from the superior border of the posterior staphyloma in a patient with macular detachment, in whom intravitreal injections of bevacizumab were highly effective in eliminating the fluid.
  • Kimiko Shimizu, Yohei Hashimoto, Keiko Azuma, Yoko Nomura, Ryo Obata, Hidenori Takahashi, Yasuo Yanagi
    Clinical ophthalmology (Auckland, N.Z.) 11 1505 - 1512 2017年 [査読有り][通常論文]
     
    PURPOSE: To evaluate the morphological changes in retinal microstructures following modified photodynamic therapy (PDT) for chronic central serous chorioretinopathy. SUBJECTS AND METHODS: Retrospective study of 21 consecutive eyes (age, 59±8.0 years [mean ± SD]) of 21 patients with chronic central serous chorioretinopathy. Inner foveal thickness (the distance between the internal limiting membrane and external limiting membrane), photoreceptor outer segment (PROS) length at the point without serous retinal detachment and choroidal thickness were assessed with enhanced depth imaging optical coherence tomography before treatment and at 1, 3 and 6 months after modified PDT. RESULTS: Six eyes had half-dose and 15 eyes had half-fluence PDT. PROS length within the irradiated area was significantly decreased by 3.9% at 1 month compared with that before modified PDT (43.5±5.72 and 40.5±7.53, P=0.020 [paired t-test]) and returned to baseline length at 3 and 6 months (43.0±5.42 and 43.5±4.33 μm [mean ± SD]; P=0.53 and 1.00 [paired t-test]). PROS length of the nonirradiated area at 1, 3 and 6 months after modified PDT did not significantly differ from that before PDT (41.8±6.35, 41.4±5.33, 41.9±4.67 and 42.3±4.26 μm [mean ± SD]; P=0.66, 0.90 and 0.60, respectively [paired t-test]). There was no significant change in inner foveal thickness during the observation period. At all time points, choroidal thickness was significantly thinner than it was before PDT (P<0.001, paired t-test). CONCLUSION: Modified PDT may cause mild temporary microstructural changes.
  • Keiko Azuma, Ryo Obata, Yoko Nomura, Xue Tan, Hidenori Takahashi, Yasuo Yanagi
    RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES 36 11 2158 - 2165 2016年11月 [査読有り][通常論文]
     
    Purpose: The aim of this study was to study the angiopathic findings of ranibizumabresistant polypoidal choroidal vasculopathy after switching to a treat-and-extend regimen with intravitreal aflibercept. Methods: The authors retrospectively reviewed 17 eyes of 17 Japanese patients with polypoidal choroidal vasculopathy (10 men and 7 women, age: 73.8 +/- 7.4 years) who were treated with intravitreal aflibercept (2 mg/0.05 mL) injections from February 2013 to August 2014 at Tokyo University Hospital. All patients had switched to aflibercept because their polypoidal choroidal vasculopathy had been refractory to ranibizumab. Results: The mean logMAR best-corrected visual acuity at baseline and after 12 months of therapy was 0.30 +/- 0.29 (Snellen equivalent: 20/40) and 0.17 +/- 0.26 (20/30) (paired t-test P, 0.001). Visual acuity remained stable in 5 cases (29%), deteriorated in 3 (18%), and improved in 9 (53%). Branching vascular networks persisted in all 17 eyes but shrank in 15 (88%). The mean lesion diameter was 3329 +/- 1261 mm at baseline and 3180 +/- 1247 mm after 12 months (P = 0.0002). Conclusion: A treat-and-extend regimen with intravitreal aflibercept for ranibizumabresistant patients resulted in branching vascular network shrinkage over a 1-year period.
  • 添田めぐみ, 新井悠介, 髙橋秀徳, 藤野雄次郎, 田邊樹郎, 井上裕治, 川島秀俊
    Retinal Cases and Brief Reports 2016年10月 [査読有り][通常論文]
  • Yaqiong Wu, Suguru Nakagawa, Hidenori Takahashi, Yukari Kawabata, Etsu Suzuki, Yoshio Uehara
    HYPERTENSION RESEARCH 39 5 295 - 301 2016年05月 [査読有り][通常論文]
     
    Angiotensin II (Ang II) reportedly enhances regulator of G-protein signaling 2 (RGS2), thus making a negative feedback loop for Ang II signal transduction. However, few studies have reported whether Ang II receptor (ATR) antagonists influence RGS2 mRNA expression. We investigated RGS2 mRNA expression when Ang II binding to ATR was blocked with Ang II subtype-1 receptor (AT(1)R) blockers using vascular smooth muscle cells from the thoracic aorta of male Wistar rats. RGS2 mRNA expression significantly increased with Ang II stimulation, and this increase was almost completely abolished by olmesartan, a potent AT(1)R-specific blocker. Ang II subtype-2 receptor (AT(2)R) was not involved in Ang II-mediated RGS expression. In contrast, the AT(1)R blocker, losartan, partially decreased Ang II-mediated RGS2 mRNA expression because this antagonist directly stimulated RGS2 mRNA expression in Ang II-free medium. EXP3174, which is an active metabolite of losartan, almost completely blunted Ang II-mediated RGS2 mRNA expression without direct stimulation of RGS2 mRNA expression. Moreover, pretreatment with olmesartan abolished Ang II-mediated RGS2 mRNA expression. Treatment with a protein kinase C inhibitor partially decreased losartan-mediated RGS2 mRNA expression. These results suggest that AT(1)R blockers inhibit RGS2 mRNA expression in response to Ang II via an AT(1)R-mediated mechanism. However, the AT(1)R blocker, losartan, behaves as a direct agonist for RGS2 mRNA expression via AT(1)R through protein kinase C-dependent and -independent pathways. In conclusion, losartan exhibits dual effects on RGS2 mRNA expression, and the direct upregulation of RGS2 mRNA expression may provide a new strategy for the treatment of hypertension.
  • Wu Y, Takahashi H, Suzuki E, Kruzliak P, Soucek M, Uehara Y
    Hypertens Res. 39 4 210 - 216 2016年04月 [査読有り][通常論文]
     
    Dahl salt-sensitive (Dahl S) rats are prone to salt-dependent hypertension with severe organ damage, including stroke, cardiac failure and renal insufficiency. The mechanism for this susceptibility to kidney injury has not been elucidated. The present study proposed that an upregulation of intracellular signaling of angiotensin II (Ang-II) is responsible for the susceptibility to hypertensive kidney injury in Dahl S rats. Spontaneously hypertensive rats exhibited higher systolic blood pressure (SBP) and lower kidney damage than Dahl S rats fed a high-salt diet for 2 weeks. Ang-II infusion for 4 weeks significantly increased SBP in Dahl S and Dahl salt-resistant (Dahl R) rats fed a low-salt diet. The increase in SBP in Dahl S rats was associated with significant kidney injury with greater glomerular sclerosis (P < 0.001). The expression of regulatory protein of G alpha q signaling-2 (RGS2) mRNA in the aortic walls in response to Ang-II infusion was lower in Dahl S than Dahl R rats (P < 0.05). Ang-II significantly increased RGS2 mRNA in the aorta in Dahl R rats, but the response was apparently blunted in Dahl S rats. These results suggest that Dahl S rats exhibit a blunted RGS2 response to Ang-II, and this blunted response may be partially responsible for the susceptibility to renal injury in Dahl S rats.
  • 加齢黄斑変性に対するラニビズマブとアフリベルセプト短期予後の差と中心網膜厚の関連
    坂本 晋一, 高橋 秀徳, 井上 裕治, 柳 靖雄, 佐藤 彩, 竹澤 美貴子, 田邊 樹郎, 藤野 雄次郎, 川島 秀俊
    日本眼科学会雑誌 120 臨増 276 - 276 (公財)日本眼科学会 2016年03月
  • Hidenori Takahashi, Yoko Nomura, Junko Nishida, Yujiro Fujino, Yasuo Yanagi, Hidetoshi Kawashima
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 57 2 462 - 466 2016年02月 [査読有り][通常論文]
     
    PURPOSE. Commercially available enzyme-linked immunosorbent assay (ELISA) kits are often used to monitor vascular endothelial growth factor (VEGF) levels in exudative age-related macular degeneration. To test their accuracy, this study performed measurements using the ELISA kits in the presence of anti-VEGF drugs. METHODS. The concentrations of bevacizumab, pegaptanib, or ranibizumab at 28 days and aflibercept at 28 and 56 days after an injection were estimated based on previous pharmacokinetic studies. Vascular endothelial growth factor concentrations were measured with two widely used VEGF ELISA kits in the presence of anti-VEGF drugs or control mouse immunoglobulin G (IgG). The monocyte chemotactic protein-1 (MCP-1) ELISA kit was used as a non-VEGF ELISA control kit. RESULTS. The concentrations of aflibercept, bevacizumab, pegaptanib, and ranibizumab were estimated at 0.14 to 7.2, 4.9, 8.6, and 0.11 to 1.1 mu g/mL, respectively. ELISA underestimated the VEGF concentration 2- to 100-fold lower in the presence of an anti-VEGF drug, except for pegaptanib, at all VEGF concentrations tested (7.8-1500 pg/mL). Vascular endothelial growth factor at 1000 pg/mL was measured as 92, 150, and 170 pg/mL in the presence of aflibercept (7.2 mu g/mL), bevacizumab (4.9 mu g/mL), and ranibizumab (1.1 mu g/mL), respectively (all P < 0.0001), and the measured VEGF concentration decreased proportionately by 90% to 92% with aflibercept, 85% to 94% with bevacizumab, and 83% to 99% with ranibizumab. The control mouse IgG did not interfere with the measurement of VEGF. Ranibizumab did not affect the measurements with MCP-1 ELISA. CONCLUSIONS. Investigators should exercise caution when interpreting measurements of VEGF ELISA in patients being treated with an anti-VEGF drug.
  • 反保 宏信, 大河原 百合子, 高橋 秀徳, 牧野 伸二, 佐藤 幸裕
    あたらしい眼科 33 1 119 - 123 (株)メディカル葵出版 2016年01月 
    目的:散瞳下での2方向と4方向カラー眼底撮影を、9方向蛍光眼底造影(FA)を含めて比較し、2方向の病期診断における有用性を検討した。方法:散瞳下に画角50°のデジタルカメラで、1眼につき2、4方向カラー撮影と9方向FAを行った167例287眼を後ろ向きに調査した。2、4方向カラー撮影、FAの順に判定し、網膜症なし、単純、前増殖、増殖網膜症に病期分類して比較した。結果:2方向と4方向カラー撮影の病期診断一致率は97%であった。また、2方向とFAの一致は84%、4方向とFAの一致は87%であり、有意差はなかった。FAでの病期診断との一致率を2方向、4方向で見ると、単純網膜症で95%、97%、前増殖網膜症で87%、88%、増殖網膜症で61%、72%であり、2方向と4方向で差がないものの、病期が進行するに伴い低率となった。結論:2方向と4方向の病期診断はほぼ一致しており、2方向で十分と考えられるが、前増殖網膜症や増殖網膜症の診断には限界があることに留意する必要がある。(著者抄録)
  • Yoko Nomura, Hidenori Takahashi, Yujiro Fujino, Hidetoshi Kawashima, Yasuo Yanagi
    RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES 36 1 192 - 198 2016年01月 [査読有り][通常論文]
     
    Purpose:To investigate the association of subfoveal choroidal thickness with intraocular inflammatory cytokines and chemokines.Methods:The subjects consisted of 76 eyes of consecutive cataract patients at the Japan Community Health Care Organization Tokyo Shinjuku Medical Center between September 2010 and August 2012. In addition, two autopsy eyes from elderly males were used for immunohistochemical study. Subfoveal choroidal thickness was measured using spectral domain optical coherence tomography before cataract surgery. At the beginning of cataract surgery, a sample of undiluted aqueous humor was manually aspirated and the concentrations of the following cytokines were determined using a multiplex cytokine assay: IP-10, MCP-1, MMP-9, IL-6, IL-10, CXCL1, CXCL12, CXCL13, and CCL11. The association of subfoveal choroidal thickness with intraocular cytokine concentration was analyzed. Expression of CXCL13 was examined in autopsy eyes.Results:Among these factors, higher concentration of CXCL13 was associated with thicker choroid. In particular, multiple regression analysis showed that the concentration of CXCL13 was associated with subfoveal choroidal thickness (P = 0.001), independently of axial length (P = 0.049). By immunostaining, CXCL13 was clearly detected in choroidal endothelial cells.Conclusion:Aqueous humor concentration of CXCL13 is correlated with subfoveal choroidal thickness in normal subjects.
  • Yoko Nomura, Hidenori Takahashi, Xue Tan, Yujiro Fujino, Hidetoshi Kawashima, Yasuo Yanagi
    GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY 254 1 53 - 57 2016年01月 [査読有り][通常論文]
     
    Background To investigate the association of posterior vitreous detachment (PVD) with aqueous levels of vascular endothelial growth factor (VEGF) in eyes with exudative age-related macular degeneration (AMD). Methods This is a prospective comparative study. Subjects are 33 eyes with exudative AMD. PVD was examined by B-mode ultrasonography and the subjects were divided into a complete PVD group (PVD group) or a group with partial or no PVD (without PVD group). At the beginning of intravitreal injection of ranibizumab, aqueous humor was collected and the concentration of VEGF was measured using ELISA. The concentration was compared between the two groups. Results Complete PVD was observed in 13 (39 %) eyes. The mean concentration of VEGF was 58 pg/ml in the PVD group and 91 pg/ml in the without PVD group. Multiple regression analysis revealed that the concentration of VEGF was significantly lower in the eyes with PVD than in those without PVD independent of age and sex (P=0.02). Conclusions Complete PVD is related to the lower concentration of aqueous VEDF in AMD eyes.
  • 野村 陽子, 高橋 秀徳, 小畑 亮
    眼科 57 13 1689 - 1692 金原出版(株) 2015年12月
  • Two Cases of Rapid Thinning of the Choroid Prior to Appearance of Polypoid Lesions
    Sakamoto S, Arai Y, Takahashi H, Fujino Y, Obata R, Yanagi Y, Kawashima H
    JSM Ophthalmology 3 1033  2015年10月 [査読有り][通常論文]
  • Hidenori Takahashi, Yoko Nomura, Xue Tan, Yujiro Fujino, Hidetoshi Kawashima, Yasuo Yanagi
    BRITISH JOURNAL OF OPHTHALMOLOGY 99 8 1065 - 1069 2015年08月 [査読有り][通常論文]
     
    Purpose To investigate the association of posterior vitreous detachment (PVD) with aqueous levels of vascular endothelial growth factor (VEGF) and other inflammatory cytokines. Methods These are prospective comparative studies. Subjects comprised 98 eyes for VEGF concentration and 80 eyes for other cytokines, which are normal except for cataract. PVD was examined by B-mode ultrasonography, and the subjects were divided into complete PVD group (PVD group) or the other group (without PVD group). At the beginning of cataract surgery, aqueous humour was collected and the concentrations of VEGF and other inflammatory cytokines were determined using ELISA and a multiplex cytokine assay, respectively. The concentrations of these cytokines were compared between the two groups. Results Complete PVD was observed in 56 (57%) eyes for VEGF concentration analysis, and 51 (64%) eyes for the other cytokines analysis. The concentrations of VEGF, adjusted for the average age, axial length and gender distribution, was 47 pg/ mL in the PVD group and 72 pg/mL in the without PVD group. The concentrations of IP10, MCP-1, CXCL13 and CCL11 were 53, 450, 3.8 and 6.0 pg/ mL in the PVD group, and 100, 560, 7.0 and 8.4 pg/ mL in the without PVD group, respectively. Multiple regression analysis revealed that the logarithmic concentration of VEGF, IP-10, MCP-1, CXCL13 and CCL11 were significantly lower in the eyes with PVD than in those without PVD independently of age, sex and axial length (p = 0.01, p = 0.002, p = 0.009, 0.006 and 0.03, respectively). Conclusions PVD is related to the change in the multiple intraocular inflammatory cytokines.
  • 柳 靖雄, 譚 雪, 野村 陽子, Saadat Kahndakar A.S.M., 村上 祐介, 池田 康宏, 安川 力, 高橋 秀徳, 川島 英俊, 岡田 栄一, 藤野 雄二郎
    日本眼科学会雑誌 119 3 195 - 215 (公財)日本眼科学会 2015年03月 
    本総説では加齢黄斑変性について,我々が行ってきた研究の結果から新たになった知見について述べる.まずは加齢黄斑変性における脈絡膜異常の重要性について検討したところ,ポリープ状脈絡膜血管症では典型加齢黄斑変性と比較すると脈絡膜血管透過性亢進所見を高頻度で認めたが,典型加齢黄斑変性でもポリープ状脈絡膜血管症よりも頻度は少ないものの脈絡膜血管透過性亢進所見を一定の割合に認めた.脈絡膜血管透過性亢進所見を有する加齢黄斑変性症例は広い領域で脈絡膜厚の増加を認め,眼底自発蛍光検査でも高頻度に異常を認めることが分かった.このように,加齢黄斑変性は脈絡膜血管透過性亢進所見を有する加齢黄斑変性と有さない加齢黄斑変性に大別して捉えることで説明される所見も存在する.さらに,加齢黄斑変性の予後因子としての網膜硝子体癒着の重要性について検討した.従来は加齢黄斑変性においては後部硝子体剥離により血管内皮増殖因子(vascular endothelial growth factor:VEGF)濃度が低下することが抗VEGF療法の良好な成績につながると考えられて受け入れられつつあったが,今回の検討により後部硝子体剥離は血管新生促進因子であるVEGF以外にも血管新生抑制因子であるinterferon-inducible protein 10(IP-10)の発現などにも影響を及ぼすことが判明した.したがって後部硝子体剥離の関与はこれまでに考えられてきたほど単純ではなく,眼内環境に及ぼす影響は大きく,これまでに想定されていない分子の変化も伴う可能性があり,多様な影響を及ぼすものと結論づけられる.また,最後のパートでは前駆病変の進行メカニズムの基礎的な側面について説明した.我々の行った検討により,加齢によるオートファジー活性の低下が加齢黄斑変性の前駆病変の原因になっている可能性が示唆された.(著者抄録)
  • 滲出型加齢黄斑変性に対する抗血管内皮増殖因子療法中の過度な網膜菲薄化と視力低下
    高橋 秀徳, 坂本 晋一, 垣沼 奈津子, 富永 聡子, 佐藤 彩, 竹澤 美貴子, 斎藤 由香, 斎藤 信一郎, 新井 悠介, 藤野 雄次郎, 川島 秀俊, 柳 靖雄
    日本眼科学会雑誌 119 臨増 241 - 241 (公財)日本眼科学会 2015年03月
  • 反保 宏信, 大河原 百合子, 高橋 秀徳, 牧野 伸二, 佐藤 幸裕
    あたらしい眼科 32 2 274 - 278 (株)メディカル葵出版 2015年02月 
    目的:無散瞳デジタル眼底カメラを用いた糖尿病症例の眼底スクリーニングの有用性と限界を検討した。方法:画角45°のカメラで、1眼につき1、2、4方向のカラー撮影を行った糖尿病症例492例894眼を後ろ向きに調査した。1、2、4方向の順に、網膜症なし、単純、前増殖、増殖網膜症に病期診断して比較した。結果:病期診断の一致率は、1と2方向93.1%、2と4方向98.7%、1と4方向91.7%で、2と4方向の一致率が有意に高率であった。不一致例を具体的に検討すると、4方向での単純網膜症を網膜症なし、前増殖網膜症を単純網膜症としたものが、2方向に比較し1方向で有意に高率であった。結論:1方向は2方向に比較して網膜症の見逃しや、より軽症に判定する比率が有意に高く、病期診断には適さないと考えた。一方、2方向は4方向と非常に高い一致率を示し有用だが、非常に低頻度ながら見逃しや、軽症に判定する可能性がある。(著者抄録)
  • Xue Tan, Hidenori Takahashi, Junko Nishida, Aya Aoki, Tatsuya Inoue, Yasuo Yanagi
    EXPERIMENTAL EYE RESEARCH 131 77 - 83 2015年02月 [査読有り][通常論文]
     
