記述言語：英語   掲載種別：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.

DOI： 10.3389/fmed.2023.1095423

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

To reveal optimal antibiotic prophylactic regimen for postoperative endophthalmitis (POE), we conducted systematic review and network meta-analysis. A total of 51 eligible original articles, including two randomized controlled trials, were identified. In total, 4502 POE cases occurred in 6,809,732 eyes (0.066%). Intracameral injection of vancomycin had the best preventive effect (odds ratio [OR] 0.03, 99.6% confidence interval [CI] 0.00-0.53, corrected P-value = 0.006, P-score = 0.945) followed by intracameral injection of cefazoline (OR 0.09, 99.6% CI 0.02-0.42, corrected P-value < 0.001, P-score = 0.821), cefuroxime (OR 0.18, 99.6% CI 0.09-0.35, corrected P-value < 0.001, P-score = 0.660), and moxifloxacin (OR 0.36, 99.6% CI 0.16-0.79, corrected P-value = 0.003, P-score = 0.455). While one randomized controlled trial supported each of intracameral cefuroxime and moxifloxacin, no randomized controlled trial evaluated vancomycin and cefazoline. Sensitivity analysis focusing on the administration route revealed that only intracameral injection (OR 0.19, 99.4% CI 0.12-0.30, corrected P-value < 0.001, P-score = 0.726) significantly decreased the risk of postoperative endophthalmitis. In conclusion, intracameral injection of either vancomycin, cefazoline, cefuroxime, or moxifloxacin prevented POE.

DOI： 10.1038/s41598-022-21423-w

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記述言語：英語   掲載種別：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.

DOI： 10.1007/s10384-022-00927-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The induction of T cell-mediated immunity is crucial in vaccine development. The most effective vaccine is likely to employ both cellular and humoral immune responses. The efficacy of a vaccine depends on T cells activated by antigen-presenting cells. T cells also play a critical role in the duration and cross-reactivity of vaccines. Moreover, pre-existing T-cell immunity is associated with a decreased severity of infectious diseases. Many technical and delivery platforms have been designed to induce T cell-mediated vaccine immunity. The immunogenicity of vaccines is enhanced by controlling the kinetics and targeted delivery. Viral vectors are attractive tools that enable the intracellular expression of foreign antigens and induce robust immunity. However, it is necessary to select an appropriate viral vector considering the existing anti-vector immunity that impairs vaccine efficacy. mRNA vaccines have the advantage of rapid and low-cost manufacturing and have been approved for clinical use as COVID-19 vaccines for the first time. mRNA modification and nanomaterial encapsulation can help address mRNA instability and translation efficacy. This review summarizes the T cell responses of vaccines against various infectious diseases based on vaccine technologies and delivery platforms and discusses the future directions of these cutting-edge platforms.

DOI： 10.3390/vaccines10081367

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：英語   掲載種別：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.

DOI： 10.1080/09273948.2022.2092007

PubMed

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記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞目的:uveal effusion(UE)に対しては通常,強膜開窓術が第一選択となる。しかし,強膜開窓術は経験を要する術式である。また,合併症として脈絡膜出血や脈絡膜穿孔がある。今回筆者らは,UEに対するより簡便な術式として,経毛様体扁平部硝子体切除術を併用し,25Gトロカールを用いた脈絡膜下液の排出を行った。その結果,脈絡膜の良好な復位を得ることができたので報告する。症例:58歳,男性。1週間前より視力低下を自覚し近医を受診したところ,横浜市立大学附属病院眼科に紹介となった。初診時の左視力は(0.6),左眼底に全周性の脈絡膜剥離,裂孔を伴わない漿液性網膜剥離,移動性のある網膜下液がみられた。また,蛍光眼底造影検査では,網膜下への蛍光漏出はみられず,leopard spot patternと思われる顆粒状の過蛍光がみられた。超音波断層検査で強膜の肥厚を認め,左眼軸長が22.27mmであったことから,湖崎・宇山分類II型のUEの診断となった。1ヵ月後に25Gトロカールの先端を毛様体下に位置するように調整しつつ留置し,トロカールから脈絡膜下液を排液したうえで硝子体切除術を施行した。速やかに脈絡膜下液は消失し,網膜下液は徐々に減少した。術後6ヵ月で網膜下液は完全に消失し,脈絡膜剥離の再発もない。結論:UEにおいて,経毛様体扁平部硝子体切除術を併用した25Gトロカールによる排液が有効かつ安全であると考えた。

