Researchers Database

KABURAKI TOSHIKATSU

    ComprehensiveMedicine2 Professor
Last Updated :2021/12/07

Researcher Information

J-Global ID

Research Interests

  • infectious uveitis   disease susceptibility gene   glaucoma   Intraocular lymphoma   Behcet's disease   uveitis   

Research Areas

  • Life sciences / Ophthalmology

Academic & Professional Experience

  • 2019/08 - Today  自治医科大学附属さいたま医療センター眼科教授
  • 2016/11 - 2019/07  東京大学附属病院眼科准教授
  • 2007/06 - 2016/10  東京大学附属病院眼科講師
  • 2001/04 - 2007/05  東京大学附属病院眼科助教
  • 1995/04 - 1997/03  東京大学附属病院眼科助手
  • 1993/05 - 1995/03  武蔵野赤十字病院眼科医員
  • 1992/04 - 1993/05  東京大学附属病院眼科研修医

Education

  • 1997/04 - 2001/03  The University of Tokyo  Graduate School of Medicine
  • 1986/04 - 1998/03  東京大学理科三類
  • 1988/04 - 1992/03  東京大学医学部医学科

Published Papers

  • Nozomi Igarashi, Megumi Honjo, Reiko Yamagishi, Makoto Kurano, Yutaka Yatomi, Koji Igarashi, Toshikatsu Kaburaki, Makoto Aihara
    Journal of biomedical science 28 (1) 47 - 47 2021/06 
    BACKGROUND: Elevated transforming growth factor (TGF)-β2 in aqueous humor (AH) has been suggested to contribute to trabecular meshwork (TM) fibrosis and intraocular pressure (IOP) regulation in primary open-angle glaucoma (POAG), but TGF-β2 is downregulated in secondary open-angle glaucoma (SOAG). Because autotaxin (ATX) is upregulated in SOAG, we investigated the relationships and trans-signaling interactions of these mediators. METHODS: The level of ATX in AH was determined using a two-site immunoenzymetric assay, and TGF-β levels were measured using the Bio-Plex Pro TGF-β Assay. RNA scope was used to assess the expression of ATX and TGF-β2 in human's eye specimen. And in vitro studies were performed using hTM cells to explore if trans-signaling of TGF-β2 regulates ATX expressions. RESULTS: TGF-β2/ATX ratio was significantly high in AH of control or POAG compared with SOAG, and negatively correlated with IOP. RNA scope revelated positive expressions of both TGF-β2 and ATX in ciliary body (CB) and TM in control, but ATX expressions was significantly enhanced in SOAG. In hTM cells, ATX expressions were regulated by TGF-β2 with concentration-dependent manner. In counter, ATX also induced TGF-β1, TGF-β2 and TGFBI upregulations and activation of the Smad-sensitive promoter, as well as upregulation of fibrotic markers, and these upregulation was significantly suppressed by both TGF-β and ATX inhibition. CONCLUSIONS: Trans-signaling of TGF-β2 regulates ATX expressions and thereby induced upregulations of TGF-βs or fibrosis of hTM. TGF-β2 trans-signaling potently regulate ATX transcription and signaling in hTM cells, which may reflect different profile of these mediators in glaucoma subtypes. Trial Registration This prospective observational study was approved by the Institutional Review Board of the University of Tokyo and was registered with the University Hospital Medical Information Network Clinical Trials Registry of Japan (ID: UMIN000027137). All study procedures conformed to the Declaration of Helsinki. Written informed consent was obtained from each patient.
  • Shintaro Shirahama, Kenzui Taniue, Shuhei Mitsutomi, Rie Tanaka, Toshikatsu Kaburaki, Tomohito Sato, Masaru Takeuchi, Hidetoshi Kawashima, Yoshihiro Urade, Makoto Aihara, Nobuyoshi Akimitsu
    Scientific reports 11 (1) 12164 - 12164 2021/06 
    Acute retinal necrosis (ARN) is a form of infectious uveitis caused by alpha herpesviruses, including herpes simplex virus type 1 (HSV-1). We previously found that the long non-coding RNA (lncRNA) U90926 is upregulated in murine retinal photoreceptor cells following HSV-1 infection, leading to host cell death. However, to date, an orthologous transcript has not been identified in humans. We investigated U90926 orthologous transcript in humans and examined its utility as a prognostic marker for visual acuity in patients with ARN. We identified two human orthologous transcripts (1955 and 592 bases) of lncRNA U90926. The amount of the longer human U90926 transcript was approximately 30- and 40-fold higher in the vitreous fluid of patients with ARN than in those with sarcoidosis and intraocular lymphoma, respectively. Furthermore, the expression of the longer human U90926 transcript in the vitreous fluid was highly correlated with the final best-corrected logarithm of the minimum angle of resolution visual acuity in patients with ARN (r = 0.7671, p = 0.0079). This suggests higher expression of the longer human U90926 transcript in the vitreous fluid results in worse visual prognosis; therefore, expression of the longer human U90926 transcript is a potential negative prognostic marker for visual acuity in patients with ARN.
  • Takafumi Suzuki, Toshikatsu Kaburaki, Rie Tanaka, Shintaro Shirahama, Keiko Komae, Hisae Nakahara, Mitsuko Takamoto, Hidetoshi Kawashima, Makoto Aihara
    International ophthalmology 2021/05 
    PURPOSE: The patterns of uveitis in Tokyo have recently changed due to advances in examination tools. We aimed to investigate the changes in the patterns of uveitis between 2004-2015 and 2016-2018. METHODS: We retrospectively reviewed the data of 732 patients who visited the Uveitis Clinic at the University of Tokyo Hospital between January 2016 and December 2018. Background characteristics, laboratory results, and imaging findings were analysed. We compared the incidences of uveitis in 2016-2018 and 2004-2015 to identify changes in the patterns. RESULTS: The most frequent diagnoses were sarcoidosis (8.9%), herpetic iridocyclitis (6.7%), intraocular lymphoma (5.5%), Vogt-Koyanagi-Harada disease (4.8%), unclassified acute anterior uveitis (4.6%), Behçet's disease (4.5%), bacterial endophthalmitis (2.9%), and Posner-Schlossman syndrome (2.6%). Suspected sarcoidosis (20.9%) was the most common cause of unclassified uveitis. The incidence of intraocular lymphoma was significantly higher in 2016-2018 than in 2004-2015. Between 2004 and 2018, herpetic iridocyclitis, bacterial endophthalmitis, and juvenile chronic iridocyclitis exhibited an increasing trend, and the incidences of Posner-Schlossman syndrome, unclassified acute anterior uveitis, Behçet's disease, and Vogt-Koyanagi-Harada disease exhibited a decreasing trend. CONCLUSION: The changing patterns of uveitis were characterised by increases in the incidence of intraocular lymphoma. This may be attributed to recent advances in examination tools, the changes in the referred patient population, and the aging Japanese population.
  • Suguru Nakagawa, Hitoha Ishii, Mitsuko Takamoto, Toshikatsu Kaburaki, Kiyoshi Ishii, Takashi Miyai
    BMC ophthalmology 21 (1) 194 - 194 2021/05 
    BACKGROUND: Cytomegalovirus (CMV) has been known to cause unilateral corneal endotheliitis with keratic precipitates and localized corneal edema, iridocyclitis, and secondary glaucoma. CMV endotheliitis is diagnosed based on clinical manifestations and viral examination using qualitative polymerase chain reaction (PCR) of the aqueous humor. CASE PRESENTATION: An 80-year-old woman was referred to our department for bullous keratopathy. Pigmented keratic precipitates were found in the right eye without significant anterior chamber inflammation. After 8 months there was inflammation relapse with mutton fat keratic precipitates and PCR on aqueous humor was performed, with negative results for CMV, herpes simplex virus, and varicella zoster virus. Keratic precipitates disappeared with steroid instillation, and Descemet-stripping automated endothelial keratoplasty (DSAEK) was performed for the right eye. CMV-DNA was positive at 6.0 × 102 copies/ GAPDH 105 copies in real time PCR of corneal endothelial specimen removed during DSAEK with negative results for all the other human herpes viruses. After diagnosis of CMV corneal endotheliitis, treatment with systemic and topical ganciclovir was initiated and there was resolution of symptoms. No recurrence of iridocyclitis or corneal endotheliitis was observed at 6 months follow up. CONCLUSIONS: This case report suggests that PCR should be performed using the endothelium removed during DSAEK for bullous keratopathy of an unknown cause, even if PCR for aqueous humor yields negative results.
  • 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 (公財)日本眼科学会 125 (4) 415 - 424 0029-0203 2021/04 
    目的:日本における結核性ぶどう膜炎の臨床像と治療内容を明らかにすること.対象と方法:多施設後ろ向き研究にて2001年1月〜2012年12月の間に結核性ぶどう膜炎と診断された130例192眼の年齢,性別,臨床所見,結核菌感染の検査法,治療について検討した.結果:130例中,男性78例(60%),女性52例(40%)で,年齢は48.5±16.7:20〜88歳(平均値±標準偏差:範囲)であった.192眼中,11眼(5.7%)が前部ぶどう膜炎,92眼(47.9%)が後部ぶどう膜炎,88眼(45.8%)が汎ぶどう膜炎であった.眼所見では網膜血管炎142眼(74.0%),硝子体混濁89眼(46.4%),前房炎症88眼(45.8%),網膜滲出斑73眼(38.0%)であった.結核菌感染検査ではツベルクリン反応123例(94.6%),インターフェロン-γ遊離試験(IGRA)83例(63.8%)の順に実施率が高く,陽性率はそれぞれ95.2%,75.9%であった.108例(83.1%)で抗結核薬が投与され,うち41例(38.0%)で副腎皮質ステロイド内服が併用された.全身結核病変を合併していた症例は14例(10.8%)であった.結論:結核性ぶどう膜炎で多い臨床像は網膜血管炎,硝子体混濁であった.全身結核病変を合併していた症例は1割と少なく,臨床像が多彩な結核性ぶどう膜炎の診断にはツベルクリン反応やIGRAが重要であると考えられた.(著者抄録)
  • Rie Tanaka, Toshikatsu Kaburaki, Kazuki Taoka, Ayako Karakawa, Hideki Tsuji, Masako Nishikawa, Yutaka Yatomi, Aya Shinozaki-Ushiku, Tetsuo Ushiku, Fumiyuki Araki
    Ocular immunology and inflammation 1 - 7 2021/04 
    PURPOSE: To establish diagnostic criteria for vitreoretinal lymphoma (VRL) using cytology and laboratory tests from vitreous samples: interleukin (IL)-10/IL-6 ratio, immunoglobulin (Ig) H gene rearrangement, and clonal B-cells on flow cytometry. METHODS: Fifty-six patients with and 39 without VRL were included. We assessed the sensitivity and specificity of each test and those of diagnostic criteria based on combinations of these tests. RESULTS: The sensitivity values for malignant cytology, IL-10/IL-6 > 1, IgH gene rearrangement, and flow cytometry were 0.554, 0.821, 0.732, and 0.625 with specificity of 1.000, 1.000, 0.846, and 0.974, respectively. When the diagnostic criteria were set at malignant cytology or at two or more of of four tests (atypical cells, IL-10/IL-6 > 1, IgH gene rearrangement, and flow cytometry), the sensitivity and specificity values for accurate diagnosis were 0.929 and 1.00, respectively. CONCLUSION: Malignant cytology or positive results for two or more of four tests may be adequate for VRL diagnosis.
  • 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 2021/03 
    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.
  • 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 (公財)日本眼科学会 125 (臨増) 212 - 212 0029-0203 2021/03
  • Shintaro Shirahama, Hirotsugu Soga, Rie Tanaka, Hisako Fukunaga, Hidetomo Izawa, Keiko Komae, Hisae Nakahara, Hidetoshi Kawashima, Makoto Aihara, Toshikatsu Kaburaki
    International ophthalmology 2021/02 
    PURPOSE: To clarify the clinical features of uveitis in elderly patients in central Tokyo. METHODS: We retrospectively identified 1424 patients with uveitis who visited the Uveitis Clinic of the University of Tokyo Hospital between January 2013 and December 2018. The patients were categorized into two groups based on their ages at the time of disease onset: patients aged 65 years or older were included in Group A, whereas those younger than 65 years were included in Group B. The etiological classification of uveitis and its causes were investigated for each group. RESULTS: Group A presented significantly higher rates of infectious uveitis (35.5% vs. 17.8%, p < 0.0001) and masquerade syndromes (17.9% vs. 5.0%, p < 0.0001) than Group B. Furthermore, Group A had significantly higher rates of sarcoidosis (23.1% vs. 9.3%, p < 0.0001), intraocular lymphoma (16.6% vs. 4.6%, p < 0.0001), cytomegalovirus iritis (11.0% vs. 5.6%, p = 0.0043), and cytomegalovirus retinitis (5.2% vs. 1.5%, p = 0.0020) than Group B. CONCLUSION: Our results demonstrate a clear difference in the causative diseases of uveitis between elderly and non-elderly patients. These findings may support ophthalmologists in their diagnostic process for elderly patients with uveitis.
  • Nozomi Igarashi, Megumi Honjo, Ryo Asaoka, Makoto Kurano, Yutaka Yatomi, Koji Igarashi, Kazunori Miyata, Toshikatsu Kaburaki, Makoto Aihara
    Scientific reports 11 (1) 1408 - 1408 2021/01 
    The purpose of this study is to examine if aqueous autotaxin (ATX) and TGF-β levels could be used for differentiating glaucoma subtypes. This prospective observational study was performed using aqueous humor samples obtained from 281 consecutive patients. Open angle glaucoma patients were classified into three groups: primary open-angle glaucoma (POAG), secondary open-angle glaucoma (SOAG), and exfoliation glaucoma (XFG). Aqueous levels of ATX and TGF-βs were quantified. The AUC as well as sensitivity and specificity for the classification into normal and glaucoma subtypes using four indicators-ATX, TGF-β1, TGF-β2, and TGF-β3, upon the application of three machine learning methods. ATX, TGF-β1, and TGF-β3 were positively correlated with IOP, and ATX was significantly and negatively correlated with the mean deviation. From least absolute shrinkage and selection operator regression analysis, the AUC values to distinguish each subgroup [normal, POAG, SOAG, and XFG] ranged between 0.675 (POAG vs. normal) and 0.966 (XFG vs. normal), when four variables were used. High AUC values were obtained with ATX for discriminating XFG from normal eyes and with TGF-β3 for discriminating XFG from normal eyes, POAG, or SOAG. Aqueous TGF-β and ATX exhibited high diagnostic performance in detecting glaucoma subtypes, and could be promising biomarkers for glaucoma.
  • Lourdes Ortiz Fernández, Patrick Coit, Vuslat Yilmaz, Sibel P Yentür, Fatma Alibaz-Oner, Kenan Aksu, Eren Erken, Nursen Düzgün, Gokhan Keser, Ayse Cefle, Ayten Yazici, Andac Ergen, Erkan Alpsoy, Carlo Salvarani, Bruno Casali, Bünyamin Kısacık, Ina Kötter, Jörg Henes, Muhammet Çınar, Arne Schaefer, Rahime M Nohutcu, Alexandra Zhernakova, Cisca Wijmenga, Fujio Takeuchi, Shinji Harihara, Toshikatsu Kaburaki, Meriam Messedi, Yeong-Wook Song, Timuçin Kaşifoğlu, F David Carmona, Joel M Guthridge, Judith A James, Javier Martin, María Francisca González Escribano, Güher Saruhan-Direskeneli, Haner Direskeneli, Amr H Sawalha
    Arthritis & rheumatology (Hoboken, N.J.) 2021/01 
    OBJECTIVE: Behçet's disease is a complex systemic inflammatory vasculitis of incompletely understood etiology. We performed a large genetic study in Behçet's disease in a diverse multi-ethnic population. METHODS: A total of 9,444 patients and controls from seven different populations were included in this study. Genotyping was performed using the Infinium ImmunoArray-24 V.1.0 or V.2.0 BeadChip. Analysis of expression data from stimulated monocytes, and epigenetic and chromatin interaction analyses were performed. RESULTS: We identified two novel genetic susceptibility loci for Behçet's disease, including a risk locus in IFNGR1 (rs4896243, p value= 2.42 X 10-9 ; OR=1.25) and within the intergenic region LNCAROD/DKK1 (rs1660760, p value= 2.75 x 10-8 ; OR= 0.78). The risk variants in IFNGR1 significantly increase IFNGR1 mRNA expression in lipopolysaccharide-stimulated monocytes. In addition, our results replicated the association (p value< 5 x 10-8 ) of six previously identified susceptibility loci in Behçet's disease: IL10, IL23R, IL12A-AS1, CCR3, ADO, and LACC1, reinforcing these loci as strong genetic factors in Behçet's disease shared across ancestries. We also identified >30 genetic susceptibility loci with a suggestive level of association (p value< 5 x 10-5 ), which will require replication. Finally, functional annotation of genetic susceptibility loci in Behçet's disease uncovered their possible regulatory roles and suggested potential causal genes and molecular mechanisms that could be further investigated. CONCLUSION: We performed the largest genetic association study in Behçet's disease to date and revealed novel putative functional variants associated with the disease. We also replicate and extend the genetic associations in other loci across multiple ancestries.
  • Yukiko Tsubota, Yujiro Fujino, Kazuyoshi Ohtomo, Koji Ueda, Junko Yoshida, Takashi Miyai, Toshikatsu Kaburaki, Chihiro Mayama
    International journal of ophthalmology 14 (3) 468 - 471 2021
  • Shintaro Shirahama, Rena Onoguchi-Mizutani, Kentaro Kawata, Kenzui Taniue, Atsuko Miki, Akihisa Kato, Yasushi Kawaguchi, Rie Tanaka, Toshikatsu Kaburaki, Hidetoshi Kawashima, Yoshihiro Urade, Makoto Aihara, Nobuyoshi Akimitsu
    Scientific reports 10 (1) 19406 - 19406 2020/11 
    Long non-coding RNAs (lncRNAs) play vital roles in the pathogenesis of infectious diseases, but the role of lncRNAs in herpes simplex virus 1 (HSV-1) infection remains unknown. Using RNA sequencing analysis, we explored lncRNAs that were highly expressed in murine retinal photoreceptor cell-derived 661W cells infected with HSV-1. U90926 RNA (522 nucleotides) was the most upregulated lncRNA detected post HSV-1 infection. The level of U90926 RNA was continuously increased post HSV-1 infection, reaching a 100-fold increase at 24 h. Cellular fractionation showed that U90926 RNA was located in the nucleus post HSV-1 infection. Downregulation of U90926 expression by RNA interference markedly suppressed HSV-1 DNA replication (80% reduction at 12 h post infection) and HSV-1 proliferation (93% reduction at 12 h post infection) in 661W cells. The survival rates of U90926-knockdown cells were significantly increased compared to those of control cells (81% and 21%, respectively; p < 0.0001). Thus, lncRNA U90926 is crucial for HSV-1 proliferation in retinal photoreceptor cells and consequently leads to host cell death by promoting HSV-1 proliferation.
  • Eric B Suhler, Glenn J Jaffe, Eric Fortin, Lyndell L Lim, Pauline T Merrill, Andrew D Dick, Antoine P Brezin, Quan Dong Nguyen, Jennifer E Thorne, Joachim Van Calster, Luca Cimino, Alfredo Adan, Hiroshi Goto, Toshikatsu Kaburaki, Michal Kramer, Albert T Vitale, Martina Kron, Alexandra P Song, Jianzhong Liu, Sophia Pathai, Kevin M Douglas, Ariel Schlaen, Cristina Muccioli, Mirjam E J Van Velthoven, Manfred Zierhut, James T Rosenbaum
    Ophthalmology 2020/11 
    PURPOSE: To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. DESIGN: Open-label, multicenter, phase 3 extension study (VISUAL III). PARTICIPANTS: Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or who discontinued the study after meeting treatment failure criteria (active uveitis). METHODS: Patients received subcutaneous adalimumab 40 mg every other week. Data were collected for ≤ 362 weeks. Adverse events (AEs) were recorded until 70 days after the last dose. MAIN OUTCOME MEASURES: Long-term safety and quiescence; other efficacy variables included inflammatory lesions, anterior chamber cell and vitreous haze grade, macular edema, visual acuity, and dose of uveitis-related systemic corticosteroids. RESULTS: At study entry, 67% of patients (283/424) showed active uveitis and 33% (141/424) showed inactive uveitis; 60 patients subsequently met exclusion criteria, and 364 were included in the intention-to-treat analysis. Efficacy variables were analyzed through week 150, when approximately 50% of patients (214/424) remained in the study. Patients showing quiescence increased from 34% (122/364) at week 0 to 85% (153/180) at week 150. Corticosteroid-free quiescence was achieved by 54% (66/123) and 89% (51/57) of patients with active or inactive uveitis at study entry. Mean daily dose of systemic corticosteroids was reduced from 9.4 ± 17.1 mg/day at week 0 (n = 359) to 1.5 ± 3.9 mg/day at week 150 (n = 181). The percentage of patients who achieved other efficacy variables increased over time for those with active uveitis at study entry and was maintained for those with inactive uveitis. The most frequently reported treatment-emergent AEs of special interest were infections (n = 275; 79 events/100 patient-years [PY]); AEs and serious AEs occurred at a rate of 396 events/100 PY and 15 events/100 PY, respectively. CONCLUSIONS: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and led to maintenance of quiescence for those with inactive uveitis. AEs were comparable with those reported in the parent trials and consistent with the known safety profile of adalimumab.
  • Han Peng Zhou, Rie Tanaka, Toshikatsu Kaburaki
    Ocular immunology and inflammation 1 - 6 2020/09 [Refereed][Not invited]
     