    As a part of the visual cycle, all-trans-retinol (all-trans-ROL), the major form of vitamin A in circulating blood, is transported to the retinal pigment epithelium (RPE). All-trans-ROL is essential for normal retina function. However, recent researches have shown that excessive retinol intake can cause increase of all-trans-retinal. This can lead to the accumulation of lipofuscin, which is important in the pathogenesis of retina degeneration disease, such as dry type age-related macular degeneration (AMD). Since there are few reports regarding the involvement of all-trans-ROL in exudative AMD, we investigated the effects of all-trans-ROL in vitro and in vivo. We evaluated vascular endothelial growth factor (VEGF) expression in ARPE-19 cells and THP-1 cells after all-trans-ROL treatment using ELISA and real-time RT-PCR. In-vitro tube formation assay was performed with HUVEC cells using the conditioned medium (CM) obtained from ARPE-19 cells treated with all-trans-ROL. Transcriptional activity of retinoic acid receptor (RAR) was evaluated using luciferase assay. In mice, VEGF expressions were investigated in the retina and RPE/choroid after three weeks of excessive oral retinol intake. Laser-induced choroidal neovascularization (CNV) models were evaluated after they were fed with various doses of retinol. VEGF mRNA expression and VEGF production were significantly increased in all-trans-ROL treated ARPE-19 cells, which were inhibited by an RAR antagonist LE540. In contrast, there were no significant changes in VEGF production in THP-1 cells. Transcriptional activity of RAR was upregulated by all-trans-ROL treatment in ARPE-19 cells. The CM, obtained from ARPE-19 cells treated with all-trans-ROL, induced more capillary-like tube formation than cells treated with control vehicles. In vivo, the high retinal diet group has increased VEGF expression in the RPE/choroid and larger lesion size was induced. Our results suggest that all-trans-ROL is a pro-angiogenic factor. Excessive retinoid intake may be a potential risk factor for exudative AMD. (C) 2015 Elsevier Ltd. All rights reserved.
  • Hidenori Takahashi, Yuko Ohkubo, Aya Sato, Mikiko Takezawa, Yujiro Fujino, Yasuo Yanagi, Hidetoshi Kawashima
    Retina 35 7 1331 - 1338 2015年 [査読有り][通常論文]
     
    Background: In age-related macular degeneration, various factors in clinical practice cause delays to arise between the time exudative change is observed and the time antivascular endothelial growth factor drugs are actually injected. We investigated the influence of injection delay on prognosis. Methods: Subjects were 50 eyes (50 patients from 2 hospitals) that were administered ranibizumab monotherapy for age-related macular degeneration for 1 year since exudative change was first observed. We investigated the mean number of delay days for each injection. Results: Mean injection delay was between 0 and 104 days. Significant prognostic factors for visual acuity were initial best-corrected visual acuity (P , 0.01) and mean injection delay (P = 0.03). We estimated that for an initial best-corrected visual acuity of 0.40 logMAR unit (20/50 Snellen equivalent), the respective best-corrected visual acuity values after 1 year for mean injection delays of 0, 7, 14, 28, and 56 days would be 0.22 (20/33), 0.24 (20/35), 0.26 (20/37), 0.31 (20/40), and 0.39 (20/49). For an initial best-corrected visual acuity of 0.097 (20/25), the respective values would be 0.054 (20/23), 0.075 (20/24), 0.10 (20/25), 0.14 (20/28), and 0.22 (20/33). Conclusion: Long-term visual acuity prognosis worsened when scheduling problems delayed intravitreal injection of anti-vascular endothelial growth factor drugs.
  • Yoko Nomura, Hidenori Takahashi, Xue Tan, Ryo Obata, Yasuo Yanagi
    Clinical ophthalmology (Auckland, N.Z.) 9 9 297 - 304 2015年 [査読有り][通常論文]
     
    PURPOSE: To investigate the clinical findings that characterize exudative age-related macular degeneration (AMD) with choroidal vascular hyperpermeability (CVH). DESIGN: Retrospective comparative study. PARTICIPANTS: Forty-eight consecutive patients attending the outpatient clinic of Tokyo University Hospital between May 2013 and July 2013. METHODS: The presence or absence of CVH was determined with indocyanine green angiography performed at the latest visit. When CVH was observed, the eye was categorized as CVH(+) AMD, otherwise it was categorized as CVH(-) AMD. Using high-penetration optical coherence tomography, we measured choroidal thickness at the fovea and at four midperipheral areas (mean choroidal thickness at points on 6- and 9-papilla diameter circles superior, inferior, temporal, and nasal to the fovea). Ultrawide field retinal imaging was used to investigate abnormalities in midperipheral fundus autofluorescence (FAF). Choroidal thickness and the proportion of FAF abnormalities were compared between the CVH(+) AMD and CVH(-) AMD eyes and between eyes with polypoidal choroidal vasculopathy and typical AMD. Multiple regression analysis was used to control for treatment history and other characteristics. RESULTS: CVH was observed in 17 cases. Choroidal thickness was higher in the CVH(+) AMD eyes than in the CVH(-) AMD eyes at the fovea (325 μm versus 229 μm, respectively; P=0.0010, t-test), superior point (277 μm versus 215 μm, respectively; P=0.0021, t-test), inferior point (225 μm versus 161 μm, respectively; P=0.0002, t-test), and nasal point (202 μm versus 165 μm, respectively; P=0.042, t-test). The significance was maintained after controlling for possible confounders. The choroid was thicker at the fovea and at the inferior point in polypoidal choroidal vasculopathy than in typical AMD. The rate of midperipheral FAF abnormality was significantly higher in the CVH(+) AMD eyes than in the CVH(-) AMD eyes (82% versus 48%, respectively; P=0.031). CONCLUSION: AMD with CVH is associated with widespread choroidal thickening and peripheral FAF abnormalities.
  • Yoko Nomura, Hidenori Takahashi, Xue Tan, Shigeto Fujimura, Ryo Obata, Yasuo Yanagi
    JAPANESE JOURNAL OF OPHTHALMOLOGY 58 5 443 - 447 2014年09月 [査読有り][通常論文]
     
    Purpose To investigate the effects of vitreomacular adhesion (VMA) on intravitreal ranibizumab treatment in Japanese patients with exudative age-related macular degeneration (AMD). Methods This was a retrospective comparative study that included 123 eyes from 123 patients with exudative AMD. The presence or absence of VMA was examined by spectral domain optical coherence tomography. The association of VMA with best-corrected visual acuity (BCVA) and central retinal thickness (CRT) at 3, 6, and 12 months after ranibizumab treatment was evaluated. Results In the group of eyes without VMA [VMA(-)], the mean BCVA was 0.41 logMAR at baseline and significantly improved to 0.28, 0.30, and 0.29 logMAR at 3, 6, and 12 months following the initiation of treatment (P<0.0001,<0.0001,<0.0001), respectively. In the group of eyes with VMA [VMA(+)], the mean BCVA was 0.42 logMAR at baseline, and there was no improvement at any of the measurement time-points during the follow-up period [0.39, 0.40, and 0.39 logMAR at 3, 6, and 12 months (P = 0.53, 0.75, 0.67), respectively]. The mean baseline CRT in the VMA(-) and VMA(+) groups was 326 and 370 mu m, respectively, decreasing to 195 and 293 mu m (P<0.0001 and P = 0.0070), respectively, at 12 months. A better baseline BCVA was associated with poor visual response to intravitreal ranibizumab. Conclusions Our study of Japanese patients with AMD managed in real-world clinical practice revealed that both VMA and BCVA at baseline were associated with a poor visual response to intravitreal ranibizumab. These results are in agreement with previously reported findings for other ethnic groups.
  • Hidenori Takahashi, Takaaki Hayashi, Hiroshi Tsuneoka, Tadashi Nakano, Hisashi Yamada, Satoshi Katagiri, Yujiro Fujino, Yasuo Noda, Miwako Yoshimoto, Hidetoshi Kawashima
    DOCUMENTA OPHTHALMOLOGICA 129 1 49 - 56 2014年08月 [査読有り][通常論文]
     
    The purpose of this study was to present an atypical case of occult macular dystrophy (OMD) with bilateral chronic subfoveal serous retinal detachment (SRD). A 53-year-old man was ophthalmologically evaluated because of decreased visual acuity in both eyes. Genomic DNA was extracted from venous blood samples. Mutational analysis of the retinitis pigmentosa 1-like 1 (RP1L1) gene was performed by Sanger sequencing. Best-corrected visual acuity (BCVA) was 0.1 logMAR in both eyes until the age of 53, after which it gradually declined. Full-field electroretinography (ERG) was unremarkable, while multifocal ERG revealed a reduced central response in both eyes. Optical coherence tomography showed subfoveal SRD in both eyes, and fundus fluorescein angiography yielded unremarkable results. His brother and cousin had similar subjective symptoms. At age 58, his logMAR BCVA was 0.532 (OD) and 0.347 (OS). He was given 23 administrations of intravitreal bevacizumab (IVB; 1.25 mg) in both eyes alternately over a 2-year period and also underwent reduced-fluence photodynamic therapy in both eyes. Two years after the first administration of IVB, a reduction in SRD was obtained, and IVB was therefore discontinued. Three years after the first administration, logMAR BCVA was 0.155 (OD) and 0.523 (OS). Mutational analysis revealed a novel heterozygous missense mutation (p.S1199P). We describe in detail a case of bilateral chronic subfoveal SRD in an atypical OMD patient carrying a novel heterozygous RP1L1 mutation (p.S1199P). Our results further extend the phenotypic spectrum of RP1L1-associated OMD.
  • 糖尿病患者の眼底スクリーニング 散瞳4方向と9方向カラー撮影の比較
    反保 宏信, 大河原 百合子, 高橋 秀徳, 牧野 伸二, 佐藤 幸裕
    日本糖尿病眼学会誌 18 63 - 67 日本糖尿病眼学会 2014年03月 
    糖尿病網膜症62例102眼(男39例、女23例、平均59.4歳)の治療方針について検討するため、散瞳下に画角50°のデジタル眼底カメラで行われた4方向および9方向のカラー眼底撮影と、9方向蛍光眼底造影(FA)の画像を比較した。判定された病期は4方向カラーで単純網膜症33眼、前増殖網膜症57眼、増殖網膜症10眼、網膜症なし(NDR)2眼、9方向カラーではそれぞれ35眼、58眼、9眼、0眼、FAでは28眼、60眼、14眼、0眼で、病期の頻度に有意差はなかった。診断一致率は4方向と9方向カラーが98%、4、9方向カラーとFAが85%であった。FAと4、9方向カラーとの不一致例は、網膜内最小血管異常(IRMA)を判定されなかったのが各7眼、微細な網膜新生血管をIRMAと判定が各6眼などであった。4方向で写らない領域に9方向カラーで何らかの所見を認めたのは網膜出血95眼、硬性白斑17眼、白線化血管4眼などで、網膜出血2眼はNDRと判定されていた。
  • Shigeto Fujimura, Takashi Ueta, Hidenori Takahashi, Ryo Obata, R. Theodore Smith, Yasuo Yanagi
    GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY 251 12 1 - 9 2013年12月 [査読有り][通常論文]
     
    The main purpose of this study is to investigate the characteristics of fundus autofluorescence (FAF) and area of soft drusen among the fellow eyes of unilateral typical age-related macular degeneration (typical AMD) and polypoidal choroidal vasculopathy (PCV) in Japanese patients. FAF images were obtained from the fellow eyes of unilateral typical AMD (n = 64), unilateral PCV (n = 95), unilateral retinal angiomatous proliferation (RAP) (n = 4) and 56 control subjects, then classified into normal, minimal-change, and abnormal patterns by two graders. Interobserver variability between two graders and intraobserver variability were assessed for FAF classifications, and cases with inconsistent decisions were finally classified by the third grader. Soft drusen were segmented and their total areas were compared between the fellow eyes of typical AMD and PCV. Area(s) with increased autofluorescence were segmented to assess the relationship with soft drusen area(s). Assessment for interobserver variability between two graders and intraobserver variability in one grader showed substantial agreement (kappa = 0.70) and almost perfect agreement (kappa = 0.85), respectively. In the final decision mediated by third grader, the proportions of eyes with either minimal-change FAF pattern or abnormal FAF pattern in the fellow eyes of both typical AMD (37 cases, 58 %) and PCV (47 cases, 49 %) were significantly higher than that of the control cases (15 cases, 27 %; p < 0.01). The proportion of abnormal FAF pattern in the fellow eyes of typical AMD (20 cases, 31 %) was higher than that of PCV (15 cases, 16 %; p < 0.05). Total soft drusen areas in the fellow eyes of typical AMD (0.369 +/- 0.718 mm(2)) were larger than those of PCV (0.173 +/- 0.408 mm(2); p < 0.05), and those in the eyes with abnormal FAF pattern were larger than those with minimal-change FAF pattern or normal FAF pattern (p < 0.01). Image analysis revealed a relationship between increased autofluorescence and soft drusen, especially in the cases with large total soft drusen areas. FAF characteristics were different between the fellow eyes of unilateral typical AMD and PCV in Japan, which might be due to the difference of total soft drusen areas between them.
  • 加齢黄斑変性に対するラニビズマブ投与推奨から実際の投与までの遅れと視力予後の関連
    高橋 秀徳, 佐藤 彩, 竹澤 美貴子, 藤野 雄次郎, 柳 靖雄, 川島 秀俊
    眼科臨床紀要 6 10 834 - 835 眼科臨床紀要会 2013年10月
  • Ryo Obata, Hidenori Takahashi, Takashi Ueta, Kentaro Yuda, Kayo Kure, Yasuo Yanagi
    Retina (Philadelphia, Pa.) 33 6 1201 - 10 2013年06月 [査読有り][通常論文]
     
    PURPOSE: To describe detailed clinical features of eyes with focal choroidal excavation. METHODS: Twenty-one eyes of 17 patients with focal choroidal excavation were retrospectively studied. All eyes underwent thorough examination including funduscopy, visual field analysis, fundus autofluorescence imaging, fluorescein angiography, indocyanine green angiography, and B-scan ultrasonography. RESULTS: Patients' age ranged between 25 years and 70 years. Four patients (24%) were affected bilaterally. Spherical equivalent of refractive error ranged from 0.5 diopters to -10.0 diopters (D). Funduscopic examination showed hypopigmentation (n = 12) and yellowish plaquelike appearances (n = 2). Indocyanine green angiography showed not only filling defects at the excavation (n = 16) but also choroidal vascular hyperpermeability (n = 7) and punctate hyperfluorescent spots (n = 7). Cicatrized subretinal neovascularization was seen in three eyes. The mean follow-up period was 37 months (6-66 months). There was no change in the appearance of excavation. Central serous chorioretinopathy (n = 1) and choroidal neovascularization (n = 1) developed during follow-up. CONCLUSION: Background factors and ophthalmic findings are similar to those that have been reported previously, including relatively stable findings even after a long observation and the occurrence of central serous chorioretinopathy and choroidal neovascularization. Bilateral cases are not rare in the current cohort, and choroidal vascular hyperpermeability is frequently observed in indocyanine green angiography, suggesting there were choroidal hemodynamic changes around the excavation.
  • 加齢黄斑変性および正常対象眼における後部硝子体剥離と各種サイトカイン濃度の関連
    高橋 秀徳, 譚 雪, 柳 靖雄, 野村 陽子, 藤野 雄次郎, 川島 秀俊
    日本眼科学会雑誌 117 臨増 330 - 330 (公財)日本眼科学会 2013年03月
  • Kazuhiro Yamamoto, Hidenori Takahashi, Mikiko Kanno, Yasuo Noda, Yujiro Fujino
    Journal of Ophthalmic Inflammation and Infection 3 1 1 - 4 2013年 [査読有り][通常論文]
     
    Background: The time courses of retinal and choroidal thickness changes in dengue fever-associated maculopathy are not known. We measured central macular thickness (CMT), parafoveal retinal thickness (PRT), and subfoveal choroidal thickness (SCT), in one case, employing optical coherence tomography. Findings: The patient was a 43-year-old man diagnosed with dengue fever in Sri Lanka. He became aware of blurred vision bilaterally and visited our department 2 weeks after the onset. He showed reduced visual acuity. The Amsler test revealed a doughnut-shaped relative scotoma. Based on the course of this condition, dengue fever-associated maculopathy was diagnosed. One month later, 20 mg triamcinolone was injected into sub-Tenon space of the left eye. Both eyes showed subsequent improvement. PRT of both eyes increased 1 week after the first visit and decreased thereafter, reaching a plateau 1 month after the first visit. The change in CMT was minimal. SCT changed markedly, with the similar pattern in both eyes, though no particular tendency was noted during the observation period. Conclusions: Dengue fever-associated maculopathy appears to be closely associated with thickening of the inner layer of the retina, but not with changes in choroidal thickness. © 2013 Yamamoto et al.
  • Kentaro Yuda, Hidenori Takahashi, Tatsuya Inoue, Takashi Ueta, Aya Iriyama, Kazuaki Kadonosono, Yasuhiro Tamaki, Hiroyuki Aburatani, Ryozo Nagai, Yasuo Yanagi
    AMERICAN JOURNAL OF PATHOLOGY 181 4 1464 - 1472 2012年10月 [査読有り][通常論文]
     
    The molecular mechanism that leads to age-related macular degeneration (AMD) is poorly understood. Gene expression profiling identified adrenomedullin (ADM) as a possible molecular target for the treatment of AMD and expression of ADM was upregulated in eyes with laser-induced choroidal neovascularization (CNV). In vivo experiments strongly indicated that ADM inhibits laser-induced CNV. In vitro tube formation assay demonstrated that neither ADM nor conditioned medium from the retinal pigment epithelial (RPE) cells, D407 cells, treated with ADM affected the capillary-formation of human umbilical vein endothelial cells. In contrast, in vitro macrophage migration assay clearly demonstrated that the conditioned medium of D407 inhibited macrophage migration. Furthermore, the expression of C-C motif chemokine 2 (CCL2) was significantly inhibited in D407 cells after ADM treatment. In vivo experiments using a laser-induced CNV model in ADM(+/-) mice demonstrated that CCL2 expression was upregulated in ADM(+/-) mice with concomitant increase in macrophage migration in the subretinal space. Additionally, the effect of ADM was abrogated in CCL2 knockout mice. These results suggest that administration of ADM inhibits macrophage migration in the subretinal space and leads to the suppression of laser-induced CNV in an animal model. The inhibition of macrophage migration occurred through the CCL2 from RPE. This study provides a novel potential therapeutic target for AMD which does not substantially disrupt VEGF-A signaling mediated vasculogenesis. (Am J Pathol 2012, 181:14641472 http://dx.dot.org/10.1016/j.ajpath.2012.06.028)
  • Shigeto Fujimura, Hidenori Takahashi, Kentaro Yuda, Takashi Ueta, Aya Iriyama, Tatsuya Inoue, Toshikatsu Kaburaki, Yasuhiro Tamaki, Kouji Matsushima, Yasuo Yanagi
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 53 4 1999 - 2006 2012年04月 [査読有り][通常論文]
     
