南場 研一 (ナンバ ケンイチ)

医学研究院 専門医学系部門 感覚器病学分野准教授
北海道大学病院准教授
Last Updated :2025/11/11

■研究者基本情報

学位

  • 医学博士, 北海道大学大学院医学研究科

Researchmap個人ページ

研究キーワード

  • ぶどう膜炎
  • EAU
  • 実験的自己免疫性網膜ぶどう膜炎
  • OCH
  • TLR
  • 糖鎖
  • グライコミクス
  • Jα-281ノックアウトマウス
  • aGalCel
  • CD1ノックアウトマウス
  • 樹状細胞
  • α-GC
  • CD1
  • NKT細胞
  • Ja281
  • グライコブロッティング
  • ベーチェット病
  • 難治性内眼炎
  • マイクロサテライト
  • 原田病
  • アデノウイルス角結膜炎
  • 流行性結膜炎
  • pooled DNA法
  • 院内感染株
  • エンドトキシ
  • コキサンチン
  • 遺伝子
  • 臨床遺伝子
  • 免疫学
  • 臨床

研究分野

  • ライフサイエンス, 眼科学

担当教育組織

■経歴

経歴

  • 2023年 - 現在
    北海道大学, 大学院医学研究院 眼科学教室, 准教授, 日本国
  • 1999年
    米国ハーバード大学, 医学部 スケペンス眼研究所, ポスドク研究員, アメリカ合衆国
  • 1999年
    北海道大学, 大学院 医学研究科, 博士課程 終了, 日本国
  • 1992年
    北海道大学, 医学部 卒業, 日本国

学歴

  • 1995年04月 - 1999年03月, 北海道大学大学院医学研究科, Graduate School of Medicine
  • 1986年04月 - 1992年03月, 北海道大学医学部, School of Medicine