    PURPOSE: Diagnosis of intraocular lymphoma (IOL) is usually achieved by histopathological analysis. However, it may lead to inconclusive results due to the scarcity of malignant cells obtained by biopsy, hence leading to delayed diagnosis. We report two cases of IOL with pseudo-hypopyon, a rare feature of IOL, as their initial ocular feature, diagnosed using a multidisciplinary diagnostic approach. Common clinical features of IOL with pseudo-hypopyon were also investigated. METHODS: Retrospective case series and literature review. RESULTS: Two cases of IOL, a 78-year-old female and a 59-year-old male, whom had been diagnosed with systemic B-cell lymphoma developed pseudo-hypopyon and visual impairment during the course of their chemotherapy. Diagnosis of IOL was achieved from anterior chamber aspiration samples with supplementary diagnostic tools including flow cytometric immunophenotyping, interleukin and IgH gene rearrangement analysis in addition to the conventional histopathological analysis. Generally, pseudo-hypopyon was more commonly seen in secondary IOL and may associate with hyphema and high intraocular pressure. CONCLUSION: Pseudo-hypopyon is a rare feature of IOL, more commonly seen in secondary IOL, which can be accompanied by hyphema and high intraocular pressure. Supplementary diagnostic tools such as flow cytometric immunophenotyping, interleukin analysis, and immunogloblin H gene rearrangement analysis are useful for supporting the diagnosis of IOL with pseudo-hypopyon.
  • 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 2020/08 [Refereed][Not invited]
     
    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.
  • Nozomi Igarashi, Megumi Honjo, Toshikatsu Kaburaki, Makoto Aihara
    Investigative ophthalmology & visual science 61 (10) 5 - 5 2020/08 [Refereed][Not invited]
     
    Purpose: To examine the role of aqueous tumor necrosis factor α (TNF-α)-RhoA-Rho kinase (ROCK) signaling in cytomegalovirus (CMV)-induced apoptosis and the barrier function of cultured human corneal endothelial cells (hCECs) in CMV-positive Posner-Schlossman syndrome (CMV+/PSS) patients. Methods: Aqueous levels of TNF-α, IL-8, IL-10, and several other cytokines in 19 CMV+/PSS patients and 20 healthy control subjects were quantitated using a multiplex assay. The expression of active RhoA in hCECs post-CMV infection was determined using western blotting (WB). The expression levels of TNF-α and nuclear factor kappa B (NF-κB) in CMV-infected hCECs were examined by immunocytochemistry (ICC) and WB with and without ROCK inhibitors. The apoptotic rate and barrier integrity in CMV-infected hCECs were also examined. Results: The expression levels of TNF-α, monocyte chemoattractant protein-1 (MCP-1), IL-8, and IL-10 were upregulated in the aqueous humor of CMV+/PSS patients, and among these upregulated cytokines aqueous TNF-α was negatively correlated with the number of corneal endothelial cells. In CMV-infected hCECs, upregulation of TNF-α and NF-κB was determined by WB and ICC. In hCECs, CMV infection induced apoptosis and significantly impaired cell-cell contacts, effects that were attenuated by treatment with a ROCK inhibitor. Conclusions: Aqueous TNF-α was upregulated in CMV+/PSS patients, which may have triggered corneal endothelial cell loss. Modulation of TNF-α, including its downstream Rho-ROCK signaling, could serve as a novel treatment modality for corneal endothelial cell loss in CMV+/PSS patients.
  • Nozomi Kinoshita, Yasuhiro Konno, Naoki Hamada, Yoshinobu Kanda, Machiko Shimmura-Tomita, Toshikatsu Kaburaki, Akihiro Kakehashi
    Scientific reports 10 (1) 12750 - 12750 2020/07 [Refereed][Not invited]
     
    Eighty Japanese children, aged 8-12 years, with a spherical equivalent refraction (SER) of - 1.00 to - 6.00 dioptres (D) were randomly allocated into two groups to receive either a combination of orthokeratology (OK) and 0.01% atropine solution (combination group) or monotherapy with OK (monotherapy group). Seventy-three subjects completed the 2-year study. Over the 2 years, axial length increased by 0.29 ± 0.20 mm (n = 38) and 0.40 ± 0.23 mm (n = 35) in the combination and monotherapy groups, respectively (P = 0.03). Interactions between combination treatment and age or SER did not reach significance level (age, P = 0.18; SER, P = 0.06). In the subgroup of subjects with an initial SER of - 1.00 to - 3.00 D, axial length increased by 0.30 ± 0.22 mm (n = 27) and 0.48 ± 0.22 mm (n = 23) in the combination and monotherapy groups, respectively (P = 0.005). In the - 3.01 to - 6.00 D subgroup, axial length increased by 0.27 ± 0.15 mm (n = 11) and 0.25 ± 0.17 mm (n = 12) in the combination and monotherapy groups, respectively (P = 0.74). The combination therapy may be effective for slowing axial elongation, especially in children with low initial myopia.
  • 田岡 和城, 遠山 和博, 田中 理恵, 蕪城 俊克, 相原 一, 黒川 峰夫
    日本リンパ網内系学会会誌 (一社)日本リンパ網内系学会 60 78 - 78 1342-9248 2020/07
  • 関 沙織, 田中 理恵, 蕪城 俊克, 小前 恵子, 中原 久恵, 伊沢 英知, 白濱 新多朗, 曽我 拓嗣, 高本 光子, 相原 一
    臨床眼科 (株)医学書院 74 (5) 589 - 594 0370-5579 2020/05 
    <文献概要>目的:炎症性腸疾患に伴う眼炎症の臨床的特徴の検討。対象と方法:1996〜2018年に東京大学医学部附属病院眼科を受診し,炎症性腸疾患に伴う眼炎症疾患と診断された症例を対象とした。患者背景,炎症性腸疾患の内訳,眼炎症の病型,再発歴,眼合併症,治療,視力予後について検討した。結果:症例は,男性4例,女性8例,初診時年齢35〜77歳(平均48.7±13.4歳)。原因疾患は,潰瘍性大腸炎10例,クローン病2例であった。原因疾患に対する治療としては,5-アミノサリチル酸製剤内服8例,外科手術4例,栄養療法1例,インフリキシマブ投与1例が行われていた。炎症性腸疾患の発症から当院初診までの期間は9〜34年(平均19.1±7.9年)であった。眼炎症の病型は,前部ぶどう膜炎11例,上強膜炎1例であった。前部ぶどう膜炎のうち,非肉芽腫性は10例,1例は詳細不明であった。両眼性は9例,片眼性は3例であった。再発歴は9例に認めた。眼合併症としては続発緑内障1例であった。眼科治療として,ステロイド点眼12例,デキサメタゾン結膜下注射5例,トリアムシノロンアセトニドテノン嚢下注射1例,ステロイド内服2例が施行されていた。最終観察時に眼炎症が原因で視力低下をきたしていた症例はなかった。結論:原因疾患は潰瘍性大腸炎が多くみられた。両眼性の前部ぶどう膜炎で再発歴を認めることが多かったが,視力予後は良好であった。
  • Tomohito Sato, Wataru Yamamoto, Atsushi Tanaka, Haruna Shimazaki, Sunao Sugita, Toshikatsu Kaburaki, Masaru Takeuchi
    Journal of clinical medicine 9 (4) 2020/04 [Refereed][Not invited]
     
    Acute retinal necrosis (ARN) is a rare viral endophthalmitis, and human herpesvirus is the principal pathogen. Early diagnosis and treatment are critical to avoid visual impairment by ARN, and pars plana vitrectomy (PPV) is required in advanced cases. In this study, we evaluated the transition of viral load in ocular fluids of ARN eyes with varicella-zoster virus (VZV) after intravenous acyclovir treatment. Fourteen eyes of 13 patients were analyzed retrospectively. All patients received intravenous acyclovir treatment, and eventually, all eyes underwent PPV. A polymerase chain reaction (PCR) test showed a 100% detection rate in all aqueous humor samples collected before the treatment (Pre-AH), as well as aqueous humor (Post-AH) and vitreous fluid samples (VF), collected during PPV conducted after the treatment. Within eight days or less of acyclovir treatment, viral loads both in AH and VF did not decrease significantly. Furthermore, the viral load of Pre-AH had a strong correlation with that of VH. These data suggest that in ARN eyes with VZV infection, the AH sample for the PCR test was reliable to confirm the pathogen. We propose that short-term treatment of intravenous acyclovir may be insufficient for reducing intraocular viral load, and the Pre-AH sample could be a predictor of viral activity in the eyes after acyclovir treatment.
  • 日下部 茉莉, 蕪城 俊克, 田中 理恵, 大友 一義, 高本 光子, 中原 久惠, 冲永 貴美子, 白濱 新多朗, 沼賀 二郎, 藤野 雄次郎, 相原 一
    臨床眼科 (株)医学書院 74 (4) 395 - 404 0370-5579 2020/04 
    <文献概要>目的:近年,わが国におけるトキソプラズマ網脈絡膜炎の多数例での報告は少ない。近年のわが国における活動性のトキソプラズマ網脈絡膜炎の臨床像を明らかにすることを目的として検討を行った。対象と方法:2000年1月〜2019年3月に東京大学医学部附属病院眼科を受診し活動性のトキソプラズマ網脈絡膜炎と診断された患者13例14眼について,鬼木の分類に従って先天性・後天性に分類し,臨床像を検討した。結果:片眼例が12例,両眼例が1例であった。黄斑部病変が7眼,周辺部病変が7眼にみられた。先天性トキソプラズマ症は2例2眼で,平均発症年齢は17.5歳,2眼とも黄斑部病変であった。後天性症例は8例9眼で平均発症年齢は44.9歳,黄斑部病変4眼,周辺部病変5眼であった。不明例は3例3眼で平均発症年齢は61.0歳,3例とも周辺部病変であった。全例でアセチルスピラマイシン投与が行われ,7例でプレドニゾロン内服が併用された。経過中に再燃が4例でみられ,黄斑部型症例が3例,周辺部型症例が1例であった。結論:近年のトキソプラズマ網膜症は両眼性が少なく,先天性より後天性症例が多く,後天性症例で周辺型が半分以上を占めた。アセチルスピラマイシン治療は,安全で多くの症例で有効であった。
  • Marie Kitano, Rie Tanaka, Toshikatsu Kaburaki, Hisae Nakahara, Shintaro Shirahama, Takafumi Suzuki, Keiko Komae, Makoto Aihara
    Ocular immunology and inflammation 1 - 7 2020/03 [Refereed][Not invited]
     
    Purpose: To investigate the clinical features and visual outcome of young Japanese patients with uveitis.Methods: Patients younger than 18 years who presented with uveitis at the University of Tokyo Hospital between 2000 and 2018 were retrospectively reviewed.Results: The study comprised 98 patients whose mean age was 12.3 ± 3.8 years. Anterior uveitis was present in 52.0%, panuveitis in 37.8%, and posterior uveitis in 10.2%. The most common diagnosis was juvenile chronic iridocyclitis (JCI) (29.6%) followed by tubulointerstitial nephritis and uveitis syndrome (4.1%) and neuroretinitis (4.1%). Thirty-nine patients received systemic anti-inflammatory treatment. Among all subjects, 56% presented with ocular complications and 20% underwent ocular surgery. Visual acuity of 20/200 or less was observed in 6.2%. The common causes of decreased vision were hypotony, serous retinal detachment, and pupil disorder.Conclusions: JCI was the most common diagnosis. Hypotony, serous retinal detachment, and pupil disorder can lead to visual loss.
  • Rie Tanaka, Toshikatsu Kaburaki, Atsushi Yoshida, Mitsuko Takamoto, Tempei Miyaji, Takuhiro Yamaguchi
    Ocular immunology and inflammation 1 - 5 2020/03 [Refereed][Not invited]
     
    Purpose: To compare standard fluorescein angiography (FA) and ultra-wide-field (UWF) FA in evaluating sarcoid uveitis activity using the scoring system adopted by the Angiography Scoring for Uveitis Working Group (ASUWG).Methods: Standard and UWF FA images of 36 eyes with sarcoid uveitis were acquired on the same day. Three graders independently graded 72 FA images using the ASUWG scoring system. We evaluated inter-observer variability using the intra-class correlation coefficient (ICC) and compared scores of each angiographic sign.Results: The ICC was 0.77 for standard FA and 0.87 for UWF FA, with respective total scores of 12.0 and 14.6. UWF FA had higher scores than standard FA for optic disc hyperfluorescence, posterior retinal vascular staining and/or leakage, and peripheral capillary leakage.Conclusions: The scores for UWF FA had a higher ICC than those for standard FA in evaluating sarcoid uveitis. Peripheral capillary leakage scores were particularly high for UWF FA.
  • ANCA関連血管炎に伴う強膜炎14例の臨床像
    三原 現, 田中 理恵, 小前 恵子, 中原 久恵, 伊沢 英知, 白濱 新多朗, 曽我 拓嗣, 小野 久子, 蕪城 俊克
    日本眼科学会雑誌 (公財)日本眼科学会 124 (臨増) 243 - 243 0029-0203 2020/03
  • 蕪城 俊克, 田中 理恵, 福永 久子, 唐川 綾子, 白濱 新多朗, 曽我 拓嗣, 小前 恵子, 中原 久恵, 伊沢 英知, 相原 一, 井上 達也, 川島 秀俊, 辻 英貴, 竹内 二士夫, 佐藤 智人, 竹内 大, 裏出 良博, 和田 洋一郎, 田岡 和城, 黒川 峰夫
    日本眼科学会雑誌 (公財)日本眼科学会 124 (3) 220 - 246 0029-0203 2020/03 
    ぶどう膜炎の病態は動物疾患モデルを用いた研究などにより理解は進み,その成果はtumor necrosis factor(TNF)阻害薬などの新しい治療薬に応用されているが,依然として不明な点も多い.眼炎症性疾患であるBehcet病(以下,ベーチェット病),網膜血管炎,眼内リンパ腫に対して,その病態解明と新規治療法の開発に向けた我々の研究を報告する.1.ベーチェット病の臨床像とリンパ球を活性化するHLA関連抗原の解析 ベーチェット病ぶどう膜炎は内因性ぶどう膜炎の中でも最も重篤なぶどう膜炎である.我々は新しいベーチェット病ぶどう膜炎の活動性評価法としてBehcet's disease ocular attack score 24(BOS24)を作成し,視力変化と有意に相関することを示した.一方,ヒト白血球抗原(HLA)はリンパ球への抗原提示に必要な分子で,ベーチェット病ぶどう膜炎ではHLA-B*5101またはA*2601陽性症例が約8割を占める.我々はHLA-A*2601を持つ症例は,視力予後不良例が多いことを報告した.またHLA-B*51のポケット構造と結合力の高いアミノ酸配列を三次元的分子力学シミュレーションにより選定する方法を考案し,ベーチェット病患者リンパ球との反応性が報告されている既知の抗原における親和性の高いアミノ酸配列を推定した.それらのペプチドはベーチェット病患者の末梢血リンパ球の増殖を有意に促進した.HLAと抗原ペプチドの親和性がリンパ球の活性化に直接関与する可能性が示唆された.2.ぶどう膜炎における網膜血管炎の新しい理解 網膜血管炎はぶどう膜炎やさまざまな網膜疾患でみられ,フルオレセイン蛍光眼底造影(FA)での画像所見上,動脈炎,静脈炎,毛細血管炎に分類される.我々はさまざまなぶどう膜炎疾患のFA画像を検討し,感染性ぶどう膜炎では非感染性ぶどう膜炎と比べて網膜動脈炎および動静脈閉塞が高率にみられることを見出した.この機序を明らかにするために,活動期のさまざまなぶどう膜炎疾患の硝子体液中の炎症性サイトカインを網羅的に検討した.ぶどう膜炎疾患では共通してTNF-αやケモカインが上昇しており,眼内リンパ腫ではinterleukin(IL)-10,急性網膜壊死ではinterferon(IFN)-α2,細菌性眼内炎ではIL-6,IL-17A,顆粒球コロニー刺激因子(G-CSF)が特異的に上昇していた.ぶどう膜炎の原因疾患によって硝子体液中の炎症性サイトカインの発現パターンに特徴がみられることが明らかとなった.3.眼内リンパ腫の診断と治療 近年,ぶどう膜炎に占める眼内リンパ腫の割合は増加しており,他のぶどう膜炎疾患と誤診されやすく,脳中枢神経系病変を来しやすいため生命予後の不良な疾患である.本疾患の明確な診断基準および標準治療は未だ確立していない.我々は,眼内原発リンパ腫に対し,メトトレキサート硝子体内注射,全身化学療法,予防的低線量全脳照射を組み合わせた治療の前向き研究を行い,本疾患の生命予後を改善し,脳再発を抑制できることを示した.一方,二次性眼内リンパ腫は眼・脳中枢神経系以外の臓器を原発としたリンパ腫が眼内に進展した状態である.二次性眼内リンパ腫の臨床像および治療成績を後ろ向きに検討したところ,さまざまな治療にもかかわらず再燃を繰り返し,きわめて予後不良であることが明らかとなった.眼内リンパ腫,特に二次性眼内リンパ腫に対する新たな治療法の確立が急務である.(著者抄録)
  • 眼内悪性リンパ腫の網膜病変の有無と臨床像の関連性
    日下部 茉莉, 田中 理恵, 小前 恵子, 伊沢 英知, 田岡 和城, 中原 久恵, 白濱 新多朗, 相原 一, 川島 秀俊, 蕪城 俊克
    日本眼科学会雑誌 (公財)日本眼科学会 124 (臨増) 244 - 244 0029-0203 2020/03
  • Shintaro Shirahama, Toshikatsu Kaburaki, Sachiko Takada, Hisae Nakahara, Rie Tanaka, Keiko Komae, Yujiro Fujino, Hidetoshi Kawashima, Makoto Aihara
    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 258 (3) 639 - 645 2020/03 [Refereed][Not invited]
     
    PURPOSE: To clarify the prevalence of secondary glaucoma (SG) and its speed of progression in patients with herpes simplex virus (HSV)-anterior uveitis (AU), varicella zoster virus (VZV)-AU, and cytomegalovirus (CMV)-AU. METHODS: In total, 170 patients with herpetic AU were enrolled in this retrospective observational case series. Patients with visual field (VF) defects and glaucomatous disc abnormalities were diagnosed with SG. Moreover, the speed of SG progression was defined as decreasing mean deviation (MD) values per year. SG prevalence and annual MD-value decrease were compared among the three types of herpetic AU. RESULTS: SG prevalence was 16%, 9%, and 72% in patients with HSV-AU, VZV-AU, and CMV-AU, respectively. Patients with CMV-AU had the highest SG prevalence (odds ratio = 3.15; 95% confidence interval = 1.15-8.65; P < 0.05). Furthermore, the annual MD-value change was significantly higher in SG caused by CMV-AU than in that caused by HSV/VZV-AU (-2.6 ± 2.4 dB/year and -0.45 ± 0.54 dB/year, respectively; P < 0.05). CONCLUSIONS: Our results demonstrated that patients with CMV-AU may have a higher risk and faster speed of progression of SG than patients with HSV/VZV-AU. Therefore, clinicians should monitor glaucoma onset and VF-defect progression in patients with CMV-AU.
  • Toshikatsu Kaburaki, Hisako Fukunaga, Rie Tanaka, Hisae Nakahara, Hidetoshi Kawashima, Shintaro Shirahama, Hidetomo Izawa, Keiko Komae, Mitsuko Takamoto, Hirotsugu Soga, Makoto Aihara
    Japanese journal of ophthalmology 64 (2) 150 - 159 2020/03 [Refereed][Not invited]
     
    PURPOSE: Retinal vasculitis and occlusive changes are important signs of posterior uveitis and are possible diagnostic markers for uveitis. However, the frequency of arteritis and phlebitis in various uveitis entities, including infectious uveitis (IU) and non-infectious uveitis (NIU), have not been systematically investigated. STUDY DESIGN: Retrospective. METHODS: We investigated the frequency of retinal vascular inflammatory and occlusive changes in patients with IU and NIU. The study included 283 patients with intermediate, posterior, or pan-uveitis who were diagnosed with IU (presumed tuberculous uveitis, acute retinal necrosis, cytomegalovirus retinitis, human T-cell lymphotropic virus type 1-associated uveitis, toxoplasmic retinitis, syphilitic uveitis, rubella virus-associated uveitis, fungal endophthalmitis, and bacterial endophthalmitis) or NIU (sarcoidosis, Behçet's disease, Vogt-Koyanagi-Harada disease, human leukocyte antigen-B27-associated uveitis, systemic lupus erythematosus retinopathy, psoriatic uveitis, rheumatoid arthritis/collagen disease-associated uveitis, multiple sclerosis-associated uveitis, and sympathetic ophthalmia). All patients underwent fluorescein angiography (FA) and color photography examinations of the fundus. Presence of inflammatory and occlusive changes was determined by FA images. RESULTS: Significantly higher positive ratios of phlebitis, vein sheathing, vein occlusion, arteritis, artery sheathing, artery occlusion, and avascular areas were observed in the IU group than in the NIU group (p < 0.05). Notably, the discrepancy between IU and NIU was prominent with regard to retinal arterial changes (arteritis [57.9% vs 11.2%], inflammatory artery sheathing [33.7% vs 0%], and artery occlusion [22.1% vs 3.7%], respectively; p < 0.0001). CONCLUSION: Findings of vasculitis and occlusion, especially in retinal arteries, in FA strongly suggest an infectious origin of active uveitis.
  • Hisako Fukunaga, Toshikatsu Kaburaki, Shintaro Shirahama, Rie Tanaka, Hiroshi Murata, Tomohito Sato, Masaru Takeuchi, Hideto Tozawa, Yoshihiro Urade, Mari Katsura, Mika Kobayashi, Youichiro Wada, Hirotsugu Soga, Hidetoshi Kawashima, Takahide Kohro, Makoto Aihara
    Scientific reports 10 (1) 2783 - 2783 2020/02 [Refereed][Not invited]
     