    PURPOSE. Several recent studies suggest that some chemokines/chemokine receptors are involved in choroidal neovascularization (CNV). CXCR3 was the focus of the present study because microarray analysis for murine laser-induced CNV model showed the increased expression of CXCR3. The purpose of this study was to evaluate the effect of CXCR3 on CNV. METHODS. Microarray analysis was performed for the mouse eyes with laser-induced CNV. CXCR3 expressions on the CNV were evaluated by immunohistochemistry and real-time RT-PCR. CNV was compared between CXCR3-deficient mice and wild-type mice, between mice treated with anti-CXCR3/anti-IP10 neutralizing antibody and mice treated with control IgG. Macrophage recruitment into CNV was also investigated. Ocular expressions of vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), C-C chemokine ligand-2 (CCL2), and complement component-3 (C3) were evaluated by real-time PCR. RESULTS. Microarray analysis and real-time RT-PCR revealed the elevation of CXCR3 and IP-10 in laser-treated mouse eyes compared with control eyes. Immunohistochemistry showed CXCR3 expression on the endothelial cells of CNV. Laser-induced CNV of CXCR3-deficient mice was significantly larger, with greater leakage in fluorescein angiography, and with greater macrophage-infiltration compared with wild-type mice (P < 0.01). Intravitreal injection of anti-CXCR3/anti-IP-10 neutralizing antibody exacerbated CNV. The CCL2 expression in the laser-treated eyes of CXCR3-deficient mice was higher than in those of wild-type mice (P < 0.05), whereas VEGF, PEDF, and C3 showed no differences. CONCLUSIONS. These results suggested that CXCR3 expressed on CNV could have an angiostatic effect on it. (Invest Ophthalmol Vis Sci. 2012;53:1999-2006) DOI:10.1167/iovs.11-8232
  • マウス高酸素負荷網膜血管新生モデルにおけるCXCR3の影響
    湯田 健太郎, 藤村 茂人, 高橋 秀徳, 門之園 一明, 柳 靖雄
    日本眼科学会雑誌 116 臨増 289 - 289 (公財)日本眼科学会 2012年03月
  • 抗VEGF抗体存在下のELISAによるVEGF濃度測定誤差
    高橋 秀徳, 藤野 雄次郎, 柳 靖雄
    日本眼科学会雑誌 116 臨増 344 - 344 (公財)日本眼科学会 2012年03月
  • ポリープ状脈絡膜血管症に対するラニビズマブ治療の1年成績に関連する治療前因子
    小畑 亮, 柳 靖雄, 湯田 健太郎, 上田 高志, 藤村 茂人, 入山 彩, 高橋 秀徳, 本多 麻衣子, 足立 知子, 井上 裕治, 野村 陽子, 井上 達也, 玉置 泰裕
    日本眼科学会雑誌 116 臨増 334 - 334 (公財)日本眼科学会 2012年03月
  • 日本人加齢黄斑変性患者におけるreticular pseudodrusenの頻度
    高橋 秀徳, 藤村 茂人, 湯田 健太郎, 野村 陽子, 呉 香代, 上田 高志, 入山 彩, 本多 麻衣子, 井上 達也, 小畑 亮, 足立 知子, 玉置 泰裕, 柳 靖雄
    眼科臨床紀要 4 10 984 - 984 眼科臨床紀要会 2011年10月
  • 脈絡膜新生血管におけるケモカイン受容体CXCR3の関与
    藤村 茂人, 高橋 秀徳, 湯田 健太郎, 上田 高志, 井上 達也, 柳 靖雄, 蕪城 俊克, 玉置 泰裕, 松島 綱治
    日本眼科学会雑誌 115 臨増 219 - 219 (公財)日本眼科学会 2011年04月
  • 後部硝子体剥離と前房中VEGF濃度の関連
    高橋 秀徳, 柳 靖雄, 小畑 亮, 藤野 雄次郎, 稲用 和也, 野田 康雄, 玉置 泰裕
    日本眼科学会雑誌 115 臨増 271 - 271 (公財)日本眼科学会 2011年04月
  • クラシックCNV所見を有するポリープ状脈絡膜血管症へのラニビズマブの効果
    小畑 亮, 柳 靖雄, 湯田 健太郎, 呉 香代, 上田 高志, 藤村 茂人, 入山 彩, 高橋 秀徳, 本多 麻衣子, 足立 知子, 井上 達也, 玉置 泰裕
    日本眼科学会雑誌 115 臨増 276 - 276 (公財)日本眼科学会 2011年04月
  • 特異な中心窩下隆起病巣により片眼性に視力低下を来したクリスタリン網膜症の2例
    高橋 秀徳, 入山 彩, 井上 祐治, 玉置 泰裕, 柳 靖雄
    眼科臨床紀要 3 10 1019 - 1019 眼科臨床紀要会 2010年10月
  • 食塩感受性高血圧ラットにおける網膜血管の白血球接着の計測による腎障害の予測
    高橋 秀徳, 中川 卓, 呉 雅瓊, 川畑 ゆかり, 沼部 敦司, 柳 靖雄, 玉置 泰裕, 上原 譽志夫, 新家 眞
    日本眼科学会雑誌 114 臨増 254 - 254 (公財)日本眼科学会 2010年03月
  • Adrenomedullinノックアウトマウスにおける炎症細胞浸潤を介した脈絡膜新生血管促進
    湯田 健太郎, 井上 達也, 上田 高志, 高橋 秀徳, 永井 良三, 柳 靖雄, 玉置 泰裕, 新家 眞
    日本眼科学会雑誌 114 臨増 311 - 311 (公財)日本眼科学会 2010年03月
  • Takashi Ueta, Ryo Obata, Yuji Inoue, Aya Iriyama, Hidenori Takahashi, Takuhiro Yamaguchi, Yasuhiro Tamaki, Yasuo Yanagi
    OPHTHALMOLOGY 116 12 2400 - 2406 2009年12月 [査読有り][通常論文]
     
    Objective: To compare background factors of the 2 most dominant subtypes of exudative age-related macular degeneration (AMD) in the Japanese population: typical AMD and polypoidal choroidal vasculopathy (PCV). Design: Cross-sectional comparison. Participants: Consecutive patients with typical AMD (n = 89) and PCV (n = 138) for the primary survey. For the secondary survey, the number of participants was extended to include 148 typical AMD and 170 PCV patients. All the patients included in the present study had been followed up at The University of Tokyo Hospital outpatient macular clinic. Methods: Background data on gender; age; body mass index; smoking; alcohol consumption; and histories of hypertension, diabetes mellitus (DM), hyperlipidemia, ischemic heart disease, stroke, intensive light exposure, central serous chorioretinopathy (CSC), cataract surgery, glaucoma, and steroid use were obtained mainly through interview. The interviewers were masked to the subtype diagnosis of AMD. Univariate and multivariate logistic regression analyses were performed to identify differences in the background factors between typical AMD and PCV. In the secondary survey, the association of a history of CSC and PCV was confirmed further, and funduscopic findings of an atrophic retinal pigment epithelial (RIDE) tract and focal photocoagulation scars that could indicate a history of CSC were investigated. Main Outcome Measures: Frequency and mean of background factors inpatients with typical AMD or PCV. Results: The 2 groups showed similar backgrounds with the exception of their histories of DM and CSC. A history of DM was more frequent in typical AMD (24.7% vs. 13.0% in the primary survey; P = 0.027), whereas a history of CSC was more prevalent in PCV (3.4% vs. 14.7% in the secondary survey; P = 0.0005). Funduscopic findings of an atrophic RPE tract or focal photocoagulation scars were found more frequently in PCV (0.7% vs. 7.6%; P = 0.002). Conclusions: Background factors of typical AMD and PCV are similar but not identical. A history of DM and CSC are more frequent in typical AMD and PCV, respectively.
  • Wrapped Liposome siRNAを用いた抗VEGF療法のマウスにおける全身的影響
    高橋 秀徳, 八木 信宏, 山内 雅博, 柳 靖雄, 玉置 泰裕, 真鍋 一郎, 永井 良三
    眼科臨床紀要 2 11 1046 - 1046 眼科臨床紀要会 2009年11月
  • Aya Iriyama, Yuji Inoue, Hidenori Takahashi, Yasuhiro Tamaki, Woo-Dong Jang, Yasuo Yanagi
    JOURNAL OF CELLULAR PHYSIOLOGY 220 2 469 - 475 2009年08月 [査読有り][通常論文]
     
    A recent study in vitro demonstrated that a major lipofuscin component, A2E, serves as a retinoic acid receptor ligand. The current study investigated the effects of A2E on retinal pigment epithelial (RPE) cells in vivo and was performed to extend the understanding of the effects of A2E. Firstly, subretinal injection of A2E was performed and 3 weeks after the injection, and it was demonstrated that subretinal injection of A2E induced RPE cell death, and concomitant upregulation of vascular endothelial growth factor (VEGF) in the RPE and choroid. The upregulation of VEGF was attenuated by an RAR alpha antagonist. Next we performed laser photocoagulation in mice that accumulated A2E either after subretinal injection, by Ccl2 gene knockout or by aging demonstrated that mice that accumulated A2E in the RPE, which showed higher rates of choroidal neobascularization (CNV) formation after weak laser injury than the controls and the formation of CNV was inhibited by an RAR alpha antagonist in all models tested. The data suggest that A2E accumulation induces RPE cell death, and concomitant increase of VEGF. Accumulation of A2E alone is not sufficient to induce CNV in vivo, but induces the expression of VEGF in RPE and choroid. The mice that accumulated A2E in RPE cells are vulnerable to CNV development via RAR activation, at least in part. J. Cell. Physiol. 220: 469-475, 2009. (C) 2009 Wiley-Liss, Inc.
  • VEGF及び受容体を標的にしたWrapped Liposome/siRNA全身投与における臓器副作用の検討
    高橋 秀徳, 八木 信宏, 山内 雅博, 柳 靖雄, 玉置 泰裕, 真鍋 一郎, 永井 良三
    日本眼科学会雑誌 113 臨増 201 - 201 (公財)日本眼科学会 2009年03月
  • 中心性漿液性網脈絡膜症の既往とポリープ状脈絡膜血管症の発症
    上田 高志, 柳 靖雄, 藤村 茂人, 井上 達也, 入山 彩, 高橋 秀徳, 小畑 亮, 井上 裕治, 玉置 泰裕
    日本眼科学会雑誌 113 臨増 310 - 310 (公財)日本眼科学会 2009年03月
  • Kayo Kure, Kayo Kure, Yasuo Yanagi, Ryo Obata, Yuji Inoue, Hidenori Takahashi, Aya Iriyama, Tomoko Adachi, Takashi Ueta, Yasuhiro Tamaki
    Japanese Journal of Clinical Ophthalmology 62 1551 - 1555 2008年10月 [査読無し][通常論文]
     
    To report the outcome of intravireal injection of bevacizumab for retinal vein occlusion with macular edema in eyes with or without previous vitrectomy. Cases and Method : This study was made on 14 eyes of 14 patients. Central retinal vein occlusion was present in 2 eyes and branch retinal vein occlusion in 12 eyes. The series comprised 9 males and 5 females. Vitrectomy had been performed on 7 eyes. All the 14 eyes had macular edema. Each eye received intravitreal injection of 1.25 mg bevacizumab. Visual acuity was evaluated as logMAR. Changes by 0.2 or more were regarded as significant. Cases were followed up for 5 months or longer. Results : Visual acuity improved or remained unchanged in all he eyes. Foveal thickness decreased in 12 eyes 2 weeks after treatment. Macular edema improved in 11 eyes and remained unchanged in 3 eyes irrespective of previous vitrectomy. Conclusion : Intravitreal bevacizumab is effective for macular edema in eyes with or without previous vitrectomy.
  • ダール食塩感受性高血圧ラットにおける腎障害と網膜細動脈への白血球接着の関連
    高橋 秀徳, 呉 雅瓊, 川畑 ゆかり, 沼部 敦司, 柳 靖雄, 玉置 泰裕, 清木 興介, 上原 譽志夫, 新家 眞
    日本高血圧学会総会プログラム・抄録集 31回 264 - 264 (NPO)日本高血圧学会 2008年10月
  • 呉 香代, 柳 靖雄, 小畑 亮, 井上 裕治, 高橋 秀徳, 入山 彩, 足立 知子, 上田 高志, 玉置 泰裕
    臨床眼科 62 9 1551 - 1555 (株)医学書院 2008年09月 
    目的:網膜静脈閉塞症に続発した黄斑浮腫眼に硝子体手術を行い,その後ベバシズマブを硝子体に注入した結果の報告。対象と方法:14例14眼を対象とした。網膜中心静脈閉塞症2眼,網膜静脈分枝閉塞症12眼で,男性9眼,女性5眼であった。14眼中7眼には硝子体手術の既往があった。全例に黄斑浮腫があり,ベバシズマブ1.25mgを硝子体に注入した。視力はlogMARで評価し,0.2以上の変化を有意とした。結果:術後5ヵ月間の観察で,視力は全例で改善または不変であった。初回投与前と投与2週間後で,中心窩厚は12眼で減少し,硝子体手術の既往とは無関係であった。黄斑浮腫は11眼で改善,3眼で不変であり,硝子体手術の既往とは無関係であった。結論:ベバシズマブの硝子体内投与は黄斑浮腫に有効であり,硝子体手術の既往とは無関係である。(著者抄録)
  • 足立 知子, 高橋 秀徳, 上田 高志
    臨床眼科 62 9 1473 - 1476 医学書院 2008年09月 [査読無し][通常論文]
  • Takashi Ueta, Aya Iriyama, Jasmine Francis, Hidenori Takahashi, Tomoko Adachi, Ryo Obata, Yuji Inoue, Yasuhiro Tamaki, Yasuo Yanagi
    AMERICAN JOURNAL OF OPHTHALMOLOGY 146 1 96 - 101 2008年07月 [査読有り][通常論文]
     
    PURPOSE: To investigate the development of typical age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) in fellow eyes of Japanese patients with exudative AMD. DESIGN: Retrospective observational consecutive case series. METHODS: Two hundred and sixteen Japanese patients were enrolled in this study from the outpatient clinic of the University of Tokyo Hospital. Ninety-one patients had typical AMD and one hundred and twenty-five patients had PCV. The average follow-up period was 33.6 and 25.1 months for typical AMD and PCV patients. RESULTS: The cumulative incidence of involvement in fellow eyes with overall exudative AMD, including both typical AMD and PCV, was 3.4% in one year, 9.3% in three years, and 11.3% in five years. It was 3.6%, 7.3%, and 11.2% in typical AMD, and 3.2%, 11.1%, and 11.1% in PCV in one, three, and five years, respectively. Before the development of exudative AMD, patients with typical AMD had a variety of funduscopic findings including retinal pigment epithelium (RPE) atrophy, drusen, drusenoid pigment epithelial detachments (PED), and normal macula. PCV patients, on the other hand, had funduscopic findings of RPE atrophy. Inner choroidal vascular abnormality of vascular network and polypoidal. formation was observed in several eyes before the clinical manifestation of exudative changes. CONCLUSIONS: Typical AMD and PCV had similar probabilities of involving the fellow eye in unilaterally affected Japanese patients. RPE atrophy was a prevailing finding in fellow eyes of patients who developed PCV. In PCV, choroidal vascular network and polypoidal formation gradually grow before exudative changes.
  • Aya Iriyama, Ryoji Fujiki, Yuji Inoue, Hidenori Takahashi, Yasuhiro Tamaki, Shinichiro Takezawa, Kenichi Takeyama, Woo-Dong Jang, Shigeaki Kato, Yasuo Yanagi
    JOURNAL OF BIOLOGICAL CHEMISTRY 283 18 11947 - 11953 2008年05月 [査読有り][通常論文]
     
    Lipofuscin contains fluorophores, which represent a biomarker for cellular aging. Although it remains unsubstantiated clinically, experimental results support that the accumulation of lipofuscin is related to an increased risk of choroidal neovascularization due to age-related macular degeneration, a leading cause of legal blindness. Here, we report that a major lipofuscin component, A2E, activates the retinoic acid receptor (RAR). In vitro experiments using luciferase reporter assay, competitional binding assay, analysis of target genes, and chromatin immunoprecipitation (ChIP) assay strongly suggest that A2E is a bona fide ligand for RAR and induces sustained activation of RAR target genes. A2E-induced vascular endothelial growth factor (VEGF) expression in a human retinal pigment epithelial cell line (ARPE-19) and RAR antagonist blocked the up-regulation of VEGF. The conditioned medium of A2E-treated ARPE-19 cells induced tube formation in human umbilical vascular endothelial cells, which was blocked by the RAR antagonist and anti-VEGF antibody. These results suggest that A2E accumulation results in the phenotypic alteration of retinal pigment epithelial cells, predisposing the environment to choroidal neovascularization development. This is mediated through the agonistic function of A2E, at least in part. The results of this study provide a novel potential therapeutic target for this incurable condition.
  • Hidenori Takahashi, Hidenobu Ishizaki, Hideaki Tahara, Yasuhiro Tamaki, Yasuo Yanagi
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 49 5 2143 - 2147 2008年05月 [査読有り][通常論文]
     