■研究活動情報

論文

  • Severe Aqueous-Deficient Dry Eye Following Herpes Zoster Ophthalmicus With Periocular Inflammation: A Case Series.
    Rina Kanaya, Yoshiaki Tagawa, Kenichi Namba, Mayuko Kimura, Susumu Ishida
    Cureus, 17, 8, e90569, 2025年08月, [国際誌]
    英語, 研究論文(学術雑誌), This series aimed to describe the clinical characteristics and course of severe aqueous-deficient dry eye (ADDE), a condition characterized by tear deficiency and reduced corneal sensation, following ophthalmic herpes zoster infection with periocular inflammation. Four cases of ADDE that developed after ophthalmic herpes zoster infection were retrospectively examined. Clinical data, including disease course, medical history, imaging findings, tear volume assessment, corneal sensitivity testing, and treatment outcomes, were collected. Our patients exhibited severe tear deficiency, significant corneal hypoesthesia, and serious corneal complications, accompanied by persistent ocular pain despite reduced corneal sensation. Imaging studies revealed dacryoadenitis in two cases and suggested severe periocular inflammation in all cases. Persistent superficial punctate keratopathy (SPK) was observed in all patients, with complications including corneal ulcers, perforation, persistent epithelial defects, and filamentary keratitis. Neuropathic pain was believed to contribute to persistent ocular pain. Treatment with topical rebamipide, autologous serum eye drops, punctal plugs, and eyelid closure effectively managed corneal epithelial damage and associated complications. Herpes zoster-induced dacryoadenitis and corneal sensory nerve damage probably contributed to ADDE pathogenesis. Given the potential for severe corneal complications, careful long-term monitoring is crucial in these patients.
  • Clinical characteristics of multiple evanescent white dot syndrome with poor visual prognosis in Japanese patients.
    Takayuki Tanaka, Michiyuki Saito, Satoru Kase, Zhenyu Dong, Ryo Ando, Kenichi Namba, Kiriko Nishiyama-Hirooka, Yui Yamashita, Susumu Ishida
    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 2025年07月04日, [国際誌]
    英語, 研究論文(学術雑誌), PURPOSE: Multiple evanescent white dot syndrome (MEWDS) typically resolves spontaneously and is expected to have a favorable visual prognosis. Therefore, the initial manifestations of MEWDS have yet to be well studied. This study aimed to investigate the clinical characteristics of primary and secondary MEWDS patients and evaluate factors responsible for poor visual prognosis. METHODS: The medical records of 36 patients diagnosed with MEWDS between 2004 and 2021 at Hokkaido University Hospital were retrospectively reviewed. The study evaluated patient demographics, clinical characteristics, and multimodal imaging findings. The clinical factors involving final logMAR best-corrected visual acuity (BCVA) were analyzed. In addition, clinical characteristics of secondary MEWDS cases with poor visual prognosis were investigated. RESULTS: Twelve of the 36 patients (33.3%) had active chorioretinal lesions distinct from MEWDS lesions, resulting in a prevalence of secondary MEWDS of 33.3%. Four patients presented with foveal active chorioretinal lesions (11.1%). Retinal atrophy developed in these lesions in all four cases during the follow-up period. Compared to primary MEWDS, secondary MEWDS with foveal involvement of active chorioretinal lesions was associated with significantly worse visual acuity at the initial visit (p = 0.004), and showed a trend toward poorer visual acuity was also observed at the final visit (p = 0.11). In simple linear regression analysis, coexisting foveal involvement of active chorioretinal lesions was significantly associated with worse final logMAR BCVA (p = 0.002). In multiple stepwise linear regression analysis, coexisting foveal involvement (p < 0.001) and male sex (p = 0.03) remained independently associated with poorer visual outcomes. CONCLUSIONS: The presence of foveal active chorioretinal lesions in MEWDS may be associated with poorer visual prognosis. KEY MESSAGE: WHAT IS KNOWN : • Recent reports characterized the clinical aspects of primary and secondary multiple evanescent white dot syndrome (MEWDS), but the visual prognosis of these variants is only slowly unfolding. WHAT IS NEW: • Secondary MEWDS associated with foveal involvement of active chorioretinal lesions had significantly poorer visual acuity at the initial visit and showed a trend toward poorer visual acuity at the final visit compared to primary MEWDS. • In both simple and multiple linear regression analyses, foveal involvement of active chorioretinal lesions was associated with poorer visual outcomes. • The presence of foveal active chorioretinal lesions in MEWDS may be associated with poorer visual prognosis.
  • Questionnaire survey among ophthalmic allergists on dupilumab-associated ocular surface disease in Japan.
    Jun Shoji, Yousuke Asada, Rumi Adachi, Noriko Inada, Eiichi Uchio, Yoko Kataoka, Norito Katoh, Tatsuma Kishimoto, Eisuke Shimizu, Tamaki Sumi, Etsuko Takamura, Kenichi Namba, Yuuko Hara, Kazuhiro Harada, Akira Hirota, Atsuki Fukushima, Ken Fukuda, Hiroshi Fujishima, Moe Matsuzawa, Akira Matsuda, Tatsuya Mimura, Dai Miyazaki, Hiroyuki Yazu, Kaori Yamamoto, Kazuma Kitsu, Nobuyuki Ebihara
    Allergology international : official journal of the Japanese Society of Allergology, 74, 2, 333, 335, 2025年04月, [国際誌]
    英語
  • Use of explainable AI on slit-lamp images of anterior surface of eyes to diagnose allergic conjunctival diseases.
    Michiko Yonehara, Yuji Nakagawa, Yuji Ayatsuka, Yuko Hara, Jun Shoji, Nobuyuki Ebihara, Takenori Inomata, Tianxiang Huang, Ken Nagino, Ken Fukuda, Tatsuma Kishimoto, Tamaki Sumi, Atsuki Fukushima, Hiroshi Fujishima, Moeko Kawai, Etsuko Takamura, Eiichi Uchio, Kenichi Namba, Ayumi Koyama, Tomoko Haruki, Shin-Ich Sasaki, Yumiko Shimizu, Dai Miyazaki
    Allergology international : official journal of the Japanese Society of Allergology, 74, 1, 86, 96, 2024年08月17日, [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: Artificial intelligence (AI) is a promising new technology that has the potential of diagnosing allergic conjunctival diseases (ACDs). However, its development is slowed by the absence of a tailored image database and explainable AI models. Thus, the purpose of this study was to develop an explainable AI model that can not only diagnose ACDs but also present the basis for the diagnosis. METHODS: A dataset of 4942 slit-lamp images from 10 ophthalmological institutions across Japan were used as the image database. A sequential pipeline of segmentation AI was constructed to identify 12 clinical findings in 1038 images of seasonal and perennial allergic conjunctivitis (AC), atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC), giant papillary conjunctivitis (GPC), and normal subjects. The performance of the pipeline was evaluated by determining its ability to obtain explainable results through the extraction of the findings. Its diagnostic accuracy was determined for 4 severity-based diagnosis classification of AC, AKC/VKC, GPC, and normal. RESULTS: Segmentation AI pipeline efficiently extracted crucial ACD indicators including conjunctival hyperemia, giant papillae, and shield ulcer, and offered interpretable insights. The AI pipeline diagnosis had a high diagnostic accuracy of 86.2%, and that of the board-certified ophthalmologists was 60.0%. The pipeline had a high classification performance, and the area under the curve (AUC) was 0.959 for AC, 0.905 for normal subjects, 0.847 for GPC, 0.829 for VKC, and 0.790 for AKC. CONCLUSIONS: An explainable AI model created by a comprehensive image database can be used for diagnosing ACDs with high degree of accuracy.
  • 若年性慢性虹彩毛様体炎の臨床像の検討
    鈴木 佳代, 南場 研一, 金子 優, 大黒 伸行, 竹内 正樹, 伊東 崇子, 永田 健児, 臼井 嘉彦, 蕪城 俊克, 田中 理恵, 柳井 亮二, 楠原 仙太郎, 慶野 博, 丸山 和一, 竹内 大, 若年性慢性虹彩毛様体炎研究グループ
    日本眼科学会雑誌, 128, 臨増, 208, 208, (公財)日本眼科学会, 2024年03月
    日本語
  • A case of tubulointerstitial nephritis and uveitis syndrome accompanied by subclinical choroiditis.
    Takuya Arita, Kenichi Namba, Daiju Iwata, Kayo Suzuki, Yo Ogino, Kazuomi Mizuuchi, Miki Hiraoka, Nobuyoshi Kitaichi, Susumu Ishida
    BMC ophthalmology, 23, 1, 424, 424, 2023年10月20日, [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: Tubulointerstitial nephritis and uveitis (TINU) syndrome is an uveits characterized by complications of idiopathic acute tubulointerstitial nephritis, and most cases present only anterior uveitis. We report a case of TINU syndrome in which the presence of choroiditis was revealed by multimodal imaging. CASE PRESENTATION: A 12-year-old male visited our hospital with a 6-day history of ocular pain and hyperemia. Conjunctival and ciliary injections, 1 + flare and 3 + cells of anterior chamber inflammation with mutton fat keratic precipitates were observed in both eyes (OU), together with redness and swelling of the optic disc OU. Laboratory tests showed slightly high levels of soluble IL-2R and serum β2 microglobulin and markedly high levels of urinary β2 microglobulin. The diagnosis of probable TINU syndrome was established on the basis of bilateral uveitis and urinalysis results in accordance with a clinical criteria of tubulointerstitial nephritis. With treatment with oral prednisolone (PSL) at 20 mg/day, ocular findings improved, and the dose of PSL was gradually reduced and withdrawn 6 months later. However, 1 month later from the withdrawal, ocular inflammation recurred with the presence of retinal exudates and snowball vitreous opacities in the peripheral retina OU. Fluorescein angiography showed leakages from peripheral retinal vessels and staining corresponding to retinal exudates. Indocyanine green angiography showed hypofluorescent dots scattered over the ocular fundus. Optical coherence tomography revealed the presence of choroidal thickening. Laser speckle flowgraphy color map showed a relatively cooler color. Findings from these multimodal images indicated the presence of subclinical choroiditis; therefore, oral PSL was administered again, and ocular inflammatory findings were improved. CONCLUSIONS: TINU syndrome can exhibit subclinical choroiditis detected with multimodal imaging. Further studies are necessary to determine the frequency of subclinical choroiditis in TINU syndrome.
  • A case of APMPPE-like panuveitis presenting with extensive outer retinal layer impairment following COVID-19 vaccination.
    Yo Ogino, Kenichi Namba, Daiju Iwata, Kayo Suzuki, Kazuomi Mizuuchi, Miki Hiraoka, Nobuyoshi Kitaichi, Susumu Ishida
    BMC ophthalmology, 23, 1, 233, 233, 2023年05月24日, [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: Vaccination against the worldwide pandemic coronavirus disease 2019 (COVID-19) is underway; however, some cases of new onset uveitis after vaccination have been reported. We report a case of bilateral acute posterior multifocal placoid pigment epitheliopathy-like (AMPPE-like) panuveitis after COVID-19 vaccination in which the patient's pathological condition was evaluated using multimodal imaging. CASE PRESENTATION: A 31-year-old woman experienced bilateral hyperemia and blurred vision starting 6 days after her second inoculation of the COVID-19 vaccination. At her first visit, her visual acuity was decreased bilaterally, and severe bilateral anterior chamber inflammation and bilateral scattering of cream-white placoid lesions on the fundus were detected. Optical coherence tomography (OCT) showed serous retinal detachment (SRD) and choroidal thickening in both eyes (OU). Fluorescein angiography (FA) revealed hypofluorescence in the early phase and hyperfluorescence in the late phase corresponding to the placoid legions. Indocyanine green angiography (ICGA) showed sharply marginated hypofluorescent dots of various sizes throughout the mid-venous and late phases OU. The patient was diagnosed with APMPPE and was observed without any medications. Three days later, her SRD disappeared spontaneously. However, her anterior chamber inflammation continued, and oral prednisolone (PSL) was given to her. Seven days after the patient's first visit, the hyperfluorescent lesions on FA and hypofluorescent dots on ICGA partially improved; however, the patient's best corrected visual acuity (BCVA) recovered only to 0.7 OD and 0.6 OS, and the impairment of the outer retinal layer was broadly detected as hyperautofluorescent lesions on fundus autofluorescence (FAF) examination and as irregularity in or disappearance of the ellipsoid and interdigitation zones on OCT, which were quite atypical for the findings of APMPPE. Steroid pulse therapy was performed. Five days later, the hyperfluorescence on FAF had disappeared, and the outer retinal layer improved on OCT. Moreover, the patient's BCVA recovered to 1.0 OU. Twelve months after the end of treatment, the patient did not show any recurrences. CONCLUSIONS: We observed a case of APMPPE-like panuveitis after COVID-19 vaccination featuring some atypical findings for APMPPE. COVID-19 vaccination may induce not only known uveitis but also atypical uveitis, and appropriate treatment is required for each case.
  • The Steroid-Sparing Effect of Adalimumab in the Treatment for the Recurrent Phase of Vogt-Koyanagi-Harada Disease.
    Mayuko Shinagawa, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Keitaro Hase, Kayo Suzuki, Kiriko Hirooka, Nobuyoshi Kitaichi, Miki Hiraoka, Susumu Ishida
    Ocular immunology and inflammation, 31, 3, 501, 505, 2023年04月, [国際誌]
    英語, 研究論文(学術雑誌), PURPOSE: To reveal the steroid-sparing effect of adalimumab (ADA) in the treatment for the chronic recurrent phase of Vogt-Koyanagi-Harada (VKH) disease. CASES AND METHODS: Thirty-six eyes from 18 cases of the recurrent phase of VKH disease treated with ADA over 12 months were examined retrospectively. Before the introduction of ADA, 4 cases received prednisolone (PSL) monotherapy and other 14 cases received PSL and cyclosporine A (CYA) combination therapy. RESULTS: In cases treated with PSL and CYA, CYA was discontinued when ADA was introduced. The minimum dose of PSL to control intraocular inflammation (min dose of PSL) could be reduced in all cases after the introduction of ADA (from 16.9 ± 7.9 mg to 6.3 ± 3.1 mg). No serious adverse events were observed in the observational periods. CONCLUSION: By comparing the min dose of PSL before and after the introduction of ADA, the steroid-sparing effect of ADA was confirmed.
  • 日本におけるフックス虹彩毛様体炎症候群の低い有病率の原因についての検討
    米田 優, 臼井 嘉彦, 田中 理恵, 長谷 敬太郎, 南場 研一, 鴨居 功樹, 高瀬 博, 竹内 正樹, 松宮 亘, 楠原 仙太郎, 武田 篤信, 八幡 信代, 柳井 亮二, 日山 知奈, 原田 陽介, 橋田 徳康, 丸山 和一, 中井 慶, 田口 諒, 蕪城 俊克, 水木 信久, 後藤 浩, 藤野 雄次郎, 竹内 大
    日本眼科学会雑誌, 127, 臨増, 270, 270, (公財)日本眼科学会, 2023年03月
    日本語
  • A Case of Intraocular Metastasis of Lung Cancer Diagnosed Using Cell Block Preparation of the Vitreous Humor.
    Kohei Matsumoto, Satoru Kase, Kenichi Namba, Daiju Iwata, Yoshihiro Matsuno, Susumu Ishida
    Cancer diagnosis & prognosis, 3, 1, 130, 134, 2023年, [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND/AIM: Masquerade syndrome is characterized by uveitis-like manifestations caused by tumor cell infiltration into the ocular tissues. The aim of the study was to report a lung cancer patient with persistent unilateral vitreous opacity, who was eventually diagnosed with masquerade syndrome using cell block preparation. CASE REPORT: An 82-year-old female complained of blurred vision in her left eye (OS). Because of pulmonary adenocarcinoma, she had previously received anticancer drug treatment at another Hospital and achieved partial remission. Ophthalmic examinations revealed anterior chamber inflammation and vitreous opacity OS. Corticosteroid eye drops were administered, but the inflammation did not improve, and was referred to the Hokkaido University Hospital. The left best-corrected visual acuity was 0.1 with normal intraocular pressure. Anterior chamber inflammation was 2+ cells, and vitreous haze was 4+ OS. B-mode ultrasonography showed diffuse heterogeneous high echoic changes in the vitreous cavity. She underwent vitrectomy, and cell block preparation of the vitreous infusion fluids was performed. Cytopathology revealed adenocarcinoma cells with a high nuclear/cytoplasmic ratio and glandular formation. The immunocytochemical study showed that tumor cells were positive for thyroid transcription factor-1 (TTF-1), napsin A, and CK7, therefore diagnosis of masquerade syndrome due to intraocular metastasis of pulmonary adenocarcinoma was reached. Chemoradiotherapy was administered, and the eye got phthisis bulbi after irradiation 2 years after diagnosis. CONCLUSION: Cell block preparation using vitreous humor may be useful in the diagnosis and management of intraocular metastasis of pulmonary adenocarcinoma in patients with prolonged vitreous opacity.
  • Involvement of Angiopoietin 2 and vascular endothelial growth factor in uveitis.
    Kayo Suzuki, Daiju Iwata, Kenichi Namba, Keitaro Hase, Miki Hiraoka, Miyuki Murata, Nobuyoshi Kitaichi, Richard Foxton, Susumu Ishida
    PloS one, 18, 11, e0294745, 2023年, [国際誌]
    英語, 研究論文(学術雑誌), PURPOSE: Angiopoietin (Ang) 2 is released from vascular endothelial cells by the stimulation of vascular endothelial growth factor (VEGF)A. Ang2 increases the expression of leukocyte adhesion molecules on endothelial cells via nuclear factor κB. The aim of this study was to evaluate the effects of Ang2 and VEGFA on ocular autoimmune inflammation. METHODS: We measured the concentrations of Ang2 and VEGFA in vitreous samples among patients with uveitis. Vitreous samples were collected from 16 patients with idiopathic uveitis (uveitis group) and 16 patients with non-inflammatory eye disease (control group). Experimental autoimmune uveoretinitis (EAU) was induced in B10.BR mice with a human interphotoreceptor retinoid-binding protein-derived peptide. The retinochoroidal tissues of the EAU mice were removed, and the mRNA levels of Ang2 and VEGFA were examined. EAU mice treated with anti-Ang2, anti-VEGFA, a combination of anti-Ang2 and anti-VEGFA, anti-Ang2/VEGFA bispecific, or IgG control antibodies were clinically and histopathologically evaluated. RESULTS: The protein levels of Ang2 and VEGFA were significantly higher in the vitreous samples of patients with uveitis than in controls (P<0.05). The retinochoroidal mRNA levels of Ang2 and VEGFA were significantly upregulated in EAU mice compared to controls (n = 6, P<0.05). Although there was no significant difference, treatment with anti-VEGFA antibody reduced the clinical and histopathological scores. However, treatment with anti-Ang2 antibody reduced the clinical and histopathological scores (n = 18-20, P<0.05). Furthermore, these scores were further decreased when treated by inhibiting both Ang2 and VEGFA. CONCLUSIONS: Based on these results, VEGFA and Ang2 were shown to be upregulated locally in the eye of both uveitis patients and models of uveitis. Dual inhibition of Ang2 and VEGFA is suggested to be a new therapeutic strategy for uveitis.
  • Ten-year follow-up of infliximab treatment for uveitis in Behçet disease patients: A multicenter retrospective study.
    Masaru Takeuchi, Yoshihiko Usui, Kenichi Namba, Hiroshi Keino, Masaki Takeuchi, Hiroshi Takase, Koju Kamoi, Keitaro Hase, Takako Ito, Kei Nakai, Kazuichi Maruyama, Eri Kobayashi, Hisashi Mashimo, Tomohito Sato, Nobuyuki Ohguro, Junko Hori, Annabelle A Okada, Koh-Hei Sonoda, Nobuhisa Mizuki, Hiroshi Goto
    Frontiers in medicine, 10, 1095423, 1095423, 2023年, [国際誌]
    英語, 研究論文(学術雑誌), PURPOSE: To evaluate 10-year outcome of infliximab (IFX) treatment for uveitis in Behçet disease (BD) patients using a standardized follow-up protocol. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: 140 BD uveitis patients treated with IFX enrolled in our previous study. METHODS: Medical records were reviewed for demographic information, duration of IFX treatment, number of ocular attacks before IFX initiation, best corrected visual acuity (VA) at baseline and 1, 2, 3, 4, 5, and 10 years after IFX initiation, uveitis recurrence after IFX initiation and main anatomical site, concomitant therapies, and adverse events (AEs). MAIN OUTCOME MEASURES: 10-year IFX continuation rate and change in LogMAR VA. RESULTS: Of 140 BD patients, 106 (75.7%) continued IFX treatment for 10 years. LogMAR VA improved gradually after initiation of IFX, and the improvement reached statistical significance from 2 years of treatment. Thereafter, significant improvement compared with baseline was maintained until 10 years, despite a slight deterioration of logMAR VA from 5 years. However, eyes with worse baseline decimal VA < 0.1 showed no significant improvement from baseline to 10 years. Uveitis recurred after IFX initiation in 50 patients (recurrence group) and did not recur in 56 (non-recurrence group). Ocular attacks/year before IFX initiation was significantly higher in the recurrence group (2.82 ± 3.81) than in the non-recurrence group (1.84 ± 1.78). In the recurrence group, uveitis recurred within 1 year in 58% and within 2 years in 74%. Seventeen patients (34%) had recurrent anterior uveitis, 17 (34%) had posterior uveitis, and 16 (32%) had panuveitis, with no significant difference in VA outcome. In addition, logMAR VA at 10 years did not differ between the recurrence and non-recurrence groups. AEs occurred among 43 patients (30.7%), and 24 (17.1%) resulted in IFX discontinuation before 10 years. CONCLUSIONS: Among BD patients with uveitis who initiated IFX, approximately 75% continued treatment for 10 years, and their VA improved significantly and was maintained for 10 years. Uveitis recurred in one-half of the patients, but visual acuity did not differ significantly from the patients without recurrence.
  • Fundus autofluorescence imaging in acute posterior multifocal placoid pigment epitheliopathy.
    Koichi Yokoi, Kenichi Namba, Daiju Iwata, Kazuomi Mizuuchi, Keitaro Hase, Kayo Suzuki, Ryo Ando, Kiriko Hirooka, Nobuko Sekine, Nobuyoshi Kitaichi, Miki Hiraoka, Susumu Ishida
    American journal of ophthalmology case reports, 28, 101732, 101732, 2022年12月, [国際誌]