    Treatment of uveitis is complicated because of its multiple aetiologies and elevation of various inflammatory mediators. To determine the mediators that are elevated in the vitreous humor according to the aetiology of the uveitis, we examined the concentrations of 21 inflammatory cytokines, 7 chemokines, and 5 colony-stimulating/growth factors in vitreous samples from 57 eyes with uveitis associated with intraocular lymphoma (IOL, n = 13), sarcoidosis (n = 15), acute retinal necrosis (ARN, n = 13), or bacterial endophthalmitis (BE, n = 16). Samples from eyes with idiopathic epiretinal membrane (n = 15), which is not associated with uveitis, were examined as controls. Heat map analysis demonstrated that the patterns of inflammatory mediators in the vitreous humor in eyes with uveitis were disease-specific. Pairwise comparisons between the 5 diseases showed specific elevation of interferon-α2 in ARN and interleukin (IL)-6, IL-17A, and granulocyte-colony stimulating factor in BE. Pairwise comparisons between IOL, ARN, and BE revealed that levels of IL-10 in IOL, RANTES (regulated on activation, normal T cell expressed and secreted) in ARN, and IL-22 in BE were significantly higher than those in the other 2 types of uveitis. These mediators are likely to be involved in the immunopathology of specific types of uveitis and may be useful biomarkers.
  • Worawit Louthrenoo, Nuntana Kasitanon, Kessara Pathanapitoon, Suparaporn Wangkaew, Shoji Kuwata, Ai Nishi, Toshikatsu Kaburaki, Rie Tanaka, Fujio Takeuchi
    International journal of rheumatic diseases 23 (2) 247 - 255 2020/02 [Refereed][Not invited]
     
    AIMS: To investigate susceptible human leukocyte antigen (HLA) alleles and their associations with clinical features in Thai patients with Behçet's disease (BD). METHOD: Eighteen HLA-A and 36 HLA-B alleles were determined in 42 Thai BD patients and 99 healthy controls (HCs) by reverse line blot assay, and reconfirmed by MICRO SSP assay. RESULTS: The BD patients had significantly higher allele frequency (AF) of HLA-B*51 than the HCs (13.10% vs 5.05%, P = .025). The AF of HLA-A*26, -A*26:01 and -B*51:01 also was higher and almost reached statistical significance (5.59% vs 1.52%, P = .054, 5.95% vs 1.52%, P = .054 and 10.71% vs 4.04%, P = .051, respectively). However, the BD patients had significantly higher AF of either HLA-A*26:01 or -B*51:01 (16.67% vs 5.56%, P = .005), or -A*26:01 or -B*51X (19.05% vs 6.56%, P = .003). The AF of HLA-B*51:01 and -B*51X increased significantly in -A*26:01 non-carrier BD patients (12.16% vs 4.17%, P = .024 and 14.86% vs 5.21%, P = .019, respectively); and that of HLA-A*26:01 was significantly higher in -B*51X non-carrier BD patients (7.58% vs 1.67%, P = .034). HLA-B*51:01 associated significantly with the presence of posterior uveitis and visual impairment (18.18% vs 2.50%, P = .031 for both conditions). HLA-B*51:01 was not observed in BD patients with gastrointestinal involvement or arthritis. Furthermore, the AF of HLA-B*51:01 was significantly higher in HLA-A*26:01 non-carrier BD patients without arthritis (17.30% vs 0%, P = .050). CONCLUSION: HLA-B*51:01 was a susceptible allele for Thai BD patients, and associated with posterior uveitis and visual impairment. HLA-A*26:01 was another susceptible allele in HLA-B*51X non-carrier patients. The protective effect of HLA-B*51:01 on arthritis needs further investigation.
  • Hisae Nakahara, Toshikatsu Kaburaki, Rie Tanaka, Atsushi Yoshida, Mitsuko Takamoto, Mikiko Kawata, Yujiro Fujino, Hidetoshi Kawashima, Makoto Aihara
    Ocular immunology and inflammation 28 (2) 262 - 269 2020 [Refereed][Not invited]
     
    Purpose: We investigated clinical characteristics of ocular Behçet's disease (BD) patients treated in the 1990s and the 2000s.Methods: We retrospectively examined records of 68 newly arrived patients with ocular BD followed for more than 4 months during the 2000s and compared to those of 107 patients during the 1990s. Patient profiles, ocular and systemic symptoms, frequency of ocular attacks, BD ocular attack score 24-6 months (BOS24-6M), best-corrected visual acuity (BCVA), and immunomodulatory treatment were noted.Results: Clinical characteristics in the 2000s showed increases in iridocyclitis type, intestinal-, vasculo-, and neuro-BD cases, oral corticosteroid, methotrexate, and infliximab therapy usage, cataract and glaucoma surgery, and pseudophakia, and decreases in BOS24-6M and cyclophosphamide usage. BCVA of 20/30 or better at the final visit was slightly increased in the 2000s.Conclusions: Milder ocular BD tendency was seen in cases in the 2000s, whereas the incidence of special type of BD might be increasing.
  • Shintaro Shirahama, Atsuko Miki, Toshikatsu Kaburaki, Nobuyoshi Akimitsu
    Frontiers in genetics 11 454 - 454 2020 [Refereed][Not invited]
     
    Recently developed technologies have revealed that the genomes of many organisms produce transcripts that do not encode proteins. These are called non-coding RNAs. Long non-coding RNAs (lncRNAs) are important regulators of the expression of their target genes at the levels of transcription, translation, and degradation. Multiple studies have demonstrated a role for lncRNAs in various biological responses, including pathogenic infection. Upon pathogenic infection, the expression levels of lncRNAs are dynamically altered, suggesting that lncRNAs are involved in the host immune response or propagation of pathogens. In this review, we focused on host lncRNAs that are involved in pathogenic infection. Some host lncRNAs act as host defense molecules to prevent pathogenic proliferation, while others are utilized by the pathogen to enhance the propagation of pathogens.
  • BDUMPが疑われた1例
    木村 至, 平林 豊, 永原 幸, 小畑 亮, 蕪城 俊克
    眼科臨床紀要 眼科臨床紀要会 12 (11) 865 - 865 1882-5176 2019/11
  • Rie Tanaka, Toshikatsu Kaburaki, Hisae Nakahara, Keiko Komae
    International ophthalmology 39 (11) 2649 - 2659 2019/11 [Refereed][Not invited]
     
    PURPOSE: To investigate the clinical features of patients with ocular inflammation associated with relapsing polychondritis in Japan. METHODS: Ocular findings, systemic symptoms, and therapies were analysed retrospectively. RESULTS: Nine of 11 patients had scleritis (diffuse scleritis: six patients, posterior scleritis: two patients, episcleritis: one patient) and two patients had anterior uveitis. All cases were bilateral, and ten patients experienced recurrent episodes. Auricular chondritis was the most common systemic symptom. Ten patients were administered systemic steroids, and five patients were administered other immunosuppressive medications for severe systemic symptoms. At their last visit, none of the patients had decreased visual acuity that resulted from relapsing polychondritis-associated ocular inflammation. CONCLUSIONS: Ocular inflammation is often bilateral and recurring. Patients with ocular inflammation must be questioned regarding systemic symptoms so that the signs of relapsing polychondritis are not overlooked. Early diagnosis and prompt, appropriate treatment are important because relapsing polychondritis is a potentially lethal disease.
  • Manabu Mochizuki, Justine R Smith, Hiroshi Takase, Toshikatsu Kaburaki, Nisha R Acharya, Narsing A Rao
    The British journal of ophthalmology 103 (10) 1418 - 1422 2019/10 [Refereed][Not invited]
     
    AIMS: International criteria for the diagnosis of ocular sarcoidosis (OS) was established by the first International Workshop on Ocular Sarcoidosis (IWOS) and validations studies revealed certain limitations of the criteria. To overcome the limitations, revised IWOS criteria was established in an international meeting. This manuscript was aimed at reporting the revised IWOS criteria. METHODS: A consensus workshop was carried out to discuss and revise the IWOS criteria. The workshop was held on 27 April 2017, in Nusa Dua, Bali, Indonesia. Prior to the workshop, a questionnaire proposing revised criteria and consisting of one item for differential diagnosis, seven items for ocular clinical signs, 10 items for systemic investigations and three categories of diagnostic criteria was circulated to 30 uveitis specialists. Questionnaire items with over 75% support were taken as consensus agreement; items with below 50% support were taken as consensus disagreement and items with 50%-75% support were discussed at the workshop. Of the latter items, those supported by two-thirds majority in the workshop were taken as consensus agreement. RESULTS: The survey and subsequent workshop reached consensus agreements of the revised criteria for the diagnosis of OS as follows: (1) other causes of granulomatous uveitis must be ruled out; (2) seven intraocular clinical signs suggestive of OS; (3) eight results of systemic investigations in suspected OS and (4) three categories of diagnostic criteria depending on biopsy results and combination of intraocular signs and results of systemic investigations. CONCLUSIONS: Revised IWOS criteria were proposed by a consensus workshop.
  • Shintaro Shirahama, Toshikatsu Kaburaki, Junko Matsuda, Rie Tanaka, Hisae Nakahara, Keiko Komae, Hidetoshi Kawashima, Makoto Aihara
    Ocular immunology and inflammation 28 (8) 1 - 5 2019/08 [Refereed][Not invited]
     
    Purpose: To clarify the relationship between fluorescein angiography (FA) leakage after infliximab therapy and ocular attack relapse in patients with ocular Behçet's disease (BD). Methods: Patients with ocular BD were divided into two groups based on the presence (Group 1) or absence (Group 2) of ocular attacks after IFX therapy. FA leakage was evaluated by FA score in each of the optic discs, macula, large retinal vessels, and capillary vessels. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the relationship between FA score after IFX therapy and ocular attack relapse. Results: The areas under the curves obtained from the ROC curve of optic disc score and capillary vessels score after IFX therapy were 0.867 (95% confidence interval [CI]: 0.788-0.946) and 0.788 (95% CI: 0.649-0.927), respectively. Conclusions: FA leakage in the optic disc and capillary vessels after IFX therapy was strongly related to ocular attack relapse.
  • Shintaro Shirahama, Toshikatsu Kaburaki, Hisae Nakahara, Rie Tanaka, Keiko Komae, Yujiro Fujino, Hidetoshi Kawashima, Makoto Aihara
    Scientific reports 9 (1) 8612 - 8612 2019/06 [Refereed][Not invited]
     
    This study aimed to clarify the association between the retinal leakage site on fluorescein angiography (FA) and subfoveal choroidal thickness (SCT) measured using enhanced depth imaging optical coherence tomography (EDI-OCT). Twenty-two patients with Behçet's uveitis were retrospectively selected in this study. They underwent EDI-OCT and FA in both the active and convalescent phases. The associations of the changes between the active and convalescent phases in SCT and in FA leakage in various retinal areas (total retina, peripheral retina, macula, and optic disc) were examined. The changing rates of SCT between the two investigated phases were significantly associated with the changes in total FA leakage scores (y = 1.79X+ 11.7, r2 = 0.210, p < 0.05). Furthermore, the changes in FA leakage scores in the macula were correlated with the changing rates in SCT (y = 3.72X+ 13.9, r2 = 0.219, p < 0.05). By contrast, there were no significant associations between the changes in SCT and those in leakage from the peripheral retina or the optic disc on FA. These findings demonstrate that SCT may reflect macular vasculitis as determined using FA, and SCT measurement could be a non-invasive method to investigate inflammation near the macula in Behçet's uveitis.
  • Shotaro Asano, Rie Tanaka, Hidetoshi Kawashima, Toshikatsu Kaburaki
    Case Reports in Ophthalmology 10 (1) 145 - 152 2019/05 
    Background: Adalimumab, a human anti-tumor necrosis factor-ɑ monoclonal antibody, was recently reported to be effective in lowering the risk of recurrence of noninfectious uveitis. This is the first case series of adalimumab administrations for relentless placoid chorioretinitis (RPC) patients. Case Presentation: We report 2 cases of RPC where successful treatments were achieved with adalimumab. A 34-year-old woman developed conjunctival hyperemia, mild iridocyclitis, and multiple atrophic retinal lesions, along with exudative changes that were widespread from the posterior pole to peripheral retina in both eyes. The diagnosis of RPC was made based on the characteristic recurrences of choroiditis despite systemic corticosteroid and cyclosporine. Adalimumab therapy was introduced to the patient, and thereafter no recurrence was observed while tapering the immunosuppressive agents. The second case was a 22-year-old man with visual deterioration in both eyes who exhibited widespread multiple chorioretinal atrophic lesions. We diagnosed the case as RPC based on characteristic clinical findings and recurring chorioretinitis during tapering of systemic corticosteroids. Adalimumab therapy was administrated, and immunosuppressant dosage was successfully reduced without any recurrences. Conclusions: In the current two RPC cases, adalimumab was quite effective and useful to reduce the dosages of systemic immunosuppressants. Further study is necessary to confirm the effectiveness of adalimumab in RPC patients.
  • 偏光OCTによる眼底偏光特性の人種間比較
    甘利 達明, 小畑 亮, 藤田 あさひ, 南 貴紘, 山本 素士, 小松 佳代子, 小川 麻湖, 山藤 大輔, 青木 信頼, 山成 正宏, 杉山 聡, 大島 進, 東 恵子, 井上 達也, 本庄 恵, 蕪城 俊克, 相原 一, 加藤 聡
    日本眼科学会雑誌 123 (臨増) 176 - 176 0029-0203 2019/03
  • PS-OCTエントロピーと近赤外線自家蛍光を用いた眼底の観察(Fundus observation using PS-OCT entropy and near-infrared autofluorescence)
    南 貴紘, 藤田 あさひ, 小畑 亮, 山本 素士, 小松 佳代子, 小川 麻湖, 山藤 大輔, 青木 伸頼, 山成 正宏, 杉山 聡, 大島 進, 甘利 達明, 東 恵子, 井上 達也, 本庄 恵, 蕪城 俊克, 相原 一, 加藤 聡
    日本眼科学会雑誌 123 (臨増) 292 - 292 0029-0203 2019/03
  • 前立腺癌によるBilateral Diffuse Uveal Melanocytic Proliferationが疑われた1例
    平林 豊, 永原 幸, 小畑 亮, 蕪城 俊克, 木村 至
    日本眼科学会雑誌 (公財)日本眼科学会 123 (臨増) 311 - 311 0029-0203 2019/03
  • ぶどう膜炎疾患の硝子体液中サイトカイン濃度の比較
    小野 久子, 蕪城 俊克, 田中 理恵, 佐藤 智人, 竹内 大, 戸澤 英人, 桂 真理, 和田 洋一郎, 白濱 新多朗, 曽我 拓嗣, 川島 秀俊, 相原 一
    日本眼科学会雑誌 (公財)日本眼科学会 123 (臨増) 227 - 227 0029-0203 2019/03
  • インフリキシマブ導入後5年以上経過観察を行ったベーチェット病ぶどう膜炎の治療成績
    冲永 貴美子, 田中 理恵, 小前 恵子, 伊沢 英知, 中原 久恵, 白濱 新多朗, 曽我 拓嗣, 小野 久子, 吉田 淳, 川島 秀俊, 蕪城 俊克
    日本眼科学会雑誌 (公財)日本眼科学会 123 (臨増) 229 - 229 0029-0203 2019/03
  • Masaru Takeuchi, Takayuki Kanda, Toshikatsu Kaburaki, Rie Tanaka, Kenichi Namba, Koju Kamoi, Kazuichi Maruyama, Etsuko Shibuya, Nobuhisa Mizuki
    Medicine 98 (9) e14668  2019/03 [Refereed][Not invited]
     
    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.
  • Miyano Ryoji, Kurihara Masanori, Orimo Kenta, Mano Tatsuo, Kaburaki Toshikatsu, Tanaka Rie, Nishijima Hironobu, Ikemura Masako, Takahashi Miwako, Mori Harushi, Mutoh Tatsuro, Hamada Masashi, Hayashi Toshihiro, Toda Tatsushi
    Neurology and Clinical Neuroscience 7 (2) 75 - 77 2049-4173 2019/03 [Refereed][Not invited]
     
    A 71-year-old woman with a 6-month history of relapsing bilateral anterior scleritis presented with severe right visual impairment due to posterior scleritis. Despite radiological signs of encephalitis, the patient and her family members noticed no cognitive decline. The patient subsequently developed slight auricular pain without any visual changes such as redness or swelling, which, however, showed increased uptake of F-18-fluorodeoxyglucose on positron emission tomography. Auricular cartilage biopsy revealed perichondrial inflammation suggesting relapsing polychondritis. Steroid therapy improved her symptoms and radiological findings. This case illustrates that asymptomatic brain inflammatory lesions can precede clinical signs of chondritis in relapsing polychondritis, and that auricular cartilage biopsy should be considered even with mild auricular pain without apparent clinical findings of inflammation.
  • Nozomi Igarashi, Hiromasa Sawamura, Toshikatsu Kaburaki, Makoto Aihara
    Neuro-ophthalmology (Aeolus Press) 43 (1) 36 - 42 2019/02 [Refereed][Not invited]
     
    A 73-year-old female with a past medical history of breast cancer, who 10 years earlier experienced complete remission, complained of bilateral visual field disturbances and photopsia, 2 months prior. Tumour recurrence and metastatic lesions were not found during the medical examination, but antibodies against recoverin were detected in her serum. Despite immunosuppressive treatment with prednisolone and plasmapheresis, rapid and diffuse degeneration of the patient's photoreceptors and deterioration of her visual field were observed. This is a rare case of cancer-associated retinopathy with a long interval (10 years) between the diagnosis of the malignancy and visual loss.
  • 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 0927-3948 2019 [Refereed][Not invited]
     
    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.
  • Yung-Ray Hsu, Jerry Chien-Chieh Huang, Yong Tao, Toshikatsu Kaburaki, Christopher Seungkyu Lee, Tai-Chi Lin, Chih-Chien Hsu, Shih-Hwa Chiou, De-Kuang Hwang
    Eye (London, England) 33 (1) 66 - 77 2019/01 [Refereed][Not invited]
     
    Uveitis is a sight-threatening disease. Up to 35% of patients may have impaired vision. Inflammation of the uvea tissue has more than 60 etiologies. Previous reports have shown that 20-40% of uveitis cases were noninfectious. Some of them may be associated with systemic rheumatological and autoimmune diseases but some may affect the eyes only. The epidemiology and clinical situations of some specific uveitis entities vary worldwide because they are influenced by genetic, ethnic, environmental, and socioeconomic factors. The Asia-Pacific region comprises more than 30 countries. Epidemiology and patterns of uveitis vary greatly in this region. However, some uveitis entities, such as Behcet's disease, sarcoidosis, and Vogt-Koyanagi-Harada disease, are more common in this region. Many studies on the epidemiology, risk factors, and immune pathogenesis of this disease have been conducted. In this article, we review the epidemiology of noninfectious uveitis and special situations of these three uveitis entities in the Asia-Pacific region.
  • Kei Takayama, Toshikatsu Kaburaki, Masaru Takeuchi
    Ocular immunology and inflammation 27 (7) 1067 - 1070 2019 [Refereed][Not invited]
     
    Purpose: To report a case of acute retinal necrosis (ARN) caused by varicella-zoster virus (VZV) in an elderly patient with ocular sarcoidosis after oral corticosteroid indication. Methods: Retrospective case report. Results: A 75-year-old male with a past history of ocular sarcoidosis came with blurred left vision. Ocular findings in the left eye were consistent with ocular sarcoidosis, while no inflammation in the right eye. On day 14, intraocular inflammation in the left eye resolved by topical corticosteroid, but inflammatory cells were found in the right eye. Suspecting recurrence of ocular sarcoidosis, systemic corticosteroid was initiated. On day 21, inflammation worsened, and the presence of extended yellowish white peripheral retinal lesion in the right eye suggested ARN. Polymerase chain reaction (PCR) testing using ocular fluid detected 3.0 × 107 copies/ml of VZV DNA. Conclusions: In the case of poor response to immunosuppressive therapy in elderly uveitis, infection including ARN should be considered. Immediate PCR testing for pathogen screening is required.
  • Toshikatsu Kaburaki, Hisae Nakahara, Rie Tanaka, Kimiko Okinaga, Hidetoshi Kawashima, Youichiro Hamasaki, Thanyada Rungrotmongkol, Supot Hannongbua, Hiroshi Noguchi, Makoto Aihara, Fujio Takeuchi
    PloS one 14 (9) e0222384  2019 [Refereed][Not invited]
     
    Several proteins have been proposed as candidate auto-antigens in the pathogenesis of Behçet's disease (BD). In this study, we aimed to confirm the cellular responses to candidate peptide autoantigens with high affinity for the HLA-B*51:01 molecule using computerized binding predictions and molecular dynamics simulations. We identified two new candidate peptides (HSP65PD, derived from heat shock protein-65, and B51PD, derived from HLA-B*51:01) with high-affinity to the HLA-B*51:01 binding pocket using the Immune Epitope Database for Major Histocompatibility Complex-I Binding Prediction and molecular dynamics simulations. The peptide-induced proliferation of lymphocytes from patients with BD, sarcoidosis, Vogt-Koyanagi-Harada disease (VKH) with panuveitis, systemic scleroderma (SSc) without uveitis, and healthy controls (HC) was investigated using the bromodeoxyuridine assay. The proliferative response of leukocytes to HSP65PD was significantly higher in BD (SI 1.92 ± 0.65) than that in sarcoidosis (SI 1.38 ± 0.46), VKH (SI 1.40 ± 0.33), SSc (SI 1.32 ± 0.31), and HC (SI 1.27 ± 0.28) (P = 0.0004, P = 0.0007, P < 0.0001, P < 0.0001, respectively, Mann-Whitney's U-test). The proliferative response of leukocytes to B51PD was also higher in BD than that in sarcoidosis, VKH, SSc without uveitis, and HC, whereas no significant differences were observed among the five groups in response to a control peptide derived from topoisomerase 1. A significantly higher response to HPS65PD and B51PD was observed in the HLA-B*51:01-positive patients with BD than in the HLA-B*51:01-negative patients. In conclusion, two peptides that had high affinity to HLA-B*51:01 in computerized binding prediction showed significantly higher response in HLA-B*51:01-positive patients with BD, indicating the usefulness of computerized simulations for identifying autoreactive peptides to HLAs.
  • Ayako Karakawa, Kazuki Taoka, Toshikatsu Kaburaki, Rie Tanaka, Aya Shinozaki-Ushiku, Hiroyuki Hayashi, Akiko Miyagi-Maeshima, Yu Nishimura, Toshimasa Uekusa, Yui Kojima, Masashi Fukayama, Mineo Kurokawa, Makoto Aihara
    British journal of haematology 183 (4) 668 - 671 0007-1048 2018/11 [Refereed][Not invited]
  • 井関 萌, 澤村 裕正, 蕪城 俊克, 相原 一
    神経眼科 日本神経眼科学会 35 (増補1) 96 - 96 0289-7024 2018/11
  • Shintaro Shirahama, Toshikatsu Kaburaki, Hisae Nakahara, Rie Tanaka, Mitsuko Takamoto, Yujiro Fujino, Hidetoshi Kawashima, Makoto Aihara
    BMC ophthalmology 18 (1) 189 - 189 2018/08 [Refereed][Not invited]
     
