Use of explainable AI on slit-lamp images of anterior surface of eyes to diagnose allergic conjunctival diseases.
Michiko Yonehara, Yuji Nakagawa, Yuji Ayatsuka, Yuko Hara, Jun Shoji, Nobuyuki Ebihara, Takenori Inomata, Tianxiang Huang, Ken Nagino, Ken Fukuda, Tatsuma Kishimoto, Tamaki Sumi, Atsuki Fukushima, Hiroshi Fujishima, Moeko Kawai, Etsuko Takamura, Eiichi Uchio, Kenichi Namba, Ayumi Koyama, Tomoko Haruki, Shin-Ich Sasaki, Yumiko Shimizu, Dai Miyazaki
Allergology international : official journal of the Japanese Society of Allergology, 2024年08月17日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Artificial intelligence (AI) is a promising new technology that has the potential of diagnosing allergic conjunctival diseases (ACDs). However, its development is slowed by the absence of a tailored image database and explainable AI models. Thus, the purpose of this study was to develop an explainable AI model that can not only diagnose ACDs but also present the basis for the diagnosis. METHODS: A dataset of 4942 slit-lamp images from 10 ophthalmological institutions across Japan were used as the image database. A sequential pipeline of segmentation AI was constructed to identify 12 clinical findings in 1038 images of seasonal and perennial allergic conjunctivitis (AC), atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC), giant papillary conjunctivitis (GPC), and normal subjects. The performance of the pipeline was evaluated by determining its ability to obtain explainable results through the extraction of the findings. Its diagnostic accuracy was determined for 4 severity-based diagnosis classification of AC, AKC/VKC, GPC, and normal. RESULTS: Segmentation AI pipeline efficiently extracted crucial ACD indicators including conjunctival hyperemia, giant papillae, and shield ulcer, and offered interpretable insights. The AI pipeline diagnosis had a high diagnostic accuracy of 86.2%, and that of the board-certified ophthalmologists was 60.0%. The pipeline had a high classification performance, and the area under the curve (AUC) was 0.959 for AC, 0.905 for normal subjects, 0.847 for GPC, 0.829 for VKC, and 0.790 for AKC. CONCLUSIONS: An explainable AI model created by a comprehensive image database can be used for diagnosing ACDs with high degree of accuracy.

若年性慢性虹彩毛様体炎の臨床像の検討　　　　　　　　　　　　　　　
鈴木 佳代, 南場 研一, 金子 優, 大黒 伸行, 竹内 正樹, 伊東 崇子, 永田 健児, 臼井 嘉彦, 蕪城 俊克, 田中 理恵, 柳井 亮二, 楠原 仙太郎, 慶野 博, 丸山 和一, 竹内 大, 若年性慢性虹彩毛様体炎研究グループ
日本眼科学会雑誌, 128, 臨増, 208, 208, (公財)日本眼科学会, 2024年03月
日本語

A case of tubulointerstitial nephritis and uveitis syndrome accompanied by subclinical choroiditis.
Takuya Arita, Kenichi Namba, Daiju Iwata, Kayo Suzuki, Yo Ogino, Kazuomi Mizuuchi, Miki Hiraoka, Nobuyoshi Kitaichi, Susumu Ishida
BMC ophthalmology, 23, 1, 424, 424, 2023年10月20日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Tubulointerstitial nephritis and uveitis (TINU) syndrome is an uveits characterized by complications of idiopathic acute tubulointerstitial nephritis, and most cases present only anterior uveitis. We report a case of TINU syndrome in which the presence of choroiditis was revealed by multimodal imaging. CASE PRESENTATION: A 12-year-old male visited our hospital with a 6-day history of ocular pain and hyperemia. Conjunctival and ciliary injections, 1 + flare and 3 + cells of anterior chamber inflammation with mutton fat keratic precipitates were observed in both eyes (OU), together with redness and swelling of the optic disc OU. Laboratory tests showed slightly high levels of soluble IL-2R and serum β2 microglobulin and markedly high levels of urinary β2 microglobulin. The diagnosis of probable TINU syndrome was established on the basis of bilateral uveitis and urinalysis results in accordance with a clinical criteria of tubulointerstitial nephritis. With treatment with oral prednisolone (PSL) at 20 mg/day, ocular findings improved, and the dose of PSL was gradually reduced and withdrawn 6 months later. However, 1 month later from the withdrawal, ocular inflammation recurred with the presence of retinal exudates and snowball vitreous opacities in the peripheral retina OU. Fluorescein angiography showed leakages from peripheral retinal vessels and staining corresponding to retinal exudates. Indocyanine green angiography showed hypofluorescent dots scattered over the ocular fundus. Optical coherence tomography revealed the presence of choroidal thickening. Laser speckle flowgraphy color map showed a relatively cooler color. Findings from these multimodal images indicated the presence of subclinical choroiditis; therefore, oral PSL was administered again, and ocular inflammatory findings were improved. CONCLUSIONS: TINU syndrome can exhibit subclinical choroiditis detected with multimodal imaging. Further studies are necessary to determine the frequency of subclinical choroiditis in TINU syndrome.

A case of APMPPE-like panuveitis presenting with extensive outer retinal layer impairment following COVID-19 vaccination.
Yo Ogino, Kenichi Namba, Daiju Iwata, Kayo Suzuki, Kazuomi Mizuuchi, Miki Hiraoka, Nobuyoshi Kitaichi, Susumu Ishida
BMC ophthalmology, 23, 1, 233, 233, 2023年05月24日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Vaccination against the worldwide pandemic coronavirus disease 2019 (COVID-19) is underway; however, some cases of new onset uveitis after vaccination have been reported. We report a case of bilateral acute posterior multifocal placoid pigment epitheliopathy-like (AMPPE-like) panuveitis after COVID-19 vaccination in which the patient's pathological condition was evaluated using multimodal imaging. CASE PRESENTATION: A 31-year-old woman experienced bilateral hyperemia and blurred vision starting 6 days after her second inoculation of the COVID-19 vaccination. At her first visit, her visual acuity was decreased bilaterally, and severe bilateral anterior chamber inflammation and bilateral scattering of cream-white placoid lesions on the fundus were detected. Optical coherence tomography (OCT) showed serous retinal detachment (SRD) and choroidal thickening in both eyes (OU). Fluorescein angiography (FA) revealed hypofluorescence in the early phase and hyperfluorescence in the late phase corresponding to the placoid legions. Indocyanine green angiography (ICGA) showed sharply marginated hypofluorescent dots of various sizes throughout the mid-venous and late phases OU. The patient was diagnosed with APMPPE and was observed without any medications. Three days later, her SRD disappeared spontaneously. However, her anterior chamber inflammation continued, and oral prednisolone (PSL) was given to her. Seven days after the patient's first visit, the hyperfluorescent lesions on FA and hypofluorescent dots on ICGA partially improved; however, the patient's best corrected visual acuity (BCVA) recovered only to 0.7 OD and 0.6 OS, and the impairment of the outer retinal layer was broadly detected as hyperautofluorescent lesions on fundus autofluorescence (FAF) examination and as irregularity in or disappearance of the ellipsoid and interdigitation zones on OCT, which were quite atypical for the findings of APMPPE. Steroid pulse therapy was performed. Five days later, the hyperfluorescence on FAF had disappeared, and the outer retinal layer improved on OCT. Moreover, the patient's BCVA recovered to 1.0 OU. Twelve months after the end of treatment, the patient did not show any recurrences. CONCLUSIONS: We observed a case of APMPPE-like panuveitis after COVID-19 vaccination featuring some atypical findings for APMPPE. COVID-19 vaccination may induce not only known uveitis but also atypical uveitis, and appropriate treatment is required for each case.

The Steroid-Sparing Effect of Adalimumab in the Treatment for the Recurrent Phase of Vogt-Koyanagi-Harada Disease.
Mayuko Shinagawa, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Keitaro Hase, Kayo Suzuki, Kiriko Hirooka, Nobuyoshi Kitaichi, Miki Hiraoka, Susumu Ishida
Ocular immunology and inflammation, 31, 3, 501, 505, 2023年04月, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: To reveal the steroid-sparing effect of adalimumab (ADA) in the treatment for the chronic recurrent phase of Vogt-Koyanagi-Harada (VKH) disease. CASES AND METHODS: Thirty-six eyes from 18 cases of the recurrent phase of VKH disease treated with ADA over 12 months were examined retrospectively. Before the introduction of ADA, 4 cases received prednisolone (PSL) monotherapy and other 14 cases received PSL and cyclosporine A (CYA) combination therapy. RESULTS: In cases treated with PSL and CYA, CYA was discontinued when ADA was introduced. The minimum dose of PSL to control intraocular inflammation (min dose of PSL) could be reduced in all cases after the introduction of ADA (from 16.9 ± 7.9 mg to 6.3 ± 3.1 mg). No serious adverse events were observed in the observational periods. CONCLUSION: By comparing the min dose of PSL before and after the introduction of ADA, the steroid-sparing effect of ADA was confirmed.

A Case of Intraocular Metastasis of Lung Cancer Diagnosed Using Cell Block Preparation of the Vitreous Humor.
Kohei Matsumoto, Satoru Kase, Kenichi Namba, Daiju Iwata, Yoshihiro Matsuno, Susumu Ishida
Cancer diagnosis & prognosis, 3, 1, 130, 134, 2023年, ［国際誌］
英語, BACKGROUND/AIM: Masquerade syndrome is characterized by uveitis-like manifestations caused by tumor cell infiltration into the ocular tissues. The aim of the study was to report a lung cancer patient with persistent unilateral vitreous opacity, who was eventually diagnosed with masquerade syndrome using cell block preparation. CASE REPORT: An 82-year-old female complained of blurred vision in her left eye (OS). Because of pulmonary adenocarcinoma, she had previously received anticancer drug treatment at another Hospital and achieved partial remission. Ophthalmic examinations revealed anterior chamber inflammation and vitreous opacity OS. Corticosteroid eye drops were administered, but the inflammation did not improve, and was referred to the Hokkaido University Hospital. The left best-corrected visual acuity was 0.1 with normal intraocular pressure. Anterior chamber inflammation was 2+ cells, and vitreous haze was 4+ OS. B-mode ultrasonography showed diffuse heterogeneous high echoic changes in the vitreous cavity. She underwent vitrectomy, and cell block preparation of the vitreous infusion fluids was performed. Cytopathology revealed adenocarcinoma cells with a high nuclear/cytoplasmic ratio and glandular formation. The immunocytochemical study showed that tumor cells were positive for thyroid transcription factor-1 (TTF-1), napsin A, and CK7, therefore diagnosis of masquerade syndrome due to intraocular metastasis of pulmonary adenocarcinoma was reached. Chemoradiotherapy was administered, and the eye got phthisis bulbi after irradiation 2 years after diagnosis. CONCLUSION: Cell block preparation using vitreous humor may be useful in the diagnosis and management of intraocular metastasis of pulmonary adenocarcinoma in patients with prolonged vitreous opacity.

Involvement of Angiopoietin 2 and vascular endothelial growth factor in uveitis.
Kayo Suzuki, Daiju Iwata, Kenichi Namba, Keitaro Hase, Miki Hiraoka, Miyuki Murata, Nobuyoshi Kitaichi, Richard Foxton, Susumu Ishida
PloS one, 18, 11, e0294745, 2023年, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: Angiopoietin (Ang) 2 is released from vascular endothelial cells by the stimulation of vascular endothelial growth factor (VEGF)A. Ang2 increases the expression of leukocyte adhesion molecules on endothelial cells via nuclear factor κB. The aim of this study was to evaluate the effects of Ang2 and VEGFA on ocular autoimmune inflammation. METHODS: We measured the concentrations of Ang2 and VEGFA in vitreous samples among patients with uveitis. Vitreous samples were collected from 16 patients with idiopathic uveitis (uveitis group) and 16 patients with non-inflammatory eye disease (control group). Experimental autoimmune uveoretinitis (EAU) was induced in B10.BR mice with a human interphotoreceptor retinoid-binding protein-derived peptide. The retinochoroidal tissues of the EAU mice were removed, and the mRNA levels of Ang2 and VEGFA were examined. EAU mice treated with anti-Ang2, anti-VEGFA, a combination of anti-Ang2 and anti-VEGFA, anti-Ang2/VEGFA bispecific, or IgG control antibodies were clinically and histopathologically evaluated. RESULTS: The protein levels of Ang2 and VEGFA were significantly higher in the vitreous samples of patients with uveitis than in controls (P<0.05). The retinochoroidal mRNA levels of Ang2 and VEGFA were significantly upregulated in EAU mice compared to controls (n = 6, P<0.05). Although there was no significant difference, treatment with anti-VEGFA antibody reduced the clinical and histopathological scores. However, treatment with anti-Ang2 antibody reduced the clinical and histopathological scores (n = 18-20, P<0.05). Furthermore, these scores were further decreased when treated by inhibiting both Ang2 and VEGFA. CONCLUSIONS: Based on these results, VEGFA and Ang2 were shown to be upregulated locally in the eye of both uveitis patients and models of uveitis. Dual inhibition of Ang2 and VEGFA is suggested to be a new therapeutic strategy for uveitis.

Ten-year follow-up of infliximab treatment for uveitis in Behçet disease patients: A multicenter retrospective study.
Masaru Takeuchi, Yoshihiko Usui, Kenichi Namba, Hiroshi Keino, Masaki Takeuchi, Hiroshi Takase, Koju Kamoi, Keitaro Hase, Takako Ito, Kei Nakai, Kazuichi Maruyama, Eri Kobayashi, Hisashi Mashimo, Tomohito Sato, Nobuyuki Ohguro, Junko Hori, Annabelle A Okada, Koh-Hei Sonoda, Nobuhisa Mizuki, Hiroshi Goto
Frontiers in medicine, 10, 1095423, 1095423, 2023年, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: To evaluate 10-year outcome of infliximab (IFX) treatment for uveitis in Behçet disease (BD) patients using a standardized follow-up protocol. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: 140 BD uveitis patients treated with IFX enrolled in our previous study. METHODS: Medical records were reviewed for demographic information, duration of IFX treatment, number of ocular attacks before IFX initiation, best corrected visual acuity (VA) at baseline and 1, 2, 3, 4, 5, and 10 years after IFX initiation, uveitis recurrence after IFX initiation and main anatomical site, concomitant therapies, and adverse events (AEs). MAIN OUTCOME MEASURES: 10-year IFX continuation rate and change in LogMAR VA. RESULTS: Of 140 BD patients, 106 (75.7%) continued IFX treatment for 10 years. LogMAR VA improved gradually after initiation of IFX, and the improvement reached statistical significance from 2 years of treatment. Thereafter, significant improvement compared with baseline was maintained until 10 years, despite a slight deterioration of logMAR VA from 5 years. However, eyes with worse baseline decimal VA < 0.1 showed no significant improvement from baseline to 10 years. Uveitis recurred after IFX initiation in 50 patients (recurrence group) and did not recur in 56 (non-recurrence group). Ocular attacks/year before IFX initiation was significantly higher in the recurrence group (2.82 ± 3.81) than in the non-recurrence group (1.84 ± 1.78). In the recurrence group, uveitis recurred within 1 year in 58% and within 2 years in 74%. Seventeen patients (34%) had recurrent anterior uveitis, 17 (34%) had posterior uveitis, and 16 (32%) had panuveitis, with no significant difference in VA outcome. In addition, logMAR VA at 10 years did not differ between the recurrence and non-recurrence groups. AEs occurred among 43 patients (30.7%), and 24 (17.1%) resulted in IFX discontinuation before 10 years. CONCLUSIONS: Among BD patients with uveitis who initiated IFX, approximately 75% continued treatment for 10 years, and their VA improved significantly and was maintained for 10 years. Uveitis recurred in one-half of the patients, but visual acuity did not differ significantly from the patients without recurrence.

Fundus autofluorescence imaging in acute posterior multifocal placoid pigment epitheliopathy.
Koichi Yokoi, Kenichi Namba, Daiju Iwata, Kazuomi Mizuuchi, Keitaro Hase, Kayo Suzuki, Ryo Ando, Kiriko Hirooka, Nobuko Sekine, Nobuyoshi Kitaichi, Miki Hiraoka, Susumu Ishida
American journal of ophthalmology case reports, 28, 101732, 101732, 2022年12月, ［国際誌］
英語, PURPOSE: Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is a disease characterized by multiple yellowish-white placoid lesions. Although most lesions resolve spontaneously, some turn into scars and lead to permanent visual dysfunction. In this report, we found suggestive findings in fundus autofluorescence (FAF) that may be useful for distinguishing severe lesions requiring treatment in APMPPE. OBSERVATION: Case 1: A 29-year-old woman was referred to our hospital with multiple yellowish-white placoid lesions on the fundi of both eyes (OU). FAF showed hyperautofluorescence in some of these placoid lesions. Based on the findings of fluorescein angiography, a diagnosis of APMPPE was established, and oral prednisolone (PSL) was initiated, given that some lesions were located in the macula. One week later, exacerbation occurred with the newly developed hyperautofluorescent lesions. Some lesions in the right eye (OD) that were hyperautofluorescent at the first visit became hypoautofluorescent. Afterward, although all hypoautofluorescent lesions persisted, most of the hyperautofluorescent lesions disappeared, so oral PSL could be stopped. Two months later, however, the recurrence occurred along with multiple new placoid lesions. Some lesions located at the macula were hyperautofluorescent on FAF OU, indicating the possibility of becoming scar lesions with hypoautofluorescence. Accordingly, oral PSL was given again. CASE 2: A 47-year-old woman noticed decreased vision OD, and she was referred to us. Multiple yellowish-white placoid lesions were seen in the fundi OU. FAF showed hyperautofluorescence both with and without corresponding hypoautofluorescence in the placoid lesions OU. A diagnosis of APMPPE was established, and oral PSL was initiated. Four months later, some lesions that were hyperautofluorescent at the first visit had turned isoautofluorescent, and some lesions OU became hypoautofluorescent. However, all hypoautofluorescent lesions remained hypoautofluorescent OU. Only some hyperautofluorescent lesions recovered to isoautofluorescence without scars. CONCLUSIONS AND IMPORTANCE: In APMPPE, lesions showing hyperautofluorescence on FAF may change into hypoautofluorescence indicating scar formation. Therefore, the presence of hyperautofluorescent lesions in the macula may be a good indicator of the need for intensive corticosteroid treatments to avoid leaving hypoautofluorescent scars that are related to irreversible visual dysfunction.

Clinical significance of serum and vitreous soluble interleukin-2 receptor in patients with intraocular lymphoma.
Kayo Suzuki, Kenichi Namba, Satoru Kase, Yo Ogino, Keitaro Hase, Daiju Iwata, Kazuomi Mizuuchi, Miki Hiraoka, Nobuyoshi Kitaichi, Susumu Ishida
BMC ophthalmology, 22, 1, 428, 428, 2022年11月10日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Intraocular lymphoma (IOL) is a masquerade syndrome that mimics uveitis, making diagnosis difficult. The serum soluble interleukin-2 receptor (sIL-2R), which is cleaved by matrix metalloproteinase (MMP) -2 and MMP-9, has been recognized as a tumor-related biomarker of malignant lymphomas. The aim of this study was to review the reliability of serum and vitreous sIL-2R for distinguishing IOL from uveitis. METHODS: Patients who underwent diagnostic vitrectomy for marked vitreous haze at Hokkaido University Hospital between April 2014 and June 2019 were enrolled. The patients were divided into an IOL group and a uveitis group, according to the pathology of their vitreous samples. The IOL group was further divided at the time of vitrectomy into patients who already had extraocular involvement (IOL with extraocular involvement group) and patients with no evidence of having extraocular involvement (IOL without extraocular involvement group). Serum sIL-2R, and intravitreal sIL-2R, MMP-2, and MMP-9 levels were assessed. RESULTS: Twenty-five eyes of 25 patients, and 15 eyes of 15 patients were included in the IOL group and uveitis group, respectively. The serum sIL-2R levels were significantly lower in the IOL group than in the uveitis group (P < 0.05), and 20.0% and 66.7% in the IOL and the uveitis group showed high sIL-2R value above the normal range. Vitreous sIL-2R tended to be higher in the IOL group than in the uveitis group (P = 0.80). Serum sIL-2R was significantly lower in the IOL without extraocular involvement group than in the IOL with extraocular involvement group (P < 0.05); 5.9% in the IOL without extraocular involvement group and 50.0% in the IOL with extraocular involvement group showed high sIL-2R value above the normal range. Vitreous sIL-2R, MMP-2, and MMP-9 tended to be higher in the IOL with extraocular involvement group than in the IOL without extraocular involvement group (P = 0.30, < 0.05, 0.16). CONCLUSIONS: Serum sIL-2R is often within the normal range in IOL patients. Even if it is within the normal range, the possibility of IOL should be considered. Serum sIL-2R is not a reliable biomarker for IOL, whereas vitreous sIL-2R may be useful for the diagnosis of IOL.

Executive summary: Japanese guidelines for allergic conjunctival diseases 2021.
Dai Miyazaki, Atsuki Fukushima, Eiichi Uchio, Jun Shoji, Kenichi Namba, Nobuyuki Ebihara, Etsuko Takamura, Ken Fukuda, Akira Matsuda, Shigeki Okamoto, Kazumi Fukagawa, Hiroshi Fujishima, Shigeaki Ohno, Yuichi Ohashi
Allergology international : official journal of the Japanese Society of Allergology, 71, 4, 459, 471, 2022年10月, ［国際誌］
英語, 研究論文（学術雑誌）, Allergic conjunctival disease (ACD) is an inflammatory disease of the conjunctiva that is mainly caused by type I hypersensitivity response to allergens and accompanied by subjective symptoms and other findings induced by antigens. ACD is classified as allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. This article summarizes the third edition of the Japanese guidelines for allergic conjunctival diseases published in 2021 and outlines the diagnosis, pathogenesis, and treatment of ACD. Since the introduction of immunosuppressive eye drops, the treatment strategies for severe ACDs have significantly changed. To clarify the recommended standard treatment protocols for ACD, the advantages and disadvantages of these treatments were assessed using clinical questions, with a focus on the use of steroids and immunosuppressive drugs. This knowledge will assist healthcare providers and patients in taking an active role in medical decision making.

Clinical features of ocular sarcoidosis: severe, refractory, and prolonged inflammation.
Kayo Suzuki, Mami Ishihara, Kenichi Namba, Shigeaki Ohno, Hiroshi Goto, Hiroshi Takase, Shigeru Kawano, Etsuko Shibuya, Keitaro Hase, Daiju Iwata, Kazuomi Mizuuchi, Nobuyoshi Kitaichi, Nobuhisa Mizuki, Susumu Ishida
Japanese journal of ophthalmology, 66, 5, 447, 454, 2022年09月, ［国内誌］
英語, 研究論文（学術雑誌）, PURPOSE: To clarify the proportion of ocular sarcoidosis with severe, refractory, and prolonged inflammation and their association with ocular complications and visual prognosis. STUDY DESIGN: Multicenter, retrospective, longitudinal cohort study. METHODS: Three hundred and twenty-three eyes of 164 patients (45 men; 119 women) with ocular sarcoidosis who visited Hokkaido University Hospital and Yokohama City University Hospital from 2010 to 2015. We newly defined severe, refractory, and prolonged inflammation in ocular sarcoidosis, and investigated their proportions, ocular complications and final visual acuity from medical records of our sarcoidosis patients. RESULTS: The eyes with severe inflammation numbered 72/323 (22.3%), with refractory inflammation, 80/323 (24.8%), and with prolonged inflammation, 91/323 (28.2%). The number of eyes having neither severe, refractory, nor prolonged inflammation (defined as none) was 114/323 (35.3%). The numbers of eyes that reached irreversible visual dysfunction were 6/72 (8.3%) of those with severe inflammation, 10/80 (12.5%) with refractory inflammation, 12/91 (13.2%) with prolonged inflammation, and 4/114 (6.2%) with none. As complications, cataract (62.2%), glaucoma (28.5%), epiretinal membrane (24.1%), cystoid macular edema (22.6%), vitreous hemorrhage (2.8%), choroidal atrophy (2.5%), macular degeneration (1.2%), macular hole (0.9%) and retinal detachment (0.3%) were identified. Among them, secondary glaucoma (16 eyes) and macular degeneration (4 eyes) were major complications related to irreversible visual dysfunction. CONCLUSIONS: Although most of the patients with ocular sarcoidosis had a relatively good visual prognosis, some developed severe, refractory, and/or prolonged inflammation related to the development of ocular complications, that resulted in poor visual prognosis.

Long-term Outcomes of Modified 360-Degree Suture Trabeculotomy for Uveitic Glaucoma Compared With Primary Open Angle Glaucoma.
Riki Kijima, Yasuhiro Shinmei, Shinki Chin, Rina Kanaya, Akihiro Shinkai, Takeshi Ohguchi, Kenichi Namba, Susumu Ishida
Journal of glaucoma, 31, 8, 682, 688, 2022年08月01日, ［国際誌］
英語, 研究論文（学術雑誌）, PRCIS: A Kaplan-Meier survival curve analysis showed no significant differences in success rates between uveitic glaucoma (UG) and primary open angle glaucoma (POAG) 120 months after modified 360-degree suture trabeculotomy, which was effective for both groups in the long term. PURPOSE: The aim of this study was to examine the outcomes of modified 360-degree suture trabeculotomy in patients with UG as compared with those with POAG. PATIENTS AND METHODS: This was a retrospective, nonrandomized, and comparative case series study. Modified 360-degree trabeculotomy using a 5-0 nylon suture (S-LOT) was performed on 51 eyes of 51 patients (54.4±13.4 y) with UG between October 2005 and January 2012 at Hokkaido University Hospital. Age-matched patients with POAG who underwent S-LOT during the same period were enrolled as controls. Written informed consent was obtained from all patients enrolled in the present study. Surgical success was defined as an intraocular pressure (IOP) <18 mm Hg with similar or lower doses of antiglaucoma medications. Kaplan-Meier survival curves of surgical failure were analyzed and compared between UG and POAG. RESULTS: The mean follow-up periods (±SD) for UG and POAG were 104.8±44.0 and 98.1±36.3 months ( P =0.23), respectively. Mean preoperative IOP in UG and POAG were 34.9±11.0 and 25.3±9.4 mm Hg ( P <0.001), respectively. After surgery, mean IOP in UG and POAG decreased to 12.0±4.1 and 13.8±3.2 mm Hg, respectively, at 60 months, and 12.1±5.6 and 12.4±1.8 mm Hg ( P =0.86), respectively, at 120 months. The Kaplan-Meier survival curve analysis showed no significant differences in success rates between UG and POAG at the end of the follow-up (Log-rank test, P =0.13). Success rates in UG and POAG were 70.0 and 62.5% at 60 months, and 67.5 and 41.2% at 120 months, respectively. CONCLUSION: These results suggest that S-LOT is effective for UG and POAG alike.

Use of systemic corticosteroids in patients newly registered at a claims database with a diagnosis of non-infectious uveitis: results from a real-world claims database analysis.
Akihiko Umazume, Nobuyuki Ohguro, Annabelle A Okada, Kenichi Namba, Koh-Hei Sonoda, Hidekazu Tsuruga, Kazuo Morita, Hiroshi Goto
Japanese journal of ophthalmology, 66, 4, 394, 404, 2022年07月, ［国内誌］
英語, 研究論文（学術雑誌）, PURPOSE: To investigate the real-world dose of systemic corticosteroids in the treatment of non-infectious uveitis (NIU) in Japan. STUDY DESIGN: A retrospective, observational study. METHODS: Patients newly registered at the Japan Medical Data Center health insurance claims database with a diagnosis of NIU who received systemic corticosteroids were identified, and their systemic corticosteroid dose (prednisolone equivalent) was assessed over 12 months of treatment (data extraction period: January 2008 to May 2017). RESULTS: The mean cumulative systemic corticosteroid dose in 12 months in 1641 new patients with NIU who received systemic corticosteroids was 593.7 mg. The mean systemic corticosteroid dose was highest at month 1 (10.7, 218.1, 16.7, and 23.0 mg/day in Behçet's disease [BD]-associated NIU [n = 19], Vogt-Koyanagi-Harada [VKH] disease-associated NIU [n = 49], sarcoidosis-associated NIU [n = 27], and "undifferentiated NIU" [NIU without specific primary disease information, n = 1545], respectively) and decreased over time. Systemic corticosteroids were prescribed at month 12 to 68.4%, 22.4%, 44.4%, and 5.6% of patients with BD-associated NIU, VKH disease-associated NIU, sarcoidosis-associated NIU, and undifferentiated NIU, respectively (mean dose, 6.0-14.3 mg/day). Multivariate regression analysis identified female sex, middle age (30 to < 40 years), VKH disease, and immunosuppressive agent use as background factors associated with higher systemic corticosteroid dose. CONCLUSIONS: The systemic corticosteroid dose was highest at month 1 and decreased over time in all disease categories. This database research revealed that some patients with NIU continued being prescribed systemic corticosteroids for at least 1 year.

Efficacy and Safety of Adalimumab for Exacerbation or Relapse of Ocular Inflammation in Patients with Vogt-Koyanagi-Harada Disease: A Multicenter Study.
Shunsaku Nakai, Masaru Takeuchi, Yoshihiko Usui, Kenichi Namba, Kayo Suzuki, Yosuke Harada, Sentaro Kusuhara, Toshikatsu Kaburaki, Rie Tanaka, Masaki Takeuchi, Nobuhisa Mizuki, Kei Nakai, Hiroshi Goto, Carl P Herbort Jr
Ocular immunology and inflammation, 1, 9, 2022年06月24日, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: We investigated efficacy and safety of adalimumab (ADA) treatment for exacerbation or recurrence of Vogt-Koyanagi-Harada (VKH) patients. METHODS: Medical records of 70 VKH patients who received ADA treatment for more than 6 months were retrospectively investigated. RESULTS: The mean age of VKH patients was 54.8 ± 15.1 years, and male/female ratio was 34/36, and sunset glow fundus was observed in 71.4%. Subfoveal choroidal thickness, indocyanine green angiography scores, and corticosteroid and cyclosporine doses were significantly reduced by ADA treatment for 6 months compared to baseline, while LogMAR and flare counts were also improved without being statistically significant. Adverse events were observed in 17.1%, in which tuberculosis was at 7.14% and psoriasis was at 2.86%; however, ADA treatment was continued in 91.4%. CONCLUSIONS: ADA was shown to be effective to achieve remission of VKH disease refractory to conventional treatments and was generally well tolerated with few serious adverse events.

Long-Term Safety and Effectiveness of Adalimumab in Japanese Patients with Noninfectious Intermediate, Posterior, or Panuveitis: Post-Marketing Surveillance of 251 Patients.
Kenichi Namba, Toshikatsu Kaburaki, Hidekazu Tsuruga, Yohei Ogawa, Eri Iwashita, Hiroshi Goto
Ophthalmology and therapy, 11, 3, 1147, 1161, 2022年06月, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: The aim of this nationwide, prospective post-marketing surveillance was to assess the safety and effectiveness of up to 52 weeks of adalimumab treatment in patients with noninfectious intermediate, posterior, or panuveitis in Japanese clinical practice. METHODS: This post-marketing surveillance was conducted at 60 medical facilities in Japan from October 2016 to June 2020. Patients with noninfectious intermediate, posterior, or panuveitis who were administered adalimumab (Humira®, AbbVie Inc.) for the first time were eligible. Subcutaneous adalimumab was initially administered at 80 mg, followed by 40 mg 1 week later, then 40 mg every 2 weeks. Safety measures included the incidence of adverse events (AEs) and adverse drug reactions (ADRs; primary endpoint). Effectiveness measures included visual acuity, anterior chamber cell grade, vitreous haze, macular edema, foveal retinal thickness, uveitis recurrence rate, and oral corticosteroid dose. Health-related quality of life was evaluated using the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25). RESULTS: During 52 weeks of surveillance, AEs and ADRs occurred in 70 (27.9%) and 47 (18.7%) of 251 patients, respectively. The most common ADR was infection (21/251 patients; 8.4%), including serious infections in eight (3.2%) patients. ADRs were more frequent in patients ≥ 65 years of age, those with concurrent diseases, and those with past medical history. Four patients developed tuberculosis. The uveitis recurrence rate was 24.8% (61/246 patients). All effectiveness measures tended to improve from baseline to week 52, and mean corticosteroid doses decreased. Clinically meaningful changes were observed for most VFQ-25 subscales. CONCLUSIONS: The safety profile of adalimumab was generally consistent with previous reports, and no new safety concerns were identified. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02916017.

Diagnostic Accuracy of Cell Block Preparations and Clinical Features Affecting It in Vitreoretinal Lymphoma.
Satoru Kase, Kenichi Namba, Daiju Iwata, Kazuomi Mizuuchi, Kayo Suzuki, Takako Ito, Keitaro Hase, Nobuyoshi Kitaichi, Susumu Ishida
Journal of clinical medicine, 11, 5, 2022年03月03日, ［国際誌］
英語, 研究論文（学術雑誌）, Purpose: The purpose of this study was to examine the diagnostic accuracy of the cell block (CB) method and clinical features affecting it in patients with vitreoretinal lymphoma (VRL). Methods: This study enrolled 38 eyes in 33 VRL patients, and 7 eyes in 7 patients with idiopathic uveitis who underwent diagnostic vitrectomy. Medical records including the results of CB cytology, interleukin (IL)-10/-6 concentrations, and immunoglobulin heavy chain gene (IgH) rearrangement were retrospectively searched. Results: Patients with VRL comprised 16 women and 17 men, and the age of onset ranged from 44 to 85 years (mean: 70 years). CB preparations detected large malignant cells in 35 eyes (92%), whereas the other 3 VRL eyes were negative. Two of the latter three eyes showed subretinal infiltrates, which existed in 7 of 35 CB-positive eyes. Intravitreal IL-10 and -6 concentrations were 1866 ± 4088 pg/mL and 98 ± 139 pg/mL, respectively, and the rate of IL-10/-6 >1 was 86.9%. The presence of IgH monoclonality was 63.2%. In patients with uveitis, CB specimens revealed no atypical but small inflammatory cells. IL-6 concentration was 311.1 ± 240 pg/mL, whereas IL-10 was undetectable in six eyes, and the IL-negative rate was 85.7%. Six eyes (85.7%) with uveitis showed no IgH monoclonality. Conclusions: Diagnostic accuracy of CB preparations in VRL could achieve an equivalent outcome to IL ratio calculation and IgH monoclonality detection. The appearance of subretinal infiltrates may diminish the CB positivity.

Posterior scleritis with anti-neutrophil cytoplasmic antibody-associated vasculitis utilizing rituximab therapy to maintain remission: A case report.
Xinyu Weng, Daiju Iwata, Kenichi Namba, Kayo Suzuki, Kazuomi Mizuuchi, Hiroyuki Nakamura, Tatsuya Atsumi, Susumu Ishida
American journal of ophthalmology case reports, 25, 101333, 101333, 2022年03月, ［国際誌］
英語, PURPOSE: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a necrotizing vasculitis syndrome characterized by the destruction of small vessels, leading to various organ disorders. Here, we report a case of posterior scleritis with AAV successfully treated with prednisolone and rituximab (RTX) combination therapy. OBSERVATIONS: A 69-year-old female suffered from ocular pain and redness in her left eye for 2.5 years. She had been diagnosed with idiopathic otitis media before a year. At her initial visit, scleral injection with nodular elevated scleral lesions, vitreous haze, and serous retinal detachment (SRD) in the inferior periphery were observed in the left eye. Enhanced computed tomography revealed the enhancement and thickening of the left sclera. The results of laboratory analysis were positive for myeloperoxidase ANCA. Accordingly, she was diagnosed with AAV. Owing to the exacerbation of vitreous haze and SRD, topical treatment and steroid pulse therapy were initiated. Following therapy, anterior and posterior scleritis improved, and additional RTX was administered to maintain the remission. Following treatment, the patient has maintained remission with 10 mg/day prednisolone to date. CONCLUSIONS AND IMPORTANCE: We encountered a case of posterior scleritis with AAV in which inflammatory manifestations subsided with RTX and glucocorticoid combination therapy. RTX administration likely contributed to the maintenance of remission.

A case of Epstein-Barr virus acute retinal necrosis successfully treated with foscarnet.
Kayo Suzuki, Kenichi Namba, Keitaro Hase, Kazuomi Mizuuchi, Daiju Iwata, Takako Ito, Nobuyoshi Kitaichi, Hiroshi Takase, Susumu Ishida
American journal of ophthalmology case reports, 25, 101363, 101363, 2022年03月, ［国際誌］
英語, PURPOSE: Epstein-Barr virus (EBV) is a herpes virus known to cause infectious mononucleosis and several other human disorders. Ocular EBV infections that have been reported include uveitis, retinal vasculitis, and acute retinal necrosis (ARN). ARN is usually caused by herpes simplex virus (HSV) or varicella-zoster virus (VZV). ARN that is caused by EBV (EBV-ARN) is rarely seen, and only a few cases have been reported. The visual prognosis for EBV-ARN is poor, and no treatment strategy has been established. We report on a patient who was treated successfully for EBV-ARN. OBSERVATION: An 80-year-old female who had been treated with prednisolone at 5 mg/day and methotrexate at 2 mg/week for rheumatoid arthritis visited our hospital because of blurred vision in her left eye. Her left visual acuity was 20/50, and extensive white-yellowish retinal lesions at the temporal periphery with retinal hemorrhages were seen through vitreous haze. The DNA sequence of EBV, but not of HSV, VZV, or cytomegalovirus, was detected by a polymerase chain reaction (PCR) assay in the aqueous humor (4.2 × 106 copies/ml), with EBV also being positive in serum (3.5 × 102 copies/ml). The patient received 2 mg of intravitreal ganciclovir injections twice with a 3-day interval and intravenous infusion of acyclovir at 750 mg/day for 7 days; however, the retinal white lesions expanded rapidly, then dose of prednisolone was increased (40 mg/day) and vitrectomy was performed 10 days after the initial visit. After the surgery, the retinal lesion continued to enlarge. Vitreous samples showed high copies of EBV (1.2 × 108 copies/ml). Following treatment with intravenous foscarnet (4800 mg/day), which replaced the acyclovir application, the retinal white lesions gradually diminished, leaving retinal scars. To date, the patient has developed no retinal detachment and shows visual acuity over 6/60 in the left eye along with silicone oil. CONCLUSIONS: We experienced a case of EBV-ARN that was refractory to systemic acyclovir and topical ganciclovir but responded effectively to systemic foscarnet after vitrectomy. Although the clinical management remains challenging in this disease, foscarnet is considered to be one of the candidate drugs for EBV infections.