    PURPOSE. It has been shown that vaccination with peptides derived from human vascular endothelial growth factor receptor 2 (VEGFR2) induces cytotoxic T lymphocytes (CTLs) with potent cytotoxicity against endothelial cells expressing VEGFR2 in a A2/Kb transgenic mice system expressing human HLA-A*0201. The present study examined the efficacy of this immunotherapy against age-related macular degeneration (AMD) using a choroidal neovascularization (CNV) model. METHODS. Seven-to 10- week-old A2/Kb transgenic mice expressing human HLA-A*0201 were used. The mice were divided into three groups of 15 animals each: phosphate-buffered saline (PBS) treatment ( control); immunity adjuvant ( incomplete Freund adjuvant [IFA]); and antigen peptide of human VEGFR 2 and IFA ( peptide vaccination group). Immunization was given on days 0 and 11. On day 20, six CNVs were induced in both eyes of each animal using a semiconductor laser set to 75 mu m, 200 mW, and 0.05 seconds. Leakage from the CNV was measured by fluorescein angiography 7 days after laser treatment. CNV volume was measured using a choroidal flatmount after perfusing the mice with fluorescein conjugate lectin. RESULTS. There were no significant differences in the leakage or the area of CNV in the IFA-treated group compared with controls. In contrast, the fluorescent leakage index in the peptide vaccination group was reduced to 80% and the CNV area to 18% compared with the control group (P < 0.0001 and P < 0.05, respectively). CONCLUSIONS. This model provides a rationale for immunotherapy using the epitope peptides derived from VEGFR2 for the treatment of CNV.
  • 高血圧ラットの臓器障害に及ぼすFluvastatinの影響と網膜血管の白血球接着との関連性
    高橋 秀徳, Wu Yaqiong, 入山 彩, 小畑 亮, 井上 裕治, 柳 靖雄, 玉置 泰裕, 沼部 敦司, 上原 譽志夫, 新家 眞
    日本眼科学会雑誌 112 臨増 195 - 195 (公財)日本眼科学会 2008年03月
  • 3次元光干渉断層計による加齢黄斑変性前駆病変の観察
    小畑 亮, 上田 高志, 入山 彩, 高橋 秀徳, 井上 裕治, 足立 知子, 柳 靖雄, 玉置 泰裕
    日本眼科学会雑誌 112 臨増 226 - 226 (公財)日本眼科学会 2008年03月
  • 日本人の加齢黄斑変性症における光線力学療法 初診後1年の視力予後評価
    上田 高志, 柳 靖雄, 入山 彩, 高橋 秀徳, 足立 知子, 小畑 亮, 井上 裕治, 玉置 泰裕
    日本眼科学会雑誌 112 臨増 238 - 238 (公財)日本眼科学会 2008年03月
  • 狭義加齢黄斑変性とポリープ状脈絡膜血管症における硝子体牽引の病態への関与
    野村 陽子, 上田 高志, 入山 彩, 高橋 秀徳, 小畑 亮, 井上 裕治, 足立 知子, 柳 靖雄, 玉置 泰裕
    日本眼科学会雑誌 112 臨増 306 - 306 (公財)日本眼科学会 2008年03月
  • Aya Iriyama, Ryo Obata, Yuji Inoue, Hidenori Takahashi, Yasuhiro Tamaki, Yasuo Yanagi
    GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY 246 3 339 - 344 2008年03月 [査読有り][通常論文]
     
    Purpose To evaluate the effect of posterior juxtascleral triamcinolone acetonide (TA) injection combined with photodynamic therapy with verteporfin (PDT) for treating exudative age-related macular degeneration (AMD), the best-corrected visual acuity (BCVA), the retreatment rates and the rate of choroidal hypoperfusion were investigated. Methods A total of 67 eyes with subfoveal choroidal neovascularization (CNV) due to AMD were included. Forty-four eyes underwent PDT alone (PDT-alone group), and 23 eyes underwent PDT with the posterior juxtascleral injection of TA (PDT+TA group). Every 3 months after the PDT, the eyes were evaluated with regard to BCVA and requirement for retreatment by fluorescein angiography (FA) with the aid of optical coherence tomography (OCT). Choroiocapillaris hypoperfusion was assessed by indocyanine green angiography (ICGA) at 3 and 12 months. All patients completed a 1-year follow-up. Results At the baseline, there was no difference in lesion type, size or visual acuity between the two groups. At 1 year, the change in BCVA was -0.0811 logarithm of the minimum angle of resolution (LogMAR) in the PDT-alone group, compared with -0.0432 logMAR in the PDT+TA group. There was no significant difference in the change in BCVA between the two groups (P=0.6910). The PDT+TA group required a lower mean number of treatments (1.64 compared with 2.34 [P=0.0223]) and showed a higher rate of choriocapillaris occlusion at 3 months, but no significant difference at 1 year (P=0.9243) Conclusions Fewer retreatments were required in the TA+PDT group. There was no significant difference in the change in BCVA between the two groups. Adjacent TA may promote short-term choriocapillaris hypoperfusion.
  • 高橋秀徳, 上田高志, 入山彩, 小畑亮, 井上裕治, 足立知子, 柳靖雄, 玉置泰裕
    臨床眼科 62 8 1347 - 1353 (株)医学書院 2008年 [査読有り][通常論文]
     
    目的:加齢黄斑変性に対し光線力学療法後にベバシズマブを硝子体内に投与した4症例の報告。症例:病変の最大径が5mmを超える滲出型加齢黄斑変性4例4眼を対象とした。男性3例,女性1例で,年齢は70〜79歳であった。4例ともoccult with no classicであった。光線力学療法から5日〜2ヵ月後にベバシズマブ1.25mgを硝子体に注入した。結果:術前視力は0.1〜0.4であった。6ヵ月後に1例で2段階以上の視力低下があり,3眼では不変であった。初回治療から3ヵ月後に2例,6ヵ月後に3例が再治療を要した。6ヵ月以上の経過中に,1乳頭径以上の網膜出血,網膜剥離,眼内炎などはなかった。結論:加齢黄斑変性に対するベバシズマブを併用する光線力学療法は,無害であり,奏効することがある。(著者抄録)
  • Hidenori Takahashi, Yasuhiro Tamaki, Nobuya Ishii, Nobuhiro Oikawa, Eisaku Mizuguchi, Jasmine H. Francis, Yuji Inoue, Aya Iriyama, Ryo Obata, Yasuo Yanagi
    CURRENT EYE RESEARCH 33 11-12 1002 - 1010 2008年 [査読有り][通常論文]
     
    Purpose: To select a novel orally administered VEGFR-2 (KDR/flk-1) specific tyrosine kinase inhibitor in a murine model of choroidal neovascularization (CNV). Methods: From a compound library, potent VEGFR2 inhibitors were selected by VEGF-induced phosphorylation of VEGFR-2 and RAF kinases and the proliferation analysis by HUVEC cultures and in vitro tube formation assay. CNV was induced in C57/BL6 mice using diode laser photocoagulation. The antiangiogenic effect of selected compounds was assessed by angiographic examination, in which extent of fluorescein leakage was scored and histological analysis, allowing for measurement of CNV membrane under light microscope. In addition, C57/BL6 mice were treated with daily oral administration of selected compounds for 14 days and body weights were measured. Results: Six compounds that potently inhibited VEGFR-2 were selected for further investigation. Selected compounds-treated conditions showed a dose-dependent inhibition of phosphorylation of VEGFR-2 tyrosine kinase with an IC50 of 0.0022 to 0.098 m. Selected compounds did not inhibit the HCT116 proliferation but did demonstrate a strong inhibition effect for VEGFR-2 dependant HUVEC (IC50 = 0.0018 to 0.058 m). Selected compounds treatment also resulted in a dose-dependent attenuation of in vitro tube formation. In the murine CNV model, #0451 is the most effective compound. The intensity of fluorescein leakage was significantly lower in doses of 12.5, 25, 50, and 100 mg/kg #0451-treated eyes compared to controls. Histologically, CNV membrane volumes were significantly reduced in #0451-treated eyes in a dose-dependent manner. At therapeutic doses of 100 mg/kg or less, there was no significant weight loss between the treated and untreated groups. Conclusion: Oral administration of #0451, a novel VEGFR-2 (KDR/flk-1)-specific tyrosine kinase inhibitor, demonstrates anti-angiogenic effects in our murine model of CNV. #0451 may be useful to treat the choroidal neovascularization associated with AMD.
  • Yuji Inoue, Yasuo Yanagi, Kyosuke Matsuura, Hidenori Takahashi, Yasuhiro Tamaki, Makoto Araie
    BRITISH JOURNAL OF OPHTHALMOLOGY 91 12 1720 - 1721 2007年12月 [査読有り][通常論文]
  • Dahl食塩感受性ラットの易腎障害性の機序と血圧上昇の役割
    Wu Yaqiong, 高橋 秀徳, 沼部 敦司, 柳 靖雄, 玉置 泰裕, 新家 眞, 上原 譽志夫
    日本高血圧学会総会プログラム・抄録集 30回 215 - 215 (NPO)日本高血圧学会 2007年10月
  • Dahl食塩感受性ラット腎障害に及ぼすアンギオテンシン受容体拮抗薬の影響と血管白血球接着との関連性
    高橋 秀徳, Wu Yaqiong, 柳 靖雄, 玉置 泰裕, 沼部 敦司, 新家 眞, 上原 譽志夫
    日本高血圧学会総会プログラム・抄録集 30回 215 - 215 (NPO)日本高血圧学会 2007年10月
  • Yuji Inoue, Aya Iriyama, Shuji Ueno, Hidenori Takahashi, Mineo Kondo, Yasuhiro Tamaki, Makoto Araie, Yasuo Yanagi
    EXPERIMENTAL EYE RESEARCH 85 2 234 - 241 2007年08月 [査読有り][通常論文]
     
    Because there is no effective treatment for this retinal degeneration, potential application of cell-based therapy has attracted considerable attention. Several investigations support that bone marrow mesenchymal stem cells (MSCs) can be used for a broad spectrum of indications. Bone marrow MSCs exert their therapeutic effect in part by secreting trophic factors to promote cell survival. The current study investigates whether bone marrow MSCs secrete factor(s) to promote photoreceptor cell survival and whether subretinal transplantation of bone marrow MSCs promotes photoreceptor survival in a retinal degeneration model using Royal College of Surgeons (RCS) rats. In vitro, using mouse retinal cell culture, it was demonstrated that the conditioned medium of the MSCs delays photoreceptor cell apoptosis, suggesting that the secreted factor(s) from the MSCs promote photoreceptor cell survival. In vivo, the MSCs were injected into the subretinal space of the RCS rats and histological analysis, real-time RT-PCR and electrophysiological analysis demonstrated that the subretinal transplantation of MSCs delays retinal degeneration and preserves retinal function in the RCS rats. These results suggest that MSC is a useful cell source for cell-replacement therapy for some forms of retinal degeneration. (c) 2007 Elsevier Ltd. All rights reserved.
  • 血管内皮増殖因子受容体2由来抗原ワクチン療法のマウス脈絡膜新生血管モデルでの検討
    高橋 秀徳, 石崎 秀信, 柳 靖雄, 玉置 泰裕, 田原 秀晃
    日本眼科学会雑誌 111 臨増 228 - 228 (公財)日本眼科学会 2007年03月
  • 血管内皮増殖因子受容体2選択的阻害薬の同定、および、マウス脈絡膜新生血管モデルを用いた検討
    高橋 秀徳, 石井 暢也, 及川 信宏, 水口 栄作, 玉置 泰裕, 柳 靖雄, 井上 裕治
    日本眼科学会雑誌 111 臨増 302 - 302 (公財)日本眼科学会 2007年03月
  • 狭義滲出型加齢黄斑変性症とポリープ状脈絡膜血管症の片眼発症症例の僚眼発症率の比較
    上田 高志, 柳 靖雄, 小畑 亮, 入山 彩, 高橋 秀徳, 井上 裕治, 足立 知子, 玉置 泰裕
    日本眼科学会雑誌 111 臨増 222 - 222 (公財)日本眼科学会 2007年03月
  • 光線力学療法後の経過と光干渉断層計所見
    小畑 亮, 入山 彩, 高橋 秀徳, 井上 裕治, 足立 知子, 上田 高志, 柳 靖雄, 玉置 泰裕
    日本眼科学会雑誌 111 臨増 264 - 264 (公財)日本眼科学会 2007年03月
  • 玉置泰裕, 柳靖雄, 出田隆一, 井上裕治, 入山彩, 高橋秀徳, 小畑亮, 村中公正, 上順子, 新家眞, 西山伸宏, Ahang GD, Jang WD, 片岡一則, 原田敦史, 相田卓三, 近藤峰生, 伊藤逸毅, 上野真治, 宮田健太郎, 子安俊行, 寺崎浩子, 井上達也, 古川貴久, 大石高生, 田坂文孝, 石井康雄
    日本眼科學會雑誌 111 3 232 - 268 (公財)日本眼科学会 2007年 [査読無し][招待有り]
     
    加齢に伴う変化がその発症および進展にかかわる眼疾患のひとつに加齢黄斑変性(age-related macular degeneration,AMD)がある.本疾患は,欧米では成人失明原因の第一位であり,特に脈絡膜新生血管(choroidal neovascularization,CNV)により惹起される滲出型AMDは,視力予後が不良で,その治療法の開発は急務である.そこで,AMDに対する新規治療法の開発を目的として,CNVに対する抗血管新生療法,および障害された網膜再生医療の両面から,新しいアプローチを試みた.Polyion complex(PIC)ミセルは静電相互作用により形成される直径数十nmのナノ粒子であり,enhanced permeability and retention(EPR)効果により固形腫瘍に高い集積性を示す.Fluorescein isothiocyanateで標識したpoly-L-lysine[FITC-P(Lys)]を内包したPICミセルをラットCNVモデルに静脈内投与した検討では,CNVにおける集積は投与168時間後まで持続し,ラットCNV部に高い集積性を示した.PICミセルはCNVに対するドラッグデリバリーシステムとして有用である可能性が示された.光線力学療法(PDT)はAMDに対する現在の標準的治療法であるが,問題点として施行後のCNV再発がある.AMDに対するPDTの効果を高めるためには,光増感剤をCNV領域へ選択的に送達することと,CNV領域での効果的な光力学反応を惹起することの双方が必要である.デンドリマー型光増感剤は内核に位置する光増感剤が高濃度においても凝集しないという性質により,高効率の光力学反応を惹起することが期待できる.Dendrimer porphyrin(DP)をミセル化したDPミセルにより,CNVへのDPの高い集積性が得られ,より低いエネルギー照射のPDTによりCNV閉塞が可能となった.DPミセルを用いたPDTは,CNV閉塞効率が高いのみならず,正常な網脈絡膜血管や皮膚に対する障害も少ないことが示された.デンドリマー型光増感剤とそのミセル化はCNVに対するPDTにおいて非常に有用であることが強く示唆された.生体内において遺伝子の導入部位の制御が可能となればAMDを含む眼局所の疾患に対する遺伝子治療にとって非常に有用である.光応答性遺伝子導入はDNA/ぺプチド複合体とともに光増感剤を作用させ,エンドソーム膜を障害することにより導入効率を上げる遺伝子導入法であるが,その細胞毒性のためin vivoには応用されていない.そこで,DNA/ぺプチド複合体がデンドリマー型光増感剤(デンドリマーフタロシアニン)の外殻に覆われた新規三元系コンプレックスを調製し,ラット結膜下へ注入した後にPDT用レーザーを照射したところ,光線照射部位に特異的なレポーター遺伝子の発現上昇を認め,光線照射により眼組織への遺伝子導入を制御可能な遺伝子キャリアとなり得ることが示唆された.網膜色素上皮(RPE)へのリポフスチンの沈着は滲出型AMDの前駆病変と考えられている.リポフスチンの構成成分であるA2E(N-retinyledin-N-retinylethanolamin)は,レチノイン酸受容体を活性化し,RPEの表現型の変化を来し,血管新生因子を活性化することによりCNVの発生に関与していることが示唆され,CNV治療の新しいターゲットとなり得る可能性が示された.AMDにより損なわれた視機能の回復には,障害網膜の再生が必須である.マウス骨髄間葉系幹細胞を網膜変性モデルラット網膜下に移植し,網膜変性に対する網膜変性抑制効果を組織学的および電気生理学的に検討した.骨髄間葉系幹細胞移植眼では,形態的および機能的に網膜変性抑制効果が認められ,細胞移植療法の細胞ソースとなり得ることが示唆された.AMDで障害される黄斑形成にかかわる遺伝子やその形成の分子機構について検討するため,発生期のアカゲザル網膜を黄斑部と周辺部に分けて採取し,サルゲノムマイクロアレイを用いて黄斑部と網膜周辺部での遺伝子発現比較を行った.さらに,黄斑部に高い発現がみられるもの,あるいは黄斑部の形成時期に特異的に発現する遺伝子群を選び,これらの発現をin situハイブリダイゼーションによって検討した.本研究は,黄斑形成の分子機構の解明,さらには錐体の再生医療を可能にする基盤研究になり得ると期待される.(著者抄録)
  • 高橋秀徳, 小畑亮, 入山彩, 井上裕治, 柳靖雄, 玉置泰裕
    臨床眼科 61 3 373 - 378 (株)医学書院 2007年 [査読有り][通常論文]
     
    53歳女性。患者は8年前より糖尿病境界型の指摘を受け、約2年前より視力低下を自覚した。今回、精査のため紹介受診となったが、矯正視力は右(0.2)、左(0.4)で、眼圧は右18mmHg、左19mmHgであった。一方、眼底検査では両眼の黄斑部耳側に灰白色混濁が認められ、右眼に軽度の網膜下出血と耳側に拡張した網膜血管、左眼にはクリスタリン様の沈着物を認めた。また、フルオレセイン蛍光眼底造影(FA)では早期に網膜毛細血管叢の拡張を、後期には同部に組織染を認め、右眼の白色隆起病変の中央に軽度蛍光漏出を認めて網膜下新生血管(SRN)の合併が疑われた。更に光干渉断層計(OCT)では両眼に視細胞層の途絶と中心窩のlamellar cystがみられた。以上より、本症例はIdiopathic juxtafoveolar retinal telangiectasis(特発性傍中心窩毛細血管拡張症) group 2Aと診断され、右眼にトリアムシノロンアセトニドのテノン嚢下投与を行った。その結果、投与3ヵ月後のFA後期では隆起病変の蛍光漏出は減少したものの、視力には変化が認められなかった。
  • R. Obata, A. Iriyama, Y. Inoue, H. Takahashi, Y. Tamaki, Y. Yanagi
    BRITISH JOURNAL OF OPHTHALMOLOGY 91 1 100 - 104 2007年01月 [査読有り][通常論文]
     
    Objective: To investigate the expression of proangiogenic and antiangiogenic factors, vascular endothelial growth factor ( VEGF) and pigment epithelium-derived factor ( PEDF) in retinal pigment epithelial ( RPE) cells after photodynamic therapy ( PDT), especially focusing on their change in the presence of triamcinolone acetonide. Methods: Firstly, the cellular uptake of verteporfin was quantified after confluent ARPE-19 ( human retinal pigment epithelial) cells were exposed to 5 mu g/ml verteporfin combined with or without 1 mu g/ml triamcinolone acetonide for 1 h. Secondly, ARPE-19 cells exposed to various doses of verteporfin were irradiated with 120 mJ/cm(2) light. After incubation with or without 1 mu g/ml triamcinolone acetonide for 2 days, cell viability and expressions of VEGF and PEDF were assessed. Results: Cellular uptake of verteporfin was not significantly changed by the presence of 1 mu g/ml triamcinolone acetonide. In addition, 0.01 - 0.1 mg/ml of verteporfin showed a dose-dependent toxicity on the ARPE-19 cells 2 days after the light exposure. The presence of verteporfin at a concentration of 0.01 mg/ml did not affect the cell viability but significantly increased VEGF ( p < 0.001) and reduced PEDF ( p = 0.03) expression. Administration of triamcinolone acetonide significantly suppressed both this increase in VEGF ( p < 0.001) and decrease in PEDF ( p = 0.001). Conclusions: VEGF was increased and PEDF reduced in cultured RPE cells shortly after PDT even at a sublethal dose. Triamcinolone acetonide suppressed this proangiogenic response.
  • Hidenori Takahashi, Ryo Obata, Yasuhiro Tamaki
    JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS 22 4 213 - 218 2006年08月 [査読有り][通常論文]
     