    BACKGROUND: The distribution of uveitis varies with genetic, ethnic, geographic, environmental, and lifestyle factors. Epidemiological information about the patterns of uveitis is useful when an ophthalmologist considers the diagnosis of uveitis. Therefore, it is important to identify the causes of uveitis over the years in different regions. The purposes of this study were to characterize the uveitis patients who first arrived at the University of Tokyo Hospital in 2013-2015, and to analyze the changes in the patterns of uveitis from 2004 to 2012 to 2013-2015. METHODS: We retrospectively identified 750 newly arrived patients with uveitis who visited the Uveitis Clinic in the University of Tokyo Hospital between January 2013 and December 2015, using clinical records. We extracted data on patient age, sex, diagnosis, anatomic location of inflammation, laboratory test results of blood and urine, and chest X-ray and fluorescein fundus angiography findings for each patient. In addition, we compared these data with those from 2004 to 2012 to analyze the changes in the patterns of uveitis. RESULTS: A definite diagnosis was established in 445 patients (59.3%). The most common diagnoses were herpetic iridocyclitis (7.5%), sarcoidosis (6.1%), Behçet's disease (4.4%), Vogt-Koyanagi-Harada disease (4.1%), and intraocular lymphoma (4.1%). The most frequent unclassified type of uveitis was suspected sarcoidosis (22.3%). Analysis of the changes in the patterns of uveitis in the central Tokyo area from 2004 to 2012 to 2013-2015 revealed notable increasing trends of herpetic iridocyclitis and intraocular lymphoma, and increasing trends of bacterial endophthalmitis, fungal endophthalmitis, and juvenile chronic iridocyclitis. In contrast, the frequency of sarcoidosis, Behçet's disease, and Vogt-Koyanagi-Harada disease decreased. CONCLUSIONS: The patterns of uveitis changed considerably from 2004 to 2012 to 2013-2015. Continuous investigations about the epidemiology of uveitis are needed to diagnose uveitis more accurately.
  • Tomohito Sato, Riki Kitamura, Toshikatsu Kaburaki, Masaru Takeuchi
    Medicine 97 (31) e11663  0025-7974 2018/08 [Refereed][Not invited]
     
    RATIONALE: Chronic uveitis with immunosuppressive agents could develop chronic herpetic retinitis with varicella-zoster virus (VZV) or herpes simplex virus (HSV). Ocular Epstein-Barr virus (EBV) infection develops uveitis and vitritis, but the clinical feature of EBV retinitis is not typical as a viral retinitis. EBV retinitis is rare, and only a few cases of EBV retinitis have been reported. Herein, we describe a case of retinitis with EBV and VZV which were the primary viruses verified by multiplex polymerase chain reaction (PCR). PATIENT CONCERNS: A 75-year-old woman suffered from sudden visual loss in the left eye. She had been diagnosed with rheumatoid arthritis. At presentation, visual acuity (VA) was 20/400 in the left eye. Slit lamp examination disclosed fine white keratic precipitates with infiltrating cells and dense vitreous opacities in the anterior segment and vitreous. Fundus photographs showed multifocal chorioretinal scars in macula and peripheral retina, and granular lesions surrounding arcade vessels. DIAGNOSES: Ocular toxoplasmosis was primarily suspected. INTERVENTIONS: However, serological test showed negative of toxoplasmosis. Therefore, a diagnostic and therapeutic vitrectomy was performed. Vitreous fluid sample was used for multiplex PCR for detection of human herpesvirus (HHV) -1 to -8, toxoplasmosis and toxocariasis. OUTCOMES: Multiplex PCR detected 5.8 × 10 copies/mL of EBV-deoxyribonucleic acid (DNA), and 3.6 × 10 copies/mL of VZV-DNA in the sample. Therefore, we could diagnose the unidentified panuveitis a retinitis associated with double infection of EBV and VZV. At 85 days after the vitrectomy, VA of the left eye recovered to be 20/16. LESSONS: Elderly patients under immunosuppression may be susceptible to develop retinitis associated with infection of multiple HHVs, and multiplex PCR is an excellent tool to diagnose an unidentified panuveitis resembling this case.
  • Eric B Suhler, Alfredo Adán, Antoine P Brézin, Eric Fortin, Hiroshi Goto, Glenn J Jaffe, Toshikatsu Kaburaki, Michal Kramer, Lyndell L Lim, Cristina Muccioli, Quan Dong Nguyen, Joachim Van Calster, Luca Cimino, Martina Kron, Alexandra P Song, Jianzhong Liu, Sophia Pathai, Anne Camez, Ariel Schlaen, Mirjam E J van Velthoven, Albert T Vitale, Manfred Zierhut, Samir Tari, Andrew D Dick
    Ophthalmology 125 (7) 1075 - 1087 1549-4713 2018/07 [Refereed][Not invited]
     
    PURPOSE: To evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. DESIGN: Phase 3, open-label, multicenter clinical trial extension (VISUAL III). PARTICIPANTS: Adults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF. METHODS: Patients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 through 78. MAIN OUTCOME MEASURES: Disease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff. RESULTS: Of 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65%) patients had active uveitis; 60% (145/242, NRI) achieved quiescence at week 78, and 66% (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35%) patients had inactive uveitis; 74% (96/129, NRI) achieved quiescence at week 78, and 93% (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR; left and right eyes; as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5-1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials. CONCLUSIONS: Patients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified.
  • Rie Tanaka, Toshikatsu Kaburaki, Kazuyoshi Ohtomo, Mitsuko Takamoto, Keiko Komae, Jiro Numaga, Yujiro Fujino, Makoto Aihara
    Japanese journal of ophthalmology 62 (4) 517 - 524 1613-2246 2018/07 [Refereed][Not invited]
     
    PURPOSE: To investigate the clinical characteristics of Japanese patients with scleritis STUDY DESIGN: Retrospective study METHODS: The clinical records of 123 patients with scleritis, who presented to the University of Tokyo Hospital between January, 2004 and December, 2015, were retrospectively reviewed. RESULTS: The cohort comprised 55 men and 68 women (mean age, 57.8±16.4 years), of which 76 showed anterior diffuse scleritis, 17 showed anterior nodular scleritis, 10 showed anterior necrotizing scleritis, and 20 showed posterior scleritis. The underlying etiology was identified in 39 patients. Autoimmune diseases were present in 32 patients, including eight with rheumatoid arthritis, seven with antineutrophil cytoplasmic antibody-associated vascular disease, and six with relapsing polychondritis. Ocular hypertension was the most common ocular complication (41%), followed by anterior chamber cells (38%). Fifty-three percent of patients required systemic immunosuppressive medication. Systemic corticosteroids were the most commonly used medication (45%), followed by methotrexate (11%). A, decrease in vision was observed in one-third of patients with anterior necrotizing scleritis or posterior scleritis, of which secondary glaucoma and optic neuritis were the major causes. CONCLUSION: Autoimmune diseases were present in 26% of patients. One-third of patients with anterior necrotizing scleritis or posterior scleritis experienced decreased vision, mostly due to secondary glaucoma and optic neuritis. Therefore, controlling intraocular pressure by methods such as administration of steroid-sparing immunosuppressive medication and appropriate treatment for posterior scleritis are essential for scleritis treatment.
  • Hisae Nakahara, Toshikatsu Kaburaki, Rie Tanaka, Junko Matsuda, Mitsuko Takamoto, Kazuyoshi Ohtomo, Kimiko Okinaga, Keiko Komae, Jiro Numaga, Yujiro Fujino, Makoto Aihara
    BMC ophthalmology 18 (1) 74 - 74 1471-2415 2018/03 [Refereed][Not invited]
     
    BACKGROUND: Fuchs' uveitis (FU) is occasionarlly complicated with heavy vitreous opacity. We have performed vitrectomy procedures to remove vitreous opacity in affected patients as part of differential diagnosis for primary vitreoretinal lymphoma (PVRL). CASE PRESENTATION: We retrospectively reviewed the clinical records of five patients who first visited the Uveitis Clinic of the University of Tokyo Hospital between 2009 and 2013, were diagnosed with FU and underwent a vitrectomy for removal of dense vitreous opacity. All were diagnosed as FU by ocular findings and elevation of Goldmann-Witmer coefficient (GWC) value for the rubella virus (RV) antibody. In examinations of the vitreous body, cytological diagnosis, elevation of IL-10/IL-6 ratio, and the kappa/lambda ratio in flow cytometry findings were negative in all cases, whereas monoclonal immunoglobulin heavy chain (IgH) gene rearrangement was positive in 4 cases and negative in 1 case. CONCLUSIONS: Although monoclonal IgH gene rearrangement is thought to be a reliable biomarker for PVRL, a high percentage of vitreous specimens from our FU patients showed pseudo-positive results. Ophthalmologists must take care regarding possible pseudo-positive findings when performing differential diagnosis between FU and PVRL. Combinations of results of cytological diagnosis, IL-10/IL-6 ratio, kappa/lambda ratio, and IgH gene rearrangement may be necessary for a definitive diagnosis of PVRL and differentiation from FU.
  • Shinya Yamamoto, Mahoko Ikeda, Fumie Fujimoto, Koh Okamoto, Yoshitaka Wakabayashi, Tomoaki Sato, Keita Tatsuno, Toshikatsu Kaburaki, Shuntaro Yoshida, Shu Okugawa, Kazuhiko Koike, Kyoji Moriya
    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 24 (2) 147 - 149 1341-321X 2018/02 [Refereed][Not invited]
     
    Candida lusitaniae is an uncommon cause of candidiasis in humans. Ocular manifestations of C. lusitaniae infection have not been reported. C. lusitaniae is either intrinsically resistant to amphotericin B or can acquire such resistance. We describe a case of bilateral endophthalmitis due to C. lusitaniae bloodstream infection in a liver transplant patient with rectal cancer. The patient suffered fungemia and endophthalmitis and was treated with liposomal amphotericin B. The isolate was identified as C. lusitaniae by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, the system based on biochemical tests, and sequencing of the internal transcribed spacer region. The minimal inhibitory concentrations were 0.06 μg/mL for amphotericin B and 2.0 μg/mL for fluconazole. Repeat blood cultures were negative and the endophthalmitis improved following treatment with liposomal amphotericin B. However, the treatment was changed to fluconazole due to nephrotoxicity. No recurrence occurred after completion of treatment.
  • Tomohito Sato, Rina Kinoshita, Manzo Taguchi, Sunao Sugita, Toshikatsu Kaburaki, Yutaka Sakurai, Masaru Takeuchi
    Medicine 97 (2) e9491  1536-5964 2018/01 [Refereed][Not invited]
     
    Vitreous opacity (VO) is a common feature of intermediate uveitis, posterior uveitis, and panuveitis. Fundus observation is critical for determining the etiology of uveitis, however, is often interfered with VO. In these clinical settings, vitrectomy contributes to a correct diagnosis and guides alternative management strategies. The purpose of this study was to evaluate the diagnostic yield and surgical outcome of vitrectomy in uveitic patients with VO and compare the visual outcome between infectious and noninfectious uveitis. Forty-five eyes with uveitis-associated VO underwent diagnostic and therapeutic vitrectomy, and etiological diagnosis of uveitis was confirmed in 34 of 45 eyes (75.6%). The diagnoses were infectious uveitis in 13 eyes (28.9%), noninfectious uveitis in 21 eyes (46.7%), and unidentified uveitis in 11 eyes (24.4%). Visual acuity (VA) improvement rates at 6 months after surgery were 69.2%, 76.2%, and 90.9% in the infectious, noninfectious, and unidentified uveitis groups, with no significant difference among 3 groups. Significant decrease in inflammation score after vitrectomy was observed only in the infectious uveitis group. This study demonstrated that diagnostic vitrectomy for inflammatory eyes with VO of unknown etiology was effective in infectious and noninfectious uveitis, and the therapeutic effect of VA improvement was observed in both types of uveitis.
  • Rie Tanaka, Keiichi Sakurai, Toshikatsu Kaburaki
    Ocular immunology and inflammation 26 (5) 767 - 769 2018 [Refereed][Not invited]
     
    A 31-year-old woman developed bilateral painful red eyes. A slit-lamp examination revealed anterior diffuse scleritis. She had been diagnosed with palmoplantar pustulosis 2 years before. Further evaluation revealed hyperostosis of the sacroiliac joint and inflammation of the bilateral sternoclavicular joints and right sternocostal joint. Ultimately, she was diagnosed with SAPHO syndrome by rheumatologists after excluding other causative diseases. Scleritis associated with SAPHO syndrome is relatively uncommon. An identification of any systemic symptoms and early consultation with rheumatologists are key to making an early and correct diagnosis.
  • Takahiro Arai, Rie Tanaka, Toshikatsu Kaburaki
    Ocular immunology and inflammation 26 (5) 779 - 782 2018 [Refereed][Not invited]
     
    PURPOSE: We report three cases of ocular inflammation and polymyalgia rheumatica without concomitant giant-cell arteritis. METHODS: Report of three cases. RESULTS: Polymyalgia rheumatica onset was at a mean age of 66.7 years, and ocular inflammation, which developed 7-21 months later, was bilateral in all patients. Ocular inflammation presented as episcleritis, scleritis, or anterior uveitis, and it emerged during the tapering of low-dose prednisolone prescribed for polymyalgia rheumatica in all patients. Recurrence of ocular inflammation was observed in two patients. CONCLUSIONS: Ocular inflammation associated with polymyalgia rheumatica was often bilateral and occurred during steroid tapering. Although this presentation is relatively uncommon, polymyalgia rheumatica should be considered in the differential diagnosis of older patients presenting with ocular inflammation, especially those with proximal myalgia and elevated inflammatory markers.
  • 青山 祐里香, 澤村 裕正, 蕪城 俊克, 若倉 雅登, 相原 一
    神経眼科 日本神経眼科学会 34 (増補1) 110 - 110 0289-7024 2017/10
  • 浅野 祥太郎, 澤村 裕正, 蕪城 俊克, 山上 明子, 相原 一
    神経眼科 日本神経眼科学会 34 (増補1) 115 - 115 0289-7024 2017/10
  • Toshikatu Kaburaki, Kazuki Taoka, Junko Matsuda, Hideomi Yamashita, Izuru Matsuda, Hideki Tsuji, Rie Tanaka, Kumi Nakazaki, Fumihiko Nakamura, Kohei Kamiya, Mineo Kurokawa, Kuni Ohtomo, Makoto Aihara
    British journal of haematology 179 (2) 246 - 255 2017/10 [Refereed][Not invited]
     
    Primary intraocular lymphoma (IOL) has a propensity for central nervous system (CNS) relapse within 2 years of initial diagnosis, affecting clinical outcome. To reduce CNS relapse, we performed the combination treatment protocols of intravitreal methotrexate injections, methotrexate-based systemic induction chemotherapy and consolidation high-dose cytarabine and reduced-dose whole brain radiation therapy (rdWBRT, 23·4 Gy) for B-cell primary IOL with or without newly diagnosed CNS involvement. All patients underwent longitudinal brain magnetic resonance imaging (MRI) and cognitive assessment for evaluation of treatment-induced leucoencephalopathy. Seventeen patients initiated and 16 completed the protocol treatment. CNS relapse occurred in 2 patients and intraocular relapse in 3. Four-year progression-free survival (PFS) was 74·9% and 4-year overall survival (OS) was 86·3%, with a median follow-up period of 48·9 months. Of 11 patients without CNS involvement, 1 had CNS relapse and 3 intraocular relapse, and 4-year PFS and OS was 72·7% and 88·9%, respectively. Although white matter abnormalities shown by MRI were significantly increased at 4 years after rdWBRT, only one patient developed mild cognitive impairment. The combination of intravitreal chemotherapy, prophylactic systemic chemotherapy and rdWBRT for primary IOL showed a potential to reduce CNS relapse rate and improved 4-year PFS and OS without increase of cognitive dysfunction.
  • Keiko Komae, Mitsuko Takamoto, Rie Tanaka, Makoto Aihara, Kazuyoshi Ohtomo, Kimiko Okinaga, Junko Matsuda, Hisae Nakahara, Yujiro Fujino, Toshikatsu Kaburaki
    Journal of glaucoma 26 (7) 603 - 607 1057-0829 2017/07 [Refereed][Not invited]
     
    PURPOSE: To examine clinical outcomes following an initial trabeculectomy with mitomycin-C for secondary glaucoma associated with uveitis in Behçet disease (BD) patients. DESIGN: Retrospective interventional case series. PATIENTS AND METHODS: Twenty-two eyes in 18 patients with uveitic glaucoma (UG) associated with Behçet disease who underwent an initial trabeculectomy with mitomycin-C between January 1996 and August 2014 were retrospectively reviewed. The main outcome measures were intraocular pressure (IOP) control, persistence of a filtering bleb, incidence of postoperative complications, and preopertaive and postoperative frequency of uveitic attacks. We analyzed persistence rates using Kaplan-Meier life tables based on 3 definitions of target IOP control (≤21, ≤18, ≤15 mm Hg) and filtering bleb persistence. RESULT: The persistence rates of postoperative IOP at ≤21, ≤18, and ≤15 mm Hg at 5 years after surgery were 76.1%, 71.5%, and 68.1%, respectively, whereas that of a filtering bleb was 54.4%. Hypotony as a postoperative complication was observed in 4 (18.2%) cases. No significant difference was observed between the preoperative and postoperative frequency of uveitic attacks (1.36±1.15 vs. 0.95±1.49 times/y, P=0.16). There was 1 case in which recurrence of uveitis after surgery caused a loss of filtering bleb, which required a reoperation. CONCLUSIONS: At 5 years after surgery, the persistence rate of postoperative IOP control (≤21 mm Hg) was 76.1% and that of a filtering bleb was 54.4%. The frequency of uveitis recurrence did not significantly increase after surgery. Attention must be paid to avoid such recurrence to maintain the filtering bleb.
  • 活動性および非活動性の非感染性ぶどう膜炎に対するアダリムマブの使用経験
    伊沢 英知, 田中 理恵, 高本 光子, 中原 久恵, 冲永 貴美子, 白濱 新多朗, 相原 一, 蕪城 俊克
    日本眼科学会雑誌 (公財)日本眼科学会 121 (臨増) 172 - 172 0029-0203 2017/03
  • 眼内悪性リンパ腫における網膜血管炎の頻度
    小林 芙美, 蕪城 俊克, 田中 理恵, 小野 久子, 藤野 雄次郎, 白濱 新多朗, 高本 光子, 冲永 貴美子, 辻 英貴, 相原 一
    日本眼科学会雑誌 (公財)日本眼科学会 121 (臨増) 172 - 172 0029-0203 2017/03
  • 前眼部OCTを用いたサイトメガロウィルス虹彩炎における虹彩体積の評価
    芝原 勇磨, 蕪城 俊克, 藤野 雄次郎, 間山 千尋, 田中 理恵, 白濱 新多朗, 大友 一義, 高本 光子, 冲永 貴美子, 相原 一
    日本眼科学会雑誌 (公財)日本眼科学会 121 (臨増) 251 - 251 0029-0203 2017/03
  • 白濱 新多朗, 蕪城 俊克, 澤村 裕正, 山上 明子, 清澤 源弘
    あたらしい眼科 (株)メディカル葵出版 34 (3) 450 - 454 0910-1810 2017/03 
    目的:3施設における病型別の視神経炎の臨床像の違いについて検討する。対象および方法:視神経炎と診断された57例84眼を対象として、脳脊髄病変の有無および血液検査の結果から、特発性群、自己抗体陽性群、抗Aquaporin-4抗体陽性群(抗AQP4群)、多発性硬化症群(multiple sclerosis:MS群)の4群に病型分類した。病型ごとに性別、発症時年齢、罹患眼(両眼・片眼)、眼痛の有無、初診時のステロイド治療の有無、自己抗体の陽性率、再発率、再発頻度、経過中最低矯正視力、最終矯正視力を比較した。結果:MS群と抗AQP4群は女性が多かった。特発性群と自己免疫性群は眼痛が多く、抗AQP4群、MS群は眼痛が少なかった。抗AQP4群は他群に比べ経過中最低矯正視力、最終矯正視力ともに低かった。抗AQP4群は脳脊髄病変の有無によらず経過中最低矯正視力、最終矯正視力に差は認めなかった。結論:抗AQP4抗体陽性の場合、脳脊髄病変の有無にかかわらず、経過中最低矯正視力、最終矯正視力ともに、他の視神経炎に比べ不良であると考えられた。(著者抄録)
  • Candida lusitaniaeによる真菌血症、内因性真菌性眼内炎の一例
    山本 真也, 池田 麻穂子, 宮下 馨, 岡本 耕, 若林 義賢, 龍野 桂太, 奥川 周, 小池 和彦, 森屋 恭爾, 藤本 文恵, 佐藤 智明, 吉田 俊太郎, 蕪城 俊克
    感染症学雑誌 (一社)日本感染症学会 91 (臨増) 321 - 321 0387-5911 2017/03 [Refereed][Not invited]
  • Nozomi Igarashi, Hiromasa Sawamura, Toshikatsu Kaburaki, Makoto Aihara
    Neuro-ophthalmology (Aeolus Press) 41 (1) 24 - 29 2017/02 [Refereed][Not invited]
     