    英語, 研究論文(学術雑誌), PURPOSE: Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is a disease characterized by multiple yellowish-white placoid lesions. Although most lesions resolve spontaneously, some turn into scars and lead to permanent visual dysfunction. In this report, we found suggestive findings in fundus autofluorescence (FAF) that may be useful for distinguishing severe lesions requiring treatment in APMPPE. OBSERVATION: Case 1: A 29-year-old woman was referred to our hospital with multiple yellowish-white placoid lesions on the fundi of both eyes (OU). FAF showed hyperautofluorescence in some of these placoid lesions. Based on the findings of fluorescein angiography, a diagnosis of APMPPE was established, and oral prednisolone (PSL) was initiated, given that some lesions were located in the macula. One week later, exacerbation occurred with the newly developed hyperautofluorescent lesions. Some lesions in the right eye (OD) that were hyperautofluorescent at the first visit became hypoautofluorescent. Afterward, although all hypoautofluorescent lesions persisted, most of the hyperautofluorescent lesions disappeared, so oral PSL could be stopped. Two months later, however, the recurrence occurred along with multiple new placoid lesions. Some lesions located at the macula were hyperautofluorescent on FAF OU, indicating the possibility of becoming scar lesions with hypoautofluorescence. Accordingly, oral PSL was given again. CASE 2: A 47-year-old woman noticed decreased vision OD, and she was referred to us. Multiple yellowish-white placoid lesions were seen in the fundi OU. FAF showed hyperautofluorescence both with and without corresponding hypoautofluorescence in the placoid lesions OU. A diagnosis of APMPPE was established, and oral PSL was initiated. Four months later, some lesions that were hyperautofluorescent at the first visit had turned isoautofluorescent, and some lesions OU became hypoautofluorescent. However, all hypoautofluorescent lesions remained hypoautofluorescent OU. Only some hyperautofluorescent lesions recovered to isoautofluorescence without scars. CONCLUSIONS AND IMPORTANCE: In APMPPE, lesions showing hyperautofluorescence on FAF may change into hypoautofluorescence indicating scar formation. Therefore, the presence of hyperautofluorescent lesions in the macula may be a good indicator of the need for intensive corticosteroid treatments to avoid leaving hypoautofluorescent scars that are related to irreversible visual dysfunction.
  • Clinical significance of serum and vitreous soluble interleukin-2 receptor in patients with intraocular lymphoma.
    Kayo Suzuki, Kenichi Namba, Satoru Kase, Yo Ogino, Keitaro Hase, Daiju Iwata, Kazuomi Mizuuchi, Miki Hiraoka, Nobuyoshi Kitaichi, Susumu Ishida
    BMC ophthalmology, 22, 1, 428, 428, 2022年11月10日, [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: Intraocular lymphoma (IOL) is a masquerade syndrome that mimics uveitis, making diagnosis difficult. The serum soluble interleukin-2 receptor (sIL-2R), which is cleaved by matrix metalloproteinase (MMP) -2 and MMP-9, has been recognized as a tumor-related biomarker of malignant lymphomas. The aim of this study was to review the reliability of serum and vitreous sIL-2R for distinguishing IOL from uveitis. METHODS: Patients who underwent diagnostic vitrectomy for marked vitreous haze at Hokkaido University Hospital between April 2014 and June 2019 were enrolled. The patients were divided into an IOL group and a uveitis group, according to the pathology of their vitreous samples. The IOL group was further divided at the time of vitrectomy into patients who already had extraocular involvement (IOL with extraocular involvement group) and patients with no evidence of having extraocular involvement (IOL without extraocular involvement group). Serum sIL-2R, and intravitreal sIL-2R, MMP-2, and MMP-9 levels were assessed. RESULTS: Twenty-five eyes of 25 patients, and 15 eyes of 15 patients were included in the IOL group and uveitis group, respectively. The serum sIL-2R levels were significantly lower in the IOL group than in the uveitis group (P < 0.05), and 20.0% and 66.7% in the IOL and the uveitis group showed high sIL-2R value above the normal range. Vitreous sIL-2R tended to be higher in the IOL group than in the uveitis group (P = 0.80). Serum sIL-2R was significantly lower in the IOL without extraocular involvement group than in the IOL with extraocular involvement group (P < 0.05); 5.9% in the IOL without extraocular involvement group and 50.0% in the IOL with extraocular involvement group showed high sIL-2R value above the normal range. Vitreous sIL-2R, MMP-2, and MMP-9 tended to be higher in the IOL with extraocular involvement group than in the IOL without extraocular involvement group (P = 0.30, < 0.05, 0.16). CONCLUSIONS: Serum sIL-2R is often within the normal range in IOL patients. Even if it is within the normal range, the possibility of IOL should be considered. Serum sIL-2R is not a reliable biomarker for IOL, whereas vitreous sIL-2R may be useful for the diagnosis of IOL.
  • Executive summary: Japanese guidelines for allergic conjunctival diseases 2021.
    Dai Miyazaki, Atsuki Fukushima, Eiichi Uchio, Jun Shoji, Kenichi Namba, Nobuyuki Ebihara, Etsuko Takamura, Ken Fukuda, Akira Matsuda, Shigeki Okamoto, Kazumi Fukagawa, Hiroshi Fujishima, Shigeaki Ohno, Yuichi Ohashi
    Allergology international : official journal of the Japanese Society of Allergology, 71, 4, 459, 471, 2022年10月, [国際誌]
    英語, 研究論文(学術雑誌), Allergic conjunctival disease (ACD) is an inflammatory disease of the conjunctiva that is mainly caused by type I hypersensitivity response to allergens and accompanied by subjective symptoms and other findings induced by antigens. ACD is classified as allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. This article summarizes the third edition of the Japanese guidelines for allergic conjunctival diseases published in 2021 and outlines the diagnosis, pathogenesis, and treatment of ACD. Since the introduction of immunosuppressive eye drops, the treatment strategies for severe ACDs have significantly changed. To clarify the recommended standard treatment protocols for ACD, the advantages and disadvantages of these treatments were assessed using clinical questions, with a focus on the use of steroids and immunosuppressive drugs. This knowledge will assist healthcare providers and patients in taking an active role in medical decision making.
  • Clinical features of ocular sarcoidosis: severe, refractory, and prolonged inflammation.
    Kayo Suzuki, Mami Ishihara, Kenichi Namba, Shigeaki Ohno, Hiroshi Goto, Hiroshi Takase, Shigeru Kawano, Etsuko Shibuya, Keitaro Hase, Daiju Iwata, Kazuomi Mizuuchi, Nobuyoshi Kitaichi, Nobuhisa Mizuki, Susumu Ishida
    Japanese journal of ophthalmology, 66, 5, 447, 454, 2022年09月, [国内誌]
    英語, 研究論文(学術雑誌), PURPOSE: To clarify the proportion of ocular sarcoidosis with severe, refractory, and prolonged inflammation and their association with ocular complications and visual prognosis. STUDY DESIGN: Multicenter, retrospective, longitudinal cohort study. METHODS: Three hundred and twenty-three eyes of 164 patients (45 men; 119 women) with ocular sarcoidosis who visited Hokkaido University Hospital and Yokohama City University Hospital from 2010 to 2015. We newly defined severe, refractory, and prolonged inflammation in ocular sarcoidosis, and investigated their proportions, ocular complications and final visual acuity from medical records of our sarcoidosis patients. RESULTS: The eyes with severe inflammation numbered 72/323 (22.3%), with refractory inflammation, 80/323 (24.8%), and with prolonged inflammation, 91/323 (28.2%). The number of eyes having neither severe, refractory, nor prolonged inflammation (defined as none) was 114/323 (35.3%). The numbers of eyes that reached irreversible visual dysfunction were 6/72 (8.3%) of those with severe inflammation, 10/80 (12.5%) with refractory inflammation, 12/91 (13.2%) with prolonged inflammation, and 4/114 (6.2%) with none. As complications, cataract (62.2%), glaucoma (28.5%), epiretinal membrane (24.1%), cystoid macular edema (22.6%), vitreous hemorrhage (2.8%), choroidal atrophy (2.5%), macular degeneration (1.2%), macular hole (0.9%) and retinal detachment (0.3%) were identified. Among them, secondary glaucoma (16 eyes) and macular degeneration (4 eyes) were major complications related to irreversible visual dysfunction. CONCLUSIONS: Although most of the patients with ocular sarcoidosis had a relatively good visual prognosis, some developed severe, refractory, and/or prolonged inflammation related to the development of ocular complications, that resulted in poor visual prognosis.
  • Long-term Outcomes of Modified 360-Degree Suture Trabeculotomy for Uveitic Glaucoma Compared With Primary Open Angle Glaucoma.
    Riki Kijima, Yasuhiro Shinmei, Shinki Chin, Rina Kanaya, Akihiro Shinkai, Takeshi Ohguchi, Kenichi Namba, Susumu Ishida
    Journal of glaucoma, 31, 8, 682, 688, 2022年08月01日, [国際誌]
    英語, 研究論文(学術雑誌), PRCIS: A Kaplan-Meier survival curve analysis showed no significant differences in success rates between uveitic glaucoma (UG) and primary open angle glaucoma (POAG) 120 months after modified 360-degree suture trabeculotomy, which was effective for both groups in the long term. PURPOSE: The aim of this study was to examine the outcomes of modified 360-degree suture trabeculotomy in patients with UG as compared with those with POAG. PATIENTS AND METHODS: This was a retrospective, nonrandomized, and comparative case series study. Modified 360-degree trabeculotomy using a 5-0 nylon suture (S-LOT) was performed on 51 eyes of 51 patients (54.4±13.4 y) with UG between October 2005 and January 2012 at Hokkaido University Hospital. Age-matched patients with POAG who underwent S-LOT during the same period were enrolled as controls. Written informed consent was obtained from all patients enrolled in the present study. Surgical success was defined as an intraocular pressure (IOP) <18 mm Hg with similar or lower doses of antiglaucoma medications. Kaplan-Meier survival curves of surgical failure were analyzed and compared between UG and POAG. RESULTS: The mean follow-up periods (±SD) for UG and POAG were 104.8±44.0 and 98.1±36.3 months ( P =0.23), respectively. Mean preoperative IOP in UG and POAG were 34.9±11.0 and 25.3±9.4 mm Hg ( P <0.001), respectively. After surgery, mean IOP in UG and POAG decreased to 12.0±4.1 and 13.8±3.2 mm Hg, respectively, at 60 months, and 12.1±5.6 and 12.4±1.8 mm Hg ( P =0.86), respectively, at 120 months. The Kaplan-Meier survival curve analysis showed no significant differences in success rates between UG and POAG at the end of the follow-up (Log-rank test, P =0.13). Success rates in UG and POAG were 70.0 and 62.5% at 60 months, and 67.5 and 41.2% at 120 months, respectively. CONCLUSION: These results suggest that S-LOT is effective for UG and POAG alike.
  • Use of systemic corticosteroids in patients newly registered at a claims database with a diagnosis of non-infectious uveitis: results from a real-world claims database analysis.
    Akihiko Umazume, Nobuyuki Ohguro, Annabelle A Okada, Kenichi Namba, Koh-Hei Sonoda, Hidekazu Tsuruga, Kazuo Morita, Hiroshi Goto
    Japanese journal of ophthalmology, 66, 4, 394, 404, 2022年07月, [国内誌]
    英語, 研究論文(学術雑誌), PURPOSE: To investigate the real-world dose of systemic corticosteroids in the treatment of non-infectious uveitis (NIU) in Japan. STUDY DESIGN: A retrospective, observational study. METHODS: Patients newly registered at the Japan Medical Data Center health insurance claims database with a diagnosis of NIU who received systemic corticosteroids were identified, and their systemic corticosteroid dose (prednisolone equivalent) was assessed over 12 months of treatment (data extraction period: January 2008 to May 2017). RESULTS: The mean cumulative systemic corticosteroid dose in 12 months in 1641 new patients with NIU who received systemic corticosteroids was 593.7 mg. The mean systemic corticosteroid dose was highest at month 1 (10.7, 218.1, 16.7, and 23.0 mg/day in Behçet's disease [BD]-associated NIU [n = 19], Vogt-Koyanagi-Harada [VKH] disease-associated NIU [n = 49], sarcoidosis-associated NIU [n = 27], and "undifferentiated NIU" [NIU without specific primary disease information, n = 1545], respectively) and decreased over time. Systemic corticosteroids were prescribed at month 12 to 68.4%, 22.4%, 44.4%, and 5.6% of patients with BD-associated NIU, VKH disease-associated NIU, sarcoidosis-associated NIU, and undifferentiated NIU, respectively (mean dose, 6.0-14.3 mg/day). Multivariate regression analysis identified female sex, middle age (30 to < 40 years), VKH disease, and immunosuppressive agent use as background factors associated with higher systemic corticosteroid dose. CONCLUSIONS: The systemic corticosteroid dose was highest at month 1 and decreased over time in all disease categories. This database research revealed that some patients with NIU continued being prescribed systemic corticosteroids for at least 1 year.
  • Efficacy and Safety of Adalimumab for Exacerbation or Relapse of Ocular Inflammation in Patients with Vogt-Koyanagi-Harada Disease: A Multicenter Study.
    Shunsaku Nakai, Masaru Takeuchi, Yoshihiko Usui, Kenichi Namba, Kayo Suzuki, Yosuke Harada, Sentaro Kusuhara, Toshikatsu Kaburaki, Rie Tanaka, Masaki Takeuchi, Nobuhisa Mizuki, Kei Nakai, Hiroshi Goto, Carl P Herbort Jr
    Ocular immunology and inflammation, 32, 4, 1, 9, 2022年06月24日, [国際誌]
    英語, 研究論文(学術雑誌), PURPOSE: We investigated efficacy and safety of adalimumab (ADA) treatment for exacerbation or recurrence of Vogt-Koyanagi-Harada (VKH) patients. METHODS: Medical records of 70 VKH patients who received ADA treatment for more than 6 months were retrospectively investigated. RESULTS: The mean age of VKH patients was 54.8 ± 15.1 years, and male/female ratio was 34/36, and sunset glow fundus was observed in 71.4%. Subfoveal choroidal thickness, indocyanine green angiography scores, and corticosteroid and cyclosporine doses were significantly reduced by ADA treatment for 6 months compared to baseline, while LogMAR and flare counts were also improved without being statistically significant. Adverse events were observed in 17.1%, in which tuberculosis was at 7.14% and psoriasis was at 2.86%; however, ADA treatment was continued in 91.4%. CONCLUSIONS: ADA was shown to be effective to achieve remission of VKH disease refractory to conventional treatments and was generally well tolerated with few serious adverse events.
  • Long-Term Safety and Effectiveness of Adalimumab in Japanese Patients with Noninfectious Intermediate, Posterior, or Panuveitis: Post-Marketing Surveillance of 251 Patients.
    Kenichi Namba, Toshikatsu Kaburaki, Hidekazu Tsuruga, Yohei Ogawa, Eri Iwashita, Hiroshi Goto
    Ophthalmology and therapy, 11, 3, 1147, 1161, 2022年06月, [国際誌]
    英語, 研究論文(学術雑誌), INTRODUCTION: The aim of this nationwide, prospective post-marketing surveillance was to assess the safety and effectiveness of up to 52 weeks of adalimumab treatment in patients with noninfectious intermediate, posterior, or panuveitis in Japanese clinical practice. METHODS: This post-marketing surveillance was conducted at 60 medical facilities in Japan from October 2016 to June 2020. Patients with noninfectious intermediate, posterior, or panuveitis who were administered adalimumab (Humira®, AbbVie Inc.) for the first time were eligible. Subcutaneous adalimumab was initially administered at 80 mg, followed by 40 mg 1 week later, then 40 mg every 2 weeks. Safety measures included the incidence of adverse events (AEs) and adverse drug reactions (ADRs; primary endpoint). Effectiveness measures included visual acuity, anterior chamber cell grade, vitreous haze, macular edema, foveal retinal thickness, uveitis recurrence rate, and oral corticosteroid dose. Health-related quality of life was evaluated using the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25). RESULTS: During 52 weeks of surveillance, AEs and ADRs occurred in 70 (27.9%) and 47 (18.7%) of 251 patients, respectively. The most common ADR was infection (21/251 patients; 8.4%), including serious infections in eight (3.2%) patients. ADRs were more frequent in patients ≥ 65 years of age, those with concurrent diseases, and those with past medical history. Four patients developed tuberculosis. The uveitis recurrence rate was 24.8% (61/246 patients). All effectiveness measures tended to improve from baseline to week 52, and mean corticosteroid doses decreased. Clinically meaningful changes were observed for most VFQ-25 subscales. CONCLUSIONS: The safety profile of adalimumab was generally consistent with previous reports, and no new safety concerns were identified. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02916017.
  • Diagnostic Accuracy of Cell Block Preparations and Clinical Features Affecting It in Vitreoretinal Lymphoma.
    Satoru Kase, Kenichi Namba, Daiju Iwata, Kazuomi Mizuuchi, Kayo Suzuki, Takako Ito, Keitaro Hase, Nobuyoshi Kitaichi, Susumu Ishida
    Journal of clinical medicine, 11, 5, 2022年03月03日, [国際誌]
    英語, 研究論文(学術雑誌), Purpose: The purpose of this study was to examine the diagnostic accuracy of the cell block (CB) method and clinical features affecting it in patients with vitreoretinal lymphoma (VRL). Methods: This study enrolled 38 eyes in 33 VRL patients, and 7 eyes in 7 patients with idiopathic uveitis who underwent diagnostic vitrectomy. Medical records including the results of CB cytology, interleukin (IL)-10/-6 concentrations, and immunoglobulin heavy chain gene (IgH) rearrangement were retrospectively searched. Results: Patients with VRL comprised 16 women and 17 men, and the age of onset ranged from 44 to 85 years (mean: 70 years). CB preparations detected large malignant cells in 35 eyes (92%), whereas the other 3 VRL eyes were negative. Two of the latter three eyes showed subretinal infiltrates, which existed in 7 of 35 CB-positive eyes. Intravitreal IL-10 and -6 concentrations were 1866 ± 4088 pg/mL and 98 ± 139 pg/mL, respectively, and the rate of IL-10/-6 >1 was 86.9%. The presence of IgH monoclonality was 63.2%. In patients with uveitis, CB specimens revealed no atypical but small inflammatory cells. IL-6 concentration was 311.1 ± 240 pg/mL, whereas IL-10 was undetectable in six eyes, and the IL-negative rate was 85.7%. Six eyes (85.7%) with uveitis showed no IgH monoclonality. Conclusions: Diagnostic accuracy of CB preparations in VRL could achieve an equivalent outcome to IL ratio calculation and IgH monoclonality detection. The appearance of subretinal infiltrates may diminish the CB positivity.
  • Posterior scleritis with anti-neutrophil cytoplasmic antibody-associated vasculitis utilizing rituximab therapy to maintain remission: A case report.
    Xinyu Weng, Daiju Iwata, Kenichi Namba, Kayo Suzuki, Kazuomi Mizuuchi, Hiroyuki Nakamura, Tatsuya Atsumi, Susumu Ishida
    American journal of ophthalmology case reports, 25, 101333, 101333, 2022年03月, [国際誌]
    英語, 研究論文(学術雑誌), PURPOSE: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a necrotizing vasculitis syndrome characterized by the destruction of small vessels, leading to various organ disorders. Here, we report a case of posterior scleritis with AAV successfully treated with prednisolone and rituximab (RTX) combination therapy. OBSERVATIONS: A 69-year-old female suffered from ocular pain and redness in her left eye for 2.5 years. She had been diagnosed with idiopathic otitis media before a year. At her initial visit, scleral injection with nodular elevated scleral lesions, vitreous haze, and serous retinal detachment (SRD) in the inferior periphery were observed in the left eye. Enhanced computed tomography revealed the enhancement and thickening of the left sclera. The results of laboratory analysis were positive for myeloperoxidase ANCA. Accordingly, she was diagnosed with AAV. Owing to the exacerbation of vitreous haze and SRD, topical treatment and steroid pulse therapy were initiated. Following therapy, anterior and posterior scleritis improved, and additional RTX was administered to maintain the remission. Following treatment, the patient has maintained remission with 10 mg/day prednisolone to date. CONCLUSIONS AND IMPORTANCE: We encountered a case of posterior scleritis with AAV in which inflammatory manifestations subsided with RTX and glucocorticoid combination therapy. RTX administration likely contributed to the maintenance of remission.
  • A case of Epstein-Barr virus acute retinal necrosis successfully treated with foscarnet.
    Kayo Suzuki, Kenichi Namba, Keitaro Hase, Kazuomi Mizuuchi, Daiju Iwata, Takako Ito, Nobuyoshi Kitaichi, Hiroshi Takase, Susumu Ishida
    American journal of ophthalmology case reports, 25, 101363, 101363, 2022年03月, [国際誌]
    英語, 研究論文(学術雑誌), PURPOSE: Epstein-Barr virus (EBV) is a herpes virus known to cause infectious mononucleosis and several other human disorders. Ocular EBV infections that have been reported include uveitis, retinal vasculitis, and acute retinal necrosis (ARN). ARN is usually caused by herpes simplex virus (HSV) or varicella-zoster virus (VZV). ARN that is caused by EBV (EBV-ARN) is rarely seen, and only a few cases have been reported. The visual prognosis for EBV-ARN is poor, and no treatment strategy has been established. We report on a patient who was treated successfully for EBV-ARN. OBSERVATION: An 80-year-old female who had been treated with prednisolone at 5 mg/day and methotrexate at 2 mg/week for rheumatoid arthritis visited our hospital because of blurred vision in her left eye. Her left visual acuity was 20/50, and extensive white-yellowish retinal lesions at the temporal periphery with retinal hemorrhages were seen through vitreous haze. The DNA sequence of EBV, but not of HSV, VZV, or cytomegalovirus, was detected by a polymerase chain reaction (PCR) assay in the aqueous humor (4.2 × 106 copies/ml), with EBV also being positive in serum (3.5 × 102 copies/ml). The patient received 2 mg of intravitreal ganciclovir injections twice with a 3-day interval and intravenous infusion of acyclovir at 750 mg/day for 7 days; however, the retinal white lesions expanded rapidly, then dose of prednisolone was increased (40 mg/day) and vitrectomy was performed 10 days after the initial visit. After the surgery, the retinal lesion continued to enlarge. Vitreous samples showed high copies of EBV (1.2 × 108 copies/ml). Following treatment with intravenous foscarnet (4800 mg/day), which replaced the acyclovir application, the retinal white lesions gradually diminished, leaving retinal scars. To date, the patient has developed no retinal detachment and shows visual acuity over 6/60 in the left eye along with silicone oil. CONCLUSIONS: We experienced a case of EBV-ARN that was refractory to systemic acyclovir and topical ganciclovir but responded effectively to systemic foscarnet after vitrectomy. Although the clinical management remains challenging in this disease, foscarnet is considered to be one of the candidate drugs for EBV infections.