    Aim: An oral, multitargeted receptor tyrosine kinase inhibitor, SU11248, inhibits vascular endothelial growth factor receptor 2 (VEG FR2, kinase domain receptor F1K1), platelet-derived growth factor receptor, stem cell factor receptor (Kit), and fetal liver tyrosine kinase 3. In this study, we administered SU11248 beyond the completion of an experimental choroidal neovascularization (CNV) model to determine whether CNV growth can be inhibited in vivo. Methods: C57B6J mice were treated with daily oral administration (40, 80, and 150 mg/kg) of SU11248 during 5 days after diode laser endophotocoagulation and subjected to angiographic examination and histological analysis. Results: Intensity of fluorescein leakage from the experimental CNV decreased significantly compared to the control eyes. Histological study also revealed that the volume of CNV membrane was significantly reduced in the SU11248-treated eyes. Conclusions: Oral administration of this compound is potentially beneficial in treating CNV caused by age-related macular degeneration (AMD) and other causal diseases. Considering the tolerance the clinical studies for malignant tumors previously demonstrated, further studies to evaluate the clinical efficacy of the drug for AMD might be indicated.
  • Ryo Obata, Yasuo Yanagi, Junko Kami, Hidenori Takahashi, Yuji Inoue, Yasuhiro Tamaki
    JAPANESE JOURNAL OF OPHTHALMOLOGY 50 4 354 - 360 2006年07月 [査読有り][通常論文]
     
    Purpose: To determine the percentage of Japanese patients with age-related macular degeneration (AMD) who are eligible for photodynamic therapy (PDT) with verteporfin who have either polypoidal choroidal vasculopathy (PCV) or choroidal neovascularization (CNV) with retinochoroidal anastomosis (RCA). Methods: The medical charts of 82 consecutive patients (83 eyes) with subfoveal CNV due to AMD were reviewed. Initially, we determined which of these eyes were eligible for PDT by using the criteria reported by two large randomized control studies, that is, the Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) study and the Verteporfin in Photodynamic Therapy (VIP) study. Among the PDT-eligible patients, the percentage of eyes with PCV or CNV with RCA was determined by indocyanine green angiography (ICGA). Results: In total, 36 eyes (43%) of the 83 eyes were PDT-eligible; 17 (20%) based on the TAP study criteria, and 19 (23%) based on the VIP study criteria. Among these PDT-eligible eyes, ICGA revealed that 12 (33%) had PCV and 2 (6%) had CNV with RCA. Conclusions: With ICGA, PCV or CNV with RCA were recognized in a substantial proportion of cases eligible for PDT based on the two clinical studies. Considering that the treatment efficacy of PDT for PCV or RCA has not been established, detection of PCV or RCA prior to PDT with ICGA is highly recommended.
  • 網膜変性症モデルラットに対する骨髄間葉系幹細胞網膜下移植による網膜変性抑制効果
    井上 裕治, 入山 彩, 高橋 秀徳, 柳 靖雄, 相原 一, 玉置 泰裕, 新家 眞, 上野 真治, 近藤 峰生
    日本眼科学会雑誌 110 臨増 107 - 107 (公財)日本眼科学会 2006年03月
  • リポフスチン構成成分A2eの網膜色素上皮細胞および脈絡膜新生血管に及ぼす影響
    入山 彩, 柳 靖雄, 井上 裕治, 高橋 秀徳, 玉置 泰裕
    日本眼科学会雑誌 110 臨増 133 - 133 (公財)日本眼科学会 2006年03月
  • マウス脈絡膜新生血管モデルにおけるインスリン受容体基質2の作用
    高橋 秀徳, 小畑 亮, 柳 靖雄, 玉置 泰裕, 寺内 康夫, 門脇 孝
    日本眼科学会雑誌 110 臨増 134 - 134 (公財)日本眼科学会 2006年03月
  • KDR阻害薬の脈絡膜新生血管抑制効果
    小畑 亮, 高橋 秀徳, 柳 靖雄, 玉置 泰裕
    日本眼科学会雑誌 110 臨増 198 - 198 (公財)日本眼科学会 2006年03月
  • Wrapped Liposome siRNAのマウス脈絡膜新生血管モデルにおける動態検討
    高橋 秀徳, 小畑 亮, 柳 靖雄, 玉置 泰裕, 真鍋 一郎, 八木 信宏, 山内 雅博, 永井 良三
    日本眼科学会雑誌 110 臨増 275 - 275 (公財)日本眼科学会 2006年03月
  • N Nishiyama, A Iriyama, WD Jang, K Miyata, K Itaka, Y Inoue, H Takahashi, Y Yanagi, Y Tamaki, H Koyama, K Kataoka
    NATURE MATERIALS 4 12 934 - 941 2005年12月 [査読有り][通常論文]
     
    The control of gene transfection in the body is a core issue in gene therapy. Photochemical internalization is a technology that allows light-induced delivery of DNA, drugs or other biological factors directly inside cells. Usually it requires that a photosensitizer be added to the drug-delivery system to photochemically destabilize the endosomal membrane. Here we present a system for in vivo DNA delivery in which these two components are assembled into one structure. This is a ternary complex composed of a core containing DNA packaged with cationic peptides and enveloped in the anionic dendrimer phthalocyanine, which provides the photosensitizing action. The ternary complex showed more than 100-fold photochemical enhancement of transgene expression in vitro with reduced photocytotoxicity. In an animal experiment, subconjuctival injection of the ternary complex followed by laser irradiation resulted in transgene expression only in the laser-irradiated site. This work demonstrates a new biomedical application for dendrimers, and the first success in the photochemical-internalization-mediated gene delivery in vivo.
  • K Muranaka, Y Yanagi, Y Tamaki, H Takahashi, T Usui, K Ohashi, H Matsuoka, T Senda
    FEBS LETTERS 579 27 6084 - 6088 2005年11月 [査読有り][通常論文]
     
    The effect of a synthetic cyclic disulfide compound, SA3443, on neovascularization was investigated. In vitro, enzyme-linked immunosorbent assay and RT-PCR demonstrated that SA3443 suppressed the expression of the hypoxia-induced vascular endothelial growth factor (VEGF) at both protein and mRNA levels in ARPE-19 cells. In vivo, the administration of SA3443 to mice with laser-induced choroidal neovascularization (CNV) suppressed the leakage from the lesions and reduced their size. Furthermore, the expression level of VEGF protein was significantly reduced by the administration of SA3443. Taken together, our results demonstrate that SA3443 suppresses VEGF production and reduces vascular leakage and the growth of mouse experimental CNV. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
  • Fujisawa N, Fujisawa T, Fujita K, Takahashi H, Nakajima A
    Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology 102 8 994 - 1003 2005年08月 [査読有り][通常論文]
  • 新規3元系コンプレックスによる網膜組織への光選択的遺伝子導入
    井上 裕治, 入山 彩, 高橋 秀徳, 柳 靖雄, 玉置 泰裕, 西山 信宏, 張 ウードン, 片岡 一則
    日本眼科学会雑誌 109 臨増 117 - 117 (公財)日本眼科学会 2005年02月
  • マウス脈絡膜新生血管モデルにおけるアドレノメデュリンの作用
    高橋 秀徳, 上 順子, 柳 靖雄, 玉置 泰裕, 武田 憲文, 新藤 隆行
    日本眼科学会雑誌 109 臨増 143 - 143 (公財)日本眼科学会 2005年02月
  • マウス脈絡膜新生血管モデルにおけるADAMTS-1の作用
    上 順子, 高橋 秀徳, 柳 靖雄, 玉置 泰裕, 武田 憲文, 新藤 隆行
    日本眼科学会雑誌 109 臨増 208 - 208 (公財)日本眼科学会 2005年02月
  • ヒト血清含有培地を用いた,脈絡膜新生血管摘出標本からの網膜色素上皮細胞培養
    小畑 亮, 高橋 秀徳, 井上 裕治, 柳 靖雄, 玉置 泰裕
    日本眼科学会雑誌 109 臨増 85 - 85 (公財)日本眼科学会 2005年02月
  • 25Gシステム硝子体手術の眼内照明による光毒性の検討
    柳 靖雄, 小畑 亮, 井上 裕治, 高橋 秀徳, 玉置 泰裕, 門之園 一明
    日本眼科学会雑誌 109 臨増 121 - 121 (公財)日本眼科学会 2005年02月
  • マウス脈絡膜新生血管モデルの活動性に対する加齢の影響
    高橋 秀徳, 小畑 亮, 柳 靖雄, 玉置 泰裕
    日本眼科学会雑誌 109 臨増 250 - 250 (公財)日本眼科学会 2005年02月
  • N Kinoshita, Y Yanagi, Y Tamaki, R Obata, H Takahashi
    RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES 25 2 225 - 227 2005年02月 [査読有り][通常論文]
  • H Takahashi, Y Yanagi, Y Tamaki, S Uchida, K Muranaka
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 325 2 461 - 466 2004年12月 [査読有り][通常論文]
     
    Cyclooxygenases (COXs) are involved in choroidal neovascularization (CNV). However, the relative contribution of COX-1 and -2 to CNV has not been determined. In this study, the expression of COX-2 was investigated in CNVs in a murine laser-induced model. Subsequently, we found that experimental CNV expressed COX-2, most remarkably around the highly vascularized lesions. To examine the effect of COX-2 inhibition on CNV, etodolac, a non-steroidal anti-inflammatory drug with a high COX-2 selectivity, was tested on murine CNV model. The results demonstrated that the intensity of fluorescein leakage from the photocoagulated lesions decreased significantly compared to the control eyes following etodolac administration. The area of CNV lesions, as examined using histological sections and choroidal flatmounts at day 7, demonstrated that the average size of the CNV lesions was significantly reduced in the etodolac-treated eyes compared to the control eyes. Together, our results demonstrated that selective COX-2 inhibition suppresses CNV. (C) 2004 Elsevier Inc. All rights reserved.
  • 高橋 秀徳, 渋井 洋文, 松尾 寛, 新家 眞
    あたらしい眼科 = Journal of the eye 21 9 1245 - 1248 メディカル葵出版 2004年09月 [査読有り][通常論文]
  • H Takahashi, Y Yanagi, Y Tamaki, K Muranaka, T Usui, M Sata
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 320 2 372 - 375 2004年07月 [査読有り][通常論文]
     
    We investigated the involvement of bone-marrow derived cells to experimental choroidal neovascularization (CNV) in mice, whose bone marrow was reconstituted by either unfractionated bone-marrow cells or Lin(-)c(-)Kit(+)Sca-1(+) enriched presumable hematopoietic stem cells from the green fluorescent protein (GFP) transgeneic mice. Immunohistochemical analysis demonstrated the presence of GFP-positive cells in the CNV lesion after unfractionated bone-marrow transplantation, as well as Lin(-)c(-)Kit(+)Sca(-)1(+) cell transplantation. Some of the GFP-expressing cells also expressed CD-31 and PanEC antigen, markers of vascular endothelial cells. Our results suggest that bone-marrow derived cells may contribute endothelial cells in CNV. (C) 2004 Published by Elsevier Inc.
  • Y Yanagi, Y Tamaki, H Takahashi, H Sekine, M Mori, T Hirato, O Okajima
    RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES 24 2 267 - 274 2004年04月 [査読有り][通常論文]
     
    Background: Crystalline retinopathy is an infrequently encountered disorder characterized by reflective retinal crystalline deposits. The clinical findings of seven patients with crystalline retinopathy are documented. Methods: Clinical features of crystalline retinopathy were studied retrospectively in seven patients, three of whom were followed up for 2 to 5 years. Results: Six patients had a similar fundus appearance, that is, the reflective yellow deposits located mainly in the deep retina with retinal pigment epithelium atrophy throughout the posterior pole and midperipheral retina and with choriocapillaris atrophy at the posterior pole. However, the results from electroretinogram responses were markedly variable. Two of the patients showed marked electroretinogram functional impairment. In addition, other sibling patients only 3 years apart in age had different degrees of disease expression. Conclusion: There is considerable variability in functional manifestations among patients with crystalline retinopathy, even in intrafamilial cases.
  • レチノイン酸受容体特異的アゴニストによるマウス脈絡膜新生血管モデルの抑制効果
    上 順子, 高橋 秀徳, 柳 靖雄, 玉置 泰裕, 影近 弘之, 新藤 隆行, 永井 良三
    日本眼科学会雑誌 108 臨増 209 - 209 (公財)日本眼科学会 2004年03月
  • マウス未熟児網膜症モデルにおけるintestinal kruppel-like factorの作用
    高橋 秀徳, 松浦 恭祐, 井上 祐治, 村中 公正, 柳 靖雄, 玉置 泰裕, 武田 憲文, 新藤 隆行, 永井 良三
    日本眼科学会雑誌 108 臨増 240 - 240 (公財)日本眼科学会 2004年03月
  • 高橋秀徳, 小畑亮, 柳靖雄, 玉置泰裕
    臨床眼科 58 9 1773 - 1777 (株)医学書院 2004年 [査読有り][通常論文]
     
    2000年1月〜2003年7月の間のAMN症例4例6眼(男1例,女3例,25〜55歳,平均34歳)を対象とした.黄斑部に限局する赤〜紫・茶色,楔状または花弁状または小円形の病巣があった.アムスラーチャート,microperimetryでは暗点は病巣に一致していた.フルオレセイン蛍光眼底造影は正常または高度のもので僅かな低蛍光であった.インドシアニングリーン眼底造影,網膜電図は正常であった.光干渉断層計は正常または網膜外層に高輝度層であった.以上の検査所見を診断根拠とした.初診視力は0.01から1.0に分布していた.6眼全てに,暗点と一致する黄斑部外層の網膜に赤色の円形病巣があり,黄斑以外には異常はなかった.最終視力は初診時のそれとほぼ同じであった.発症の誘因として,食物アレルギー,膀胱炎に対して抗生物質を1ヵ月内服,妊娠などがあった.AMNは若年女性に多く(83%),また両眼性が多く(68%),様々な誘因が関与している可能性がある.有効な治療法はない
  • 高橋 秀徳, 櫻井 真彦, 渋井 洋文, 今村 明香, 福島 はるみ, 蕪城 克俊
    眼科手術 = Journal of ophthalmic surgery 16 2 259 - 262 2003年04月 [査読有り][通常論文]
  • ラット脈絡膜新生血管モデルに対する高分子ミセル投与時の眼内移行の検討
    出田 隆一, 高橋 秀徳, 村中 公正, 臼井 智彦, 加治 優一, 玉置 泰裕, 片岡 一則, 原田 敦史, 柳 靖雄
    日本眼科学会雑誌 107 臨増 152 - 152 (公財)日本眼科学会 2003年03月
  • マウス脈絡膜血管新生モデルにおける骨髄細胞の関与
    高橋 秀徳, 村中 公正, 上 順子, 玉置 泰裕, 佐田 政隆, 柳 靖雄
    日本眼科学会雑誌 107 臨増 183 - 183 (公財)日本眼科学会 2003年03月
  • マウス脈絡膜血管新生モデルにおけるSA3443経口投与の血管新生抑制効果
    村中 公正, 高橋 秀徳, 松岡 秀仁, 千田 俊彦, 柳 靖雄, 玉置 泰裕
    日本眼科学会雑誌 107 臨増 277 - 277 (公財)日本眼科学会 2003年03月
  • マウス脈絡膜血管新生モデルにおけるエトドラク経口投与の血管新生抑制効果
    高橋 秀徳, 新 卓也, 村中 公正, 上 順子, 柳 靖雄, 玉置 泰裕
    日本眼科学会雑誌 106 臨増 188 - 188 (公財)日本眼科学会 2002年04月
  • マウス脈絡膜血管新生モデルにおけるイルソグラジン経口投与の血管新生抑制効果
    新 卓也, 高橋 秀徳, 村中 公正, 上 順子, 柳 靖雄, 玉置 泰裕
    日本眼科学会雑誌 106 臨増 188 - 188 (公財)日本眼科学会 2002年04月
  • A Deep-Learning Approach in Rebubbling After Descemet’s Membrane Endothelial Keratoplasty
    Hayashi T, Tabuchi H, Masumoto H, Morita S, Oyakawa I, Inoda S, Kato N, Takahashi H
    Eye Contact Lens [査読有り][通常論文]