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記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞目的:ブロルシズマブは加齢黄斑変性(AMD)に対して新たに承認された抗血管内皮増殖因子(VEGF)薬であり,維持期には12週という長い投与間隔で有効とされている。今回,ラニビズマブ0.5mg併用光線力学療法(PDT)後に再発した滲出型AMDに対してブロルシズマブ6mgが単独で効果を示した症例を経験したので報告する。症例:患者は71歳,男性。他院にてアフリベルセプト2mg硝子体内注射を6回施行するも網膜下液(SRF)が軽快しないため,2019年11月PDT目的で当科を紹介され受診した。2019年12月中旬にラニビズマブ0.5mg併用PDTを施行したがSRFが再発し,2020年5月下旬に再度ラニビズマブ0.5mg併用PDTを施行した。2回施行後にSRFが再発したため,2020年9月,12月,2021年3月,7月,9月にブロルシズマブ6mg硝子体内注射を施行した。結果:ブロルシズマブ6mg投与によりSRFの消退と漿液性網膜色素上皮剥離の軽快を認めた。ぶどう膜炎,網膜血管炎,網膜血管閉塞など,ブロルシズマブで報告されている有害事象はみられていない。結論:近年PDTには抗VEGF療法が併用されることが多い。今回ラニビズマブ併用PDTを2回施行後にSRFが再発した滲出型AMDに対して,ブロルシズマブが単独で効果を示した症例を経験した。ブロルシズマブは抗VEGF薬併用PDT後に再発した滲出型AMDに対して,単独療法でも有効である可能性がある。

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記述言語：日本語   出版者・発行元：(株)メディカル葵出版  

目的:硝子体検査からStaphylococcus lugdunensis(S.lugdunensis)が培養された良好な視力経過をたどった白内障術後眼内炎の1例を報告する。症例:64歳、女性。左眼白内障手術施行後8日目に霧視を自覚し前医を受診し、当院紹介となった。左眼矯正視力は20cm手動弁まで低下しており、前房蓄膿と硝子体混濁を認め、左眼白内障術後眼内炎と診断した。霧視出現の翌日に眼内レンズ抜去と硝子体切除術を施行し、術後に硝子体検体からS.lugdunensisが培養された。培養されたS.lugdunensisはセフタジジムとバンコマイシンに感受性を示し、レボフロキサシンに中間耐性を示した。術後経過は良好であり、左眼矯正視力は(1.2)まで改善した。結語:眼内炎の起因菌として、S.lugdunensisも考慮する必要がある。早期の硝子体手術と抗菌薬の硝子体注射により眼内炎の予後は良好となりうる。(著者抄録)

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞目的:片眼の白内障手術後当日に術眼および非術眼の毛様体浮腫,浅前房ならびに眼圧上昇をきたした症例を経験したので報告する。症例:57歳,男性。右視力低下を主訴に受診した。両眼の核白内障および右後嚢下白内障を認め,前眼部,眼底には特記すべき所見を認めなかった。視力は右(0.15),左(1.2),眼圧は右16mmHg,左18mmHg,前房深度は右3.46mm,左3.38mm,眼軸は右24.25mm,左24.07mmであった。所見:右眼の超音波水晶体乳化吸引術,眼内レンズ(IOL)挿入術を行い,合併症なく終了した。術後3時間より頭痛,僚眼の霧視を自覚し,術後9時間で受診した。右IOLは嚢内中央に固定され前房の炎症も軽度であったが,両眼とも著明な浅前房であり,眼圧は右70mmHg,左62mmHgと上昇していた。左眼の超音波生体顕微鏡検査で毛様体浮腫を認めた。D-マンニトール点滴とアセタゾラミド内服,眼圧下降薬点眼,アトロピン硫酸塩水和物点眼,ベタメタゾン0.1%点眼とプレドニゾロン20mg内服を開始し,術後10日目には前房深度と眼圧は正常化した。結論:片眼の白内障手術後に両眼の眼圧上昇をきたし,眼圧下降薬点眼と散瞳・調節麻痺点眼,副腎皮質ステロイド薬で軽快した症例を経験した。薬剤性毛様体浮腫や眼炎症性疾患などの可能性が示唆される。