ベーチェット病ぶどう膜炎に対するインフリキシマブ治療の5年以上の検討 多施設研究　　　　　　　　　　　　　　　
竹内 大, 臼井 嘉彦, 南場 研一, 慶野 博, 竹内 正樹, 高瀬 博, 鴨居 功樹, 長谷 敬太郎, 伊東 崇子, 中井 慶, 丸山 和一, 小林 恵理, 堀 純子, 真下 永, 佐藤 智人, 大黒 伸行, 岡田 アナベルあやめ, 園田 康平, 後藤 浩, 水木 信久
日本眼科学会雑誌, 126, 臨増, 238, 238, (公財)日本眼科学会, 2022年03月
日本語

Multicenter, retrospective, observational study for the Treatment Pattern of systemic corticoSTERoids for relapse of non-infectious uveitis accompanying Vogt-Koyanagi-Harada disease or sarcoidosis.
Kenichi Namba, Hiroshi Takase, Yoshihiko Usui, Fumihiko Nitta, Kazuichi Maruyama, Sentaro Kusuhara, Masaki Takeuchi, Atsushi Azumi, Ryoji Yanai, Yutaka Kaneko, Eiichi Hasegawa, Kei Nakai, Hidekazu Tsuruga, Kazuo Morita, Toshikatsu Kaburaki
Japanese journal of ophthalmology, 66, 2, 130, 141, 2022年03月, ［国内誌］
英語, 研究論文（学術雑誌）, PURPOSE: Non-infectious uveitis associated with Vogt-Koyanagi-Harada (VKH) disease or sarcoidosis is commonly treated with systemic corticosteroids (SCS). We assessed the use of SCS for non-infectious uveitis relapses in Japanese clinical practice. STUDY DESIGN: Multicenter, retrospective chart review (UMIN Clinical Trial Registry; UMIN000032390). METHODS: One hundred fifty-seven patients (15- ≤ 75 years; 103 VKH disease, 54 sarcoidosis) given SCS to treat a relapse of non-infectious intermediate, posterior, or panuveitis accompanying VKH disease or sarcoidosis were studied (August 2011-December 2018). SCS dose and duration, concomitant medications, subsequent relapses, and steroid-related adverse drug reactions (ADRs) were analyzed for 12 months after target relapse treatment. Relationships between background factors and total SCS dose were analyzed (logistic regression). RESULTS: Mean (± SD) total SCS dose over 12 months after target relapse treatment was 3874 ± 2775 mg, and was higher in patients with immunosuppressants than in those without (4575 mg vs 3496 mg). Immunosuppressant use was the only factor significantly associated with higher total SCS dose (p = 0.0196). Mean duration of SCS treatment for relapse was 318.7 ± 89.3 days. Only 29.3% of patients were steroid-free after 12 months; the percentage was higher in patients without immunosuppressants (36.3% vs 16.4%). Subsequent relapse was experienced by 39.5% of patients, and 13.4% had a steroid-related ADR (mostly glaucoma or diabetes). CONCLUSION: In Japanese clinical practice, many patients with recurrent uveitis accompanying VKH disease or sarcoidosis received SCS for relapse for ≥ 300 days, suggesting that reducing corticosteroids is challenging in patients with difficulty suppressing inflammation.

ベーチェット病ぶどう膜炎に対するインフリキシマブ治療の5年以上の検討 多施設研究　　　　　　　　　　　　　　　
竹内 大, 臼井 嘉彦, 南場 研一, 慶野 博, 竹内 正樹, 高瀬 博, 鴨居 功樹, 長谷 敬太郎, 伊東 崇子, 中井 慶, 丸山 和一, 小林 恵理, 堀 純子, 真下 永, 佐藤 智人, 大黒 伸行, 岡田 アナベルあやめ, 園田 康平, 後藤 浩, 水木 信久
日本眼科学会雑誌, 126, 臨増, 238, 238, (公財)日本眼科学会, 2022年03月
日本語

[DIAGNOSIS AND TREATMENT OF SEASONAL ALLERGIC CONJUNCTIVITIS BY POLLEN].
Kayo Suzuki, Kenichi Namba
Arerugi = [Allergy], 71, 5, 353, 358, 2022年, ［国内誌］
日本語, 研究論文（学術雑誌）

Adalimumab treatment for chronic recurrent Vogt-Koyanagi-Harada disease with sunset glow fundus: A multicenter study.
Masaru Takeuchi, Shunsaku Nakai, Yoshihiko Usui, Kenichi Namba, Kayo Suzuki, Yosuke Harada, Sentaro Kusuhara, Toshikatsu Kaburaki, Rie Tanaka, Masaki Takeuchi, Nobuhisa Mizuki, Kei Nakai, Hiroshi Goto, Carl P Herbort Jr
Saudi journal of ophthalmology : official journal of the Saudi Ophthalmological Society, 36, 4, 380, 386, 2022年, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: We investigated the efficacy and safety of adalimumab (ADA) treatment for chronic recurrent Vogt-Koyanagi-Harada (VKH) patients with sunset glow fundus (SGF). METHODS: Medical records of 50 chronic recurrent VKH patients with SGF who received ADA treatment for more than 6 months were retrospectively reviewed. RESULTS: The mean age of chronic recurrent VKH patients with SGF was 55.9 ± 14.4 years, and the male/female ratio was 26/24. Before ADA treatment, the mean daily dose of systemic corticosteroids was 16.5 ± 12.7 mg, and 22 patients (44%) were under immunosuppressors. LogMAR visual acuity (VA), flare counts, subfoveal choroidal thickness (SFCT), indocyanine green angiography scores, and corticosteroid and cyclosporine doses were significantly reduced by ADA treatment at 6 months compared to baseline. Among all parameters, flare count was significantly related to LogMAR VA. LogMAR VA was significantly related to flare counts but not to SFCT nor to ICGA scores. ADA treatment was continued in 94%. CONCLUSION: ADA was shown to be effective in achieving remission of chronic recurrent VKH disease with SGF refractory to conventional treatments, and was generally well tolerated with few serious adverse events.

The Expression of Matrix Metalloproteinases in Eyes with Intraocular Lymphoma.
Kanae Fukutsu, Satoru Kase, Daiju Iwata, Kayo Suzuki, Kenichi Namba, Susumu Ishida
Ocular immunology and inflammation, 30, 7-8, 1798, 1802, 2022年, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: The purpose of this study is to investigate matrix metalloproteinases (MMPs) expression in human intraocular lymphoma (IOL). METHODS: Two enucleated eyes and seven cell-block samples obtained from patients with IOL who underwent vitrectomy were used. Immunopathological examinations were performed for detection of MMP-2, MMP-9, and TIMP-4 expressions. RESULTS: In the enucleated eye with primary IOL (PIOL), MMP-2 was negative, and MMP-9 and TIMP-4 were positive in the lymphoma cells, while in the enucleated eye with secondary IOL (SIOL), all the molecules were positive. Among the cell-block samples with PIOL, the positive rate in lymphoma cells of MMP-2, MMP-9, and TIMP-4 was 75%, 100%, and 75%, respectively. In the cell-block samples with SIOL, the positive rates of MMP-2, MMP-9, and TIMP-4 were all 100%. CONCLUSIONS: MMP-2, MMP-9, and TIMP-4 were expressed in lymphoma cells using the specimens of human IOL, suggesting that MMPs may play an important role in the development of IOL.

Factors associated with low prevalence of Fuchs' uveitis syndrome in Japan.
Yu Yoneda, Yoshihiko Usui, Rie Tanaka, Keitaro Hase, Kenichi Namba, Koju Kamoi, Hiroshi Takase, Masaki Takeuchi, Wataru Matsumiya, Sentaro Kusuhara, Atsunobu Takeda, Nobuyo Yawata, Ryoji Yanai, Tomona Hiyama, Yosuke Harada, Noriyasu Hashida, Kazuichi Maruyama, Kei Nakai, Ryo Taguchi, Toshikatsu Kaburaki, Nobuhisa Mizuki, Hiroshi Goto, Yujiro Fujino, Masaru Takeuchi
Frontiers in medicine, 9, 999804, 999804, 2022年, ［国際誌］
英語, 研究論文（学術雑誌）, AIM: To investigate the causes of low prevalence of Fuchs' uveitis syndrome (FUS) in Japan. METHODS: Medical records of 160 patients diagnosed with FUS at 14 uveitis specialty facilities in Japan were reviewed retrospectively. RESULTS: In 160 FUS patients, mean follow-up period before referral to our uveitis facilities was 31.6 ± 50.9 months. The most common reason for referral was idiopathic uveitis (61.9%), followed by cataract (25.0%), high intraocular pressure (IOP) including glaucoma (16.3%), and FUS (14.4%). Unilateral involvement was 96.9%. The most frequent ocular finding of FUS was anterior inflammation (91.9%), followed by stellate-shaped keratic precipitates (88.1%), cataract/pseudophakia (88.1%), diffuse iris atrophy (84.4%), vitreous opacity (62.5%), heterochromia (53.1%) and high IOP including glaucoma (36.3%). As treatments of these ocular findings, cataract surgery was performed in 52.5%, glaucoma surgery in 10.6%, and vitrectomy in 13.8%. Mean logMAR VA was 0.28 ± 0.59 at the initial visit, and decreased significantly to 0.04 ± 0.32 at the last visit. Proportions of FUS patients with BCVA <0.1 and 0.1 to <0.5 decreased, while that of ≥0.5 increased at the last visit compared with the initial visit. CONCLUSIONS: Ocular findings of FUS in Japanese FUS patients were consistent with the characteristic features. The low prevalence of FUS in Japan may be a result of being overlooked and misdiagnosed as mild idiopathic uveitis, cataract, and/or glaucoma.

Macrophage-like iPS-derived Suppressor Cells Reduce Th1-mediated Immune Response to a Retinal Antigen.
Keitaro Hase, Kenichi Namba, Haruka Wada, Hyuma Tsuji, Aoi Maeda, Tomoki Murata, Ryo Otsuka, Daiju Iwata, Atsuhiro Kanda, Kousuke Noda, Nobuyoshi Kitaichi, Ken-Ichiro Seino, Susumu Ishida
Current eye research, 46, 12, 1908, 1916, 2021年12月, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: To investigate the immunotherapeutic effects of macrophage-like induced pluripotent stem (iPS) cell-derived suppressor cells (SCs) in ocular immune response and experimental autoimmune uveoretinitis (EAU). METHODS: The genes of Oct3/4, Sox2, Klf4, and c-Myc were transferred to B cells enriched from the spleen cells of C57BL/6 mice by using retrovirus vectors. Transferred B cells were cultured for 17 days to obtain colonies of iPS cells. Through additional steps, iPS-SCs were induced. An antigen-specific T cell proliferation assay was performed with CD4+ T cells collected from draining lymph nodes of the mice immunized with human interphotoreceptor retinoid-binding protein (hIRBP) peptide and co-cultured with iPS-SCs. Cytokine concentrations in the culture supernatant were examined. Mice were immunized with hIRBP peptide to induce EAU. The iPS-SCs were administered into the mice one day before the induction of EAU. RESULTS: The iPS-SCs decreased hIRBP-specific T cell proliferation depending on the number of cells. Productions of tumor necrosis factor-α and interferon-γ were significantly decreased; however, transforming growth factor-β1, nitric oxide, interleukin (IL)-13, IL-17A, and IL-17 F levels were elevated in the supernatant when the collected T cells were co-cultured with iPS-SCs. The iPS-SCs had immunosuppressant effects even without cell-to-cell contact, and their effects were non-specific to the antigen preloaded on iPS-SCs. EAU was significantly milder in the mice administered iPS-SCs prior to immunization. CONCLUSIONS: Macrophage-like iPS-SCs reduced Th1 immune response to a retinal antigen and Th1-mediated EAU in mice. These results showed the possibility of the application of iPS technology to the treatment of noninfectious ocular inflammation, endogenous uveitis, in the future.

Prevalence and incidence rates and treatment patterns of non-infectious uveitis in Japan: real-world data using a claims database
Akihiko Umazume, Nobuyuki Ohguro, Annabelle A. Okada, Kenichi Namba, Koh-Hei Sonoda, Hidekazu Tsuruga, Kazuo Morita, Hiroshi Goto
Japanese Journal of Ophthalmology, 65, 5, 657, 665, Springer Japan, 2021年09月01日
英語, 研究論文（学術雑誌）, Purpose: To estimate the nationwide, longitudinal prevalence and incidence rates and assess treatment patterns of non-infectious uveitis (NIU) in Japan. Study design: A retrospective study. Methods: Health insurance claims’ data of patients with NIU were extracted from the Japan Medical Data Center (JMDC) database and analyzed descriptively (data extraction period, January 2011 to May 2017). Behçet’s disease (BD), Vogt-Koyanagi-Harada (VKH) disease, and sarcoidosis were selected as the primary diseases of NIU. Results: From 2011 to 2016, the mean and median age of patients increased. Most (>
90%) patients were categorized as “undifferentiated NIU” (NIU without specific primary disease information after excluding BD-, VKH disease-, and sarcoidosis-associated NIU). Over 60% of patients with NIU were treated at non-hospital clinics, while the rest were treated at university, public, or other hospitals. The estimated prevalence rate of NIU was 386.5 per 100,000 persons (95% confidence interval [CI], 374.5–398.6) in 2011 and 439.3 per 100,000 persons (95% CI, 432.3–446.3) in 2016
the estimated incidence rate was 189.7 per 100,000 persons (95% CI, 181.2–198.5) in 2012 and 207.8 per 100,000 persons (95% CI, 202.2–213.5) in 2016. Most patients’ prescribed uveitis drugs were ophthalmic drops over the first 6 months after patient presentation and entry into the JMDC database, followed by systemic corticosteroids. Conclusion: The estimated prevalence of NIU in Japan in recent years was approximately 400 with incidence of 200 per 100,000 persons.

アレルギー性結膜疾患診療ガイドライン(第3版)
宮崎 大, 内尾 英一, 海老原 伸行, 庄司 純, 南場 研一, 福島 敦樹, 大野 重昭, 大橋 裕一, 岡本 茂樹, 佐竹 良之, 高村 悦子, 深川 和己, 福田 憲, 藤島 浩, 松田 彰, 明田 直彦, 江原 二三枝, 大津 洋, 岸本 達真, 栗田 淳貴, 上月 直之, 高 良太, 清水 映輔, 鈴木 佳代, 矢津 啓之, 井上 幸次, 大久保 公裕, 加藤 則人, 斎藤 博久, 島崎 潤, 白石 敦, 外園 千恵, 園田 康平, 園部 まり子, 中西 里映子, 堀 裕一, 松本 健治, 山口 正雄, 日本眼科アレルギー学会診療ガイドライン作成委員会
日本眼科学会雑誌, 125, 8, 741, 785, (公財)日本眼科学会, 2021年08月
日本語

アレルギー性結膜疾患診療ガイドライン(第3版)　　　　　　　　　　　　　　　
宮崎 大, 内尾 英一, 海老原 伸行, 庄司 純, 南場 研一, 福島 敦樹, 大野 重昭, 大橋 裕一, 岡本 茂樹, 佐竹 良之, 高村 悦子, 深川 和己, 福田 憲, 藤島 浩, 松田 彰, 明田 直彦, 江原 二三枝, 大津 洋, 岸本 達真, 栗田 淳貴, 上月 直之, 高 良太, 清水 映輔, 鈴木 佳代, 矢津 啓之, 井上 幸次, 大久保 公裕, 加藤 則人, 斎藤 博久, 島崎 潤, 白石 敦, 外園 千恵, 園田 康平, 園部 まり子, 中西 里映子, 堀 裕一, 松本 健治, 山口 正雄, 日本眼科アレルギー学会診療ガイドライン作成委員会
日本眼科学会雑誌, 125, 8, 741, 785, (公財)日本眼科学会, 2021年08月
日本語

Correction to: Development of cytomegalovirus retinitis after negative conversion of cytomegalovirus antigenemia due to systemic antiviral therapy (Graefe's Archive for Clinical and Experimental Ophthalmology, (2021), 259, 4, (971-978), 10.1007/s00417-020-05011-0)
Kayo Suzuki, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Takako Ito, Keitaro Hase, Nobuyoshi Kitaichi, Susumu Ishida
Graefe's Archive for Clinical and Experimental Ophthalmology, 259, 4, 1083, Springer Science and Business Media Deutschland GmbH, 2021年04月01日
英語, 研究論文（学術雑誌）, The published online version contain mistake for the explanation of ‘Zone 1’. The correct presentation is given in this version. The original article has been corrected.

Development of cytomegalovirus retinitis after negative conversion of cytomegalovirus antigenemia due to systemic antiviral therapy
Kayo Suzuki, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Takako Ito, Keitaro Hase, Nobuyoshi Kitaichi, Susumu Ishida
Graefe's Archive for Clinical and Experimental Ophthalmology, 259, 4, 971, 978, Springer Science and Business Media Deutschland GmbH, 2021年04月01日
英語, 研究論文（学術雑誌）, Purpose: Cytomegalovirus (CMV) antigenemia assays have been widely used as adjunct tests to diagnose tissue invasive CMV diseases, including cytomegalovirus retinitis (CMVR). In this study, we examined CMVR cases to assess the presence of CMV in sera and aqueous humor and antiviral therapy received prior to the onset of CMVR. Methods: A total of 37 eyes from 26 different cases of CMVR in patients who visited Hokkaido University Hospital between 2007 and 2015 were enrolled. The diagnosis of CMVR was established based on characteristic ophthalmoscopic findings and the presence of local and/or systemic CMV infection. Among the 26 cases, 3 cases (12%) were HIV-positive, while the other 23 cases (88%) were HIV-negative. The records of clinical and laboratory results were reviewed from clinical charts retrospectively. Results: CMV antigenemia was positive at the onset of CMVR in 14 cases (53.8%) and negative in the other 12 cases. In 9 cases among the antigenemia-negative cases (75.0%), the antigenemia had been previously positive and had turned negative before the onset of CMVR. In 12 of the 14 antigenemia-positive cases (85.7%) and in 8 of the 9 antigenemia-negative cases (88.9%) that were previously positive, systemic antiviral therapies had never been used or had been used before but had been discontinued prior to the onset of CMVR. Conclusion: Even if viremia turns negative, the risk of developing CMVR exists for more than several weeks after the completion of systemic therapy. [Figure not available: see fulltext.].

結核性ぶどう膜炎の臨床像と治療の検討
多田 明日美, 岩橋 千春, 中井 慶, 南場 研一, 岡田 アナベルあやめ, 慶野 博, 高瀬 博, 福田 祥子, 後藤 浩, 臼井 嘉彦, 蕪城 俊克, 水木 信久, 安積 淳, 園田 康平, 武田 篤信, 大黒 伸行
日本眼科学会雑誌, 125, 4, 415, 424, (公財)日本眼科学会, 2021年04月
日本語, 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)

結核性ぶどう膜炎の臨床像と治療の検討
多田 明日美, 岩橋 千春, 中井 慶, 南場 研一, 岡田 アナベルあやめ, 慶野 博, 高瀬 博, 福田 祥子, 後藤 浩, 臼井 嘉彦, 蕪城 俊克, 水木 信久, 安積 淳, 園田 康平, 武田 篤信, 大黒 伸行
日本眼科学会雑誌, 125, 4, 415, 424, (公財)日本眼科学会, 2021年04月
日本語, 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)

Distinguishing Features of Anterior Uveitis Caused by Herpes Simplex Virus, Varicella-Zoster Virus and Cytomegalovirus.
Yukiko Terada, Toshikatsu Kaburaki, Hiroshi Takase, Hiroshi Goto, Satoko Nakano, Yoshitsugu Inoue, Kazuichi Maruyama, Kazunori Miyata, Kenichi Namba, Koh-Hei Sonoda, Yutaka Kaneko, Jiro Numaga, Masaya Fukushima, Noe Horiguchi, Mitsunao Ide, Fumie Ehara, Dai Miyazaki, Eiichi Hasegawa, Manabu Mochizuki
American journal of ophthalmology, 2021年03月24日, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: To determine distinguishing features of the clinical characteristics of anterior uveitis (AU) caused by herpes simplex virus (HSV), varicella-zoster virus (VZV) and cytomegalovirus (CMV). DESIGN: Retrospective, multicenter, case series. METHODS: Consecutive patients with herpetic AU examined at 11 tertiary centers in Japan between January 2012 and December 2017 and who were followed for 3 months or longer were evaluated. Diagnosis was made by polymerase chain reaction (PCR) for HSV, VZV or CMV in the aqueous humor, or classical signs of herpes zoster ophthalmicus. RESULTS: This study enrolled 259 herpetic AU patients, including PCR-proven HSV-AU (30 patients), VZV-AU (50) and CMV-AU (147); and herpes zoster ophthalmicus (32). All HSV-AU and VZV-AU patients were unilateral, while 3% of CMV-AU patients were bilateral. Most HSV-AU and VZV-AU patients were sudden onset with an acute clinical course, while CMV-AU had a more insidious onset and chronic course. There were no significant differences for all surveyed symptoms, signs and complications between HSV-AU and VZV-AU. However, significant differences were detected for many items between CMV-AU and the other two herpetic AU types. Ocular hyperemia and pain, blurring of vision, ciliary injection, medium to large keratic precipitates (KPs), cells and flare in the anterior chamber, and posterior synechia occurred significantly more often in HSV-AU and VZV-AU versus CMV-AU. In contrast, small KPs, coin-shaped KPs, diffuse iris atrophy, elevated intraocular pressure and glaucoma surgery were significantly more frequent in CMV-AU versus HSV-AU and VZV-AU. CONCLUSION: This multicenter retrospective study identified distinguishing features of HSV-AU, VZV-AU and CMV-AU.

Epidemiology of uveitis in Japan: a 2016 retrospective nationwide survey
Koh-Hei Sonoda, Eiichi Hasegawa, Kenichi Namba, Annabelle A. Okada, Nobuyuki Ohguro, Hiroshi Goto, JOIS (Japanese Ocular Inflammation Society) Uveitis Survey Working Group
Japanese Journal of Ophthalmology, 65, 2, 184, 190, Springer Japan, 2021年03月01日
英語, 研究論文（学術雑誌）, Purpose: To investigate the epidemiology of uveitis in Japan and assess its changes over time. Study design: Retrospective multicenter study Methods: Sixty-six hospitals in Japan with uveitis specialty clinics participated in this retrospective nationwide survey. A questionnaire was sent to each hospital to survey the total number of patients who made a first visit to the outpatient uveitis clinic of each hospital between 1 April 2016 and 31 March 2017. The diagnosis of uveitis was based on guidelines when available or on commonly used diagnostic criteria. Results: In 2016, new patients with uveitis accounted for 3.2% of the total number of new patients with ophthalmic diseases. A total of 5378 patients were enrolled in the survey
3408 cases could be classified with a specific uveitis entity, and 1970 cases were described as unclassified intraocular inflammation. Among the classified cases, the most frequent disease was sarcoidosis (10.6%), followed by Vogt–Koyanagi–Harada disease (8.1%), herpetic iritis (6.5%), acute anterior uveitis (5.5%), sclerouveitis (4.4%), Behçet’s disease (4.2%), malignant disease (2.6%), acute retinal necrosis (1.7%), Posner–Schlossman syndrome (1.7%), and diabetic iritis (1.4%). The rates of sarcoidosis, Vogt–Koyanagi–Harada disease, and Behçet’s disease were similar
however, the rate of herpes iritis increased (4.2–6.5%) when compared with the 2009 survey. Conclusions: Some changes were observed between the previous nationwide surveys (2002 and 2009) and the present survey. It must be valuable to continue such nationwide epidemiologic surveys at regular intervals.

Validation of systemic parameters for the diagnosis of ocular sarcoidosis
Kayo Suzuki, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Takako Ito, Keitaro Hase, Nobuyoshi Kitaichi, Susumu Ishida
Japanese Journal of Ophthalmology, 65, 2, 191, 198, Springer Japan, 2021年03月01日
英語, 研究論文（学術雑誌）, Purpose: Ocular sarcoidosis is diagnosed based on suggestive intraocular findings and systemic investigations. In this study, we assessed the clinical usefulness of systemic parameters in the diagnosis of ocular sarcoidosis. Study design: A retrospective study. Methods: This study included 79 cases (19 men, 60 women) with ocular sarcoidosis who visited Hokkaido University Hospital from 2011 to 2015 and were followed up for more than one year. The control group was 91 cases of other uveitis (38 men, 53 women). All cases underwent blood examination for the measurement of angiotensin-converting enzyme (ACE), Krebs von den Lungen-6 (KL-6), soluble interleukin-2 receptor (sIL-2R), and calcium (Ca) levels. Bilateral hilar lymphadenopathy (BHL) was also examined by plain chest X-ray and contrasting chest computed tomography (CT). Results: The sensitivity for sIL-2R (76.4%) was higher than for ACE (37.7%), KL-6 (26.3%), and Ca (11.8%), although all showed high specificity: ACE (97.5%), KL-6 (96.2%), sIL-2R (93.8%), and Ca (95.1%). From these results, the Youden index of sIL-2R (0.70) was higher than that of ACE (0.35), KL-6 (0.26), and Ca (0.07). Imaging tests revealed better detection of BHL by contrasting chest CT (82.7%) than by plain chest X-ray (29.5%). Conclusion: The present findings indicate that the systemic parameters, particularly serum sIL-2R levels and BHL on contrasting chest CT, are useful biomarkers for the diagnosis of ocular sarcoidosis.

VKH病及び眼サルコイドーシス再燃時における全身ステロイド薬の使用実態調査　　　　　　　　　　　　　　　
南場 研一, 高瀬 博, 臼井 嘉彦, 新田 文彦, 丸山 和一, 楠原 仙太郎, 竹内 正樹, 安積 淳, 柳井 亮二, 金子 優, 長谷川 英一, 中井 慶, 鶴我 英和, 守田 和央, 蕪城 俊克
日本眼科学会雑誌, 125, 臨増, 212, 212, (公財)日本眼科学会, 2021年03月
日本語

VKH病及び眼サルコイドーシス再燃時における全身ステロイド薬の使用実態調査　　　　　　　　　　　　　　　
南場 研一, 高瀬 博, 臼井 嘉彦, 新田 文彦, 丸山 和一, 楠原 仙太郎, 竹内 正樹, 安積 淳, 柳井 亮二, 金子 優, 長谷川 英一, 中井 慶, 鶴我 英和, 守田 和央, 蕪城 俊克
日本眼科学会雑誌, 125, 臨増, 212, 212, (公財)日本眼科学会, 2021年03月
日本語

Recent Clinical Features of Intraocular Inflammation in Hokkaido, Japan - Comparison with the Previous Decade.
Daiju Iwata, Kenichi Namba, Taku Yamamoto, Kazuomi Mizuuchi, Wataru Saito, Shigeaki Ohno, Nobuyoshi Kitaichi, Susumu Ishida
Ocular immunology and inflammation, 1, 7, 2021年02月11日, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: This study aimed to investigate the clinical features of intraocular inflammation (uveitis) in Hokkaido and to assess the etiology trends in comparison with those of our previous survey. METHODS: We retrospectively reviewed the medical records of 1,616 new referral uveitis patients (1,020 females and 596 males) in Hokkaido University Hospital between 2004 and 2014. RESULTS: Sarcoidosis was the most frequent etiology (17.4%), followed by Vogt-Koyanagi-Harada disease (8.1%), Behçet's disease (4.5%), and human leukocyte antigen B27 -associated uveitis (2.5%). The etiologies in 48.7% of the patients were unclassified. Compared to the previous survey between 1994 and 2003, the rate of Behçet's disease decreased and that of sarcoidosis increased. The rates of infectious uveitis and vitreoretinal lymphoma increased. CONCLUSION: Although the order of the top four etiologies was the same in the two surveys, the rate of sarcoidosis increased and that of Behçet's disease decreased.

Clinical Features of Primary Vitreoretinal Lymphoma: A Single-center Study.
Satoru Kase, Kenichi Namba, Daiju Iwata, Kazuomi Mizuuchi, Takako Ito, Keitaro Hase, Kayo Suzuki, Masahiro Onozawa, Nobuyoshi Kitaichi, Susumu Ishida
Cancer diagnosis & prognosis, 1, 2, 69, 75, 2021年, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND/AIM: This study aimed to demonstrate the clinical outcomes of primary vitreoretinal lymphoma (PVRL). PATIENTS AND METHODS: Seventeen patients with PVRL who had been treated at Hokkaido University Hospital were enrolled in this study. They were diagnosed based on their cytology, interleukin-10/-6 ratio, and immunoglobulin heavy chain (IgH) gene rearrangement. RESULTS: Diagnostic tests detected cytological malignancy among 14 cases (82.3%), high interleukin-10/-6 ratios among 16 cases (94.1%), and IgH monoclonality in 13 cases (76.5%). Systemic corticosteroids were given to seven (41.2%) patients before their diagnosis of PVRL. Treatments after diagnosis comprised intravitreal methotrexate injection, local radiation, and intravenous chemotherapy for 11, seven, and five cases, respectively. Central nervous system and systemic involvements were observed in nine and one case, respectively, and these complications occurred at 3 to 43 months (mean=16 months) after initial ocular presentation. CONCLUSION: Many of our patients did not receive any systemic intervention, and almost half of patients with PVRL developed central nervous system involvement during their follow-up period.

Optic Nerve Head Microcirculation in Eyes with Vogt-Koyanagi-Harada Disease Accompanied by Anterior Ischemic Optic Neuropathy
Yui Yamashita, Yuki Hashimoto, Kenichi Namba, Kazuomi Mizuuchi, Susumu Ishida
Case Reports in Ophthalmology, 899, 908, S. Karger AG, 2021年
英語, 研究論文（学術雑誌）, Anterior ischemic optic neuropathy (AION) is infrequently complicated with Vogt-Koyanagi-Harada (VKH) disease. We quantitatively examined sequential changes in the morphology and circulation hemodynamics, using a C-scan of optical coherence tomography (OCT) and laser speckle flowgraphy (LSFG) in a patient with VKH disease accompanied by AION. A 65-year-old female complained of blurred vision in both of her eyes. The patient presented with optic disc swelling and remarkable choroidal thickening detected by OCT bilaterally. The diagnosis of VKH disease was established based on the presence of pleocytosis detected in the cerebrospinal fluid and hypofluorescent dark dots scattered all around the fundus, detected by indocyanine green angiography. Goldmann perimetry detected visual field defects, similar to superior altitudinal hemianopsia in the right eye and similar to inferior altitudinal hemianopsia in the left eye. The patient was suspected to have developed AION in both eyes. The patient received methylprednisolone pulse therapy, followed by oral prednisolone. With these treatments, the optic disc swelling disappeared. However, optic disc atrophy with visual field defects remained in both eyes. An OCT C-scan showed the ganglion cell complex (GCC) and circumpapillary retinal nerve fiber layer (cpRNFL) thickness getting thinner below the normal range, and LSFG showed the decrease in optic nerve head (ONH) tissue microcirculation. These results supported the occurrence of AION in this patient with VKH disease. The analysis of GCC and cpRNFL thickness and ONH microcirculation would be useful for supporting the occurrence of AION in a case of VKH disease.

Surgical Outcomes of Trabeculectomy in Uveitic Glaucoma: A Long-Term, Single-Center, Retrospective Case-Control Study.
Rina Kanaya, Riki Kijima, Yasuhiro Shinmei, Akihiro Shinkai, Takeshi Ohguchi, Kenichi Namba, Shinki Chin, Susumu Ishida
Journal of ophthalmology, 2021, 5550776, 5550776, 2021年, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: To evaluate the long-term outcomes of trabeculectomy with mitomycin C (MMC-TLE) in patients with uveitic glaucoma (UG). Patients and Methods. This was a retrospective, nonrandomized case series study. MMC-TLE was performed on 50 eyes with UG between February 2001 and January 2015 at Hokkaido University Hospital. Age- and sex-matched patients with primary open angle glaucoma (POAG) who underwent MMC-TLE were matched by age and sex and enrolled as controls. Surgical success was defined as an intraocular pressure (IOP) less than 18 or 15 mmHg. The Kaplan-Meier survival curves for surgical failure were analyzed. RESULTS: The mean preoperative IOP in UG and POAG was 27.6 ± 10.6 and 18.0 ± 4.5 mmHg, respectively. After the surgery, the mean IOP in UG and POAG was reduced to 11.7 ± 4.2 and 12.2 ± 3.8 mmHg at 12 months, 11.9 ± 7.0 and 12.1 ± 3.1 mmHg at 36 months, and 13.0 ± 5.2 and 10.6 ± 1.2 mmHg at 120 months, respectively. The success rates (IOP <18 mmHg, IOP reduction >20%) in UG and POAG were 91.7% and 88.0% at 12 months, 82.2% and 75.6% at 36 months, and 66.5% and 61.8% at 120 months, respectively. The success rates (IOP <15 mmHg) in UG and POAG were 64.0% and 58.0% at 12 months, 55.1% and 45.5% at 36 months, and 47.9% and 37.8% at 120 months, respectively. There was no significant difference in the success rate between UG and POAG at 120 months after surgery by either definition of surgical success. CONCLUSIONS: MMC-TLE effectively reduced IOP in both UG and POAG. There was no significant difference in the success rate between UG and POAG. Following sufficient inflammation suppression, surgical outcomes of UG may be comparable with those of POAG.

Multiple evanescent white dot syndrome and panuveitis: a case report
Kazuomi Mizuuchi, Wataru Saito, Kenichi Namba, Susumu Ishida
Journal of Ophthalmic Inflammation and Infection, 10, 1, Springer Science and Business Media Deutschland GmbH, 2020年12月01日
英語, 研究論文（学術雑誌）, Aim: To report a patient with multiple evanescent white dot syndrome (MEWDS) complicated by iridocyclitis and vitritis. Case description: A 70-year-old woman developed multiple subretinal white dots, iritis, and diffuse vitreous opacity. Angiographic and macular morphological features were consistent with those of MEWDS. Inflammatory findings including the white dots improved following only topical dexamethasone within 1 month after the initial visit. Best-corrected visual acuity recovered to 1.0 with restored photoreceptor structure. Conclusion: The presence of iridocyclitis and vitritis, atypical to MEWDS, indicates the concurrent development of panuveitis associated with MEWDS. These results suggest that MEWDS is a clinical entity of uveitis.

Reduced steroid-induced intraocular pressure elevation in tacrolimus-treated refractory allergic ocular diseases.
Dai Miyazaki, Daisuke Shimizu, Atsuki Fukushima, Nobuyuki Ebihara, Eiichi Uchio, Jun Shoji, Kenichi Namba, Yoshitsugu Inoue, Yuichi Ohashi, Shigeki Okamoto, Etsuko Takamura, Hiroshi Fujishima
Japanese journal of ophthalmology, 64, 6, 568, 576, 2020年11月, ［国内誌］
英語, 研究論文（学術雑誌）, PURPOSE: To determine whether topical tacrolimus can lessen steroid-induced intraocular pressure (IOP) elevation. STUDY DESIGN: Open cohort post hoc analysis study. METHODS: Five hundred eleven patients with vernal keratoconjunctivitis or atopic keratoconjunctivitis (mean age 17.0 ± 9.2 years) were studied. All 511 patients were treated with topical tacrolimus with or without topical steroids, and the changes in IOP were measured monthly for 3 months. The elevation in IOP induced by use of topical steroids was calculated using mixed linear regression analyses. The relationship between the elevation in IOP within 4 weeks and the use or nonuse of tacrolimus reported in published data was analyzed using metaregression analysis to estimate the effects of tacrolimus on the IOP in eyes treated with topical steroids. RESULTS: The mean topical steroid-induced IOP elevation in tacrolimus-treated eyes was lower, by 5.2 mmHg (P = 0.04), than that in earlier published data without tacrolimus as the control. In the tacrolimus-treated eyes, the mean betamethasone-induced IOP elevation was 1.3 mmHg without discontinuation of the steroid. Metaregression analysis indicated that glaucoma history and younger age had significant effects on topical steroid-induced IOP elevation, by 4.0 mmHg (P = 0.002) and 3.9 mmHg (P = 0.01), respectively. In tacrolimus-treated eyes, the most significant effect on the IOP was associated with glaucoma history or medication; however, its effect on the IOP was limited to 1.7 mmHg elevation (P = 0.006). CONCLUSIONS: Topical tacrolimus may lessen the steroid-induced elevation in IOP in younger individuals and may be a good adjunctive therapy to avoid IOP elevation in refractory cases.

Alteration of oral flora in Mongolian patients with Behçet's disease: a multicentre study.
Javzandulam Balt, Osamu Uehara, Yoshihiro Abiko, Baasankhuu Jamyanjav, Sarantuya Jav, Toshiyuki Nagasawa, Mari Mori, Yukihiro Horie, Mari Fujita, Anton Lennikov, Tohru Ohta, Miki Hiraoka, Daiju Iwata, Kenichi Namba, Shigeaki Ohno, Nobuyoshi Kitaichi
Clinical and experimental rheumatology, 38 Suppl 127, 5, 80, 85, 2020年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: Behçet's disease (BD) is characterised by repeated acute inflammatory attacks with aphthous ulcers of the oral mucosa, uveitis of the eyes, skin symptoms, and genital ulcers. Although its aetiology is still unknown, there is evidence of the involvement of oral bacteria in systemic diseases. Various types of oral bacteria may be involved in the development and progression of BD. The present study investigated alterations in the oral flora of patients with BD in Mongolia. We collected saliva samples from the Mongolian BD group and healthy control (HC) group, and the oral flora were analysed using next-generation sequencer (NGS). METHODS: DNA was extracted from the unstimulated saliva samples from the 47 BD and 48 HC subjects. The DNA was amplified from the V3-V4 region of 16S rRNA using PCR, and the data were acquired using NGS. Based on the obtained data, we analysed the alpha diversity, beta diversity, and bacterial taxonomy of the salivary flora. RESULTS: Beta diversity differed significantly between the BD and HC flora, but no significant differences were observed in alpha diversity. We found that the proportions of three genera - an S24-7 family unknown species, a mitochondria family unknown species, and Akkermansia species associated with IL-10 production - were significantly lower in the BD than in the HC group. CONCLUSIONS: The reduced proportions of the S24-7 family and symbiotic Akkermansia species may be key phenomena in the oral flora of patients with BD.

Clinical Characteristics, Management, and Factors Associated with Poor Visual Prognosis of Acute Retinal Necrosis.
Hiroshi Takase, Hiroshi Goto, Kenichi Namba, Nobuhisa Mizuki, Annabelle A Okada, Nobuyuki Ohguro, Koh-Hei Sonoda, Makoto Tomita, Hiroshi Keino, Takeshi Kezuka, Reo Kubono, Kazuomi Mizuuchi, Etsuko Shibuya, Hiroyuki Takahashi, Ryoji Yanai, Manabu Mochizuki
Ocular immunology and inflammation, 1, 6, 2020年09月18日, ［国際誌］
英語, 研究論文（学術雑誌）, Purpose: To identify the clinical characteristics of acute retinal necrosis (ARN) and clarify factors associated with poor visual prognosis. Methods: a nationwide multi-center retrospective chart review study was performed in Japan using data from the medical records of 149 consecutive ARN patients. Demographics, ocular signs, virologic testing of intraocular fluids, and treatment were examined. Factors associated with poor visual prognosis were investigated by regression analysis. Results: At initial presentation, anterior chamber cells or mutton-fat keratic precipitates (97%), unilaterality (93%), and yellow-white retinal lesions (86%) were recognized. In the clinical course, rapid circumferential expansion of retinal lesions (39%), development of retinal break or retinal detachment (55%), and optic atrophy (43%) were recorded. Four variables were identified as associated with poor visual prognosis. Conclusions: The present study identified clinical characteristics and factors associated with poor visual prognosis of ARN.