講演・口頭発表等

  • 人口知能(AI)による糖尿病網膜症の診断  [招待講演]
    髙橋秀徳
    第64回日本糖尿病学会年次学術集会 2021年05月 シンポジウム・ワークショップパネル(指名)
  • ブロルシズマブ投与後内眼炎を来した滲出型加齢黄斑変性6例背景検討  [通常講演]
    吉田花, 新井悠介, 高橋秀徳, 橋本悠人, 譚雪, 伊野田悟, 高橋良太, 藤野雄次郎, 川島秀俊, 柳靖雄
    第125回日本眼科科学会総会 2021年03月 口頭発表(一般)
  • ブロルシズマブ投与後内眼炎6例の臨床経過  [通常講演]
    月井里香, 坂本晋一, 高橋秀徳, 藤野雄次郎, 橋本悠人, 高橋良太, 伊野田悟, 新井悠介, 川島秀俊
    第125回日本眼科科学会総会 2021年03月 口頭発表(一般)
  • ブロルシズマブ切替後内眼炎の投与前前房水中タンパク質濃度プロファイル  [通常講演]
    橋本悠人, 伊野田悟, 高橋秀徳, 吉田花, 高橋良太, 坂本晋一, 新井悠介, 川島秀俊, 柳靖雄
    第125回日本眼科科学会総会 2021年03月 口頭発表(一般)
  • A hybrid deep learning framework for keratoconus detection based on anterior and posterior corneal maps  [通常講演]
    Al-Timemy,Ali H, Hazarbassanov,Rossen M, Mosa,Zahraa M, Alyasseri,Zaid, Lavric,Alexandru, da Rosa, Claudio A, Griz Camila P, Takahashi Hidenori, Yousefi Siamak
    ARVO imaging Conference 2021年02月 ポスター発表
  • 加齢黄斑変性による多量の網膜下血腫に対し経結膜網膜下灌流を施行した  [通常講演]
    高橋宏典, 新井悠介, 野口久美子, 高橋秀徳, 川島秀俊
    第44回日本眼科手術学会学術総会 2020年12月 口頭発表(一般)
  • Evaluation of keratoconus detection from elevation, topography and pachymetry raw data using machine learning  [通常講演]
    Rossen M.Hazarbassanov, Alexandru Lavric, Jose Arthur Pinto Milhomens Filho, Liliana Anchidin, Valentin Popa, Ali H.AI-Timemy, Zaid Alyasseri, Hidenori Takahashi, Siamak Youself
    2021年 ポスター発表
  • Detecting Keratoconus severity from corneal date of different populations with machine learning  [通常講演]
    Hidenori Takahashi, Ali H.Al-Timemy, Zahraa M.Mosa, Zaid Alyasseri, Alexandru Lavric, Jose Arthur Pinto Milhomens Filho, Kentaro Yuda, Rossen M.Hazarbassanov, Siamak Yousefi
    2021年 ポスター発表
  • AIを利用した効率的な糖尿病網膜症健診  [招待講演]
    髙橋秀徳
    第26回日本糖尿病眼学会総会 シンポジウム・ワークショップパネル(指名)
  • 原因不明の硝子体出血に対する硝子体手術の治療成績  [通常講演]
    吉田 花, 坂本 晋一, 新井悠介, 高橋秀徳, 牧野 伸二, 川島 秀俊
    第59回日本網膜硝子体学会総会 口頭発表(一般)
  • 緑内障眼に生じた網膜分離、中心窩剥離に内境界膜剥離併用硝子体手術を施行した1例  [通常講演]
    月井 里香, 新井 悠介, 牧野 伸二, 坂本 晋一, 髙橋 秀徳, 川島 秀俊
    第59回日本網膜硝子体学会総会 口頭発表(一般)
  • 網膜色素上皮剥離を主体とする滲出型加齢黄斑変性に対する半量光線力学的療法:前向き研究  [通常講演]
    近藤由佳, 新井悠介, 伊野田, 悟, 坂本晋一, 反保宏信, 髙橋秀徳, 井上裕治, 川島 秀俊
    第59回日本網膜硝子体学会総会 口頭発表(一般)
  • 白内障AI2020アップデート  [招待講演]
    髙橋秀徳, 田淵仁志
    第35回JSCRS学術総会 シンポジウム・ワークショップパネル(指名)
  • 眼底読影・診断・診療アシスト(読影、治療方針の提案など)  [招待講演]
    髙橋秀徳
    第124回日本眼科学会総会 2020年04月 シンポジウム・ワークショップパネル(指名)
  • AI(人工知能)  [招待講演]
    高橋秀徳, 田淵仁志
    第34回JSCRS学術総会 2019年06月
  • Wound-assited法にて眼内レンズ挿入したところレンズが角膜実質内に迷入した1例  [通常講演]
    守屋穣, 坂本晋一, 新井悠介, 髙橋秀徳, 川島英俊
    第34回JSCRS学術総会 2019年06月
  • 若年者の増殖糖尿病網膜症に対する硝子体手術成績  [通常講演]
    案浦加奈子, 新井悠介, 伊野田 悟, 坂本晋一, 佐野一矢, 井上裕治, 高橋秀徳, 川島秀俊
    第57回日本網膜硝子体学会総会 2018年12月
  • 眼科医にもできる人工知能AI研究  [招待講演]
    髙橋 秀徳
    第57回日本網膜硝子体学会総会 2018年12月
  • 網膜静脈分枝閉塞症に伴う黄斑浮腫に対するアフリベルセプト投与のmTAE法  [通常講演]
    新井悠介, 高橋秀徳, 青木真祐, 齋藤信一郎, 高橋雄二, 芝原勇麿, 大久保 彰, 伊野田 悟, 譚 雪, 間山千尋, 川島秀俊, 柳 靖雄
    第72回日本臨床眼科学会 2018年10月
  • Cherry-red spot を呈したgalactosialidosis の1例  [通常講演]
    福与波音, 井上裕治, 高橋秀徳, 川島秀俊
    第72回日本臨床眼科学会 2018年10月
  • 自治医大における網膜静脈分枝閉塞症に伴う硝子体出血に対する硝子体手術の検討  [通常講演]
    近藤由佳, 新井悠介, 髙橋秀徳, 坂本晋一, 伊野田 悟, 佐野一矢, 井上裕治, 川島秀俊
    第72回日本臨床眼科学会 2018年10月
  • 原因不明のβ-Dグルカン高値が継続しているASPPCの1例  [通常講演]
    高橋良太, 井上裕治, 渡辺芽里, 髙橋秀徳, 川島秀俊
    第55回日本眼感染症学会 2018年07月
  • Relationship between pachychoroid and aqueous humor concentrations of inflammatory cytokines in age-related macular degeneration  [通常講演]
    Onda M, Takahashi H, Inoue Y, Tan X, Arai Y, Takahashi R, Inoda S, Sakamoto S, Sano I, Fujino Y, Kawashima H
    ARVO Annual Meeting 2018 2018年05月
  • Correlation between iris posterior synechia severity and anterior chamber volume following Descemet’s Membrane Endothelial Keratoplasty  [通常講演]
    Shimizu T, Hayashi T, Yuda K, Takahashi H, Yamazaki K, Oyakawa I, Mizuki N, kato N
    ARVO Annual Meeting 2018 2018年04月
  • Deep-learning estimation of choroidal thickness from color fundus photographs: a validation study  [通常講演]
    Takahashi H, Arai Y, Yamashita T, Hasegawa T, Ohgami T, Sonoda S, Tanaka Y, Tampo H, Inoda S, Sakamoto S, Kakehashi A, Kawashima H
    ARVO Annual Meeting 2018 2018年04月
  • Aqueous humour metabolic profiles in typical age-related macular degeneration and polypoidal choroidal vasculopathy  [通常講演]
    Yanagi Y, Gao Y, Zhou L, Takahashi H, Fujino Y, Kawashima H
    ARVO Annual Meeting 2018 2018年04月
  • 深層学習によるカラー眼底写真からの脈絡膜厚推測―多施設での妥当性検討―  [通常講演]
    新井悠介, 高橋秀徳, 山下高明, 長谷川哲也, 大上智弘, 園田祥三, 田中克明, 反保宏信, 伊野田 悟, 坂本晋一, 梯 彰弘, 川島秀俊, 柳 靖雄
    第122回日本眼科学会総会 2018年04月
  • 加齢性黄斑変性における脈絡膜透過性亢進の有無による光線力学療法への反応性の検討  [通常講演]
    長岡広祐, 高橋良太, 添田めぐみ, 伊野田 悟, 坂本晋一, 新井悠介, 井上裕治, 髙橋秀徳, 川島秀俊
    第122回日本眼科学会総会 2018年04月
  • 滲出型加齢黄斑変性におけるpachyvessel 所見の有無と炎症性サイトカインの関連  [通常講演]
    恩田昌紀, 髙橋秀徳, 井上裕治, 譚雪, 新井悠介, 高橋良太, 伊野田 悟, 坂本晋一, 佐野一矢, 藤野雄次郎, 川島秀俊, 柳 靖雄
    第122回日本眼科学会総会 2018年04月
  • 網膜色素上皮剝離から中心性漿液性脈絡網膜症に移行した2例  [通常講演]
    恩田昌紀, 井上裕治, 伊野田悟, 坂本晋一, 新井悠介, 髙橋秀徳, 川島秀俊
    第56回日本網膜硝子体学会総会 2017年12月
  • 視力良好な加齢黄斑変性に対するアフリベルセプトの視力維持の条件検討  [通常講演]
    伊野田悟, 髙橋秀徳, 新井悠介, 坂本晋一, 井上裕治, 藤野雄次郎, 川島秀俊, 柳靖雄
    第56回日本網膜硝子体学会総会 2017年12月
  • 網脈絡膜萎縮発症時に脈絡膜肥厚と脈絡膜から色素上皮上への滲出が観察された1例  [通常講演]
    粕谷友香, 新井悠介, 髙橋秀徳, 伊野田悟, 坂本晋一, 井上裕治, 川島秀俊, 柳靖雄
    第71回日本臨床眼科学会 2017年10月
  • 視力良好ポリープ状脈絡膜血管症に対するアフリベルセプト:タイプ別解析  [通常講演]
    新井悠介, 髙橋秀徳, 伊野田悟, 坂本晋一, 井上裕治, 藤野雄次郎, 川島秀俊, 柳靖雄
    第71回日本臨床眼科学会 2017年10月
  • Deep-learning estimation choroidal thickness form color fundus photographs  [通常講演]
    Tampo H, Takahashi H, Yanagi Y, Sakamoto S, Inoda S, Kawashima H, Inoue Y, Arai Y, Takahashi R, Soeta M
    The Association for Research in Vision and Ophthalmology 2017年05月
  • 深層学習によるカラー眼底写真からの脈絡膜厚推測  [通常講演]
    反保宏信, 髙橋秀徳, 添田めぐみ, 高橋良太, 伊野田悟, 坂本晋一, 新井悠介, 井上裕治, 川島秀俊, 柳靖雄
    第121回日本眼科学会総会 2017年04月
  • 滲出型加齢黄斑変性の視力良好例に対するアフリベルセプト計画的投与  [通常講演]
    坂本晋一, 髙橋秀徳, 富永聡子, 佐藤彩, 竹澤美貴子, 井上裕治, 藤野雄次郎, 田邊樹郎, 川島秀俊
    第55回日本網膜硝子体学会総会 2016年12月
  • 脈絡膜新生血管を伴わない網膜色素上皮剥離のベルテポルフィン半量光線力学療法の検討  [通常講演]
    伊野田悟, 反保宏信, 髙橋秀徳, 井上裕治, 佐藤彩, 竹澤美貴子, 川島秀俊
    第70回日本臨床眼科学会 2016年11月
  • Effects of central macular thickness on visual and anatomical outcomes in age-related macular degeneration patients: comparison between ranibizumab and aflibercept  [通常講演]
    Sakamoto S, Takahashi H, Inoue Y, Yanagi Y, Sato A, Takezawa M, Tanabe T, Fujino Y, Kawashima H
    The Association for Research in Vision and Ophthalmology 2016年05月
  • 加齢黄斑変性に対するラニビズマブとアフリベルセプト短期予後の差と中心網膜厚の関連  [通常講演]
    坂本晋一, 髙橋秀徳, 井上裕治, 柳靖雄, 佐藤彩, 竹澤美貴子, 田邊樹郎, 藤野雄次郎, 川島秀俊
    第120回日本眼科学会総会 2016年04月
  • 滲出型加齢黄斑変性の視力良好例に対するアフリベルセプト計画的投与  [通常講演]
    坂本晋一, 髙橋秀徳, 富永聡子, 佐藤彩, 竹澤美貴子, 井上裕治, 藤野雄次郎, 田邊樹郎, 川島秀俊
    第54回日本網膜硝子体学会総会 2015年12月
  • 硝子体側に血管進展があり硝子体出血を繰り返すRetinalastrocytic hamartomaの特殊例  [通常講演]
    添田めぐみ, 新井悠介, 髙橋秀徳, 井上裕治, 藤野雄次郎, 田邊樹郎, 川島秀俊
    第69回日本臨床眼科学会 2015年10月
  • 脈絡膜新生血管におけるケモカイン受容体CXCR3の関与  [通常講演]
    髙橋 秀徳, 藤村茂人, 湯田健太郎, 上田高志, 井上達也, 柳靖雄, 蕪城俊克, 玉置泰裕, 松島綱冶
    第115回日本眼科学会総会 2015年05月
  • Aqueous humor inflammatory cytokine levels in chronic retinal vein occlusion  [通常講演]
    Inoda S, Takahashi H, Tan X, Kakinuma N, Nomura Y, Sakamoto S, Arai Y, Fujino Y, Kawashima H, Yanagi Y
    The Association for Research in Vision and Ophthalmology 2015年05月
  • 滲出型加齢黄斑変性に対する抗血管内皮増殖因子療法中の過度な網膜菲薄化と視力低下  [通常講演]
    髙橋秀徳, 坂本晋一, 垣沼奈津子, 富永聡子, 佐藤彩, 竹澤美貴子, 斎藤由香, 斎藤信一郎, 新井悠介, 藤野雄次郎, 川島秀俊, 柳靖雄
    第119回日本眼科学会総会 2015年04月
  • 増殖糖尿病網膜症に対する硝子体手術の合併症-20ゲージと23ゲージの比較  [通常講演]
    嘉村由美, 中島基宏, 大河原百合子, 髙橋秀徳, 佐藤幸裕
    第119回日本眼科学会総会 2015年04月
  • 網膜静脈閉塞症慢性期における前房中炎症性サイトカイン濃度  [通常講演]
    伊野田悟, 髙橋秀徳, 譚雪, 垣沼奈津子, 野村陽子, 坂本晋一, 新井悠介, 富永聡子, 佐藤彩, 藤野雄次郎, 川島秀俊, 柳靖雄
    第119回日本眼科学会総会 2015年04月
  • 糖尿病患者の眼底スクリーニング―散瞳2方向と4方向カラー撮影の比較  [通常講演]
    反保宏信, 大河原百合子, 髙橋秀徳, 佐藤幸裕
    第20回日本糖尿病眼学会総会 2015年03月
  • 滲出型加齢黄斑変性における炎症系サイトカイン前房中濃度と治療予後の関連  [通常講演]
    髙橋秀徳, 譚雪, 垣沼奈津子, 坂本晋一, 野村陽子, 藤野雄次郎, 新井悠介, 佐藤彩, 竹澤美貴子, 川島秀俊, 青木彩, 柳靖雄
    第68回日本臨床眼科学会 2014年11月
  • Changes in the concentrations of various cytokines in the anterior chamber at the induction phase of ranibizumab treatment in age-related macular degeneration  [通常講演]
    Sakamoto Shinichi, Takahashi Hidenori, Tan Xue, Nomura Youko, Iriyama Aya, Fujino Yujiro, Sato Aya, Takezawa Mikiko, Kawashima Hidetoshi, Yanagi Yasuo
    The Association for Research in Vision and Ophthalmology 2014年05月
  • 増殖硝子体網膜症に対する硝子体手術後の血管新生緑内障  [通常講演]
    大河原百合子, 髙橋秀徳, 佐藤幸裕
    第118回日本眼科学会総会 2014年04月
  • Two age-related macular degeneration patients whose choroidal thickness has decreased rapidly before polypoid leseion appeared  [通常講演]
    Shin-ichi Sakamoto, Hidenori Takahashi, Yujiro Fujino, Yasuo Yanagi, Hidetoshi Kawashima
    The World Ophthalmology Congress (WOC) 2014年04月
  • Occult Macular Dystrophy With Bilateral Chronic Subfoveal Serous Retinal Detachment.  [通常講演]
    Hidenori Takahashi, Takaaki Hayashi, Hiroshi Tsuneoka, Yujiro Fujino, Miwako Yoshimoto, Hidetoshi Kawashima
    Annual Meeting of Japanese Retina and Vitreous SocietyThe 8th Congress of Asia Pacific Vitreo-retina Society (APVRS) 2013年12月
  • ラニビズマブ頻回投与中に脈絡膜が著明に菲薄化した1例  [通常講演]
    坂本晋一, 新井悠介, 髙橋秀徳, 藤野雄次郎, 小畑亮, 柳靖雄, 川島秀俊
    第30回日本眼循環学会 2013年07月
  • Associations between Posterior Vitreous Detachment and Concentrations of Various Cytokines in Eyes with Age-related Macular Degeneration and Normal Control Eyes  [通常講演]
    Hidenori Takahashi, Tan Xue, Nomura Youko, Iriyama Aya, Fujino Yujiro, Okubo Yuko, Sato Aya, Takezawa Mikiko, Kawashima Hidetoshi, Yanagi, Yasuo
    The Association for Research in Vision and Ophthalmology 2013年05月
  • 加齢黄斑変性および正常対象眼における後部硝子体剥離と各種サイトカイン濃度の関連  [通常講演]
    髙橋 秀徳, 譚雪, 柳靖雄, 野村陽子, 藤村茂人, 川島秀俊
    第117回日本眼科学会総会 2013年04月
  • In vitroにおけるレチノールの網膜色素上皮細胞に対する作用  [通常講演]
    髙橋 秀徳, 譚雪, 入山彩, 湯田健太郎, 野村陽子, 井上達也, 小畑亮, 柳靖雄
    厚生労働省難治性疾患克服研究事業網膜脈絡膜・視神経萎縮症調査研究班平成24年度班会議 2013年01月
  • 加齢黄斑変性および正常対象眼における後部硝子体剥離と各種サイトカイン濃度の関連  [通常講演]
    髙橋 秀徳, 譚雪, 野村陽子, 藤村茂人, 湯田健太郎, 入山彩, 藤野雄次郎, 大久保裕子, 佐藤彩, 竹澤美貴子, 川島秀俊, 柳靖雄
    厚生労働省難治性疾患克服研究事業網膜脈絡膜・視神経萎縮症調査研究班平成24年度班会議 2013年01月
  • 加齢黄斑変性に対するラニビズマブ投与推奨から実際の投与までの遅れと視力予後の関連  [通常講演]
    髙橋 秀徳, 佐藤彩, 竹澤美貴子, 藤野雄次郎, 柳靖雄, 川島秀俊
    第51回日本網膜硝子体学会総会 2012年11月
  • Association Of Dietary Intake Of N-3 Fatty Acid And Exudative Age Related Macular Degeneration In Japan  [通常講演]
    Aya Iriyama, Kayo Kure, Yoko Nomura, Kenichirou Yuda, Hidenori Takahashi, Tkashi Ueta, Tatuya Inoue, Ryo Obata, Yasuo Yanagi
    The Association for Research in Vision and Ophthalmology Fort Lauderdale 2012年05月
  • Errors In Measuring VEGF Concentrations In The Presence Of Anti-VEGF Antibodies By Using ELISA  [通常講演]
    Hidenori Takahashi, Yujiro Fujino, Yasuo Yanagi
    The Association for Research in Vision and Ophthalmology Fort Lauderdale 2012年05月
  • ポリープ状脈絡膜血管症に対するラニビズマブ治療の1年成績に関連する治療前因子  [通常講演]
    髙橋 秀徳, 小畑亮, 柳靖雄, 湯田健太郎, 上田高志, 藤村茂人, 入山彩, 本多麻衣子, 足立知子, 井上裕治, 野村陽子, 井上達也, 玉置泰裕
    第116回日本眼科学会総会 2012年04月
  • マウス高酸素負荷網膜血管新生モデルにおけるCXCR3の影響  [通常講演]
    髙橋 秀徳, 湯田健太郎, 藤村茂人, 門之園一明, 柳靖雄
    第116回日本眼科学会総会 2012年04月
  • 抗VEGF抗体存在下のELISAによるVEGF濃度測定誤差  [通常講演]
    髙橋 秀徳, 藤野雄次郎, 柳靖雄
    第116回日本眼科学会総会 2012年04月
  • 狭義加齢黄斑変性およびポリープ状脈絡膜血管症に対するラニビズマブ硝子体注入の効果  [通常講演]
    髙橋 秀徳, 入山彩, 呉香代, 湯田健太郎, 上田高志, 井上達也, 小畑亮, 柳靖雄, 玉置泰裕
    第65回日本臨床眼科学会 2011年10月
  • 片眼性の滲出性加齢黄斑変性僚眼の脈絡膜異常血管を有する頻度と経過  [通常講演]
    髙橋 秀徳, 本多麻衣子, 上田高志, 藤村茂人, 柳靖雄, 玉置泰裕
    第65回日本臨床眼科学会 2011年10月
  • 加齢黄斑変性における後部硝子体剥離と前房水中VEGF濃度の関連  [通常講演]
    髙橋 秀徳, 柳靖雄, 小畑亮, 藤野雄次郎, 入山彩, 玉置泰裕
    第65回日本臨床眼科学会 2011年10月
  • 加齢黄斑変性と後部硝子体剥離に関連はあるか?  [通常講演]
    髙橋 秀徳
    第9回「TOKYO眼科病診連携の会」 2011年07月
  • デング熱罹患後に視力低下を認めた1例  [通常講演]
    髙橋 秀徳, 山本和弘, 譚雪, 杉山浩司, 野田康雄, 菅野美貴子, 藤野雄次郎
    第48回日本眼感染症学会 2011年07月
  • クラシックCNV所見を有するポリープ状脈絡膜血管症へのラニビズマプの効果  [通常講演]
    髙橋 秀徳, 小畑亮, 柳靖雄, 湯田健太郎, 呉香代, 上日高志, 藤村茂人, 入山彩, 本多麻衣子, 足立知子, 井上達也, 玉置泰裕
    第115回日本眼科学会総会 2011年05月
  • 後部硝子体剥離と前房中VEGF濃度の関連  [通常講演]
    髙橋 秀徳, 柳靖雄, 小畑亮, 藤野雄次郎, 稲用和也, 野田康雄, 玉置泰裕
    第115回日本眼科学会総会 2011年05月
  • Relationship between Posterior Vitreous Detachment and Concentration of VEGF in Fluid of the Anterior Chamber  [通常講演]
    Hidenori Takahashi, Yasuo Yanagi, Ryo Obata, Yujiro Fujino, Kazuya Inamochi, Yasuo Noda, Yasuhiro Tamaki
    The Association for Research in Vision and Ophthalmology 2011年05月
  • 日本人加齢黄斑変性患者におけるreticular pseudodrusenの頻度  [通常講演]
    髙橋 秀徳, 藤村茂人, 湯田健太郎, 野村陽子, 呉香代, 上田高志, 入山彩, 本多麻衣子, 井上達也, 小畑亮, 足立知子, 玉置泰裕, 柳靖雄
    第49回日本網膜硝子体学会総会 2010年11月