    A 68-year-old male presented with blurred vision in both eyes. Ophthalmoscopy revealed bilateral prominent disc swelling and vitritis. No systematic neurological symptoms were observed. Magnetic resonance imaging revealed bilateral meningeal enhancement of the optic nerve. Small cell carcinoma was found, and antibodies against collapsing response-mediating protein-5 (CRMP-5) were detected in the serum. Ophthalmological manifestations disappeared during a decrease in tumour size with treatment for the malignancy. This case report describes this rare case of anti-CRMP-5 antibody-positive paraneoplastic perioptic neuritis without neurological symptoms, showing that prompt diagnosis and timely treatment of the underlying tumour are crucial to prevent increased levels of autoantibodies and irreversible damage to the nervous system.
  • Hisae Nakahara, Toshikatsu Kaburaki, Rie Tanaka, Mitsuko Takamoto, Kazuyoshi Ohtomo, Ayako Karakawa, Keiko Komae, Kimiko Okinaga, Junko Matsuda, Yujiro Fujino
    Ocular immunology and inflammation 25 (sup1) S8-S14 - S14 0927-3948 2017 [Refereed][Not invited]
     
    PURPOSE: To investigate the frequency of conditions of newly arrived patients with uveitis from 2010 to 2012 and compare this frequency with that since 2004. METHODS: We retrospectively analyzed clinical records of patients who visited the outpatient clinic from January 2010 to December 2012, and compared them with those from 2004-2009. RESULTS: From 2010 to 2012, 695 new patients with uveitis visited Tokyo University Hospital, with a definite diagnosis made in 431 (62.0%). The most common diagnosis was scleritis (8.3%), followed by sarcoidosis (8.1%); herpetic iridocyclitis (5.5%); Behçet disease (4.6%); Vogt-Koyanagi-Harada disease (4.0%); acute anterior uveitis (3.7%); Posner-Schlossman syndrome (3.6%); intraocular malignant lymphoma (3.0%); and bacterial endophthalmitis (1.9%). The most frequent unclassified type of uveitis was sarcoidosis-suspected (14.8%). CONCLUSIONS: When compared with years 2004-2009, the present series showed an increasing trend of intraocular malignant lymphoma, bacterial endophthalmitis, and chronic iridocyclitis, and a notable increase in chronic iridocyclitis in young girls, with decreasing trends of scleritis and Vogt-Koyanagi-Harada disease.
  • Koji Komatsu, Tsutomu Sakai, Toshikatsu Kaburaki, Hideki Tsuji, Hiroshi Tsuneoka
    BMC ophthalmology 16 (1) 171 - 171 2016/10 [Refereed][Not invited]
     
    BACKGROUND: In 2014, Pang et al. reported three cases with vitelliform submaculopathy as a preceding lesion of primary intraocular lymphoma (PIOL). Here, we report a case with an atypical presentation of PIOL who initially presented with vitelliform submaculopathy, vitreous haze and preripheral retinal focus. CASE PRESENTATION: A 73-year-old female initially visited another hospital with a chief complaint of acute reduced vision in the right eye. Funduscopic examination of the right eye showed a yellowish retinal lesion at the fovea with vitreous haze and retinal foci scattered in the peripheral region. Spectral-domain optic coherence tomography (SD-OCT) revealed a hyperreflective subretinal debris above the retinal pigment epithelium (RPE) at the fovea, suggesting vitelliform submaculopathy. Vitrectomy was performed to improve visualization of the retinal lesions and for examination of PIOL. Vitreous cytology was class III and cytokine analysis of vitreous fluid showed increased IL-10 and an IL-10/IL-6 ratio >1, suggesting PIOL. Thereafter, there was a sub-RPE infiltration of presumed lymphoma in the nasal retina, and PCR analysis of anterior chamber fluid indicated IgH gene rearrangement, leading to diagnosis of PIOL. Three months later, there was complete disappearance of the vitelliform submacular lesion, with resultant disruption and thinning of the outer retinal layers on SD-OCT images. CONCLUSIONS: Clinicians should be aware of atypical manifestations of PIOL such as vitelliform submaculopathy and peripheral retinal foci with vitreous haze. The patient's unusual funduscopic changes are findings that have not reported in patients with PIOL.
  • 原発巣が認められなかった癌関連網膜症に対して血漿交換療法を施行した一例
    五十嵐 希望, 澤村 裕正, 蕪城 俊克, 花房 規男, 藤代 貴志, 相原 一
    神経眼科 日本神経眼科学会 33 (増補1) 92 - 92 0289-7024 2016/10
  • Boston keratoprosthesis術後に硝子体出血と網膜滲出斑を生じた1例
    李 真煕, 荒木 章之, 高尾 宗之, 臼井 智彦, 蕪城 俊克, 山上 聡
    眼科臨床紀要 眼科臨床紀要会 9 (7) 602 - 602 1882-5176 2016/07
  • ベーチェット病ぶどう膜炎の活動性と脈絡膜厚および蛍光眼底造影の蛍光漏出
    白濱 新多朗, 蕪城 俊克, 田中 理恵, 大友 一義, 小前 恵子, 相原 一, 高本 光子, 冲永 貴美子, 藤野 雄次郎
    眼科臨床紀要 眼科臨床紀要会 9 (7) 602 - 602 1882-5176 2016/07
  • Rie Tanaka, Hiroshi Murata, Mitsuko Takamoto, Kazuyoshi Ohtomo, Kimiko Okinaga, Atsushi Yoshida, Hidetoshi Kawashima, Hisae Nakahara, Yujiro Fujino, Toshikatsu Kaburaki
    The British journal of ophthalmology 100 (7) 990 - 994 0007-1161 2016/07 [Refereed][Not invited]
     
    AIMS: To investigate the ability of the Behçet's disease ocular attack score 24 (BOS24) scoring system to predict visual acuity (VA) in patients with ocular Behçet's disease. DESIGN: This is a retrospective study. METHODS: We included 91 eyes of 50 patients with ocular Behçet's disease (33 males, 17 females) who were referred to our hospital between 1986 and 2008 with >5 years follow-up. Total BOS24 scores over a 5-year period, BOS24-5Y, were calculated as the sum of BOS24 scores for each attack over the 5-year study period for each eye. Change in VA was defined as change in best-corrected visual acuity (BCVA) from the first remission to the last remission at the end of the target period. Factors related to change in VA (age, gender, BCVA at the first remission, total number of immunosuppressive medications and total number of ocular attacks during the 5-year period and BOS24-5Y) were evaluated using a linear mixed model. RESULTS: BCVA (logarithm of the minimal angle resolution) deteriorated from 0.16±0.30 (mean±SD) to 0.21±0.37 over the 5-year study period, but there was no statistical difference. The total number of ocular attacks during the 5-year period and BOS24-5Y scores were 10.0±7.9 and 36.8±40.8, respectively. Linear mixed-model analysis revealed that BOS24-5Y was the most important index for VA deterioration, followed by BCVA at the first remission. CONCLUSIONS: BOS24-5Y was found to be a significant positive prognostic index for VA deterioration in patients with ocular Behçet's disease.
  • 両側乳頭浮腫を契機に発見された傍腫瘍性視神経症の一例
    五十嵐 希望, 蕪城 俊克, 澤村 裕正
    日本眼科学会雑誌 (公財)日本眼科学会 120 (臨増) 321 - 321 0029-0203 2016/03
  • Xue Tan, Katsuhito Fujiu, Ichiro Manabe, Junko Nishida, Reiko Yamagishi, Yuya Terashima, Kouji Matsushima, Toshikatsu Kaburaki, Ryozo Nagai, Yasuo Yanagi
    PloS one 11 (8) e0160985  2016 [Refereed][Not invited]
     
    PURPOSE: To determine the involvement of sympathetic activity in choroidal neovascularization (CNV) using laser-induced CNV in a mouse model. METHODS: We investigated changes in the proportions of intraocular lymphocytes, granulocytes, and three macrophage subtypes (Ly6Chi, Ly6Cint, and Ly6Clo) after laser injury in mice using flow cytometry, and evaluated CNV lesion size in mice lacking inflammatory cells. Further, we evaluated the lesion size in mice administered the β3 receptor antagonist, splenic-denervated and splenectomized mice. We also assessed changes in the proportions of intraocular macrophages and peripheral blood monocytes in splenic-denervated and splenectomized mice. Lastly, lesion size was compared between splenic-denervated mice with or without adoptive transfer of macrophages following laser injury. After Ly5.1 mice spleen-derived Ly6Chi cells were transferred into Ly5.2 mice, the proportions of intraocular Ly5.1+Ly6Chi cells were compared. RESULTS: In WT mice, the proportion of CD4+ T cells recruited into the eye increased progressively from day 3 to day 7 after laser injury, whereas, intraocular CD8+ T cells did not change significantly. Proportions of B220+ cells, granulocytes, and two subtypes of intraocular macrophages (Ly6Chi and Ly6Clo) peaked at day 3 following laser injury. In contrast, Ly6Cint/loCD64+ subtype showed a significantly higher percentage at day 7 after laser injury. There were no differences in lesion size between CD4-/-or Rag2-/-mice and controls, whereas lesion size was significantly reduced in CCR2-/- mice and clodronate liposome-treated mice. CNV lesion area was significantly reduced in mice with β3 blocker treatment, splenic-denervated and splenectomized mice compared with controls. Intraocular Ly6Chi macrophages were also reduced by splenic denervation or splenectomy. Adoptive transfer of spleen-derived Ly6Chi cells increased the lesion size in splenic-denervated mice. Compared with controls, intraocular donor-derived Ly6Chi cells recruited into the eye were reduced in splenic-denervated and splenectomized mice. CONCLUSIONS: Although lymphocytes had little effect on CNV formation, Ly6Chi macrophages/monocytes exacerbated CNV in mice. Sympathetic activity might contribute to CNV via the recruitment of macrophages to the eye.
  • Satoru Inoda, Yukihiro Sato, Yusuke Arai, Hiroto Obata, Jun Suzuki, Toshikatsu Kaburaki, Katsuhiko Kamei
    Nippon Ganka Gakkai zasshi 119 (9) 632 - 9 0029-0203 2015/09 [Refereed][Not invited]
     
    BACKGROUND: We report a case with bilateral endogenous fungal subretinal abscesses. To our knowledge, this is the first report from Japan in which Scedosporium prolificans (S. prolificans) was cultured from intraocular tissue. CASE: A 74-year-old man, receiving chemotherapy for acute myeloid leukemia, complained of visual loss in both eyes. Best-corrected visual acuity was hand motion in the right and 2/200 in the left eye. His right eye showed exophthalmos, inflammation in the anterior chamber and iris neovascularization. Funduscopy revealed no details as there was vitreous opacity in the right eye, and irregular round yellowish-white subretinal lesions involving the macula in the left eye. Blood culture was negative, and C-reactive protein (CRP) and β-D glucan titers were high. An antifungal drug and broad-spectrum antibiotics were initiated. Two days after the initial visit, right visual acuity had deteriorated to light perception. Enucleation of the right eye was performed for diagnosis and treatment. Fungi were cultured from the subretinal lesion, confirming a diagnosis of S. prolificans infection. After systemic administration and intravitreal injections of antifungal agents, the subretinal abscess in the left eye gradually diminished. At present, six months after the first visit, left visual acuity is 20/200. CONCLUSION: Although S. prolificans endophthalmitis can be intractable, this case suggests that repeated intravitreal antifungal agent injections can be effective.
  • Hisae Nakahara, Toshikatsu Kaburaki, Mitsuko Takamoto, Kimiko Okinaga, Junko Matsuda, Yasuhiro Konno, Hidetoshi Kawashima, Jiro Numaga, Yujiro Fujino, Shiro Amano
    Ocular immunology and inflammation 23 (4) 291 - 296 0927-3948 2015/08 [Refereed][Not invited]
     
    PURPOSE: To investigate the frequencies of the diseases in the new patients with uveitis during 2007-2009 and compare them with previously-reported data from the University of Tokyo Hospital. METHODS: We retrospectively analyzed the clinical records of patients who visited the outpatient clinic from January 2007 to December 2009, and compared them with those of 1963-2006. RESULTS: During 2007-2009, 468 new patients visited our hospital. Definite diagnoses were made in 63.0%. Frequent diagnoses include sarcoidosis (9.4%), Vogt-Koyanagi-Harada (VKH) disease (7.9%), herpetic iritis (6.0%), Behçet's disease (5.6%), Posner-Schlossman syndrome (4.3%), HLA-B27-associated uveitis (3.0%), and intraocular malignant lymphoma (2.8%). Compared with our former findings, the ratios of sarcoidosis, herpetic iritis, CMV retinitis, Fuch's heterochromic iridocyclitis, acute retinal necrosis and intraocular lymphoma increased, while that of Behçet's disease decreased. CONCLUSIONS: Top three uveitis during 2007-2009 were sarcoidosis, VKH disease, herpetic iritis. Reduced frequency of Behçet's disease was one of the most prominent characteristics.
  • Rie Tanaka, Mitsuko Takamoto, Keiko Komae, Kazuyoshi Ohtomo, Yujiro Fujino, Toshikatsu Kaburaki
    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 253 (7) 1175 - 80 0721-832X 2015/07 [Refereed][Not invited]
     
    PURPOSE: To investigate the clinical features of psoriatic uveitis in Japanese patients. METHODS: Clinical features of 13 consecutive patients with psoriatic uveitis treated at our facility were retrospectively examined using medical records. In this study, we collected data about psoriasis type, uveitis laterality, onset type, HLA types, visual acuity, ocular inflammation localization, anterior segment findings, funduscopy findings, complications, recurrence, and medical treatments for uveitis and skin diseases. RESULTS: The cohort comprised ten males and three females (43.6 ± 7.1 years old), and types of psoriasis included psoriasis vulgaris (seven cases), psoriatic arthritis (four cases), pustular psoriasis (three cases) and psoriatic erythroderma (one case). Two cases represented complicated cases of pustular psoriasis and psoriatic arthritis. Seven cases were unilateral, and six cases were bilateral. All cases had acute non-granulomatous anterior uveitis, whereas panuveitis occurred in one case. Furthermore, macular edema and vascular leakage on fluorescein angiography occurred in four cases, and hyperemic disc occurred in two cases. Recurrence occurred in nine cases. In addition to topical corticosteroid treatment, eight cases underwent oral immunosuppressive treatment or biologics. All six cases undergoing HLA typing were HLA-A2 positive. CONCLUSIONS: Cases of psoriatic uveitis in Japan appear to present with acute non-granulomatous uveitis; other symptoms may include macular edema, retinal vasculitis, or hyperemic disc.
  • 視神経炎の病型と臨床像の検討
    白濱 新多朗, 蕪城 俊克, 澤村 裕正, 田中 理恵, 山上 明子, 清澤 源弘, 若倉 雅登
    日本眼科学会雑誌 (公財)日本眼科学会 119 (臨増) 213 - 213 0029-0203 2015/03
  • Sirilak Kongkaew, Pathumwadee Yotmanee, Thanyada Rungrotmongkol, Nopporn Kaiyawet, Arthitaya Meeprasert, Toshikatsu Kaburaki, Hiroshi Noguchi, Fujio Takeuchi, Nawee Kungwan, Supot Hannongbua
    PloS one 10 (9) e0135575  2015 [Refereed][Not invited]
     
    Behçet's disease (BD), a multi-organ inflammatory disorder, is associated with the presence of the human leukocyte antigen (HLA) HLA-B*51 allele in many ethnic groups. The possible antigen involvement of the major histocompatibility complex class I chain related gene A transmembrane (MICA-TM) nonapeptide (AAAAAIFVI) has been reported in BD symptomatic patients. This peptide has also been detected in HLA-A*26:01 positive patients. To investigate the link of BD with these two specific HLA alleles, molecular dynamics (MD) simulations were applied on the MICA-TM nonapeptide binding to the two BD-associated HLA alleles in comparison with the two non-BD-associated HLA alleles (B*35:01 and A*11:01). The MD simulations were applied on the four HLA/MICA-TM peptide complexes in aqueous solution. As a result, stabilization for the incoming MICA-TM was found to be predominantly contributed from van der Waals interactions. The P2/P3 residue close to the N-terminal and the P9 residue at the C-terminal of the MICA-TM nonapeptide served as the anchor for the peptide accommodated at the binding groove of the BD associated HLAs. The MM/PBSA free energy calculation predicted a stronger binding of the HLA/peptide complexes for the BD-associated HLA alleles than for the non-BD-associated ones, with a ranked binding strength of B*51:01 > B*35:01 and A*26:01 > A*11:01. Thus, the HLAs associated with BD pathogenesis expose the binding efficiency with the MICA-TM nonapeptide tighter than the non-associated HLA alleles. In addition, the residues 70, 73, 99, 146, 147 and 159 of the two BD-associated HLAs provided the conserved interaction for the MICA-TM peptide binding.
  • Kenichi Namba, Hiroshi Goto, Toshikatsu Kaburaki, Nobuyoshi Kitaichi, Nobuhisa Mizuki, Yuri Asukata, Yujiro Fujino, Akira Meguro, Shunya Sakamoto, Etsuko Shibuya, Katsutoshi Yokoi, Shigeaki Ohno
    Ocular immunology and inflammation 23 Suppl 1 S1-23 - 23 0927-3948 2015 [Refereed][Not invited]
     
    Diagnosis and treatment of Behçet's disease (BD) have continued to undergo new changes in recent years. We organized a Compilation Committee for Guidelines on Diagnosis and Treatment of Ocular Behçet's Disease with five ophthalmology research facilities in Japan (Hokkaido University, Health Sciences University of Hokkaido, University of Tokyo, Tokyo Medical University, and Yokohama City University), and accomplished the Major review of Current aspects of Ocular Behçet's Disease in Japan. The review consist of four chapters: introduction, ocular lesions, diagnosis, and treatment. We are very pleased if the guidelines are found to be effective and useful in improving the quality of life (QOL) and quality of vision (QOV) of BD patients in the world.
  • Masaru Takeuchi, Takeshi Kezuka, Sunao Sugita, Hiroshi Keino, Kenichi Namba, Toshikatsu Kaburaki, Kazuichi Maruyama, Kei Nakai, Kuniaki Hijioka, Etsuko Shibuya, Keiko Komae, Junko Hori, Nobuyuki Ohguro, Koh-hei Sonoda, Nobuhisa Mizuki, Annabelle A Okada, Tatsuro Ishibashi, Hiroshi Goto, Manabu Mochizuki
    Ophthalmology 121 (10) 1877 - 84 0161-6420 2014/10 [Refereed][Not invited]
     
    PURPOSE: To evaluate the long-term efficacy and safety of infliximab for the treatment of uveitis in Behçet's disease (BD). DESIGN: Retrospective multicenter study using a questionnaire. PARTICIPANTS: A total of 164 consecutive patients with BD treated with infliximab for more than 1 year were studied. The mean age at initiation of infliximab treatment was 42.6±11.7 years, and the mean treatment duration was 32.9±14.4 months. METHODS: Data before and at the last visit during infliximab treatment were analyzed in 4 groups divided by duration of treatment: group A (n = 43, 12-<24 months), group B (n = 62, 24-<36 months), group C (n = 42, 36-<48 months), and group D (n = 17, ≥48 months). MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), relapse of ocular inflammation, numbers of ocular inflammatory attacks per year, and adverse effects of infliximab therapy. RESULTS: The frequency of ocular attacks decreased in all groups (from 5.3±3.0 to 1.0±0.3 in group A, 4.8±4.6 to 1.4±0.3 in group B, 4.1±2.9 to 0.9±0.3 in group C, and 9.5±5.8 to 1.6±0.5 in group D; all P < 0.05). The BCVA was improved in approximately 55% of the eyes after treatment. Mean BCVA converted to logarithm of the minimum angle of resolution was improved after treatment with infliximab in groups A to C (from 0.79±1.04 to 0.59±0.94 in group A, 0.59±1.07 to 0.41±1.04 in group B, and 1.15±1.77 to 0.92±1.73 in group C; all P < 0.05) but not in group D. Uveitis relapsed in 59.1% of all patients after infliximab treatment, and no difference in duration until relapse was observed between individual groups. Approximately 80% of relapses occurred within 1 year after the initiation of infliximab treatment in all groups, 90% of which were controlled by increasing doses of topical corticosteroids and shortening the interval of infliximab infusion. Adverse effects were observed in 65 cases or 35% of all subjects. Infliximab treatment was continued in 85% of the patients, but 15% of the patients discontinued infliximab treatment because of adverse effects or insufficient efficacy. CONCLUSIONS: Infliximab reduced the frequency of ocular attacks and improved visual acuity in patients with BD-related uveitis and was generally well tolerated with few serious adverse events.
  • Toshikatsu Kaburaki, Kenichi Namba, Koh-hei Sonoda, Takeshi Kezuka, Hiroshi Keino, Takako Fukuhara, Koju Kamoi, Kei Nakai, Nobuhisa Mizuki, Nobuyuki Ohguro
    Japanese journal of ophthalmology 58 (2) 120 - 30 0021-5155 2014/03 [Refereed][Not invited]
     
    PURPOSE: We developed a novel scoring system for uveitis due to Behçet's disease (BD), termed Behçet's disease ocular attack score 24 (BOS24), and examined its validity and usefulness by estimating changes in ocular disease activities both before and after initiation of infliximab therapy. METHODS: BOS24 consists of a total 24 points divided into 6 parameters of ocular inflammatory symptoms. To examine the validity of our scoring system, 5 uveitis specialists examined the severity of 50 ocular attacks in clinical charts using both our system and a physician's impression score (grade 1-10). In addition, ocular disease activities both before and after initiation of infliximab were retrospectively examined in 150 cases of ocular BD using BOS24. RESULTS: The average BOS24 for the 5 doctors was highly correlated with the average physician's impression score (p < 0.0001), whereas the coefficient of variance for BOS24 among doctors was much lower than that for the physician's impression score (p < 0.0001). Summation of BOS24 over a 6-month period (BOS24-6M) was significantly reduced after starting infliximab therapy (p < 0.0001). The average BOS24 for individual ocular attacks was also significantly decreased after starting infliximab, with scores for the posterior pole and fovea notably improved. CONCLUSIONS: BOS24 was highly related to severity noted by the physician's impression and had a low level of variability among the examined doctors. Using our novel scoring system, infliximab therapy was shown to reduce not only the frequency of ocular attacks, but also the severity of each attack. BOS24 is a promising tool for evaluating ocular BD activities.
  • Yusuke Arai, Yukihiro Sato, Atsushi Yoshida, Hidetoshi Kawashima, Toshikatsu Kaburaki, Harumi Gomi
    Clinical ophthalmology (Auckland, N.Z.) 8 2151 - 4 1177-5467 2014 [Refereed][Not invited]
     