Genetic control of CCL24, POR, and IL23R contributes to the pathogenesis of sarcoidosis.
Akira Meguro, Mami Ishihara, Martin Petrek, Ken Yamamoto, Masaki Takeuchi, Frantisek Mrazek, Vitezslav Kolek, Alzbeta Benicka, Takahiro Yamane, Etsuko Shibuya, Atsushi Yoshino, Akiko Isomoto, Masao Ota, Keisuke Yatsu, Noriharu Shijubo, Sonoko Nagai, Etsuro Yamaguchi, Tetsuo Yamaguchi, Kenichi Namba, Toshikatsu Kaburaki, Hiroshi Takase, Shin-Ichiro Morimoto, Junko Hori, Keiko Kono, Hiroshi Goto, Takafumi Suda, Soichiro Ikushima, Yasutaka Ando, Shinobu Takenaka, Masaru Takeuchi, Takenosuke Yuasa, Katsunori Sugisaki, Nobuyuki Ohguro, Miki Hiraoka, Nobuyoshi Kitaichi, Yukihiko Sugiyama, Nobuyuki Horita, Yuri Asukata, Tatsukata Kawagoe, Ikuko Kimura, Mizuho Ishido, Hidetoshi Inoko, Manabu Mochizuki, Shigeaki Ohno, Seiamak Bahram, Elaine F Remmers, Daniel L Kastner, Nobuhisa Mizuki
Communications biology, 3, 1, 465, 465, 2020年08月21日, ［国際誌］
英語, 研究論文（学術雑誌）, Sarcoidosis is a genetically complex systemic inflammatory disease that affects multiple organs. We present a GWAS of a Japanese cohort (700 sarcoidosis cases and 886 controls) with replication in independent samples from Japan (931 cases and 1,042 controls) and the Czech Republic (265 cases and 264 controls). We identified three loci outside the HLA complex, CCL24, STYXL1-SRRM3, and C1orf141-IL23R, which showed genome-wide significant associations (P < 5.0 × 10-8) with sarcoidosis; CCL24 and STYXL1-SRRM3 were novel. The disease-risk alleles in CCL24 and IL23R were associated with reduced CCL24 and IL23R expression, respectively. The disease-risk allele in STYXL1-SRRM3 was associated with elevated POR expression. These results suggest that genetic control of CCL24, POR, and IL23R expression contribute to the pathogenesis of sarcoidosis. We speculate that the CCL24 risk allele might be involved in a polarized Th1 response in sarcoidosis, and that POR and IL23R risk alleles may lead to diminished host defense against sarcoidosis pathogens.

Pseudo-inflammatory manifestations of choroidal lymphoma resembling Vogt-Koyanagi-Harada disease: case report based on multimodal imaging.
Kanae Fukutsu, Kenichi Namba, Daiju Iwata, Kazuomi Mizuuchi, Satoru Kase, Kayo Suzuki, Hiroshi Shimizu, Yukiko Shibata, Fumihiko Yamawaki, Masahiro Onozawa, Susumu Ishida
BMC ophthalmology, 20, 1, 94, 94, 2020年03月10日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Hematologic malignancies occasionally cause serous retinal detachment (SRD); however, its pathogenesis remains unclear. Here we present the imaging characteristics of metastatic choroidal lymphoma masquerading as Vogt-Koyanagi-Harada (VKH) disease. CASE PRESENTATION: A 45-year-old Japanese woman was referred to our clinic because of bilateral SRD with blurred vision. Fluorescein angiography revealed multiple pinpoint leakage followed by pooling OU. Enhanced depth imaging optical coherence tomography showed marked choroidal thickening OU. Laser speckle flowgraphy detected choroidal circulation impairment OU. Although these results totally agreed with the inflammatory manifestations of acute VKH disease, indocyanine green angiography demonstrated various sizes of sharply marginated hypofluorescent lesions that seemed atypical for the finding of VKH disease, i.e., vaguely marginated hypofluorescent small dots. Cerebrospinal fluid pleocytosis was not detected. Blood tests revealed leukocytosis together with elevation of lactate dehydrogenase and soluble interleukin-2 receptor levels. Corticosteroid pulse therapy did not improve any ocular findings. Bone marrow biopsy was then performed, leading to a definite diagnosis of diffuse large B-cell lymphoma. After starting systemic chemotherapy, both SRD and choroidal thickening resolved rapidly with visual recovery. However, choroidal hypoperfusion persisted, which contrasted distinctly with the inflammatory pattern of VKH disease, i.e., the restoration of choroidal blood flow in parallel with normalization of choroidal thickness. CONCLUSIONS: Our detailed multimodal observations highlighted the differential imaging features of choroidal lymphoma despite close resemblance to VKH disease especially at the initial stage. Impaired circulation in the thickened choroid marked the pseudo-inflammatory pathogenesis of SRD due to choroidal involvement with neoplastic, but not inflammatory cells.

Variants in IL23R-C1orf141 and ADO-ZNF365-EGR2 are associated with susceptibility to Vogt-Koyanagi-Harada disease in Japanese population.
Takuto Sakono, Akira Meguro, Masaki Takeuchi, Takahiro Yamane, Takeshi Teshigawara, Nobuyoshi Kitaichi, Yukihiro Horie, Kenichi Namba, Shigeaki Ohno, Kumiko Nakao, Taiji Sakamoto, Tsutomu Sakai, Tadashi Nakano, Hiroshi Keino, Annabelle A Okada, Atsunobu Takeda, Takako Ito, Hisashi Mashimo, Nobuyuki Ohguro, Shinichirou Oono, Hiroshi Enaida, Satoshi Okinami, Nobuyuki Horita, Masao Ota, Nobuhisa Mizuki
PloS one, 15, 5, e0233464, 2020年, ［国際誌］
英語, 研究論文（学術雑誌）, Vogt-Koyanagi-Harada (VKH) disease is a systemic inflammatory disorder that affects pigment cell-containing organs such as the eye (e.g., chronic and/or recurrent granulomatous panuveitis). While the exact etiology and pathogenic mechanism of VKH disease are unclear, HLA-DR4 alleles have been documented to be strongly associated with VKH disease in various ethnic groups. Recently, a genome-wide association study (GWAS) found two new genetic risk factors (IL23R-C1orf141 and ADO-ZNF365-EGR2) in a non-HLA region from a Han Chinese population. In this study, we replicated these GWAS findings in a Japanese population. A total of 1,643 Japanese samples (380 cases with VKH disease and 1,263 healthy controls) were recruited. We assessed four single nucleotide polymorphisms (SNPs) shown in previous GWAS: rs78377598 and rs117633859 in IL23R-C1orf141, and rs442309 and rs224058 in ADO-ZNF365-EGR2. A significant allelic association with VKH disease was observed for all of the four SNPs (rs78377598: pc = 0.0057; rs117633859: pc = 0.0017; rs442309: pc = 0.021; rs224058: pc = 0.035). In genotypic association analysis, the minor alleles of IL23R-C1orf141 rs78377598 and rs117633859 had the strongest association with disease susceptibility under the additive model (pc = 0.0075 and pc = 0.0026, respectively). The minor alleles of ADO-ZNF365-EGR2 rs442309 and rs224058 were most strongly associated with disease susceptibility under the dominant model (pc = 0.00099 and pc = 0.0023, respectively). The meta-analysis of the current and previous studies found that all of the four SNPs exhibited a significantly strong association with VKH disease (meta-p < 0.00001: rs78377598, meta-odds ratio (OR) = 1.69; rs1176338, meta-OR = 1.82; rs442309, meta-OR = 1.34; rs224058, meta-OR = 1.33). In summary, our study replicated significant associations with VKH disease susceptibility reported in a previous GWAS. Thus, the IL23R-C1orf141 and ADO-ZNF365-EGR2 loci may play important roles in the development of VKH disease through genetic polymorphisms.

Air pollution significantly associated with severe ocular allergic inflammatory diseases.
Miyazaki D, Fukagawa K, Fukushima A, Fujishima H, Uchio E, Ebihara N, Shoji J, Takamura E, Namba K, Ohashi Y, Okamoto S, Satake Y, Ohtsu H, Shimizu Y, Inoue Y
Scientific reports, 9, 1, 18205, 2019年12月, ［査読有り］

Comparison of clinical characteristics in patients with Vogt-Koyanagi-Harada disease with and without anti-retinal antibodies.
Yuki Hashimoto, Wataru Saito, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Kousuke Noda, Atsuhiro Kanda, Susumu Ishida
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 257, 8, 1751, 1758, 2019年08月, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: To compare the clinical characteristics of Vogt-Koyanagi-Harada (VKH) disease patients with and without anti-retinal antibodies (ARAs) that are frequently detected in autoimmune retinopathy. METHODS: Using immunoblot analyses, serum autoantibodies for recoverin, carbonic anhydrase II, and α-enolase were examined in 20 treatment-naïve patients with VKH disease. Clinical factors before and after systemic corticosteroid therapy, including best-corrected visual acuity (BCVA) and macular outer retinal morphology, were statistically compared between patients with VKH disease with and without ARAs. RESULTS: Serum ARAs were detected in 50.0% of patients with VKH disease. There were no significant differences in clinical factors between the two groups, including final BCVA, frequency of uveitis recurrence, and recovery of the macular ellipsoid zone after systemic corticosteroid therapy. CONCLUSIONS: Our results suggest that the detected ARAs did not influence visual outcomes, the chronicity of uveitis, or outer retinal morphology in patients with VKH disease.

Topical Tacrolimus for Chronic Allergic Conjunctival Disease with and without Atopic Dermatitis
Jun Shoji, Yuichi Ohashi, Atsuki Fukushima, Dai Miyazaki, Eiichi Uchio, Etsuko Takamura, Hiroshi Fujishima, Kenichi Namba, Naoki Kumagai, Nobuyuki Ebihara, Shigeki Okamoto
Current Eye Research, 44, 7, 796, 805, Taylor and Francis Ltd, 2019年07月03日
英語, 研究論文（学術雑誌）, Purpose/Aim: This study evaluated the efficacy of topical 0.1% tacrolimus ophthalmic suspension for treating chronic allergic conjunctival disease with and without atopic dermatitis. Materials and Methods: This study was conducted as a prospective observational post-market survey. Our large-scale study protocol was accepted by the Pharmaceuticals and Medical Devices Agency in Japan and included patients who were prescribed topical tacrolimus for the treatment of chronic allergic conjunctival disease from May 2008 to Aug 2010 in Japan. Topical tacrolimus was instilled 2 times daily for 6 months. The primary endpoint was the change from baseline in papillae-limbus-cornea clinical signs score (based on the presence of papillae, giant papillae, Trantas’ dots, limbal swelling, and corneal epithelial signs). Remission rate following topical tacrolimus treatment was investigated using generalized estimating equations. Results: A total of 1821 subjects were included in the analyses. Six months into treatment, 83.0% and 87.7% of subjects with and without atopic dermatitis, respectively, were in remission (based on the papillae-limbus-cornea grading score). Topical tacrolimus treatment was equally effective in improving papillae-limbus-cornea grading scores from baseline in both study groups after 6 months of treatment. Additionally, the odds ratio for remission increased over time. The concomitant use of topical steroids improved papillae-limbus-cornea grading scores, including papillary signs with a statistically significant, but low odds ratio. Conclusion: Tacrolimus ophthalmic suspension is useful for treating chronic allergic conjunctival disease with and without atopic dermatitis. Clinical response to local tacrolimus therapy is dependent upon treatment duration.

Cyclosporine and prednisolone combination therapy as a potential therapeutic strategy for relentless placoid chorioretinitis.
Takehiko Uraki, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Shigeaki Ohno, Nobuyoshi Kitaichi, Susumu Ishida
American journal of ophthalmology case reports, 14, 87, 91, 2019年06月, ［査読有り］, ［国際誌］
英語, Purpose: Relentless placoid chorioretinitis (RPC) is a new disease concept that was proposed by Jones et al. in 2000. Some cases of RPC have been reported; however, a treatment strategy has not yet been established. We report herein four cases of patients diagnosed with RPC. Observations: We experienced four cases of RPC in patients aged 24-51 years. All patients exhibited retinal lesions similar to that seen in acute posterior multifocal placoid pigment epitheliopathy or serpiginous choroiditis from the posterior pole to the surrounding region. Although patients underwent systemic prednisolone (PSL) therapy, recurrence was observed and the retinal scar formation was progressive; they were then diagnosed with RPC. In all cases, cyclosporine (CyA) was administered in addition to PSL, no recurrence was observed thereafter. Conclusions and Importance: RPC is a rare disease, and a treatment strategy has not yet been established. CyA and PSL combination therapy is considered to be effective in the treatment of RPC.

人工多能性幹細胞由来マクロファージ様免疫抑制細胞を用いたぶどう膜炎モデルの軽症化　　　　　　　　　　　　　　　
長谷 敬太郎, 南場 研一, 北市 伸義, 岩田 大樹, 辻 飛雄馬, 和田 はるか, 清野 研一郎, 石田 晋
日本眼科学会雑誌, 123, 臨増, 226, 226, (公財)日本眼科学会, 2019年03月
日本語

Real-world evidence of treatment for relapse of noninfectious uveitis in tertiary centers in Japan: A multicenter study.
Masaru Takeuchi, Takayuki Kanda, Toshikatsu Kaburaki, Rie Tanaka, Kenichi Namba, Koju Kamoi, Kazuichi Maruyama, Etsuko Shibuya, Nobuhisa Mizuki
Medicine, 98, 9, e14668, 2019年03月, ［査読有り］, ［国際誌］
英語, Noninfectious uveitis (NIU), which pathogenesis is often autoimmune nature, occurs as a symptom of systemic syndromes or only in the eye. The standard treatment of NIU is local, topical, and oral administration of corticosteroids (CS) in combination with immunomodulatory therapy (IMT). However, additional therapeutic strategies involving topical and systemic administration of CS or others to treat relapse or exacerbation of ocular inflammation in NIU which present as various ocular manifestations have not been established. The aim of this study was to investigate therapeutic strategies used for various ocular inflammations in relapse or exacerbation of NIU and to evaluate factors associated with the treatment pattern in Japan. The subjects were 198 eyes of 156 NIU patients with relapse or exacerbation of ocular inflammation at 6 university hospitals in Japan. The most frequent disease was sarcoidosis in 23.7% of the cases, followed by Behçet disease (BD) in 21.2%, Vogt-Koyanagi-Harada (VKH) disease in 13.6%, acute anterior uveitis (AAU) in 5.6%, tubulointerstitial nephritis and uveitis syndrome (TINU) in 4.0%, and juvenile idiopathic arthritis (JIA)-associated uveitis in 3.0%. Common ocular findings were worsened anterior inflammation (AI) in 67.2% of the cases, vitreous opacity (VO) in 46.5%, macular edema (ME) in 26.8%, retinal vasculitis (RV) in 23.7%, serous retinal detachment (SRD) in 9.1%, and optic perineuritis (OPN) in 4.0%. Reinforcement of betamethasone eye drop (ED) monotherapy for only AI in both unilateral and bilateral AI, sub-tenon injection of triamcinolone acetonide (STTA) for unilateral posterior inflammation including VO and ME, and systemic therapy using CS and/or IMT for bilateral anterior and posterior inflammation were significantly more frequent. Frequencies of exacerbated individual ocular findings in sarcoidosis and BD were similar, and severe ocular inflammation associated with panuveitis required both topical and systemic therapies. These results demonstrate that reinforcement of betamethasone EDs, topical administration of triamcinolone acetonide, and long-term administration of systemic corticosteroids are the major therapeutic strategies, and reinforcement of betamethasone EDs was used for exacerbated AI independently from its use for posterior inflammation. In addition, STTA was preferentially used for VO and ME associated with posterior inflammation.

A case of nodular posterior scleritis simulating intraocular tumor.
Yukiko Shibata, Satoru Kase, Kenichi Namba, Susumu Ishida
International journal of ophthalmology, 12, 4, 685, 688, 2019年, ［国際誌］
英語, 研究論文（学術雑誌）

Association Study of ARMC9 Gene Variants with Vogt-Koyanagi-Harada Disease in Japanese Patients.
Tomoko Ohno, Akira Meguro, Masaki Takeuchi, Takahiro Yamane, Takeshi Teshigawara, Nobuyoshi Kitaichi, Yukihiro Horie, Kenichi Namba, Shigeaki Ohno, Kumiko Nakao, Taiji Sakamoto, Tsutomu Sakai, Tadashi Nakano, Hiroshi Keino, Annabelle A Okada, Atsunobu Takeda, Takako Fukuhara, Hisashi Mashimo, Nobuyuki Ohguro, Shinichirou Oono, Hiroshi Enaida, Satoshi Okinami, Nobuhisa Mizuki
Ocular immunology and inflammation, 27, 5, 699, 705, 2019年, ［査読有り］, ［国際誌］
英語, Purpose: To investigate whether variants in the ARMC9 gene encoding KU-MEL-1 are associated with Vogt-Koyanagi-Harada (VKH) disease in a Japanese population. Methods: We recruited 380 Japanese patients with VKH disease and 744 Japanese healthy controls to genotype seven single-nucleotide polymorphisms (SNPs) in ARMC9. We also performed imputation analysis of the ARMC9 region and 195 imputed SNPs were included in the statistical analysis. Results: We observed an increased frequency of the A allele of rs28690417 in patients compared with controls (P = 0.0097, odds ratio (OR) = 1.46). The A allele had a dominant effect on VKH disease risk (P = 0.011, OR = 1.51). However, these significant differences disappeared after Bonferroni correction (corrected P > 0.05). The remaining 201 SNPs did not show any significant association with disease risk. Conclusions: Our study suggests that ARMC9 variants do not play a critical role in the development of VKH disease.

Adalimumab in Active and Inactive, Non-Infectious Uveitis: Global Results from the VISUAL I and VISUAL II Trials.
Hiroshi Goto, Masahiro Zako, Kenichi Namba, Noriyasu Hashida, Toshikatsu Kaburaki, Masanori Miyazaki, Koh-Hei Sonoda, Toshiaki Abe, Nobuhisa Mizuki, Koju Kamoi, Antoine P Brézin, Andrew D Dick, Glenn J Jaffe, Quan Dong Nguyen, Noritaka Inomata, Nisha V Kwatra, Anne Camez, Alexandra P Song, Martina Kron, Samir Tari, Shigeaki Ohno
Ocular immunology and inflammation, 27, 1, 40, 50, 2019年, ［査読有り］, ［国際誌］
英語, PURPOSE: Report global adalimumab safety and efficacy outcomes in patients with non-infectious uveitis. METHODS: Adults with non-infectious intermediate, posterior, or panuveitis were randomized 1:1 to receive placebo or adalimumab in the VISUAL I (active uveitis) or VISUAL II (inactive uveitis) trials. Integrated global and Japan substudy results are reported. The primary endpoint was time to treatment failure (TF). RESULTS: In the integrated studies, TF risk was significantly reduced (hazard ratio [95% CI]) with adalimumab versus placebo (VISUAL I: HR = 0.56 [0.40-0.76], p < 0.001; VISUAL II: HR = 0.52 [0.37-0.74], p < 0.001). In Japan substudies, no consistent trends were observed between groups (VISUAL I: HR = 1.20 [0.41-3.54]; VISUAL II: HR = 0.45 [0.20-1.03]). Adverse event rates were similar between treatment groups in both studies (854 to 1063 events/100 participant-years). CONCLUSIONS: Adalimumab lowered time to TF versus placebo in the integrated population; no consistent trends were observed in Japan substudies. Safety results were consistent between studies.

Immunohistochemical and Immunocytochemical Analyses in Patients with Vitreoretinal Lymphoma.
Kase S, Namba K, Kanno-Okada H, Onozawa M, Hidaka D, Iwata D, Mizuuchi K, Fukuhara T, Fukuhara J, Kitaichi N, Matsuno Y, Ishida S
Ocular immunology and inflammation, 1, 9, 2018年10月, ［査読有り］

Two cases of cytomegalovirus panuveitis in immunocompetent patients
Masato Sakai, Hiroshi Takase, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Susumu Ishida
American Journal of Ophthalmology Case Reports, 10, 189, 191, Elsevier Inc, 2018年06月01日, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose: To report two cases of panuveitis in immunocompetent patients in which cytomegalovirus was involved. Observation: Case 1 was a 46-year-old man who had a history of recurrent anterior chamber inflammations in his left eye. After Nd:YAG laser posterior capsulotomy, he developed panuveitis with vitreous haze and periphlebitis. Polymerase chain reaction (PCR) examination revealed the presence of cytomegalovirus (CMV) DNA in the anterior chamber (AC). He responded well to a series of intravitreal injections of ganciclovir (GCV). Case 2 was a 63-year-old woman who had a history of recurrent anterior uveitis in her left eye. Two years after cataract surgery, AC inflammation, diffuse vitreous haze, and periphlebitis had developed. CMV DNA was detected in the AC. Intravitreal injections of GCV and oral valganciclovir were administered, and ocular inflammation finally improved. Conclusions: and importance: We experienced two cases of CMV panuveitis in immunocompetent adults, both of which responded well to anti-viral therapies.

Cytopathologic findings of cell block materials from the vitreous: Diagnostic distinction between intraocular lymphoma and non-lymphomatous diseases
Hiromi Kanno-Okada, Emi Takakuwa, Yoshiaki Tagawa, Satoru Kase, Kanako C. Hatanaka, Yutaka Hatanaka, Kenichi Namba, Tomoko Mitsuhashi, Yoshihiro Matsuno
PATHOLOGY INTERNATIONAL, 67, 7, 342, 349, WILEY, 2017年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Intraocular lymphoma is a rare neoplasm that occurs only in the eyes and/or central nervous system. Diagnosis of intraocular lymphoma is difficult because its clinical manifestations mimic chronic uveitis. Pathological examination of the vitreous is one of the main diagnostic tools for intraocular lymphoma, but this is challenging due to the sparse cellularity and specimen degeneration. Here, we reviewed 33 cell block preparations from vitreous perfusion fluid in order to examine the significance of cytopathological findings for differential diagnosis using vitreous samples. The cases comprised 12 intraocular lymphomas and 21 non-lymphomatous diseases. Cytologically, vitreous samples from non-lymphoma cases showed lower cellularity than the lymphoma cases. Whereas vitreous material from cases with infectious endophthalmitis showed prominent neutrophilic infiltration, material from sarcoidosis cases showed infiltration of small lymphoid cells, especially CD4-positive T cells. On the other hand, lymphoma cases showed higher cellularity, with large, irregular and atypical lymphoid cells, frequent necrotic cells in the background, and less pronounced neutrophil infiltration. Immunocytochemically, 11 of the 12 lymphoma cases were of the B-cell phenotype and the remaining case was of the T/NK-cell phenotype. In conclusion, careful cytopathological examination or immunocytochemistry of vitreous material facilitates appropriate diagnosis of intraocular lymphoma.

A Novel Single-Strand RNAi Therapeutic Agent Targeting the (Pro)renin Receptor Suppresses Ocular Inflammation
Atsuhiro Kanda, Erdal Tan Ishizuka, Atsushi Shibata, Takahiro Matsumoto, Hidekazu Toyofuku, Kousuke Noda, Kenichi Namba, Susumu Ishida
MOLECULAR THERAPY-NUCLEIC ACIDS, 7, 116, 126, CELL PRESS, 2017年06月, ［査読有り］
英語, 研究論文（学術雑誌）, The receptor-associated prorenin system (RAPS) refers to the pathogenic mechanism whereby prorenin binding to the (pro) renin receptor [ (P) RR] dually activates the tissue reninangiotensin system (RAS) and RAS-independent intracellular signaling. Here we revealed significant upregulation of prorenin and soluble (P) RR levels in the vitreous fluid of patients with uveitis compared to non-inflammatory controls, together with a positive correlation between these RAPS components and monocyte chemotactic protein-1 among several upregulated cytokines. Moreover, we developed a novel single-strand RNAi agent, proline-modified short hairpin RNA directed against human and mouse (P) RR [ (P) RR-PshRNA], and we determined its safety and efficacy in vitro and in vivo. Application of (P) RR-PshRNA in mice caused significant amelioration of acute (uveitic) and chronic (diabetic) models of ocular inflammation with no apparent adverse effects. Our findings demonstrate the significant implication of RAPS in the pathogenesis of human uveitis and the potential usefulness of (P) RR-PshRNA as a therapeutic agent to reduce ocular inflammation.

Evaluating the efficacy of epinastine ophthalmic solution using a conjunctivitis allergen challenge model in patients with birch pollen allergic conjunctivitis
Yoshiaki Tagawa, Kenichi Namba, Yumi Nakazono, Daiju Iwata, Susumu Ishida
ALLERGOLOGY INTERNATIONAL, 66, 2, 338, 343, JAPANESE SOCIETY ALLERGOLOGY, 2017年04月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: The efficacy of epinastine 0.05% ophthalmic solution for pollen allergic conjunctivitis has already been shown in a conjunctival allergen challenge (CAC) test using cedar pollen as a challenge. The present study investigated the efficacy of this solution against birch pollen conjunctivitis in a CAC test.
Methods: Ten adult subjects (eight males and two females) with asymptomatic birch pollen conjunctivitis were enrolled in this study. The average age of the subjects was 41.1 years. This study was conducted during a period without birch pollen dispersion. In each subject, the epinastine 0.05% ophthalmic solution was instilled in one eye, and an artificial tear fluid was instilled in the fellow eye in a double-blind manner. Five minutes or 4 h after the drug instillation, both eyes were challenged with an optimal concentration of birch pollen, and ocular itching and conjunctival hyperemia were then graded. Tears were collected before the drug instillation and 20 min after the pollen challenge, and the histamine level was measured.
Results: The ocular itching scores and palpebral conjunctival hyperemia scores of the epinastine-treated eyes were significantly lower than those of the contralateral control eyes when the eyes were pretreated with the drug 4 h before the CAC. There was a significant correlation between the tear histamine level and mean ocular itching score of three time points (3, 5 and 10 min) following the CAC in the control eyes but not the epinastine-treated eyes.
Conclusions: Epinastine is effective in suppressing ocular itching and conjunctival hyperemia in birch pollen conjunctivitis. Copyright (C) 2017, Japanese Society of Allergology. Production and hosting by Elsevier B.V.

Japanese guidelines for allergic conjunctival diseases 2017
Etsuko Takamura, Eiichi Uchio, Nobuyuki Ebihara, Shigeaki Ohno, Yuichi Ohashi, Shigeki Okamoto, Naoki Kumagai, Yoshiyuki Satake, Jun Shoji, Yayoi Nakagawa, Kenichi Namba, Kazumi Fukagawa, Atsuki Fukushima, Hiroshi Fujishima
ALLERGOLOGY INTERNATIONAL, 66, 2, 220, 229, JAPANESE SOCIETY ALLERGOLOGY, 2017年04月, ［査読有り］
英語, The definition, classification, pathogenesis, test methods, clinical findings, criteria for diagnosis, and therapies of allergic conjunctival disease are summarized based on the Guidelines for Clinical Management of Allergic Conjunctival Disease (Second Edition) revised in 2010. Allergic conjunctival disease is defined as "a conjunctival inflammatory disease associated with a Type I allergy accompanied by some subjective or objective symptoms." Allergic conjunctival disease is classified into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. Representative subjective symptoms include ocular itching, hyperemia, and lacrimation, whereas objective symptoms include conjunctival hyperemia, swelling, folliculosis, and papillae. Patients with vernal keratoconjunctivitis, which is characterized by conjunctival proliferative changes called giant papilla accompanied by varying extents of corneal lesion, such as corneal erosion and shield ulcer, complain of foreign body sensation, ocular pain, and photophobia. In the diagnosis of allergic conjunctival diseases, it is required that type I allergic diathesis is present, along with subjective and objective symptoms accompanying allergic inflammation. The diagnosis is ensured by proving a type I allergic reaction in the conjunctiva. Given that the first-line drug for the treatment of allergic conjunctival disease is an antiallergic eye drop, a steroid eye drop will be selected in accordance with the severity. In the treatment of vernal keratoconjunctivitis, an immunosuppressive eye drop will be concomitantly used with the abovementioned drugs. Copyright (C) 2016, Japanese Society of Allergology. Production and hosting by Elsevier B.V.

Long-term use of tacrolimus ophthalmic suspension for vernal keratoconjunctivitis　　　　　　　　　　　　　　　
Mayuko Shinagawa, Kenichi Namba, Nobuyoshi Kitaichi, Susumu Ishida
Japanese Journal of Clinical Ophthalmology, 71, 3, 343, 348, Igaku-Shoin Ltd, 2017年03月01日
日本語, 研究論文（学術雑誌）, Purpose: To report the long-term use of tacrolimus ophthalmic suspension for vernal keratoconjunctivitis. Case and Method: This retrospective study was made on 30 eyes of 16 cases who received 0.1 % tacrolimus ophthalmic suspension for vernal keratoconjunctivitis for one year or longer. All the cases had failed to respond to topical cyclosporine before. The age ranged from 6 to 19 years, average 15 years. Atopic dermatitis was present in 14 cases, asthma in 5 cases, and allergic rhinitis in 3 cases. Nine cases received topical corticosteroid and 8 cases received systemic corticosteroid concomitantly. Results: Objective findings of vernal keratoconjunctivitis improved in all the cases after one year of treatment. Tacrilimus instillation could be reduced from twice daily to once daily in the majority of cases. Topical corticosteroid was used in 30% of cases at the start of tacrolimus and in 10% one year later. Systemic corticosteroid was used in 25% of cases at the start of tacrolimus and in 6% one year later. Temporary exacerbation of vernal keratoconjuntivitis occurred in 16 out of 30 eyes during the follow-up for one year or longer. Herpetic keratitis developed in one eye 38 months after start of tacrolimus and cured by treatment. Conclusion: Topical tacrolimus treatment for one year resulted in improved objective manifestations of vernal keratoconjunctivitis.

Investigation of the association between IL10 gene polymorphisms and Vogt-Koyanagi-Harada disease in a Japanese population
Kaori Higashi, Akira Meguro, Masaki Takeuchi, Takahiro Yamane, Nobuyoshi Kitaichi, Yukihiro Horie, Kenichi Namba, Shigeaki Ohno, Kumiko Nakao, Taiji Sakamoto, Tsutomu Sakai, Hiroshi Tsuneoka, Hiroshi Keino, Annabelle A. Okada, Atsunobu Takeda, Takako Fukuhara, Hisashi Mashimo, Nobuyuki Ohguro, Shinichirou Oono, Hiroshi Enaida, Satoshi Okinami, Nobuhisa Mizuki
OPHTHALMIC GENETICS, 38, 2, 187, 189, TAYLOR & FRANCIS INC, 2017年03月, ［査読有り］
英語

Steroid-Sparing Effect of 0.1% Tacrolimus Eye Drop for Treatment of Shield Ulcer and Corneal Epitheliopathy in Refractory Allergic Ocular Diseases
Dai Miyazaki, Atsuki Fukushima, Yuichi Ohashi, Nobuyuki Ebihara, Eiichi Uchio, Shigeki Okamoto, Jun Shoji, Etsuko Takamura, Yayoi Nakagawa, Kenichi Namba, Hiroshi Fujishima
OPHTHALMOLOGY, 124, 3, 287, 294, ELSEVIER SCIENCE INC, 2017年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose: To evaluate the effects of 0.1% topical tacrolimus alone or in combination with steroids for the treatment of shield ulcers and corneal epitheliopathy in patients with refractory allergic ocular diseases.
Design: Open cohort study.
Participants: Patients with refractory allergic conjunctivitis epitheliopathy, shield ulcers, or corneal plaques (N = 791).
Methods: The 791 patients were treated with topical tacrolimus alone or in combination with topical or oral steroids. The effectiveness of the treatments was determined by a corneal epitheliopathy score during the 3-month follow-up period. The clinical signs were rated on a 4-grade scale. Corneal epitheliopathy with no corneal staining was graded as 0, and shield ulcers or plaques were graded as 3, the highest grade. The effects of tacrolimus with and without topical steroids on the epitheliopathy scores were assessed after adjustments for the severity of the clinical signs and characteristics.
Main Outcome Measures: Changes in the corneal epitheliopathy score.
Results: Adjusted mean epitheliopathy score at the baseline was 1.73 (95% confidence interval [CI], 1.65-1.81) for patients treated with tacrolimus alone, and this was significantly reduced by -0.93 at 1 month. The reduction of the score by topical and oral steroids was -0.02 for fluorometholone, 0.02 for betamethasone, and -0.02 for oral steroids, and these reductions were not significant compared with the reduction effect of topical tacrolimus alone at -0.93. The 238 patients with shield ulcer (score 3) were analyzed with adjustments, and the mean epitheliopathy score at 1 month was reduced to 1.38 with tacrolimus alone (95% CI, 1.24-1.51), 1.41 (95% CI, 1.26-1.56) with adjuvant fluorometholone, and 1.46 (95% CI, 1.32-1.61) with adjuvant betamethasone. No significant difference was observed in the adjunctive topical steroids. The presence of severe palpebral conjunctival symptoms, including giant papillae, was a significant resisting factor for topical tacrolimus.
Conclusions: The significant effects of topical tacrolimus alone on shield ulcers and corneal epitheliopathy suggest that it may be used without the need for steroids. (C) 2016 by the American Academy of Ophthalmology.

Early post-treatment choroidal thickness to alert sunset glow fundus in patients with Vogt-Koyanagi- Harada disease treated with systemic corticosteroids
Kiriko Hirooka, Wataru Saito, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Yuki Hashimoto, Susumu Ishida
PLOS ONE, 12, 2, e0172612, PUBLIC LIBRARY SCIENCE, 2017年02月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose
To determine if early post-treatment central choroidal thickness (CCT) changes can predict sunset glow fundus (SGF) development in patients with Vogt-Koyanagi-Harada (VKH) disease treated using systemic corticosteroids.
Methods
This retrospective case series included 39 eyes of 21 treatment-naive patients with acute VKH disease who could be followed up for more than 12 months after systemic corticosteroid therapy. The eyes were divided into two groups according to whether SGF was present or absent at 12 months (9 eyes of 5 patients versus 30 eyes of 16 patients, respectively). Using enhanced depth imaging optical coherence tomography, CCT values were measured before treatment, then at 1 week and 1 and 3 months after treatment in both groups and compared between the two groups.
Results
Development of SGF was found 4-11 months after treatment. Mean post-treatment CCT decreased significantly at all examinations compared with baseline in both groups, along with resolution of serous retinal detachment. One week after treatment, mean CCT was significantly higher in eyes with SGF than in those without (P = 0.024). SGF was present at 12 months in 9 of 22 eyes with CCT values > 410 mu m at 1 week after starting treatment, in contrast with none of 17 eyes with CCT <= 410 mu m at this time (P = 0.003).
Conclusions
The current study suggested the potential validity of early post-treatment CCT as a feasible index to alert future progression to SGF in patients with VKH disease treated using systemic corticosteroids.

HLA-B51 Carriers are Susceptible to Ocular Symptoms of Behçet Disease and the Association between the Two Becomes Stronger towards the East along the Silk Road: A Literature Survey.
Horie Y, Meguro A, Ohta T, Lee EB, Namba K, Mizuuchi K, Iwata D, Mizuki N, Ota M, Inoko H, Ishida S, Ohno S, Kitaichi N
Ocular immunology and inflammation, 25, 1, 37, 40, TAYLOR & FRANCIS INC, 2017年, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose: Behcet disease (BD) is predominantly found between East Asia and the Mediterranean basin along the historic Silk Road. HLA-B51 is known to be strongly associated with BD. We investigated the association between HLA-B51 and the ocular manifestations of BD among various ethnic groups.
Methods: A literature survey was conducted, and 18 articles written in English were reviewed.
Results: A strong correlation was found between HLA-B51 and ocular lesions in the entire cohort discussed in the reviewed articles (OR = 1.76, p = 0.000057). HLA-B51 was shown to have a strong association with ocular manifestations of BD patients in East-Eurasian (OR = 2.40, p = 0.0030) and Middle-Eurasian (OR = 1.87, p = 0.0045), but not in West-Eurasian (OR = 1.28, p = 0.35) areas. This correlation seemed to become stronger towards the east.
Conclusions: A meta-analysis showed that the correlation became stronger towards the east along the Silk Road. The study results may facilitate understanding of the etiology and characteristics of BD.

Serial Frequencies and Clinical Features of Uveitis in Hokkaido, Japan
Daiju Iwata, Kazuomi Mizuuchi, Koki Aoki, Yukihiro Horie, Satoru Kase, Kenichi Namba, Shigeaki Ohno, Susumu Ishida, Nobuyoshi Kitaichi
OCULAR IMMUNOLOGY AND INFLAMMATION, 25, sup1, S15, S18, TAYLOR & FRANCIS INC, 2017年, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose: Environmental and lifestyle changes influence the clinical features of uveitis. This study reviewed the epidemiologic trends of uveitis in the Japanese population.Methods: A retrospective review of the past 80 years of reports from Hokkaido University Hospital.Results: In the 1930s, tuberculosis accounted for 46% and syphilitic uveitis for 31% of cases. The frequency of these diseases decreased to 12% in the 1950s; 8% in 1969; 0.6% in the 1990s; and 0.8% in the 2000s, while the rate of non-infectious uveitis increased. The three most common specific diagnoses were: sarcoidosis, Vogt-Koyanagi-Harada disease, and Behcet disease. Although Behcet disease was the most frequent non-infectious uveitis until the 1980s, sarcoidosis is now the most frequent cause of newly diagnosed non-infectious uveitis.Conclusions: The etiology of uveitis has changed with the times. Tubercular and syphilitic cases have greatly decreased, and sarcoidosis is the most frequent type of uveitis today.

Invariant natural killer T cells play dual roles in the development of experimental autoimmune uveoretinitis.
Satoh M, Namba KI, Kitaichi N, Endo N, Kitamei H, Iwata D, Ohno S, Ishida S, Onoé K, Watarai H, Taniguchi M, Ishibashi T, Stein-Streilein J, Sonoda KH, Van Kaer L, Iwabuchi K
Experimental eye research, 153, 79, 89, 2016年12月, ［査読有り］, ［国際誌］
英語, Experimental autoimmune uveoretinitis (EAU) represents an experimental model for human endogenous uveitis, which is caused by Th1/Th17 cell-mediated inflammation. Natural killer T (NKT) cells recognize lipid antigens and produce large amounts of cytokines upon activation. To examine the role of NKT cells in the development of uveitis, EAU was elicited by immunization with a peptide from the human interphotoreceptor retinoid-binding protein (hIRBP1-20) in complete Freund's adjuvant and histopathology scores were evaluated in C57BL/6 (WT) and NKT cell-deficient mice. NKT cell-deficient mice developed more severe EAU pathology than WT mice. When WT mice were treated with ligands of the invariant subset of NKT cells (α-GalCer or RCAI-56), EAU was ameliorated in mice treated with RCAI-56 but not α-GalCer. IRBP-specific Th1/Th17 cytokines were reduced in RCAI-56-treated compared with vehicle-treated mice. Although the numbers of IRBP-specific T cells detected by hIRBP3-13/I-Ab tetramers in the spleen and the draining lymph node were the same for vehicle and RCAI-56 treatment groups, RORγt expression by tetramer-positive cells in RCAI-56-treated mice was lower than in control mice. Moreover, the eyes of RCAI-56-treated mice contained fewer IRBP-specific T cells compared with control mice. These results suggest that invariant NKT (iNKT) cells suppress the induction of Th17 cells and infiltration of IRBP-specific T cells into the eyes, thereby reducing ocular inflammation. However, in sharp contrast to the ameliorating effects of iNKT cell activation during the initiation phase of EAU, iNKT cell activation during the effector phase exacerbated disease pathology. Thus, we conclude that iNKT cells exhibit dual roles in the development of EAU.