  • ベーチェット病ぶどう膜炎に対するインフリキシマブ治療の5年以上の検討 多施設研究               
    竹内 大, 臼井 嘉彦, 南場 研一, 慶野 博, 竹内 正樹, 高瀬 博, 鴨居 功樹, 長谷 敬太郎, 伊東 崇子, 中井 慶, 丸山 和一, 小林 恵理, 堀 純子, 真下 永, 佐藤 智人, 大黒 伸行, 岡田 アナベルあやめ, 園田 康平, 後藤 浩, 水木 信久
    日本眼科学会雑誌, 126, 臨増, 238, 238, (公財)日本眼科学会, 2022年03月
    日本語
  • Multicenter, retrospective, observational study for the Treatment Pattern of systemic corticoSTERoids for relapse of non-infectious uveitis accompanying Vogt-Koyanagi-Harada disease or sarcoidosis.
    Kenichi Namba, Hiroshi Takase, Yoshihiko Usui, Fumihiko Nitta, Kazuichi Maruyama, Sentaro Kusuhara, Masaki Takeuchi, Atsushi Azumi, Ryoji Yanai, Yutaka Kaneko, Eiichi Hasegawa, Kei Nakai, Hidekazu Tsuruga, Kazuo Morita, Toshikatsu Kaburaki
    Japanese journal of ophthalmology, 66, 2, 130, 141, 2022年03月, [国内誌]
    英語, 研究論文(学術雑誌), PURPOSE: Non-infectious uveitis associated with Vogt-Koyanagi-Harada (VKH) disease or sarcoidosis is commonly treated with systemic corticosteroids (SCS). We assessed the use of SCS for non-infectious uveitis relapses in Japanese clinical practice. STUDY DESIGN: Multicenter, retrospective chart review (UMIN Clinical Trial Registry; UMIN000032390). METHODS: One hundred fifty-seven patients (15- ≤ 75 years; 103 VKH disease, 54 sarcoidosis) given SCS to treat a relapse of non-infectious intermediate, posterior, or panuveitis accompanying VKH disease or sarcoidosis were studied (August 2011-December 2018). SCS dose and duration, concomitant medications, subsequent relapses, and steroid-related adverse drug reactions (ADRs) were analyzed for 12 months after target relapse treatment. Relationships between background factors and total SCS dose were analyzed (logistic regression). RESULTS: Mean (± SD) total SCS dose over 12 months after target relapse treatment was 3874 ± 2775 mg, and was higher in patients with immunosuppressants than in those without (4575 mg vs 3496 mg). Immunosuppressant use was the only factor significantly associated with higher total SCS dose (p = 0.0196). Mean duration of SCS treatment for relapse was 318.7 ± 89.3 days. Only 29.3% of patients were steroid-free after 12 months; the percentage was higher in patients without immunosuppressants (36.3% vs 16.4%). Subsequent relapse was experienced by 39.5% of patients, and 13.4% had a steroid-related ADR (mostly glaucoma or diabetes). CONCLUSION: In Japanese clinical practice, many patients with recurrent uveitis accompanying VKH disease or sarcoidosis received SCS for relapse for ≥ 300 days, suggesting that reducing corticosteroids is challenging in patients with difficulty suppressing inflammation.
  • ベーチェット病ぶどう膜炎に対するインフリキシマブ治療の5年以上の検討 多施設研究
    竹内 大, 臼井 嘉彦, 南場 研一, 慶野 博, 竹内 正樹, 高瀬 博, 鴨居 功樹, 長谷 敬太郎, 伊東 崇子, 中井 慶, 丸山 和一, 小林 恵理, 堀 純子, 真下 永, 佐藤 智人, 大黒 伸行, 岡田 アナベルあやめ, 園田 康平, 後藤 浩, 水木 信久
    日本眼科学会雑誌, 126, 臨増, 238, 238, (公財)日本眼科学会, 2022年03月
    日本語
  • 1.花粉結膜炎の診断と治療
    鈴木佳代, 南場研一
    アレルギー, 71, 5, 353, 358, 2022年, [国内誌]
    日本語
  • Adalimumab treatment for chronic recurrent Vogt-Koyanagi-Harada disease with sunset glow fundus: A multicenter study.
    Masaru Takeuchi, Shunsaku Nakai, Yoshihiko Usui, Kenichi Namba, Kayo Suzuki, Yosuke Harada, Sentaro Kusuhara, Toshikatsu Kaburaki, Rie Tanaka, Masaki Takeuchi, Nobuhisa Mizuki, Kei Nakai, Hiroshi Goto, Carl P Herbort Jr
    Saudi journal of ophthalmology : official journal of the Saudi Ophthalmological Society, 36, 4, 380, 386, 2022年, [国際誌]
    英語, 研究論文(学術雑誌), PURPOSE: We investigated the efficacy and safety of adalimumab (ADA) treatment for chronic recurrent Vogt-Koyanagi-Harada (VKH) patients with sunset glow fundus (SGF). METHODS: Medical records of 50 chronic recurrent VKH patients with SGF who received ADA treatment for more than 6 months were retrospectively reviewed. RESULTS: The mean age of chronic recurrent VKH patients with SGF was 55.9 ± 14.4 years, and the male/female ratio was 26/24. Before ADA treatment, the mean daily dose of systemic corticosteroids was 16.5 ± 12.7 mg, and 22 patients (44%) were under immunosuppressors. LogMAR visual acuity (VA), flare counts, subfoveal choroidal thickness (SFCT), indocyanine green angiography scores, and corticosteroid and cyclosporine doses were significantly reduced by ADA treatment at 6 months compared to baseline. Among all parameters, flare count was significantly related to LogMAR VA. LogMAR VA was significantly related to flare counts but not to SFCT nor to ICGA scores. ADA treatment was continued in 94%. CONCLUSION: ADA was shown to be effective in achieving remission of chronic recurrent VKH disease with SGF refractory to conventional treatments, and was generally well tolerated with few serious adverse events.
  • The Expression of Matrix Metalloproteinases in Eyes with Intraocular Lymphoma.
    Kanae Fukutsu, Satoru Kase, Daiju Iwata, Kayo Suzuki, Kenichi Namba, Susumu Ishida
    Ocular immunology and inflammation, 30, 7-8, 1798, 1802, 2022年, [国際誌]
    英語, 研究論文(学術雑誌), PURPOSE: The purpose of this study is to investigate matrix metalloproteinases (MMPs) expression in human intraocular lymphoma (IOL). METHODS: Two enucleated eyes and seven cell-block samples obtained from patients with IOL who underwent vitrectomy were used. Immunopathological examinations were performed for detection of MMP-2, MMP-9, and TIMP-4 expressions. RESULTS: In the enucleated eye with primary IOL (PIOL), MMP-2 was negative, and MMP-9 and TIMP-4 were positive in the lymphoma cells, while in the enucleated eye with secondary IOL (SIOL), all the molecules were positive. Among the cell-block samples with PIOL, the positive rate in lymphoma cells of MMP-2, MMP-9, and TIMP-4 was 75%, 100%, and 75%, respectively. In the cell-block samples with SIOL, the positive rates of MMP-2, MMP-9, and TIMP-4 were all 100%. CONCLUSIONS: MMP-2, MMP-9, and TIMP-4 were expressed in lymphoma cells using the specimens of human IOL, suggesting that MMPs may play an important role in the development of IOL.
  • Factors associated with low prevalence of Fuchs' uveitis syndrome in Japan.
    Yu Yoneda, Yoshihiko Usui, Rie Tanaka, Keitaro Hase, Kenichi Namba, Koju Kamoi, Hiroshi Takase, Masaki Takeuchi, Wataru Matsumiya, Sentaro Kusuhara, Atsunobu Takeda, Nobuyo Yawata, Ryoji Yanai, Tomona Hiyama, Yosuke Harada, Noriyasu Hashida, Kazuichi Maruyama, Kei Nakai, Ryo Taguchi, Toshikatsu Kaburaki, Nobuhisa Mizuki, Hiroshi Goto, Yujiro Fujino, Masaru Takeuchi
    Frontiers in medicine, 9, 999804, 999804, 2022年, [国際誌]
    英語, 研究論文(学術雑誌), AIM: To investigate the causes of low prevalence of Fuchs' uveitis syndrome (FUS) in Japan. METHODS: Medical records of 160 patients diagnosed with FUS at 14 uveitis specialty facilities in Japan were reviewed retrospectively. RESULTS: In 160 FUS patients, mean follow-up period before referral to our uveitis facilities was 31.6 ± 50.9 months. The most common reason for referral was idiopathic uveitis (61.9%), followed by cataract (25.0%), high intraocular pressure (IOP) including glaucoma (16.3%), and FUS (14.4%). Unilateral involvement was 96.9%. The most frequent ocular finding of FUS was anterior inflammation (91.9%), followed by stellate-shaped keratic precipitates (88.1%), cataract/pseudophakia (88.1%), diffuse iris atrophy (84.4%), vitreous opacity (62.5%), heterochromia (53.1%) and high IOP including glaucoma (36.3%). As treatments of these ocular findings, cataract surgery was performed in 52.5%, glaucoma surgery in 10.6%, and vitrectomy in 13.8%. Mean logMAR VA was 0.28 ± 0.59 at the initial visit, and decreased significantly to 0.04 ± 0.32 at the last visit. Proportions of FUS patients with BCVA <0.1 and 0.1 to <0.5 decreased, while that of ≥0.5 increased at the last visit compared with the initial visit. CONCLUSIONS: Ocular findings of FUS in Japanese FUS patients were consistent with the characteristic features. The low prevalence of FUS in Japan may be a result of being overlooked and misdiagnosed as mild idiopathic uveitis, cataract, and/or glaucoma.
  • Macrophage-like iPS-derived Suppressor Cells Reduce Th1-mediated Immune Response to a Retinal Antigen.
    Keitaro Hase, Kenichi Namba, Haruka Wada, Hyuma Tsuji, Aoi Maeda, Tomoki Murata, Ryo Otsuka, Daiju Iwata, Atsuhiro Kanda, Kousuke Noda, Nobuyoshi Kitaichi, Ken-Ichiro Seino, Susumu Ishida
    Current eye research, 46, 12, 1908, 1916, 2021年12月, [国際誌]
    英語, 研究論文(学術雑誌), PURPOSE: To investigate the immunotherapeutic effects of macrophage-like induced pluripotent stem (iPS) cell-derived suppressor cells (SCs) in ocular immune response and experimental autoimmune uveoretinitis (EAU). METHODS: The genes of Oct3/4, Sox2, Klf4, and c-Myc were transferred to B cells enriched from the spleen cells of C57BL/6 mice by using retrovirus vectors. Transferred B cells were cultured for 17 days to obtain colonies of iPS cells. Through additional steps, iPS-SCs were induced. An antigen-specific T cell proliferation assay was performed with CD4+ T cells collected from draining lymph nodes of the mice immunized with human interphotoreceptor retinoid-binding protein (hIRBP) peptide and co-cultured with iPS-SCs. Cytokine concentrations in the culture supernatant were examined. Mice were immunized with hIRBP peptide to induce EAU. The iPS-SCs were administered into the mice one day before the induction of EAU. RESULTS: The iPS-SCs decreased hIRBP-specific T cell proliferation depending on the number of cells. Productions of tumor necrosis factor-α and interferon-γ were significantly decreased; however, transforming growth factor-β1, nitric oxide, interleukin (IL)-13, IL-17A, and IL-17 F levels were elevated in the supernatant when the collected T cells were co-cultured with iPS-SCs. The iPS-SCs had immunosuppressant effects even without cell-to-cell contact, and their effects were non-specific to the antigen preloaded on iPS-SCs. EAU was significantly milder in the mice administered iPS-SCs prior to immunization. CONCLUSIONS: Macrophage-like iPS-SCs reduced Th1 immune response to a retinal antigen and Th1-mediated EAU in mice. These results showed the possibility of the application of iPS technology to the treatment of noninfectious ocular inflammation, endogenous uveitis, in the future.
  • Prevalence and incidence rates and treatment patterns of non-infectious uveitis in Japan: real-world data using a claims database
    Akihiko Umazume, Nobuyuki Ohguro, Annabelle A. Okada, Kenichi Namba, Koh-Hei Sonoda, Hidekazu Tsuruga, Kazuo Morita, Hiroshi Goto
    Japanese Journal of Ophthalmology, 65, 5, 657, 665, Springer Japan, 2021年09月01日, [国内誌]
    英語, 研究論文(学術雑誌)
  • アレルギー性結膜疾患診療ガイドライン(第3版)
    宮崎 大, 内尾 英一, 海老原 伸行, 庄司 純, 南場 研一, 福島 敦樹, 大野 重昭, 大橋 裕一, 岡本 茂樹, 佐竹 良之, 高村 悦子, 深川 和己, 福田 憲, 藤島 浩, 松田 彰, 明田 直彦, 江原 二三枝, 大津 洋, 岸本 達真, 栗田 淳貴, 上月 直之, 高 良太, 清水 映輔, 鈴木 佳代, 矢津 啓之, 井上 幸次, 大久保 公裕, 加藤 則人, 斎藤 博久, 島崎 潤, 白石 敦, 外園 千恵, 園田 康平, 園部 まり子, 中西 里映子, 堀 裕一, 松本 健治, 山口 正雄, 日本眼科アレルギー学会診療ガイドライン作成委員会
    日本眼科学会雑誌, 125, 8, 741, 785, (公財)日本眼科学会, 2021年08月
    日本語
  • アレルギー性結膜疾患診療ガイドライン(第3版)               
    宮崎 大, 内尾 英一, 海老原 伸行, 庄司 純, 南場 研一, 福島 敦樹, 大野 重昭, 大橋 裕一, 岡本 茂樹, 佐竹 良之, 高村 悦子, 深川 和己, 福田 憲, 藤島 浩, 松田 彰, 明田 直彦, 江原 二三枝, 大津 洋, 岸本 達真, 栗田 淳貴, 上月 直之, 高 良太, 清水 映輔, 鈴木 佳代, 矢津 啓之, 井上 幸次, 大久保 公裕, 加藤 則人, 斎藤 博久, 島崎 潤, 白石 敦, 外園 千恵, 園田 康平, 園部 まり子, 中西 里映子, 堀 裕一, 松本 健治, 山口 正雄, 日本眼科アレルギー学会診療ガイドライン作成委員会
    日本眼科学会雑誌, 125, 8, 741, 785, (公財)日本眼科学会, 2021年08月
    日本語
  • Correction to: Development of cytomegalovirus retinitis after negative conversion of cytomegalovirus antigenemia due to systemic antiviral therapy (Graefe's Archive for Clinical and Experimental Ophthalmology, (2021), 259, 4, (971-978), 10.1007/s00417-020-05011-0)
    Kayo Suzuki, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Takako Ito, Keitaro Hase, Nobuyoshi Kitaichi, Susumu Ishida
    Graefe's Archive for Clinical and Experimental Ophthalmology, 259, 4, 1083, 1083, Springer Science and Business Media Deutschland GmbH, 2021年04月01日, [国際誌]
    英語, 研究論文(学術雑誌)
  • Development of cytomegalovirus retinitis after negative conversion of cytomegalovirus antigenemia due to systemic antiviral therapy
    Kayo Suzuki, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Takako Ito, Keitaro Hase, Nobuyoshi Kitaichi, Susumu Ishida
    Graefe's Archive for Clinical and Experimental Ophthalmology, 259, 4, 971, 978, Springer Science and Business Media Deutschland GmbH, 2021年04月01日, [国際誌]
    英語, 研究論文(学術雑誌)
  • 結核性ぶどう膜炎の臨床像と治療の検討
    多田 明日美, 岩橋 千春, 中井 慶, 南場 研一, 岡田 アナベルあやめ, 慶野 博, 高瀬 博, 福田 祥子, 後藤 浩, 臼井 嘉彦, 蕪城 俊克, 水木 信久, 安積 淳, 園田 康平, 武田 篤信, 大黒 伸行
    日本眼科学会雑誌, 125, 4, 415, 424, (公財)日本眼科学会, 2021年04月
    日本語
  • 結核性ぶどう膜炎の臨床像と治療の検討
    多田 明日美, 岩橋 千春, 中井 慶, 南場 研一, 岡田 アナベルあやめ, 慶野 博, 高瀬 博, 福田 祥子, 後藤 浩, 臼井 嘉彦, 蕪城 俊克, 水木 信久, 安積 淳, 園田 康平, 武田 篤信, 大黒 伸行
    日本眼科学会雑誌, 125, 4, 415, 424, (公財)日本眼科学会, 2021年04月
    日本語
  • Distinguishing Features of Anterior Uveitis Caused by Herpes Simplex Virus, Varicella-Zoster Virus and Cytomegalovirus.
    Yukiko Terada, Toshikatsu Kaburaki, Hiroshi Takase, Hiroshi Goto, Satoko Nakano, Yoshitsugu Inoue, Kazuichi Maruyama, Kazunori Miyata, Kenichi Namba, Koh-Hei Sonoda, Yutaka Kaneko, Jiro Numaga, Masaya Fukushima, Noe Horiguchi, Mitsunao Ide, Fumie Ehara, Dai Miyazaki, Eiichi Hasegawa, Manabu Mochizuki
    American journal of ophthalmology, 227, 191, 200, 2021年03月24日, [国際誌]
    英語, 研究論文(学術雑誌), PURPOSE: To determine distinguishing features of the clinical characteristics of anterior uveitis (AU) caused by herpes simplex virus (HSV), varicella-zoster virus (VZV) and cytomegalovirus (CMV). DESIGN: Retrospective, multicenter, case series. METHODS: Consecutive patients with herpetic AU examined at 11 tertiary centers in Japan between January 2012 and December 2017 and who were followed for 3 months or longer were evaluated. Diagnosis was made by polymerase chain reaction (PCR) for HSV, VZV or CMV in the aqueous humor, or classical signs of herpes zoster ophthalmicus. RESULTS: This study enrolled 259 herpetic AU patients, including PCR-proven HSV-AU (30 patients), VZV-AU (50) and CMV-AU (147); and herpes zoster ophthalmicus (32). All HSV-AU and VZV-AU patients were unilateral, while 3% of CMV-AU patients were bilateral. Most HSV-AU and VZV-AU patients were sudden onset with an acute clinical course, while CMV-AU had a more insidious onset and chronic course. There were no significant differences for all surveyed symptoms, signs and complications between HSV-AU and VZV-AU. However, significant differences were detected for many items between CMV-AU and the other two herpetic AU types. Ocular hyperemia and pain, blurring of vision, ciliary injection, medium to large keratic precipitates (KPs), cells and flare in the anterior chamber, and posterior synechia occurred significantly more often in HSV-AU and VZV-AU versus CMV-AU. In contrast, small KPs, coin-shaped KPs, diffuse iris atrophy, elevated intraocular pressure and glaucoma surgery were significantly more frequent in CMV-AU versus HSV-AU and VZV-AU. CONCLUSION: This multicenter retrospective study identified distinguishing features of HSV-AU, VZV-AU and CMV-AU.
  • Epidemiology of uveitis in Japan: a 2016 retrospective nationwide survey
    Koh-Hei Sonoda, Eiichi Hasegawa, Kenichi Namba, Annabelle A. Okada, Nobuyuki Ohguro, Hiroshi Goto, JOIS (Japanese Ocular Inflammation Society) Uveitis Survey Working Group
    Japanese Journal of Ophthalmology, 65, 2, 184, 190, Springer Japan, 2021年03月01日, [国内誌]
    英語, 研究論文(学術雑誌)
  • Validation of systemic parameters for the diagnosis of ocular sarcoidosis
    Kayo Suzuki, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Takako Ito, Keitaro Hase, Nobuyoshi Kitaichi, Susumu Ishida
    Japanese Journal of Ophthalmology, 65, 2, 191, 198, Springer Japan, 2021年03月01日, [国内誌]
    英語, 研究論文(学術雑誌)
  • VKH病及び眼サルコイドーシス再燃時における全身ステロイド薬の使用実態調査
    南場 研一, 高瀬 博, 臼井 嘉彦, 新田 文彦, 丸山 和一, 楠原 仙太郎, 竹内 正樹, 安積 淳, 柳井 亮二, 金子 優, 長谷川 英一, 中井 慶, 鶴我 英和, 守田 和央, 蕪城 俊克
    日本眼科学会雑誌, 125, 臨増, 212, 212, (公財)日本眼科学会, 2021年03月
    日本語
  • VKH病及び眼サルコイドーシス再燃時における全身ステロイド薬の使用実態調査               
    南場 研一, 高瀬 博, 臼井 嘉彦, 新田 文彦, 丸山 和一, 楠原 仙太郎, 竹内 正樹, 安積 淳, 柳井 亮二, 金子 優, 長谷川 英一, 中井 慶, 鶴我 英和, 守田 和央, 蕪城 俊克
    日本眼科学会雑誌, 125, 臨増, 212, 212, (公財)日本眼科学会, 2021年03月
    日本語
  • Recent Clinical Features of Intraocular Inflammation in Hokkaido, Japan - Comparison with the Previous Decade.
    Daiju Iwata, Kenichi Namba, Taku Yamamoto, Kazuomi Mizuuchi, Wataru Saito, Shigeaki Ohno, Nobuyoshi Kitaichi, Susumu Ishida
    Ocular immunology and inflammation, 30, 4, 1, 7, 2021年02月11日, [国際誌]
    英語, 研究論文(学術雑誌), PURPOSE: This study aimed to investigate the clinical features of intraocular inflammation (uveitis) in Hokkaido and to assess the etiology trends in comparison with those of our previous survey. METHODS: We retrospectively reviewed the medical records of 1,616 new referral uveitis patients (1,020 females and 596 males) in Hokkaido University Hospital between 2004 and 2014. RESULTS: Sarcoidosis was the most frequent etiology (17.4%), followed by Vogt-Koyanagi-Harada disease (8.1%), Behçet's disease (4.5%), and human leukocyte antigen B27 -associated uveitis (2.5%). The etiologies in 48.7% of the patients were unclassified. Compared to the previous survey between 1994 and 2003, the rate of Behçet's disease decreased and that of sarcoidosis increased. The rates of infectious uveitis and vitreoretinal lymphoma increased. CONCLUSION: Although the order of the top four etiologies was the same in the two surveys, the rate of sarcoidosis increased and that of Behçet's disease decreased.
  • Clinical Features of Primary Vitreoretinal Lymphoma: A Single-center Study.
    Satoru Kase, Kenichi Namba, Daiju Iwata, Kazuomi Mizuuchi, Takako Ito, Keitaro Hase, Kayo Suzuki, Masahiro Onozawa, Nobuyoshi Kitaichi, Susumu Ishida
    Cancer diagnosis & prognosis, 1, 2, 69, 75, 2021年, [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND/AIM: This study aimed to demonstrate the clinical outcomes of primary vitreoretinal lymphoma (PVRL). PATIENTS AND METHODS: Seventeen patients with PVRL who had been treated at Hokkaido University Hospital were enrolled in this study. They were diagnosed based on their cytology, interleukin-10/-6 ratio, and immunoglobulin heavy chain (IgH) gene rearrangement. RESULTS: Diagnostic tests detected cytological malignancy among 14 cases (82.3%), high interleukin-10/-6 ratios among 16 cases (94.1%), and IgH monoclonality in 13 cases (76.5%). Systemic corticosteroids were given to seven (41.2%) patients before their diagnosis of PVRL. Treatments after diagnosis comprised intravitreal methotrexate injection, local radiation, and intravenous chemotherapy for 11, seven, and five cases, respectively. Central nervous system and systemic involvements were observed in nine and one case, respectively, and these complications occurred at 3 to 43 months (mean=16 months) after initial ocular presentation. CONCLUSION: Many of our patients did not receive any systemic intervention, and almost half of patients with PVRL developed central nervous system involvement during their follow-up period.
  • Optic Nerve Head Microcirculation in Eyes with Vogt-Koyanagi-Harada Disease Accompanied by Anterior Ischemic Optic Neuropathy
    Yui Yamashita, Yuki Hashimoto, Kenichi Namba, Kazuomi Mizuuchi, Susumu Ishida
    Case Reports in Ophthalmology, 12, 3, 899, 908, S. Karger AG, 2021年, [国際誌]
    英語, 研究論文(学術雑誌)
  • Surgical Outcomes of Trabeculectomy in Uveitic Glaucoma: A Long-Term, Single-Center, Retrospective Case-Control Study.
    Rina Kanaya, Riki Kijima, Yasuhiro Shinmei, Akihiro Shinkai, Takeshi Ohguchi, Kenichi Namba, Shinki Chin, Susumu Ishida
    Journal of ophthalmology, 2021, 5550776, 5550776, 2021年, [国際誌]
    英語, 研究論文(学術雑誌), PURPOSE: To evaluate the long-term outcomes of trabeculectomy with mitomycin C (MMC-TLE) in patients with uveitic glaucoma (UG). Patients and Methods. This was a retrospective, nonrandomized case series study. MMC-TLE was performed on 50 eyes with UG between February 2001 and January 2015 at Hokkaido University Hospital. Age- and sex-matched patients with primary open angle glaucoma (POAG) who underwent MMC-TLE were matched by age and sex and enrolled as controls. Surgical success was defined as an intraocular pressure (IOP) less than 18 or 15 mmHg. The Kaplan-Meier survival curves for surgical failure were analyzed. RESULTS: The mean preoperative IOP in UG and POAG was 27.6 ± 10.6 and 18.0 ± 4.5 mmHg, respectively. After the surgery, the mean IOP in UG and POAG was reduced to 11.7 ± 4.2 and 12.2 ± 3.8 mmHg at 12 months, 11.9 ± 7.0 and 12.1 ± 3.1 mmHg at 36 months, and 13.0 ± 5.2 and 10.6 ± 1.2 mmHg at 120 months, respectively. The success rates (IOP <18 mmHg, IOP reduction >20%) in UG and POAG were 91.7% and 88.0% at 12 months, 82.2% and 75.6% at 36 months, and 66.5% and 61.8% at 120 months, respectively. The success rates (IOP <15 mmHg) in UG and POAG were 64.0% and 58.0% at 12 months, 55.1% and 45.5% at 36 months, and 47.9% and 37.8% at 120 months, respectively. There was no significant difference in the success rate between UG and POAG at 120 months after surgery by either definition of surgical success. CONCLUSIONS: MMC-TLE effectively reduced IOP in both UG and POAG. There was no significant difference in the success rate between UG and POAG. Following sufficient inflammation suppression, surgical outcomes of UG may be comparable with those of POAG.
  • Multiple evanescent white dot syndrome and panuveitis: a case report
    Kazuomi Mizuuchi, Wataru Saito, Kenichi Namba, Susumu Ishida
    Journal of Ophthalmic Inflammation and Infection, 10, 1, 26, 26, Springer Science and Business Media Deutschland GmbH, 2020年12月01日, [国際誌]
    英語, 研究論文(学術雑誌)
  • Reduced steroid-induced intraocular pressure elevation in tacrolimus-treated refractory allergic ocular diseases.
    Dai Miyazaki, Daisuke Shimizu, Atsuki Fukushima, Nobuyuki Ebihara, Eiichi Uchio, Jun Shoji, Kenichi Namba, Yoshitsugu Inoue, Yuichi Ohashi, Shigeki Okamoto, Etsuko Takamura, Hiroshi Fujishima
    Japanese journal of ophthalmology, 64, 6, 568, 576, 2020年11月, [国内誌]