    PURPOSE: Candida albicans subretinal abscess is extremely rare. To our knowledge, only one unilateral case has been reported. Herein, we report one bilateral case. Mixed bacterial infection was also suspected based on broad-range real-time polymerase chain reaction. METHODS: A 64-year-old man being treated with oral corticosteroids for interstitial pneumonia visited us for visual loss in the left eye. Best corrected visual acuity (BCVA) was 20/20 in the right eye and 8/200 in the left eye. Funduscopy revealed round yellowish-white subretinal lesions with retinal hemorrhage in both eyes. RESULTS: Broad-range polymerase chain reaction of the vitreous fluid from the left eye showed a high copy count of bacterial 16s ribosome RNA. Despite large doses of antibiotics, the abscess expanded and vision decreased to light perception in the left eye. Exenteration of the left eye was performed followed by microscopic examination showing Gram-negative bacilli, and C. albicans was also cultured. Antibiotics and the maximum doses of antifungal drugs were administered. However, the abscess in the right eye expanded, and BCVA decreased to 2/200. Vitrectomy and silicone oil tamponade were performed. Vitreous fluid culture revealed C. albicans. At 16 months follow-up, BCVA was stable at 4/200 with healing of the subretinal abscess under silicone oil. CONCLUSION: Since C. albicans subretinal abscess is extremely rare and there was a concurrent mixed bacterial infection, diagnostic procedures in our bilateral case were more complicated than usual. C. albicans infection should be included in the differential diagnosis of subretinal abscesses.
  • Toshikatsu Kaburaki, Qi Zhang, Xiangyuan Jin, Masateru Uchiyama, Yujiro Fujino, Hisae Nakahara, Mitsuko Takamoto, Kazuyoshi Otomo, Masanori Niimi
    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 251 (12) 2733 - 9 0721-832X 2013/12 [Refereed][Not invited]
     
    PURPOSE: It has been suggested thatSairei-to (TJ114), a traditional Japanese herbal medicine, has immunomodulatory activities. To evaluate the effects of TJ114 on uveitis, we examined the effectiveness of oral administration in a murine model of experimental autoimmune uveitis (EAU). METHODS: Murine EAU was induced by subcutaneous injection of human inter-photoreceptor retinoid-binding protein (IRBP) peptide mixed with complete Freund's adjuvant. In the TJ114-treated group, 2 g/kg was administrated orally from 0 to 20 days after immunization. Clinical scoring, histopathological scoring of EAU, cell proliferation, cytokine assessment, and adoptive transfer experiment of splenic T cells into naïve mice were performed. RESULTS: EAU development occurred in 32 of 38 mice (86 %) in the untreated group and 12 of 33 (36 %) in the TJ114-treated group. The clinical scores for EAU in the vehicle-treated and TJ114-treated groups were 1.56 ± 1.65 and 0.59 ± 0.63 respectively, at 14 days after immunization (p < 0.01, Mann-Whitney U-test), and 2.26 ± 1.56 and 0.75 ± 1.31 respectively at 21 days (p < 0.001, Mann-Whitney U-test), while the histopathological scores at 21 days were 1.47 ± 1.42 and 0.54 ± 0.84 respectively (p < 0.01, Mann-Whitney U-test). Interferon (IFN)-γ and tumor necrosis factor (TNF)-α production by cervical lymph node cells obtained from the TJ114-treated group were significantly reduced as compared with those from the vehicle-treated group (p < 0.01, Student's unpaired t-test). Moreover, the levels of C-C motif chemokine 2 (CCL2) and IFN-γ were significantly reduced in splenocytes of TJ114-treated mice as compared with the vehicle-treated group (p < 0.01, Student's unpaired t-test). Mice that received adoptive transfer of splenic T cells from TJ114-treated EAU mice caused significantly lower severity of EAU compared to those that received from vehicle-treated EAU mice. CONCLUSION: Oral administration of TJ114 has an inhibitory effect on a murine model of EAU, possibly via reduction in cytokine production by helper type-1 T cells.
  • Shugo Yotsumoto, Akira Meguro, Mami Ishihara, Riyo Uemoto, Masao Ota, Shin-ichiro Morimoto, Toshikatsu Kaburaki, Yasutaka Ando, Shinobu Takenaka, Shigeaki Ohno, Hidetoshi Inoko, Nobuhisa Mizuki
    Ocular immunology and inflammation 21 (3) 234 - 6 0927-3948 2013/06 [Refereed][Not invited]
  • Junko Matsuda, Toshikatsu Kaburaki, Shigeto Kobayashi, Jiro Numaga
    Japanese journal of ophthalmology 57 (1) 104 - 7 0021-5155 2013/01 [Refereed][Not invited]
     
    BACKGROUND: We describe a HLA-B27-positive Japanese man with recurrent severe anterior uveitis OU and ankylosing spondylitis (AS) who was successfully treated with infliximab. CASE: A 25-year-old HLA-B27-positive Japanese man presented with recurrent anterior uveitis OU. The symptoms were consistent with typical HLA-B27-associated uveitis, whereas the subsequent course, which consisted of frequent episodes of recurrent severe anterior uveitis, was atypical. Although the patient was treated with intensive topical corticosteroids, cycloplegic treatment, sub-Tenon triamcinolone acetonide injections, systemic corticosteroids and immunosuppressive agents, recurrence of the anterior uveitis persisted. Over 8 years there were 14 documented episodes of recurrent anterior uveitis OD and 10 OSs. At age 33, the patient was diagnosed with AS after a radiographic examination. We began infusions of infliximab (2.5 mg/kg) at 0, 2 and 6 weeks, and then every 8 weeks thereafter. The recurrent uveitis disappeared, and the immunosuppressive agents and oral corticosteroids were tapered and discontinued without relapse. All drugs other than infliximab were successfully stopped in October 2010. During the follow-up period, there were no adverse events. CONCLUSION: A case of severe recurrent anterior uveitis OU in a patient with AS with infliximab was successfully treated. This is the first report describing the efficacy of infliximab in AS-associated uveitis in Japan.
  • 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 0021-5155 2013/01 [Refereed][Not invited]
     
    PURPOSE: To examine the factors associated with anatomic and visual outcomes in Japanese patients with acute retinal necrosis (ARN). METHODS: One hundred four patients with ARN who were followed for more than 1 year at nine referral centers were reviewed. Retinal involvement at initial presentation was classified into four groups: zone 1 (posterior pole, n = 22), zone 2 (midperiphery, n = 54), zone 3 (periphery, n = 25), and unknown (n = 3). Forty-eight eyes underwent prophylactic vitrectomy before development of retinal detachment (vitrectomy group); 56 eyes were treated conventionally without prophylactic vitrectomy (observation group). RESULTS: The retina was attached in 28 of 48 eyes (58.3 %) in the vitrectomy group and 42 of 56 eyes (75.0 %) in the observation group at the final visit (P = 0.071). At 1 year, 56 eyes (53.8 %) had a best-corrected visual acuity (BCVA) of 20/200 or worse. Multivariate logistic regression analyses identified zone 1 disease (odds ratio = 4.983) and optic nerve involvement (odds ratio = 5.084) as significantly associated with BCVA of 20/200 or worse. Among the zone 3 eyes, significantly (P = 0.012) more eyes in the observation group than in the vitrectomy group had an attached retina. CONCLUSIONS: Prophylactic vitrectomy did not improve the final BCVA in any eyes. Zone 3 eyes had better outcomes without prophylactic vitrectomy.
  • Atsushi Yoshida, Toshikatsu Kaburaki, Kimiko Okinaga, Mitsuko Takamoto, Hidetoshi Kawashima, Yujiro Fujino
    Japanese journal of ophthalmology 56 (6) 536 - 43 0021-5155 2012/11 [Refereed][Not invited]
     
    PURPOSE: To examine the factors affecting the efficacy of infliximab (IFX) as a treatment for uveitis in Behçet's disease. METHODS: Clinical records of 29 patients with refractory uveoretinitis were examined retrospectively for the period between 6 months before the initiation of IFX therapy to 12 months thereafter. The patients were divided into two groups based on the absence (Group 1) or occurrence (Group 2) of ocular inflammatory attacks during the observation period after IFX therapy, and the clinical records of the groups were compared RESULTS: The mean age at onset of ocular inflammation in Group 1 patients (n = 17) was lower than that in Group 2 patients (n = 12) (p = 0.023). Compared to Group 2 patients, the period from onset to IFX therapy in Group 1 was longer (p = 0.037), and the frequency of ocular inflammatory attacks before IFX therapy was lower (p = 0.013). The rates of ocular fundus attacks before IFX therapy were 0.82 ± 0.28 in Group 1 and 0.96 ± 0.10 in Group 2 (p = 0.040). Three of 33 (9.1 %) eyes in Group 1 and nine of 24 eyes (37.5 %) in Group 2 had an improved best-corrected visual acuity of >0.2 logarithm of the minimal angle resolution (p < 0.01). CONCLUSIONS: Patients in Group 1 tended to have fewer intraocular attacks (fewer fundus attacks in particular) prior to IFX therapy and have a longer period from onset of intraocular inflammation to IFX therapy. The improvement of the BCVA in Group 2 tended to be better.
  • 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 - 15 2012/10 [Refereed][Not invited]
     
    PURPOSE: Sarcoidosis is a heterogeneous and multisystem granulomatous disorder. The etiology still is uncertain, but the disease currently is thought to be triggered by various genetic as well as environmental factors. Recently, an association between sarcoidosis and the butyrophilin-like 2 (BTNL2) gene located in close proximity to the HLA-DRB1 gene was reported. The purpose of our study was to verify the relationship between BTNL2 and HLA risk alleles for the susceptibility to sarcoidosis, and to assess whether the BTNL2 association is independent of the HLA risk alleles. METHODS: In our study, 11 single nucleotide polymorphisms (rs28362677, rs2076533, rs2076530, rs2076529, rs2294881, rs3763304, rs2076523, rs28362682, rs3806156, rs9268499, rs3763317), including the functional rs2076530 (G > A) of the BTNL2 gene, and HLA-DRB1 and -DQB1 alleles, were genotyped in 237 Japanese patients diagnosed with sarcoidosis and 287 healthy Japanese control subjects. RESULTS: In the patient group, the HLA-DRB1*08:03 (P = 6.15 × 10(-5), odds ratio [OR] = 2.43) and BTNL2 rs2076530_A (P = 6.90 × 10(-6), OR = 1.84) were associated with disease susceptibility. Upon stratification analysis in search for a synergistic effect given the extensive linkage disequilibrium between BTNL2 rs2076530_A and HLA-DRB1*08:03, our results suggested that the risk-bearing allele of these two loci interact negatively. No significant differences were observed in allele frequencies for alleles in patients with ocular and other systemic sarcoidosis. CONCLUSIONS: Our studies implicated that the HLA-DRB1 allele is a major contributing genetic factor in the development of sarcoidosis in Japan. However, further studies are needed to verify how HLA or BTNL2 alleles confer the disease phenotype, severity of sarcoidosis.
  • Kazuyoshi Otomo, Toshikatsu Kaburaki, Takashi Shigeeda, Mituko Takamoto, Hidetoshi Kawashima, Makoto Araie
    International ophthalmology 32 (4) 401 - 3 2012/08 [Refereed][Not invited]
     
    We report a case of bilateral iridocyclitis accompanied by bacterial meningitis in an immunocompetent patient. Case report. A 48 year-old healthy female visited our hospital with strong headache, fever, bilateral hyperemia, and blurred vision in both eyes. A slit-lamp examination revealed moderate cells and flare in the anterior chamber of both eyes, with fine keratoprecipitates. There were no obvious inflammatory changes in the vitreous, retina, and optic disc of both eyes. Elevation of peripheral blood white blood cells, C-reactive protein, and an elevated number of cerebrospinal fluid (CSF) cells suggested bacterial meningitis. The patient was admitted to our hospital and received intravenous antibiotics. Finally, a CSF culture revealed infection with gram-positive rods, suspected Listeria monocytogenes, confirming bacterial meningitis. For iridocyclitis, we prescribed betamethasone eyedrops and 0.5 % tropicamide eyedrops with intravenous adminstration of systemic antibiotics. 3 days later, her headache and bilateral hyperemia disappeared. This case is better described as sterile reactive uveitis rather than endogenous bacterial endophthalmitis, because bilateral anterior uveitis was resolved without chronic uveitis, iris atrophy, and vitreous opacity. When clinicians see patients with meningitis and bilateral anterior uveitis, sterile reactive uveitis should be considered in the differential diagnosis of uveitis.
  • Shigeto Fujimura, Hidenori Takahashi, Kentaro Yuda, Takashi Ueta, Aya Iriyama, Tatsuya Inoue, Toshikatsu Kaburaki, Yasuhiro Tamaki, Kouji Matsushima, Yasuo Yanagi
    Investigative ophthalmology & visual science 53 (4) 1999 - 2006 0146-0404 2012/04 [Refereed][Not invited]
     
    PURPOSE: Several recent studies suggest that some chemokines/chemokine receptors are involved in choroidal neovascularization (CNV). CXCR3 was the focus of the present study because microarray analysis for murine laser-induced CNV model showed the increased expression of CXCR3. The purpose of this study was to evaluate the effect of CXCR3 on CNV. METHODS: Microarray analysis was performed for the mouse eyes with laser-induced CNV. CXCR3 expressions on the CNV were evaluated by immunohistochemistry and real-time RT-PCR. CNV was compared between CXCR3-deficient mice and wild-type mice, between mice treated with anti-CXCR3/anti-IP-10 neutralizing antibody and mice treated with control IgG. Macrophage recruitment into CNV was also investigated. Ocular expressions of vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), C-C chemokine ligand-2 (CCL2), and complement component-3 (C3) were evaluated by real-time PCR. RESULTS: Microarray analysis and real-time RT-PCR revealed the elevation of CXCR3 and IP-10 in laser-treated mouse eyes compared with control eyes. Immunohistochemistry showed CXCR3 expression on the endothelial cells of CNV. Laser-induced CNV of CXCR3-deficient mice was significantly larger, with greater leakage in fluorescein angiography, and with greater macrophage-infiltration compared with wild-type mice (P < 0.01). Intravitreal injection of anti-CXCR3/anti-IP-10 neutralizing antibody exacerbated CNV. The CCL2 expression in the laser-treated eyes of CXCR3-deficient mice was higher than in those of wild-type mice (P < 0.05), whereas VEGF, PEDF, and C3 showed no differences. CONCLUSIONS: These results suggested that CXCR3 expressed on CNV could have an angiostatic effect on it.
  • Mitsuko Takamoto, Toshikatsu Kaburaki, Akihiko Mabuchi, Makoto Araie, Shiro Amano, Makoto Aihara, Atsuo Tomidokoro, Aiko Iwase, Fumihiko Mabuchi, Kenji Kashiwagi, Shiroaki Shirato, Noriko Yasuda, Hidetoshi Kawashima, Fumiko Nakajima, Jiro Numaga, Yoshiya Kawamura, Tsukasa Sasaki, Katsushi Tokunaga
    PloS one 7 (7) e40107  2012 [Refereed][Not invited]
     
    Although intraocular pressure (IOP) is the most definitive cause of glaucoma, a subtype of open angle glaucoma (OAG) termed normal tension glaucoma (NTG), which occurs in spite of normal IOP, accounts for a large part of glaucoma cases, especially in Japan. To find common genetic variants contributing to NTG in Japanese patients, we conducted a genome-wide association study (GWAS). We performed the first screening for 531,009 autosomal SNPs with a discovery cohort of 286 cases and 557 controls, and then a second screening for the top 30 suggestive loci in an independent cohort of 183 cases and 514 controls. Our findings identified a significantly associated SNP; rs523096 [combined p-value = 7.40× 10(-8), odds ratio (OR)= 2.00 with 95% confidence interval (CI) 1.55-2.58] located 10 kbp upstream of CDKN2B on chromosome 9p21. Moreover, analysis of another independent case-control set successfully replicated the results of the screening studies (combined values of all 3 stages p = 4.96 × 10(-11), OR= 2.13 with 95% CI 1.69-2.68). The SNPs near rs523096 were recently reported to be associated with OAG associated with elevated IOP in primary open-angle glaucoma (POAG), the predominant subtype of glaucoma in Caucasian populations. Our results revealed that the 9p21 locus is also associated with NTG in Japanese. In addition, we identified SNPs more strongly associated with NTG.
  • 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 18 512 - 8 2012 [Refereed][Not invited]
     
    PURPOSE: To investigate whether interleukin 10 (IL10) gene polymorphisms are associated with the development of sarcoidosis in Japanese patients. METHODS: Two hundred and eighty-eight Japanese sarcoidosis patients and 310 Japanese healthy controls were recruited. We genotyped 9 single-nucleotide polymorphisms in IL10 and assessed the allelic diversity between cases and controls. RESULTS: No significant differences in the frequency of IL10 alleles, genotypes, and haplotypes in the sarcoidosis cases compared to the controls were detected. CONCLUSIONS: Our results suggest that IL10 polymorphisms are not significantly related to the pathogenesis of sarcoidosis in the Japanese population.
  • Reina Fukuda, Tatsuro Tanabe, Hiromasa Sawamura, Mikiko Kawata, Hideki Tsuji, Toshikatsu Kaburaki
    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 249 (12) 1883 - 7 2011/12 [Refereed][Not invited]
     
    BACKGROUND: Most intraocular metastatic tumors occur in the uveal tract, while isolated metastasis to the optic nerve is rarely found. We report a case of metastasis to the optic disc from primary lung cancer, diagnosed from biopsy findings obtained during a vitrectomy. PATIENT AND METHODS: A 69-year-old male presented with gradual visual impairment due to a milky white tumour that extended from the optic disc into the vitreous cavity. A systemic examination revealed primary squamous cell lung cancer. RESULTS: A biopsy specimen was obtained from the optic disc tumor during a vitrectomy, which led to a diagnosis of metastasis from lung cancer. Despite courses of chemotherapy and radiotherapy, the patient died of brain metastasis. DISCUSSION: There are few reports of secondary optic disc tumors and pathological biopsy findings are rare. When a milky white tumor is observed extending from the optic disc, a possible differential diagnosis is metastatic neoplasm.
  • 脈絡膜新生血管におけるケモカイン受容体CXCR3の関与
    藤村 茂人, 高橋 秀徳, 湯田 健太郎, 上田 高志, 井上 達也, 柳 靖雄, 蕪城 俊克, 玉置 泰裕, 松島 綱治
    日本眼科学会雑誌 (公財)日本眼科学会 115 (臨増) 219 - 219 0029-0203 2011/04
  • 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 17 731 - 6 2011/03 [Refereed][Not invited]
     
    PURPOSE: Sarcoidosis is a systemic inflammatory disease characterized by the formation of non-caseating granulomas, with varied clinical manifestations. The common etiology of sarcoidosis is uncertain, but it is thought to be triggered by an exogenous antigenic stimulus, such as some bacterial proteins. Toll-like receptors (TLRs) recognize microbial components and elicit innate as well as adaptive immune responses. It has been reported that polymorphisms in TLR2 might be important in a small group of Caucasian sarcoidosis patients. The present study aimed to establish whether these findings are relevant to the Japanese population. METHODS: We genotyped 5 single-nucleotide polymorphisms (SNPs) in TLR2 and assessed the allelic diversity between 257 Japanese sarcoidosis patients and 193 Japanese healthy controls. RESULTS: No significant differences in the frequency of TLR2 alleles and haplotypes in the sarcoidosis cases were found in comparison with the controls. However, marginal associations were observed for TLR2 at rs3804099 and rs3804100 in sarcoidosis patients with cutaneous manifestations. CONCLUSIONS: Our results suggest that TLR2 polymorphisms are not significantly related to the pathogenesis of sarcoidosis in the Japanese population.
  • T. Kaburaki, M. Takamoto, J. Numaga, H. Kawashima, M. Araie, Y. Ohnogi, S. Harihara, S. Kuwata, F. Takeuchi
    CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 28 (4) S39 - S44 0392-856X 2010/07 [Refereed][Not invited]
     
    Objective. Behcet's disease (BD) is known to be associated with HLA-B*51, especially HLA-B*5101, in many different ethnic groups. Recently, several HLA-A or -B alleles have been proposed as possible candidate genes for BD in addition to HLA-B*5101. To investigate those associations, we studied HLA-A and -B alleles in Japanese ocular BD patients and the association of possible susceptibility HLA genes with visual prognosis. Methods. Eighty-eight Japanese BD patients with uveitis and 104 healthy controls were enrolled for analyses of HLA-A and B alleles. Statistical analysis was performed with Fisher's exact test and odds ratio (OR). Association of the possible susceptible HLA gene and visual prognosis was also examined. Results. The phenotype frequency (PF) of HLA-A*2601 was significantly higher in the patients (37.5%) than the controls (14.4%) (pc=0.00529, OR=3.56), especially in patients without HLA-B*510.1 (57.4% vs. 14.1%, pc=4.58x10(-6), OR=8.21). In contrast, the PF of HLA-A*2601 was not increased in patients with HLA-B*5101 (14.6% vs. 15.8%). Also, the PF in patients possessing HLA-A*2601 or HLA-B*5101 was increased up to 77.3%. Interestingly, the PF of HLA-A*2601 was significantly associated with poor visual prognosis corresponding to visual acuity of 0.1 or less in the worse eye (p=0.0262). Conclusion. Our results indicate that HLA-A*2601 is possibly associated with ocular BD, independent of HLA-B*5101, indicating that HLA-A*2601 is an additional susceptibility allele candidate of ocular BD in Japan. HLA-A*2601 would also be a possible marker for poor visual prognosis.
  • Toshikatsu Kaburaki, Fumiyuki Araki, Mitsuko Takamoto, Kimiko Okinaga, Atsushi Yoshida, Jiro Numaga, Yujiro Fujino, Hidetoshi Kawashima
    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 248 (5) 709 - 14 0721-832X 2010/05 [Refereed][Not invited]
     