Choroidal circulation impairment during the anterior recurrence of Vogt-Koyanagi-Harada disease confirmed with indocyanine green angiography and laser speckle flowgraphy
Yuko Takemoto, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Tomoe Uno, Shigeaki Ohno, Kiriko Hirooka, Yuki Hashimoto, Wataru Saito, Kazuhisa Sugiyama, Susumu Ishida
ACTA OPHTHALMOLOGICA, 94, 7, E629, E636, WILEY-BLACKWELL, 2016年11月, ［査読有り］
英語, 研究論文（学術雑誌）, PurposeTo assess choroidal inflammation-related circulatory changes associated with the anterior recurrence of Vogt-Koyanagi-Harada (VKH) disease, using indocyanine green angiography (ICGA) and laser speckle flowgraphy (LSFG).
MethodsThis retrospective case series included 17 eyes of 11 patients with VKH disease showing recurrent inflammatory findings in the anterior, but not posterior, segment (i.e. anterior recurrence). Indocyanine green angiography (ICGA) and LSFG were performed at the time of recurrence and one month after the initiation of corticosteroid therapy. The number and total area of hypofluorescent dark dots (HDDs) on ICGA were independently counted by three physicians and measured with ImageJ, respectively. Mean blur rate (MBR), a quantitative index of relative blood flow velocity, was calculated via the LSFG Analyzer software.
ResultsHypofluorescent dark dots (HDDs) were identified on ICGA in 13 of 17 eyes (76%) with the anterior recurrence of VKH disease. The number and total area of HDDs significantly decreased from 203101 dots to 59 +/- 51 dots and from 48789 +/- 24251 pixels to 15664 +/- 13254 pixels, respectively. The change ratio of MBR significantly increased by 17.9 +/- 16.3% after the treatment. Importantly, there was no significant association between the change ratios of HDDs and MBR.
ConclusionsThese findings on LSFG and ICGA clearly demonstrated subclinical involvement as well as post-treatment improvement of choroidal circulation impairment due to granulomatous inflammation in eyes with the anterior recurrence of VKH disease. The present data suggest the validity of using these two examinations, capable of detecting different circulatory changes, in the management of recurrent VKH disease.

Choroidal thickening prior to anterior recurrence in patients with Vogt-Koyanagi-Harada disease
Yoshiaki Tagawa, Kenichi Namba, Kazuomi Mizuuchi, Yuko Takemoto, Daiju Iwata, Tomoe Uno, Takako Fukuhara, Kiriko Hirooka, Nobuyoshi Kitaichi, Shigeaki Ohno, Susumu Ishida
BRITISH JOURNAL OF OPHTHALMOLOGY, 100, 4, 473, 477, BMJ PUBLISHING GROUP, 2016年04月, ［査読有り］
英語, 研究論文（学術雑誌）, Aim To assess choroidal thickness changes associated with anterior segment recurrences in patients with Vogt-Koyanagi-Harada (VKH) disease using enhanced depth imaging optical coherence tomography (EDI-OCT).
Methods EDI-OCT images were obtained periodically from 11 patients with VKH disease (22 eyes) who were followed-up due to anterior segment recurrences. Subfoveal choroidal thickness (SCT) values at the following stages were evaluated: (1) during the remission phase, (2) 1 month before detecting the anterior recurrence, (3) during the anterior recurrence and (4) after systemic prednisolone (PSL) treatment leading to remission. In comparison with SCT values in remission as baseline, the changing ratios of SCT were statistically analysed at subsequent three stages.
Results The average of the SCT changing ratios compared with the remission phase significantly increased to 1.45 +/- 0.11 during anterior segment recurrences (p=0.00044) lacking any funduscopic signs of posterior involvement. Interestingly, the average SCT ratio 1 month before detecting the recurrence had already increased to 1.30 +/- 0.08 (p=0.002). After the PSL treatment, the ratio of SCT recovered to 0.95 +/- 0.03, which was equivalent to the remission level. However, in patients with their remission SCT values less than 240 mm, the SCT ratio did not increase significantly at any time points evaluated.
Conclusions The choroid in eyes with VKH disease thickened in association with the anterior segment recurrence, and this thickening was observed prior to the recurrence. EDI-OCT may be useful for detecting latent choroidal inflammation in VKH disease, whereas it may not for patients with the relatively thin choroid.

Diagnostic efficacy of cell block method for vitreoretinal lymphoma
Satoru Kase, Kenichi Namba, Daiju Iwata, Kazuomi Mizuuchi, Nobuyoshi Kitaichi, Yoshiaki Tagawa, Hiromi Okada-Kanno, Yoshihiro Matsuno, Susumu Ishida
DIAGNOSTIC PATHOLOGY, 11, 29, BIOMED CENTRAL LTD, 2016年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Vitreoretinal lymphoma (VRL) is a life- and sight-threatening disorder. The aim of this study was to analyze the usefulness of the cell block method for diagnosis of VRL.
Methods: Sixteen eyes in 12 patients with VRL, and 4 eyes in 4 patients with idiopathic uveitis presenting with vitreous opacity were enrolled in this study. Both undiluted vitreous and diluted fluids were isolated during micro-incision vitrectomy. Cell block specimens were prepared in 19 eyes from diluted fluid containing shredding vitreous. These specimens were then submitted for HE staining as well as immunocytological analyses with antibodies against the B-cell marker CD20, the T-cell marker CD3, and cell proliferation marker Ki67. Conventional smear cytology was applied in 14 eyes with VRL using undiluted vitreous samples. The diagnosis of VRL was made based on the results of cytology, concentrations of interleukin (IL)-10 and IL-6 in undiluted vitreous, and immunoglobulin heavy chain gene rearrangement analysis.
Results: Atypical lymphoid cells were identified in 14 out of 15 cell block specimens of VRL (positive rate: 93.3 %), but in 5 out of 14 eyes in conventional smear cytology (positive rate: 35.7 %). Atypical lymphoid cells showed immunoreactivity for CD20 and Ki67. Seven cell block specimens were smear cytology-negative and cell block-positive. The cell block method showed no atypical lymphoid cells in any patient with idiopathic uveitis.
Conclusions: Cell block specimens using diluted vitreous fluid demonstrated a high diagnostic sensitivity and a low pseudo-positive rate for the cytological diagnosis of VRL. The cell block method contributed to clear differentiation between VRL and idiopathic uveitis with vitreous opacity.

Behçet’s disease
Shigeaki Ohno, Kenichi Namba, Yuko Takemoto
Intraocular Inflammation, 785, 795, Springer Berlin Heidelberg, 2016年01月01日, ［査読有り］
英語, 論文集(書籍)内論文, Behçet’s disease (BD) is a relapsing multisystemic disorder with obliterative vasculitis affecting both arteries and veins including vasculopathy of capillaries. In 1937, Hulusi Behçet described oral aphthous ulcers, genital ulcers, and hypopyon uveitis as a triad.

Kawasaki disease
Shigeaki Ohno, Kenichi Namba, Hirokuni Kitamei
Intraocular Inflammation, 755, 759, Springer Berlin Heidelberg, 2016年01月01日, ［査読有り］
英語, 論文集(書籍)内論文, Kawasaki disease, or mucocutaneous lymph node syndrome, is an acute systemic vasculitis that mainly develops in children younger than 5 years of age. It was first described in 1967 by Dr Tomisaku Kawasaki et al. [4].

Posner-schlossman syndrome
Shigeaki Ohno, Kenichi Namba, Akiko Miyazaki
Intraocular Inflammation, 1007, 1012, Springer Berlin Heidelberg, 2016年01月01日, ［査読有り］
英語, 論文集(書籍)内論文, Posner-Schlossman syndrome is characterized by recurrent, unilateral attacks of acute ocular hypertension associated with a mild anterior uveitis. It was first described by Posner and Schlossman in 1948. This syndrome is often called glaucomatocyclitic crisis. Although intraocular pressure is severely elevated, the anterior chamber angle is open. Ocular hypertension mostly becomes normal after 1 month with reduction of ocular inflammation. Intraocular pressure (IOP) is normal in the convalescent stage (Table 92.1).

A Case of Severe Panuveitis Associated with Psoriasis Vulgaris Successfully Treated with Infliximab
Yuri Sakurai, Kenichi Namba, Kazuomi Mizuuchi, Toshihumi Nomura, Susumu Ishida
Case Reports in Ophthalmology, 7, 1, 191, 194, S. Karger AG, 2016年, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose: Uveitis associated with psoriasis vulgaris is usually seen as an anterior segment inflammation, and it is very rare that the inflammation extends to the posterior segment. We herein report a case of severe panuveitis associated with psoriasis vulgaris presenting as retinal neovascularization, leading to vitreous hemorrhages that were successfully treated with infliximab (IFX). Case Report: A 27-year-old male with psoriasis vulgaris was referred to our hospital due to prolonged severe uveitis OU. He showed a severe anterior chamber inflammation with fibrin formation and total posterior iris synechia OU. With topical corticosteroid treatment, these conditions were relieved for a short time
however, the intraocular inflammation was exacerbated with vitreous hemorrhages caused by retinal neovascularization OS. After the administration of IFX therapy, the intraocular inflammation and retinal neovascularization was resolved, and so far, no severe recurrences have been seen for 3 years with the therapy. Conclusion: When we see patients with severe panuveitis associated with psoriasis extending to the posterior segment, IFX treatment may be a good therapeutic option.

Ocular Behçet's disease is less complicated with allergic disorders. A nationwide survey in Japan.
Horie Y, Kitaichi N, Hijioka K, Sonoda KH, Saishin Y, Kezuka T, Goto H, Takeuchi M, Nakamura S, Kimoto T, Shimakawa M, Kita M, Sugita S, Mochizuki M, Hori J, Iwata M, Shoji J, Fukuda M, Kaburaki T, Numaga J, Kawashima H, Fukushima A, Joko T, Takai N, Ozawa Y, Meguro A, Mizuki N, Namba K, Ishida S, Ohno S
Clinical and experimental rheumatology, 34, 6 Suppl 102, 111, 114, Clinical and Experimental Rheumatology S.A.S., 2016年, ［査読有り］
英語, 研究論文（学術雑誌）, Objective. Behçet's disease (BD) is a systemic inflammatory disorder polarised to the Th1 and Th17 immune systems. Allergic diseases are polarised to the Th2 immune system. The aim of the present study is to investigate the prevalence of allergic diseases in patients who have BD. Methods. The study involved a largescale interview survey of Japanese patients with BD at 21 institutes of ophthalmology
353 patients (255 males and 98 females) were recruited for this study. We analysed the history of allergic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), bronchial asthma (BA) and drug/food allergies (FA). Results. Oral aphthous ulcers, ocular lesions, skin lesions, genital ulcers, arthritis, neurological lesions, intestinal lesions, deep vein thrombosis and epididymitis were reported in 95.8%, 98.6%, 72.5%, 44.8%, 13.9%, 6.8%, 6.2%, 3.7% and 1.4% of the patients, respectively. It was also reported that 73 patients (20.7%) had histories of allergic diseases: AD (5 cases, 1.4%), AR (36 cases, 10.2%), BA (19 cases, 5.4%) and FA (30 cases, 8.5%). This percentage was significantly lower than in a survey that Japan's Ministry of Health, Labour and Welfare conducted for healthy population (47.6%) (odds ratio = 0.29, 95% confidence interval = 0.22-0.38, p=4.9×10-22). Frequencies of posterior/pan-uveitis, relatively severe ocular findings, and visual prognosis were not affected by a history of allergic diseases in BD. Conclusion. Patients with BD had fewer complications from allergic diseases than did the entire population of Japan.

Significant role of the choroidal outer layer during recovery from choroidal thickening in Vogt-Koyanagi-Harada disease patients treated with systemic corticosteroids
Kiriko Hirooka, Wataru Saito, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Yuki Hashimoto, Susumu Ishida
BMC OPHTHALMOLOGY, 15, 181, BIOMED CENTRAL LTD, 2015年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Which of the choroidal layers suffers the most extensive morphological changes during the course of Vogt-Koyanagi-Harada (VKH) disease is still unknown. The aim of this study was to investigate the relationship between total thickness and the thickness of inner or outer layers in the choroid during systemic corticosteroid therapy in patients with VKH disease.
Methods: This retrospective case series included 15 eyes of 10 patients with treatment-naive VKH disease (4 men and 6 women; mean age, 41.4 +/- 14.7 years) received systemic corticosteroid therapy. Whole, inner, and outer choroidal thickness was measured manually at 1 week and at 1 and 3 months after initiation of systemic corticosteroid therapy using enhanced depth imaging optical coherence tomography. The mean thickness values of the layers were compared at each stage.
Results: Compared with the 1-week baseline, the mean whole and outer choroidal layer thicknesses were significantly lower at 1 (P = 0.008 and 0.03, respectively) and 3 months (P = 0.008 and 0.02, respectively), whereas the inner layer did not significantly thin. Importantly, there was a significant positive correlation between the rates of change of whole and outer layer thickness from 1 week to 3 months (R = 0.9312, P < 0.0001), but not between the rates of whole and inner layer thickness changes.
Conclusions: The thinning of total choroidal thickness observed after treatment with corticosteroids strongly correlated with outer layer thinning, suggesting that the choroidal outer layer is the primary target in acute-stage VKH disease.

A case of tuberculous endophthalmitis successfully treated with vitrectomy followed by antituberculous agents
Keitaro Hase, Kenichi Namba, Wataru Saito, Shigeaki Ohno, Susumu Ishida
Journal of Ophthalmic Inflammation and Infection, 5, 1, 14, Springer Verlag, 2015年12月01日, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Tuberculous endophthalmitis is very rare with only 18 reports published worldwide and only a few cases in Japan. We report a case of tuberculous endophthalmitis successfully treated with vitrectomy followed by antituberculous agents. Findings: An 81-year-old man was referred to us due to the exacerbation of vitreous opacity on his left eye(OS) after he had received the corticosteroid therapy. His best corrected visual acuity was light perception OS, and he had severe intraocular inflammation with fibrin formation in the anterior chamber and dense vitreous opacity. A chest CT showed miliary nodules indicating miliary tuberculosis, and pars plana vitrectomy was performed. Intraoperative observation showed that the vitreous cavity was filled by fibrin, and large elevated subretinal yellow-white lesions were present at the mid-periphery. The patient immediately received triple antituberculous agents orally, and Mycobacterium tuberculosis was detected in vitreous fluids. The intraocular inflammation gradually decreased, and the subretinal mass regressed within 2 weeks. Conclusions: We encountered a case of tuberculous endophthalmitis successfully treated with vitrectomy followed by antituberculous agents. If endophthalmitis is suspected in a patient with systemic tuberculosis infection, prompt vitrectomy along with the administration of antituberculous agents may be necessary.

Relationship between choroidal blood flow velocity and choroidal thickness during systemic corticosteroid therapy for Vogt-Koyanagi-Harada disease
Kiriko Hirooka, Wataru Saito, Kenichi Namba, Yuko Takemoto, Kazuomi Mizuuchi, Tomoe Uno, Yoshiaki Tagawa, Yuki Hashimoto, Susumu Ishida
GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 253, 4, 609, 617, SPRINGER, 2015年04月, ［査読有り］
英語, 研究論文（学術雑誌）, To investigate the relationship between circulation hemodynamics and morphology in the choroid during systemic corticosteroid therapy for patients with Vogt-Koyanagi-Harada (VKH) disease.
This retrospective case series includes 18 eyes of nine patients with VKH disease (two men and seven women; average age, 40.8 years) who received systemic corticosteroid therapy. Laser speckle flowgraphy (LSFG) and enhanced-depth imaging optical coherence tomography (EDI-OCT) were performed before treatment and at 1 week and 1 and 3 months after treatment. The average values of the mean blur rate (MBR) at the macula and the central choroidal thickness (CCT) were compared at each stage.
The changing rates of the average MBR significantly increased at all examinations after the start of treatment compared with the pre-treatment value with resolution of serous retinal detachment (SRD) (P = 0.0002 for all). The CCT decreased significantly at all examinations after the start of treatment compared with the pre-treatment value (P = 0.0002 for all). Changes in MBR and CCT during the 3-month follow-up period correlated significantly (R = -0.5913, P = 0.0097). The best-corrected visual acuity at pre-treatment correlated significantly with the changing rate of the MBR from 0 to 3 months (R = 0.5944, P = 0.0093) but not with CCT.
Our data suggest that circulatory disturbances and increased thickness of the choroid relate to the pathogenesis of VKH disease with link mutually. LSFG is useful as an index for evaluating the choroiditis activity of VKH disease as well as EDI-OCT.

Acute Zonal Occult Outer Retinopathy in Japanese Patients: Clinical Features, Visual Function, and Factors Affecting Visual Function
Saho Saito, Wataru Saito, Michiyuki Saito, Yuki Hashimoto, Shohei Mori, Kousuke Noda, Kenichi Namba, Susumu Ishida
PLOS ONE, 10, 4, e0125133, PUBLIC LIBRARY SCIENCE, 2015年04月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose
To evaluate the clinical features and investigate their relationship with visual function in Japanese patients with acute zonal occult outer retinopathy (AZOOR).
Methods
Fifty-two eyes of 38 Japanese AZOOR patients (31 female and 7 male patients; mean age at first visit, 35.0 years; median follow-up duration, 31 months) were retrospectively collected: 31 untreated eyes with good visual acuity and 21 systemic corticosteroid-treated eyes with progressive visual acuity loss. Variables affecting the logMAR values of best-corrected visual acuity (BCVA) and the mean deviation (MD) on Humphrey perimetry at initial and final visits were examined using multiple stepwise linear regression analysis.
Results
In untreated eyes, the mean MD at the final visit was significantly higher than that at the initial visit (P = 0.00002). In corticosteroid-treated eyes, the logMAR BCVA and MD at the final visit were significantly better than the initial values (P = 0.007 and P = 0.02, respectively). The final logMAR BCVA was 0.0 or less in 85% of patients. Variables affecting initial visual function were moderate anterior vitreous cells, myopia severity, and a-wave amplitudes on electroretinography; factors affecting final visual function were the initial MD values, female sex, moderate anterior vitreous cells, and retinal atrophy.
Conclusions
Our data indicated that visual functions in enrolled patients significantly improved spontaneously or after systemic corticosteroids therapy, suggesting that Japanese patients with AZOOR have good visual outcomes during the follow-up period of this study. Furthermore, initial visual field defects, gender, anterior vitreous cells, and retinal atrophy affected final visual functions in these patients.

Single center study on ethnic and clinical features of Behcet's disease in Moscow, Russia.
Lennikov Anton, Alekberova Zemfira, Goloeva Regina, Kitaichi Nobuyoshi, Denisov Lev, Namba Kenichi, Takeno Mitsuhiro, Ishigatsubo Yoshiaki, Mizuki Nobuhisa, Nasonov Eugeny, Ishida Susumu, Ohno Shigeaki
Clinical rheumatology, 34, 2, 321, 7, 2015年02月, ［査読有り］
英語, For the purpose of investigating Behcet's disease (BD) in Russia, 250 consecutive patients (177 men and 73 women) diagnosed with BD between 1990 and 2010 at the Research Institute of Rheumatology, Russian Academy of Medical Sciences in Moscow were enrolled in this study. The ethnic backgrounds of the patients were reported as follows: 23.2% (58 cases) from Russia, 12.8% (32 cases) from Azerbaijan, 14.4% (36 cases) from Armenia, 8.8% (22 cases) from Chechnya, and 21.6% (55 cases) from Dagestan. The remaining 19.2% (48 cases) were from other regions or of unknown origin. More than half (57.6%) of the Behcet's disease patients originated from Central Asia, specifically Azerbaijan, Armenia, Chechnya, and Dagestan. The mean age at disease onset was 31.5 ± 9.38 (13-60) years old, and the most typical initial manifestations were oral aphthous ulcers. Patients aged 20-39 years old were more commonly affected and displayed a wide clinical spectrum of the disease, with varieties of severe internal organ involvement. The manifestations observed throughout the course of the disease included oral aphthous ulcers (100%), various cutaneous lesions (88.8%), genital ulcers (81.2%), and ocula

Single center study on ethnic and clinical features of Behcet's disease in Moscow, Russia
Anton Lennikov, Zemfira Alekberova, Regina Goloeva, Nobuyoshi Kitaichi, Lev Denisov, Kenichi Namba, Mitsuhiro Takeno, Yoshiaki Ishigatsubo, Nobuhisa Mizuki, Eugeny Nasonov, Susumu Ishida, Shigeaki Ohno
CLINICAL RHEUMATOLOGY, 34, 2, 321, 327, SPRINGER LONDON LTD, 2015年02月, ［査読有り］
英語, 研究論文（学術雑誌）, For the purpose of investigating Behcet's disease (BD) in Russia, 250 consecutive patients (177 men and 73 women) diagnosed with BD between 1990 and 2010 at the Research Institute of Rheumatology, Russian Academy of Medical Sciences in Moscow were enrolled in this study. The ethnic backgrounds of the patients were reported as follows: 23.2 % (58 cases) from Russia, 12.8 % (32 cases) from Azerbaijan, 14.4 % (36 cases) from Armenia, 8.8 % (22 cases) from Chechnya, and 21.6 % (55 cases) from Dagestan. The remaining 19.2 % (48 cases) were from other regions or of unknown origin. More than half (57.6 %) of the Behcet's disease patients originated from Central Asia, specifically Azerbaijan, Armenia, Chechnya, and Dagestan. The mean age at disease onset was 31.5 +/- 9.38 (13-60) years old, and the most typical initial manifestations were oral aphthous ulcers. Patients aged 20-39 years old were more commonly affected and displayed a wide clinical spectrum of the disease, with varieties of severe internal organ involvement. The manifestations observed throughout the course of the disease included oral aphthous ulcers (100 %), various cutaneous lesions (88.8 %), genital ulcers (81.2 %), and ocular lesions (54.0 %). Besides these, many organs/systems were implicated in patient cases, namely joint (53.2 %), vascular (25.2 %), neurological (8.0 %), gastrointestinal (25.2 %), and cardiac (5.6 %) systems. Involvements of ocular (p < 0.01) and skin (p < 0.01) lesions were more frequent in men than in women. HLA-B51 and HLA-A26 typing was performed in 127 patients and 508 healthy controls. HLA-B51 was found in 63.0 % of BD patients compared to 20.7 % of the healthy control subjects (p < 0.001), and HLA-A26 was present in 11.3 % of BD patients and 18.9 % of the control group. This study shows the presence of BD in Russia, and it is suggested that its prevalence in Central Asian people is much higher than that in White Russian.

A Major Review: Current Aspects of Ocular Behçet's Disease in Japan.
Namba K, Goto H, Kaburaki T, Kitaichi N, Mizuki N, Asukata Y, Fujino Y, Meguro A, Sakamoto S, Shibuya E, Yokoi K, Ohno S
Ocular immunology and inflammation, 23, S1, S23, INFORMA HEALTHCARE, 2015年, ［査読有り］
英語, Diagnosis and treatment of Behcet'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 Behcet'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 Behcet'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.

A case of mature natural killer-cell neoplasm manifesting multiple choroidal lesions: Primary intraocular natural killer-cell lymphoma
Yoshiaki Tagawa, Reiki Ogasawara, Hiromi Kanno, Susumu Ishida, Kenichi Namba
Case Reports in Ophthalmology, 6, 3, 380, 384, S. Karger AG, 2015年, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose: Natural killer (NK) cell neoplasm is a rare disease that follows an acute course and has a poor prognosis. It usually emerges from the nose and appears in the ocular tissue as a metastasis. Herein, we describe a case of NK-cell neoplasm in which the eye was considered to be the primary organ. Case: A 50-year-old female displayed bilateral anterior chamber cells, vitreous opacity, bullous retinal detachment, and multiple white choroidal mass lesions. Although malignant lymphoma or metastatic tumor was suspected, various systemic examinations failed to detect any positive results. A vitrectomy was performed OS
however, histo-cytological analyses from the vitreous sample showed no definite evidence of malignancy, and IL-10 concentration was low. Enlarged choroidal masses were fused together. Three weeks after the first visit, the patient suddenly developed an attack of fever, night sweat, and hepatic dysfunction, and 5 days later, she passed away due to multiple organ failure. Im-munohistochemisty and in situ hybridization revealed the presence of atypical cells positive for CD3, CD56, and Epstein-Barr virus-encoded RNAs, resulting in the diagnosis of NK-cell neoplasm. With the characteristic clinical course, we concluded that this neoplasm was a primary intraocular NK-cell lymphoma. Conclusions: This is the first report to describe primary intraocular NK-cell neoplasm. When we encounter atypical choroidal lesions, we should consider the possibility of NK-cell lymphoma, even though it is a rare disease.

Development and validation of new diagnostic criteria for acute retinal necrosis
Hiroshi Takase, Annabelle A. Okada, Hiroshi Goto, Nobuhisa Mizuki, Kenichi Namba, Nobuyuki Ohguro, Koh-Hei Sonoda, Makoto Tomita, Hiroshi Keino, Takeshi Kezuka, Reo Kubono, Kazuomi Mizuuchi, Etsuko Shibuya, Hiroyuki Takahashi, Ryoji Yanai, Manabu Mochizuki
JAPANESE JOURNAL OF OPHTHALMOLOGY, 59, 1, 14, 20, SPRINGER JAPAN KK, 2015年01月, ［査読有り］
英語, 研究論文（学術雑誌）, The purposes of this study are to develop and validate new diagnostic criteria for acute retinal necrosis (ARN) based on the ocular findings, clinical course, and virologic testing of intraocular fluids.
The Japanese ARN Study Group, comprising 8 uveitis specialists and 1 statistician, was formed to develop new diagnostic criteria for ARN. The criteria used a combination of clinical features consistent with ARN including 6 early-stage ocular findings ([1a] anterior chamber cells or mutton-fat keratic precipitates; [1b] yellow-white lesion(s) in the peripheral retina [granular or patchy in the early stage, then gradually merging]; [1c] retinal arteritis; [1d] hyperemia of the optic disc; [1e] inflammatory vitreous opacities; and [1f] elevated intraocular pressure), 5 clinical courses ([2a] rapid expansion of the retinal lesion(s) circumferentially, [2b] development of retinal breaks or retinal detachment, [2c] retinal vascular occlusion, [2d] optic atrophy, and [2e] response to antiviral agents), and the results of virologic testing of intraocular fluids by means of either polymerase chain reaction or the Goldmann-Witmer coefficient for herpes simplex virus or varicella zoster virus. Various combinations of findings were analyzed to maximize the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The criteria were then used to retrospectively analyze patients who had been diagnosed as having ARN or control uveitis. Patients were followed at 1 of 7 tertiary uveitis clinics between 2009 and 2011.
Analysis of the data allowed delineation of 2 levels of diagnosis: "virus-confirmed ARN" (defined as the presence of both early-stage ocular findings 1a and 1b, the presence of any 1 of the 5 clinical courses, and a positive virologic test result) and "virus-unconfirmed ARN" (defined as the presence of 4 of 6 early-stage ocular findings including 1a and 1b, presence of any 2 of the 5 clinical courses, and a negative virologic test result, or when virologic testing had not been performed). The new diagnostic criteria were applied to 45 patients with ARN and 409 patients with control uveitis, resulting in a sensitivity of 0.89, a specificity of 1.00, a PPV of 1.00, and an NPV of 0.99.
New diagnostic criteria for ARN were developed and found to achieve high statistical values.

Amelioration of experimental autoimmune uveoretinitis by inhibition of glyceraldehyde-derived advanced glycation end-product formation
Zhenyu Dong, Daiju Iwata, Nobuyoshi Kitaichi, Masayoshi Takeuchi, Masashi Sato, Noriko Endo, Kazuya Iwabuchi, Ryo Ando, Junichi Fukuhara, Satoshi Kinoshita, Anton Lennikov, Mizuki Kitamura, Kazuomi Mizuuchi, Atsuhiro Kanda, Kousuke Noda, Kenichi Namba, Sho-Ichi Yamagishi, Shigeaki Ohno, Susumu Ishida
JOURNAL OF LEUKOCYTE BIOLOGY, 96, 6, 1077, 1085, FEDERATION AMER SOC EXP BIOL, 2014年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Formation of glyceraldehyde-derived advanced glycation endoproducts contributes to the pathogenesis of endogenous uvetitis in human and animals. AGEs are permanently modified macromolecule derivatives that form through nonenzymatic glycation of amino groups of proteins. Glycer-AGEs are highly toxic and play an important role in the pathogenesis of chronic inflammatory diseases. However, the contribution of glycer-AGEs to the pathogenesis of uveitis is unclear. In this study, we measured serum levels of glycer-AGEs in 100 patients with endogenous uveitis (22 with HLA-B27-associated uveitis, 20 with VKH disease, 14 with Behcet's disease, and 44 with sarcoidosis) and 33 healthy volunteers. We then examined the effect of the AGE inhibitor in a mouse model of human endogenous uveitis (EAU) by continuous oral administration of pyridoxamine at 200 or 400 mg/kg/day. Regardless of the etiology, serum glycer-AGE levels were significantly higher in patients with uveitis than in healthy subjects. Treatment with 400 mg/kg pyridoxamine significantly reduced the clinical and histological severity of EAU and was accompanied by a significant decrease in serum and retinal glycer-AGE levels and suppression of translocation of NF-B p65 into the nucleus of retinal cells. Serum glycer-AGE levels may therefore serve as a biomarker of human uveitis, as well as systemic inflammation, and may contribute to the progression of uveitis, including diabetic iritis, via the activation of NF-B.

硝子体液細胞診における眼内悪性リンパ腫の細胞学的検討　　　　　　　　　　　　　　　
山谷 幸恵, 丸川 活司, 宮越 里絵, 清水 知活, 渡部 涼子, 望月 早苗, 菅野 宏美, 藤澤 孝志, 高桑 恵美, 畑中 佳奈子, 田川 義晃, 南場 研一, 三橋 智子, 松野 吉宏
日本臨床細胞学会雑誌, 53, Suppl.2, 730, 730, (公社)日本臨床細胞学会, 2014年10月
日本語

Evaluation of the long-term efficacy and safety of infliximab treatment for uveitis in Behçet's disease: a multicenter study.
Takeuchi M, Kezuka T, Sugita S, Keino H, Namba K, Kaburaki T, Maruyama K, Nakai K, Hijioka K, Shibuya E, Komae K, Hori J, Ohguro N, Sonoda KH, Mizuki N, Okada AA, Ishibashi T, Goto H, Mochizuki M
Ophthalmology, 121, 10, 1877, 1884, ELSEVIER SCIENCE INC, 2014年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose: To evaluate the long-term efficacy and safety of infliximab for the treatment of uveitis in Behcet'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. (C) 2014 by the American Academy of Ophthalmology.

Therapeutic effects of 0.1% tacrolimus eye drops for refractory allergic ocular diseases with proliferative lesion or corneal involvement
Atsuki Fukushima, Yuichi Ohashi, Nobuyuki Ebihara, Eiichi Uchio, Shigeki Okamoto, Naoki Kumagai, Jun Shoji, Etsuko Takamura, Yayoi Nakagawa, Kenichi Namba, Hiroshi Fujishima, Dai Miyazaki
BRITISH JOURNAL OF OPHTHALMOLOGY, 98, 8, 1023, 1027, BMJ PUBLISHING GROUP, 2014年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Background The objective of this study was to investigate the efficacy of topical 0.1% tacrolimus in treating refractory allergic conjunctivitis with proliferative lesions and/or corneal involvement.
Methods This prospective observational study included 1436 patients with refractory allergic conjunctivitis whose condition had responded poorly to conventional antiallergic drugs and/or topical steroids and/or topical cyclosporine. All patients received tacrolimus eye drops twice daily during the study period. Ten clinical signs and six clinical symptoms were rated on a four-grade scale. The primary endpoint was the change from baseline in total clinical signs and symptoms score at the last observation or following 6 months of treatment.
Results Total signs and symptoms score significantly decreased after 1 month of treatment (p<0.001). Giant papillae and corneal lesions were also reduced by tacrolimus eye drop use (p<0.001). The drug proved effective in patients whose condition did not respond well to topical cyclosporine therapy. About 50% of all patients using topical steroids were weaned. The most common adverse reaction was a transient burning sensation (3.20%).
Conclusions Tacrolimus eye drops are highly effective in treating refractory allergic conjunctivitis with proliferative lesions and/or corneal involvement, and may reduce or replace topical steroid use.

[A case report of malignant lymphoma receiving infliximab therapy with Behçet's disease].
Sonoda KH, Fukuhara T, Yoshikawa H, Takeda A, Yoshimura T, Akahoshi M, Kusumoto H, Kohno K, Kato K, Akashi K, Kohashi K, Aijima S, Namba K, Ishibashi T
Nippon Ganka Gakkai zasshi, 118, 5, 440, 445, 日本眼科学会, 2014年05月, ［査読有り］
日本語

眼内悪性リンパ腫および鑑別疾患における硝子体液を用いた病理診断の有用性
菅野宏美, 藤田裕美, 畑中佳奈子, 田川義晃, 南場研一, 三橋智子, 松野吉宏
日本病理学会会誌, 103, 1, 293, 2014年03月26日
日本語

The International Criteria for Behçet's Disease (ICBD): A collaborative study of 27 countries on the sensitivity and specificity of the new criteria
F. Davatchi, S. Assaad-Khalil, K. T. Calamia, J. E. Crook, B. Sadeghi-Abdollahi, M. Schirmer, T. Tzellos, C. C. Zouboulis, M. Akhlagi, A. Al-Dalaan, Z. S. Alekberova, A. A. Ali, A. Altenburg, E. Arromdee, M. Baltaci, M. Bastos, S. Benamour, I. Ben Ghorbel, A. Boyvat, L. Carvalho, W. Chen, E. Ben-Chetrit, C. Chams-Davatchi, J. A. Correia, J. Crespo, C. Dias, Y. Dong, F. Paixão-Duarte, K. Elmuntaser, A. V. Elonakov, J. Graña Gil, A. A. Haghdoost, R. M. Hayani, H. Houman, A. R. Isayeva, A. R. Jamshidi, P. Kaklamanis, A. Kumar, A. Kyrgidis, W. Madanat, A. Nadji, K. Namba, S. Ohno, I. Olivieri, J. Vaz Patto, N. Pipitone, M. V. De Queiroz, F. Ramos, C. Resende, C. M. Rosa, C. Salvarani, M. J. Serra, F. Shahram, H. Shams, K. E. Sharquie, M. Sliti-Khanfir, T. Tribolet De Abreu, C. Vasconcelos, J. Vedes, B. Wechsler, Y. K. Cheng, Z. Zhang, N. Ziaei
Journal of the European Academy of Dermatology and Venereology, 28, 3, 338, 347, 2014年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective Behçet's disease (BD) is a chronic, relapsing, inflammatory vascular disease with no pathognomonic test. Low sensitivity of the currently applied International Study Group (ISG) clinical diagnostic criteria led to their reassessment. Methods An International Team for the Revision of the International Criteria for BD (from 27 countries) submitted data from 2556 clinically diagnosed BD patients and 1163 controls with BD-mimicking diseases or presenting at least one major BD sign. These were randomly divided into training and validation sets. Logistic regression, 'leave-one-country-out' cross-validation and clinical judgement were employed to develop new International Criteria for BD (ICBD) with the training data. Existing and new criteria were tested for their performance in the validation set. Results For the ICBD, ocular lesions, oral aphthosis and genital aphthosis are each assigned 2 points, while skin lesions, central nervous system involvement and vascular manifestations 1 point each. The pathergy test, when used, was assigned 1 point. A patient scoring ≥4 points is classified as having BD. In the training set, 93.9% sensitivity and 92.1% specificity were assessed compared with 81.2% sensitivity and 95.9% specificity for the ISG criteria. In the validation set, ICBD demonstrated an unbiased estimate of sensitivity of 94.8% (95% CI: 93.4-95.9%), considerably higher than that of the ISG criteria (85.0%). Specificity (90.5%, 95% CI: 87.9-92.8%) was lower than that of the ISG-criteria (96.0%), yet still reasonably high. For countries with at least 90%-of-cases and controls having a pathergy test, adding 1 point for pathergy test increased the estimate of sensitivity from 95.5% to 98.5%, while barely reducing specificity from 92.1% to 91.6%. Conclusion The new proposed criteria derived from multinational data exhibits much improved sensitivity over the ISG criteria while maintaining reasonable specificity. It is proposed that the ICBD criteria to be adopted both as a guide for diagnosis and classification of BD. © 2013 European Academy of Dermatology and Venereology.

Behçet's disease ocular attack score 24: evaluation of ocular disease activity before and after initiation of infliximab.
Kaburaki T, Namba K, Sonoda KH, Kezuka T, Keino H, Fukuhara T, Kamoi K, Nakai K, Mizuki N, Ohguro N, Ocular Behçet, Disease Research, Group of Japan
Japanese journal of ophthalmology, 58, 2, 120, 130, SPRINGER JAPAN KK, 2014年03月, ［査読有り］
英語, 研究論文（学術雑誌）, We developed a novel scoring system for uveitis due to Beh double dagger et's disease (BD), termed Beh double dagger et'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.
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.
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.
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.

Amelioration of endotoxin-induced uveitis treated with the sea urchin pigment echinochrome in rats
Anton Lennikov, Nobuyoshi Kitaichi, Kousuke Noda, Kazuomi Mizuuchi, Ryo Ando, Zhenyu Dong, Junichi Fukuhara, Satoshi Kinoshita, Kenichi Namba, Shigeaki Ohno, Susumu Ishida
MOLECULAR VISION, 20, 171, 177, MOLECULAR VISION, 2014年02月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose: Echinochrome is a pigment present in the shells and spines of sea urchins. It has been reported to have several biologic protective effects, including in experimental models of myocardial ischemia/reperfusion injury, for which the proposed mechanisms are scavenging reactive oxygen species (ROS) and chelating iron. Endotoxin-induced uveitis (EIU) is an animal model of acute anterior segment intraocular inflammation that is induced by the injection of lipopolysaccharide (LPS). In this study, the therapeutic effect of echinochrome was examined in uveitis using the EIU model.
Methods: EIU was induced in Lewis rats via 200 mu g subcutaneous injections of LPS from Escherichia coli. Echinochrome was administered intravenously in 10, 1, or 0.1 mg/kg doses suspended in PBS (controls were injected with PBS only). Twenty-four hours after LPS injection, the number of infiltrating cells and the protein concentration in aqueous humor were determined. Aqueous tumor necrosis factor alpha (TNF-alpha) concentration was quantified with enzyme-linked immunosorbent assay, eyes were stained with nuclear factor (NF) kappa B antibodies, and ROS production was determined by dihydroethidium staining in fresh frozen samples.
Results: The number of inflammatory aqueous cells and protein levels were lower in the groups treated with 10 and 1 mg/kg of echinochrome than in the untreated LPS group (p<0.01). Treatment with 10 and 1 mg/kg of echinochrome significantly reduced TNF-alpha concentrations in aqueous humor (p<0.01). The numbers of NF kappa B-positive cells and ROS signals were also reduced by echinochrome administration (p<0.05).
Conclusions: Echinochrome ameliorated intraocular inflammation caused by EIU by reducing ROS production, thereby also decreasing the expression of NF kappa B and TNF-alpha. As a natural pigment, echinochrome may therefore be a promising candidate for the safe treatment of intraocular inflammation. The use of sea urchin shells and spines in health foods and medical products is thus both economically and environmentally meaningful.