    英語, 研究論文(学術雑誌), PURPOSE: To determine whether topical tacrolimus can lessen steroid-induced intraocular pressure (IOP) elevation. STUDY DESIGN: Open cohort post hoc analysis study. METHODS: Five hundred eleven patients with vernal keratoconjunctivitis or atopic keratoconjunctivitis (mean age 17.0 ± 9.2 years) were studied. All 511 patients were treated with topical tacrolimus with or without topical steroids, and the changes in IOP were measured monthly for 3 months. The elevation in IOP induced by use of topical steroids was calculated using mixed linear regression analyses. The relationship between the elevation in IOP within 4 weeks and the use or nonuse of tacrolimus reported in published data was analyzed using metaregression analysis to estimate the effects of tacrolimus on the IOP in eyes treated with topical steroids. RESULTS: The mean topical steroid-induced IOP elevation in tacrolimus-treated eyes was lower, by 5.2 mmHg (P = 0.04), than that in earlier published data without tacrolimus as the control. In the tacrolimus-treated eyes, the mean betamethasone-induced IOP elevation was 1.3 mmHg without discontinuation of the steroid. Metaregression analysis indicated that glaucoma history and younger age had significant effects on topical steroid-induced IOP elevation, by 4.0 mmHg (P = 0.002) and 3.9 mmHg (P = 0.01), respectively. In tacrolimus-treated eyes, the most significant effect on the IOP was associated with glaucoma history or medication; however, its effect on the IOP was limited to 1.7 mmHg elevation (P = 0.006). CONCLUSIONS: Topical tacrolimus may lessen the steroid-induced elevation in IOP in younger individuals and may be a good adjunctive therapy to avoid IOP elevation in refractory cases.
  • Alteration of oral flora in Mongolian patients with Behçet's disease: a multicentre study.
    Javzandulam Balt, Osamu Uehara, Yoshihiro Abiko, Baasankhuu Jamyanjav, Sarantuya Jav, Toshiyuki Nagasawa, Mari Mori, Yukihiro Horie, Mari Fujita, Anton Lennikov, Tohru Ohta, Miki Hiraoka, Daiju Iwata, Kenichi Namba, Shigeaki Ohno, Nobuyoshi Kitaichi
    Clinical and experimental rheumatology, 38 Suppl 127, 5, 80, 85, 2020年10月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), OBJECTIVES: Behçet's disease (BD) is characterised by repeated acute inflammatory attacks with aphthous ulcers of the oral mucosa, uveitis of the eyes, skin symptoms, and genital ulcers. Although its aetiology is still unknown, there is evidence of the involvement of oral bacteria in systemic diseases. Various types of oral bacteria may be involved in the development and progression of BD. The present study investigated alterations in the oral flora of patients with BD in Mongolia. We collected saliva samples from the Mongolian BD group and healthy control (HC) group, and the oral flora were analysed using next-generation sequencer (NGS). METHODS: DNA was extracted from the unstimulated saliva samples from the 47 BD and 48 HC subjects. The DNA was amplified from the V3-V4 region of 16S rRNA using PCR, and the data were acquired using NGS. Based on the obtained data, we analysed the alpha diversity, beta diversity, and bacterial taxonomy of the salivary flora. RESULTS: Beta diversity differed significantly between the BD and HC flora, but no significant differences were observed in alpha diversity. We found that the proportions of three genera - an S24-7 family unknown species, a mitochondria family unknown species, and Akkermansia species associated with IL-10 production - were significantly lower in the BD than in the HC group. CONCLUSIONS: The reduced proportions of the S24-7 family and symbiotic Akkermansia species may be key phenomena in the oral flora of patients with BD.
  • Clinical Characteristics, Management, and Factors Associated with Poor Visual Prognosis of Acute Retinal Necrosis.
    Hiroshi Takase, Hiroshi Goto, Kenichi Namba, Nobuhisa Mizuki, Annabelle A Okada, Nobuyuki Ohguro, Koh-Hei Sonoda, Makoto Tomita, Hiroshi Keino, Takeshi Kezuka, Reo Kubono, Kazuomi Mizuuchi, Etsuko Shibuya, Hiroyuki Takahashi, Ryoji Yanai, Manabu Mochizuki
    Ocular immunology and inflammation, 30, 1, 1, 6, 2020年09月18日, [国際誌]
    英語, 研究論文(学術雑誌), Purpose: To identify the clinical characteristics of acute retinal necrosis (ARN) and clarify factors associated with poor visual prognosis. Methods: a nationwide multi-center retrospective chart review study was performed in Japan using data from the medical records of 149 consecutive ARN patients. Demographics, ocular signs, virologic testing of intraocular fluids, and treatment were examined. Factors associated with poor visual prognosis were investigated by regression analysis. Results: At initial presentation, anterior chamber cells or mutton-fat keratic precipitates (97%), unilaterality (93%), and yellow-white retinal lesions (86%) were recognized. In the clinical course, rapid circumferential expansion of retinal lesions (39%), development of retinal break or retinal detachment (55%), and optic atrophy (43%) were recorded. Four variables were identified as associated with poor visual prognosis. Conclusions: The present study identified clinical characteristics and factors associated with poor visual prognosis of ARN.
  • Genetic control of CCL24, POR, and IL23R contributes to the pathogenesis of sarcoidosis.
    Akira Meguro, Mami Ishihara, Martin Petrek, Ken Yamamoto, Masaki Takeuchi, Frantisek Mrazek, Vitezslav Kolek, Alzbeta Benicka, Takahiro Yamane, Etsuko Shibuya, Atsushi Yoshino, Akiko Isomoto, Masao Ota, Keisuke Yatsu, Noriharu Shijubo, Sonoko Nagai, Etsuro Yamaguchi, Tetsuo Yamaguchi, Kenichi Namba, Toshikatsu Kaburaki, Hiroshi Takase, Shin-Ichiro Morimoto, Junko Hori, Keiko Kono, Hiroshi Goto, Takafumi Suda, Soichiro Ikushima, Yasutaka Ando, Shinobu Takenaka, Masaru Takeuchi, Takenosuke Yuasa, Katsunori Sugisaki, Nobuyuki Ohguro, Miki Hiraoka, Nobuyoshi Kitaichi, Yukihiko Sugiyama, Nobuyuki Horita, Yuri Asukata, Tatsukata Kawagoe, Ikuko Kimura, Mizuho Ishido, Hidetoshi Inoko, Manabu Mochizuki, Shigeaki Ohno, Seiamak Bahram, Elaine F Remmers, Daniel L Kastner, Nobuhisa Mizuki
    Communications biology, 3, 1, 465, 465, 2020年08月21日, [国際誌]
    英語, 研究論文(学術雑誌), Sarcoidosis is a genetically complex systemic inflammatory disease that affects multiple organs. We present a GWAS of a Japanese cohort (700 sarcoidosis cases and 886 controls) with replication in independent samples from Japan (931 cases and 1,042 controls) and the Czech Republic (265 cases and 264 controls). We identified three loci outside the HLA complex, CCL24, STYXL1-SRRM3, and C1orf141-IL23R, which showed genome-wide significant associations (P < 5.0 × 10-8) with sarcoidosis; CCL24 and STYXL1-SRRM3 were novel. The disease-risk alleles in CCL24 and IL23R were associated with reduced CCL24 and IL23R expression, respectively. The disease-risk allele in STYXL1-SRRM3 was associated with elevated POR expression. These results suggest that genetic control of CCL24, POR, and IL23R expression contribute to the pathogenesis of sarcoidosis. We speculate that the CCL24 risk allele might be involved in a polarized Th1 response in sarcoidosis, and that POR and IL23R risk alleles may lead to diminished host defense against sarcoidosis pathogens.
  • Pseudo-inflammatory manifestations of choroidal lymphoma resembling Vogt-Koyanagi-Harada disease: case report based on multimodal imaging.
    Kanae Fukutsu, Kenichi Namba, Daiju Iwata, Kazuomi Mizuuchi, Satoru Kase, Kayo Suzuki, Hiroshi Shimizu, Yukiko Shibata, Fumihiko Yamawaki, Masahiro Onozawa, Susumu Ishida
    BMC ophthalmology, 20, 1, 94, 94, 2020年03月10日, [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: Hematologic malignancies occasionally cause serous retinal detachment (SRD); however, its pathogenesis remains unclear. Here we present the imaging characteristics of metastatic choroidal lymphoma masquerading as Vogt-Koyanagi-Harada (VKH) disease. CASE PRESENTATION: A 45-year-old Japanese woman was referred to our clinic because of bilateral SRD with blurred vision. Fluorescein angiography revealed multiple pinpoint leakage followed by pooling OU. Enhanced depth imaging optical coherence tomography showed marked choroidal thickening OU. Laser speckle flowgraphy detected choroidal circulation impairment OU. Although these results totally agreed with the inflammatory manifestations of acute VKH disease, indocyanine green angiography demonstrated various sizes of sharply marginated hypofluorescent lesions that seemed atypical for the finding of VKH disease, i.e., vaguely marginated hypofluorescent small dots. Cerebrospinal fluid pleocytosis was not detected. Blood tests revealed leukocytosis together with elevation of lactate dehydrogenase and soluble interleukin-2 receptor levels. Corticosteroid pulse therapy did not improve any ocular findings. Bone marrow biopsy was then performed, leading to a definite diagnosis of diffuse large B-cell lymphoma. After starting systemic chemotherapy, both SRD and choroidal thickening resolved rapidly with visual recovery. However, choroidal hypoperfusion persisted, which contrasted distinctly with the inflammatory pattern of VKH disease, i.e., the restoration of choroidal blood flow in parallel with normalization of choroidal thickness. CONCLUSIONS: Our detailed multimodal observations highlighted the differential imaging features of choroidal lymphoma despite close resemblance to VKH disease especially at the initial stage. Impaired circulation in the thickened choroid marked the pseudo-inflammatory pathogenesis of SRD due to choroidal involvement with neoplastic, but not inflammatory cells.
  • Variants in IL23R-C1orf141 and ADO-ZNF365-EGR2 are associated with susceptibility to Vogt-Koyanagi-Harada disease in Japanese population.
    Takuto Sakono, Akira Meguro, Masaki Takeuchi, Takahiro Yamane, Takeshi Teshigawara, Nobuyoshi Kitaichi, Yukihiro Horie, Kenichi Namba, Shigeaki Ohno, Kumiko Nakao, Taiji Sakamoto, Tsutomu Sakai, Tadashi Nakano, Hiroshi Keino, Annabelle A Okada, Atsunobu Takeda, Takako Ito, Hisashi Mashimo, Nobuyuki Ohguro, Shinichirou Oono, Hiroshi Enaida, Satoshi Okinami, Nobuyuki Horita, Masao Ota, Nobuhisa Mizuki
    PloS one, 15, 5, e0233464, 2020年, [国際誌]
    英語, 研究論文(学術雑誌), Vogt-Koyanagi-Harada (VKH) disease is a systemic inflammatory disorder that affects pigment cell-containing organs such as the eye (e.g., chronic and/or recurrent granulomatous panuveitis). While the exact etiology and pathogenic mechanism of VKH disease are unclear, HLA-DR4 alleles have been documented to be strongly associated with VKH disease in various ethnic groups. Recently, a genome-wide association study (GWAS) found two new genetic risk factors (IL23R-C1orf141 and ADO-ZNF365-EGR2) in a non-HLA region from a Han Chinese population. In this study, we replicated these GWAS findings in a Japanese population. A total of 1,643 Japanese samples (380 cases with VKH disease and 1,263 healthy controls) were recruited. We assessed four single nucleotide polymorphisms (SNPs) shown in previous GWAS: rs78377598 and rs117633859 in IL23R-C1orf141, and rs442309 and rs224058 in ADO-ZNF365-EGR2. A significant allelic association with VKH disease was observed for all of the four SNPs (rs78377598: pc = 0.0057; rs117633859: pc = 0.0017; rs442309: pc = 0.021; rs224058: pc = 0.035). In genotypic association analysis, the minor alleles of IL23R-C1orf141 rs78377598 and rs117633859 had the strongest association with disease susceptibility under the additive model (pc = 0.0075 and pc = 0.0026, respectively). The minor alleles of ADO-ZNF365-EGR2 rs442309 and rs224058 were most strongly associated with disease susceptibility under the dominant model (pc = 0.00099 and pc = 0.0023, respectively). The meta-analysis of the current and previous studies found that all of the four SNPs exhibited a significantly strong association with VKH disease (meta-p < 0.00001: rs78377598, meta-odds ratio (OR) = 1.69; rs1176338, meta-OR = 1.82; rs442309, meta-OR = 1.34; rs224058, meta-OR = 1.33). In summary, our study replicated significant associations with VKH disease susceptibility reported in a previous GWAS. Thus, the IL23R-C1orf141 and ADO-ZNF365-EGR2 loci may play important roles in the development of VKH disease through genetic polymorphisms.
  • Air pollution significantly associated with severe ocular allergic inflammatory diseases.
    Miyazaki D, Fukagawa K, Fukushima A, Fujishima H, Uchio E, Ebihara N, Shoji J, Takamura E, Namba K, Ohashi Y, Okamoto S, Satake Y, Ohtsu H, Shimizu Y, Inoue Y
    Scientific reports, 9, 1, 18205, 18205, 2019年12月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Ambient air pollution is a well-recognized risk for various diseases including asthma and heart diseases. However, it remains unclear whether air pollution may also be a risk of ocular allergic diseases. Using a web-based, nation-wide, cross-sectional study design, we examined whether the level of ambient air pollution is significantly associated with the prevalence of ocular allergic diseases. A web-based questionnaire was posted to invite the participants who are members of the Japan Ophthalmologist Association and their family members. The answers from 3004 respondents were used to determine whether there were significant associations between the level of the pollutants and the prevalence of ocular allergic diseases. The study period was between March to May 2017. The data of the air pollutants during 2012 to 2016 were obtained from the National Institute for Environmental Studies. The prevalence of allergic diseases was calculated by post stratification and examined for significant associations with the level of pollutants using multiple logistic regression analyses. The prevalence of seasonal allergic conjunctivitis, perennial allergic conjunctivitis, atopic keratoconjunctivitis (AKC), and vernal keratoconjunctivitis (VKC) in Japan was 45.4%, 14.0%, 5.3%, and 1.2%, respectively. The high prevalence of the severe forms of allergic conjunctivitis, including AKC and VKC, were significantly associated with the levels of the air pollutants. The prevalence of AKC was significantly associated with the levels of NO2 with an odds ratio (OR) of 1.23 (per quintile). The prevalence of VKC was significantly associated with the levels of NOx and PM10 with ORs of 1.72 and 1.54 respectively. The significant associations between the prevalence of AKC and VKC and the levels of air pollutants indicate that clinicians need to be aware that air pollutants may pose serious risks of vision threatening severe ocular allergy.
  • Comparison of clinical characteristics in patients with Vogt-Koyanagi-Harada disease with and without anti-retinal antibodies.
    Yuki Hashimoto, Wataru Saito, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Kousuke Noda, Atsuhiro Kanda, Susumu Ishida
    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 257, 8, 1751, 1758, 2019年08月, [国際誌]
    英語, 研究論文(学術雑誌), PURPOSE: To compare the clinical characteristics of Vogt-Koyanagi-Harada (VKH) disease patients with and without anti-retinal antibodies (ARAs) that are frequently detected in autoimmune retinopathy. METHODS: Using immunoblot analyses, serum autoantibodies for recoverin, carbonic anhydrase II, and α-enolase were examined in 20 treatment-naïve patients with VKH disease. Clinical factors before and after systemic corticosteroid therapy, including best-corrected visual acuity (BCVA) and macular outer retinal morphology, were statistically compared between patients with VKH disease with and without ARAs. RESULTS: Serum ARAs were detected in 50.0% of patients with VKH disease. There were no significant differences in clinical factors between the two groups, including final BCVA, frequency of uveitis recurrence, and recovery of the macular ellipsoid zone after systemic corticosteroid therapy. CONCLUSIONS: Our results suggest that the detected ARAs did not influence visual outcomes, the chronicity of uveitis, or outer retinal morphology in patients with VKH disease.
  • Topical Tacrolimus for Chronic Allergic Conjunctival Disease with and without Atopic Dermatitis
    Jun Shoji, Yuichi Ohashi, Atsuki Fukushima, Dai Miyazaki, Eiichi Uchio, Etsuko Takamura, Hiroshi Fujishima, Kenichi Namba, Naoki Kumagai, Nobuyuki Ebihara, Shigeki Okamoto
    Current Eye Research, 44, 7, 796, 805, Taylor and Francis Ltd, 2019年07月03日, [国際誌]
    英語, 研究論文(学術雑誌)
  • Cyclosporine and prednisolone combination therapy as a potential therapeutic strategy for relentless placoid chorioretinitis.
    Takehiko Uraki, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Shigeaki Ohno, Nobuyoshi Kitaichi, Susumu Ishida
    American journal of ophthalmology case reports, 14, 87, 91, 2019年06月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Purpose: Relentless placoid chorioretinitis (RPC) is a new disease concept that was proposed by Jones et al. in 2000. Some cases of RPC have been reported; however, a treatment strategy has not yet been established. We report herein four cases of patients diagnosed with RPC. Observations: We experienced four cases of RPC in patients aged 24-51 years. All patients exhibited retinal lesions similar to that seen in acute posterior multifocal placoid pigment epitheliopathy or serpiginous choroiditis from the posterior pole to the surrounding region. Although patients underwent systemic prednisolone (PSL) therapy, recurrence was observed and the retinal scar formation was progressive; they were then diagnosed with RPC. In all cases, cyclosporine (CyA) was administered in addition to PSL, no recurrence was observed thereafter. Conclusions and Importance: RPC is a rare disease, and a treatment strategy has not yet been established. CyA and PSL combination therapy is considered to be effective in the treatment of RPC.
  • 人工多能性幹細胞由来マクロファージ様免疫抑制細胞を用いたぶどう膜炎モデルの軽症化
    長谷 敬太郎, 南場 研一, 北市 伸義, 岩田 大樹, 辻 飛雄馬, 和田 はるか, 清野 研一郎, 石田 晋
    日本眼科学会雑誌, 123, 臨増, 226, 226, (公財)日本眼科学会, 2019年03月
    日本語
  • Real-world evidence of treatment for relapse of noninfectious uveitis in tertiary centers in Japan: A multicenter study.
    Masaru Takeuchi, Takayuki Kanda, Toshikatsu Kaburaki, Rie Tanaka, Kenichi Namba, Koju Kamoi, Kazuichi Maruyama, Etsuko Shibuya, Nobuhisa Mizuki
    Medicine, 98, 9, e14668, 2019年03月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Noninfectious uveitis (NIU), which pathogenesis is often autoimmune nature, occurs as a symptom of systemic syndromes or only in the eye. The standard treatment of NIU is local, topical, and oral administration of corticosteroids (CS) in combination with immunomodulatory therapy (IMT). However, additional therapeutic strategies involving topical and systemic administration of CS or others to treat relapse or exacerbation of ocular inflammation in NIU which present as various ocular manifestations have not been established. The aim of this study was to investigate therapeutic strategies used for various ocular inflammations in relapse or exacerbation of NIU and to evaluate factors associated with the treatment pattern in Japan. The subjects were 198 eyes of 156 NIU patients with relapse or exacerbation of ocular inflammation at 6 university hospitals in Japan. The most frequent disease was sarcoidosis in 23.7% of the cases, followed by Behçet disease (BD) in 21.2%, Vogt-Koyanagi-Harada (VKH) disease in 13.6%, acute anterior uveitis (AAU) in 5.6%, tubulointerstitial nephritis and uveitis syndrome (TINU) in 4.0%, and juvenile idiopathic arthritis (JIA)-associated uveitis in 3.0%. Common ocular findings were worsened anterior inflammation (AI) in 67.2% of the cases, vitreous opacity (VO) in 46.5%, macular edema (ME) in 26.8%, retinal vasculitis (RV) in 23.7%, serous retinal detachment (SRD) in 9.1%, and optic perineuritis (OPN) in 4.0%. Reinforcement of betamethasone eye drop (ED) monotherapy for only AI in both unilateral and bilateral AI, sub-tenon injection of triamcinolone acetonide (STTA) for unilateral posterior inflammation including VO and ME, and systemic therapy using CS and/or IMT for bilateral anterior and posterior inflammation were significantly more frequent. Frequencies of exacerbated individual ocular findings in sarcoidosis and BD were similar, and severe ocular inflammation associated with panuveitis required both topical and systemic therapies. These results demonstrate that reinforcement of betamethasone EDs, topical administration of triamcinolone acetonide, and long-term administration of systemic corticosteroids are the major therapeutic strategies, and reinforcement of betamethasone EDs was used for exacerbated AI independently from its use for posterior inflammation. In addition, STTA was preferentially used for VO and ME associated with posterior inflammation.
  • A case of nodular posterior scleritis simulating intraocular tumor.
    Yukiko Shibata, Satoru Kase, Kenichi Namba, Susumu Ishida
    International journal of ophthalmology, 12, 4, 685, 688, 2019年, [国際誌]
    英語, 研究論文(学術雑誌)
  • Association Study of ARMC9 Gene Variants with Vogt-Koyanagi-Harada Disease in Japanese Patients.
    Tomoko Ohno, Akira Meguro, Masaki Takeuchi, Takahiro Yamane, Takeshi Teshigawara, Nobuyoshi Kitaichi, Yukihiro Horie, Kenichi Namba, Shigeaki Ohno, Kumiko Nakao, Taiji Sakamoto, Tsutomu Sakai, Tadashi Nakano, Hiroshi Keino, Annabelle A Okada, Atsunobu Takeda, Takako Fukuhara, Hisashi Mashimo, Nobuyuki Ohguro, Shinichirou Oono, Hiroshi Enaida, Satoshi Okinami, Nobuhisa Mizuki
    Ocular immunology and inflammation, 27, 5, 699, 705, 2019年, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Purpose: To investigate whether variants in the ARMC9 gene encoding KU-MEL-1 are associated with Vogt-Koyanagi-Harada (VKH) disease in a Japanese population. Methods: We recruited 380 Japanese patients with VKH disease and 744 Japanese healthy controls to genotype seven single-nucleotide polymorphisms (SNPs) in ARMC9. We also performed imputation analysis of the ARMC9 region and 195 imputed SNPs were included in the statistical analysis. Results: We observed an increased frequency of the A allele of rs28690417 in patients compared with controls (P = 0.0097, odds ratio (OR) = 1.46). The A allele had a dominant effect on VKH disease risk (P = 0.011, OR = 1.51). However, these significant differences disappeared after Bonferroni correction (corrected P > 0.05). The remaining 201 SNPs did not show any significant association with disease risk. Conclusions: Our study suggests that ARMC9 variants do not play a critical role in the development of VKH disease.
  • Adalimumab in Active and Inactive, Non-Infectious Uveitis: Global Results from the VISUAL I and VISUAL II Trials.
    Hiroshi Goto, Masahiro Zako, Kenichi Namba, Noriyasu Hashida, Toshikatsu Kaburaki, Masanori Miyazaki, Koh-Hei Sonoda, Toshiaki Abe, Nobuhisa Mizuki, Koju Kamoi, Antoine P Brézin, Andrew D Dick, Glenn J Jaffe, Quan Dong Nguyen, Noritaka Inomata, Nisha V Kwatra, Anne Camez, Alexandra P Song, Martina Kron, Samir Tari, Shigeaki Ohno