  • 糖尿病眼合併症に対する抗VEGF抗体  [通常講演]
    髙橋 秀徳
    第4回JTNカンファレンス 2010年11月
  • Predicting Renal Damage in Salt-Sensitive Hypertensive Rats by Measuring Retinal Vascular Leukocyte Adhesion  [通常講演]
    H. Takahashi, S. Nakagawa, Y. Wu, Y. Kawabata, A. Numabe, Y. Yanagi, Y. Tamaki, Y. Uehara, M. Araie
    The Association for Research in Vision and Ophthalmology 2010年05月
  • Adrenomedullinノックアウトマウスにおける炎症細胞浸潤を介した脈絡膜新生血管促進  [通常講演]
    髙橋 秀徳, 湯田健太郎, 井上達也, 上田高志, 永井良三, 柳靖雄, 玉置泰裕, 新家眞
    第114回日本眼科学会総会 2010年04月
  • 食塩感受性高血圧ラットにおける網膜血管の白血球接着の計測による腎障害の予測  [通常講演]
    髙橋 秀徳, 中川卓, Wu Yaqiong, 川畑ゆかり, 沼部敦司, 柳靖雄, 玉置泰裕, 上原譽志夫, 新家眞
    第114回日本眼科学会総会 2010年04月
  • 特異な中心窩下隆起病巣により片眼性に視力低下を来したクリスタリン網膜症の2例  [通常講演]
    髙橋 秀徳
    第48回日本網膜硝子体学会総会 2009年12月
  • 中心性漿液性網脈絡膜症の既往とポリープ状脈絡膜血管症の発症  [通常講演]
    髙橋 秀徳, 上田高志, 柳靖雄, 藤村茂人, 井上達也, 入山彩, 小畑亮, 井上裕治, 玉置泰裕
    第113回日本眼科学会総会 2009年04月
  • VEGF及び受容体を標的にしたWrapped Liposome/siRNA全身投与における臓器副作用の検討  [通常講演]
    髙橋 秀徳, 八木信宏, 山内雅博, 柳靖雄, 玉置泰裕, 真鍋一郎, 永井良三
    第113回日本眼科学会総会 2009年04月
  • スペクトラルドメイン光干渉断層計による滲出型加齢黄斑変性僚眼の前駆病変の検討  [通常講演]
    髙橋 秀徳, 小畑亮, 湯田健太郎, 上田高志, 藤村茂人, 入山彩, 井上裕治, 柳靖雄, 玉置泰裕, 新家眞
    厚生労働省難治性疾患克服研究事業網膜脈絡膜・視神経萎縮症調査研究班2008年度班会議 2009年01月
  • ダール食塩感受性高血圧ラットにおける網膜血管の白血球接着と腎障害の関連性  [通常講演]
    髙橋 秀徳, 中川卓, Wu Yaqiong, 入山彩, 小畑亮, 井上裕治, 柳靖雄, 玉置泰裕, 沼部敦司, 上原譽志夫, 新家眞
    厚生労働省難治性疾患克服研究事業網膜脈絡膜・視神経萎縮症調査研究班2008年度班会議 2009年01月
  • Wrapped Liposome siRNAを用いた抗VEGF療法のマウスにおける全身的影響  [通常講演]
    髙橋 秀徳, 八木信宏, 山内雅博, 柳靖雄, 玉置泰裕, 真鍋一郎, 永井良三
    第47回日本網膜硝子体学会総会 2008年11月
  • スペクトラルドメインOCTによる滲出型加齢黄斑変性における網膜神経線維層厚の検討  [通常講演]
    髙橋 秀徳, 湯田健太郎, 井上裕治, 上田高志, 入山彩, 小畑亮, 足立知子, 柳靖雄, 玉置泰裕, 今野伸介, 富所敦男
    第62回日本臨床眼科学会 2008年10月
  • 視力良好なAMDに対する抗VEGF療法  [通常講演]
    髙橋 秀徳, 足立知子, 上田高志, 入山彩, 小畑亮, 井上裕治, 柳靖雄, 玉置泰裕
    第62回日本臨床眼科学会 2008年10月
  • 3次元光干渉断層計を用いた加齢黄斑変性前駆病変における網膜硝子体界面異常の観察  [通常講演]
    髙橋 秀徳, 小畑亮, 湯田健太郎, 上田高志, 藤村茂人, 入山彩, 井上裕治, 足立知子, 柳靖雄, 玉置泰裕
    第62回日本臨床眼科学会 2008年10月
  • 加齢性黄斑変性における後部硝子体癒着の有無と光線力学療法の治療成績との関連  [通常講演]
    髙橋 秀徳, 野村陽子, 上田高志, 入山彩, 小畑亮, 井上裕治, 足立知子, 柳靖雄, 玉置泰裕
    第62回日本臨床眼科学会 2008年10月
  • クリスタリン網膜症の眼底時価蛍光と3次元OCTの検討  [通常講演]
    髙橋 秀徳, 入山彩, 井上裕治, 玉置泰裕, 柳靖雄
    第62回日本臨床眼科学会 2008年10月
  • 脈絡膜新生血管に対するヒト血管内皮増殖因子受容体2由来ペプチドを用いた免疫療法  [通常講演]
    髙橋 秀徳
    第62回日本臨床眼科学会 2008年10月
  • The mechanisms of susceptibility of Dahl strain to hypertensive kidney damage  [通常講演]
    Wu Yaqiong, Hidenori Takahashi, Atsushi Numabe, Yasuo Yanagi, Yasuhiro Tamaki, Makoto Araie, Yoshio Uehara
    Hypertension 2008年06月
  • Angiotensin subtype-1 receptor antagonist losartan and regulator of G-protein signalling 2 in kidney damage in dahl salt-sensitive rat  [通常講演]
    Hidenori Takahashi, Wu Yaqiong, Atsushi Numabe, Yasuo Yanagi, Yasuhiro Tamaki, Makoto Araie, Yoshio Uehara
    Hypertension 2008年06月
  • Posterior Vitreomacular Adhesion in Exudative Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy  [通常講演]
    Yoko Momura, Takashi Ueta, Aya Iriyama, Yuji Inoue, Ryo Obata, Hidenori Takahashi, Yasuo Yanagi, Yasuhiro Tamaki
    The Association for Research in Vision and Ophthalmology 2008年04月
  • Intravitreal Bevacizumab Injection for Treatment of Macular Edema Due to Retinal Vein Occlusion in Previously Vitrectomized Eyes  [通常講演]
    Kayo Kure, Yasuo Yanagi, Ryo Obata, Yuji Inoue, Hidenori Takahashi, Aya Iriyama, Yasuhiro Tamaki
    The Association for Research in Vision and Ophthalmology 2008年04月
  • Leukocyte Adhesion to Retinal Blood Vessel is Correlated With the Renal Damage of Dahl Salt-Sensitive Rat  [通常講演]
    Hidenori Takahashi, Wu Yaqiong, Aaya Iriyama, Ryo Obata, Yuji Inoue, Atsushi Numabe, Yasuo Yanagi, Yasuhiro Tamaki, Makoto Araie, Yoshio Uehara
    The Association for Research in Vision and Ophthalmology 2008年04月
  • 狭義加齢黄斑変性とポリープ状脈絡膜血管症における硝子体牽引の病態への関与  [通常講演]
    野村陽子, 上田高志, 入山彩, 髙橋秀徳, 小畑亮, 井上裕治, 足立知子, 柳靖雄, 玉置泰裕
    第112回日本眼科学会総会 2008年04月
  • 日本人の加齢黄斑変性症における光線力学療法-初診後1年の視力予後評価  [通常講演]
    上田高志, 柳靖雄, 入山彩, 髙橋秀徳, 足立知子, 小畑亮, 井上裕治, 玉置泰裕
    第112回日本眼科学会総会 2008年04月
  • 3次元光干渉断層計による加齢黄斑変性前駆病変の観察  [通常講演]
    小畑亮, 上田高志, 入山彩, 高橋秀徳, 井上裕治, 足立知子, 柳靖雄, 玉置泰裕
    第112回日本眼科学会総会 2008年04月
  • 高血圧ラットの臓器障害に及ぼすFluvastatinの影響と網膜血管の白血球接着との関連性  [通常講演]
    髙橋 秀徳, Wu Yaqiong, 入山彩, 小畑亮, 井上裕治, 柳靖雄, 玉置泰裕, 沼部敦司, 上原譽志夫, 新家眞
    第112回日本眼科学会総会 2008年04月
  • 高血圧ラットの臓器障害に及ぼすFluvastatinの影響と網膜血管の白血球接着との関連性  [通常講演]
    髙橋 秀徳, Wu Yaqiong, 入山彩, 小畑亮, 井上裕治, 柳靖雄, 玉置泰裕, 沼部敦司, 上原譽志夫, 新家眞
    厚生労働省難治性疾患克服研究事業網膜脈絡膜・視神経萎縮症調査研究班2007年度班会議 2008年01月
  • The mechanisms of susceptibility of dahl strain to hypertensive kidney damage  [通常講演]
    Wu Qyaning, Hidenori Takahashi, Atsushi Numabe, Yasuo Yanagi, Yasuhiro Tamaki, Makoto Araie, Yoshio Uehara
    ISN NEXUS SYMPOSIUM Hypertension and the Kidney 2007年11月
  • White blood cell adhesion and angiotensin ii mechanism in kidney damage in dahl salt-sensitive rats  [通常講演]
    Hidenori Takahashi, Wu Qyaning, Atsushi Numabe, Yasuo Yanagi, Yasuhiro Tamaki, Makoto Araie, Yoshio Uehara
    ISN NEXUS SYMPOSIUM Hypertension and the Kidney 2007年11月
  • Dahl食塩感受性ラットの易腎障害性の機序と血圧上昇の役割  [通常講演]
    Wu Yaqiong, 髙橋秀徳, 柳靖雄, 玉置泰裕, 沼部敦司, 新家眞, 上原譽志夫
    第30回日本高血圧学会総会 2007年10月
  • Dahl食塩感受性ラット腎障害に及ぼすアンギオテンシン受容体拮抗薬の影響と血管白血球接着との関連性  [通常講演]
    髙橋 秀徳, Wu Yaqiong, 柳靖雄, 玉置泰裕, 沼部敦司, 新家眞, 上原譽志夫
    第30回日本高血圧学会総会 2007年10月
  • 黄斑浮腫を伴う網膜静脈閉塞症に対するbevacizumab(avastin R)硝子体注入  [通常講演]
    呉香代, 入山彩, 髙橋秀徳, 小畑亮, 井上裕治, 柳靖雄, 玉置泰裕
    第61回日本臨床眼科学会 2007年10月
  • 強度近視による脈絡膜新生血管に対する新生血管抜去術の長期成績  [通常講演]
    井上裕治, 足立知子, 小畑亮, 髙橋秀徳, 入山彩, 上田高志, 柳靖雄, 玉置泰裕
    第61回日本臨床眼科学会 2007年10月
  • 視力良好例に対するbevacizumab(Avastin)硝子体投与  [通常講演]
    足立知子, 髙橋秀徳, 上田高志, 入山彩, 小畑亮, 井上裕治, 柳靖雄, 玉置泰裕
    第61回日本臨床眼科学会 2007年10月
  • トリアムシノロン併用光線力学的療法の1年目の治療成績  [通常講演]
    入山彩, 柳靖雄, 小畑亮, 上田高志, 髙橋秀徳, 井上裕治, 足立知子, 玉置泰裕
    第61回日本臨床眼科学会 2007年10月
  • 狭義加齢性黄斑変性とポリープ状脈絡膜血管症の危険因子について  [通常講演]
    上田高志, 入山彩, 髙橋秀徳, 小畑亮, 井上裕治, 足立知子, 柳靖雄, 玉置泰裕, 新家眞
    第61回日本臨床眼科学会 2007年10月
  • 光線力学療法とベバシズマブ硝子体投与の併用療法を行った4例  [通常講演]
    髙橋 秀徳, 上田高志, 入山彩, 小畑亮, 井上裕治, 足立知子, 柳靖雄, 玉置泰裕
    第61回日本臨床眼科学会 2007年10月
  • Immunotherapy Using the Epitope Peptides Derived From Vascular Endothelial Growth Factor Receptor 2 Suppresses Choroidal Neovascularization in a Mouse Model  [通常講演]
    Hidenori Takahashi, Hidenobu Ishizaki, Yasuo Yanagi, Yasuhiro Tamaki, Hideaki Tahara
    The Association for Research in Vision and Ophthalmology 2007年05月
  • 狭義滲出型加齢黄斑変性症とポリープ状脈絡膜血管症の片眼発症症例の僚眼発症率の比較  [通常講演]
    上田高志, 柳靖雄, 小畑亮, 入山彩, 髙橋秀徳, 井上裕治, 足立知子, 玉置泰裕
    第111回日本眼科学会総会 2007年04月
  • 光線力学療法後の経過と光干渉断層計所見  [通常講演]
    小畑亮, 入山彩, 髙橋秀徳, 井上裕治, 足立知子, 上田高志, 柳靖雄, 玉置泰裕
    第111回日本眼科学会総会 2007年04月
  • 脈絡膜新生血管治療を目標とした血管内皮増殖因子受容体2由来抗原によるワクチン療法のマウスモデルでの検討  [通常講演]
    髙橋秀徳, 石崎秀信, 柳靖雄, 玉置泰裕, 田原秀晃, 新家眞
    第111回日本眼科学会総会 2007年04月
  • 血管内皮増殖因子受容体2選択的阻害薬の同定、および、マウス脈絡膜新生血管モデルを用いた検討  [通常講演]
    髙橋秀徳, 石井暢也, 及川信宏, 水口栄作, 玉置泰裕, 柳靖雄, 井上裕治
    第111回日本眼科学会総会:黄斑研究会 2007年04月
  • 片眼の視力が良好な黄斑疾患症例の視覚関連quality of life  [通常講演]
    小畑亮, 柳靖雄, 上順子, 井上裕治, 髙橋秀徳, 入山彩, 玉置泰裕, 新家眞
    厚生労働省難治性疾患克服研究事業網膜脈絡膜・視神経萎縮症調査研究班2006年度班会議 2007年01月
  • 網膜変性症モデルラットに対する骨髄間葉系幹細胞網膜下移植による網膜変性抑制効果  [通常講演]
    井上裕治, 入山彩, 髙橋秀徳, 柳靖雄, 相原一, 玉置泰裕, 新家眞, 上野真治, 近藤峰生
    厚生労働省難治性疾患克服研究事業網膜脈絡膜・視神経萎縮症調査研究班2006年度班会議 2007年01月
  • リポフスチン構成成分A2eの網膜色素上皮細胞および脈絡膜新生血管に及ぼす影響  [通常講演]
    入山彩, 髙橋秀徳, 柳靖雄, 玉置泰裕, 新家眞
    厚生労働省難治性疾患克服研究事業網膜脈絡膜・視神経萎縮症調査研究班2006年度班会議 2007年01月
  • Wrapped Liposome siRNAのマウス脈絡膜新生血管モデルにおける動態検討  [通常講演]
    髙橋秀徳, 小畑亮, 柳靖雄, 玉置泰裕, 真鍋一郎, 八木信宏, 山内雅博, 永井良三
    厚生労働省難治性疾患克服研究事業網膜脈絡膜・視神経萎縮症調査研究班2006年度班会議 2007年01月
  • Blood Pressure Rising Determines Adhesion of White Blood Cells To Retinal Artery In Young Spontaneously Hypertensive Rats  [通常講演]
    Hidenori Takahashi, Wu Yaqiong, Yasuo Yanagi, Yukari Kawabata, Hideyuki Negoro, Makoto Araie, Yoshio Uehara
    The 21st Scientific Meeting of the International Society of Hypertension 2006年10月
  • 光線力学療法の3ヶ月後の再治療率および脈絡膜毛細血管板の閉塞に対するトリアムシノロンの影響  [通常講演]
    入山彩, 柳靖雄, 小畑亮, 井上裕治, 髙橋秀徳, 上順子, 足立知子, 玉置泰裕
    第60回日本臨床眼科学会 2006年10月
  • 光干渉断層計を用いた光線力学療法後の新生血管活動性評価  [通常講演]
    小畑亮, 入山彩, 髙橋秀徳, 井上裕治, 足立知子, 柳靖雄, 玉置泰裕
    第60回日本臨床眼科学会 2006年10月
  • Idiopathic juxtafoveal telangiectasia group2Aの1症例  [通常講演]
    髙橋秀徳, 小畑亮, 入山彩, 井上裕治, 柳靖雄, 玉置泰裕
    第60回日本臨床眼科学会 2006年10月
  • Subretinal Transplantation of Bone Marrow Stromal Stem Cells Delays Retinal Degeneration in Royal College of Surgeon Rats  [通常講演]
    Y.Inoue, A.Iriyama, H.Takahashi, Y.Yanagi, S.Ueno, M.Kondo, M.Aihara, Y.Tamaki, M.Araie
    The Association for Research in Vision and Ophthalmology 2006年04月
  • Role of A2e in the Pathogenesis of CNV  [通常講演]
    A.Iriyama, Y.Yanagi, Y.Inoue, H.Takahashi, Y.Tamaki
    The Association for Research in Vision and Ophthalmology 2006年04月
  • Influence Of Insulin Receptor Substrate-2-knockout On The Activity Of Experimental Choroidal Neovascular In Mice Model  [通常講演]
    Hidenori Takahashi, Ryo Obata, Yasuo Yanagi, Yasuhiro Tamaki, Yasuo Terauchi, Takashi Kadowaki
    The Association for Research in Vision and Ophthalmology 2006年04月
  • Wrapped Liposome siRNAのマウス脈絡膜新生血管モデルにおける動態検討  [通常講演]
    髙橋秀徳, 小畑亮, 柳靖雄, 玉置泰裕, 真鍋一郎, 八木信宏, 山内雅博
    第110回日本眼科学会総会 2006年04月
  • 網膜変性症モデルラットに対する骨髄間葉系幹細胞網膜下移植による網膜変性抑制効果  [通常講演]
    井上裕治, 入山彩, 髙橋秀徳, 柳靖雄, 相原一, 玉置泰裕, 新家眞, 上野真治, 近藤峰生
    第110回日本眼科学会総会 2006年04月
  • リポフスチン構成成分A2eの網膜色素上皮細胞および脈絡膜新生血管に及ぼす影響  [通常講演]
    入山彩, 柳靖雄, 井上裕治, 髙橋秀徳, 玉置泰裕
    第110回日本眼科学会総会 2006年04月
  • KDR阻害薬の脈絡膜新生血管抑制効果  [通常講演]
    小畑亮, 髙橋秀徳, 柳靖雄, 玉置泰裕
    第110回日本眼科学会総会 2006年04月
  • マウス脈絡膜新生血管モデルにおけるインスリン受容体基質2の作用  [通常講演]
    髙橋秀徳, 小畑亮, 柳靖雄, 玉置泰裕, 寺内康夫, 門脇孝
    第110回日本眼科学会総会 2006年04月
  • 網膜変性症モデルラットに対する骨髄間葉系幹細胞網膜下移植による網膜変性抑制効果  [通常講演]
    井上裕治, 入山彩, 髙橋秀徳, 柳靖雄, 相原一, 玉置泰裕, 新家眞, 上野真治, 近藤峰生
    厚生労働省難治性疾患克服研究事業網膜脈絡膜・視神経萎縮症調査研究班2005年度班会議 2006年01月
  • リポフスチン構成成分A2eの網膜色素上皮細胞および脈絡膜新生血管に及ぼす影響  [通常講演]
    入山彩, 髙橋秀徳, 柳靖雄, 玉置泰裕, 新家眞
    厚生労働省難治性疾患克服研究事業網膜脈絡膜・視神経萎縮症調査研究班2005年度班会議 2006年01月
  • 片眼の視力が良好な黄斑疾患症例の視覚関連quality of life  [通常講演]
    小畑亮, 柳靖雄, 上順子, 井上裕治, 髙橋秀徳, 入山彩, 玉置泰裕, 新家眞
    厚生労働省難治性疾患克服研究事業網膜脈絡膜・視神経萎縮症調査研究班2005年度班会議 2006年01月
  • Wrapped Liposome siRNAのマウス脈絡膜新生血管モデルにおける動態検討  [通常講演]
    髙橋秀徳, 小畑亮, 柳靖雄, 玉置泰裕, 真鍋一郎, 八木信宏, 山内雅博, 永井良三
    厚生労働省難治性疾患克服研究事業網膜脈絡膜・視神経萎縮症調査研究班2005年度班会議 2006年01月
  • マウス脈絡膜新生血管モデルの検討方法  [通常講演]
    髙橋秀徳, 村中公正, 柳靖雄, 玉置泰裕
    第25回日本眼薬理学会 2005年07月
  • マウス脈絡膜新生血管モデルの活動性に対する加齢の影響  [通常講演]
    髙橋秀徳, 小畑亮, 柳靖雄, 玉置泰裕
    第109回日本眼科学会総会 2005年05月
  • Influence of Age on the Activity of Experimental CNV in Mice Model  [通常講演]
    H.Takahashi, R.Obata, Y.Yanagi, Y.Tamaki
    The Association for Research in Vision and Ophthalmology 2005年05月
  • 25Gシステム硝子体手術の眼内照明による光毒性の検討  [通常講演]
    柳靖雄, 小畑亮, 井上裕治, 髙橋秀徳, 玉置泰裕, 門之園一明
    第109回日本眼科学会総会 2005年03月
  • 新規3元系コンプレックスによる網膜組織の光選択的遺伝子導入  [通常講演]
    井上裕治, 入山彩, 髙橋秀徳, 柳靖雄, 玉置泰裕, 西山信宏, 張ウードン, 片岡一則
    第109回日本眼科学会総会 2005年03月
  • 光線照射部位に選択的な遺伝子導入法の開発と結膜組織への応用  [通常講演]
    入山彩, 井上裕治, 髙橋秀徳, 柳靖雄, 玉置泰裕, 西山信宏, 張ウードン, 片岡一則
    第109回日本眼科学会総会 2005年03月
  • ヒト血清含有培地を用いた、脈絡膜新生血管摘出標本からの網膜色素細胞培養  [通常講演]
    小畑亮, 髙橋秀徳, 井上裕治, 柳靖雄, 玉置泰裕
    第109回日本眼科学会総会 2005年03月
  • マウス脈絡膜新生血管モデルにおけるADAMTS-1の作用  [通常講演]
    上順子, 髙橋秀徳, 小畑亮, 柳靖雄, 玉置泰裕, 武田憲文, 新藤隆行
    第109回日本眼科学会総会 2005年03月
  • マウス脈絡膜新生血管モデルにおけるアドレノメデュリンの作用  [通常講演]
    髙橋秀徳, 上順子, 柳靖雄, 玉置泰裕, 武田憲文, 新藤隆行
    第109回日本眼科学会総会 2005年03月
  • Retinoic acid receptor agonist Am90 inhibits experimental choroidal neovasucularization  [通常講演]
    J.Kami, H.Takahashi, Y.Yanagi, Y.Tamaki, H.Kagetika, T.Shindou, R.Nagai
    The Association for Research in Vision and Ophthalmology 2004年04月
  • Roles of Intestinal Kruppel-like Factor in the genesis of retinopathy of prematurity  [通常講演]
    H.Takahashi, K.Matsuura, Y.Inoue, K.Muranaka, Y.Yanagi, Y.Tamaki, N.Takeda, T.Shindo, R.Nagai
    The Association for Research in Vision and Ophthalmology 2004年04月
  • レチノイン酸受容体特異的アゴニストによるマウス脈絡膜新生血管モデルの抑制効果  [通常講演]
    上順子, 髙橋秀徳, 柳靖雄, 玉置泰裕, 影近弘之, 新藤隆行, 永井良三, 新家眞
    厚生労働省難治性疾患克服研究事業網膜脈絡膜・視神経萎縮症調査研究班2003年度班会議 2004年01月
  • マウス未熟児網膜症モデルにおけるintestinal kruppel-like factorの役割  [通常講演]
    髙橋秀徳, 松浦恭祐, 井上祐治, 村中公正, 柳靖雄, 玉置泰裕, 武田憲文, 新藤隆行, 永井良三, 新家眞
    厚生労働省難治性疾患克服研究事業網膜脈絡膜・視神経萎縮症調査研究班2003年度班会議 2004年01月
  • マウス脈絡膜血管新生モデルにおける骨髄細胞の関与  [通常講演]
    髙橋 秀徳
    第107回日本眼科学会総会 2003年04月