新しいBehcet病ぶどう膜炎の活動性スコアによる評価の再現性の検討　　　　　　　　　　　　　　　
蕪城 俊克, 南場 研一, 園田 康平, 毛塚 剛司, 慶野 博, 福原 崇子, 鴨居 功樹, 中井 慶, Ocular Behcet Disease Research Group of Japan
日本眼科学会雑誌, 117, 11, 935, 936, (公財)日本眼科学会, 2013年11月
日本語

Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet's disease
Yun Jong Lee, Yukihiro Horie, Graham R. Wallace, Yong Seok Choi, Ji Ah Park, Ji Yong Choi, Ran Song, Young-Mo Kang, Seong Wook Kang, Han Joo Baek, Nobuyoshi Kitaichi, Akira Meguro, Nobuhisa Mizuki, Kenichi Namba, Susumu Ishida, Jinhyun Kim, Edyta Niemczyk, Eun Young Lee, Yeong Wook Song, Shigeaki Ohno, Eun Bong Lee
ANNALS OF THE RHEUMATIC DISEASES, 72, 9, 1510, 1516, BMJ PUBLISHING GROUP, 2013年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Objectives
To identify non-major histocompatibility complex susceptible genes that might contribute to Behcet's disease (BD).
Methods
We performed a genome-wide association study using DNA samples from a Korean population consisting of 379 BD patients and 800 controls. A replication study was performed in a Japanese population (363 BD patients and 272 controls). To evaluate the functional implication of the target single nucleotide polymorphisms (SNP), gene expression levels in peripheral T cells, allele-specific modulation of promoter activity and biological effect of mRNA knockdown were investigated.
Results
We found a novel association of BD to the GIMAP locus, mapped to chromosome 7q36.1 (rs1608157, p=6.01x10(-8) in a minor allele dominant model; rs11769828, allele based p=1.60x10(-6)). A fine mapping study identified an association with four additional SNP: rs1522596 (OR=1.45, p=7.70x10(-6)) in GIMAP4; rs10266069 (OR=1.32, p=2.67x10(-4)) and rs10256482 (OR=1.27, p=5.27x10(-4)) in GIMAP2; and rs2286900 (OR=1.61, p=3.53x10(-5)) in GIMAP1 areas. Replication study using DNA samples from the Japanese population validated the significant association between BD and the GIMAP locus. The GIMAP4 promoter construct plasmid with the minor allele of rs1608157 displayed significantly lower activity than one with the major allele. Moreover, CD4 T cells from BD patients showed a lower level of GIMAP4 mRNA, and GIMAP4 knockdown was protective against Fas-mediated apoptosis.
Conclusions
These results suggest that a GIMAP cluster is a novel susceptibility locus for BD, which is involved in T-cell survival, and T-cell aberration can contribute to the development of BD.

エキノクロームによるラットEIUの軽症化　　　　　　　　　　　　　　　
アントン・レニコフ, 北市 伸義, 野田 航介, 南場 研一, 石田 晋, 大野 重昭, 大黒 浩
日本眼薬理学会プログラム・抄録集, 33回, 44, 44, 日本眼薬理学会, 2013年09月
日本語

Clinical features of human T lymphotropic virus type 1-associated uveitis in Hokkaido, Japan
Satoru Kase, Kenichi Namba, Nobuyoshi Kitaichi, Daiju Iwata, Shigeaki Ohno, Susumu Ishida
JAPANESE JOURNAL OF OPHTHALMOLOGY, 57, 4, 379, 384, SPRINGER JAPAN KK, 2013年07月, ［査読有り］
英語, 研究論文（学術雑誌）, To clarify the clinical features of human lymphotropic virus type 1 (HTLV-1)-associated uveitis (HAU) in patients of Hokkaido University Hospital, Hokkaido, northern Japan.
We reviewed the records of a consecutive series of 21 patients with HAU who were followed up for more than 12 months at Hokkaido University Hospital.
Of the 21 patients enrolled in this study, 19 as well as their parents (90.5 %) were born in Hokkaido. One patient was a member of the Ainu ethnic group. Unilateral involvement was found in 16 cases (76 %). In the ophthalmological examinations, vitreous opacity was most frequently followed by keratic precipitate, iris/gonio nodules, and posterior synechiae, while hypopyon, retinal vasculitis, and neovascularization were rarely observed. Intraocular inflammation was controlled by topical treatment, while systemic corticosteroids were required in less than one-fourth of patients. Visual acuity improved in 15 patients, remained unchanged in four patients, and deteriorated in two patients. HAU was observed in two patients with adult T-cell leukemia/lymphoma (ATLL). Three out of the four patients (75 %) for whom HLA typing was available had HLA-A26.
A number of clinical features were unique to Hokkaido, namely, predominant unilateral involvement, as well as two HAU patients with ATLL. The phylogenetic difference of HTLV-1 and HLA typing may correlate with different clinical manifestations in HAU.

Trabecular meshwork depigmentation in Vogt-Koyanagi-Harada disease.
Kazuomi Mizuuchi, Nobuyoshi Kitaichi, Kenichi Namba, Yukihiro Horie, Susumu Ishida, Shigeaki Ohno
Japanese journal of ophthalmology, 57, 3, 245, 51, 2013年05月, ［査読有り］, ［国内誌］
英語, PURPOSE: Since some patients develop depigmentation of the trabecular meshwork in the course of Vogt-Koyanagi-Harada (VKH) disease, we examined the incidence of trabecular depigmentation and its correlation with other ocular findings and systemic symptoms. METHODS: We retrospectively reviewed the clinical charts of 53 Japanese patients diagnosed with VKH disease. The scores of trabecular and limbal pigmentation of all patients were recorded. We then examined the correlation between trabecular pigmentation and the presence of sunset glow fundus or skin lesions. RESULTS: Trabecular pigmentation was significantly lower in the patients with sunset glow fundus than in those without it (P = 0.022), whereas limbal pigmentation showed no significance. However, there were no significant differences in trabecular and limbal pigmentation between the patients with and those without skin lesions. Furthermore, there was no correlation between trabecular and limbal pigmentation. CONCLUSIONS: Depigmentation of the trabecular meshwork develops in some patients in the course of VKH disease. This depigmentation is significantly correlated with sunset glow fundus, but not with limbal depigmentation or skin lesions.

Acute retinal necrosis: factors associated with anatomic and visual outcomes
Chiharu Iwahashi-Shima, Atsushi Azumi, Nobuyuki Ohguro, Annabelle A. Okada, Toshikatsu Kaburaki, Hiroshi Goto, Koh-Hei Sonoda, Kenichi Namba, Nobuhisa Mizuki, Manabu Mochizuki
JAPANESE JOURNAL OF OPHTHALMOLOGY, 57, 1, 98, 103, SPRINGER JAPAN KK, 2013年01月, ［査読有り］
英語, 研究論文（学術雑誌）, To examine the factors associated with anatomic and visual outcomes in Japanese patients with acute retinal necrosis (ARN).
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).
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.
Prophylactic vitrectomy did not improve the final BCVA in any eyes. Zone 3 eyes had better outcomes without prophylactic vitrectomy.

Two cases of subfoveal choroidal neovascularization with tubulointerstitial nephritis and uveitis syndrome
Yuko Takemoto, Kenichi Namba, Kazuomi Mizuuchi, Shigeaki Ohno, Susumu Ishida
European Journal of Ophthalmology, 23, 2, 255, 257, 2013年, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose. Tubulointerstitial nephritis and uveitis (TINU) syndrome usually shows anterior segment intraocular inflammation, but severe posterior segment intraocular inflammation is rarely observed. We report 2 children with TINU syndrome complicated by subfoveal choroidal neovascularization (CNV). Methods. Case reports. Results. Patients were a 12-year-old girl and a 12-year-old boy diagnosed with probable TINU syndrome on the basis of typical ocular findings and high value of urinary β2 microglobulin even though renal biopsy was not performed. The girl showed development of CNV with subretinal macular hemorrhage along with the exacerbation of anterior chamber inflammation in her left eye. Subretinal macular hemorrhage recurred frequently even with oral prednisolone
therefore, intravitreal injection of bevacizumab (IVB) was performed. After IVB, the subretinal proliferative tissue shrunk and subretinal hemorrhage has not recurred for 5 years. The boy showed subretinal hemorrhage from CNV with severe anterior chamber inflammation in his left eye. With oral prednisolone, anterior chamber inflammation and subretinal hemorrhage disappeared, but shrunken subretinal fibrosis in the macula remained. Final visual acuity was poor due to residual subretinal fibrosis in both cases. Conclusions. Tubulointerstitial nephritis and uveitis syndrome has a potential to develop CNV that leads to severe visual loss
therefore, prompt anti-inflammatory therapy is required, and IVB should be regarded as a potential choice of treatment. © 2013 Wichtig Editore.

Bacterial endophthalmitis caused by an intraocular cilium in a patient under treatment with infliximab
Xue-Hai Jin, Kenichi Namba, Wataru Saito, Daiju Iwata, Susumu Ishida
Journal of Ophthalmic Inflammation and Infection, 3, 1, 1, 3, 2013年, ［査読有り］
英語, 研究論文（学術雑誌）, Background: We report a case of bacterial endophthalmitis caused by an intraocular cilium in a patient without any history of trauma or ocular surgery. Findings: A 32-year-old Caucasian male showed symptoms of orbital myositis and scleritis, with no intraocular inflammation in the right eye. The patient had been treated with infliximab for Crohn's disease. Three weeks after initiation of oral prednisolone therapy, he developed bacterial endophthalmitis. During pars plana vitrectomy, a cilium in the massive vitreous opacity was found. A focal scleral necrosis was detected just outside where the cilium was intraoperatively observed. Vitreous culture showed the presence of Staphylococcus aureus. Conclusions: The intraocular cilium seemed to be the aetiology of the endophthalmitis in this case, which suggests that anti-tumour necrosis factor-α therapy may play a role in the migration of cilia into the globe and the occurrence of endophthalmitis. © 2013 Jin et al.

Genetic Characterization and Susceptibility for Sarcoidosis in Japanese Patients: Risk Factors of BTNL2 Gene Polymorphisms and HLA Class II Alleles
Hitomi Suzuki, Masao Ota, Akira Meguro, Yoshihiko Katsuyama, Tatukata Kawagoe, Mami Ishihara, Yuri Asukata, Masaki Takeuchi, Norihiko Ito, Etsuko Shibuya, Eiichi Nomura, Riyo Uemoto, Tadayuki Nishide, Kenichi Namba, Nobuyoshi Kitaichi, Shin-ichiro Morimoto, Toshikatsu Kaburaki, Yasutaka Ando, Shinobu Takenaka, Jutaro Nakamura, Kozou Saeki, Shigeaki Ohno, Hidetoshi Inoko, Nobuhisa Mizuki
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 53, 11, 7109, 7115, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2012年10月, ［査読有り］
英語, 研究論文（学術雑誌）, 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 X 10(-5), odds ratio [OR] = 2.43) and BTNL2 rs2076530_A (P = 6.90 X 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. (Invest Ophthalmol Vis Sci. 2012;53:7109-7115) DOI:10.1167/iovs.12-10491

Amelioration of endotoxin-induced uveitis treated with an IκB kinase β inhibitor in rats.
Lennikov A, Kitaichi N, Noda K, Ando R, Dong Z, Fukuhara J, Kinoshita S, Namba K, Mizutani M, Fujikawa T, Itai A, Ohno S, Ishida S
Molecular vision, 18, 267-70, 2586, 2597, MOLECULAR VISION, 2012年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose: Endotoxin-induced uveitis (EIU) is an animal model for acute ocular inflammation. Several substances play major roles in the development of inflammatory changes in EIU, including tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and IL-6. These inflammatory cytokines trigger the degradation of I kappa B by activating I kappa B kinases (IKKs). Released nuclear factor kappaB (NF kappa B) subsequently translocates to the nucleus, where NF kappa B expresses its proinflammatory function. IMD-0354, N-(3,5-Bis-trifluoromethylphenyl)-5-chloro-2-hydroxybenzamide, selectively inhibits IKK beta, particularly when induced by proinflammatory cytokines, such as TNF-alpha and IL-1 beta. In the present study, we examined whether IKK beta inhibition has therapeutic effects on EIU by using IMD-0354 and its prodrug IMD-1041.
Methods: Six-week-old male Lewis rats were used. EIU was induced with subcutaneous injections of 200 mu g of lipopolysaccharide (LPS) from Escherichia coli that had been diluted in 0.1 ml of phosphate-buffered saline. IMD-0354 was administered intraperitoneally at 30, 10, 3, or 0 mg/kg, suspended in 1.0 ml of 0.5% carboxymethyl cellulose sodium. The prodrug IMD-1041 (100 mg/kg) was also administered orally. The rats were euthanized 24 h after LPS injection, and EIU severity was evaluated histologically. The number of infiltrating cells and the protein, TNF-alpha, and monocyte chemoattractant protein-1 (MCP-1) concentrations in the aqueous humor were determined. TNF-alpha and MCP-1 concentrations were quantified with enzyme-linked immunosorbent assay. Eye sections were also stained with anti-NF kappa B and phosphorylated I-kappa B alpha antibodies.
Results: The number of infiltrating cells in aqueous humor was 53.6 +/- 9.8x10(5), 72.5 +/- 17.0x10(5), 127.25 +/- 32.0x10(5), and 132.0 +/- 25.0x10(5) cells/ml in rats treated with 30, 10, 3, or 0 mg/kg of IMD-0354, respectively. The total protein concentrations of aqueous humor were 92.6 +/- 3.1 mg/ml, 101.5 +/- 6.8 mg/ml, 112.6 +/- 1.9 mg/ml, and 117.33 +/- 1.8 mg/ml in rats treated with 30, 10, 3, and 0 mg/kg of IMD-0354, respectively. Infiltrating cells and protein concentrations were significantly decreased by treatment with IMD-0354 (p < 0.01). IMD-0354 treatment significantly reduced the concentration of TNF-alpha (p < 0.05) and MCP-1 (p < 0.01) in aqueous humor. The number of NF kappa B positive nuclei was reduced when treated with IMD-0354. Furthermore, IMD-0354-treated EIU rats showed only background levels of phosphorylated I-kappa B alpha; however, it was strongly expressed in the iris-ciliary body cell cytoplasm of the IMD-0354 untreated EIU rats. Oral administration of IMD-1041 also decreased the cell number (p < 0.01) and protein concentration (p < 0.05) of aqueous humor in EIU.
Conclusions: Acute uveitis was ameliorated by inhibition of IKK beta in rats. IMD-0354 and its prodrug IMD-1041 seem to be promising candidates for treating intraocular inflammation/uveitis.

Correlation between elevation of serum antinuclear antibody titer and decreased therapeutic efficacy in the treatment of Behçet's disease with infliximab.
Iwata D, Namba K, Mizuuchi K, Kitaichi N, Kase S, Takemoto Y, Ohno S, Ishida S
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 250, 7, 1081, 1087, 7, 2012年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Infliximab, an anti-TNF-alpha monoclonal antibody, administered to Beh double dagger et's disease (BD) patients in Japan with refractory intraocular inflammation, has shown excellent clinical results. However, some patients demonstrate a decreased response to infliximab during the course of the treatment. In the present study, we investigated the correlation between this reduced therapeutic effect and elevation of the serum antinuclear antibody (ANA) titers in patients with BD who were undergoing infliximab therapy.
Seventeen patients (14 males and three females) with uveitis in BD who were undergoing treatment with infliximab for 2 years or longer were enrolled. Their blood test results and clinical histories were obtained from medical records.
One patient (5.9%) was ANA-positive prior to the initiation of infliximab, and 11 patients (64.7%) developed positive ANA during the therapy. The appearance of ANA was observed 6 months after the initiation of the infliximab therapy, and its titers gradually increased. None of the patients showed lupus symptoms. Five patients (29.4%) have suffered from ocular inflammatory attacks since the sixth month from the initiation of infliximab treatment and all of them were ANA-positive. In contrast, four patients (23.5%) who were ANA-negative experienced no ocular attacks during the follow-up period.
Here we report the positive conversion and subsequent elevation of serum ANA titers in some patients with BD after the initiation of infliximab therapy. Since all recurrences of uveitis were shown only in the ANA-positive patients, serum ANA titer may be a helpful biomarker for predicting the recurrence of ocular attacks in BD patients treated with anti-TNF-alpha antibody therapies.

Replication of a microsatellite genome-wide association study of Behcet's disease in a Korean population
Yukihiro Horie, Akira Meguro, Nobuyoshi Kitaichi, Eun Bong Lee, Atsuhiro Kanda, Kousuke Noda, Yeong Wook Song, Kyung Sook Park, Kenichi Namba, Masao Ota, Hidetoshi Inoko, Nobuhisa Mizuki, Susumu Ishida, Shigeaki Ohno
RHEUMATOLOGY, 51, 6, 983, 986, OXFORD UNIV PRESS, 2012年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective. Behcet's disease is one of the major aetiologies of uveitis causing blindness in Asian countries. A genome-wide association study identified six microsatellite markers as disease susceptibility loci for Japanese patients with Behcet's disease. To confirm our recent results, these microsatellite markers were examined in a Korean population as a replication study.
Methods. Study participants included 119 Behcet's disease patients and 141 controls. All were enrolled in Korea. Association between the six reported microsatellite markers (D3S0186i, D6S0014i, D6S0032i, 536G12A, D12S0645i and D22S0104i) and Behcet's disease was analysed. HLA-B was genotyped by sequence-based typing methods.
Results. A microsatellite marker located near the HLA-B region demonstrated significant association with Behcet's disease (P = 0.028). The genotype and phenotype frequencies of the HLA-B*51 gene were significantly increased in patients (23.1 and 39.5%, respectively) compared with healthy controls (11.2 and 20.1%, respectively; P < 0.001).
Conclusion. Microsatellite analysis revealed that the HLA-B*51 gene was strongly associated with Behcet's disease in a Korean population.

Blood Level of Tacrolimus in Patients with Severe Allergic Conjunctivitis Treated by 0.1% Tacrolimus Ophthalmic Suspension
Nobuyuki Ebihara, Yuichi Ohashi, Hiroshi Fujishima, Atsuki Fukushima, Yayoi Nakagawa, Kenichi Namba, Shigeki Okamoto, Jun Shoji, Etsuko Takamura, Eiichi Uchio, Dai Miyazaki
ALLERGOLOGY INTERNATIONAL, 61, 2, 275, 282, JAPANESE SOCIETY ALLERGOLOGY, 2012年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: To estimate the efficacy and safety of 0.1% tacrolimus ophthalmic suspension based on the blood level of tacrolimus in patients with severe allergic conjunctivitis.
Methods: Fifty-two patients in whom topical anti-allergic agents had been ineffective were treated with 0.1% tacrolimus ophthalmic suspension twice daily for 12 weeks. Adverse drug reactions were monitored, as well as ocular symptoms and signs. The blood concentration of tacrolimus was measured before the initiation of treatment and 4 and 12 weeks later.
Results: About 75% of the patients without concomitant using of tacrolimus ointment had blood levels of tacrolimus below the detection limit of the assay (0.5 ng/mL). On the other hand, 71% (week 4) and 57% (week 12) of patients with concomitant using of tacrolimus ointment had blood levels above the detection limit of the assay. However, the maximum blood concentration was less than 2 ng/mL. Adverse drug reactions occurred in 16 patients. These were disorders of the eye such as warmness, irritation, and a burning sensation. However, all of the patients could continue treatment with tacrolimus for 12 weeks. There were no serious adverse events such as increased intraocular pressure or ocular infection during the study. All symptoms and signs improved over time.
Conclusions: The good safety profile of 0.1% tacrolimus ophthalmic suspension based on the low blood concentration of tacrolimus, coupled with demonstrated efficacy, make it an important tool for treating severe allergic conjunctivitis.

Spontaneous Regression of Intraocular Lymphoma
Satoru Kase, Kenichi Namba, Xue-Hai Jin, Kanako C. Kubota, Susumu Ishida
OPHTHALMOLOGY, 119, 5, 1083, 1084, ELSEVIER SCIENCE INC, 2012年05月, ［査読有り］
英語

Chickenpox chorioretinitis with retinal exudates and periphlebitis.
Hirokuni Kitamei, Kenichi Namba, Nobuyoshi Kitaichi, Akiko Wakayama, Shigeaki Ohno, Susumu Ishida
Case reports in ophthalmology, 3, 2, 180, 4, 2, 2012年05月, ［査読有り］, ［国際誌］
英語, BACKGROUND: Chickenpox is rarely associated with posterior segment inflammation. We report on a case of unilateral chickenpox chorioretinitis with retinal exudates and periphlebitis. CASE PRESENTATION: A 21-year-old healthy man, who suffered from chickenpox 2 weeks prior to symptom development, exhibited mild anterior chamber cells, vitreous opacity, sheathing of retinal veins, and yellow-white exudates in his right eye. Varicella zoster virus DNA was detected by polymerase chain reaction in the aqueous humor. He was treated with intravenous acyclovir followed by oral prednisolone and valaciclovir. Aqueous cells quickly disappeared and retinal exudates diminished within 1 month, leaving faint retinal scarring. Retinal arteritis had never been observed in this patient. CONCLUSIONS: ALTHOUGH THE OCULAR FINDINGS IN THIS CASE WERE SIMILAR TO ACUTE RETINAL NECROSIS (ARN), THE CLINICAL FEATURES DIFFERED FROM ARN IN THE FOLLOWING POINTS: (1) mild anterior chamber inflammation, (2) absence of retinal arteritis, and (3) prompt resolution of inflammatory findings. The distinctive clinical features indicated that chorioretinitis associated with chickenpox may not have the same pathological conditions as ARN.

Lack of association between IL10 polymorphisms and sarcoidosis in Japanese patients
Kenichi Sakuyama, Akira Meguro, Masao Ota, Mami Ishihara, Riyo Uemoto, Haruyasu Ito, Eiichi Okada, Kenichi Namba, Nobuyoshi Kitaichi, Shin-ichiro Morimoto, Toshikatsu Kaburaki, Yasutaka Ando, Shinobu Takenaka, Takenosuke Yuasa, Shigeaki Ohno, Hidetoshi Inoko, Nobuhisa Mizuki
MOLECULAR VISION, 18, 56, 512, 518, MOLECULAR VISION, 2012年02月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

Intravitreal injection of bevacizumab in a case of occlusive retinal vasculitis accompanied by syphilitic intraocular inflammation
Kan Ishijima, Kenichi Namba, Shigeaki Ohno, Kiyofumi Mochizuki, Susumu Ishida
Case Reports in Ophthalmology, 3, 3, 434, 437, 2012年, ［査読有り］
英語, 研究論文（学術雑誌）, Background: We report a rare case of syphilitic intraocular inflammation with occlusive retinal vasculitis treated with intravitreal injection of bevacizumab (IVB) in addition to conventional therapy for syphilis. Case: A 24-year-old woman who complained floaters in both her eyes showed occlusive retinal vasculitis OU. According to the high titer of the Treponema antigen and characteristic cutaneous eruption, she was diagnosed as secondary syphilis. Observation: She was treated with oral amoxicillin and retinal photocoagulation OU. Then, administration of prednisolone was required to the intraocular inflammations considered as Jarisch-Herxheimer reactions. IVB was also performed toward exacerbated retinal neovascularization and showed transient effects. Conclusion: We experienced a rare case of occlusive retinal vasculitis accompanied by syphilis intraocular inflammation. IVB was considered to be effective as an adjunctive therapy for inflammatory neovascularizations. © 2012 S. Karger AG, Basel.

Investigation of Association between TLR9 Gene Polymorphisms and VKH in Japanese Patients
Ryuta Ito, Masao Ota, Akira Meguro, Yoshihiko Katsuyama, Riyo Uemoto, Eiichi Nomura, Tadayuki Nishide, Nobuyoshi Kitaichi, Yukihiro Horie, Kenichi Namba, Shigeaki Ohno, Hidetoshi Inoko, Nobuhisa Mizuki
OCULAR IMMUNOLOGY AND INFLAMMATION, 19, 3, 202, 205, INFORMA HEALTHCARE, 2011年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose: Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disorder affecting melanocytes in the skin, eyes, inner ear, and meninges. The Epstein-Barr virus and cytomegalovirus (CMV) antigen have been hypothesized as possible triggering factors for the disease. Toll-like receptors (TLRs) play an important role in the induction of defense mechanisms of the innate and adaptive immune responses to microbial pathogens. Among TLRs, TLR9 recognizes unmethylated 2'-deoxyribo (cytidine-phosphate guanosine)(CpG) DNA motifs that are frequently present in viruses and plays a central role in the host defense against viral infection. The aim of this study was to investigate whether TLR9 polymorphisms were associated with VKH in a Japanese population.
Methods: Ninety-four Japanese patients diagnosed with VKH and 125 healthy control subjects were recruited. Five single-nucleotide polymorphisms (SNPs: rs187084, rs5743836, rs352139, rs352140, rs5743845) in the TLR9 gene were genotyped, and allelic and phenotypic diversity was assessed between cases and control subjects.
Results: Strong linkage disequilibrium was observed among three SNPs (D'' > 0.99), which were located in one haplotype block. Two SNPs (rs5743836 and rs5743845) were monopolymorphic in both cases and controls. No statistically significant association was observed for any of the SNPs between cases and controls.
Conclusion: Three SNPs in the TLR9 gene were not significantly associated with susceptibility to VKH.

[A prospective, observational, all-prescribed-patients study of cyclosporine 0.1% ophthalmic solution in the treatment of vernal keratoconjunctivitis].
Takamura E, Uchio E, Ebihara N, Okamoto S, Kumagai N, Shoji J, Nakagawa Y, Namba K, Fukushima A, Fujishima H, Miyazaki D, Ohashi Y
Nippon Ganka Gakkai zasshi, 115, 6, 508, 515, 6, 2011年06月, ［査読有り］
日本語

Toll-like receptor 2 (TLR2) gene polymorphisms are not associated with sarcoidosis in the Japanese population
Mayuki Sato, Tatsukata Kawagoe, Akira Meguro, Masao Ota, Yoshihiko Katsuyama, Mami Ishihara, Kenichi Namba, Nobuyoshi Kitaichi, Shin-ichiro Morimoto, Toshikatsu Kaburaki, Yasutaka Ando, Shinobu Takenaka, Shigeaki Ohno, Hidetoshi Inoko, Nobuhisa Mizuki
MOLECULAR VISION, 17, 83, 731, 736, MOLECULAR VISION, 2011年03月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

Japanese guideline for allergic conjunctival diseases
Etsuko Takamura, Eiichi Uchio, Nobuyuki Ebihara, Shigeaki Ohno, Yuichi Ohashi, Shigeki Okamoto, Naoki Kumagai, Yoshiyuki Satake, Jun Shoji, Yayoi Nakagawa, Kenichi Namba, Kazumi Fukagawa, Atsuki Fukushima, Hiroshi Fujishima
Allergology International, 60, 2, 191, 203, Japanese Society of Allergology, 2011年, ［査読有り］
英語, The definition, classification, pathogenesis, test methods, clinical findings, criteria for diagnosis, and therapies of allergic conjunctival disease are summarized based on the Guidelines for Clinical Management of Allergic Conjunctival Disease (Second Edition) revised in 2010. Allergic conjunctival disease is defined as "a conjunctival inflammatory disease associated with a Type I allergy accompanied by some subjective or objective symptoms." Allergic conjunctival disease is classified into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. Representative subjective symptoms include ocular itching, hyperemia, and lacrimation, whereas objective symptoms include conjunctival hyperemia, swelling, folliculosis, and papillae. Patients with vernal keratoconjunctivitis, which is characterized by conjunctival proliferative changes called giant papilla accompanied by varying extents of corneal lesion, such as corneal erosion and shield ulcer, complain of foreign body sensation, ocular pain, and photophobia. In the diagnosis of allergic conjunctival diseases, it is required that type I allergic diathesis is present, along with subjective and objective symptoms accompanying allergic inflammation. The diagnosis is ensured by proving a type I allergic reaction in the conjunctiva. Given that the first-line drug for the treatment of allergic conjunctival disease is an antiallergic eye drop, a steroid eye drop will be selected in accordance with the severity. In the treatment of vernal keratoconjunctivitis, an immunosuppressive eye drop will be concomitantly used with the abovementioned drugs. ©2011 Japanese Society of Allergology.

サルコイドーシスと鑑別を要するぶどう膜炎－非肉芽腫性ぶどう膜炎－
南場 研一
日本サルコイドーシス／肉芽腫性疾患学会雑誌, 31, 1, 76, 78, Japan Society of Sarcoidosis and Other Granulomatous Disorders, 2011年
日本語

Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behçet's disease susceptibility loci.
Mizuki N, Meguro A, Ota M, Ohno S, Shiota T, Kawagoe T, Ito N, Kera J, Okada E, Yatsu K, Song YW, Lee EB, Kitaichi N, Namba K, Horie Y, Takeno M, Sugita S, Mochizuki M, Bahram S, Ishigatsubo Y, Inoko H
Nature genetics, 42, 8, 703, U83, 8, 2010年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Behcet's disease is a chronic systemic inflammatory disorder characterized by four major manifestations: recurrent ocular symptoms, oral and genital ulcers and skin lesions(1). We conducted a genome-wide association study in a Japanese cohort including 612 individuals with Behcet's disease and 740 unaffected individuals (controls). We identified two suggestive associations on chromosomes 1p31.3 (IL23R-IL12RB2, rs12119179, P = 2.7 x 10(-8)) and 1q32.1 (IL10, rs1554286, P = 8.0 x 10(-8)). A meta-analysis of these two loci with results from additional Turkish and Korean cohorts showed genome-wide significant associations (rs1495965 in IL23R-IL12RB2, P = 1.9 x 10(-11), odds ratio = 1.35; rs1800871 in IL10, P = 1.0 x 10(-14), odds ratio = 1.45).

Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behçet's disease susceptibility loci.
Mizuki Nobuhisa, Meguro Akira, Ota Masao, Ohno Shigeaki, Shiota Tomoko, Kawagoe, Tatsukata, Ito Norihiko, Kera Jiro, Okada Eiichi, Yatsu Keisuke, Song Yeong-Wook,Lee Eun-Bong, Kitaichi Nobuyoshi, Namba Kenichi, Horie Yukihiro, Takeno Mitsuhiro, Sugita Sunao, Mochizuki Manabu, Bahram Seiamak, Ishigatsubo Yoshiaki, Inoko Hidetoshi
Nature genetics, 42, 8, 703, 6, 2010年08月, ［査読有り］
英語, Behçet's disease is a chronic systemic inflammatory disorder characterized by four major manifestations: recurrent ocular symptoms, oral and genital ulcers and skin lesions. We conducted a genome-wide association study in a Japanese cohort including 612 individuals with Behçet's disease and 740 unaffected individuals (controls). We identified two suggestive associations on chromosomes 1p31.3 (IL23R-IL12RB2, rs12119179, P = 2.7 x 10(-8)) and 1q32.1 (IL10, rs1554286, P = 8.0 x 10(-8)). A meta-analysis of these two loci with results from additional Turkish and Korean cohorts showed genome-wide significant associations (rs1495965 in IL23R-IL12RB2, P = 1.9 x 10(-11), odds ratio = 1.35; rs1800871 in IL10, P = 1.0 x 10(-14), odds ratio = 1.45).

Amelioration of Experimental Autoimmune Uveoretinitis with Nuclear Factor-kappa B Inhibitor Dehydroxy Methyl Epoxyquinomicin in Mice
Daiju Iwata, Nobuyoshi Kitaichi, Akiko Miyazaki, Kazuya Iwabuchi, Kazuhiko Yoshida, Kenichi Namba, Michitaka Ozaki, Shigeaki Ohno, Kazuo Umezawa, Kenichiro Yamashita, Satoru Todo, Susumu Ishida, Kazunori Onoe
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 51, 4, 2077, 2084, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2010年04月, ［査読有り］
英語, 研究論文（学術雑誌）, PURPOSE. Experimental autoimmune uveoretinitis (EAU), a Th1/Th17 cell-mediated autoimmune disease induced in mice, serves as a model of human endogenous uveitis. In this model, proinflammatory cytokines and various stimuli activate the transcriptional factor, nuclear factor-kappa B (NF-kappa B), in the retina. The therapeutic effect of the NF-kappa B inhibitor, dehydroxy methyl epoxyquinomicin (DHMEQ), was examined on EAU.
METHODS. EAU was induced in B10.BR mice by K2 peptide immunization. DHMEQ (40 mg/kg/d) was administered daily by intraperitoneal injection. Clinical severity and histopathologic severity were assessed. Translocation of NF-kappa B p65 into the nucleus in EAU retina was assessed. T cells were collected from draining lymph nodes of the K2-immunized mice to examine antigen (Ag)-specific T-cell active responses and cytokine production in vitro.
RESULTS. Disease onset was significantly delayed in DHMEQ-treated mice (15.6 days) compared with untreated mice (12.6 days; P < 0.01). Histologic severity was significantly milder in DHMEQ-treated mice (score, 1.13) than in controls (score, 2.33; P < 0.05). DHMEQ suppressed the Ag-specific T-cell active responses and downregulated the productions of Th-1 type cytokines in vitro in a dose-dependent manner. Alternation was not observed in Th-2 type cytokines. Pretreatment of primed T cells or Ag-presenting cells with DHMEQ reduced T-cell activation and Th1/Th17 cytokine production. DHMEQ treatment suppressed the translocation of the NF-kappa B p65 subunit into the nuclei.
CONCLUSIONS. Systemic administration of DHMEQ suppressed NF-kappa B translocation in the retina, which might have reduced the inflammation of ocular tissues. DHMEQ-mediated regulation of NF-kappa B p65 could be a therapeutic target for the control of endogenous ocular inflammatory diseases. (Invest Ophthalmol Vis Sci. 2010; 51: 2077-2084) DOI:10.1167/iovs.09-4030

A Randomized, Placebo-Controlled Clinical Trial of Tacrolimus Ophthalmic Suspension 0.1% in Severe Allergic Conjunctivitis
Yuichi Ohashi, Nobuyuki Ebihara, Hiroshi Fujishima, Atsuki Fukushima, Naoki Kumagai, Yayoi Nakagawa, Kenichi Namba, Shigeki Okamoto, Jun Shoji, Etsuko Takamura, Kunihiko Hayashi
JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS, 26, 2, 165, 173, MARY ANN LIEBERT INC, 2010年04月, ［査読有り］
英語, 研究論文（学術雑誌）, Aims: To examine the efficacy of tacrolimus ophthalmic suspension 0.1% in treating severe allergic conjunctivitis.
Methods: This was a multicenter, randomized, double-masked, placebo-controlled clinical trial. Fifty-six patients with severe allergic conjunctivitis in whom topical antiallergic agents and corticosteroids had been ineffective were randomized to tacrolimus or placebo treatment. Patients were treated either with tacrolimus or placebo twice-daily for 4 weeks. Severity of objective signs in palpebral and bulbar conjunctiva, limbus, and corneal involvement was assessed using 4 grades. Seven subjective symptoms were evaluated by visual analog scale (VAS) assessment. The primary efficacy endpoint was change in the total score of objective signs at the end of treatment. The secondary efficacy endpoints included change in the score for each objective sign and change in the VAS for each subjective symptom. Safety was assessed based on the severity and the incidence of adverse events.
Results: Mean change from baseline in total score for objective signs was significantly greater in the tacrolimus (-5.6 +/- 5.1) than in the placebo group (-0.1 +/- 4.5; P < 0.001). Tacrolimus significantly improved giant papillae (P = 0.001) and corneal involvement (P = 0.005). Five subjective symptoms (itching, discharge, hyperemia, lacrimation, and foreign body sensation) were significantly better in the tacrolimus than in the placebo group. The most frequent treatment-related adverse event in the tacrolimus group was mild ocular irritation upon topical instillation, which was well-tolerated.
Conclusion: Tacrolimus ophthalmic suspension 0.1% is effective in treating severe allergic conjunctivitis.

[Infliximab treatment for Behçet's disease--beginning of the biological drug era].
Namba K
Nippon Ganka Gakkai zasshi, 114, 85, 86, 2, 2010年02月, ［査読有り］

Prevention of experimental autoimmune uveoretinitis by blockade of osteopontin with small interfering RNA
Daiju Iwata, Mizuki Kitamura, Nobuyoshi Kitaichi, Yoshinari Saito, Shigeyuki Kon, Kenichi Namba, Junko Morimoto, Akiko Ebihara, Hirokuni Kitamei, Kazuhiko Yoshida, Susumu Ishida, Shigeaki Ohno, Toshimitsu Uede, Kazunori Onoe, Kazuya Iwabuchi
EXPERIMENTAL EYE RESEARCH, 90, 1, 41, 48, ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2010年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Osteopontin (OPN) is elevated during the progression of experimental autoimmune uveoretinitis (EAU) in C57BL/6 (B6) mice. Furthermore, EAU symptoms are ameliorated in OPN knockout mice or in B6 mice treated with anti-OPN antibody (M5). Recently, OPN has been shown to promote the Th1 response not only in the extracellular space as a secretory protein but also in cytosol as a signaling component. Thus, we attempted to reduce OPN in both compartments by using a small interfering RNA (siRNA) targeting the OPN coding sequence (OPN-siRNA). EAU was induced in B6 mice by immunization with human interphotoreceptor retinoid-binding protein (hIRBP) peptide sequence 1-20. The OPN- or control-siRNA was administered with hydrodynamic methods 24 h before and simultaneously with immunization (prevention regimen). When plasma OPN levels were quantified following siRNA administration with the prevention regimen, the level in the OPN-siRNA-treated group was significantly lower than that in the control-siRNA-treated group. Accordingly, the clinical and histopathological scores of EAU were significantly reduced in B6 mice when siRNA caused OPN blockade. Furthermore, TNF-alpha, IFN-gamma, IL-2, GM-CSFand IL-17 levels in the culture supernatants were markedly suppressed in the OPN-siRNA-treated group, whereas the proliferative responses of T lymphocytes from regional lymph nodes against immunogenic peptides was not significantly reduced. On the other hand, the protection was not significant if the mice received the OPN-siRNA treatment on day 7 and day 8 after immunization when the clinical symptoms appeared overt (reversal regimen). Our results Suggest that OPN blockade with OPN-siRNA can be an alternative choice for the usage of anti-OPN antibody and controlling uveoretinitis in the preventive regimen. (C) 2009 Elsevier Ltd. All rights reserved.

Elevation of surfactant protein D, a pulmonary disease biomarker, in the sera of uveitis patients with sarcoidosis
Nobuyoshi Kitaichi, Mizuki Kitamura, Kenichi Namba, Susumu Ishida, Shigeaki Ohno
JAPANESE JOURNAL OF OPHTHALMOLOGY, 54, 1, 81, 84, SPRINGER TOKYO, 2010年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Surfactant protein D (SP-D) is found in the epithelial cells of multiple mucosal surfaces. It is commonly used to diagnose and screen for pulmonary diseases. In the present study, serum levels of SP-D were measured in patients with uveitis to ascertain whether SP-D is a clinically useful laboratory parameter to diagnose sarcoidosis.
Sera were obtained from 81 patients with sarcoidosis, 16 patients with Beh double dagger et disease, 40 patients with HLA-B27 associated uveitis, 50 patients with Vogt-Koyanagi-Harada (VKH) disease, and 33 healthy volunteers. Serum SP-D levels were quantified with an SP-D enzyme immunoassay kit.
In the healthy control subjects, the average serum SP-D level was 39.70 ng/ml; in the uveitis patients with sarcoidosis, the mean serum SP-D level was 57.0 ng/ml, and in the uveitis patients with other etiologies the mean levels were 38.63 ng/ml for Beh double dagger et disease, 38.18 ng/ml for HLA-B27 associated uveitis, and 31.32 ng/ml for the VKH patients. The average serum SP-D levels of patients with sarcoidosis were significantly higher than those of patients with any other uveitis etiologies or healthy controls (P < 0.01).
SP-D may be a less invasive and less expensive laboratory examination for sarcoidosis screening. SP-D should be considered as a new laboratory parameter for the diagnosis of uveitis and sarcoidosis.