    Ocular immunology and inflammation, 27, 1, 40, 50, 2019年, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), PURPOSE: Report global adalimumab safety and efficacy outcomes in patients with non-infectious uveitis. METHODS: Adults with non-infectious intermediate, posterior, or panuveitis were randomized 1:1 to receive placebo or adalimumab in the VISUAL I (active uveitis) or VISUAL II (inactive uveitis) trials. Integrated global and Japan substudy results are reported. The primary endpoint was time to treatment failure (TF). RESULTS: In the integrated studies, TF risk was significantly reduced (hazard ratio [95% CI]) with adalimumab versus placebo (VISUAL I: HR = 0.56 [0.40-0.76], p < 0.001; VISUAL II: HR = 0.52 [0.37-0.74], p < 0.001). In Japan substudies, no consistent trends were observed between groups (VISUAL I: HR = 1.20 [0.41-3.54]; VISUAL II: HR = 0.45 [0.20-1.03]). Adverse event rates were similar between treatment groups in both studies (854 to 1063 events/100 participant-years). CONCLUSIONS: Adalimumab lowered time to TF versus placebo in the integrated population; no consistent trends were observed in Japan substudies. Safety results were consistent between studies.
  • Immunohistochemical and Immunocytochemical Analyses in Patients with Vitreoretinal Lymphoma.
    Kase S, Namba K, Kanno-Okada H, Onozawa M, Hidaka D, Iwata D, Mizuuchi K, Fukuhara T, Fukuhara J, Kitaichi N, Matsuno Y, Ishida S
    Ocular immunology and inflammation, 28, 1, 1, 9, 2018年10月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Purpose: The aim of this study was to analyze immunohistochemical and immunocytological findings by examining enucleated eyes and vitreous cell block (CB) in patients with vitreoretinal lymphoma (VRL).Methods: Histological specimens were obtained from two enucleated eyes with VRL associated with neovascular glaucoma. CB specimens were prepared in 18 patients from diluted waste fluids containing shredded vitreous. Histological and cytological specimens were submitted for hematoxylin-eosin staining and immunopathological analyses.Results: Both specimens demonstrated massive infiltration of large lymphoma cells. The lymphoma cells were positive for CD20 and MUM-1 in enucleated eyes. Membranous immunoreactivity for CD20 was observed in lymphoma cells in CB with VRL. Bcl-6 and MUM-1 were marked in five and eight out of nine cases examined, respectivelyConclusions: Cytological findings in CB specimens indicated similar histopathological characteristics of enucleated eyes. CB specimens obtained from vitreous waste diluted fluids may serve as effective materials for cytological diagnosis of VRL.
  • Two cases of cytomegalovirus panuveitis in immunocompetent patients
    Masato Sakai, Hiroshi Takase, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Susumu Ishida
    American Journal of Ophthalmology Case Reports, 10, 189, 191, Elsevier Inc, 2018年06月01日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Cytopathologic findings of cell block materials from the vitreous: Diagnostic distinction between intraocular lymphoma and non-lymphomatous diseases
    Hiromi Kanno-Okada, Emi Takakuwa, Yoshiaki Tagawa, Satoru Kase, Kanako C. Hatanaka, Yutaka Hatanaka, Kenichi Namba, Tomoko Mitsuhashi, Yoshihiro Matsuno
    PATHOLOGY INTERNATIONAL, 67, 7, 342, 349, 2017年07月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • A Novel Single-Strand RNAi Therapeutic Agent Targeting the (Pro)renin Receptor Suppresses Ocular Inflammation
    Atsuhiro Kanda, Erdal Tan Ishizuka, Atsushi Shibata, Takahiro Matsumoto, Hidekazu Toyofuku, Kousuke Noda, Kenichi Namba, Susumu Ishida
    MOLECULAR THERAPY-NUCLEIC ACIDS, 7, 116, 126, 2017年06月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Evaluating the efficacy of epinastine ophthalmic solution using a conjunctivitis allergen challenge model in patients with birch pollen allergic conjunctivitis
    Yoshiaki Tagawa, Kenichi Namba, Yumi Nakazono, Daiju Iwata, Susumu Ishida
    ALLERGOLOGY INTERNATIONAL, 66, 2, 338, 343, 2017年04月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Japanese guidelines for allergic conjunctival diseases 2017
    Etsuko Takamura, Eiichi Uchio, Nobuyuki Ebihara, Shigeaki Ohno, Yuichi Ohashi, Shigeki Okamoto, Naoki Kumagai, Yoshiyuki Satake, Jun Shoji, Yayoi Nakagawa, Kenichi Namba, Kazumi Fukagawa, Atsuki Fukushima, Hiroshi Fujishima
    ALLERGOLOGY INTERNATIONAL, 66, 2, 220, 229, 2017年04月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • 春季カタルにおけるタクロリムス点眼薬の長期使用成績
    品川真有子, 南場研一, 北市伸義, 石田晋
    臨床眼科, 71, 3, 343, 348, Igaku-Shoin Ltd, 2017年03月01日
    日本語
  • Investigation of the association between IL10 gene polymorphisms and Vogt-Koyanagi-Harada disease in a Japanese population
    Kaori Higashi, Akira Meguro, Masaki Takeuchi, Takahiro Yamane, Nobuyoshi Kitaichi, Yukihiro Horie, Kenichi Namba, Shigeaki Ohno, Kumiko Nakao, Taiji Sakamoto, Tsutomu Sakai, Hiroshi Tsuneoka, Hiroshi Keino, Annabelle A. Okada, Atsunobu Takeda, Takako Fukuhara, Hisashi Mashimo, Nobuyuki Ohguro, Shinichirou Oono, Hiroshi Enaida, Satoshi Okinami, Nobuhisa Mizuki
    OPHTHALMIC GENETICS, 38, 2, 187, 189, 2017年03月, [査読有り], [国際誌]
    英語
  • Steroid-Sparing Effect of 0.1% Tacrolimus Eye Drop for Treatment of Shield Ulcer and Corneal Epitheliopathy in Refractory Allergic Ocular Diseases
    Dai Miyazaki, Atsuki Fukushima, Yuichi Ohashi, Nobuyuki Ebihara, Eiichi Uchio, Shigeki Okamoto, Jun Shoji, Etsuko Takamura, Yayoi Nakagawa, Kenichi Namba, Hiroshi Fujishima
    OPHTHALMOLOGY, 124, 3, 287, 294, 2017年03月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Early post-treatment choroidal thickness to alert sunset glow fundus in patients with Vogt-Koyanagi- Harada disease treated with systemic corticosteroids
    Kiriko Hirooka, Wataru Saito, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Yuki Hashimoto, Susumu Ishida
    PLOS ONE, 12, 2, e0172612, 2017年02月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • HLA-B51 Carriers are Susceptible to Ocular Symptoms of Behçet Disease and the Association between the Two Becomes Stronger towards the East along the Silk Road: A Literature Survey.
    Horie Y, Meguro A, Ohta T, Lee EB, Namba K, Mizuuchi K, Iwata D, Mizuki N, Ota M, Inoko H, Ishida S, Ohno S, Kitaichi N
    Ocular immunology and inflammation, 25, 1, 37, 40, 2017年, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Serial Frequencies and Clinical Features of Uveitis in Hokkaido, Japan
    Daiju Iwata, Kazuomi Mizuuchi, Koki Aoki, Yukihiro Horie, Satoru Kase, Kenichi Namba, Shigeaki Ohno, Susumu Ishida, Nobuyoshi Kitaichi
    OCULAR IMMUNOLOGY AND INFLAMMATION, 25, sup1, S15, S18, 2017年, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Invariant natural killer T cells play dual roles in the development of experimental autoimmune uveoretinitis.
    Satoh M, Namba KI, Kitaichi N, Endo N, Kitamei H, Iwata D, Ohno S, Ishida S, Onoé K, Watarai H, Taniguchi M, Ishibashi T, Stein-Streilein J, Sonoda KH, Van Kaer L, Iwabuchi K
    Experimental eye research, 153, 79, 89, 2016年12月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Choroidal circulation impairment during the anterior recurrence of Vogt-Koyanagi-Harada disease confirmed with indocyanine green angiography and laser speckle flowgraphy
    Yuko Takemoto, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Tomoe Uno, Shigeaki Ohno, Kiriko Hirooka, Yuki Hashimoto, Wataru Saito, Kazuhisa Sugiyama, Susumu Ishida
    ACTA OPHTHALMOLOGICA, 94, 7, E629, E636, 2016年11月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Choroidal thickening prior to anterior recurrence in patients with Vogt-Koyanagi-Harada disease
    Yoshiaki Tagawa, Kenichi Namba, Kazuomi Mizuuchi, Yuko Takemoto, Daiju Iwata, Tomoe Uno, Takako Fukuhara, Kiriko Hirooka, Nobuyoshi Kitaichi, Shigeaki Ohno, Susumu Ishida
    BRITISH JOURNAL OF OPHTHALMOLOGY, 100, 4, 473, 477, 2016年04月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Diagnostic efficacy of cell block method for vitreoretinal lymphoma
    Satoru Kase, Kenichi Namba, Daiju Iwata, Kazuomi Mizuuchi, Nobuyoshi Kitaichi, Yoshiaki Tagawa, Hiromi Okada-Kanno, Yoshihiro Matsuno, Susumu Ishida
    DIAGNOSTIC PATHOLOGY, 11, 29, 29, 2016年03月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Behçet’s disease
    Shigeaki Ohno, Kenichi Namba, Yuko Takemoto
    Intraocular Inflammation, 785, 795, Springer Berlin Heidelberg, 2016年01月01日, [査読有り]
    英語, 論文集(書籍)内論文
  • Kawasaki disease
    Shigeaki Ohno, Kenichi Namba, Hirokuni Kitamei
    Intraocular Inflammation, 755, 759, Springer Berlin Heidelberg, 2016年01月01日, [査読有り]
    英語, 論文集(書籍)内論文
  • Posner-schlossman syndrome
    Shigeaki Ohno, Kenichi Namba, Akiko Miyazaki
    Intraocular Inflammation, 1007, 1012, Springer Berlin Heidelberg, 2016年01月01日, [査読有り]
    英語, 論文集(書籍)内論文
  • A Case of Severe Panuveitis Associated with Psoriasis Vulgaris Successfully Treated with Infliximab
    Yuri Sakurai, Kenichi Namba, Kazuomi Mizuuchi, Toshihumi Nomura, Susumu Ishida
    Case Reports in Ophthalmology, 7, 1, 191, 194, S. Karger AG, 2016年, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Ocular Behçet's disease is less complicated with allergic disorders. A nationwide survey in Japan.
    Horie Y, Kitaichi N, Hijioka K, Sonoda KH, Saishin Y, Kezuka T, Goto H, Takeuchi M, Nakamura S, Kimoto T, Shimakawa M, Kita M, Sugita S, Mochizuki M, Hori J, Iwata M, Shoji J, Fukuda M, Kaburaki T, Numaga J, Kawashima H, Fukushima A, Joko T, Takai N, Ozawa Y, Meguro A, Mizuki N, Namba K, Ishida S, Ohno S
    Clinical and experimental rheumatology, 34, 6 Suppl 102, 111, 114, Clinical and Experimental Rheumatology S.A.S., 2016年, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Significant role of the choroidal outer layer during recovery from choroidal thickening in Vogt-Koyanagi-Harada disease patients treated with systemic corticosteroids
    Kiriko Hirooka, Wataru Saito, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Yuki Hashimoto, Susumu Ishida
    BMC OPHTHALMOLOGY, 15, 181, 181, 2015年12月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • A case of tuberculous endophthalmitis successfully treated with vitrectomy followed by antituberculous agents
    Keitaro Hase, Kenichi Namba, Wataru Saito, Shigeaki Ohno, Susumu Ishida
    Journal of Ophthalmic Inflammation and Infection, 5, 1, 14, 14, Springer Verlag, 2015年12月01日, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Relationship between choroidal blood flow velocity and choroidal thickness during systemic corticosteroid therapy for Vogt-Koyanagi-Harada disease
    Kiriko Hirooka, Wataru Saito, Kenichi Namba, Yuko Takemoto, Kazuomi Mizuuchi, Tomoe Uno, Yoshiaki Tagawa, Yuki Hashimoto, Susumu Ishida
    GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 253, 4, 609, 617, 2015年04月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Acute Zonal Occult Outer Retinopathy in Japanese Patients: Clinical Features, Visual Function, and Factors Affecting Visual Function
    Saho Saito, Wataru Saito, Michiyuki Saito, Yuki Hashimoto, Shohei Mori, Kousuke Noda, Kenichi Namba, Susumu Ishida
    PLOS ONE, 10, 4, e0125133, 2015年04月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Single center study on ethnic and clinical features of Behcet's disease in Moscow, Russia.
    Lennikov Anton, Alekberova Zemfira, Goloeva Regina, Kitaichi Nobuyoshi, Denisov Lev, Namba Kenichi, Takeno Mitsuhiro, Ishigatsubo Yoshiaki, Mizuki Nobuhisa, Nasonov Eugeny, Ishida Susumu, Ohno Shigeaki
    Clinical rheumatology, 34, 2, 321, 7, 2015年02月, [査読有り]
    英語, For the purpose of investigating Behcet's disease (BD) in Russia, 250 consecutive patients (177 men and 73 women) diagnosed with BD between 1990 and 2010 at the Research Institute of Rheumatology, Russian Academy of Medical Sciences in Moscow were enrolled in this study. The ethnic backgrounds of the patients were reported as follows: 23.2% (58 cases) from Russia, 12.8% (32 cases) from Azerbaijan, 14.4% (36 cases) from Armenia, 8.8% (22 cases) from Chechnya, and 21.6% (55 cases) from Dagestan. The remaining 19.2% (48 cases) were from other regions or of unknown origin. More than half (57.6%) of the Behcet's disease patients originated from Central Asia, specifically Azerbaijan, Armenia, Chechnya, and Dagestan. The mean age at disease onset was 31.5 ± 9.38 (13-60) years old, and the most typical initial manifestations were oral aphthous ulcers. Patients aged 20-39 years old were more commonly affected and displayed a wide clinical spectrum of the disease, with varieties of severe internal organ involvement. The manifestations observed throughout the course of the disease included oral aphthous ulcers (100%), various cutaneous lesions (88.8%), genital ulcers (81.2%), and ocula
  • Single center study on ethnic and clinical features of Behcet's disease in Moscow, Russia
    Anton Lennikov, Zemfira Alekberova, Regina Goloeva, Nobuyoshi Kitaichi, Lev Denisov, Kenichi Namba, Mitsuhiro Takeno, Yoshiaki Ishigatsubo, Nobuhisa Mizuki, Eugeny Nasonov, Susumu Ishida, Shigeaki Ohno
    CLINICAL RHEUMATOLOGY, 34, 2, 321, 327, 2015年02月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • A Major Review: Current Aspects of Ocular Behçet's Disease in Japan.
    Namba K, Goto H, Kaburaki T, Kitaichi N, Mizuki N, Asukata Y, Fujino Y, Meguro A, Sakamoto S, Shibuya E, Yokoi K, Ohno S
    Ocular immunology and inflammation, 23, S1, S23, 2015年, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • A case of mature natural killer-cell neoplasm manifesting multiple choroidal lesions: Primary intraocular natural killer-cell lymphoma
    Yoshiaki Tagawa, Reiki Ogasawara, Hiromi Kanno, Susumu Ishida, Kenichi Namba
    Case Reports in Ophthalmology, 6, 3, 380, 384, S. Karger AG, 2015年, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Development and validation of new diagnostic criteria for acute retinal necrosis
    Hiroshi Takase, Annabelle A. Okada, Hiroshi Goto, Nobuhisa Mizuki, Kenichi Namba, Nobuyuki Ohguro, Koh-Hei Sonoda, Makoto Tomita, Hiroshi Keino, Takeshi Kezuka, Reo Kubono, Kazuomi Mizuuchi, Etsuko Shibuya, Hiroyuki Takahashi, Ryoji Yanai, Manabu Mochizuki
    JAPANESE JOURNAL OF OPHTHALMOLOGY, 59, 1, 14, 20, 2015年01月, [査読有り], [国内誌]
    英語, 研究論文(学術雑誌)
  • Amelioration of experimental autoimmune uveoretinitis by inhibition of glyceraldehyde-derived advanced glycation end-product formation
    Zhenyu Dong, Daiju Iwata, Nobuyoshi Kitaichi, Masayoshi Takeuchi, Masashi Sato, Noriko Endo, Kazuya Iwabuchi, Ryo Ando, Junichi Fukuhara, Satoshi Kinoshita, Anton Lennikov, Mizuki Kitamura, Kazuomi Mizuuchi, Atsuhiro Kanda, Kousuke Noda, Kenichi Namba, Sho-Ichi Yamagishi, Shigeaki Ohno, Susumu Ishida
    JOURNAL OF LEUKOCYTE BIOLOGY, 96, 6, 1077, 1085, 2014年12月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • 硝子体液細胞診における眼内悪性リンパ腫の細胞学的検討
    山谷 幸恵, 丸川 活司, 宮越 里絵, 清水 知活, 渡部 涼子, 望月 早苗, 菅野 宏美, 藤澤 孝志, 高桑 恵美, 畑中 佳奈子, 田川 義晃, 南場 研一, 三橋 智子, 松野 吉宏
    日本臨床細胞学会雑誌, 53, Suppl.2, 730, 730, (公社)日本臨床細胞学会, 2014年10月
    日本語
  • Evaluation of the long-term efficacy and safety of infliximab treatment for uveitis in Behçet's disease: a multicenter study.
    Takeuchi M, Kezuka T, Sugita S, Keino H, Namba K, Kaburaki T, Maruyama K, Nakai K, Hijioka K, Shibuya E, Komae K, Hori J, Ohguro N, Sonoda KH, Mizuki N, Okada AA, Ishibashi T, Goto H, Mochizuki M
    Ophthalmology, 121, 10, 1877, 1884, 2014年10月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Therapeutic effects of 0.1% tacrolimus eye drops for refractory allergic ocular diseases with proliferative lesion or corneal involvement
    Atsuki Fukushima, Yuichi Ohashi, Nobuyuki Ebihara, Eiichi Uchio, Shigeki Okamoto, Naoki Kumagai, Jun Shoji, Etsuko Takamura, Yayoi Nakagawa, Kenichi Namba, Hiroshi Fujishima, Dai Miyazaki
    BRITISH JOURNAL OF OPHTHALMOLOGY, 98, 8, 1023, 1027, 2014年08月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • [A case report of malignant lymphoma receiving infliximab therapy with Behçet's disease].
    Sonoda KH, Fukuhara T, Yoshikawa H, Takeda A, Yoshimura T, Akahoshi M, Kusumoto H, Kohno K, Kato K, Akashi K, Kohashi K, Aijima S, Namba K, Ishibashi T
    Nippon Ganka Gakkai zasshi, 118, 5, 440, 445, 日本眼科学会, 2014年05月, [査読有り], [国内誌]
    日本語, BACKGROUND: To report a case of malignant lymphoma occurring in Behçet's disease (BD) with infliximab therapy. CASE: A 62-year-old man was diagnosed with BD in 1997. Despite treatment with colchicine, cyclosporine and prednisolone, he had frequent bilateral posterior ocular attacks. He was started on infliximab in August 2007 and for 6 months had no ocular attacks. Cyclosporine was therefore reduced. After 4 years of infliximab administration, he had neither ocular attacks nor general symptoms. However, he had general malaise and weight loss from the end of March 2012. Peripheral blood examination showed abnormal cells, so we terminated the infliximab. Bone marrow aspiration showed diffuse proliferation of medium to large lymphoid cells, and the histological diagnosis was diffuse large B-cell lymphoma. He was treated with 8 cycles of chemotherapy and 4 times intrathecal chemotherapy, and is now in remission. After termination of infliximab, he had no further ocular attacks. CONCLUSION: Although malignant lymphoma associated with BD is rare, attending ophthalmologists need to keep it in mind.
  • 眼内悪性リンパ腫および鑑別疾患における硝子体液を用いた病理診断の有用性
    菅野宏美, 藤田裕美, 畑中佳奈子, 田川義晃, 南場研一, 三橋智子, 松野吉宏
    日本病理学会会誌, 103, 1, 293, 2014年03月26日
    日本語
  • The International Criteria for Behçet's Disease (ICBD): A collaborative study of 27 countries on the sensitivity and specificity of the new criteria
    F. Davatchi, S. Assaad-Khalil, K. T. Calamia, J. E. Crook, B. Sadeghi-Abdollahi, M. Schirmer, T. Tzellos, C. C. Zouboulis, M. Akhlagi, A. Al-Dalaan, Z. S. Alekberova, A. A. Ali, A. Altenburg, E. Arromdee, M. Baltaci, M. Bastos, S. Benamour, I. Ben Ghorbel, A. Boyvat, L. Carvalho, W. Chen, E. Ben-Chetrit, C. Chams-Davatchi, J. A. Correia, J. Crespo, C. Dias, Y. Dong, F. Paixão-Duarte, K. Elmuntaser, A. V. Elonakov, J. Graña Gil, A. A. Haghdoost, R. M. Hayani, H. Houman, A. R. Isayeva, A. R. Jamshidi, P. Kaklamanis, A. Kumar, A. Kyrgidis, W. Madanat, A. Nadji, K. Namba, S. Ohno, I. Olivieri, J. Vaz Patto, N. Pipitone, M. V. De Queiroz, F. Ramos, C. Resende, C. M. Rosa, C. Salvarani, M. J. Serra, F. Shahram, H. Shams, K. E. Sharquie, M. Sliti-Khanfir, T. Tribolet De Abreu, C. Vasconcelos, J. Vedes, B. Wechsler, Y. K. Cheng, Z. Zhang, N. Ziaei
    Journal of the European Academy of Dermatology and Venereology, 28, 3, 338, 347, 2014年03月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Behçet's disease ocular attack score 24: evaluation of ocular disease activity before and after initiation of infliximab.
    Kaburaki T, Namba K, Sonoda KH, Kezuka T, Keino H, Fukuhara T, Kamoi K, Nakai K, Mizuki N, Ohguro N, Ocular Behçet, Disease Research, Group of Japan
    Japanese journal of ophthalmology, 58, 2, 120, 130, 2014年03月, [査読有り], [国内誌]
    英語, 研究論文(学術雑誌)
  • Amelioration of endotoxin-induced uveitis treated with the sea urchin pigment echinochrome in rats
    Anton Lennikov, Nobuyoshi Kitaichi, Kousuke Noda, Kazuomi Mizuuchi, Ryo Ando, Zhenyu Dong, Junichi Fukuhara, Satoshi Kinoshita, Kenichi Namba, Shigeaki Ohno, Susumu Ishida
    MOLECULAR VISION, 20, 171, 177, 2014年02月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • 新しいBehcet病ぶどう膜炎の活動性スコアによる評価の再現性の検討               
    蕪城 俊克, 南場 研一, 園田 康平, 毛塚 剛司, 慶野 博, 福原 崇子, 鴨居 功樹, 中井 慶, Ocular Behcet Disease Research Group of Japan
    日本眼科学会雑誌, 117, 11, 935, 936, (公財)日本眼科学会, 2013年11月
    日本語
  • Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet's disease
    Yun Jong Lee, Yukihiro Horie, Graham R. Wallace, Yong Seok Choi, Ji Ah Park, Ji Yong Choi, Ran Song, Young-Mo Kang, Seong Wook Kang, Han Joo Baek, Nobuyoshi Kitaichi, Akira Meguro, Nobuhisa Mizuki, Kenichi Namba, Susumu Ishida, Jinhyun Kim, Edyta Niemczyk, Eun Young Lee, Yeong Wook Song, Shigeaki Ohno, Eun Bong Lee
    ANNALS OF THE RHEUMATIC DISEASES, 72, 9, 1510, 1516, 2013年09月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • エキノクロームによるラットEIUの軽症化
    アントン・レニコフ, 北市 伸義, 野田 航介, 南場 研一, 石田 晋, 大野 重昭, 大黒 浩
    日本眼薬理学会プログラム・抄録集, 33回, 44, 44, 日本眼薬理学会, 2013年09月
    日本語
  • Clinical features of human T lymphotropic virus type 1-associated uveitis in Hokkaido, Japan
    Satoru Kase, Kenichi Namba, Nobuyoshi Kitaichi, Daiju Iwata, Shigeaki Ohno, Susumu Ishida
    JAPANESE JOURNAL OF OPHTHALMOLOGY, 57, 4, 379, 384, 2013年07月, [査読有り], [国内誌]
    英語, 研究論文(学術雑誌)
  • [Case report; a case of IgG4-related disease presented as pericardial effusion].
    Yusuke Sugiyama, Hidenobu Takei, Hitoshi Tsuyuzaki, Masahiko Furubayashi, Toshiaki Hosaka, Miyoko Nakano, Kenichi Namba
    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine, 102, 6, 1458, 60, 2013年06月10日, [国内誌]
    日本語, 研究論文(学術雑誌)
  • Trabecular meshwork depigmentation in Vogt-Koyanagi-Harada disease.
    Kazuomi Mizuuchi, Nobuyoshi Kitaichi, Kenichi Namba, Yukihiro Horie, Susumu Ishida, Shigeaki Ohno
    Japanese journal of ophthalmology, 57, 3, 245, 51, 2013年05月, [査読有り], [国内誌]
    英語, 研究論文(学術雑誌), PURPOSE: Since some patients develop depigmentation of the trabecular meshwork in the course of Vogt-Koyanagi-Harada (VKH) disease, we examined the incidence of trabecular depigmentation and its correlation with other ocular findings and systemic symptoms. METHODS: We retrospectively reviewed the clinical charts of 53 Japanese patients diagnosed with VKH disease. The scores of trabecular and limbal pigmentation of all patients were recorded. We then examined the correlation between trabecular pigmentation and the presence of sunset glow fundus or skin lesions. RESULTS: Trabecular pigmentation was significantly lower in the patients with sunset glow fundus than in those without it (P = 0.022), whereas limbal pigmentation showed no significance. However, there were no significant differences in trabecular and limbal pigmentation between the patients with and those without skin lesions. Furthermore, there was no correlation between trabecular and limbal pigmentation. CONCLUSIONS: Depigmentation of the trabecular meshwork develops in some patients in the course of VKH disease. This depigmentation is significantly correlated with sunset glow fundus, but not with limbal depigmentation or skin lesions.
  • Acute retinal necrosis: factors associated with anatomic and visual outcomes
    Chiharu Iwahashi-Shima, Atsushi Azumi, Nobuyuki Ohguro, Annabelle A. Okada, Toshikatsu Kaburaki, Hiroshi Goto, Koh-Hei Sonoda, Kenichi Namba, Nobuhisa Mizuki, Manabu Mochizuki
    JAPANESE JOURNAL OF OPHTHALMOLOGY, 57, 1, 98, 103, 2013年01月, [査読有り], [国内誌]
    英語, 研究論文(学術雑誌)