    BACKGROUND: Recent publications have suggested considerable improvements in the clinical outcomes of ocular Behcet's disease (BD) patients. However, the long-term time course of clinical ocular features of BD in recent cases remains largely unknown. In this study, we investigated annual time-course changes of best-corrected visual acuity (BCVA) during ocular convalescent stages, as well as annual frequency of ocular attacks during the initial 10 years of follow-up in patients with BD. METHODS: We studied 75 eyes in 39 patients (31 men, eight women) with BD, who were referred to our hospital between 1980 and 1996 within 1 year after the initial ocular attack and followed them up continuously for more than 10 years. The clinical courses of BCVA at the ocular convalescent stage from the onset of ocular disease were retrospectively examined, and the numbers of ocular attacks per eye per year were determined. RESULTS: Mean BCVA was 0.59 at 1 year, 0.31 at 3 years, and 0.12 at 10 years from the onset of ocular disease, while the numbers of ocular attacks per eye were 4.1 +/- 3.1 at 1 year, 2.2 +/- 1.9 at 5 years, and 1.4 +/- 1.8 at 10 years. Ocular attacks were still observed in 33 eyes (45%) of 21 patients (54%) with BD even after 10 years. Final BCVA in 42 eyes (56%) became lower than 0.5. The major reasons for poor visual prognosis were macular atrophy (41%) and chorioretinal atrophy (26%). CONCLUSIONS: The decline of BVCA continued, and nearly half the patients still suffered from ocular attacks at 10 years after the onset of ocular BD.
  • Toshikatsu Kaburaki, Mitsuko Takamoto, Fumiyuki Araki, Yujiro Fujino, Miyuki Nagahara, Hidetoshi Kawashima, Jiro Numaga
    International ophthalmology 30 (2) 203 - 6 2010/04 [Refereed][Not invited]
     
    PURPOSE: We report a case of Candida albicans endophthalmitis with subretinal abscess formation in a patient who underwent liver transplantation. METHODS: Case report. RESULTS: A 51-year-old Japanese woman complained of deep pain and ciliary injection in her right eye. Three months prior, the patient had undergone liver transplantation for cirrhosis caused by hepatitis C. A slit-lamp examination revealed intense anterior chamber inflammation with hypopyon and fundoscopy showed a yellowish-white subretinal mass lesion in the inferior peripheral fundus. Systemic and topical antibiotics did not prevent further progression of the infection. The patient underwent pars plana vitrectomy treatment three times and a histopathological study of a vitreous specimen revealed C. albicans to be the causative organism. CONCLUSION: A subretinal abscess, previously reported in Nocardia, Pseudomonas, Staphylococcus, and Aspergillus infection cases, can also occur in patients infected with Candida. Therefore, Candida infection should be considered as a potential cause of subretinal abscess in organ transplant recipients.
  • 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 2673 - 82 2009/12 [Refereed][Not invited]
     
    PURPOSE: Toll-like receptors (TLRs) are pattern-recognition receptors that play an important role in innate and adaptive immune responses to microbial pathogens. Among TLRs, TLR4 recognizes lipopolysaccharides of Gram-negative bacteria. Genetic polymorphisms within the TLR4 gene have been reported to be associated with various inflammatory diseases; therefore, TLR4 appears to be a susceptibility gene for sarcoidosis. Although sarcoidosis has various clinical manifestations, its association with uveitis is more common in Japan than in other countries. The aim of this study was to investigate whether TLR4 polymorphisms were associated with sarcoidosis-related uveitis in a Japanese population. METHODS: Two hundred twenty-three patients with sarcoidosis and 206 healthy control subjects were recruited at seven sites in Japan. Eight single-nucleotide polymorphisms (SNPs) in TLR4 were genotyped with a TaqMan assay, and allelic and phenotypic diversity were assessed in affected and control subjects. RESULTS: We found no association with susceptibility to sarcoid-related uveitis for any of the SNPs analyzed. Strong linkage disequilibrium was observed among all the SNPs analyzed (D'>/=0.78), which were located in one haplotype block. CONCLUSION: TLR4 polymorphisms do not play an important role in the development of uveitis in Japanese patients with sarcoidosis.
  • T Kaburaki, T Koshino, H Kawashima, J Numaga, A Tomidokoro, S Shirato, M Araie
    Eye (London, England) 23 (7) 1509 - 17 2009/07 [Refereed][Not invited]
     
    PURPOSE: To analyse clinical outcomes of trabeculectomy with mitomycin C (MMC) in eyes with uveitic glaucoma (UG) with inactive uveitis and compare them to those in eyes with primary open-angle glaucoma (POAG). DESIGN: Retrospective non-randomized comparative interventional case series. METHODS: A total of 53 eyes with UG and 80 eyes with POAG that received MMC trabeculectomy as an initial ocular surgery with average follow-up of 5.4 years were reviewed retrospectively. The intraocular pressure (IOP) control and persistence of filtering bleb were analysed using the Kaplan-Meier life-table method based on two definitions of successful IOP control, ie complete success (IOP
  • Wataru Omi, Takumi Taniguchi, Tomonori Kaburaki, Masaki Okajima, Masayuki Takamura, Toru Noda, Keisuke Ohta, Hiroshi Itoh, Yoshikazu Goto, Shuichi Kaneko, Hideo Inaba
    Resuscitation 78 (3) 340 - 5 2008/09 [Refereed][Not invited]
     
    BACKGROUND AND OBJECTIVES: It is essential to have a clear understanding of the present condition of cardiopulmonary resuscitation (CPR) training courses and the associated problems. The present study was performed to identify the current conditions of CPR training in Japanese high schools and the attitudes of students toward CPR. METHODS AND RESULTS: We distributed a questionnaire study to the students of 12 cooperating high schools regarding their willingness to perform CPR in 5 hypothetical scenarios of cardiopulmonary arrest: a stranger, a trauma patient, a child, an elderly person, and a relative. Between February and March 2006, a total of 3316 questionnaires were completed. Across all scenarios, only 27% of respondents from general high schools reported willingness to perform chest compression (CC) plus mouth-to-mouth ventilation (MMV), and 31% reported willingness to perform CC alone. Fifty-nine percent of students had previous CPR training, and only 35% were willing to perform CC plus MMV. Most of the respondents who reported that they would decline to perform full CPR, stated that poor knowledge and/or fear of incomplete performance of CPR were deciding factors. CONCLUSIONS: Japanese high school students are reluctant to perform CC plus MMV, despite having received training. The present educational system in Japan has limitations in encouraging high school students to perform CC plus MMV.
  • 峰村 健司, 永原 幸, 蕪城 俊克, 桜井 真彦, 新家 眞, 田中 栄, 土井 卓子, 奥川 周, 塚田 訓久
    日本眼科学会雑誌 (公財)日本眼科学会 110 (3) 188 - 192 0029-0203 2006/03 [Refereed][Not invited]
     
    目的:内因性真菌性眼内炎を発症した後,自傷行為が関与したと思われる角膜潰瘍,眼内炎を繰り返し,ミュンヒハウゼン症候群が疑われた症例を経験したので報告する.症例:44歳,女性.2000年10月に右眼に内因性真菌性眼内炎を発症,硝子体切除術で軽快したが,その後,医学的に説明のつかない角膜潰瘍および眼内炎を繰り返して失明に至った.経過中,自傷行為の物的証拠が発見され,術後に繰り返された角膜潰瘍および眼内炎には自傷行為が関与していると考えられた.精神科医のカルテ診察によりミュンヒハウゼン症候群が疑われたが,患者は精神科受診を拒否し続けた.結論:このような症例に対しては,眼科的治療だけでなく精神科的ケアをも念頭におき対応する必要があると考えられた(著者抄録)
  • Kenji Minemura, Miyuki Nagahara, Toshikatsu Kaburaki, Masahiko Sakurai, Makoto Araie, Sakae Tanaka, Takako Doi, Shu Okugawa, Kunihisa Tsukada
    Nippon Ganka Gakkai zasshi 110 (3) 188 - 92 0029-0203 2006/03 [Refereed][Not invited]
     
    PURPOSE: To report recurrent fungal endophthalmitis which developed after endogenous fungal endophthalmitis. The patient was suspected to be suffering from Munchausen syndrome. CASE: A 44-year-old woman contracted endogenous fungal endophthalmitis in her right eye in October 2000. After the endophthalmitis was healed by vitrectomy, corneal ulcer and endophthalmitis repeatedly occurred in the eye from an unknown cause. The patient finally lost the sight of her right eye. The corneal ulcer and endophthalmitis resulted from self-injury for which we found material evidence in the course of the treatment. Munchausen's syndrome was suspected but the patient persistently refused to see a psychiatrist. CONCLUSION: We must be prepared to provide mental and psychiatric care in addition to ophthalmological treatment for such a case.
  • Jiro Numaga, Nobuyuki Koseki, Toshikatsu Kaburaki, Hidetoshi Kawashima, Goji Tomita, Makoto Araie
    Current eye research 30 (10) 909 - 13 0271-3683 2005/10 [Refereed][Not invited]
     
    PURPOSE: It is still unknown which metabolite of isopropyl unoprostone is responsible for reducing intraocular pressure. This study was carried out to measure intraocular metabolites of isopropyl unoprostone in the aqueous humor of primate and human eyes. METHODS: Nine monkeys were randomly divided into three groups, all of which received isopropyl unoprostone. In group I, the drug was scheduled to be instilled at 0 hr, in group II at 1 hr, and in group III at 2 hr, prior to aqueous humor aspiration in order to determine metabolite concentration. Furthermore, 27 patients scheduled for cataract surgery and intraocular lens implantation were divided into five groups that received isopropyl unoprostone. In group A, the drug was scheduled to be instilled at 0 hr, in group B at 1 hr, in group C at 2 hr, in group D at 3 hr, and in group E at 4 hr, prior to surgery. At the beginning of the operation, the aqueous humor was aspirated. Metabolites of isopropyl unoprostone in the aqueous humor were determined by high-performance liquid chromatography. RESULTS: M1 (3-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(3-oxodecyl)cyclopentyl]propionic acid) (unoprostone free acid) and M2 ((Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(3-oxodecyl)cyclopentyl]hept-5-enoic acid), an intraocular oxidized metabolite of isopropyl unoprostone, were measured. M1:M2 in monkeys was respectively 0:0 ng/ml in group I, 150.2 +/- 45.1:9.5 +/- 1.7 (p < 0.05) in group II, and 74.6 +/- 31.4:19.2 +/- 5.3 (p < 0.01) in group III. M1:M2 in humans was respectively 0:0 ng/ml in group A, 50.6 +/- 22.3:3.2 +/- 1.3 (p < 0.05) in group B, 125.0 +/- 23.1:12.2 +/- 3.4 (p < 0.001) in group C, 144.9 +/- 33.8:24.5 +/- 6.2 (p < 0.01) in group D, and 56.7 +/- 21.5:18.7 +/- 5.3 (p < 0.05) in group E. CONCLUSIONS: A free acid of isopropyl unoprostone is the major intraocular metabolite of isopropyl unoprostone that is expected to act on target tissues in the eyes of both monkeys and humans.
  • T Kaburaki, S Sato, H Kawashima, M Sakurai, J Numaga, Y Fujino, M Araie
    Eye (London, England) 19 (6) 692 - 3 0950-222X 2005/06 [Refereed][Not invited]
  • A K Adhikary, T Inada, U Banik, A Mukouyama, Y Ikeda, M Noda, T Ogino, E Suzuki, T Kaburaki, J Numaga, N Okabe
    Journal of clinical pathology 57 (4) 411 - 6 0021-9746 2004/04 [Refereed][Not invited]
     
    AIMS: To characterise a novel strain of adenovirus (Ad) type Ad8 (genome type Ad8I) involved in an epidemic keratoconjunctivitis (EKC) outbreak in Hiroshima city using serological testing and sequence analysis of the fibre and hexon gene. METHODS: A neutralisation test (NT) was performed in microtitre plates containing a confluent monolayer of A549 cells using 100 tissue culture infectious doses of virus and type specific antisera. The haemagglutination inhibition test was also carried out in microtitre plates with rat erythrocytes using four haemagglutination units of virus and twofold dilutions of serum. The fibre gene was sequenced by generating overlapping polymerase chain reaction products or by direct sequencing of genomic DNA. Primer selection was based on alignment of the fibre genes of human adenovirus serotypes Ad8, Ad19, Ad37, Ad9, and Ad15 available from Gene Bank. RESULTS: The virus strain was specifically neutralised by anti-Ad8 antibodies, although there was a major crossreaction with anti-Ad9 antibodies. Haemagglutination was equally inhibited by anti-Ad8 and anti-Ad9 antibodies. The predicted amino acid sequences of the hypervariable regions (HVRs) of the Ad8I hexon gene showed higher homology with Ad9 (83.3%) than with Ad8 (62.0%). However, the Ad8I fibre knob was more homologous to Ad8 (94.4%) than to Ad9 (91.6%). CONCLUSIONS: Ad8I is a unique strain of adenovirus because of its lower genomic homology with Ad8, major crossreactivity with Ad9 in NT, and mixed genetic organisation of HVRs of the hexon gene. These factors may have enabled the virus to circumvent acquired immunity, resulting in the outbreak.
  • Atsushi Yoshida, Hidetoshi Kawashima, Yuta Motoyama, Hirobumi Shibui, Toshikatsu Kaburaki, Kazuyuki Shimizu, Kazuhiko Ando, Kiyono Hijikata, Yasuho Izawa, Kiyofumi Hayashi, Jiro Numaga, Yujiro Fujino, Kanjiro Masuda, Makoto Araie
    Ophthalmology 111 (4) 810 - 5 0161-6420 2004/04 [Refereed][Not invited]
     
    OBJECTIVE: To compare clinical findings in patients with Behçet's disease (BD) seen in 2 different decades (1980s and 1990s) to determine if there has been a shift toward the appearance of less severe disease. DESIGN: Retrospective, comparative case series. PARTICIPANTS: Two hundred forty patients with uveitis caused by BD who had their first visit and at least a 4-month follow-up at the uveitis clinic of University of Tokyo Hospital between January 1980 and December 1999 were enrolled. METHODS: Patients were divided into 2 groups according to the date of the first visit. The clinical profiles were then compared between the 1980s group (133 patients, observed for 33.5+/-26.4 months) and the 1990s group (107 patients, observed for 46.9+/-32.6 months). MAIN OUTCOME MEASURES: Number of ocular attacks per year, visual outcomes, and the percentage of patients who had cyclosporine or cyclophosphamide therapy. RESULTS: Age of onset, type of inflammation, incidence of secondary glaucoma, and surgical history of glaucoma and cataract did not differ between the 1980s and the 1990s. Conversely, in patients in the 1990s, the number of ocular attacks per year and the percentage of patients with cyclosporine or cyclophosphamide therapy decreased significantly. Furthermore, the percentage of eyes with good visual acuity (VA) (?20/30) increased, and the percentage of eyes with poor VA (<20/200) decreased significantly at both the first and the last examinations. There was a trend for less bilateral disease and fewer genital ulcers in the 1990s as well. CONCLUSIONS: Through a study of Japanese patients, we confirmed that the clinical outcomes of BD, especially judging by the number of ocular attacks per year and VA, indeed improved during the 1990s.
  • Masuhiro Kodama, Jiro Numaga, Atsushi Yoshida, Toshikatsu Kaburaki, Tetsuro Oshika, Yujiro Fujino, Guey-Shuang Wu, Narsing A Rao, Hidetoshi Kawashima
    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 241 (11) 927 - 33 0721-832X 2003/11 [Refereed][Not invited]
     
    BACKGROUND: To investigate the effects of a new biodegradable dexamethasone drug delivery system, Surodex, in two experimental intraocular inflammation models; endotoxin-induced uveitis (EIU) and experimental autoimmune uveoretinitis (EAU). METHODS: Surodex was inserted into the right anterior chambers (ACs) of rats. In the EIU experiment, protein concentration, cell infiltration, and myeloperoxidase (MPO) activity in the aqueous humor were measured 24 h after injection. Eyes were evaluated histopathologically. In the EAU experiment, firstly, Surodex was administered at various days after immunization. Then, Surodex was administered on day 9 and eyes were evaluated histopathologically. Intraocular cytokine levels (IFN-gamma and IL-4) were investigated. RESULTS: In the EIU experiments, eyes with Surodex exhibited significantly reduced inflammation compared with contralateral controls. Protein concentrations, cell infiltrations, as well as MPO activity were reduced. In the EAU experiments, all rats with Surodex given on days 0 or 7 showed no or significantly reduced inflammation in both eyes. Rats treated on day 12 developed reduced inflammation only in the treated eyes. IFN-gamma levels were significantly lower in the eyes with Surodex, whereas IL-4 was not detectable. CONCLUSIONS: This new, biodegradable corticosteroid drug-delivery system is highly effective in suppressing intraocular inflammation, and should be a useful tool to manage uveitis in humans.
  • Kyoko Ono, Shiho Kunimatsu, Jiro Numaga, Toshikatsu Kaburaki, Yujiro Fujino, Hidetoshi Kawashima
    Clinical & experimental ophthalmology 31 (4) 365 - 6 1442-6404 2003/08 [Refereed][Not invited]
  • M Kodama, J Numaga, T Kaburaki, A Imamura, M Sakurai, Y Fujino, H Kawashima
    Eye (London, England) 17 (6) 782 - 4 0950-222X 2003/08 [Refereed][Not invited]
  • Toshikatsu Kaburaki, Yujiro Fujino, Hidetoshi Kawashima, Guillermo Merino, Jiro Numaga, Jun Chen, Kouji Matsushima
    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 241 (5) 353 - 8 0721-832X 2003/05 [Refereed][Not invited]
     
    BACKGROUND: Chemokines are a family of chemoattractants of leukocytes that play a critical role for leukocyte recruitment in various inflammatory diseases. The purpose of this study is to investigate the involvement of chemokines, interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in the peripheral blood, with a special reference to disease activities of the patients with Behçet's disease (BD). METHODS: The study population consisted of totally 55 patients with BD who had panuveitis (20 patients with active BD, 35 patients with inactive BD) as well as 19 healthy volunteers as control. Disease activity was defined according to the existence of ocular inflammation. IL-8 and MCP-1 concentration levels in the plasma and whole-blood samples were measured by enzyme-linked immunosorbent assay. Whole-blood samples were obtained by lysing cell membranes of peripheral blood cells. RESULTS: Most of the plasma IL-8 samples were below the detectable limit. Whole-blood IL-8 levels were readily measured. The levels in the patients with active BD were significantly higher than the other two groups. The patients with active and inactive BD showed higher plasma and whole-blood levels of MCP-1 than controls. The plasma and whole-blood MCP-1 levels of the samples collected at the same time showed a linear correlation. CONCLUSION: A close relationship was found to exist between the cell-associated IL-8 and the disease activity, while a persistent role of MCP-1 was observed in BD. Measuring the whole-blood levels of chemokines is useful for monitoring the disease activity.
  • A K Adhikary, J Numaga, T Kaburaki, H Kawashima, M Araie, Y Ikeda, T Ogino, E Suzuki, H Ushijima, A Mukoyama, S Matsuno, T Inada, N Okabe
    Journal of clinical pathology 56 (2) 120 - 5 0021-9746 2003/02 [Refereed][Not invited]
     
    AIMS: To investigate the genetic differences among the strains of adenovirus type 8 (Ad8) circulating in Hiroshima city, Japan, and to study their circulation pattern. METHODS: One hundred and twenty nine strains of adenovirus type 8 (Ad8) were isolated in Hiroshima City over a 15 year period (1983-97) from patients with keratoconjunctivitis, and analysed with six restriction enzymes-BamHI, HindIII, PstI, SacI, SalI, and SmaI-to investigate possible relations among the isolates and their genetic variability. Seven hypervariable regions of the hexon gene that carry the type specific epitope were also sequenced to investigate the variation among the genome types. RESULTS: Restriction endonuclease analyses yielded three known genome types (Ad8A, 13 samples; Ad8B, seven samples; and Ad8E, 35 samples) and a novel genome type (Ad8I, 74 samples). Ad8A, Ad8B, and Ad8E were closely related, with 96% homology, whereas Ad8I had only 71% homology. Ad8A, Ad8B, and Ad8E shared 91.8% and 96.4% homology with regard to their amino acid and nucleotide sequences, respectively, with the isolate 1127 (accession no X74663). However, when compared with Ad8A, Ad8B, Ad8E, and isolate 1127, Ad8I shared only 62.7% and 69.9% homology with regard to amino acid and nucleotide sequences, respectively. Ad8A, Ad8B, and Ad8E had a unique 31 amino acid deletion in the hypervariable region 1 of the hexon gene, whereas Ad8I had a 33 residue deletion. The Ad8E strain that circulated from 1984 to 1995 was stable among the study population. Ad8I was isolated from an outbreak of epidemic keratoconjunctivitis in 1995 and was also isolated from sporadic cases until 1997. CONCLUSIONS: These results confirmed that genetic variability occurs in Ad8 in the microenvironment and revealed the emergence of a new genome type (Ad8I).
  • Shosaku Narumi, Toshikatu Kaburaki, Hiroyuki Yoneyama, Hiroyuki Iwamura, Yuko Kobayashi, Kouji Matsushima
    European journal of immunology 32 (6) 1784 - 91 0014-2980 2002/06 [Refereed][Not invited]
     
    We examined the effect of a monoclonal antibody (mAb) against interferon (IFN)-inducible protein 10 (IP-10)/CXCL10 on the development of experimental autoimmune encephalomyelitis (EAE) in rats induced by injecting xenogeneic brain homogenates into footpads. Treatment with neutralizing mAb against CXCL10 exacerbated EAE with increased infiltrating CD4+ cells in the central nervous system. Furthermore, the exacerbation by the mAb treatment was accompanied by less enlarged draining popliteal lymph nodes (LN) in parallel with cell number compared with those of EAE rats treated with control mAb, whereas other lymphoid organs such as the spleen and thymus were not significantly different between rats treated with anti-CXCL10 and the control mAb. Induction of gene expression of CXCL9/Mig and CXCL10 and their receptor CXCR3 was confirmed in the draining LN in EAE rats. Induction of the third CXCR3 ligand, CXCL11/I-TAC was not seen in the draining LN, whereas all three CXCR3 ligands and CXCR3 itself were markedly detected in the spinal cords following the development of EAE. These findings suggest that CXCL10 produced in the LN plays a specific inhibitory role in the development of Th1-mediated diseases such as EAE by holding sensitized and activated Th1s expressing CXCR3 in the draining LN.
  • T Kaburaki, M Nakamura, K Nagasawa, M Nagahara, S Joko, Y Fujino
    JAPANESE JOURNAL OF OPHTHALMOLOGY 45 (6) 628 - 633 0021-5155 2001/11 [Refereed][Not invited]
     