Lack of association between toll-like receptor 4 gene polymorphisms and sarcoidosis-related uveitis in Japan
Yuri Asukata, Masao Ota, Akira Meguro, Yoshihiko Katsuyama, Mami Ishihara, Kenichi Namba, Nobuyoshi Kitaichi, Shin-ichiro Morimoto, Toshikatsu Kaburaki, Yasutaka Ando, Shinobu Takenaka, Hidetoshi Inoko, Shigeaki Ohno, Nobuhisa Mizuki
MOLECULAR VISION, 15, 283-88, 2673, 2682, MOLECULAR VISION, 2009年12月, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

Clinical features of intraocular inflammation in Hokkaido, Japan
Hirokuni Kitamei, Nobuyoshi Kitaichi, Kenichi Namba, Satoshi Kotake, Chiho Goda, Mizuki Kitamura, Akiko Miyazaki, Shigeaki Ohno
ACTA OPHTHALMOLOGICA, 87, 4, 424, 428, WILEY-BLACKWELL PUBLISHING, INC, 2009年06月, ［査読有り］
英語, 研究論文（学術雑誌）, We aimed to investigate the clinical features of intraocular inflammation/uveitis in Hokkaido, Japan.
We retrospectively reviewed the medical records of 1240 uveitis patients (511 men, 729 women) who visited Hokkaido University Hospital, Sapporo, Japan between 1994 and 2003.
Mean age at disease onset was 41.7 +/- 17.8 years in men and 45.7 +/- 18.3 years in women. Anterior, posterior and combined anterior and posterior segment intraocular inflammation accounted for 45.1%, 4.7% and 50.2% of cases, respectively. Sarcoidosis was the most frequent aetiology (14.9%), followed by Vogt-Koyanagi-Harada (VKH) disease (9.7%) and Behcet's disease (6.7%). Aetiologies in 49.8% patients were unknown. In sarcoidosis, women represented 72.4% of patients, and disease onset occurred at 35.1 +/- 19.0 years of age in men and 50.3 +/- 16.5 years in women. In VKH disease, 54.2% of patients were women, and disease onset took place at 45.9 +/- 15.8 years in men and 46.4 +/- 14.1 years in women. In Behcet's disease, men accounted for 56.6% of patients, and disease onset occurred at 35.5 +/- 8.5 years in men and 44.5 +/- 11.5 years in women.
Women were more prone to developing sarcoidosis compared with men. By contrast, men were more prone to developing Behcet's disease. The mean age at disease onset in both sarcoidosis and Behcet's disease was significantly lower in men than in women.

Association of TLR4 polymorphisms with Behets disease in a Korean population
Yukihiro Horie, Akira Meguro, Masao Ota, Nobuyoshi Kitaichi, Yoshihiko Katsuyama, Yuko Takemoto, Kenichi Namba, Kazuhiko Yoshida, Yeong Wook Song, Kyung Sook Park, Eun Bong Lee, Hidetoshi Inoko, Nobuhisa Mizuki, Shigeaki Ohno
RHEUMATOLOGY, 48, 6, 638, 642, OXFORD UNIV PRESS, 2009年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Objectives. HLA-B51 is strongly associated with Behets disease (BD) in any ethnic background. We recently reported that another gene, Toll-like receptor-4 (TLR4) is also implicated in BD in a Japanese population. To confirm these results, we investigated polymorphisms in the TLR4 gene in Korean patients with BD.
Methods. In this study, 119 patients with BD and 141 healthy controls were enrolled; every participant was a Korean. Nine single nucleotide polymorphisms previously detected in TLR4 by direct sequencing were analysed for an association with BD.
Results. The most frequent haplotype, TAGCGGTAA, was significantly increased in HLA-B51-positive BD patients (49.5), compared with healthy control participants [32.3; P0.029; odds ratio (OR)2.01; 95 CI 1.253.23]. This haplotype was also significantly increased in BD patients with arthritis (48.2; P0.003; OR1.96; 95 CI 1.263.26). There were no significant differences in the allele and genotype frequencies of patients and controls for each single nucleotide polymorphism.
Conclusions. The haplotype of TLR4 may increase the risk for developing BD and the complication of arthritis in the Korean population.

Elevated choroidal blood flow velocity during systemic corticosteroid therapy in Vogt-Koyanagi-Harada disease
Shigeki Hirose, Wataru Saito, Kazuhiko Yoshida, Michiyuki Saito, Zhenyu Dong, Kenichi Namba, Hisao Satoh, Shigeaki Ohno
ACTA OPHTHALMOLOGICA, 86, 8, 902, 907, WILEY-BLACKWELL PUBLISHING, INC, 2008年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Laser speckle flowgraphy (LSFG) can be used to non-invasively visualize the haemodynamics of choroidal circulation and the vascular pattern. The purpose of this study was to examine the ability of LSFG to quantitatively evaluate blood flow velocity at the macula in patients with Vogt-Koyanagi-Harada (VKH) disease before and after systemic corticosteroid therapy.
Prednisolone (200 mg/day) was systemically administered in 10 VKH disease patients with serous retinal detachment at the macular area. The drug was gradually tapered to zero over a 6-month period. Laser speckle flowgraphy measurements were taken in the 20 eyes of these patients at their initial visit and at 1, 4 and 12 weeks after the onset of therapy. Square blur rate (SBR), a quantitative index of relative blood flow velocity, was calculated using LSFG.
Serous retinal detachment resolved within 4 weeks after treatment and visual acuities improved to > 1.0 in almost all cases. There were significant increases in average SBR at the macula at 4 weeks after treatment compared with at 1 week after treatment, and also at 12 weeks after treatment compared with at 4 weeks after treatment.
These results suggest that systemic corticosteroid therapy improves inflammation-related impairment in choroidal blood flow velocity at the macula. Laser speckle flowgraphy can evaluate the effect of systemic corticosteroid therapy by enabling comparisons between measurements of blood flow velocity, which is considered to reflect inflammation activity in the choroid.

Re-evaluation of heterogeneity in HLA-B*510101 associated with Behçet's disease.
Takemoto Y, Naruse T, Namba K, Kitaichi N, Ota M, Shindo Y, Mizuki N, Gul A, Madanat W, Chams H, Davatchi F, Inoko H, Ohno S, Kimura A
Tissue antigens, 72, 4, 347, 353, 2008年10月, ［査読有り］

Efficacy and complications of intravitreal injection of triamcinolone acetonide for refractory cystoid macular edema associated with intraocular inflammation
Zhenyu Dong, Kenichi Namba, Nobuyoshi Kitaichi, Chiho Goda, Mizuki Kitamura, Shigeaki Ohno
JAPANESE JOURNAL OF OPHTHALMOLOGY, 52, 5, 374, 379, SPRINGER TOKYO, 2008年09月, ［査読有り］
英語, 研究論文（学術雑誌）, To assess the effects and complications of intravitreal injection of triamcinolone acetonide (IVTA) for posterior sub-Tenon injection of triamcinolone acetonide (PSTA)-resistant cystoid macular edema (CME) with intraocular inflammation.
Medical records of eight eyes of six patients with PSTA-resistant CME were retrospectively examined. Each eye received a 4-mg IVTA, and an additional injection was performed when CME recurred. Visual acuity as logarithm of the minimum angle of resolution (logMAR), intraocular pressure (IOP), and central macular thickness (CMT) were assessed before and after each treatment.
CME improved in six eyes (75%) with mean visual acuity recovering from 0.56 +/- 0.29 to 0.41 +/- 0.195 (logMAR, P = 0.13) and mean CMT decreasing from 470 mu m (range, 275-660 mu m) to 297 mu m (range, 150-697 mu m) (P = 0.04) 2 months after the initial IVTA. CME recurred an average of 9 months (range, 5-11 months) after IVTA. A higher dose (16-mg) IVTA was effective for two eyes refractory to repeated 4-mg IVTA. IOP was elevated in two eyes (25%), of which one required filtration surgery (12.5%). In phakic eyes, cataracts progressed and necessitated surgery.
IVTA is effective for PSTA-resistant CME with intraocular inflammation, and its efficacy might be dose dependent.

Mutation screening of the CARD15 gene in sarcoidosis.
Akahoshi M, Ishihara M, Namba K, Kitaichi N, Ando Y, Takenaka S, Ishida T, Ohno S, Mizuki N, Nakashima H, Shirakawa T
Tissue antigens, 71, 6, 564, 567, 2008年06月, ［査読有り］

H2-D-d-mediated upregulation of interleukin-4 production by natural killer T-cell and dendritic cell interaction
Kazuomi Mizuuchi, Yoshiki Yanagawa, Kazuya Iwabuchi, Kenichi Namba, Nobuyoshi Kitaichi, Shigeaki Ohno, Kazunori Onoe
IMMUNOLOGY, 124, 1, 102, 111, BLACKWELL PUBLISHING, 2008年05月, ［査読有り］
英語, 研究論文（学術雑誌）, Natural killer T (NKT) cells are capable of subserving apparently opposite functions, the interferon-gamma (IFN-gamma)-mediated enhancement of host defence and interleukin-4 (IL-4) -mediated immune regulation. Although dendritic cells (DCs) potently activate NKT cells, DC regulation of the IL-4-IFN-gamma balance via NKT-cell activation is not well characterized. In the present study, we examined the effect of DC treatment with CpG oligodeoxynucleotide (ODN), a Toll-like receptor 9 ligand, on the induction of NKT-cell cytokine production. CpG-ODN-conditioned and alpha-galactosylceramide (alpha-GalCer)-loaded myeloid DCs (CpG-DCs) from BALB/c mice showed enhanced ability to induce NKT-cell production of IL-4, but not IFN-gamma, compared to alpha-GalCer-loaded control DCs (not treated with CpG-ODN). The CpG-DCs expressed significantly higher levels of H2-D-d than control DCs, and blocking of the H2-D-d and Ly49 receptor interaction during antigen presentation completely abolished the enhanced ability of the CpG-DCs to induce NKT-cell production of IL-4. These findings demonstrate that DC recognition of the CpG motif leads to induction of enhanced IL-4 production by NKT cells via interaction of the augmented H2-D-d with Ly49 receptors on NKT cells.

Sister cases of Behcet's disease and Vogt-Koyanagi-Harada disease
Yukihiro Horie, Kenichi Namba, Nobuyoshi Kitaichi, Shigeaki Ohno
BRITISH JOURNAL OF OPHTHALMOLOGY, 92, 3, 433, 434, B M J PUBLISHING GROUP, 2008年03月, ［査読有り］
英語

Polymorphism of IFN-gamma gene and Vogt-Koyanagi-Harada disease
Yukihiro Horie, Nobuyoshi Kitaichi, Yuko Takemoto, Kenichi Namba, Kazuhiko Yoshida, Shigeto Hirose, Yukiko Hasumi, Masao Ota, Hidetoshi Inoko, Nobuhisa Mizuki, Shigeaki Ohno
MOLECULAR VISION, 13, 261-65, 2334, 2338, MOLECULAR VISION, 2007年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose: Interferon-gamma (IFN-gamma) is a key cytokine in inflammatory disorders. Elevated aqueous and serum levels of IFN-gamma levels have been reported to be elevated in patients with Vogt-Koyanagi-Harada (VKH) disease. The aim of this study was to determine the IFN-gamma gene polymorphisms in VKH disease.
Methods: The study involved 136 VKH patients and 176 healthy controls, who were genotyped for functional single nucleotide polymorphism (SNP; rs2430561; A/T) and functional microsatellite (CA) repeats (rs3138557) in the first intron of the IFN-gamma gene. Moreover, clinical manifestations of the patients were also analyzed.
Results: Diffuse choroiditis/staining of fluorescein angiography was seen in all VKH patients in this study. Sunset glow fundus and nummular chorioretinal depigmented scars were observed in 83.9%, and 36.1% of the patients, respectively. Neurological and auditory disorders were observed in 90.1% of the patients: meningismus (79.8%), tinnitus (53.0%), and cerebrospinal fluid pleocytosis (70.0%). Dermatologic manifestations were observed in 22.9% of the patients, manifesting as alopecia (6.9%), poliosis (17.6%), and vitiligo (13.0%). In addition, 22.1% of the patients were classified as having complete VKH disease, while 65.4% as having incomplete VKH disease, and 12.5% as having probable VKH disease. There were no significant differences in the allele and genotype frequencies between VKH patients and healthy controls. In addition, we found no association between each clinical manifestation and SNP (re2430561) in the healthy control subject. A strong linkage disequilibrium (LD) was found in the functional SNP T allele and functional microsatellite 12 (CA) repeats (D' = 0.96-0.99).
Conclusions: The functional SNP T allele and microsatellite 12 (CA) repeats were found to have a strong LD, although a genetic susceptibility for the IFN-gamma gene could not be demonstrated among the Japanese VKH patients.

Osteopontin aggravates experimental autoimmune uveoretinitis in mice
Mizuki Kitamura, Kazuya Iwabuchi, Nobuyoshi Kitaichi, Shigeyuki Kon, Hirokuni Kitamei, Kenichi Namba, Kazuhiko Yoshida, David T. Denhardt, Susan R. Rittling, Shigeaki Ohno, Toshimitsu Uede, Kazunori Onoe
JOURNAL OF IMMUNOLOGY, 178, 10, 6567, 6572, AMER ASSOC IMMUNOLOGISTS, 2007年05月, ［査読有り］
英語, 研究論文（学術雑誌）, Human endogenous uveitis is a common sight-threatening intraocular inflammatory disease and has been studied extensively using a murine model of experimental autoimmune uveoretinitis (EAU). It is possibly mediated by Th1 immune responses. In the present study, we investigated the role of osteopontin (OPN), a protein with pleiotropic functions that contributes to the development of Th1 cell-mediated immunity. Accompanying EAU progression, OPN was elevated in wild-type (WT) mice that had been immunized with human interphotoreceptor retinoid-binding protein (hIRBP) peptide 1-20. OPN-deficient (OPN-/-) mice showed milder EAU progression in clinical and histopathological scores compared with those of WT mice. The T cells from hIRBPimmunized OPN-/- mice exhibited reduced Ag-specific proliferation and proinflammatory cytokine (TNF-alpha and IFN-,gamma) production compared with those of WT T cells. When hIRBP-immunized WT mice were administered M5 Ab reacting to SLAYGLR sequence, a cryptic binding site to integrins within OPN, EAU development was significantly ameliorated. T cells from hIRBPimmunized WT mice showed significantly reduced proliferative responses and proinflammatory cytokine production upon stimulation with hIRBP peptide in the presence of M5 Ab in the culture. Our present results demonstrate that OPN may represent a novel therapeutic target to control uveoretinitis. The Journal of Immunology, 2007, 178: 6567-6572.

サルコイドーシスの診断基準と診断の手引き 2006
石原 麻美, 大原 國俊, 臼井 正彦, 大黒 伸行, 大野 重昭, 岡田 アナベルあやめ, 沖波 聡, 蕪城 俊克, 川島 英俊, 幸野 敬子, 後藤 浩, 南場 研一, 望月 學, 「サルコイドーシス眼病変の診断の手引き」改訂委員会
日本眼科学会雑誌, 111, 2, 117, 121, (公財)日本眼科学会, 2007年02月
日本語

Genetic polymorphisms in the promoter of the interferon gamma receptor 1 gene are associated with atopic cataracts
Akira Matsuda, Nobuyuki Ebihara, Naoki Kumagai, Ken Fukuda, Koji Ebe, Koji Hirano, Chie Sotozono, Mamoru Tei, Koichi Hasegawa, Makiko Shimizu, Mayumi Tamari, Kenichi Namba, Shigeaki Ohno, Nobuhisa Mizuki, Zenro Ikezawa, Taro Shirakawa, Junji Hamuro, Shigeru Kinoshita
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 48, 2, 583, 589, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2007年02月, ［査読有り］
英語, 研究論文（学術雑誌）, PURPOSE. Previous reports have shown genetic predisposition for atopic dermatitis ( AD). Some of the severe complications of AD manifest in the eye, such as cataract, retinal detachment, and keratoconjunctivitis. This study was conducted to examine the genetic association between the atopy-related genes and patients with ocular complications ( ocular AD).
METHODS. Seventy-eighty patients with ocular AD and 282 healthy control subjects were enrolled in an investigation of the association between the atopy-related genes ( FCERB, IL13, and IFNGR1) and ocular AD. Genetic association studies and functional analysis of single nucleotide polymorphisms ( SNPs) were performed.
RESULTS. The -56TT genotype in the IFNGR1 promoter region was significantly associated with an increased risk of ocular AD under recessive models ( chi(2) test, raw P = 0.0004, odds ratio 2.57). The -56TT genotype was more common in atopic cataracts. A reporter gene assay showed that, after stimulation with IFN-gamma, the IFNGR1 gene promoter construct that contained the -56T allele, a common allele in ocular AD patients, manifested higher transcriptional activity in lens epithelial cells ( LECs) than did the construct with the -56C allele. Real-time PCR analysis demonstrated higher IFNGR1 mRNA expression in the LECs in atopic than in senile cataracts. iNOS expression by IFNGR1-overexpressing LECs was enhanced on stimulation with IFN-gamma and LPS.
CONCLUSIONS. The -56T allele in the IFNGR1 promoter results in higher IFNGR1 transcriptional activity and represents a genetic risk factor for atopic cataracts.

Association of heat shock protein 70 induction and the amelioration of experimental autoimmune uveoretinitis in mice
Hirokuni Kitamei, Nobuyoshi Kitaichi, Kazuhiko Yoshida, Akira Nakai, Mitsuaki Fujimoto, Mizuki Kitamura, Kazuya Iwabuchi, Akiko Miyazaki, Kenichi Namba, Shigeaki Ohno, Kazunori Onoe
IMMUNOBIOLOGY, 212, 1, 11, 18, ELSEVIER GMBH, URBAN & FISCHER VERLAG, 2007年, ［査読有り］
英語, 研究論文（学術雑誌）, Experimental autoimmune uveoretinitis (EAU) serves as a model of human endogeneous uveitis. In the present study we examined whether induction of heat shock protein (HSP) 70 by oral geranylgeranyl acetone (GGA) administration had a therapeutic effect on murine EAU. When C57BL/6 mice that had received oral administration of GGA (500mg/kg) were immunized with interphotoreceptor retinoid-binding protein (IRBP)-derived peptide plus adjuvants, the expression levels of HSP70 mRNA and protein were rapidly and transiently upregulated in eyes of the GGA-treated mice, compared with those from vehicle-pretreated and IRBP-immunized mice. The antigen-specific T cell proliferation was partially suppressed in these mice treated with GGA. The mean EAU scores of the GGA-treated mice on day 21 and 28 (2.4 +/- 0.2 and 2.1 +/- 0.2, respectively) were significantly lower than those in the controls (3.0 +/- 0.1 and 2.6 +/- 0.2, respectively p < 0.01). The histopathological severity of the GGA-treated mice (average 0.33) was markedly milder than that in the controls (average 1.63, p < 0.05) at day 21. The present findings demonstrate that the pharmacological induction of HSP70 may be applicable to the amelioration of ocular autoimmune diseases. (c) 2006 Elsevier GmbH. All rights reserved.

Repeated exacerbations of ocular inflammation with vitreous hemorrhage in a patient with HLA-B27 associated uveitis
Satoru Kase, Kenichi Namba, Yukihiro Horie, Satoshi Kotake, Shigeaki Ohno
Journal of Medical Investigation, 54, 3-4, 350, 353, 3-4, 2007年, ［査読有り］
英語, 研究論文（学術雑誌）, HLA-B27 associated uveitis is characterized by recurrent alternating acute unilateral attacks of intraocular inflammation in the anterior chamber. The aim of this study was to report an unusual case of repeated exacerbations with vitreous hemorrhage in HLA-B27 associated uveitis. Thirty four-year-old man was diagnosed as HLA-B27 associated uveitis in his right eye. He showed repeated exacerbation of ocular inflammation with retinal vein dilation and small retinal hemorrhage following vitreous hemorrhage. Fluorescein fundus angiography a week before the appearance of vitreous hemorrhage showed no neovascularization. Oral prednisolone administration was started from 40 mg/day with gradual tapering. About 3 weeks after the onset, most of the vitreous hemorrhage disappeared and visual acuity was improved to 20/20. Through the decreased vitreous hemorrhage, Weiss ring was detected later. The vitreous hemorrhage found in this patient is a severe exacerbation, and might be a consequence of the vitritis that leads to posterior vitreous detachment.

Elevation of serum Krebs von den Lunge-6 levels in patients with tubulointerstitial nephritis and Uveitis syndrome
Satoru Kase, Nobuyoshi Kitaichi, Kenichi Namba, Akiko Miyazaki, Kazuhiko Yoshida, Kenji Ishikura, Masahiro Ikeda, Taiji Nakashima, Shigeaki Ohno
AMERICAN JOURNAL OF KIDNEY DISEASES, 48, 6, 935, 941, W B SAUNDERS CO-ELSEVIER INC, 2006年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Background Tubulointerstitial nephritis and uveitis (TINU) syndrome is characterized by a combination of idiopathic acute tubulointerstitial nephritis and uveitis. Krebs von den Lunge-6 (KL-6) is a human glycoprotein secreted by type II alveolar cells in the lung, and its serum levels increase in patients with pneumonia of various causes, as well as ocular sarcoidosis. The aim of the present study is to quantify serum KL-6 levels in patients with TINU syndrome, which has no pulmonary and sarcoid lesions, and elucidate the usefulness of KL-6 for the diagnosis and follow-up of this syndrome. Methods: Serum and urinary samples were obtained from 17 patients with TINU syndrome and 36 age-matched patients with uveitis from other causes. Sarcoidosis was eliminated because serum KL-6 levels increased during their lung lesion. Serum KL-6 level was determined by using a human KL-6 electrochemiluminescence immunoassay. Formalin-fixed paraffin-embedded renal tissue sections were incubated with anti-KL-6 monoclonal antibody, then examined immunohistochemically. Results: Mean serum KL-6 levels for patients with TINU syndrome and those with uveitis from other causes were 363.35 +/- 51.06 and 213.19 +/- 10.28 U/mL, respectively (P < 0.001). Urinary beta(2)-Microglobulin levels of patients with TINU syndrome and uveitis from other causes were 4.06.+/- 1.31 and 0.16 +/- 0.20 mg/L, respectively (P < 0.001). All patients with TINU syndrome showed a simultaneous decrease in serum KL-6 and urinary beta(2)-Microglobulin levels after the beginning of treatment. Strong immunoreactivity for KL-6 was observed in renal distal tubules in biopsy tissue of patients with TINU syndrome. Conclusion: We show a significant increase in serum KL-6 levels in patients with TINU syndrome, whereas levels were normal in patients with other causes of uveitis without nephritis. Renal distal tubules stained strongly with anti-KL-6 antibody, suggesting that high KL-6 levels may reflect the renal lesion of TINU syndrome. Serum KL-6 may be a potential laboratory parameter for the diagnosis and follow-up of patients with TINU syndrome that could complement urinary beta(2)-Microglobulin measurements.

Tyrosinase gene family and Vogt-Koyanagi-Harada disease in Japanese patients
Yukihiro Horie, Yuko Takemoto, Akiko Miyazaki, Kenichi Namba, Satoru Kase, Kazuhiko Yoshida, Masao Ota, Yukiko Hasumi, Hidetoshi Inoko, Nobuhisa Mizuki, Shigeaki Ohno
MOLECULAR VISION, 12, 182-86, 1601, 1605, MOLECULAR VISION, 2006年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose: The aim of the present study was to examine the genetic background of Vogt-Koyanagi-Harada (VKH) disease in a Japanese population by analyzing the tyrosinase gene family (TYR, TYRP1, and dopachrome tautomerase (DCT)).
Methods: 87 VKH patients and 122 healthy controls were genotyped using seven microsatellite markers on the candidate loci. We analyzed microsatellite (MS) polymorphisms at regions within tyrosinase gene family loci. In addition, the haplotype frequencies were also estimated and statistical analysis was performed. HLA-DRB1 genotyping was performed by the PCR-restriction fragment length polymorphism (RFLP) method.
Results: No significant evidence for an association was found. HLA-DRB1*0405 showed a highly significant association with VKH disease compared with the healthy controls (Pc=0.000000079), as expected.
Conclusions: We concluded that there is no genetic susceptibility or increased risk attributed to the tyrosinase gene family. Our results suggest the need for further genetic study and encourage a search for novel genetic loci and predisposing genes in order to elucidate the genetic mechanisms underlying VKH disease.

Chronic panuveitis and scleritis in a patient with cryptogenic organizing pneumonia
Wataru Saito, Akari Saito, Kenichi Namba, Satoru Kase, Masanori Shiratori, Shigeaki Ohno
JAPANESE JOURNAL OF OPHTHALMOLOGY, 50, 6, 558, 561, ELSEVIER SCIENCE INC, 2006年11月, ［査読有り］
英語

Granulocytapheresis in patients with refractory ocular Behcet's disease
Kenichi Namba, Koh-Hei Sonoda, Hirokuni Kitamei, Kenji Shiratori, Akiko Ariyama, Kazuya Iwabuchi, Kazunori Onoe, Abby R. Saniabadi, Shoichi Inaba, Tatsuro Ishibashi, Shigeaki Ohno
JOURNAL OF CLINICAL APHERESIS, 21, 2, 121, 128, WILEY-LISS, 2006年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Intraocular inflammation (uveoretinitis) is one major complication of Behcet's disease (BD) and responds poorly to drug therapy. This open prospective study was to assess the efficacy of selective granulocytapheresis in patients with refractory uveoretinitis of BD. Fourteen patients aged 20-56 years were treated. Granulocytapheresis was done with an Adacolumn filled with cellulose acetate leucocyte carries or beads that adsorb granulocytes and monocytes from the blood in the column. Each patient received 5 Adacolumn sessions at one session/week over 5 consecutive weeks. The study was designed to allow each patient to serve as his or her own control. The total numbers of ocular attacks (OA) were monitored for 6 months before and after 5 Adacolumn sessions. The number of OA (mean SD) per patient for the 6 months before Adacolumn was 4.21 +/- 1.6 and for the 6 months post Adacolumn was 2.93 +/- 1.39 (P = 0.0275). Nine patients (64%) improved and 5 did not change or worsened. Further, for a sub-group (n = 7) with duration of BD >= 5 years, the number of OA were 4.71 +/- 1.89 for the first 6 months and 2.29 +/- 1.38 for the second 6 months (P = 0.0054). The corresponding values for a sub-group (n = 7) with duration of BD < 5 years were 3.71 +/- 1.25 and 3.57 +/- 1.13, indicating that patients with long duration of BD are better responders. We conclude that granulocytapheresis might be effective and safe for patients with refractory ocular BD. Further studies are necessary to fully evaluate the clinical efficacy of granulocytapheresis for BD.

Amelioration of experimental autoimmune uveoretinitis (EAU) with an inhibitor of nuclear factor-kappa B (NF-kappa B), pyrrolidine dithiocarbamate
Hirokuni Kitamei, Kazuya Iwabuchi, Kenichi Namba, Kazuhiko Yoshida, Yoshiki Yanagawa, Nobuyoshi Kitaichi, Mizuki Kitamura, Shigeaki Ohno, Kazunori Onoe
JOURNAL OF LEUKOCYTE BIOLOGY, 79, 6, 1193, 1201, FEDERATION AMER SOC EXP BIOL, 2006年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Experimental autoimmune uveoretinitis (EAU) is a T helper type I cell-mediated autoimmune disease, which serves as a model of human chronic uveitis. In this model, cells of a monocyte/ macrophage lineage and retinal antigen (Ag)-specific T cells infiltrate into the retina and cause inflammatory lesion, where proinflammatory cytokines and various stimuli activate a transcriptional factor, nuclear factor-kappa B (NF-kappa B), which modulates inflammation and enhances immune responses. In the present study, the therapeutic effect of administration of a NF-kappa B inhibitor, pyrrolidine dithiocarbamate (PDTC), was examined in a murine EAU model. It was shown that PDTC ameliorated the clinical symptoms of EAU mice and significantly reduced the histopathological score compared with those in untreated mice. mRNA expressions of tumor necrosis factor alpha and interleukin-1 beta were suppressed in eyes of PDTC-treated EAU juice. However, when T cells from PDTC-treated EAU mice, Ag-presenting cells (APC), and the retinal Ag peptides were cocultured, these T cells showed the same level of proliferation as those from control mice. Furthermore, addition of PDTC in the culture of T cells from EAU mice, Ag, and APC completely abrogated the T cell-proliferative response and cytokine production. Pretreatment of Ag-primed T cells or APC with PDTC in vitro also reduced these responses. These results indicate that the inhibitory effect of PDTC is attributed mainly to the suppression of effector-phase responses including inflammation but not to the inhibition of T cell priming. Regulation of NF-kappa B pathway in the lesion could be a novel target for the successful control of uveoretinitis.

Usefulness of quantifying serum KL-6 levels in the follow-up of uveitic patients with sarcoidosis
N Kitaichi, T Ariga, S Kase, K Yoshida, K Namba, S Ohno
GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 244, 4, 433, 437, SPRINGER, 2006年04月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: KL-6 is a human glycoprotein secreted by type II alveolar cells in the lung, and its serum levels increase in pneumonia of various causes. We previously reported that serum KL-6 levels in uveitis patients with sarcoidosis were significantly higher than those of other uveitis patients and healthy controls. Additionally, the combined measurement of serum KL-6 and angiotensin converting enzyme (ACE) was useful for screening uveitic patients to diagnose sarcoidosis. The purpose of the present study was to investigate the clinical usefulness of quantifying serum KL-6 levels for following-up the patients with sarcoidosis. Methods: Sera were obtained from 36 uveitic patients diagnosed with sarcoidosis and the same number of healthy volunteers. To examine the influence of systemic medication, we also collected blood samples from four more sarcoidosis patients, who were systemically treated with corticosteroid or angiotensin converting enzyme (ACE) inhibitor, an anti-hypertensive drug. The serum concentration of KL-6 was measured by a human KL-6 electrochemiluminescence immunoassay (ECLIA). Results: The mean KL-6 concentrations of sarcoidosis patients and healthy controls were 449.3 +/- 66.3 (mean +/- SE) and 192.1 +/- 11.3, respectively. The average levels of serum KL-6 were significantly elevated in sarcoidosis patients compared with healthy control subjects (P < 0.001), and there were significant correlations between serum KL-6 and ACE levels in the patients with sarcoidosis (r=0.70 and P < 0.0001). Moreover, serum KL-6 concentrations were less affected by systemic corticosteroid, and unaffected by ACE inhibitory drugs in contrast to ACE levels. Conclusions: Measurement of serum KL-6 in the uveitic patients may be useful to follow-up the diagnosed sarcoidosis, as well as for diagnosing sarcoidosis, because the serum KL-6 level was well correlated with the ACE level, and less affected by systemic medication than ACE levels.

Epstein-Barr virus infected cells in the aqueous humour originated from nasal NK/T cell lymphoma
S Kase, K Namba, N Kitaichi, S Ohno
BRITISH JOURNAL OF OPHTHALMOLOGY, 90, 2, 244, 245, B M J PUBLISHING GROUP, 2006年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Clinical features in tubulointerstitial nephritis and uveitis (TINU) syndrome
C Goda, S Kotake, A Ichiishi, K Namba, N Kitaichi, S Ohno
AMERICAN JOURNAL OF OPHTHALMOLOGY, 140, 4, 637, 641, ELSEVIER SCIENCE INC, 2005年10月, ［査読有り］
英語, 研究論文（学術雑誌）, PURPOSE: To analyze clinical features of the tubulointerstitial nephritis and uveitis (TINU) syndrome in Japan, especially exacerbations or recurrences of uveitis.
DESIGN: Retrospective observational study.
METHODS: We reviewed the clinical features in 12 patients with TINU syndrome diagnosed by renal biopsy, who were evaluated and treated at the Department of Ophthalmology, Hokkaido University Hospital. Visual acuity was measured using decimal visual acuity.
RESULTS: Patient age ranged from 10 to 33 years (mean 21 years), and females accounted for 83% of the cases. Both eyes were affected in 11 patients (92%). All 12 patients initially experienced ocular symptoms, with hyperemia being the chief complaint. We diagnosed patients as having uveitis and conducted blood tests and urinalysis. Urinalysis did show characteristic findings, most notably glucosuria, increased beta 2 microglobulin that were >= 10 times that of normal levels, and increased N-acetylglucosaminidose levels in a high percentage of patients. Recurrent or exacerbating uveitis was seen in six patients (50%). In exacerbated or recurrent uveitis, inflammation was more severe (>= 3 + cells of the anterior eye segment). The ocular inflammation generally responded well to treatment with oral corticosteroids, and the number of recurrences was lower at corticosteroid doses of :prednisolone 40 mg.
CONCLUSIONS: Ophthalmologists play an important role in the initial discovery of patients with TINU syndrome. Because inflammation was more severe in exacerbated or recurrent uveitis, in instances where uveitis is refractory to local therapy, oral corticosteroids should be considered as early as possible. (Am J Ophthalmol 2005. (c) 2005 by Elsevier Inc. All rights reserved.)

Expression of thymidine phosphorylase in choroidal malignant melanoma associated with neovascular glaucoma
S Kase, W Saito, K Yoshida, K Namba, M Osaki, K Ohgami, K Shiratori, N Kitaichi, H Adachi, H Ito, S Ohno
PATHOLOGY INTERNATIONAL, 55, 9, 569, 573, BLACKWELL PUBLISHING, 2005年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Reported herein is a case of 62-year-old man who complained of blurred vision and ocular pain in his right eye. The patient was diagnosed with choroidal melanoma complicated by neovascular glaucoma (NVG) and total retinal detachment, and he underwent enucleation of the eye. The isolated tumor was 2.5 x 2.5 cm in size. It was accompanied by intratumoral calcification, and consisted of epithelioid and spindle melanoma cells. There were a variety of microvessels in the stroma of the iris. The expression of thymidine phosphorylase (dThdPase), an angiogenic factor, was examined immunohistochemically. Cytoplasmic immunoreactivity for dThdPase was more prominent in the epithelioid cells than in spindle tumor cells. Another case of choroidal melanoma without NVG had less marked immunoreactivity. These results suggest that the production of dThdPase by melanoma cells correlates with the pathogenesis of NVG.

Comparative study of two sets of criteria for the diagnosis of Vogt-Koyanagi-Harada's disease
M Kitamura, K Takami, N Kitachi, K Namba, H Kitamei, S Kotake, S Ohno
AMERICAN JOURNAL OF OPHTHALMOLOGY, 139, 6, 1080, 1085, ELSEVIER SCIENCE INC, 2005年06月, ［査読有り］
英語, 研究論文（学術雑誌）, PURPOSE: The Vogt-Koyanagi-Harada's (VKH) Dis- ease Committee established the "Revised diagnostic criteria for VKH disease" in 2001. The purpose of the present study was to assess the concordance between these criteria and the traditional Sugiura's diagnosis system. DESIGN: Observational case series.
METHODS: The medical records of patients previously diagnosed with VKH disease based upon Sugiura's criteria at the Uveitis Survey Clinic of the Hokkaido University Hospital between 1991 and 2003 were retrospectively reevaluated using the VKH Committee's revised diagnostic criteria for VKH disease.
RESULTS: Sugiura's criteria were used to identify 169 patients with VKH disease. All patients were Japanese, and 95 cases (56%) were women. Mean age at the time of their first visit to our clinic was 44.7 +/- 13.9 years (range, 9 to 74 years). Using the VKH Committee's new criteria, 91.7% of the previously diagnosed VKH patients were classified as having the disease. Of this group, 11.8% were classified as complete, 71% incomplete, and 8.9% as probable VKH disease.
CONCLUSIONS: The VKH Committee's revised diagnostic criteria proved useful for VKH disease diagnosis, as the concordance rate for the two criteria was more than 90%. However, patients who had prior cataract surgery or who lacked signs of serous retinal detachment were not classified as having VKH disease because of exclusion by the VKH Committee's new criteria. (c) 2005 by Elsevier Inc. All rights reserved.

Clinicopathological features of primary choroidal malignant melanoma　　　　　　　　　　　　　　　
Satoru Kase, Kazuhiko Yoshida, Wataru Saito, Ken-Ichi Namba, Naoko Tsujino, Masahiro Muramatsu, Naoki Furudate, Shigeaki Ohno
Japanese Journal of Clinical Ophthalmology, 59, 5, 705, 709, 2005年05月
日本語, 研究論文（学術雑誌）, Purpose: To describe clinicopathological findings in 4 eyes of primary choroidal malignant melanoma. Cases and Method: Four eyes of 4 patients with primary choroidal malignant melanoma underwent histopathological examinations. They were 29-year-old male, 50-year-old female, 62-year-old male, and 66-year-old female. Enucleated eyes were fixed in 4% paraformaldehyde and embedded in paraffin. Sliced specimens were stained by hematoxylin-eosin and by hematoxylin after demelanization. Findings: All the eyes had bullous retinal detachment. Total retinal detachment was present in 1 eye. The tumor size ranged from 13 × 13 mm to 25 × 25 mm. The interval between visual impairment and enucleatrion ranged from 2 to 9 months. Cases enucleated later tended to have larger tumor with advanced stage. All the eyes showed massive deposit of melanin in the tumor. Demelanization facilitated observation of morphological features of the tumor including mitosis. Tumor cells with spindle-shaped nuclei were the prevalent features in 2 eyes. The other 2 eyes showed mixture of epithelioid cells. Conclusion: While primary choroidal malignant melanoma is relatively rare in Japan. Detailed clinicopathological evaluation is mandatory.

Inducible immune regulation following autoimmune disease in the immune-privileged eye
N Kitaichi, K Namba, AW Taylor
JOURNAL OF LEUKOCYTE BIOLOGY, 77, 4, 496, 502, FEDERATION AMER SOC EXP BIOL, 2005年04月, ［査読有り］
英語, 研究論文（学術雑誌）, The immune-privileged eye has the potential to induce regulatory immunity along with local mechanisms of immunosuppression. Rodent models of human antoimmune uveoretinitis [experimental antoimmune uveoretinitis (EAU)] recover without spontaneous recurrence of uveitis, which differs from uveitis in some humans. This raises the possibility that the mechanism of immune privilege in the rodent eye can reimpose itself during autoimmune uveoretinitis and re-establish tolerance to antoantigen. To investigate this possibility, we examined the spleens of EAU-recovered mice for regulatory immunity. We detected regulatory immunity when we adoptively transferred post-EAU spleen cells into other mice immunized for EAU. We could not detect this regulatory immunity in enucleated mice nor in naive mice. Moreover, unlike the mechanisms of anterior chamber-associated immune deviation, the suppression was only mediated by post-EAU CD4(+) T cells, which required activation with antoantigen presented by post-EAU spleen antigen-presenting cells (APC). Our results demonstrate that when the immune-privileged ocular microenvironment recovers from an autoimmune response, it has influenced systemic immunity to retinal antoantigen by affecting APC and mediating induction of potential regulatory CD4+ T cells laying in wait in the post-EAU spleen for restimulation.