  • Two cases of subfoveal choroidal neovascularization with tubulointerstitial nephritis and uveitis syndrome
    Yuko Takemoto, Kenichi Namba, Kazuomi Mizuuchi, Shigeaki Ohno, Susumu Ishida
    European Journal of Ophthalmology, 23, 2, 255, 257, 2013年, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Bacterial endophthalmitis caused by an intraocular cilium in a patient under treatment with infliximab
    Xue-Hai Jin, Kenichi Namba, Wataru Saito, Daiju Iwata, Susumu Ishida
    Journal of Ophthalmic Inflammation and Infection, 3, 1, 1, 3, 2013年, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Genetic Characterization and Susceptibility for Sarcoidosis in Japanese Patients: Risk Factors of BTNL2 Gene Polymorphisms and HLA Class II Alleles
    Hitomi Suzuki, Masao Ota, Akira Meguro, Yoshihiko Katsuyama, Tatukata Kawagoe, Mami Ishihara, Yuri Asukata, Masaki Takeuchi, Norihiko Ito, Etsuko Shibuya, Eiichi Nomura, Riyo Uemoto, Tadayuki Nishide, Kenichi Namba, Nobuyoshi Kitaichi, Shin-ichiro Morimoto, Toshikatsu Kaburaki, Yasutaka Ando, Shinobu Takenaka, Jutaro Nakamura, Kozou Saeki, Shigeaki Ohno, Hidetoshi Inoko, Nobuhisa Mizuki
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 53, 11, 7109, 7115, 2012年10月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Amelioration of endotoxin-induced uveitis treated with an IκB kinase β inhibitor in rats.
    Lennikov A, Kitaichi N, Noda K, Ando R, Dong Z, Fukuhara J, Kinoshita S, Namba K, Mizutani M, Fujikawa T, Itai A, Ohno S, Ishida S
    Molecular vision, 18, 267-70, 2586, 2597, 2012年10月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Correlation between elevation of serum antinuclear antibody titer and decreased therapeutic efficacy in the treatment of Behçet's disease with infliximab.
    Iwata D, Namba K, Mizuuchi K, Kitaichi N, Kase S, Takemoto Y, Ohno S, Ishida S
    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 250, 7, 1081, 1087, 2012年07月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Replication of a microsatellite genome-wide association study of Behcet's disease in a Korean population
    Yukihiro Horie, Akira Meguro, Nobuyoshi Kitaichi, Eun Bong Lee, Atsuhiro Kanda, Kousuke Noda, Yeong Wook Song, Kyung Sook Park, Kenichi Namba, Masao Ota, Hidetoshi Inoko, Nobuhisa Mizuki, Susumu Ishida, Shigeaki Ohno
    RHEUMATOLOGY, 51, 6, 983, 986, 2012年06月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Blood Level of Tacrolimus in Patients with Severe Allergic Conjunctivitis Treated by 0.1% Tacrolimus Ophthalmic Suspension
    Nobuyuki Ebihara, Yuichi Ohashi, Hiroshi Fujishima, Atsuki Fukushima, Yayoi Nakagawa, Kenichi Namba, Shigeki Okamoto, Jun Shoji, Etsuko Takamura, Eiichi Uchio, Dai Miyazaki
    ALLERGOLOGY INTERNATIONAL, 61, 2, 275, 282, 2012年06月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Spontaneous Regression of Intraocular Lymphoma
    Satoru Kase, Kenichi Namba, Xue-Hai Jin, Kanako C. Kubota, Susumu Ishida
    OPHTHALMOLOGY, 119, 5, 1083, 1084, 2012年05月, [査読有り], [国際誌]
    英語
  • Chickenpox chorioretinitis with retinal exudates and periphlebitis.
    Hirokuni Kitamei, Kenichi Namba, Nobuyoshi Kitaichi, Akiko Wakayama, Shigeaki Ohno, Susumu Ishida
    Case reports in ophthalmology, 3, 2, 180, 4, 2, 2012年05月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: Chickenpox is rarely associated with posterior segment inflammation. We report on a case of unilateral chickenpox chorioretinitis with retinal exudates and periphlebitis. CASE PRESENTATION: A 21-year-old healthy man, who suffered from chickenpox 2 weeks prior to symptom development, exhibited mild anterior chamber cells, vitreous opacity, sheathing of retinal veins, and yellow-white exudates in his right eye. Varicella zoster virus DNA was detected by polymerase chain reaction in the aqueous humor. He was treated with intravenous acyclovir followed by oral prednisolone and valaciclovir. Aqueous cells quickly disappeared and retinal exudates diminished within 1 month, leaving faint retinal scarring. Retinal arteritis had never been observed in this patient. CONCLUSIONS: ALTHOUGH THE OCULAR FINDINGS IN THIS CASE WERE SIMILAR TO ACUTE RETINAL NECROSIS (ARN), THE CLINICAL FEATURES DIFFERED FROM ARN IN THE FOLLOWING POINTS: (1) mild anterior chamber inflammation, (2) absence of retinal arteritis, and (3) prompt resolution of inflammatory findings. The distinctive clinical features indicated that chorioretinitis associated with chickenpox may not have the same pathological conditions as ARN.
  • Lack of association between IL10 polymorphisms and sarcoidosis in Japanese patients
    Kenichi Sakuyama, Akira Meguro, Masao Ota, Mami Ishihara, Riyo Uemoto, Haruyasu Ito, Eiichi Okada, Kenichi Namba, Nobuyoshi Kitaichi, Shin-ichiro Morimoto, Toshikatsu Kaburaki, Yasutaka Ando, Shinobu Takenaka, Takenosuke Yuasa, Shigeaki Ohno, Hidetoshi Inoko, Nobuhisa Mizuki
    MOLECULAR VISION, 18, 56, 512, 518, 2012年02月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Intravitreal injection of bevacizumab in a case of occlusive retinal vasculitis accompanied by syphilitic intraocular inflammation
    Kan Ishijima, Kenichi Namba, Shigeaki Ohno, Kiyofumi Mochizuki, Susumu Ishida
    Case Reports in Ophthalmology, 3, 3, 434, 437, 2012年, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Investigation of Association between TLR9 Gene Polymorphisms and VKH in Japanese Patients
    Ryuta Ito, Masao Ota, Akira Meguro, Yoshihiko Katsuyama, Riyo Uemoto, Eiichi Nomura, Tadayuki Nishide, Nobuyoshi Kitaichi, Yukihiro Horie, Kenichi Namba, Shigeaki Ohno, Hidetoshi Inoko, Nobuhisa Mizuki
    OCULAR IMMUNOLOGY AND INFLAMMATION, 19, 3, 202, 205, 2011年06月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • [A prospective, observational, all-prescribed-patients study of cyclosporine 0.1% ophthalmic solution in the treatment of vernal keratoconjunctivitis].
    Takamura E, Uchio E, Ebihara N, Okamoto S, Kumagai N, Shoji J, Nakagawa Y, Namba K, Fukushima A, Fujishima H, Miyazaki D, Ohashi Y
    Nippon Ganka Gakkai zasshi, 115, 6, 508, 515, 6, 2011年06月, [査読有り]
    日本語
  • Toll-like receptor 2 (TLR2) gene polymorphisms are not associated with sarcoidosis in the Japanese population
    Mayuki Sato, Tatsukata Kawagoe, Akira Meguro, Masao Ota, Yoshihiko Katsuyama, Mami Ishihara, Kenichi Namba, Nobuyoshi Kitaichi, Shin-ichiro Morimoto, Toshikatsu Kaburaki, Yasutaka Ando, Shinobu Takenaka, Shigeaki Ohno, Hidetoshi Inoko, Nobuhisa Mizuki
    MOLECULAR VISION, 17, 83, 731, 736, 2011年03月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Japanese guideline for allergic conjunctival diseases
    Etsuko Takamura, Eiichi Uchio, Nobuyuki Ebihara, Shigeaki Ohno, Yuichi Ohashi, Shigeki Okamoto, Naoki Kumagai, Yoshiyuki Satake, Jun Shoji, Yayoi Nakagawa, Kenichi Namba, Kazumi Fukagawa, Atsuki Fukushima, Hiroshi Fujishima
    Allergology International, 60, 2, 191, 203, Japanese Society of Allergology, 2011年, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • サルコイドーシスと鑑別を要するぶどう膜炎-非肉芽腫性ぶどう膜炎-
    南場 研一
    日本サルコイドーシス/肉芽腫性疾患学会雑誌, 31, 1, 76, 78, Japan Society of Sarcoidosis and Other Granulomatous Disorders, 2011年
    日本語
  • Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behçet's disease susceptibility loci.
    Mizuki N, Meguro A, Ota M, Ohno S, Shiota T, Kawagoe T, Ito N, Kera J, Okada E, Yatsu K, Song YW, Lee EB, Kitaichi N, Namba K, Horie Y, Takeno M, Sugita S, Mochizuki M, Bahram S, Ishigatsubo Y, Inoko H
    Nature genetics, 42, 8, 703, U83, 2010年08月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behçet's disease susceptibility loci.
    Mizuki Nobuhisa, Meguro Akira, Ota Masao, Ohno Shigeaki, Shiota Tomoko, Kawagoe, Tatsukata, Ito Norihiko, Kera Jiro, Okada Eiichi, Yatsu Keisuke, Song Yeong-Wook,Lee Eun-Bong, Kitaichi Nobuyoshi, Namba Kenichi, Horie Yukihiro, Takeno Mitsuhiro, Sugita Sunao, Mochizuki Manabu, Bahram Seiamak, Ishigatsubo Yoshiaki, Inoko Hidetoshi
    Nature genetics, 42, 8, 703, 6, 2010年08月, [査読有り]
    英語, Behçet's disease is a chronic systemic inflammatory disorder characterized by four major manifestations: recurrent ocular symptoms, oral and genital ulcers and skin lesions. We conducted a genome-wide association study in a Japanese cohort including 612 individuals with Behçet's disease and 740 unaffected individuals (controls). We identified two suggestive associations on chromosomes 1p31.3 (IL23R-IL12RB2, rs12119179, P = 2.7 x 10(-8)) and 1q32.1 (IL10, rs1554286, P = 8.0 x 10(-8)). A meta-analysis of these two loci with results from additional Turkish and Korean cohorts showed genome-wide significant associations (rs1495965 in IL23R-IL12RB2, P = 1.9 x 10(-11), odds ratio = 1.35; rs1800871 in IL10, P = 1.0 x 10(-14), odds ratio = 1.45).
  • Amelioration of Experimental Autoimmune Uveoretinitis with Nuclear Factor-kappa B Inhibitor Dehydroxy Methyl Epoxyquinomicin in Mice
    Daiju Iwata, Nobuyoshi Kitaichi, Akiko Miyazaki, Kazuya Iwabuchi, Kazuhiko Yoshida, Kenichi Namba, Michitaka Ozaki, Shigeaki Ohno, Kazuo Umezawa, Kenichiro Yamashita, Satoru Todo, Susumu Ishida, Kazunori Onoe
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 51, 4, 2077, 2084, 2010年04月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • A Randomized, Placebo-Controlled Clinical Trial of Tacrolimus Ophthalmic Suspension 0.1% in Severe Allergic Conjunctivitis
    Yuichi Ohashi, Nobuyuki Ebihara, Hiroshi Fujishima, Atsuki Fukushima, Naoki Kumagai, Yayoi Nakagawa, Kenichi Namba, Shigeki Okamoto, Jun Shoji, Etsuko Takamura, Kunihiko Hayashi
    JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS, 26, 2, 165, 173, 2010年04月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • [Infliximab treatment for Behçet's disease--beginning of the biological drug era].
    Namba K
    Nippon Ganka Gakkai zasshi, 114, 85, 86, 2, 2010年02月, [査読有り]
  • Prevention of experimental autoimmune uveoretinitis by blockade of osteopontin with small interfering RNA
    Daiju Iwata, Mizuki Kitamura, Nobuyoshi Kitaichi, Yoshinari Saito, Shigeyuki Kon, Kenichi Namba, Junko Morimoto, Akiko Ebihara, Hirokuni Kitamei, Kazuhiko Yoshida, Susumu Ishida, Shigeaki Ohno, Toshimitsu Uede, Kazunori Onoe, Kazuya Iwabuchi
    EXPERIMENTAL EYE RESEARCH, 90, 1, 41, 48, 2010年01月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Elevation of surfactant protein D, a pulmonary disease biomarker, in the sera of uveitis patients with sarcoidosis
    Nobuyoshi Kitaichi, Mizuki Kitamura, Kenichi Namba, Susumu Ishida, Shigeaki Ohno
    JAPANESE JOURNAL OF OPHTHALMOLOGY, 54, 1, 81, 84, 2010年01月, [査読有り], [国内誌]
    英語, 研究論文(学術雑誌)
  • Lack of association between toll-like receptor 4 gene polymorphisms and sarcoidosis-related uveitis in Japan
    Yuri Asukata, Masao Ota, Akira Meguro, Yoshihiko Katsuyama, Mami Ishihara, Kenichi Namba, Nobuyoshi Kitaichi, Shin-ichiro Morimoto, Toshikatsu Kaburaki, Yasutaka Ando, Shinobu Takenaka, Hidetoshi Inoko, Shigeaki Ohno, Nobuhisa Mizuki
    MOLECULAR VISION, 15, 283-88, 2673, 2682, 2009年12月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Clinical features of intraocular inflammation in Hokkaido, Japan
    Hirokuni Kitamei, Nobuyoshi Kitaichi, Kenichi Namba, Satoshi Kotake, Chiho Goda, Mizuki Kitamura, Akiko Miyazaki, Shigeaki Ohno
    ACTA OPHTHALMOLOGICA, 87, 4, 424, 428, 2009年06月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Association of TLR4 polymorphisms with Behets disease in a Korean population
    Yukihiro Horie, Akira Meguro, Masao Ota, Nobuyoshi Kitaichi, Yoshihiko Katsuyama, Yuko Takemoto, Kenichi Namba, Kazuhiko Yoshida, Yeong Wook Song, Kyung Sook Park, Eun Bong Lee, Hidetoshi Inoko, Nobuhisa Mizuki, Shigeaki Ohno
    RHEUMATOLOGY, 48, 6, 638, 642, 2009年06月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Elevated choroidal blood flow velocity during systemic corticosteroid therapy in Vogt-Koyanagi-Harada disease
    Shigeki Hirose, Wataru Saito, Kazuhiko Yoshida, Michiyuki Saito, Zhenyu Dong, Kenichi Namba, Hisao Satoh, Shigeaki Ohno
    ACTA OPHTHALMOLOGICA, 86, 8, 902, 907, 2008年12月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Re-evaluation of heterogeneity in HLA-B*510101 associated with Behçet's disease.
    Takemoto Y, Naruse T, Namba K, Kitaichi N, Ota M, Shindo Y, Mizuki N, Gul A, Madanat W, Chams H, Davatchi F, Inoko H, Ohno S, Kimura A
    Tissue antigens, 72, 4, 347, 353, 2008年10月, [査読有り]
  • Efficacy and complications of intravitreal injection of triamcinolone acetonide for refractory cystoid macular edema associated with intraocular inflammation
    Zhenyu Dong, Kenichi Namba, Nobuyoshi Kitaichi, Chiho Goda, Mizuki Kitamura, Shigeaki Ohno
    JAPANESE JOURNAL OF OPHTHALMOLOGY, 52, 5, 374, 379, 2008年09月, [査読有り], [国内誌]
    英語, 研究論文(学術雑誌)
  • Mutation screening of the CARD15 gene in sarcoidosis.
    Akahoshi M, Ishihara M, Namba K, Kitaichi N, Ando Y, Takenaka S, Ishida T, Ohno S, Mizuki N, Nakashima H, Shirakawa T
    Tissue antigens, 71, 6, 564, 567, 2008年06月, [査読有り]
  • H2-D-d-mediated upregulation of interleukin-4 production by natural killer T-cell and dendritic cell interaction
    Kazuomi Mizuuchi, Yoshiki Yanagawa, Kazuya Iwabuchi, Kenichi Namba, Nobuyoshi Kitaichi, Shigeaki Ohno, Kazunori Onoe
    IMMUNOLOGY, 124, 1, 102, 111, 2008年05月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Sister cases of Behcet's disease and Vogt-Koyanagi-Harada disease
    Yukihiro Horie, Kenichi Namba, Nobuyoshi Kitaichi, Shigeaki Ohno
    BRITISH JOURNAL OF OPHTHALMOLOGY, 92, 3, 433, 434, 2008年03月, [査読有り], [国際誌]
    英語
  • Polymorphism of IFN-gamma gene and Vogt-Koyanagi-Harada disease
    Yukihiro Horie, Nobuyoshi Kitaichi, Yuko Takemoto, Kenichi Namba, Kazuhiko Yoshida, Shigeto Hirose, Yukiko Hasumi, Masao Ota, Hidetoshi Inoko, Nobuhisa Mizuki, Shigeaki Ohno
    MOLECULAR VISION, 13, 261-65, 2334, 2338, 2007年12月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Osteopontin aggravates experimental autoimmune uveoretinitis in mice
    Mizuki Kitamura, Kazuya Iwabuchi, Nobuyoshi Kitaichi, Shigeyuki Kon, Hirokuni Kitamei, Kenichi Namba, Kazuhiko Yoshida, David T. Denhardt, Susan R. Rittling, Shigeaki Ohno, Toshimitsu Uede, Kazunori Onoe
    JOURNAL OF IMMUNOLOGY, 178, 10, 6567, 6572, 2007年05月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • サルコイドーシスの診断基準と診断の手引き 2006
    石原 麻美, 大原 國俊, 臼井 正彦, 大黒 伸行, 大野 重昭, 岡田 アナベルあやめ, 沖波 聡, 蕪城 俊克, 川島 英俊, 幸野 敬子, 後藤 浩, 南場 研一, 望月 學, 「サルコイドーシス眼病変の診断の手引き」改訂委員会
    日本眼科学会雑誌, 111, 2, 117, 121, (公財)日本眼科学会, 2007年02月
    日本語
  • Genetic polymorphisms in the promoter of the interferon gamma receptor 1 gene are associated with atopic cataracts
    Akira Matsuda, Nobuyuki Ebihara, Naoki Kumagai, Ken Fukuda, Koji Ebe, Koji Hirano, Chie Sotozono, Mamoru Tei, Koichi Hasegawa, Makiko Shimizu, Mayumi Tamari, Kenichi Namba, Shigeaki Ohno, Nobuhisa Mizuki, Zenro Ikezawa, Taro Shirakawa, Junji Hamuro, Shigeru Kinoshita
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 48, 2, 583, 589, 2007年02月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Association of heat shock protein 70 induction and the amelioration of experimental autoimmune uveoretinitis in mice
    Hirokuni Kitamei, Nobuyoshi Kitaichi, Kazuhiko Yoshida, Akira Nakai, Mitsuaki Fujimoto, Mizuki Kitamura, Kazuya Iwabuchi, Akiko Miyazaki, Kenichi Namba, Shigeaki Ohno, Kazunori Onoe
    IMMUNOBIOLOGY, 212, 1, 11, 18, 2007年, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Repeated exacerbations of ocular inflammation with vitreous hemorrhage in a patient with HLA-B27 associated uveitis
    Satoru Kase, Kenichi Namba, Yukihiro Horie, Satoshi Kotake, Shigeaki Ohno
    Journal of Medical Investigation, 54, 3-4, 350, 353, 3-4, 2007年, [査読有り], [国内誌]
    英語, 研究論文(学術雑誌)
  • Elevation of serum Krebs von den Lunge-6 levels in patients with tubulointerstitial nephritis and Uveitis syndrome
    Satoru Kase, Nobuyoshi Kitaichi, Kenichi Namba, Akiko Miyazaki, Kazuhiko Yoshida, Kenji Ishikura, Masahiro Ikeda, Taiji Nakashima, Shigeaki Ohno
    AMERICAN JOURNAL OF KIDNEY DISEASES, 48, 6, 935, 941, 2006年12月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Tyrosinase gene family and Vogt-Koyanagi-Harada disease in Japanese patients
    Yukihiro Horie, Yuko Takemoto, Akiko Miyazaki, Kenichi Namba, Satoru Kase, Kazuhiko Yoshida, Masao Ota, Yukiko Hasumi, Hidetoshi Inoko, Nobuhisa Mizuki, Shigeaki Ohno
    MOLECULAR VISION, 12, 182-86, 1601, 1605, 2006年12月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Chronic panuveitis and scleritis in a patient with cryptogenic organizing pneumonia
    Wataru Saito, Akari Saito, Kenichi Namba, Satoru Kase, Masanori Shiratori, Shigeaki Ohno
    JAPANESE JOURNAL OF OPHTHALMOLOGY, 50, 6, 558, 561, 2006年11月, [査読有り], [国内誌]
    英語
  • Granulocytapheresis in patients with refractory ocular Behcet's disease
    Kenichi Namba, Koh-Hei Sonoda, Hirokuni Kitamei, Kenji Shiratori, Akiko Ariyama, Kazuya Iwabuchi, Kazunori Onoe, Abby R. Saniabadi, Shoichi Inaba, Tatsuro Ishibashi, Shigeaki Ohno
    JOURNAL OF CLINICAL APHERESIS, 21, 2, 121, 128, 2006年07月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Amelioration of experimental autoimmune uveoretinitis (EAU) with an inhibitor of nuclear factor-kappa B (NF-kappa B), pyrrolidine dithiocarbamate
    Hirokuni Kitamei, Kazuya Iwabuchi, Kenichi Namba, Kazuhiko Yoshida, Yoshiki Yanagawa, Nobuyoshi Kitaichi, Mizuki Kitamura, Shigeaki Ohno, Kazunori Onoe
    JOURNAL OF LEUKOCYTE BIOLOGY, 79, 6, 1193, 1201, 2006年06月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Usefulness of quantifying serum KL-6 levels in the follow-up of uveitic patients with sarcoidosis
    N Kitaichi, T Ariga, S Kase, K Yoshida, K Namba, S Ohno
    GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 244, 4, 433, 437, 2006年04月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Epstein-Barr virus infected cells in the aqueous humour originated from nasal NK/T cell lymphoma
    S Kase, K Namba, N Kitaichi, S Ohno
    BRITISH JOURNAL OF OPHTHALMOLOGY, 90, 2, 244, 245, 2006年02月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Clinical features in tubulointerstitial nephritis and uveitis (TINU) syndrome
    C Goda, S Kotake, A Ichiishi, K Namba, N Kitaichi, S Ohno
    AMERICAN JOURNAL OF OPHTHALMOLOGY, 140, 4, 637, 641, 2005年10月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Expression of thymidine phosphorylase in choroidal malignant melanoma associated with neovascular glaucoma
    S Kase, W Saito, K Yoshida, K Namba, M Osaki, K Ohgami, K Shiratori, N Kitaichi, H Adachi, H Ito, S Ohno
    PATHOLOGY INTERNATIONAL, 55, 9, 569, 573, 2005年09月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Comparative study of two sets of criteria for the diagnosis of Vogt-Koyanagi-Harada's disease
    M Kitamura, K Takami, N Kitachi, K Namba, H Kitamei, S Kotake, S Ohno
    AMERICAN JOURNAL OF OPHTHALMOLOGY, 139, 6, 1080, 1085, 2005年06月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • 脈絡膜原発悪性黒色腫の臨床病理学的検討
    加瀬諭, 吉田和彦, 斎藤航, 南場研一, 辻野奈緒子, 村松昌裕, 古館直樹, 大野重昭
    臨床眼科, 59, 5, 705, 709, 2005年05月
    日本語
  • Inducible immune regulation following autoimmune disease in the immune-privileged eye
    N Kitaichi, K Namba, AW Taylor
    JOURNAL OF LEUKOCYTE BIOLOGY, 77, 4, 496, 502, 2005年04月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Increase of KL-6 in sera of uveitis patients with sarcoidosis
    N Kitaichi, S Kotake, H Shibuya, Y Yamada, H Chiba, K Namba, S Ohno
    GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 241, 11, 879, 883, 2003年11月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • The change of clinical manifestations of patients with Behçet's disease in Japan.
    Kotake S, Namba K, Higashi K, Goda C, Ariga T, Ogawa A, Ohno S
    Advances in experimental medicine and biology, 528, 83, 84, 2003年, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • Induction of regulatory T cells by the immunomodulating cytokines alpha-melanocyte-stimulating hormone and transforming growth factor-beta 2
    K Namba, N Kitaichi, T Nishida, AW Taylor
    JOURNAL OF LEUKOCYTE BIOLOGY, 72, 5, 946, 952, 2002年11月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌)
  • In vitro induction of CD25(+) CD4(+) regulatory T cells by the neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH)
    AW Taylor, K Namba
    IMMUNOLOGY AND CELL BIOLOGY, 79, 4, 358, 367, 2001年07月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Amelioration of experimental autoimmune uveoretinitis by pretreatment with a pathogenic peptide in liposome and anti-CD40 ligand monoclonal antibody
    K Namba, K Ogasawara, N Kitaichi, T Morohashi, Y Sasamoto, S Kotake, H Matsuda, K Iwabuchi, C Iwabuchi, S Ohno, K Onoe
    JOURNAL OF IMMUNOLOGY, 165, 6, 2962, 2969, 2000年09月
    英語, 研究論文(学術雑誌)
  • Neuropeptide regulation of immunity - The immunosuppressive activity of alpha-melanocyte-stimulating hormone (alpha-MSH)
    AW Taylor, DG Yee, T Nishida, K Namba
    NEUROIMMUNOMODULATION, 917, 239, 247, 2000年, [査読有り]
    英語, 研究論文(学術雑誌)
  • Effective priming of cytotoxic T lymphocyte precursors by subcutaneous administration of peptide antigens in liposomes accompanied by Anti-CD40 and Anti-CTLA-4 antibodies
    Daisuke Ito, Daisuke Ito, Kazumasa Ogasawara, Kazuhiro Matsushita, Taiki Morohashi, Kenichi Namba, Naoto Matsuki, Nobuyoshi Kitaichi, Yukio Inuyama, Masuo Hosokawa, Eiichi Nakayama, Kazuya Iwabuchi, Kazunori Onoé, Kazunori Onoé
    Immunobiology, 201, 527, 540, 2000年01月01日
  • Inhibition of experimental autoimmune uveoretinitis with anti-macrophage migration inhibitory factor antibodies
    KITAICHI N, MATSUDA A, KOTAKE S, NAMBA K, TAGAWA Y, SASAMOTO Y, OGASAWARA K, IWABUCHI K, ONOE K, MATSUDA H, NISHIHIRA
    CURRENT EYE RESEARCH, 20, 2, 109, 114, 2000年, [査読有り]
  • Prominent increase of macrophage migration inhibitory factor in the sera of patients with uveitis
    KITAICHI N, KOTAKE S, SASAMOTO Y, NAMBA K, MATSUDA A, OGASAWARA K, ONOE K, MATSUDA H, NISHIHIRA
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 40, 1, 247, 250, 1999年, [査読有り]
  • Interaction of pigeon cytochrome c-(43-58) peptide analogs with either T cell antigen receptor or I-Ab molecule
    Yasushi Itoh, Kiichj Kajino, Kazumasa Ogasawara, Akio Takahashi, Ken-Ichi Namba, Izumi Negishi, Naoto Matsuki, Kazuya Iwabuchi, Mitsuaki Kakinuma, Robert A. Good, Kazunori Onoé
    Proceedings of the National Academy of Sciences of the United States of America, 94, 22, 12047, 12052, 1997年10月28日, [査読有り]
    英語, 研究論文(学術雑誌)
  • Determination of the allele-specific antigen-binding site on I-A(kappa) and I-A(b) molecules
    Y Itoh, K Kajino, K Ogasawara, M Kotoh, K Namba, K Takami, K Iwabuchi, NS Braunstein, K Onoe
    EUROPEAN JOURNAL OF IMMUNOLOGY, 26, 6, 1314, 1321, 1996年06月
    英語, 研究論文(学術雑誌)