MISC

  • AIで眼底画像診断の効率性を上げ失明が少ない社会をめざす
    髙橋秀徳 厚生労働 (11) 56 -57 2021年11月 [査読無し][招待有り]
  • 眼科医が一からはじめるAIの開発・研究
    髙橋秀徳 Journal of Retina Medicine 10 (2) 15 -20 2021年10月 [査読無し][招待有り]
  • 眼科向けクラウドAI画像診断支援ソリューションが医療機関にもたらすもの
    髙橋秀徳 月刊新医療 48 (9) 50 -53 2021年09月 [査読無し][招待有り]
  • 眼科向けAI画像診断支援ソリューション”DeepEyeVison"による読影医師負担低減
    髙橋秀徳 デジタルヘルストレンド 2021 「医療4.0」時代に向けた100社の取り組み 146 -147 2021年03月 [査読無し][招待有り]
  • 眼科向けAI眼底写真診断支援ソリューション"DeepEyeVison"が創出する診断品質および読影負担軽減
    髙橋秀徳 腎と透析 90 (2) 242 -246 2021年02月 [査読無し][招待有り]
  • 予防医学におけるAI画像診断の現状と展望 ー内視鏡AI,脳MRI,眼底画像診断を例にー
    多田智裕, 島原佑基, 髙橋秀徳 Medical Practice 38 (2) 188 -194 2021年 [査読無し][招待有り]
  • 眼科向けクラウドAI画像診断支援ソリューション”DeepEyeVison"が創出する診断品質及び医師負担低減への貢献~大学病院付属検診センターでの活用実績も含め~
    髙橋秀徳 月刊新医療 48 (1) 50 -53 2021年01月 [査読無し][招待有り]
  • ビッグデータ活用による眼科医療の近未来
    髙橋秀徳 日本眼科学会雑誌 124 (11) 851 -852 2020年11月 [査読無し][招待有り]
  • 緑内障:プロスタグランジン関連薬と瞳孔間距離
    善岡尊文, 伊野田 悟, 高橋秀徳 あたらしい眼科 37 (10) 97 -98 2020年10月 [査読無し][通常論文]
  • 眼科領域におけるAIを活用した診断支援ソリューションの開発経緯と今後の展開
    髙橋秀徳 月刊インナービジョン 35 (7) 44 -46 2020年07月 [査読無し][招待有り]
  • AIを用いた眼科研究の基本と進め方
    高橋秀徳 日本の眼科 91 (4) 502 -507 2020年04月 [査読無し][招待有り]
  • AIによる眼底診断
    髙橋 秀徳 プレシジョン メディシン 3 (2) 26 -29 2020年02月 [査読無し][招待有り]
  • 眼科のAIの動向
    髙橋 秀徳 カレントテラピー 38 (445) 82 -82 2020年02月 [査読無し][招待有り]
  • AIを用いた眼科研究
    髙橋秀徳 あたらしい眼科 37 (3) 95 -95 2020年 [査読無し][招待有り]
  • 伊野田 悟, 高橋 秀徳 あたらしい眼科 37 (1) 61 -62 2020年01月 [査読無し][通常論文]
     
    人工知能(AI)による画像解析の報告は日々増加している。光干渉断層計画像解析は広く行われ、加齢黄斑変性での漿液性網膜剥離の同定も可能となってきている。また、他科でもその高い画像解析能力を応用した臨床応用が試みられている。本稿ではAIの治療適応への応用について述べる。(著者抄録)
  • ディープラーニングって何ですか?
    髙橋 秀徳 先端医学社 RETINA Medicine 8 (2) 85 -85 2019年10月 [査読無し][招待有り]
  • 眼科AI(人工知能)
    髙橋 秀徳 IOL&RS 33 (2) 278 -283 2019年06月 [査読無し][招待有り]
  • 伊野田 悟, 高橋 秀徳 あたらしい眼科 36 (4) 441 -447 2019年04月 [査読無し][通常論文]
  • 石田 晋, 小沢 洋子, 近藤 峰生, 園田 康平, 高橋 秀徳, 中澤 徹, 三宅 正裕, 安川 力, 山城 健児 Retina Medicine 8 (1) 1 -9 2019年04月 [査読無し][招待有り]
  • 深層学習による光干渉断層計像からの最高矯正視力推測
    伊野田 悟, 高橋 秀徳, 新井 悠介, 反保 宏信, 坂本 晋一, 松井 良諭, 川島 秀俊, 柳 靖雄 日本眼科学会雑誌 123 (臨増) 291 -291 2019年03月 [査読無し][通常論文]
  • 糖尿病網膜症ディープラーニング
    髙橋 秀徳, 伊野田悟 全日本病院出版会 OCULISTA IT・AI未来眼科 69 17 -25 2018年12月 [査読無し][招待有り]
  • AIで変わる眼科診療
    髙橋 秀徳 先端医学社 RETINA Medicine 7 (2) 50 -54 2018年10月 [査読無し][招待有り]
  • 視力良好な加齢黄斑変性に対するアフリベルセプトの視力維持の条件検討
    伊野田 悟, 高橋 秀徳, 新井 悠介, 坂本 晋一, 井上 裕治, 藤野 雄次郎, 川島 秀俊, 柳 靖雄 眼科臨床紀要 11 (9) 708 -708 2018年09月 [査読無し][通常論文]
  • 滲出型加齢黄斑変性におけるpachyvessel所見の有無と炎症性サイトカインの関連
    恩田 昌紀, 高橋 秀徳, 井上 裕治, 譚 雪, 新井 悠介, 高橋 良太, 伊野田 悟, 坂本 晋一, 佐野 一矢, 藤野 雄次郎, 川島 秀俊, 柳 靖雄 眼科臨床紀要 11 (9) 718 -718 2018年09月 [査読無し][通常論文]
  • 糖尿病網膜症の新しい診断~従来の病期診断と人工知能(AI)の進歩について
    髙橋 秀徳 金原出版 眼科 60 (9) 927 -933 2018年09月 [査読無し][招待有り]
  • 眼科における人工知能
    髙橋 秀徳 医学書院 臨床眼科 72 (8) 1055 -1060 2018年08月 [査読無し][招待有り]
  • Masatoshi Onda, Hidenori Takahashi, Yuji Inoue, Xue Tan, Yusuke Arai, Ryota Takahashi, Satoru Inoda, Shinichi Sakamoto, Ichiya Sano, Yujiro Fujino, Hidetoshi Kawashima, Yasuo Yanagi INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 59 (9) 2018年07月 
    0
  • 網脈絡膜萎縮発症時に脈絡膜肥厚と脈絡膜から色素上皮上への滲出が観察された1例
    粕谷 友香, 新井 悠介, 高橋 秀徳, 伊野田 悟, 坂本 晋一, 井上 裕治, 川島 秀俊, 柳 靖雄 眼科臨床紀要 11 (5) 402 -402 2018年05月 [査読無し][通常論文]
  • 滲出型加齢黄斑変性におけるpachyvessel所見の有無と炎症性サイトカインの関連
    恩田 昌紀, 高橋 秀徳, 井上 裕治, 譚 雪, 新井 悠介, 高橋 良太, 伊野田 悟, 坂本 晋一, 佐野 一矢, 藤野 雄次郎, 川島 秀俊, 柳 靖雄 日本眼科学会雑誌 122 (臨増) 177 -177 2018年03月 [査読無し][通常論文]
  • 深層学習によるカラー眼底写真からの脈絡膜厚推測 多施設での妥当性検討
    新井 悠介, 高橋 秀徳, 山下 高明, 長谷川 哲也, 大上 智弘, 園田 祥三, 田中 克明, 反保 宏信, 伊野田 悟, 坂本 晋一, 梯 彰弘, 川島 秀俊, 柳 靖雄 日本眼科学会雑誌 122 (臨増) 235 -235 2018年03月 [査読無し][通常論文]
  • インキュベーションスペース『KERNEL』メンバーが語るキャリア
    髙橋 秀徳, 根本紘志, 荒川陸, 井上瑛未里, モハメッド・バトラン 株式会社POL LabBase Magazine SUMMER 2 25 -26 2018年 [査読無し][招待有り]
  • 深層学習によるカラー眼底写真からの脈絡膜厚推測
    反保 宏信, 高橋 秀徳, 添田 めぐみ, 高橋 良太, 伊野田 悟, 坂本 晋一, 新井 悠介, 井上 裕次, 川島 秀俊, 柳 靖雄 日本眼科学会雑誌 121 (臨増) 213 -213 2017年03月 [査読無し][通常論文]
  • Shinichi Sakamoto, Hidenori Takahashi, Yuji Inoue, Yasuo Yanagi, Aya Sato, Mikiko Takezawa, Tatsuro Tanabe, Yujiro Fujino, Hidetoshi Kawashima INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 57 (12) 2016年09月 [査読無し][通常論文]
  • Satoru Inoda, Hidenori Takahashi, Xue Tan, Natsuko Kakinuma, Yoko Nomura, Shin-ichi Sakamoto, Yusuke Arai, Yujiro Fujino, Hidetoshi Kawashima, Yasuo Yanagi INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 56 (7) 2015年06月 [査読無し][通常論文]
  • 網膜静脈閉塞症慢性期における前房中炎症性サイトカイン濃度
    伊野田 悟, 高橋 秀徳, 譚 雪, 垣沼 奈津子, 野村 陽子, 坂本 晋一, 新井 悠介, 富永 聡子, 佐藤 彩, 藤野 雄次郎, 川島 秀俊, 柳 靖雄 日本眼科学会雑誌 119 (臨増) 164 -164 2015年03月 [査読無し][通常論文]
  • 後部硝子体剥離と眼内サイトカイン濃度
    髙橋 秀徳, 監修, 坂本泰二, 山下英俊 あたらしい眼科 34 2015年03月 [査読無し][招待有り]
  • 各時点における網膜剥離に対する治療選択は特に間違ったものではなく、早い段階で硝子体手術をしていたとしても予後は変わらなかった可能性はある
    髙橋 秀徳 医療判例解説Japanese Journal of Mecical Treatment Precedent Commentary 54 99 -101 2015年02月 [査読無し][招待有り]
  • Keiko Azuma, Hidenori Takahashi, Ryo Obata, Yasuo Yanagi INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 54 (15) 2013年06月 
    0
  • 反保宏信, 大河原百合子, 高橋秀徳, 牧野伸二, 佐藤幸裕 新しい眼科 30 (10) 1461 -1465 2013年 [査読無し][通常論文]
     
    目的:眼底カメラでの糖尿病症例の眼底スクリーニングは、無散瞳と散瞳、1〜7方向撮影などさまざまである。散瞳下の4方向と9方向カラー撮影を比較した。方法:散瞳下に画角50°のデジタル眼底カメラで、4、9方向カラー撮影と9方向蛍光眼底造影(FA)を行った62例102眼を後ろ向きに調査した。4、9方向カラー撮影、FAの順に判定し、単純、前増殖、増殖網膜症に病期分類して比較した。結果:4方向と9方向カラー撮影の病期診断一致率は98%であった。4方向、9方向カラー撮影とFAの病期診断一致率はいずれも85%で差はなかったが、微細な網膜新生血管をカラー撮影で網膜内細小血管異常と判定していたものが各6%あった。結論:4方向と9方向カラー撮影の病期診断はほぼ一致しており、4方向カラー撮影で十分と考えた。ただし、カラー撮影では微細な網膜新生血管の判定に限界があることに留意する必要がある。(著者抄録)
  • Hidenori Takahashi, Wu Yaqiong, Yasuo Yanagi, Yukari Kawabata, Hideyuki Negoro, Makoto Araie, Yoshio Uehara JOURNAL OF HYPERTENSION 24 246 -246 2006年12月 [査読無し][通常論文]
  • H Takahashi, R Obata, Y Yanagi, Y Tamaki INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 46 2005年 [査読無し][通常論文]
  • H Takahashi, K Matsuura, Y Inoue, K Muranaka, Y Yanagi, Y Tamaki, N Takeda, T Shindo, R Nagai INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 45 U733 -U733 2004年04月 [査読無し][通常論文]
  • J Kami, H Takahashi, Y Yanagi, Y Tamaki, H Kagetika, T Shindou, R Nagai INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 45 U731 -U731 2004年04月 [査読無し][通常論文]

産業財産権

  • 特許US 10,945,598 B2:教師なし機械学習を使用して角膜重症度の同定を支援する方法  
    ヨーゼフ シアマック, 髙橋 秀徳, 林 孝彦
  • 特許6745496:糖尿病網膜症の病期判定支援システムおよび糖尿病網膜症の病期の判定を支援する方法    2020年08月26日
    髙橋 秀徳
  • 特開2020-124460:教師なし機械学習を使用して角膜重症度の同定を支援する方法  2020年08月20日
    ヨーゼフィ シアマック, 髙橋 秀徳, 林 孝彦  学校法人自治医科大学・林孝彦

学術貢献活動

  • 第36回JSCRS学術総会シンポジウム7白内障手術と人工知能 座長
    期間 : 2021年06月27日
    役割 : パネル司会・セッションチェア等
    種別 : 学会・研究会等
    主催者・責任者 : JSCRS


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