    Background: Frosted branch angiitis usually occurs in children, and has a good prognosis. We report two cases of unilateral frosted branch angiitis in adults. Both had poor visual outcomes because of associated central retinal vein occlusion and neovascular glaucoma. Cases: Case 1 was a 36-year-old woman. Almost all retinal veins and some retinal arteries showed vasculitis in her right eye, and veins were slightly dilated and sheathed. Case 2 was a 23-year-old woman. Angle hypopyon was observed in her left eye. Retinal veins were dilated, meandering, and sheathed. Retinal hemorrhages were also observed. In both cases, after systemic steroid therapy the retinal vasculitis gradually decreased, but central retinal vein occlusions gradually developed. Despite systemic administration of urokinase and panretinal photocoagulation, neovascular glaucoma developed, and visual acuity diminished in both cases. Conclusions: Two cases of frosted branch angiitis complicated by retinal vein occlusion are reported. Careful observation of retinal blood flow is necessary in frosted branch angiitis in adults. (C) 2001 Japanese Ophthalmological Society.
  • Y Kato, J Numaga, S Kato, T Kaburaki, H Kawashima, Y Fujino
    Clinical & experimental ophthalmology 29 (5) 335 - 6 1442-6404 2001/10 [Refereed][Not invited]
  • A K Adhikary, J Numaga, T Kaburaki, H Kawashima, S Kato, M Araie, K Miyata, H Shimizu, F Yagyu, E Suzuki, H Ushijima
    Investigative ophthalmology & visual science 42 (9) 2010 - 5 0146-0404 2001/08 [Refereed][Not invited]
     
    PURPOSE: To develop a new detection and typing method of oculopathogenic strains of subgenus D adenoviruses directly from conjunctival scrapings by a combination of polymerase chain reaction (PCR) and restriction enzyme analysis (REA). METHODS: A new PCR method using primer pairs of AF2/AR2, which are specific for the fiber genes, were developed to amplify 1150-bp products from nine oculopathogenic prototypes of subgenus D adenoviruses. Amplicons were cleaved with three restriction enzymes: DdeI, HinfI, and RsaI. Clinical specimens of 102 conjunctival scrapings were also evaluated by this PCR method. Restriction patterns of prototypes were used for the typing of clinical samples. Detection limit was determined by the PCR amplification of a known amount of purified adenovirus serotype 8 DNA. RESULTS: A novel PCR method based on the fiber genes allowed the amplification of nine oculopathogenic serotypes of subgenus D (Ad8, Ad9, Ad15, Ad17, Ad19, Ad22, Ad28, Ad37, and Ad39). As little as 38.4 fg of adenovirus type 8 could be detected by this method. Positive results were obtained from 48 of 102 samples (47%) by both hexon- and fiber-based PCR, whereas only 29 of 102 (28.4%) yielded positive results by culture isolation/neutralization test (NT). All positive specimens (29 samples) of culture isolation and PCR-RFLP methods showed positive results by our new fiber-based PCR method, and no positive products were detected from other subgenus of adenovirus or nonadenoviral DNA. CONCLUSIONS: A newly developed fiber-based PCR-REA method for the detection and typing of adenoviruses is faster than any former PCR methods. This all-in-1-day detection and typing method will be quite useful to the rapid diagnosis of subgenus D adenovirus infection.
  • T Kaburaki, S Nakamura, K Nagasawa, M Nagahara, S Joko, Y Fujino
    Nippon Ganka Gakkai zasshi 103 (8) 617 - 25 0029-0203 1999/08 [Refereed][Not invited]
     
    BACKGROUND: Frosted retinal angiitis usually occurs in children, and has a good prognosis. We report two cases of unilateral frosted retinal angiitis in adults. They resulted in visual degradation because of associated central retinal vein occlusion and neovascular glaucoma. CASES: Case 1 was a 36-year-old female. Almost all retinal veins and some retinal arteries had vasculitis in her right eye, and the veins were slightly dilated and sheathed. Case 2 was a 23-year-old female. Angle hypopyon was observed in her left eye. Retinal veins were dilated, meandered, and sheathed. Retinal hemorrhages were also observed. In both cases, systemic steroid therapy gradually improved the retinal vasculitis, but central retinal vein occlusions gradually developed, and in spite of systemic administration of urokinase and panretinal photocoagulation, neovascular glaucoma developed, and visual acuity became degraded in both cases. CONCLUSION: Two cases of frosted retinal angiitis complicated by retinal vein occlusion were reported. Careful observation of retinal blood flow is necessary in frosted retinal angiitis in adults.
  • S Yamagami, M Isobe, H Yamagami, J Hori, T Kaburaki, T Tsuru
    Transplantation proceedings 29 (4) 2288 - 9 0041-1345 1997/06 [Refereed][Not invited]
  • H Obata, T Kaburaki, M Kato, H Yamashita
    Current eye research 15 (3) 335 - 40 0271-3683 1996/03 [Refereed][Not invited]
     
    Transforming growth factor beta (TGF-beta) transduces signals through mediation of type I and type II serine/threonine kinase receptors. The expression of TGF-beta type I (T beta R-I) and II (T beta R-II) receptors in rat eyes was investigated immunohistochemically. T beta R-I and T beta R-II immunoreactivity was detected in corneal and conjunctival epithelial cells, corneal endothelial cells, ciliary epithelial cells, lens epithelial cells, retinal pigment epithelial cells, and choroidal vessels. This co-expression of T beta R-I and T beta R-II indicates that the above cells respond to TGF-beta and, because TGF-beta is reported to be produced in ocular tissues, that it may have important autocrine and/or paracrine roles in the growth and metabolism of ocular tissues in situ.
  • M Aihara, M Araie, T Kaburaki, S Shirato
    Nippon Ganka Gakkai zasshi 98 (6) 540 - 4 0029-0203 1994/06 [Refereed][Not invited]
     
    We investigated the effects of long-term instillation of bunazosin hydrochloride--alpha 1 specific adrenergic antagonist--on the aqueous humor dynamics and blood-aqueous barrier in rabbit eyes. We examined intraocular pressure, aqueous flow rate, and blood-aqueous barrier permiability for albumin after four weeks application of 0.05% bunazosin. The effect of bunazosin on blood-aqueous barrier destruction by laser iridophotocoagulation was also examined. During four weeks, bunazosin reduced the intraocular pressure by 1.7 +/- 0.6 mmHg (mean +/- SEM). Continuous application of bunazosin had no significant influence on aqueous flow rate and fluorescein isothiocyanate-labeled rabbit albumin (FITC-Alb) concentration in the anterior chamber. Bunazosin had no effect on the rise of the FITC-Alb concentration after iris photocoagulation, but the intraocular pressure in bunazosin treated eyes was significantly lower than in control eyes one hour after photocoagulation.

MISC

  • 三好由希子, 田中理恵, 伊沢英知, 南貴紘, 小前恵子, 小野久子, 曽我拓嗣, 白濱新多朗, 蕪城俊克  日本眼科学会雑誌  125-  2021
  • Yukiko Terada, Toshikatsu Kaburaki, Hiroshi Takase, Satoko Nakano, Hiroshi Goto, Yoshitsugu Inoue, Kazuichi Maruyama, Kazunori Miyata, Kenichi Namba, Koh-hei Sonoda, Yutaka Kaneko, Jiro Numaga, Manabu Mochizuki  INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  61-  (7)  2020/06  
    0
  • Nozomi Igarashi, Megumi Honjo, Reiko Yamagishi, Makoto Kurano, Yutaka Yatomi, Koji Igarashi, Toshikatsu Kaburaki, Makoto Aihara  Scientific reports  10-  (1)  6265  -6265  2020/04  [Refereed][Not invited]
     
    To examine whether autotaxin (ATX) in the aqueous humor causes elevated intraocular pressure (IOP) in patients with Posner-Schlossman syndrome (PSS). ATX and transforming growth factor beta (TGF-β) in the aqueous humor were quantified in PSS patients. The expression of ATX and TGF-β in cytomegalovirus (CMV)-infected-human trabecular meshwork (hTM) cells was examined. Biological changes in hTM cells and monkey Schlemm's canal endothelial (SCE) cells cultured in the conditioned medium of CMV-infected hTM cells were analyzed. The expression of ATX and TGF-β1 was upregulated in the aqueous humor of CMV-positive PSS patients, and the level of ATX in the aqueous humor was positively correlated with IOP. CMV infection upregulated ATX and TGF-β1 in hTM cells. The conditioned medium induced fibrotic changes in hTM cells and reduced SCE permeability, which was attenuated by an ATX inhibitor, a lysophosphatidic acid receptor antagonist, and a Rho kinase inhibitor. ATX in the aqueous humor induced by CMV infection may trigger elevated IOP. Modulating ATX activity may be a novel treatment modality for PSS.
  • Tatsuaki Amari, Ryo Obata, Asahi Fujita, Takahiro Minami, Motoshi Yamamoto, Asako Ogawa, Daisuke Santo, Nobuyori Aoki, Masahiro Yamanari, Satoshi Sugiyama, Susumu Oshima, Keiko Azuma, Megumi Honjo, Toshikatsu Kaburaki, Makoto Aihara, Satoshi Kato  INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  60-  (9)  2019/07  
    0
  • Takahiro Minami, Nobuyori Aoki, Masahiro Yamanari, Satoshi Sugiyama, Susumu Oshima, Motoshi Yamamoto, Daisuke Santo, Ryo Obata, Megumi Honjo, Toshikatsu Kaburaki, Makoto Aihara, Satoshi Kato  INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  60-  (9)  2019/07  
    0
  • 大野 重昭, 岡田 アナベルあやめ, 後藤 浩, 南場 研一, 北市 伸義, 有賀 俊英, 石原 麻美, 臼井 嘉彦, 大黒 伸行, 蕪城 俊克, 慶野 博, 杉田 直, 鈴木 潤, 園田 康平, 堤 雅幸, 中尾 久美子, 堀江 幸弘, 水木 信久, 八代 成子, 横井 克俊, 日本眼炎症学会ぶどう膜炎診療ガイドライン作成委員会  日本眼科学会雑誌  123-  (6)  635  -696  2019/06  [Not refereed][Not invited]
  • 後藤 浩, 南場 研一, 蕪城 俊克, 毛塚 剛司, 園田 康平, 高瀬 博, 大黒 伸行, 大野 重昭, 水木 信久, 日本眼炎症学会TNF阻害薬使用検討委員会  日本眼科学会雑誌  123-  (6)  697  -705  2019/06  [Not refereed][Not invited]
  • 脳炎・視神経障害が全身の炎症所見に先行した再発性多発軟骨炎の71歳女性例
    宮野 涼至, 織茂 賢太, 栗原 正典, 蕪城 俊克, 西嶌 大宣, 池村 雅子, 間野 達雄, 濱田 雅, 林 俊宏, 戸田 達史  日本内科学会関東地方会  638回-  39  -39  2017/12  [Not refereed][Not invited]
  • 根本 穂高, 蕪城 俊克, 田中 理恵, 大友 一義, 高本 光子, 川島 秀俊, 藤野 雄次郎, 相原 一  あたらしい眼科  34-  (5)  707  -712  2017/05
  • 日本サルコイドーシスにおけるHLA領域の疾患感受性遺伝子
    石原 麻美, 目黒 明, 南場 研一, 大野 重昭, 蕪城 俊克, 高瀬 博, 望月 學, 後藤 浩, 竹内 大, 堀 純子, 北市 伸義, 水木 信久  日本眼科学会雑誌  121-  (臨増)  172  -172  2017/03  [Not refereed][Not invited]
  • 後藤 浩, 南場 研一, 蕪城 俊克, 毛塚 剛司, 園田 康平, 高瀬 博, 大黒 伸行, 大野 重昭, 水木 信久, 日本眼炎症学会TNF阻害薬使用検討委員会  日本眼科学会雑誌  121-  (1)  34  -41  2017/01  [Not refereed][Not invited]
  • 非感染性ぶどう膜炎に対するTNF阻害薬使用指針および安全対策マニュアル(2016年版)
    後藤 浩, 南場 研一, 蕪城 俊克, 毛塚 剛司, 園田 康平, 高瀬 博, 大黒 伸行, 大野 重昭, 水木 信久, 日本眼炎症学会T, 阻害薬使用検討委員会  日本眼科学会雑誌  121-  (1)  34  -41  2017/01  [Not refereed][Not invited]
  • Junko Matsuda, Toshikatsu Kaburaki, Rie Tanaka, Mitsuko Takamoto, Hisae Nakahara, Kazuyoshi Ohtomo, Yujiro Fujino, Jiro Numaga, Hideomi Yamashita, Mineo Kurokawa, Makoto Aihara  INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  57-  (12)  2016/09  [Not refereed][Not invited]
  • Rie Tanaka, Kazuyoshi Ohtomo, Mitsuko Takamoto, Keiko Komae, Jiro Numaga, Yujiro Fujino, Makoto Aihara, Toshikatsu Kaburaki  INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  57-  (12)  2016/09  [Not refereed][Not invited]
  • Hisae Nakahara, Toshikatsu Kaburaki, Rie Tanaka, Kazuyoshi Ohtomo, Mitsuko Takamoto, Ayako Karakawa, Kimiko Okinaga, Junko Matsuda, Yujiro Fujino, Hidetoshi Kawashima, Makoto Aihara  INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE  57-  (12)  2016/09  [Not refereed][Not invited]
  • ゲノムワイド関連解析を用いた眼サルコイドーシス感受性遺伝子のスクリーニング
    石原 麻美, 目黒 明, 南場 研一, 大野 重昭, 蕪城 俊克, 高瀬 博, 望月 學, 後藤 浩, 竹内 大, 堀 純子, 北市 伸義, 水木 信久  日本眼科学会雑誌  120-  (臨増)  223  -223  2016/03  [Not refereed][Not invited]
  • Toshikatsu Kaburaki, Shinji Harihara, Rie Tanaka, Hiromasa Sawamura, Ai Nishi, Atsushi Hatamochi, Jun Shimizu, Masumi Takeuchi, Shoji Kuwata, Hidetoshi Kawashima, Fujio Takeuchi  ARTHRITIS & RHEUMATOLOGY  67-  2015/10  [Not refereed][Not invited]
  • Sachiko Takada, Rie Tanaka, Naoyuki Kurita, Kiyoshi Ishii, Toshikatsu Kaburaki  Clinical & experimental ophthalmology  43-  (6)  593  -4  2015/08  [Refereed][Not invited]
  • 日本人における新規サルコイドーシス関連候補遺伝子
    石原 麻美, 目黒 明, 南場 研一, 大野 重昭, 蕪城 俊克, 高瀬 博, 望月 學, 後藤 浩, 竹内 大, 堀 純子, 北市 伸義, 水木 信久  日本眼科学会雑誌  119-  (臨増)  188  -188  2015/03  [Not refereed][Not invited]
  • Rie Tanaka, Ryo Obata, Hiromasa Sawamura, Kazuyoshi Ohtomo, Toshikatsu Kaburaki  Canadian journal of ophthalmology. Journal canadien d'ophtalmologie  49-  (5)  e115-8  -E118  2014/10  [Refereed][Not invited]
  • 結核性ぶどう膜炎の臨床像および治療予後の検討
    多田 明日美, 岩橋 千春, 中井 慶, 南場 研一, 田岡 アナベルあやめ, 高瀬 博, 後藤 浩, 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  118-  (10)  857  -857  2014/10  [Not refereed][Not invited]
  • KABURAKI Toshikatsu, KAWASHIMA Hidetoshi  あたらしい眼科 = Journal of the eye  30-  (3)  329  -335  2013/03
  • Kazuki Taoka, Go Yamamoto, Toshikatsu Kaburaki, Tsuyoshi Takahashi, Makoto Araie, Mineo Kurokawa  British journal of haematology  157-  (2)  252  -4  2012/04  [Refereed][Not invited]
  • 大野 重昭, 蕪城 俊克, 北市 伸義, 後藤 浩, 南場 研一, 水木 信久, 飛鳥田 有里, 坂本 俊哉, 渋谷 悦子, 藤野 雄次郎, 目黒 明, 横井 克俊, ベーチェット病眼病変診療ガイドライン作成委員会  日本眼科学会雑誌  116-  (4)  394  -426  2012/04  [Not refereed][Not invited]
  • サルコイドーシスにおけるTLR(toll-like receptor)遺伝子多型解析
    石原 麻美, 目黒 明, 勝山 善彦, 森本 紳一郎, 南場 研一, 北市 伸義, 蕪城 俊克, 岳中 耐夫, 猪子 英俊, 水木 信久, 太田 正穂  日本サルコイドーシス/肉芽腫性疾患学会雑誌  31-  (サプリメント号)  37  -37  2011/10  [Not refereed][Not invited]
  • 石ケ坪良明, 岳野光洋, 廣畑俊成, 黒沢美智子, 大野重昭, 蕪城俊克, 新見正則, 水木信久, 後藤浩, 金子史男, 中村晃一郎, 菊地弘敏  ベーチェット病に関する調査研究 平成21年度 総括・分担研究報告書  11  -22  2010  [Not refereed][Not invited]
  • 日本人サルコイドーシスにおけるannexin A11(ANX A11)遺伝子多型解析
    石原 麻美, 目黒 明, 高野 翠, 森本 紳一郎, 南場 研一, 北市 伸義, 蕪城 俊克, 岳中 耐夫, 安藤 靖恭, 猪子 英俊, 河合 憲司, 水木 信久  日本サルコイドーシス/肉芽腫性疾患学会雑誌  29-  (サプリメント号)  34  -34  2009/10  [Not refereed][Not invited]
  • butyrophilin-like 2(BTNL2)遺伝子はサルコイドーシスの新しい疾患感受性遺伝子か?
    石原 麻美, 目黒 明, 水木 信久, 南場 研一, 北市 伸義, 大野 重昭, 蕪城 俊克, 安藤 靖恭, 太田 正穂  日本眼科学会雑誌  113-  (10)  999  -1000  2009/10  [Not refereed][Not invited]
  • 目黒 明, 石原 麻美, 勝山 善彦, 南場 研一, 蕪城 俊克, 安藤 靖恭, 森本 紳一郎, 岳中 耐夫, 大野 重昭, 猪子 英俊, 水木 信久, 太田 正穂  MHC: Major Histocompatibility Complex  15-  (2)  161  -161  2008/08  [Not refereed][Not invited]
  • Mitsuko Takamoto, Toshikatsu Kaburaki, Jiro Numaga, Yujiro Fujino, Hidetoshi Kawashima  JAPANESE JOURNAL OF OPHTHALMOLOGY  51-  (3)  239  -240  2007/05  [Not refereed][Not invited]
  • KABURAKI Toshikatsu, KAWASHIMA Hidetoshi  あたらしい眼科 = Journal of the eye  21-  (1)  13  -19  2004/01

Awards & Honors

  • 2019/04 Japanese Society of Ophthalmology Japan Ophthalmology Society Council Award
     
    受賞者: Toshikatsu Kaburaki

Research Grants & Projects

  • ベーチェット病に関する調査研究
    厚生労働省:厚生労働省科学研究費補助金
    Date (from‐to) : 2020/04 -2022/03 
    Author : 岳野 光洋
  • ベーチェット病の病態解明および治療法開発を目的とした全国レジストリの構築
    AMED:AMED難治性疾患実用化研究事業
    Date (from‐to) : 2020/04 -2022/03 
    Author : 水木信久
  • 眼内悪性リンパ腫に対するブルトンキナーゼ阻害剤を用いた中枢再発予防法による医師主導多施設共同治験
    AMED:AMED革新的がん医療実用化研究事業領域3
    Date (from‐to) : 2019/04 -2022/03 
    Author : 田岡和城
  • ヒト網膜動脈および静脈血管内皮細胞のエピゲノム解析
    日本学術振興会:日本学術振興会研究補助金
    Date (from‐to) : 2018/04 -2021/03
  • 難治性眼内悪性リンパ腫に対する副作用を軽減させたBruton型チロシンキナーゼ阻害剤を用いた治療プロトコールの作成
    AMED:AMED医療シーズ実用化事業
    Date (from‐to) : 2018/04 -2019/03 
    Author : 田岡和城
  • ベーチェット病に関する調査研究
    厚生労働省:厚生労働省科学研究費補助金
    Date (from‐to) : 2017/04 -2019/03 
    Author : 水木信久
  • エクソーム解析による眼内悪性リンパ腫の原因遺伝子同定(田中 理恵)
    日本学術振興会:基盤研究C
    Date (from‐to) : 2016/04 -2019/03 
    Author : 田中 理恵
  • 東アジア調査に基づくベーチェット病、強皮症の特異的HLAが病態に関わる機序の研究(竹内 二士夫)
    日本学術振興会:科学研究費補助金 (基盤研究(B)海外学術調査)
    Date (from‐to) : 2016/04 -2019/03 
    Author : 竹内 不二夫
  • ベーチェット病に関する調査研究(水木 信久)
    厚生労働省科学研究費補助金:難治性疾患実用化研究事業
    Date (from‐to) : 2014/04 -2017/03 
    Author : 蕪城 俊克
  • 眼瞼痙攣の疾患感受性遺伝子の研究
    日本学術振興会:基盤研究C
    Date (from‐to) : 2014/04 -2017/03 
    Author : 蕪城 俊克
  • ベーチェット病に関する調査研究
    厚生労働省:厚生労働省科学研究費補助金
    Date (from‐to) : 2014/04 -2016/03 
    Author : 水木信久
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