その他活動・業績

書籍等出版物

共同研究・競争的資金等の研究課題

  • ベタセルリン阻害によるぶどう膜炎抑制治療の検討
    科学研究費助成事業
    2025年04月01日 - 2028年03月31日
    南場 研一, 村上 正晃, 北市 伸義
    日本学術振興会, 基盤研究(C), 北海道大学, 25K12865
  • ベーチェット病眼症状と口腔マイクロバイオームのメタゲノム解析
    科学研究費助成事業
    2022年04月01日 - 2025年03月31日
    北市 伸義, 南場 研一
    研究計画に則り、研究を行なった。新型コロナウイルス感染症の行動制限が2023年に緩和され、ヨルダン=ハシミテ王国での現地調査を実施したヨルダンでは47人のベーチェット病患者の診察および唾液検体採取ができ、健常対象者45人からも検体採取できた。患者の平均年齢は41.9歳であり男性33例、女性14例であった。4主症状の発現頻度は口腔内アフタ性潰瘍100%、皮膚症状88.9%、外陰部潰瘍 84.4%、眼症状 71.1%であった。診察時の視力は0.8以上の良好群が69.4%、0.1以下の不良群が5.6%であった。治療はステロイド薬の内服が91.5%で処方されており、免疫抑制薬が85.1%、生物学的製剤である腫瘍壊死因子(TNF)阻害薬は29.7%で使用されていた。
    疾患関連遺伝子では最も相関が強い HLA-B51 の解析まで進んでおり、保有率は患者群で70.2%、健常対照群では15.6%であった。オッズ比は 12.8 となり、他地域と同様にHLA-B51 遺伝子はベーチェット病発症に強く相関していた。
    ヨルダン人のベーチェット病臨床像はシルクロード地域の既報と類似しており、疾患の特徴は同じであった。HLA-B51 の保有頻度は日本などより高頻度であった。近隣国のサウジアラビアやトルコ、ギリシャでも同遺伝子は高頻度であった。これらの地域では他地域より健常者でも HLA-B51保有頻度が高かった。
    現在は唾液サンプルから口腔内細菌叢のゲノムショットガン解析を試みており、詳細で有用な結果が得られると期待している。
    モンゴル国でのベーチェット病患者の臨床像と遺伝子解析は引き続き継続しており、疾患関連遺伝子と臨床像の関係を解析中である。
    日本学術振興会, 基盤研究(C), 北海道医療大学, 22K09818
  • 迷走神経刺激によるぶどう膜炎抑制治療
    科学研究費助成事業
    2022年04月01日 - 2025年03月31日
    南場 研一, 村上 正晃, 北市 伸義
    初年度である昨年度はまず、マウス実験的自己免疫性ぶどう膜網膜炎(EAU)の免疫に用いるぶどう膜炎惹起抗原ペプチドについて、従来使用しているhIRBP1-20からhIRBP651-670に変更をしてC57BL/6マウスEAUの発症率、重症度を確かめる予備実験を行った。その結果、hIRBP651-670による免疫ではEAUの発症率がほぼ100%であること、炎症のピークが17日と早く、ピーク時の平均臨床スコアが2.5と高いことが確認された。
    本年度は迷走神経の切断によりEAUが増悪する可能性について検討した。迷走神経を切断したマウスにEAUを誘導し、EAUの発症率と重症度について頸部の切開と迷走神経の同定を行い、その上で迷走神経を切断していないマウスをコントロールマウスとして、比較検討を行なった。結果、免疫後10日目には迷走神経切断群でのクリニカルスコアは0.58、コントロール群では0.083、14日目には迷走神経切断群のクリニカルスコアは2.67、コントロール群では1.17と有意に迷走神経切断群での炎症の増悪が認められた(p=0.011、p=0.0043)。免疫後17日目では14日目には迷走神経切断群のクリニカルスコアは2.58、コントロール群では1.67、21日目には迷走神経切断群のクリニカルスコアは1.58、コントロール群では1.33と迷走神経遮断群の方が炎症の増悪の傾向は認められたが有意差は認められなかった(p=0.086、p=0.29)。また、免疫後21日目に眼球摘出を行い、組織切片を作成した。その組織スコアをつけたところ組織スコアは迷走神経遮断群で1.12、コントロール群で0.87と迷走神経遮断による炎症の増悪の傾向は認められたが、有意差は認められなかった(p=0.26)。以上の通り、迷走神経遮断によりEAUの炎症の増悪することが示唆された。
    日本学術振興会, 基盤研究(C), 北海道大学, 22K09759
  • 酸化リン脂質によるぶどう膜炎での網膜細胞障害メカニズムの解明
    科学研究費助成事業
    2021年04月01日 - 2024年03月31日
    平岡 美紀, 北市 伸義, 南場 研一
    ぶどう膜炎で炎症が重篤あるいは遷延した例では、炎症がおさまった後でも網膜の不可逆的な障害により、視機能が回復しない。また、ぶどう膜炎では酸化ストレスが生じることが知られている。この酸化ストレスによって生じる酸化リン脂質とぶどう膜炎での網膜障害の関係について、明らかにするのが本研究の目的である。
    2021年度の研究計画と実施状況について、以下に記す。
    1. 臨床例での網膜障害における酸化リン脂質分布の違いを調べるために、まず、臨床検体を用いて、網膜障害のあるぶどう膜炎群と明らかな網膜障害のないぶどう膜炎群、眼内炎症のない群について、それぞれ採取した硝子体の酸化リン脂質プロファイルを質量分析(LC-MS)にて、分析を行なった。現在、統計解析中である。
    2. ぶどう膜炎の動物モデルでの網膜組織の酸化リン脂質分布を調べるために、実験的自己免疫性ぶどう膜炎モデルラットを用いて、炎症前、炎症極期の網膜を摘出し、網膜の酸化リン脂質プロファイルを質量分析(LC-MS)にて、分析を行なった。その結果、ラットの網膜では11種の短鎖型の酸化リン脂質が検出され、そのうちのいくつかは、炎症のないものと比べ炎症極期の網膜では、量が高い傾向にあった。現在、統計解析中である。
    これまでの結果から、ぶどう膜炎に引き続いて起こる酸化リン脂質の変化と網膜障害の関係を見出すことができる。これにより酸化リン脂質が網膜障害のマーカーとなり得ると考えられる。
    日本学術振興会, 基盤研究(C), 北海道医療大学, 21K09680
  • ぶどう膜炎における上皮増殖因子受容体依存性局所炎症増幅回路の検討
    科学研究費助成事業
    2019年04月01日 - 2023年03月31日
    南場 研一, 村上 正晃, 北市 伸義
    初年度には、ぶどう膜炎群(サルコイドーシス、フォークト-小柳-原田病、ベーチェット病、HLA―B27関連急性前部ぶどう膜炎)およびコントロール群として健常人について、血清中の上皮増殖因子受容体およびそのリガンドであるエピレグリン等の濃度をマルチプレックス法にて測定し、ぶどう膜炎群ではエピレグリンならびにその他の上皮増殖因子(EGF)受容体のリガンド(アンフィレグリン、ベタセルリン、TGF-アルファ、HB-EGF)がコントロール群と比べ有意に上昇していることを報告した(マンホイットニーのU検定:P<0.05)。これらの結果から、他疾患で報告されているようにぶどう膜炎患者においても上皮増殖因子の炎症増幅への関与が示唆された。昨年度はF759遺伝子変異マウスにおいて実験的自己免疫性ぶどう膜網膜炎( EAU )が増強されるかどうかを検討する予定であった。F759 遺伝子変異マウスではネガティブシグナルが阻害されてIL-6 産生が亢進し、上皮増殖因子が関与する炎症増幅経路はさらに増強されるため、EAUが強く惹起される可能性が示唆された。F759遺伝子変異マウスを当方の北海道大学医歯学共同研究動物施設に受入する手続きを進めているところで新型コロナウイルス感染拡大のため研究停止となり、現在まで受入が進んでいない。そこで、研究室に凍結保管していたぶどう膜炎患者血清を用いてEGF受容体およびそのリガンドについて測定し、症例数を増やし結果を得た。本年度は、マウスEAUの網脈絡膜を摘出し、網脈絡膜組織のmRNAからcDNAを作成し、マイクロアレイ法にて関連する分子の発現の評価を行った。EGF受容体のリガンドであるエピレグリン、アンフィレグリン、EGFが上昇していること、逆にEGF受容体は発現が低下していることが示され、マウスEAUにおいてEGF受容体を介するシグナル伝達が病態形成に関わっていることが示唆された。
    日本学術振興会, 基盤研究(C), 北海道大学, 19K09985
  • ベーチェット病発症原因としての口腔内細菌と疾患関連遺伝子の検討
    科学研究費助成事業
    2019年04月01日 - 2022年03月31日
    北市 伸義, 南場 研一, 長澤 敏行
    モンゴル国でのベーチェット病の臨床像の特徴と口腔内細菌叢の特徴の2本の英文原著論文の成果を得た。臨床像は他国と比較して大きな違いはないが、鼻粘膜潰瘍が多くみられ、中央アジア地域に共通する特徴か更なる検討が必要。口腔内細菌叢では Akkermansia 属が減少していた。
    ヨルダン・ハシミテ王国のサンプルは、新型コロナウイルス感染症の拡大により、代替案として毛髪検体を収集して DNA を抽出、 HLA タイピングを先行して進めている。
    日本人では、自己免疫疾患に関連する自己抗体がベーチェット病患者血液サンプルから特異的に検出された。
    日本学術振興会, 基盤研究(C), 北海道医療大学, 19K09975
  • 人工多能性幹細胞由来のマクロファージ様免疫抑制性細胞を用いたぶどう膜網膜炎の制御
    科学研究費助成事業
    2016年04月01日 - 2019年03月31日
    南場 研一, 清野 研一郎, 北市 伸義
    マウス脾臓B細胞由来の人工多能性幹(iPS)細胞から誘導したマクロファージ様免疫抑制性細胞(iPS-SCs)をヒト視細胞間レチノイド結合蛋白由来合成ペプチド(hIRBPp)1-20抗原から作製したマウス実験的自己免疫性ぶどう膜網膜炎 (EAU)に腹腔内投与することにより、眼底所見による臨床学的重症度とHE染色による組織学的重症度は、ともに対照群に比べ有意に炎症が軽症化した。In vitroの実験でもマウスEAUから採取したhIRBPp1-20抗原特異的なCD4陽性T細胞とhIRBPp1-20抗原と抗原提示細胞にiPS-SCsを加えて共培養すると、CD4陽性T細胞の増殖は有意に抑制された。
    日本学術振興会, 基盤研究(C), 北海道大学, 16K11310
  • ユーラシア大陸内陸部多民族におけるベーチェット病関連遺伝子の解析
    科学研究費助成事業
    2016年04月01日 - 2019年03月31日
    北市 伸義, 南場 研一
    本研究計画は(1)ユーラシア大陸内陸部にも本病患者が存在するか、(2)いるとすればその臨床症状は本邦のそれと類似しているのか、(3)疾患関連遺伝子は同じか、などが大きな柱である。
    成果:(1)アゼルバイジャン人、アルメニア人、チェチェン人、ダゲスタン人、ロシア人、カザフスタン人、モンゴル人の患者の存在を確認した。(2)その臨床症状は我が国の患者とよく類似していた。特にモンゴルには多数の患者が存在することが確認された。(3)疾患関連遺伝子では最も関連が強いHLA-B51 は諸外国の患者でもみられた。現在関連遺伝子の解析を進めている。
    日本学術振興会, 基盤研究(C), 北海道医療大学, 16K11297
  • 網羅的糖鎖解析グライコミクスによるぶどう膜炎炎症増悪マーカー探索
    科学研究費助成事業
    2013年04月01日 - 2016年03月31日
    南塲 研一, 北市 伸義, 西村 紳一郎, 天野 麻穂
    今回我々はぶどう膜炎の発症時に特異的に上昇する糖鎖について検討をおこなった。インフリキシマブ導入後もぶどう膜炎を生じる患者、特に抗インフリキシマブ抗体が陽性患者、およびコントロールとしてインフリキシマブ導入後経過良好な患者の血清について、新しい糖鎖構造解析グライコブロッティング法をもちいて網羅的糖鎖解析をおこなった。2群間比較でm/z1680, m/z2337, m/z2379, m/z3195の4つの糖鎖において比較的明確な差異が認められ、いずれも無効例に多くみられるという結果であった。
    日本学術振興会, 基盤研究(C), 北海道大学, 25462745
  • ゲノムワイド関連解析に立脚したベーチェット病関連遺伝子の中央アジア多民族解析
    科学研究費助成事業
    2013年04月01日 - 2016年03月31日
    北市 伸義, 南場 研一
    ロシア、カザフスタン、キルギスタンで医療講演と患者診察を行い、ロシアやカザフスタンにもベーチェット病患者がいることを明らかにした。
    特にロシア南部、黒海とカスピ海に挟まれたコーカサス地方出身者にベーチェット病患者が多く、中でも少数民族であるダゲスタン人、アゼルバイジャン人、チェチェン人、アルメニア人に多く見られた。臨床症状は日本人など他の民族と類似していた。
    HLA class I も検討し、他民族と同様に HLA-B51 陽性者が多かった。ただし、それらの民族の健常者における HLA-B51 の正確な保有率は不明である。
    日本学術振興会, 基盤研究(C), 北海道医療大学, 25462731
  • 難治性内因性ぶどう膜炎における網羅的自己抗体解析研究
    科学研究費助成事業
    2011年 - 2013年
    大野 重昭, 石田 晋, 南場 研一, 北市 伸義, 目黒 明, 水木 信久, 澤崎 達也
    本研究では我々が開発した自己抗体検出システムを用いて難治性内因性ぶどう膜炎の自己抗体を網羅的に検索・同定した。
    フォークト-小柳-原田病患者を3プール群に分けて検討した結果、患者3プール群すべてにおいて、健常コントロール群に比べて1.5倍以上の産生を示すタンパク質を10種類同定した。
    ベーチェット病においても同様に患者プール群すべてにおいて、健常コントロール群に比べて1.5倍以上の産生を示すタンパク質を6種類同定した。これら同定したタンパク質のうち、3種類は両疾患において共通であった。
    日本学術振興会, 基盤研究(C), 北海道大学, 23592602
  • 新たな網羅的糖鎖解析グライコブロッティング法によるぶどう膜炎の病態解明
    科学研究費助成事業
    2010年 - 2012年
    南場 研一, 西村 紳一郎, 北市 伸義, 天野 麻穂
    新しい網羅的糖鎖構造解析グライコブロッティング法を用いてぶどう膜炎の患者での糖鎖解析をおこなった。ぶどう膜炎患者では血清中の糖鎖量が増えていること、また、活動期に変動する糖鎖が3種類見られた。ベーチェット病ではHLA-B51との関連、眼外症状との関連性を示す糖鎖がみられたが、眼炎症発作との関連はみられなかった。マウス実験的自己免疫性ぶどう膜網膜炎モデルでの糖鎖変動を調べたところ、免疫により変動する糖鎖はみられたが、ぶどう膜炎特異的に変動していると思われる糖鎖はみられなかった。
    日本学術振興会, 基盤研究(C), 北海道大学, 22591927
  • 難治性内因性ぶどう膜炎再発機序に関する分子遺伝学的検討
    科学研究費助成事業
    2007年 - 2010年
    北市 伸義, 大野 重昭, 南場 研一, 吉田 和彦, 大神 一浩
    本研究ではぶどう膜炎における疾患感受性遺伝子や再発など予後に影響を与える遺伝子を検索した。まず世界14ヵ国25施設のベーチェット病臨床像をまとめ、地域による症状や予後の違いを明らかにした。日本では同病の視力予後は依然として不良で、小児発症例が少ないことも明らかとなった。並行して各国からベーチェット病や原田病、尋常性白斑などの遺伝子サンプルを収集・検討し、ベーチェット病と原田病の間で再発に関与すると考えられる遺伝子に差異が見られた。
    日本学術振興会, 基盤研究(C), 北海道大学, 19592003
  • 人種差を示す難治性内眼炎の疾患感受性遺伝子の検索と新規抗酸化治療法の開発
    科学研究費助成事業
    2007年 - 2009年
    大野 重昭, 石田 晋, 吉田 和彦, 南場 研一, 北市 伸義, 田川 義継, 小野江 和則, 水木 信久, 猪子 英俊, 水木 信久, 猪子 英俊
    ベーチェット病の全ゲノム検索ではHLA-B*510101以外にも2つの新規遺伝子を見出し、Vogt-小柳-原田病でもHLA-DRB1*0405および他の疾患感受性遺伝子との相関を見出した。一方、アデノウイルス角結膜炎の病因検索で、世界初の2種のアデノウイルス(53型、54型)を発見した。一方、新規抗酸化物質アスタキサンチンは有意にヒト眼底血流を改善した。また、新たなNF-κB阻害薬であるDHMEQは実験的ぶどう膜網膜炎を有意に消炎した。
    日本学術振興会, 基盤研究(B), 北海道大学, 19406028
  • モンゴロイドに多発する難治性内眼炎の分子遺伝学的、分子疫学的研究と世界失明予防
    科学研究費助成事業
    2004年 - 2006年
    大野 重昭, 田川 義継, 吉田 和彦, 南場 研一, 水木 信久, 猪子 秀俊
    ベーチェット病や原田病、サルコイドーシスなどに代表される難治性内眼炎は、世界疫学的にみるとモンゴロイドに多発することが知られている。本研究ではこれら難治性内眼炎の分子遺伝学的研究を行うとともに分子疫学的研究を実施したのでその結果を報告する。ベーチェット病では第6染色体短腕上に位置するHLA-B遺伝子座に加え、他の常染色体1〜22およびX染色体上に合計147個の候補遺伝子が検出された(Pc<0.05)。さらに韓国人のベーチェット患者でも日本人と同様に高いHLA-B51頻度が観察された(P=0.0006)。また、メラノコルチン5レセプターの遺伝子解析では、ベーチェット病は相関を示さないことも明らかにされた。一方、原田病ではHLA-DRB1*0405との強い相関がみられたが(Pc=0.000000079)、チロシナーゼ、チロシナーゼ関連タンパク1、チロシナーゼ関連タンパク2遺伝子との相関は見られなかった。また、インターフェロン-γ遺伝子とは皮膚症状陽性の原田病で有意の相関が見られた(P=0.003)。
    一方分子疫学的にはベーチェット病が東アジア、ユーラシア、西アジア、地中海沿岸諸国で高頻度に見られたのに対し、欧米やアフリカ中南部では稀であった。従来我々が提唱したいわゆる「シルクロード病」と一致した世界分布を示した。また、HLA-B*510101の分布もこのシルクロード地域では共通していた。これに対し、原田病はむしろ東南アジア、東アジア、そして北米、中南米の原住民に多発しており、いずれもHLA-DRB1*04との強い相関を示していた。外因としてのアデノウイルス感染症を例にとり、その世界分布を調べた所、イギリスではhAdV4型、東南アジアではhAdV8型、そして日本ではhAdV37型が流行の主要血清型であった。これらの血清型は数年ごとにその流行株が異なり、ウイルスDNA変異もしばしば見られた。
    日本学術振興会, 基盤研究(B), 北海道大学, 16406032
  • 難治性内眼炎の分子遺伝学的、免疫薬理学的研究による失明予防の新規展開
    科学研究費助成事業
    2004年 - 2006年
    大野 重昭, 吉田 和彦, 南場 研一, 水木 信久, 猪子 秀俊, 小野江 和則, 田川 義継
    ベーチェット病や原田病などを含む内因性難治性内眼炎は原因の不明なものが多く、その正しい診断や治療には多くの困難がある。また、その発症原因には遺伝的要因と外的要因が複雑に絡み合っている。本研究では難治性内眼炎の遺伝的要因を分子遺伝学的に分析するとともに、免疫薬理学的研究によって従来とは異なる新たな失明予防策の展開を試みた。
    その結果、ベーチェット病では第1染色体から第22染色体、さらにはX, Y染色体上に23、465個のマイクロサテライトマーカーを置き、全ゲノム検索を実行してきた。現在はその0.63%に相当する147個にまで相関が絞り込まれてきており、近い将来ベーチェット病に関する疾患感受性遺伝子が世界ではじめて複数個、新たに検出されることが強く期待される。また、日本人に多発する原田病では従来の第6染色体短腕上に位置するHLA-DR領域だけではなく、第6染色体長腕上にも密接に相関する遺伝因子を新たに見出した。現在はこれら遺伝子の生物学的機能解析を継続中である。原田病はメラノサイト特異的自己免疫疾患であり、その分子遺伝学的発症機序が解明されれば、他の自己免疫疾患の発症機序を理解するうえでも大きな助けとなる。
    一方、これらの難治性内眼炎では前房水、血中などので酸化窒素濃度が高値を示し、これらの抑制によって著明な抗炎症効果が得られることが見いだされた。その抗酸化作用は例えば北方系植物のハスカップ租抽出物に高い力価が見られ、投与量依存的に炎症が抑制された。また、顆粒球吸着カラムによる免疫調整治療によって、ベーチェット病の失明に直結しやすい網膜ぶどう膜炎の再発発作回数が有意に抑制されることが明らかにされた。この顆粒球吸着カラム治療は難治性内眼炎の発症後5年以上の症例ではとくに臨床効果が高いことも示された。
    日本学術振興会, 基盤研究(A), 北海道大学, 16209051
  • 調節性樹状細胞を用いた実験的自己免疫性網膜ぶどう膜炎の抑制
    科学研究費助成事業
    2004年 - 2005年
    南場 研一
    失明の原因になる難治性ぶどう膜炎の治療に調節性樹状細胞を用いた免疫治療をおこなうための基礎的な研究を行うことが目的である。
    樹状細胞にあらかじめ刺激を加えておくことにより、その後のT細胞、NKT細胞の活性化の方向性を調節できることが示唆されてきた。今回我々はToll like receptor (TLR)が免疫調節に密接に関わっている点に着目した。
    歯周病菌由来のTLR-2のリガンドであるPam(3)Cysとともに樹状細胞株を培養し、その樹状細胞株を用いてT細胞を刺激したところ、そのT細胞はTh2タイプの反応を示した。それに反してTLR-9のリガンドであるCpGとともに培養した樹状細胞株を用いた場合には、樹状細胞からのIL-12の産生がみられ、その後のT細胞への刺激をTh1タイプへ誘導すると考えられた。
    また、樹状細胞株にあらかじめ糖脂質を処理しておくことによりNKT細胞を刺激する際に、Pam(3)Cysともに培養した場合にはIL-4、IFN-γ産生を誘導し、CpGとともに培養した場合にはIL-4産生のみを強く誘導した。
    以上のようにCpGで前処理した樹状細胞はNKT細胞によるTh1/Th2サイトカイン産生バランスをTh2優位にすることが判明し、調節性樹状細胞として機能する可能性が示唆された。
    現在、そのメカニズムをさらに解析し、ex vivoにてCpGで刺激されたDCを実験的自己免疫性網膜ぶどう膜炎(EAU)マウスに投与することなどにより、それを抑制できるかどうかの実験などを行っている。
    日本学術振興会, 若手研究(B), 北海道大学, 16791036
  • 積極的NKT細胞活性化による自己免疫性ぶどう膜炎の抑制
    科学研究費助成事業
    2002年 - 2003年
    南場 研一
    NKT細胞は免疫反応の要所に活躍する細胞で、自己免疫疾患の抑制へ関わりが示唆されている。今回我々は、自己免疫性ぶどう膜炎の発症への関与を明らかにするため、マウス実験的自己免疫性網膜ぶどう膜炎(EAU)においてNKT細胞の役割について検討した。
    CD1ノックアウト(CD1KO)マウス、Ja281ノックアウト(JaKO)マウスはいずれもNKT細胞の機能が失われたマウスである。C57BL/6(ワイルドタイプ)とCD1KOマウス、JaKOマウスをヒト視細胞間結合レチノイド蛋白ペプチドで免疫してEAUを惹起したところ、ワイルドタイプに比べて、CD1KOマウス、JaKOマウスいずれにおいても優位にEAUの重症化がみられた。また、NKT細胞を活性化させるリガンドとして知られるalpha-garactoceramide(aGalCel),またはaGalCel由来のNKT細胞を選択的にTh2タイプへ活性化させる合成糖脂質(OCH)を投与することによるワイルドタイプのEAUの抑制について検討した。ところがaGalCelの投与、OCHの投与を行ってもEAUの抑制はみられなかった。
    以上のことから、NKT細胞はEAUの発症抑制に関与していると考えられるが、NKT細胞を積極的に刺激活性化しても自己免疫疾患であるEAUの抑制はできないことが示唆される。
    日本学術振興会, 若手研究(B), 北海道大学, 14770939
  • ウイルス性眼炎症の発症機構に関する分子遺伝学的,分子免疫学的研究
    科学研究費助成事業
    2002年 - 2003年
    大野 重昭, 南場 研一, 吉田 和彦, 田川 義継, 横井 匡彦, 小竹 聡
    アデノウイルス4型(AdV-4)は咽頭以外に結膜にも炎症を起こすウイルスとして知られている.2001年,札幌においてAdV-4による流行性結膜炎(EC)の院内感染が発生した.この院内感染株の特徴を明らかにするため,これまでに分離されたAdV-4と比較し,遺伝学的解析を行った.1984〜2001年の札幌市のEC患者及び,2001年の院内感染より分離され中和試験によりAdV-4と同定された36株を用いた.その結果,
    1)分離株のHexon領域956bp増幅産物の制限酵素切断パターンをAdV-1〜51標準株の切断パターンと比較した結果,Hae IIIとKpn Iの切断パターシはAdV-4pと一致したが,EcoT14 I,Hinf I,Mbo I及び,Cfr 13 Iの切断パターンは51標準株のどれとも一致しなかった.
    2)ウイルスDNAの制限酵素切断パターンをAdV-4pおよび,既知のAdV-4変異株と比較した結果,1984〜2001年のEC患者からの分離株の切断パターンは,Wadellらの示すAdV-4aの切断パターンと一致した.一方,2001年のECによる院内感染患者の分離株はEco RI,Xho Iの切断パターンはAdV-4aの切断パターンと一致したが,Bam HI,Sma IではAdV-4pおよび,既知のAdV-4変異株と異なる切断パターンを示した.
    3)分離株および,標準株のHexonとFiber全領域の塩基配列を解析した結果,分離株のHexon全領域の塩基配列は各年代別の分離株間で一致したが,Fiber領域の塩基配列では院内感染株は他の臨床分離株と異なる系統であった.
    以上の結果より,1984〜2001年の間にEC患者から分離されたAdV-4分離株は,AdV-4aと同定された,一方、2001年の院内感染の患者より分離されたAdV-4分離株は,AdV-4pおよび既知の,AdV-4変異株と異なる新しいAdV-4変異株であることが明らかとなった.
    日本学術振興会, 基盤研究(B), 北海道大学, 14370550