Increase of KL-6 in sera of uveitis patients with sarcoidosis
N Kitaichi, S Kotake, H Shibuya, Y Yamada, H Chiba, K Namba, S Ohno
GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 241, 11, 879, 883, SPRINGER-VERLAG, 2003年11月, ［査読有り］
英語, 研究論文（学術雑誌）, Background. KL-6 is a human glycoprotein secreted by type II alveolar cells in lung, and its serum levels increase in pneumonia of various causes. KL-6 is a member of the MUC-1 family, which is expressed in lung, cornea, and conjunctiva. The purpose of the present study was to investigate the clinical usefulness of quantifying serum KL-6 levels for diagnosing sarcoidosis in patients with uveitis. Methods. Sera were obtained from 24 uveitis patients diagnosed with sarcoidosis, 37 uveitis patients with other etiologies, and 138 healthy control subjects. Serum concentration of KL-6 was determined by a human KL-6 electrochemiluminescence immunoassay. Results. The average level of KL-6 in the sera of uveitis patients with sarcoidosis was 387 U/ml. This was significantly higher than in healthy subjects and uveitis patients with other etiologies. The KL-6 measurements identified 45.8% of sarcoidosis-positive patients. When the KL-6 results were combined with serum angiotensin-converting enzyme (ACE) concentrations, 87.5% of sarcoidosis patients were identified, compared to 66.7% using ACE results alone. The combined measurement identified 10.8% of the non-sarcoid patients and 0.72% of healthy subjects as positive (false positive). Conclusion. Combined measurements of serum KL-6 and ACE may be useful as a screening for sarcoidosis in uveitis patients.

The change of clinical manifestations of patients with Behçet's disease in Japan.
Kotake S, Namba K, Higashi K, Goda C, Ariga T, Ogawa A, Ohno S
Advances in experimental medicine and biology, 528, 83, 84, KLUWER ACADEMIC/PLENUM PUBL, 2003年, ［査読有り］
英語, 研究論文（学術雑誌）

Induction of regulatory T cells by the immunomodulating cytokines alpha-melanocyte-stimulating hormone and transforming growth factor-beta 2
K Namba, N Kitaichi, T Nishida, AW Taylor
JOURNAL OF LEUKOCYTE BIOLOGY, 72, 5, 946, 952, FEDERATION AMER SOC EXP BIOL, 2002年11月, ［査読有り］
英語, 研究論文（学術雑誌）, Recently, we have reported that the cytokines alpha-melanocyte-stimulating hormone (alpha-MSH) and transforming growth factor-beta2 (TGF-beta2) work in synergy to induce the activation of regulatory T (Treg) cells. When we used (alpha-MSH and TGF-beta2 to generate ocular antoantigen-specific Treg cells and adoptively transferred them into mice susceptible to experimental autoimmune uveoretinitis (EAU), there was suppression in the incidence and severity of EAU. Specificity to a retinal autoantigen was required for the Treg cells to suppress EAU. When stimulated, these Treg cells produced TGF-beta1, and their production of interferon-gamma, interleukin (IL)-10, and IL-4 was suppressed. Also, the Treg cells are suppressed in their proliferative response. Our results demonstrate that alpha-MSH with TGF-beta2 induce Treg cells that can subdue a tissue-specific autoimmune response. This also promotes the possibility of using these immono-modulating cytokines to purposely induce antigen-specific Treg cells to prevent and suppress antoimmune disease.

In vitro induction of CD25(+) CD4(+) regulatory T cells by the neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH)
AW Taylor, K Namba
IMMUNOLOGY AND CELL BIOLOGY, 79, 4, 358, 367, BLACKWELL SCIENCE ASIA, 2001年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Recently, we have found that the neuropeptide alpha-melanocyte stimulating hormone (alpha -MSH) not only suppresses IFN-gamma production, but also induces TGF-beta1 production by activated effector T cells. These alpha -MSH- treated effector T cells function as regulatory T cells in that they suppress IFN-gamma production and hypersensitivity mediated by other effector T cells. Experimental autoimmune uveoretinitis (EAU) was suppressed in its severity and incidence in mice that were injected with primed T cells activated in vitro by APC and antigen in the presence of alpha -MSH. Moreover, it appeared that alpha -MSH had converted a population of effector T cells polarized to mediate hypersensitivity into a population of T cells that now mediated immunoregulation. To characterize these alpha -MSH- treated T cells, primed T cells were TCR-stimulated in the presence of alpha -MSH in vitro and their lymphokine profile was examined. Such effector T cells displayed enhanced levels of TGF-beta1 production and no IFN-gamma or IL-10, with IL-4 levels remaining unchanged in comparison with inactivated T cells. In addition, if soluble TGF-beta receptor II was added to cocultures of alpha -MSH-treated T cells and activated Th1 cells, the alpha -MSH-treated T cells could not suppress IFN-gamma production by the Th1 cells. These results suggest that alpha -MSH induces T cells with a regulatory lymphokine pattern, and that through their production of TGF-beta1 these cells suppress other effector T cells. Examination of the alpha -MSH-treated T cells showed that alpha -MSH did not alter the phosphorylation of CD3 molecules following TCR engagement. Primed T cells express the melanocortin 5 receptor (MC5r), a receptor that is linked to an intracellular signalling pathway shared by other cytokine receptors. Blocking the receptor with antibody prevented alpha -MSH from suppressing IFN-gamma production by the activated regulatory T cells, suggesting that alpha -MSH immunoregulation is through the MC5r on primed T cells. Surface staining and cell sorting of the alpha -MSH- treated primed T cells showed that the regulatory T cells are CD25(+) CD4(+) T cells. From these results we find that alpha -MSH can mediate the induction of CD25(+) CD4(+) regulatory T cells. These regulatory T cells require specific antigen for activation, but through non-specific TGF-beta1-mediated mechanisms they can suppress other effector T cells.

Amelioration of experimental autoimmune uveoretinitis by pretreatment with a pathogenic peptide in liposome and anti-CD40 ligand monoclonal antibody
K Namba, K Ogasawara, N Kitaichi, T Morohashi, Y Sasamoto, S Kotake, H Matsuda, K Iwabuchi, C Iwabuchi, S Ohno, K Onoe
JOURNAL OF IMMUNOLOGY, 165, 6, 2962, 2969, AMER ASSOC IMMUNOLOGISTS, 2000年09月
英語, 研究論文（学術雑誌）, We have defined a peptide K2 (ADKDVVVLTSSRTGGV) that corresponds to residues 201-216 of bovine interphotoreceptor retinoid-binding protein and induces experimental autoimmune uveoretinitis (EAU)(4) in H-2A(k)-carrying mice (H-2A(k) mice). In this study, we attempted to ameliorate EAU in the H-2A(k) mice without nonspecific suppression of T cell responses, Preceding s.c. administration of liposomes including K2 (liposomal K2) specifically inhibited subsequent generation of T cell response to K2, The same result was obtained with a combination of OVA(323-339) peptide and the OVA-specific TCR-transgenic T cells. It was suggested that the inhibition was mainly attributed to peripheral anergy induction of T cells specific for the peptide Ag, although specific cell death might also be involved in the inhibition. Pretreatment with liposomal K2 also considerably abolished IFN-gamma production but not IL-4 production. The specific inhibitory effect of the pretreatment with liposomal peptide was augmented by a simultaneous administration of anti-CD40 ligand (anti-CD40L) mAb, Moreover, it was shown that the pretreatment with liposomal K2 reduced both the incidence and severity of the subsequent K2-induced EAU, and the simultaneous administration of anti-CD40L mAb augmented this preventive effect by liposomal K2, Our findings demonstrate that the s.c. administration of liposomal pathogenic peptide and anti-CD40L mAb can be applied to preventing autoimmune diseases without detrimental nonspecific suppression of T cell responses.

Neuropeptide regulation of immunity - The immunosuppressive activity of alpha-melanocyte-stimulating hormone (alpha-MSH)
AW Taylor, DG Yee, T Nishida, K Namba
NEUROIMMUNOMODULATION, 917, 239, 247, NEW YORK ACAD SCIENCES, 2000年, ［査読有り］
英語, 研究論文（学術雑誌）, The ocular microenvironment is an extreme example of regional immunity. Within its microenvironment, expression of delayed type hypersensitivity (DTH) is suppressed. This immunosuppression is mediated in part by the constitutive expression of alpha -MSH. Previously we have found that alpha -MSH suppresses the production of IFN-gamma by activated effector T cells. Recently we have found that alpha -MSH can mediate induction of TGF-beta -producing T cells that act as regulatory T cells. This has encouraged us to further examine the potential for alpha -MSH to suppress T cell-mediated inflammation (autoimmune disease) and to regulate lymphokine production by effector T cells. When alpha -MSH was injected Lv. into mice at the time of peak retinal inflammation, the severity of experimental autoimmune uveitis (EAU) was significantly suppressed. Effector T cells activated in vitro in the presence of alpha -MSH proliferated and produced IL-4 and enhanced levels of TGF-beta while their IFN-gamma and IL-10 production was suppressed. The alpha -MSH-treated T cells functioned as regulatory T cells by suppressing in vitro IFN-gamma production by other inflammatory T cells. This regulatory activity was the function of alpha -MSH-treated CD4(+) CD25(+) T cells. Therefore, alpha -MSH mediates immunosuppression by inducing a differential expression of lymphokine production and by inducing activation of regulatory functions in T cells. This implies that alpha -MSH may take part in regional mechanisms of immunosuppression and possibly peripheral tolerance. Thus, alpha -MSH can be used to suppress autoimmune disease and possibly reestablish tolerance to autoantigens.

Effective priming of cytotoxic T lymphocyte precursors by subcutaneous administration of peptide antigens in liposomes accompanied by Anti-CD40 and Anti-CTLA-4 antibodies
Daisuke Ito, Daisuke Ito, Kazumasa Ogasawara, Kazuhiro Matsushita, Taiki Morohashi, Kenichi Namba, Naoto Matsuki, Nobuyoshi Kitaichi, Yukio Inuyama, Masuo Hosokawa, Eiichi Nakayama, Kazuya Iwabuchi, Kazunori Onoé, Kazunori Onoé
Immunobiology, 201, 527, 540, 2000年01月01日
Recently it has been shown that modulation of CD40 molecules on antigen (Ag) carrying dendritic cells (DC) can bypass T cell help, resulting in priming cytotoxic T lymphocytes (CTL) specific for the Ag. In the present study we attempted to prime peptide Ag-specific CTL by a new method in which a peptide Ag in liposome (liposomal peptide), consisting of phosphatidylserine and phosphatidylcholine (3:7), was administrated subcutaneously with anti-CD40 and/or CTLA-4 monoclonal antibodies (mAb) to mice. We found that the subcutaneous administration of the liposomal peptide with both anti-CD40 and anti-CTLA-4 mAb enhanced CTL responses comparing with those induced by the liposomal peptide alone or the liposomal peptide plus each mAb. It was shown that liposomes were critical for induction of the CTL activity. Flow cytometry analysis of a peptide-bearing DC in lymph nodes (LN) and measurement of serum IL-12 indicated that anti-CD40 mAb promoted migration of DC to the LN, where DC might differentiate and acquire ability of priming CTL. These findings provide a possibility that our procedure is applicable to cancer patients.

Inhibition of experimental autoimmune uveoretinitis with anti-macrophage migration inhibitory factor antibodies
KITAICHI N, MATSUDA A, KOTAKE S, NAMBA K, TAGAWA Y, SASAMOTO Y, OGASAWARA K, IWABUCHI K, ONOE K, MATSUDA H, NISHIHIRA
CURRENT EYE RESEARCH, 20, 2, 109, 114, 2000年, ［査読有り］

Prominent increase of macrophage migration inhibitory factor in the sera of patients with uveitis
KITAICHI N, KOTAKE S, SASAMOTO Y, NAMBA K, MATSUDA A, OGASAWARA K, ONOE K, MATSUDA H, NISHIHIRA
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 40, 1, 247, 250, 1999年, ［査読有り］

Interaction of pigeon cytochrome c-(43-58) peptide analogs with either T cell antigen receptor or I-Ab molecule
Yasushi Itoh, Kiichj Kajino, Kazumasa Ogasawara, Akio Takahashi, Ken-Ichi Namba, Izumi Negishi, Naoto Matsuki, Kazuya Iwabuchi, Mitsuaki Kakinuma, Robert A. Good, Kazunori Onoé
Proceedings of the National Academy of Sciences of the United States of America, 94, 22, 12047, 12052, 1997年10月28日, ［査読有り］
英語, 研究論文（学術雑誌）, We determined that a pigeon cytochrome c-derived peptide, p43-58, possesses two anchor residues, 46 and 54, for binding with the I-Ab molecule that are compatible to the position 1 (P1) and position 9 (P9) of the core region in the major histocompatibility complex (MHC) class II binding peptides, respectively. In the present study to analyze each binding site between P1 and P9 of p43-58 to either I-Ab or T cell antigen receptor (TCR), we investigated T cell responses to a series of peptides (P2K, P3K, P4K, P5K, P6K, P7K, and P8E) that sequentially substituted charged amino acid residues for the residues at P2 to P8 of p43-58. T cells from C57BL/10 (I-Ab) mice immunized with P4K or P6K did not mount appreciable proliferative responses to the immunogens, but those primed with other peptides (P2K, P3K, P5K, P7K, and P8E) showed substantial responses in an immunogenspecific manner. It was demonstrated by binding studies that P1 and P9 functioned as mann anchors and P4 and P6 functioned as secondary anchors to I-Ab. Analyses of Vβ usage of T cell lines specific for these analogs suggested that P8 interacts with the complementarity-determining region 1 (CDR1)/CDR2 of the TCR β chain. Furthermore, sequencing of the TCR on T cell hybridomas specific for these analogs indicated that P5 interacts with the CDR3 of the TCR β chain. The present findings are consistent with the three-dimensional structure of the trimolecular complex that has been reported for TCR/peptide/MHC class I molecules.

Determination of the allele-specific antigen-binding site on I-A(kappa) and I-A(b) molecules
Y Itoh, K Kajino, K Ogasawara, M Kotoh, K Namba, K Takami, K Iwabuchi, NS Braunstein, K Onoe
EUROPEAN JOURNAL OF IMMUNOLOGY, 26, 6, 1314, 1321, VCH PUBLISHERS INC, 1996年06月
英語, 研究論文（学術雑誌）, Residues 46 and 54 on a pigeon cytochrome c 43-58 analog, 50E, function as major histocompatibility complex class II contact sites. A peptide, 46F50E54A, with phenylalanine (F) at position 46 and alanine (A) at 54 on 50E bound to A(b) and a peptide, 46D50E54A, with aspartic acid (D) at 46 and alanine at 54, bound to A(k). TO determine the allele-specific peptide contact sites on I-A molecules corresponding to the I-A contact sites of the peptides, we analyzed responses of A(k)- and/or A(b)-restricted T cell hybridomas to 46F50E54A or 46D50E54A using L cell transfectants expressing recombinant I-A molecules between A(k) and A(b) Or point mutants of A(k) as antigen presenting cells. It was shown that the N-terminal half of the alpha helix of the A alpha chain determined the allele-specific T cell responses. Furthermore, with arginine (k type amino acid) or alanine (b type amino acid) at position 56 of the A(k) alpha chain, these T cell hybridomas were stimulated predominantly by 46D50E54A (A(k) binding peptide) or 46F50E54A (A(b) binding peptide), respectively. Thus, the amino acid at position 56 of the Aa chain determines allele-specific antigen presentation. This postulate was confirmed by direct binding analysis of 50E analogs of various I-A molecules. A single amino acid change (arginine to alanine) at position 56 of the A(k) alpha chain altered the peptide binding specificity (46D50E54A to 46F50E54A).

Epidemiological aspects of allergic conjunctivitis
Dai Miyazaki, Kazumi Fukagawa, Shigeki Okamoto, Atsuki Fukushima, Eiichi Uchio, Nobuyuki Ebihara, Jun Shoji, Kenichi Namba, Yumiko Shimizu, Allergology International, 69, 4, 487, 495, 2020年10月01日
The prevalence of ocular allergies has been increasing worldwide for the past several decades. The geographical distribution and hot spots of rhinoconjunctivitis have been documented in a global survey by the International Study of Asthma and Allergies in Childhood (ISAAC). ISAAC indicated that Africa, Latin America, and Japan were notable for their high prevalence of rhinoconjunctivitis. The outcomes of follow-up studies of regional differences and the characteristics of allergic conjunctivitis are summarized in this review. Currently, comorbid diseases and socioeconomic and environmental factors, including climate and air pollution, are proposed to contribute to the regional differences in the prevalence of allergic conjunctivitis. Of them, rhinitis has been shown repeatedly to be significantly associated with allergic conjunctivitis. Their mechanistic aspects on association with the prevalence of systemic allergic diseases have been reviewed by examining the birth cohort or in vitro analyses. A vision threatening form of ocular allergy, vernal keratoconjunctivitis, is prevalent in the African countries and Japan. Of the proposed associated factors, air pollution was shown to contribute not only to aggravating the symptoms but also to the increase in the incidence of its severe forms. Its mechanistic aspects are discussed in this review in the context of comorbid diseases., Japanese Society of Allergology, 英語, 書評論文,書評,文献紹介等

Japanese guidelines for allergic conjunctival diseases 2020
Dai Miyazaki, Etsuko Takamura, Eiichi Uchio, Nobuyuki Ebihara, Shigeaki Ohno, Yuichi Ohashi, Shigeki Okamoto, Yoshiyuki Satake, Jun Shoji, Kenichi Namba, Kazumi Fukagawa, Atsuki Fukushima, Hiroshi Fujishima, The Japanese Society of Ocular Allergology, Allergology International, 69, 3, 346, 355, 2020年07月01日
The definition, classification, pathogenesis, test methods, clinical findings, criteria for diagnosis, and therapies of allergic conjunctival disease are summarized based on the Guidelines for Clinical Management of Allergic Conjunctival Disease 2019. Allergic conjunctival disease is defined as “a conjunctival inflammatory disease associated with a Type I allergy accompanied by some subjective or objective symptoms.” Allergic conjunctival disease is classified into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. Representative subjective symptoms include ocular itching, hyperemia, and lacrimation, whereas objective symptoms include conjunctival hyperemia, swelling, folliculosis, and papillae. Patients with vernal keratoconjunctivitis, which is characterized by conjunctival proliferative changes called giant papilla accompanied by varying extents of corneal lesion, such as corneal erosion and shield ulcer, complain of foreign body sensation, ocular pain, and photophobia. In the diagnosis of allergic conjunctival diseases, it is required that type I allergic diathesis is present, along with subjective and objective symptoms accompanying allergic inflammation. The diagnosis is ensured by proving a type I allergic reaction in the conjunctiva. Given that the first-line drug for the treatment of allergic conjunctival disease is an antiallergic eye drop, a steroid eye drop will be selected in accordance with the severity. In the treatment of vernal keratoconjunctivitis, an immunosuppressive eye drop will be concomitantly used with the abovementioned drugs., Japanese Society of Allergology, 英語, 書評論文,書評,文献紹介等

A multi-center retrospective study on clinical characteristics of herpetic anterior uveitis in Japan
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年06月
0, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 英語, 研究発表ペーパー・要旨（国際会議）

Attenuation of experimental autoimmune uveoretinitis in mice by IKKβ inhibitor IMD-0354.
Ye Liu, Nobuyoshi Kitaichi, Di Wu, Keitaro Hase, Masashi Satoh, Daiju Iwata, Kenichi Namba, Atsuhiro Kanda, Kousuke Noda, Akiko Itai, Kazuya Iwabuchi, Susumu Ishida, Biochemical and biophysical research communications, 2020年02月27日, ［国際誌］
Uveitis is a sight-threatening intraocular inflammatory disease that accounts for almost 10% of blindness worldwide. NF-κB signaling plays pivotal roles in inflammatory diseases. We have reported that IMD-0354, which inhibits NF-κB signaling via selective blockade of IKK-β, suppresses inflammation in several ocular disease models. Here, we examined the therapeutic effect of IMD-0354 in an experimental autoimmune uveoretinitis (EAU) model, a well-established animal model for endogenous uveitis in humans. Systemic administration of IMD-0354 significantly suppressed the clinical and histological severity, inflammatory edema, and the translocation of NF-κB p65 into the nucleus of retinas in EAU mice. Furthermore, IMD-0354 treatment significantly inhibited the levels of several Th1/Th17-mediated pro-inflammatory cytokines in vitro. Our current data demonstrate that inhibition of IKKβ with IMD-0354 ameliorates inflammatory responses in the mouse EAU model, suggesting that IMD-0354 may be a promising therapeutic agent for human endogenous uveitis., 英語

【ぶどう膜炎診療ガイドライン】
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年06月
(公財)日本眼科学会, 日本語

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(改訂第2版、2019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TNF阻害薬使用検討委員会, 日本眼科学会雑誌, 123, 6, 697, 705, 2019年06月
(公財)日本眼科学会, 日本語

【わかりやすい感覚器疾患】 感覚器の構造と機能 視覚 虹彩・隅角　　　　　　　　　　　　　　　
南場 研一, 日本医師会雑誌, 147, 特別1, S42, S43, 2018年06月
日本医師会, 日本語

トリアムシノロンTenon嚢下注射で悪化し、眼内液を用いたPCR法が診断に有用であった眼トキソプラズマ症の1例　　　　　　　　　　　　　　　
丸茂 有香, 水谷 武史, 加藤 亜紀, 野崎 実穂, 吉田 宗徳, 南場 研一, 小椋 祐一郎, あたらしい眼科, 35, 6, 815, 819, 2018年06月
目的:トリアムシノロンTenon嚢下注射により悪化し、硝子体液PCRにより眼トキソプラズマ症と診断された1例を経験したので報告する。症例:55歳、女性。2000年に左眼のトキソプラズマ症に対しアセチルスピラマイシン内服、2008年に左眼ぶどう膜炎および視神経炎に対しステロイド内服の既往があった。2015年7月に左眼難治性ぶどう膜炎の精査加療目的で名古屋市立大学病院を受診した。初診時、左眼に硝子体混濁、および限局性網膜滲出斑を認めた。ぶどう膜炎に対しステロイド内服を行ったが所見が改善しないため、2015年8月および11月にトリアムシノロンTenon嚢下注射を施行したところ炎症が悪化した。翌年3月に左眼硝子体手術を施行、硝子体液のPCR検査でトキソプラズマDNAが確認された。眼トキソプラズマ症と診断しクリンダマイシン内服治療開始、その後硝子体混濁、網脈結膜炎は改善した。結論:診断確定にはPCR法によるトキソプラズマ原虫ゲノムの検査が有用である。(著者抄録), (株)メディカル葵出版, 日本語

Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative
Andrew D. Dick, James T. Rosenbaum, Hassan A. Al-Dhibi, Rubens Belfort, Antoine P. Brézin, Soon Phaik Chee, Janet L. Davis, Athimalaipet V. Ramanan, Koh-Hei Sonoda, Ester Carreño, Heloisa Nascimento, Sawsen Salah, Sherveen Salek, Jay Siak, Laura Steeples, Massimo Accorinti, Nisha Acharya, Alfredo Adan, Rupesh Agrawal, Nurullah Akkoc, Saed Al Ghamdi, Turki Al Ghamdi, Anood Al Saati, Nasser Alsabaani, Mohamed Al-Shamarani, Artur Bachta, Talin Barisani-Asenbauer, Nicholas Beare, Fernanda Belga Ottoni Porto, Ricardo Blanco, Anita Chan Sook Yee, Vinod Chandran, Christophe Chiquet, Hiok Hee Chng, Andrius Cimbalas, Luca Cimino, Miguel Cordero-Coma, Couto Cristobal, Miguel Cuevas, João Eurico da Fonseca, Joke de Boer, Alejandra de la Torre, Ilse De Schryver, Larissa Derzko-Dzulynsky, David Diaz-Valle, Claudia Eugenia Duran Merino, Andrea Facsko, Luis Figueira, Alejandro Fonollosa, Eric Fortin, Richard Gale, Mauro Galeazzi, Sandra Garcia, Jose Maria Garcia Ruiz de Morales, Nataša Gašperšič, Debra Goldstein, Marta Guedes, Yan Guex-Crosier, Ahmet Gul, Rola Hamam, Muhammad Haroon, Kenichi Hasegawa, Arnd Heiligenhaus, Claire Hooper, Yih-Shiou Hwang, De-Kuang Hwang, Xavier Juanola, Toshikatsu Kaburaki, Sibel Kadayifcilar, John Kempen, Takeshi Kezuka, Amin Kherani, Maarja Kirsimäe, Kaisu Kotaniemi, Aleksandra Kraut, Agnieszka Kubicka-Trząska, Lucia Kuffova, Susan Lightman, Lyndell Lim, Wee Kiak Lim, Peter McCluskey, Mairide McGuire, Pierfrancesco Mirabelli, Elisabetta Miserocchi, Marta Misiuk-Hojło, Cristina Muccioli, Santiago Muñoz, Conor Murphy, Philip Murray, Zoltan Nagy, Kenichi Namba, Piergiorgio Neri, Quan Nguyen, Donncha O'Gradaigh, Mohammed Omair, Kati Otsa, Yilmaz Ozyazgan, Franco Pablo, Maria Pia Paroli, Uwe Pleyer, Gyula Poór, Rui Proença, Theodore Rabinovitch, Russell Read, Margarita Rebrov, Claudia Recillas-Gispert, Aniki Rothova, Sergio Schwartzman, Pascal Seve, Srilakshmi Sharma, Joanne Sims, Nicolette Sohár, Eric Suhler, Sándor Szántó, Zsuzsanna Szepessy, Christoph Tappeiner, Jennifer Thorne, Ilknur Tugal Tutkun, Anna Turno-Kręcicka, Joachim Van Calster, Irene van der Horst-Bruinsma, Nataša Vidovič Valentinčič, Albert Vitale, Stephanie Voorduin Ramos, Nenad Vukojevic, Denis Wakefield, François Willermain, Nilufer Yalcindag, Joyce Hisae Yamamoto, Stephen Yeh, Reda Zemaitiene, Olga Ziouzina, Fundamentals of Care for Uveitis International Consensus Group, Ophthalmology, 125, 5, 757, 773, 2018年05月01日
Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic review of the literature (English language studies from January 1996 through June 2016
Medline [OVID], the Central Cochrane library, EMBASE, CINAHL, SCOPUS, BIOSIS, and Web of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review. A total of 44 globally representative group members met in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents
what data to collect before treatment
when to modify or withdraw treatment
how to select agents based on individual efficacy and safety profiles
and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents., Elsevier Inc., 英語, 書評論文,書評,文献紹介等

PM2.5汚染は重症アレルギー性結膜疾患と関連する　　　　　　　　　　　　　　　
宮崎 大, 深川 和己, 福島 敦樹, 藤島 浩, 内尾 英一, 海老原 伸行, 庄司 純, 高村 悦子, 南場 研一, 大橋 裕一, 岡本 茂樹, 佐竹 良之, 大津 洋, アレルギー, 67, 4-5, 590, 590, 2018年05月
(一社)日本アレルギー学会, 日本語

日本の眼科医および家族におけるアレルギー性結膜疾患の有病率調査　　　　　　　　　　　　　　　
深川 和己, 宮崎 大, 福島 敦樹, 藤島 浩, 内尾 英一, 海老原 伸行, 庄司 純, 高村 悦子, 南場 研一, 大橋 裕一, 岡本 茂樹, 佐竹 良之, 大津 洋, アレルギー, 67, 4-5, 670, 670, 2018年05月
(一社)日本アレルギー学会, 日本語

経過中ぶどう膜炎を併発した尋常性乾癬の小児の1例　　　　　　　　　　　　　　　
宮澤 元, 藤田 靖幸, 村松 憲, 岩田 浩明, 南場 研一, 保科 大地, 清水 宏, 日本皮膚科学会雑誌, 128, 4, 608, 608, 2018年04月
(公社)日本皮膚科学会, 日本語

TNF阻害薬の医師基準・施設基準および導入前スクリーニング検査　　　　　　　　　　　　　　　
南場 研一, 日本眼科学会雑誌, 122, 臨増, 96, 96, 2018年03月
(公財)日本眼科学会, 日本語

日本におけるアレルギー性結膜疾患の有病率と実態調査　　　　　　　　　　　　　　　
宮崎 大, 深川 和巳, 福島 敦樹, 藤島 浩, 内尾 英一, 海老原 伸行, 庄司 純, 高村 悦子, 南場 研一, 大橋 裕一, 岡本 茂樹, 佐竹 良之, 大津 洋, 日本眼科学会雑誌, 122, 臨増, 178, 178, 2018年03月
(公財)日本眼科学会, 日本語

眼サルコイドーシスの診断における血液検査・画像検査の有用性　　　　　　　　　　　　　　　
鈴木 佳代, 南場 研一, 水内 一臣, 岩田 大樹, 福原 崇子, 長谷 敬太郎, 濱田 怜, 大野 重昭, 北市 伸義, 石田 晋, 日本眼科学会雑誌, 122, 臨増, 191, 191, 2018年03月
(公財)日本眼科学会, 日本語

【脈絡膜疾患:ここまで解明できる!】 白点症候群　　　　　　　　　　　　　　　
岩田 大樹, 南場 研一, あたらしい眼科, 34, 12, 1725, 1730, 2017年12月
(株)メディカル葵出版, 日本語

フォークト・小柳・原田病の発症年齢における脈絡膜形態および循環動態の検討　　　　　　　　　　　　　　　
橋本 勇希, 南場 研一, 廣岡 季里子, 水内 一臣, 岩田 大樹, 石田 晋, 日本視能訓練士協会誌, 46, 309, 309, 2017年12月
(公社)日本視能訓練士協会, 日本語

トリアムシノロンテノン嚢下注射で急速に増悪した眼トキソプラズマ症の一例　　　　　　　　　　　　　　　
丸茂 有香, 水谷 武史, 加藤 亜紀, 野崎 実穂, 吉田 宗徳, 南場 研一, 小椋 祐一郎, 眼科臨床紀要, 10, 11, 965, 965, 2017年11月
眼科臨床紀要会, 日本語

【眼科救急Q&A】 救急疾患ごとの基本的な対処法 ぶどう膜炎 Vogt-小柳-原田病の初発症状、鑑別、治療について教えてください　　　　　　　　　　　　　　　
岩田 大樹, 南場 研一, あたらしい眼科, 34, 臨増, 187, 189, 2017年11月
(株)メディカル葵出版, 日本語

トリアムシノロンテノン嚢下注射で急速に増悪した眼トキソプラズマ症の一例　　　　　　　　　　　　　　　
丸茂 有香, 水谷 武史, 加藤 亜紀, 野崎 実穂, 吉田 宗徳, 南場 研一, 小椋 祐一郎, 眼科臨床紀要, 10, 11, 965, 965, 2017年11月
眼科臨床紀要会, 日本語

ステロイドを用いないタクロリムス点眼治療のシールド潰瘍に対する有効性　　　　　　　　　　　　　　　
宮崎 大, 井上 幸次, 福島 敦樹, 大橋 裕一, 海老原 伸行, 内尾 英一, 岡本 茂樹, 庄司 純, 高村 悦子, 中川 やよい, 南場 研一, 藤島 浩, 眼科臨床紀要, 10, 9, 770, 770, 2017年09月
眼科臨床紀要会, 日本語

Rosai-Dorfman病に合併した続発緑内障に対し360.suture trabeculotomy変法が奏効した1例　　　　　　　　　　　　　　　
菊地 香澄, 木嶋 理紀, 新明 康弘, 大口 剛司, 陳 進輝, 南場 研一, 齋藤 航, 石田 晋, 眼科手術, 30, 3, 514, 517, 2017年07月
背景:Rosai-Dorfman病(RDD)は1969年にRosaiとDorfmanによって報告された非腫瘍性組織球増殖性疾患であり、無痛性の頸部リンパ節腫脹で発症することが多く、約半数に節外病変を生じる。節外病変としてぶどう膜炎の報告が17例あるが、その続発緑内障に対しtrabeculotomy(LOT)を施行した報告はない。今回、筆者らはRDDに合併したぶどう膜炎治療中に続発緑内障をきたし、半年以上眼圧の改善がみられなかった症例に対し、360.suture trabeculotomy変法(S-LOT)を施行し、良好な眼圧コントロールが得られた1例を経験したので報告する。症例:63歳、女性。ぶどう膜炎精査加療目的で近医より紹介。所見:両眼に汎ぶどう膜炎を認め、精査にても確定診断には至らなかった。ステロイドの内服と点眼、Tenon嚢下注射にて加療し、眼圧は正常範囲内で経過していた。初診から7年後に腎腫瘍・骨腫瘍を指摘され、生検の結果RDDと診断された。初診から10年後に両眼圧は右眼46mmHg、左眼32mmHgと上昇し、前房に炎症所見はなく、緑内障点眼やアセタゾラミドナトリウム内服にてもコントロール不良であったため、両眼にS-LOTを施行した。術後2年間にわたり、眼圧は右眼10〜16mmHg、左眼9〜13mmHgと良好であった。結論:RDDに合併したぶどう膜炎治療中に発症した続発緑内障に対し、S-LOTが有効である可能性が示唆された。(著者抄録), (公社)日本眼科手術学会, 日本語

Laser speckle flowgraphyを施行した小児発症のフォークト・小柳・原田病の1例　　　　　　　　　　　　　　　
橋本 勇希, 南場 研一, 廣岡 季里子, 水内 一臣, 岩田 大樹, 齋藤 航, 石田 晋, 眼科臨床紀要, 10, 6, 514, 514, 2017年06月
眼科臨床紀要会, 日本語

シクロスポリン(ネオーラル) (特集 生物学的製剤の時代における非感染性ぶどう膜炎の治療戦略)
南場 研一, あたらしい眼科, 34, 4, 489, 492, 2017年04月
メディカル葵出版, 日本語

臨床報告 春季カタルにおけるタクロリムス点眼薬の長期使用成績
品川 真有子, 南場 研一, 北市 伸義, 石田 晋, 臨床眼科, 71, 3, 343, 348, 2017年03月
目的:春季カタルに対する0.1%タクロリムス点眼薬の長期使用効果の報告。対象と方法:1年以上タクロリムス点眼薬で加療した春季カタル16例30眼を対象とした。全例でシクロスポリン点眼薬がそれ以前に使用され,効果不十分であった。年齢は6〜19歳,平均15歳で,26眼が眼瞼型,4眼が眼瞼輪部混合型であった。14例にアトピー性皮膚炎,5例に喘息,3例にアレルギー性鼻炎の合併があった。9眼でステロイド点眼薬,8眼でステロイド内服薬を併用していた。結果:春季カタルの他覚的所見は全例で改善した。タクロリムス点眼薬の回数は,多くの症例で当初の1日2回から1日1回になり,ステロイド点眼薬の併用は開始時30%から1年後10%,ステロイド内服薬の併用は開始時25%から1年後6%に減少した。タクロリムス点眼薬を1年以上使用した30眼中16眼で一過性の増悪があり,その多くは5月と7〜9月に生じた。1眼でタクロリムス点眼薬の使用開始から38ヵ月後に上皮性単純ヘルペス角膜炎が発症し,加療により治癒した。結論:シクロスポリン点眼薬が奏効しない春季カタルに対し,1年以上のタクロリムス点眼薬の使用で,他覚的所見と症状の改善がみられた。(著者抄録), (株)医学書院, 日本語

腫瘍性病変が疑われた結節性後部強膜炎の1例　　　　　　　　　　　　　　　
柴田 有紀子, 加瀬 諭, 南場 研一, 石田 晋, 日本眼科学会雑誌, 121, 臨増, 329, 329, 2017年03月
(公財)日本眼科学会, 日本語

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年03月
(公財)日本眼科学会, 日本語

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TNF阻害薬使用検討委員会, 日本眼科学会雑誌, 121, 1, 34, 41, 2017年01月
(公財)日本眼科学会, 日本語

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年01月
(公財)日本眼科学会, 日本語

フォークト・小柳・原田病のステロイド薬全身投与後における眼底自発蛍光　　　　　　　　　　　　　　　
橋本 勇希, 水内 一臣, 廣岡 季里子, 南場 研一, 石田 晋, 日本視能訓練士協会誌, 45, 335, 335, 2016年12月
(公社)日本視能訓練士協会, 日本語

ぶどう膜炎の救急 (特集 眼科医のための救急マニュアル)
岩田 大樹, 南場 研一, Oculista = オクリスタ, 44, 19, 25, 2016年11月
全日本病院出版会, 日本語

フォークト・小柳・原田病の発症年齢における脈絡膜形態および循環動態の検討　　　　　　　　　　　　　　　
橋本 勇希, 南場 研一, 廣岡 季里子, 水内 一臣, 岩田 大樹, 石田 晋, 日本視能矯正学会プログラム抄録集, 57回, 88, 88, 2016年10月
日本視能矯正学会, 日本語

【眼科検査の最新情報】 ぶどう膜炎 Laser speckle flowgraphyでみるぶどう膜疾患
橋本 勇希, 南場 研一, 石田 晋, 眼科, 58, 11, 1200, 1206, 2016年10月
金原出版(株), 日本語

Vogt・小柳・原田病の再発の有無によるステロイド全身投与後の脈絡膜循環動態の比較　　　　　　　　　　　　　　　
廣岡 季里子, 齋藤 航, 南場 研一, 水内 一臣, 岩田 大樹, 橋本 勇希, 齋藤 理幸, 石田 晋, 眼科臨床紀要, 9, 10, 842, 843, 2016年10月
眼科臨床紀要会, 日本語

Steroid sparing effect of 0.1% tacrolimus eye drops for treatment of shield ulcer and corneal epitheliopathy in refractory allergic ocular diseases
Dai Miyazaki, Atsuki Fukushima, Yuichi Ohashi, Nobuyuki Ebihara, Eiichi Uchio, Shigeki Okamoto, Jun Shoji, Etsuko Takamura, Yayoi Nakagawa, Kenichi Namba, Hiroshi Fujishima, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 57, 12, 2016年09月
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 英語, 研究発表ペーパー・要旨（国際会議）

Adalimumab in patients with active and inactive, non-infectious uveitis: VISUAL I and VISUAL II trials
Antoine P. Brezin, Andrew D. Dick, Glenn J. Jaffe, Shigeaki Ohno, Kenichi Namba, Hiroshi Goto, Noritaka Inomata, Alexandra P. Song, Martina Kron, Anne Camez, Quan Dong Nguyen, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 57, 12, 2016年09月
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 英語, 研究発表ペーパー・要旨（国際会議）

タクロリムス点眼によるステロイド反応性眼圧上昇抑制効果　　　　　　　　　　　　　　　
宮崎 大, 井上 幸次, 福島 敦樹, 大橋 裕一, 海老原 伸行, 内尾 英一, 岡本 茂樹, 庄司 純, 高村 悦子, 中川 やよい, 南場 研一, 藤島 浩, 眼科臨床紀要, 9, 6, 539, 540, 2016年06月
眼科臨床紀要会, 日本語

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年03月
(公財)日本眼科学会, 日本語

フォークト・小柳・原田病のステロイド全身投与前後におけるLSFGを用いた波形解析　　　　　　　　　　　　　　　
廣岡 季里子, 齋藤 航, 南場 研一, 水内 一臣, 宇野 友絵, 田川 義晃, 齋藤 理幸, 野田 航介, 石田 晋, 眼科臨床紀要, 8, 11, 850, 851, 2015年11月
眼科臨床紀要会, 日本語

フォークト・小柳・原田病のステロイド薬全身投与後における眼底自発蛍光　　　　　　　　　　　　　　　
橋本 勇希, 水内 一臣, 廣岡 季里子, 南場 研一, 石田 晋, 日本視能矯正学会プログラム抄録集, 56回, 50, 50, 2015年10月
日本視能矯正学会, 日本語

治療に苦慮した乾癬ぶどう膜炎による続発緑内障の1例　　　　　　　　　　　　　　　
田川 小百合, 陳 進輝, 田川 義晃, 新明 康弘, 大口 剛司, 木嶋 理紀, 宇野 友絵, 石嶋 漢, 新田 卓也, 南場 研一, 石田 晋, あたらしい眼科, 32, 8, 1201, 1204, 2015年08月
症例は45歳の男性で、10数年前より乾癬の診断を受け、数年前から両眼にぶどう膜炎による発作を繰り返し、プレドニゾロン内服とステロイド点眼治療を受けていた。繰り返す発作と眼圧上昇のため、北海道大学病院眼科を受診、左眼眼圧のコントロール不良に対し、左マイトマイシンC併用線維柱帯切除術を施行した。術後数ヵ月間にわたる遷延性の低眼圧が持続したため、毛様体機能不全による房水産生能低下を考え、左強膜弁縫合術を行った。その後、左眼眼圧は落ち着いたが、半年後に右眼の続発緑内障をきたし、さらに左眼眼圧の再上昇をきたしたため、前回の経過を踏まえ、右眼に360° suture trabeculotomy変法、左眼に240° trabeculotomy変法を施行した。右眼の眼圧は良好だったが、3ヵ月後に左眼眼圧が再上昇したため、左眼濾過胞再建術を追加した。その後は両眼とも眼圧が10mmHg前後と落ち着いている。(著者抄録), (株)メディカル葵出版, 日本語

Clinical features associated with steroid-induced ocular hypertensive response in eyes with refractory allergic ocular diseases with proliferative lesions or corneal involvement
Dai Miyazaki, Atsuki Fukushima, Yuichi Ohashi, Eiichi Uchio, Naoki Kumagai, Jun Shoji, Etsuko Takamura, Yayoi Nakagawa, Kenichi Namba, Hiroshi Fujishima, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 56, 7, 2015年06月
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 英語, 研究発表ペーパー・要旨（国際会議）

ぶどう膜炎と類縁疾患(2)Vogt-小柳-原田病
岩田 大樹, 南場 研一, 眼科, 57, 3, 273, 278, 2015年03月
金原出版, 日本語

若年性慢性虹彩毛様体炎の臨床像の検討　　　　　　　　　　　　　　　
宇野 友絵, 南場 研一, 水内 一臣, 岩田 大樹, 北市 伸義, 大野 重昭, 石田 晋, 日本眼科学会雑誌, 119, 臨増, 162, 162, 2015年03月
(公財)日本眼科学会, 日本語

急性帯状潜在性網膜外層症における視機能を規定する因子　　　　　　　　　　　　　　　
齋藤 航, 齊藤 沙宝, 齋藤 理幸, 橋本 勇希, 森 祥平, 安藤 亮, 野田 航介, 南場 研一, 石田 晋, 日本眼科学会雑誌, 119, 臨増, 182, 182, 2015年03月
(公財)日本眼科学会, 日本語

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年03月
(公財)日本眼科学会, 日本語

Vogt-小柳-原田病再発例に対するシクロスポリン併用療法の検討　　　　　　　　　　　　　　　
水内 一臣, 南場 研一, 岩田 大樹, 宇野 友絵, 北市 伸義, 大野 重昭, 石田 晋, 日本眼科学会雑誌, 119, 臨増, 187, 187, 2015年03月
(公財)日本眼科学会, 日本語

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年10月
(公財)日本眼科学会, 日本語

春季カタルの点眼薬治療の進歩 (特集 アレルギー性結膜疾患の病態と診療の進歩)
福原 崇子, 南場 研一, 臨床免疫・アレルギー科, 61, 4, 416, 421, 2014年04月
科学評論社, 日本語

診断に苦慮した毛様体平滑筋腫の一例　　　　　　　　　　　　　　　
石嶋 漢, 加瀬 諭, 吉川 洋, 鈴木 茂伸, 新明 康弘, 南場 研一, 山本 哲平, 野崎 真世, 野田 実香, 石田 晋, 日本眼科学会雑誌, 118, 臨増, 304, 304, 2014年03月
(公財)日本眼科学会, 日本語

日本人原田病患者におけるInterleukin 10遺伝子多型の解析　　　　　　　　　　　　　　　
奥居 晋太郎, 目黒 明, 東 香里, 伊藤 晴康, 北市 伸義, 南場 研一, 大野 重昭, 水木 信久, 日本眼科学会雑誌, 118, 臨増, 278, 278, 2014年03月
(公財)日本眼科学会, 日本語

日本人原田病患者におけるIL23R-IL12RB2遺伝子多型の解析　　　　　　　　　　　　　　　
伊藤 晴康, 目黒 明, 佐藤 理一郎, 奥居 晋太郎, 北市 伸義, 南場 研一, 大野 重昭, 水木 信久, 日本眼科学会雑誌, 118, 臨増, 278, 278, 2014年03月
(公財)日本眼科学会, 日本語

【眼科診療指針のパラダイムシフト 網膜硝子体/ぶどう膜/神経眼科/眼腫瘍・眼窩・ロービジョン【編】】 ぶどう膜 ベーチェット病の薬物療法　　　　　　　　　　　　　　　
水内 一臣, 南場 研一, 眼科, 56, 2, 225, 229, 2014年01月
金原出版(株), 日本語

急性網膜壊死のあたらしい診断基準の作成　　　　　　　　　　　　　　　
高瀬 博, 大黒 伸行, 岡田 アナベルあやめ, 後藤 浩, 園田 康平, 冨田 誠, 南場 研一, 水木 信久, 望月 學, 日本眼科学会雑誌, 117, 11, 935, 935, 2013年11月
(公財)日本眼科学会, 日本語

線維柱帯切除術後に持続性の低眼圧に陥った乾癬ぶどう膜炎による続発緑内障の一例　　　　　　　　　　　　　　　
田川 義晃, 大口 剛司, 新明 康弘, 清水 啓史, 宇野 友絵, 石嶋 漢, 新田 卓也, 南場 研一, 陳 進輝, 石田 晋, 日本緑内障学会抄録集, 24回, 163, 163, 2013年09月
日本緑内障学会, 日本語

【ぶどう膜炎 外来診療】 小児ぶどう膜炎　　　　　　　　　　　　　　　
南場 研一, 水内 一臣, OCULISTA, 5, 65, 68, 2013年08月
小児のぶどう膜炎は成人に比べ少なく、自覚症状を自ら訴えることが少ないため初期症状に気づかれないことが多く、また、慢性例が多いこと、帯状角膜変性、虹彩後癒着、併発白内障が多くみられること、原因が同定不能である例が多いことなど、成人とは異なった特徴を有している。原因疾患では、サルコイドーシス、間質性腎炎ぶどう膜炎症候群、若年性慢性虹彩毛様体炎が多く、その他、Behcet病や、Vogt-小柳-原田病、ヘルペスウイルス虹彩毛様体炎、Fuchs虹彩異色性虹彩毛様体炎、急性前部ぶどう膜炎、川崎病に伴うぶどう膜炎や、最近ではBlau症候群の報告もみられる。治療は原疾患に対するものの他、ステロイド点眼薬などの局所療法が主となる。完全な消炎を得られない場合も多いが、合併症を少なくするためにも、その使用は必要最小限にとどめたい。また、虹彩後癒着を進行させないように瞳孔管理も重要である。(著者抄録), (株)全日本病院出版会, 日本語

春季カタルに対する免疫抑制点眼薬治療
南場 研一, あたらしい眼科 = Journal of the eye, 30, 5, 645, 647, 2013年05月30日
メディカル葵出版, 日本語

Vogt-小柳-原田病の前眼部炎症再発時における脈絡膜循環障害　　　　　　　　　　　　　　　
竹本 裕子, 南場 研一, 水内 一臣, 橋本 勇希, 宇野 友絵, 北市 伸義, 大野 重昭, 石田 晋, 日本眼科学会雑誌, 117, 臨増, 255, 255, 2013年03月
(公財)日本眼科学会, 日本語

ベーチェット病眼炎症発作とインフリキシマブトラフ値・サイトカイン血中濃度との相関　　　　　　　　　　　　　　　
水内 一臣, 竹本 裕子, 南場 研一, 宇野 友絵, 大野 重昭, 石田 晋, 日本眼科学会雑誌, 117, 臨増, 317, 317, 2013年03月
(公財)日本眼科学会, 日本語

ぶどう膜炎における網羅的糖鎖解析　　　　　　　　　　　　　　　
南場 研一, 北市 伸義, 安藤 亮, 竹本 裕子, 水内 一臣, 堀江 幸弘, 大野 重昭, 天野 麻穂, 西村 紳一郎, 石田 晋, 日本眼科学会雑誌, 117, 臨増, 318, 318, 2013年03月
(公財)日本眼科学会, 日本語

周辺虹彩前癒着を伴うぶどう膜炎に続発した緑内障に対するsuture-trabeculotomyの成績　　　　　　　　　　　　　　　
大口 剛司, 新明 康弘, 新田 卓也, 山本 麻梨亜, 南場 研一, 大野 重昭, 陳 進輝, 石田 晋, 日本眼科学会雑誌, 117, 臨増, 339, 339, 2013年03月
(公財)日本眼科学会, 日本語

Behcet 病
竹本 裕子, 南場 研一, あたらしい眼科 = Journal of the eye, 29, 10, 1341, 1346, 2012年10月30日
メディカル葵出版, 日本語

隅角結節を伴う続発緑内障の臨床像　　　　　　　　　　　　　　　
竹本 裕子, 新田 卓也, 南場 研一, 水内 一臣, 宇野 友絵, 大口 剛司, 新明 康弘, 陳 進輝, 石田 晋, 日本緑内障学会抄録集, 23回, 133, 133, 2012年09月
日本緑内障学会, 日本語

アレルギー性結膜疾患診断における自覚症状, 他覚所見および涙液総IgE検査キットの有用性の検討
庄司 純, 内尾 英一, 海老原 伸行, 大橋 裕一, 大野 重昭, 岡本 茂樹, 熊谷 直樹, 佐竹 良之, 南場 研一, 深川 和己, 福島 敦樹, 藤島 浩, 高村 悦子, 日本眼科學会雜誌, 116, 5, 485, 493, 2012年05月10日
日本眼科学会, 日本語

アレルギー性結膜疾患特異的 quality of life 調査票の確立
深川 和己, 藤島 浩, 福島 敦樹, 角 環, 岡本 茂樹, 庄司 純, 佐竹 良之, 大野 重昭, 南場 研一, 北市 伸義, 海老原 伸行, 高橋 浩, 熊谷 直樹, 内野 裕一, 内野 美樹, 村山 公一, 坂田 実紀, 内尾 英一, 高村 悦子, 大橋 裕一, 大久保 公裕, 佐藤 敏彦, 日本眼科學会雜誌, 116, 5, 494, 502, 2012年05月, ［国内誌］
PURPOSE: To establish a specific quality of life (QOL) questionnaire for Japanese allergic conjunctival disease (ACD) (Japanese allergic conjunctival disease QOL questionnaire: JACQLQ). SUBJECTS AND METHODS: A multicenter study was conducted in 521 patients with ACD and 127 healthy volunteers (total 648 cases). The JACQLQ ver. 0 was developed by modifying the Japanese rhino-conjunctivitis QOL questionnaire (JRQLQ). The participants were asked to complete the questionnaire, and objective scores were determined by an ophthalmologist using a slit lamp. To confirm validity, item and factor analyses were conducted and correlation coefficients were calculated. RESULTS: The items were grouped into four subscales (Daily activity, Psychological well-being, Eye symptoms, Nasal symptoms) after factor analysis. The JACQLQ had good item-internal consistency (Cronbach's alpha: 0.846-0.934). QOL scores were correlated with eye itching, eye irritation and tearing. Objective scores were correlated with eye redness, eye itching and eye irritation. Face scores were correlated with eye itching, eye irritation and eye redness. CONCLUSION: The JACQLQ is a useful tool for assessing disease specific QOL in ACD., 日本語

S2-2 シクロスポリン点眼液の使用結果について(S2 (日本眼科アレルギー研究会)重症アレルギー性結膜疾患と免疫抑制剤点眼,シンポジウム2,第24回日本アレルギー学会春季臨床大会)
南場 研一, アレルギー, 61, 3, 390, 390, 2012年04月10日
一般社団法人日本アレルギー学会, 日本語

Behcet病(ベーチェット病)眼病変診療ガイドライン
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年04月
(公財)日本眼科学会, 日本語

外転神経麻痺、視神経炎後に水痘帯状疱疹ウイルスによる急性網膜壊死を来たした1例　　　　　　　　　　　　　　　
堀内 一宏, 竹内 朗子, 加納 崇裕, 廣谷 真, 南場 研一, 水内 一臣, 仁平 敦子, 矢部 一郎, 佐々木 秀直, 臨床神経学, 52, 3, 198, 198, 2012年03月
(一社)日本神経学会, 日本語

Vogt-小柳-原田病における隅角色素脱失(大野徴候)の検討　　　　　　　　　　　　　　　
水内 一臣, 南場 研一, 北市 伸義, 堀江 幸弘, 岩田 大樹, 石田 晋, 大野 重昭, 日本眼科学会雑誌, 116, 臨増, 249, 249, 2012年03月
(公財)日本眼科学会, 日本語

IKKβ阻害薬IMD0354によるラットEIUの軽症化　　　　　　　　　　　　　　　
アントン・レニコフ, 北市 伸義, 野田 航介, 南場 研一, 大野 重昭, 石田 晋, 日本眼科学会雑誌, 116, 臨増, 274, 274, 2012年03月
(公財)日本眼科学会, 日本語

日本人原田病患者におけるToll-like receptor 2遺伝子多型の解析　　　　　　　　　　　　　　　
伊藤 晴康, 目黒 明, 田部井 信充, 奥居 晋太郎, 北市 伸義, 南場 研一, 大野 重昭, 水木 信久, 日本眼科学会雑誌, 116, 臨増, 380, 380, 2012年03月
(公財)日本眼科学会, 日本語

日本人原田病患者におけるToll-like receptor 4遺伝子多型の解析　　　　　　　　　　　　　　　
奥居 晋太郎, 目黒 明, 後藤 さやか, 伊藤 晴康, 北市 伸義, 南場 研一, 大野 重昭, 水木 信久, 日本眼科学会雑誌, 116, 臨増, 381, 381, 2012年03月
(公財)日本眼科学会, 日本語

健康成人の片眼に発症した内因性真菌性眼内炎
宇野 友絵, 南場 研一, 加瀬 諭, 齋藤 航, 北市 伸義, 大野 重昭, 石田 晋, あたらしい眼科 = Journal of the eye, 29, 1, 135, 138, 2012年01月30日
メディカル葵出版, 日本語

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年10月
日本サルコイドーシス, 日本語

春季カタルに対するシクロスポリン点眼液0.1%の全例調査
高村 悦子, 内尾 英一, 海老原 伸行, 岡本 茂樹, 熊谷 直樹, 庄司 純, 中川 やよい, 南場 研一, 福島 敦樹, 藤島 浩, 宮崎 大, 大橋 裕一, 日本眼科學会雜誌, 115, 6, 508, 515, 2011年06月10日
日本眼科学会, 日本語

原発開放隅角緑内障(POAG)として紹介された続発緑内障の臨床像　　　　　　　　　　　　　　　
新田 卓也, 新明 康弘, 仲 昌彦, 野澤 亜紀子, 南場 研一, 陳 進輝, 石田 晋, 日本眼科学会雑誌, 115, 臨増, 316, 316, 2011年04月
(公財)日本眼科学会, 日本語

口腔におけるカセリシジンファミリー抗菌ペプチドCAP18/LL37の微生物制御
磯貝 浩, 磯貝 恵美子, 奥村 一彦, 南場 研一, 北市 伸義, 大野 重昭, 角舘 直樹, 無菌生物 = Japanese journal of germfree life and gnotobiology, 40, 2, 54, 59, 2010年12月01日
日本無菌生物ノートバイオロジー学会, 日本語

INFLIXIMAB THERAPY MAY GREATLY CHANGE OCULAR INFLAMMATION AND VISUAL PROGNOSIS IN BEHCET'S DISEASE
Shigeaki Ohno, Annabelle A. Okada, Hiroshi Goto, Ken-ichi Namba, Nobuyoshi Kitaichi, Nobuhisa Mizuki, CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, 28, 4, S122, S122, 2010年07月
CLINICAL & EXPER RHEUMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

WHY DOES BEHCET'S DISEASE DECLINE IN JAPAN? -POSSIBLE ASSOCIATION BETWEEN ECONOMIC DEVELOPMENT AND DECREASED RISK OF BEHCET'S DISEASE
Shigeaki Ohno, Emiko Isogai, Hiroshi Isogai, Fumio Kaneko, Kenichi Namba, Nobuyoshi Kitaichi, CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, 28, 4, S124, S124, 2010年07月
CLINICAL & EXPER RHEUMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

ASSOCIATION OF TLR4 POLYMORPHISMS WITH BEHCET'S DISEASE IN JAPANESE AND KOREAN POPULATIONS
Yukihiro Horie, Akira Meguro, Nobuyoshi Kitaichi, Masao Ota, Kenichi Namba, Yeong Wook Song, Kyung Sook Park, Eun Bong Lee, Hidetoshi Inoko, Nobuhisa Mizuki, Susumu Ishida, Shigeaki Ohno, CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, 28, 4, S161, S161, 2010年07月
CLINICAL & EXPER RHEUMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

GENOME-WIDE ASSOCIATION STUDIES DEFINE TWO SUSCEPTIBILITY LOCI FOR BEHCET'S DISEASE
Nobuhisa Mizuki, Akira Meguro, Masao Ota, Yeong Wook Song, Eun Bong Lee, Nobuyoshi Kitaichi, Kenichi Namba, Yukihiro, Mitsuhiro Takeno, Sunao Sugita, Manabu Mochizuki, Seiamak Bahram, Yoshiaki Ishigatsubo, Hidetoshi Inoko, Shigeaki Ohno, CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, 28, 4, S114, S114, 2010年07月
CLINICAL & EXPER RHEUMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

診断が困難な症例 網膜血管炎を合併したacute zonal occult outer retinopathyの1症例　　　　　　　　　　　　　　　
齋藤 航, 南場 研一, 石田 晋, 眼科臨床紀要, 3, 7, 693, 693, 2010年07月
眼科臨床紀要会, 日本語

炎症性眼疾患の診療(26)Behcet病
南場 研一, 北市 伸義, 大野 重昭, 臨床眼科, 64, 5, 630, 636, 2010年05月
医学書院, 日本語

内2 アレルギー性結膜疾患(教育講演,内科専門医コース2(眼科提供),第22回日本アレルギー学会春季臨床大会)
大野 重昭, 北市 伸義, 南場 研一, アレルギー, 59, 3, 261, 261, 2010年04月10日
一般社団法人日本アレルギー学会, 日本語

炎症性眼疾患の診療(25)真菌性眼内炎
北市 伸義, 齋藤 航, 南場 研一, 臨床眼科, 64, 4, 416, 420, 2010年04月
医学書院, 日本語

アレルギー性結膜炎患者の治療前後における涙液中IgEの経時的検討　　　　　　　　　　　　　　　
赤沼 正堂, 石嶋 漢, 北市 伸義, 南場 研一, 大野 重昭, 石田 晋, 日本眼科学会雑誌, 114, 臨増, 297, 297, 2010年03月
(公財)日本眼科学会, 日本語

Behcet 病に対するインフリキシマブ療法 : 生物学的製剤時代の幕開け
南場 研一, 日本眼科學会雜誌, 114, 2, 85, 86, 2010年02月10日
日本語

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年10月
(公財)日本眼科学会, 日本語

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年10月
日本サルコイドーシス, 日本語

免疫抑制剤(シクロスポリン・タクロリムス)の眼科治療 今と昔 免疫抑制剤(カルシニューリン阻害薬)の歴史・作用機序・副作用　　　　　　　　　　　　　　　
南場 研一, 石田 晋, 大野 重昭, 日本の眼科, 80, 9, 1143, 1147, 2009年09月
カルシニューリン阻害薬として使用されているものにはシクロスポリン、タクロリムスがあり、臓器移植後の拒絶反応の抑制、ベーチェット病を含む膠原病、アトピー性皮膚炎に対し内服薬として使用され、最近では外用薬(軟膏)、点眼薬として局所でも使われるようになってきた。T細胞が活性化する際に細胞内で活躍するカルシニューリンを阻害することでT細胞の活性化を抑制する薬剤である。それぞれに特有の副作用がある薬剤であり、薬剤血中濃度のモニタリングや定期的な血液検査を行いながら使用する必要がある。(著者抄録), (公社)日本眼科医会, 日本語

韓国人ベーチェット病患者におけるTLR4遺伝子の検討　　　　　　　　　　　　　　　
堀江 幸弘, 目黒 明, 太田 正穂, 北市 伸義, 勝山 義彦, 竹本 裕子, 南場 研一, 吉田 和彦, Song Yeong Wook, Park Kyung Sook, 猪子 英俊, 水木 信久, 大野 重昭, 日本眼科学会雑誌, 113, 臨増, 214, 214, 2009年03月
(公財)日本眼科学会, 日本語

ベーチェット病眼症状に対する顆粒球・単核球除去療法(<特集>血球成分除去療法の新しい展開)
園田 康平, 南場 研一, 日本アフェレシス学会雑誌, 28, 1, 68, 71, 2009年02月28日
Intraocular inflammation (uveoretinitis) is one major complication of Behcet's disease (BD). We assess the efficacy of selective granulocytapheresis in patients with refractory uveoretinitis of BD. Fourteen patients were treated. Granulocytapheresis was done with an Adacolumn filled with cellulose acetate leucocyte carriers or beads that adsorb granulocytes and monocytes from the blood in the column. Each patient received 5 Adacolumn sessions at one session/week over 5 consecutive weeks. The study was designed to allow each patient to serve as his or her own control. The number of ocular at..., 日本アフェレシス学会, 日本語

Nuclear factor-kappa B inhibitor, dehydroxy methyl epoxyquinomicin ameliorates experimental autoimmune uveoretinitis (EAU) in mice　　　　　　　　　　　　　　　
Iwata, D, Kitaichi, N, Ebihara, A, Iwabuchi, K, Yoshida, K, Namba, K, Ozaki, M, Ohno, S, Umezawa, K, Yamashita, K, Todo, S, Ishida, S, Onoé, K, IOVS, in press, 2009年

炎症性眼疾患の診療(21)HLA-B27関連ぶどう膜炎
南場 研一, 北市 伸義, 三浦 淑恵, 臨床眼科, 62, 13, 1950, 1954, 2008年12月
医学書院, 日本語

ヒト白血球抗原(HLA)
南場 研一, あたらしい眼科 = Journal of the eye, 25, 11, 1479, 1483, 2008年11月30日
メディカル葵出版, 日本語

臨床報告 春季カタルに対する0.1%シクロスポリン点眼液の臨床効果
合田 千穂, 南場 研一, 北市 伸義, 臨床眼科, 62, 9, 1583, 1588, 2008年09月
医学書院, 日本語

日本人サルコイドーシスにおけるBTNL2遺伝子多型の解析
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年08月
日本組織適合性学会, 日本語

OCULAR LESIONS OF BEHCET'S DISEASE IN JAPAN
Shigeaki Ohno, Nobuyoshi Kitaichi, Hirokuni Kitamei, Kenichi Namba, Akiko Miyazaki, Daiju Iwata, CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, 26, 4, S39, S39, 2008年07月
CLINICAL & EXPER RHEUMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

PCR-SSOP-Luminex 法を用いた日本人 Behcet 病患者における症状別HLA-A, -B遺伝子解析
上石 智子, 伊藤 良樹, 目黒 明, 西田 朋美, 佐々木 爽, 南場 研一, 大野 重昭, 猪子 英俊, 水木 信久, 日本眼科學会雜誌 = Journal of Japanese Ophthalmological Society, 112, 5, 451, 8, 2008年05月, ［国内誌］
PURPOSE: High resolution (four-digit) allele genotyping was used to determine the association of the HLA-A and -B alleles with Behçet's disease (BD) in Japanese patients. We also analyzed our results for the association of these alleles with the individual clinical features of BD. SUBJECTS AND METHODS: We enrolled 389 Japanese BD patients and 254 healthy controls in this study. Genotyping of the HLA-A, -B alleles was performed by the PCR-SSOP-Luminex method and the phenotype frequencies of the HLA-A, and -B alleles were estimated. RESULTS: Some HLA-A and -B alleles were significantly associated with BD. When we recalculated the phenotype frequencies for the HLA-B*51-negative subjects to exclude the effects of the linkage disequilibrium with the HLA-B*51 allele, HLA-A*2601 was most strongly associated with BD. In addition, we observed a significant association between several clinical features and some alleles, including HLA-A*2602. CONCLUSION: The significant increase of HLA-A* 26 in the BD patients without HLA-B*51 suggests that this allele itself might be one of the primary susceptibility genes involved in the development of BD independently of HLA-B*51., 日本眼科学会, 日本語

韓国のベーチェット病患者におけるHLA-B51遺伝子の検討　　　　　　　　　　　　　　　
堀江 幸弘, 竹本 裕子, 北市 伸義, 目黒 明, 太田 正穂, Song Yeong-Wook, Park Kyung-Soon, 南場 研一, 猪子 英俊, 水木 信久, 大野 重昭, 日本眼科学会雑誌, 112, 臨増, 286, 286, 2008年03月
(公財)日本眼科学会, 日本語

北海道大学における急性網膜壊死の臨床像
水内 一臣, 南場 研一, 小竹 聡, 大野 重昭, 日本眼科學会雜誌 = Journal of Japanese Ophthalmological Society, 112, 2, 136, 140, 2008年02月10日
日本眼科学会, 日本語

ベーチェット病による難治性網膜ぶどう膜炎に対するインフリキシマブの有効性
南場研一, リウマチ科, 39, 27, 35, 2008年

サルコイドーシス患者におけるCARD15遺伝子変異スクリーニング解析
赤星 光輝, 石原 麻美, 南場 研一, 北市 伸義, 安藤 靖恭, 岳中 耐夫, 湯浅 武之助, 石田 敬子, 大野 重昭, 水木 信久, 白川 太郎, サルコイドーシス/肉芽腫性疾患, 27, Suppl., 29, 29, 2007年10月
日本サルコイドーシス, 日本語

原田病におけるインターフェロン-γ遺伝子多型の検討　　　　　　　　　　　　　　　
堀江 幸弘, 北市 伸義, 竹本 裕子, 南場 研一, 吉田 和彦, 広瀬 茂人, 蓮見 由紀子, 水木 信久, 大野 重昭, 日本眼科学会雑誌, 111, 臨増, 233, 233, 2007年03月
(公財)日本眼科学会, 日本語

CpG反応樹状細胞によるNKT細胞からのIL-4産生誘導　　　　　　　　　　　　　　　
水内一臣, 柳川芳毅, 岩渕和也, 南場研一, 小野江和則, 大野重昭, 臨床免疫・アレルギー科, 48, 3, 236, 242, 2007年

サルコイドーシス眼病変における重症、難治性の検討
飛鳥田 有里, 石原 麻美, 蓮見 由紀子, 中村 聡, 林 清文, 水木 信久, 南場 研一, 大野 重昭, 日本眼科紀要, 57, 12, 877, 880, 2006年12月
目的:サルコイドーシス(サ症)患者における重症サ症と難治性サ症の割合と特徴を調べる。また難治化にかかわる因子について検討する。方法:眼症状発症後2年以上経過したサ症組織診断群患者87例を対象とした。重症サ症、難治性サ症を、眼科的見地から独自に定義し検討した。結果:重症サ症は47例(54.0%)、難治性サ症は23例(26.4%)であった。重症サ症の定義の7項目のうち、(1)40mmHg以上の眼圧上昇または視野変化を有する続発緑内障、(2)3+以上のびまん性硝子体混濁、(3)嚢胞様黄斑浮腫の出現頻度が高かった。難治性サ症の定義3項目のうち、(1)緑内障濾過手術または硝子体手術を必要とする、(2)副腎皮質ステロイド薬全身投与で改善しない、または減量による再燃を繰り返す症例が多かった。重症かつ難治性症例では、重症かつ非難治性症例に比べ、(1)3+以上のびまん性硝子体混濁、(2)重症と考えられる眼病変を2項目以上満たす症例が有意に多かった。結論:一般にサ症は予後の悪くない疾患といわれるが、一部には治療に苦慮する症例が存在することが再認識された。重症サ症が難治化する要因として、(1)高度の(3+以上)びまん性硝子体混濁、(2)重症と考えられる眼病変を複数もつ、ことが考えられた。(著者抄録), 日本眼科紀要会, 日本語

生物学的製剤
南場 研一, 大野 重昭, あたらしい眼科 = Journal of the eye, 23, 11, 1409, 1414, 2006年11月30日
日本語

顆粒球除去療法
園田 康平, 南場 研一, あたらしい眼科 = Journal of the eye, 23, 11, 1415, 1419, 2006年11月30日
日本語

Behcet 病眼症に対する顆粒球除去療法
園田 康平, 南場 研一, 眼科手術 = Journal of ophthalmic surgery, 19, 4, 489, 491, 2006年10月30日
日本語

広範な網脈絡膜萎縮を来した後部強膜炎の1例
三浪 梨絵子, 齋藤 航, 南場 研一, 大野 重昭, 日本眼科學会雜誌 = Journal of Japanese Ophthalmological Society, 110, 9, 730, 735, 2006年09月10日
日本眼科学会, 日本語

Comparative study of two sets of criteria for the diagnosis of Vogt-Koyanagi-Harada's disease. (vol 139, pg 1080, 2005)
M Kitamura, K Takami, N Kitachi, K Namba, H Kitamei, S Kotake, S Ohno, AMERICAN JOURNAL OF OPHTHALMOLOGY, 141, 6, 1179, 1179, 2006年06月
ELSEVIER SCIENCE INC, 英語, その他

Comparative study of two sets of criteria for the diagnosis of Vogt-Koyanagi-Harada disease - Reply
M Kitamura, N Kitaichhi, K Namba, K Kitamei, S Ohno, AMERICAN JOURNAL OF OPHTHALMOLOGY, 141, 4, 779, 779, 2006年04月
ELSEVIER SCIENCE INC, 英語, 速報，短報，研究ノート等（学術雑誌）

アレルギー性結膜疾患診療ガイドライン
大野 重昭, 内尾 英一, 海老原 伸行, 大橋 裕一, 岡本 茂樹, 熊谷 直樹, 庄司 順, 高村 悦子, 中川 やよい, 南場 研一, 福島 敦樹, 藤島 浩, 日本眼科學会雜誌 = Journal of Japanese Ophthalmological Society, 110, 2, 99, 140, 2006年02月10日
日本眼科学会, 日本語

マウス実験的自己免疫性網膜ぶどう膜炎におけるオステオポンチンの役割
北村瑞, 北村瑞, 岩淵和也, 北明大洲, 北明大洲, 北市伸義, 南場研一, 今重之, 上出利光, 小野江和則, 大野重昭, 日本眼科学会雑誌, 110, 2006年

北海道大学大学院医学研究科 病態制御学専攻感覚器病学講座 視覚器病学分野 : ヌペ(涙)からミナミナ(微笑み)へ
北明 大洲, 南場 研一, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 81, 1, 85, 87, 2006年01月01日
日本語

カラー臨床報告 大量の線維素析出を伴うぶどう膜炎を発症した潰瘍性大腸炎の1例
唐 尚子, 南場 研一, 村松 昌裕, 臨床眼科, 59, 9, 1609, 1612, 2005年09月
医学書院, 日本語

Current Review アレルギー性結膜疾患ガイドラインの話題
南場 研一, 大野 重昭, Allergia trends, 7, 3, 10, 13, 2005年09月
アステラス製薬, 日本語

Decrease in the glyceraldehayde-derived advanced glycation end products (AGEs) in the sera of patients with Vogt-Koyanagi-Harada’s disease
Kitamura, M, Kitaichi, N, Takeuchi, M, Kitamei, H, Namba, K, Yamagishi, S, Iwabuchi, K, Onoé, K, Ohno, S, Br. J. Ophthalmol., 89, 11, 1407, 1409, 2005年

臨床報告 血管内リンパ腫による仮面症候群の1例
岩田 大樹, 南場 研一, 東 こずえ, 臨床眼科, 58, 13, 2307, 2311, 2004年12月
医学書院, 日本語

HLA-B*510101の民族間比較検討 ベーチェット病は日本にどのようなルートでもたらされたか
竹本 裕子, 成瀬 妙子, 南場 研一, 水木 信久, 猪子 英俊, 大野 重昭, MHC: Major Histocompatibility Complex, 11, 2, 152, 152, 2004年08月
日本組織適合性学会, 日本語

臨床報告 Vogt-小柳-原田病新鮮例に対するステロイド大量療法とパルス療法の比較
北明 大洲, 寺山 亜希子, 南場 研一, 臨床眼科, 58, 3, 369, 372, 2004年03月
医学書院, 日本語

ぶどう膜炎併発白内障における手術適応の決定・術前後の処置
南場 研一, あたらしい眼科 = Journal of the eye, 21, 1, 3, 6, 2004年01月30日
日本語

Induction of regulatory T cells following experimental autoimmune uveoretinitis (EAU).
N Kitaichi, K Namba, AW Taylor, CLINICAL IMMUNOLOGY, 103, 3, S8, S8, 2002年06月
ACADEMIC PRESS INC ELSEVIER SCIENCE, 英語, 研究発表ペーパー・要旨（国際会議）

The uveitic ocular microenvironment reimposes tolerance to autoantigens through the induction of regulatory T cells
N Kitaichi, K Namba, AW Taylor, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 43, U342, U342, 2002年05月
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 英語, 研究発表ペーパー・要旨（国際会議）

ラットエンドトキシン誘発ブドウ膜炎モデルに対するアスタキサンチンの抑制効果　　　　　　　　　　　　　　　
大神 一浩, 小竹 聡, 矢澤 一良, 南場 研一, 水木 信久, 大野 重昭, 日本眼科学会雑誌, 106, 臨増, 139, 139, 2002年04月
(公財)日本眼科学会, 日本語

Inflammatory innate immunity antagonizes alpha-MSH-mediated immunosuppression and tolerance
AW Taylor, K Namba, FASEB JOURNAL, 15, 4, A357, A357, 2001年03月
FEDERATION AMER SOC EXP BIOL, 英語, 研究発表ペーパー・要旨（国際会議）

Emergence of regulatory cells in EAU.
K Namba, J Stein-Streilein, AW Taylor, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 42, 4, S915, S915, 2001年03月
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 英語, 研究発表ペーパー・要旨（国際会議）

Alpha-melanocyte stimulating hormone (alpha-MSH) induction of regulatory autoreactive T cells.
AW Taylor, DG Lee, T Nishida, K Namba, FASEB JOURNAL, 14, 6, A1112, A1112, 2000年04月
FEDERATION AMER SOC EXP BIOL, 英語, 研究発表ペーパー・要旨（国際会議）

Use of ocular immunosuppressive factors to suppress uveitis: Alpha-melanocyte stimulating hormone (alpha-MSH).
AW Taylor, K Namba, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 41, 4, S117, S117, 2000年03月
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 英語, 研究発表ペーパー・要旨（国際会議）

Suppression of experimental autoimmune uveoretinitis by injecting regulatory T cells induced by aqueous humor immuno-suppressive factors.
K Namba, AW Taylor, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 41, 4, S375, S375, 2000年03月
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 英語, 研究発表ペーパー・要旨（国際会議）

Innate immune regulation of ocular autoimmune disease
K Namba, J Stein-Streilein, AW Taylor, JOURNAL OF LEUKOCYTE BIOLOGY, 33, 33, 2000年
FEDERATION AMER SOC EXP BIOL, 英語, 研究発表ペーパー・要旨（国際会議）

Different influence of macrophage migration inhibitory factor (MIF) in signal transduction pathway of various T cell subsets
N Kitaichi, K Ogasawara, K Iwabuchi, J Nishihira, K Namba, K Onoe, J Konishi, S Kotake, H Matsuda, K Onoe, IMMUNOBIOLOGY, 201, 3-4, 356, 367, 2000年01月
It has been shown that macrophage migration inhibitory factor (MIF) modulates nor only macrophage functions, bur also T cell functions. However, detailed analysis of the MIF function on responses of various T cell subpopulations remained to be elucidated. In this report, using a neutralizing anti-MIF monoclonal antibody (mAb) we examined MIF functions on various T cell lineages. It was shown that anti-MIF mAb inhibited antigen-specific responses of both IFN-gamma producing and IL-4 producing T cells. The inhibition appeared to be related to blockade of the signal pathway via T cell receptor (TCR) but not that via IL-2 receptor (IL-2R). However, the anti-MIF mAb showed no inhibitory effect on NK-T cell responses stimulated through TCR. These results suggest that MIF is involved in the signal pathway via TCR in mainstream T cells but not in NK-T cells., GUSTAV FISCHER VERLAG, 英語

Regulatory T cells induced by aqueous humor factors inhibit induction of experimental autoimmune uveoretinitis
T Nishida, K Namba, AW Taylor, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 40, 4, S860, S860, 1999年03月
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 英語, 研究発表ペーパー・要旨（国際会議）

Inhibition of EAU by pretreatment of H-2A(k) mice with liposomal peptide
N Kitaichi, K Namba, K Ogasawara, Y Sasamoto, H Matsuda, K Onoe, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 40, 4, S143, S143, 1999年03月
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 英語, 研究発表ペーパー・要旨（国際会議）

Prevention of infection of influenza virus in DQ6 mice, a human model, by a peptide vaccine prepared according to the cassette theory
Matsuki, N, Ogasawara, K, Takami, K, Namba, K, Takahashi, A, Fukui, Y, Sasazuki, T, Iwabuchi, K, Good, R.A, Onoé, K, Vaccines, 17, 9-10, 1161, 1168, 1999年

Identification of a peptide inducing experimental autoimmune uveoretinitis (EAU) in H-2A^k carrying mice
Namba, K, Ogasawara, K, Kitaichi, N, Matsuki, N, Takahashi, A, Sasamoto, Y, Kotake, S, Matsuda, H, Iwabuchi, K, Ohno, S, Onoé, K, Clin. Exp. Immunol., 111, 2, 442, 449, 1998年

Rat interphotoreceptor retinoid-binding protein derived peptide induces experimental autoimmune uveoretinitis without lymphocyte proliferation
Y Sasamoto, K Namba, N Kitaichi, S Kotake, K Ogasawara, K Onoe, H Matsuda, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 38, 4, 2064, 2064, 1997年03月
LIPPINCOTT-RAVEN PUBL, 英語, 研究発表ペーパー・要旨（国際会議）