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J01537&link_issn=&doc_id=20220405150022&doc_link_id=10.11477%2Fmf.1410214358&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1410214358&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To compare the efficacy and safety of a combination therapy of prednisolone and cyclosporine and corticosteroid pulse therapy in Vogt-Koyanagi-Harada (VKH) disease. STUDY DESIGN: A prospective, multicenter, randomized, non-inferiority trial. METHODS: Patients of new-onset acute VKH disease at 11 centers in Japan between 2014 and 2018 were randomized to a combination (oral prednisolone 60 mg daily with gradual taper-off to 35 mg/day and cyclosporine 3 mg/kg/day) and corticosteroid (methylprednisolone 1000 mg for 3 days followed by oral prednisolone) groups, and were followed for 1 year. RESULTS: Thirty-four were assigned to the combination and thirty-six patients to the corticosteroid group. Recurrence/worsening risk was 0.15 (95% confidence-interval [CI] 0.03-0.27) in the combination group and 0.25 (95% CI 0.11-0.39) in the corticosteroid group, with a risk difference of - 0.10 (90% CI - 0.27 to 0.06), demonstrating non-inferiority of the combination group with a non-inferiority margin of 0.20 (P = 0.0013). Serious adverse events occurred in three patients (two with hyponatremia and one with severe headaches) in the combination group and none in the corticosteroid group. Sunset glow fundus grades and cataract rates at 1 year were 0.57 (95% CI 0.42-71) and 4.3% in the combination group and 0.91 (95% CI 0.78-1.04) and 34.0% in the corticosteroid group, respectively. CONCLUSIONS: Combination therapy was noninferior to corticosteroid therapy with respect to recurrence/worsening risk. Notably, the recurrence/worsening risk, sunset glow fundus grade, and cataract rate were lower in the combination group than in the corticosteroid group.

DOI： 10.1007/s10384-021-00878-w

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Refractive changes are reportedly affected by age, sex, and current refractive error. To clarify the pattern of refractive changes in a Japanese population, we conducted a 5-year follow-up longitudinal analysis of spherical equivalent (SE) refractive changes with stratification by sex, age, and SE in 593,273 eyes from Japanese individuals ages 3-91 years. The 5-year SE change with myopic shift dramatically increased over time after age 4 years, and the largest change was observed in both males and females who were age 8 years at baseline [males: - 2.654 ± 0.048 diopters (D); females: - 3.110 ± 0.038 D]. During school age, the 5-year myopic change was greater in females than in males, and emmetropic and low-to-moderate myopic eyes underwent larger myopic changes than hyperopic and high-to-severe myopic eyes. After the peak at age 8 years, the 5-year myopic change gradually declined with age and fell below - 0.25 D at age 27 in males and age 26 years in females. The 5-year SE changes transitioned from a myopic to a hyperopic shift at age 51 in both sexes, and hyperopization advanced more quickly in hyperopic eyes. Our findings highlight the importance of myopia prevention in school-aged children.

DOI： 10.1038/s41598-022-06898-x

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記述言語：英語   掲載種別：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.

DOI： 10.3389/fmed.2022.999804

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Immune tolerance is established in the eye to prevent permanent blindness associated with destructive damage to the cornea and retina caused by immune cell infiltration; hence, the immune responses and subsequent inflammations are strongly suppressed. While non-infectious uveitis develops from a disruption of immune tolerance in the eye, its onset is a result of accumulating etiologic factors, including genetic predisposition, environmental factors, and aging. Many non-infectious uveitis cases are genetically predisposed to human leukocyte antigen (HLA) as the most substantial disease susceptibility region. HLA class I molecules are critical for natural killer (NK) cells to distinguish between self and non-self. The killer cell Ig-like receptor (KIR) family is one of the essential components of these receptors. Evidence has accumulated that NK cells are involved in innate and acquired immunity by interacting with other immunocompetent cells to develop several autoimmune diseases. This review summarizes the possible role of KIR in the development of non-infectious uveitis.

DOI： 10.2174/1566524021666211027092124

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記述言語：英語   掲載種別：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.

DOI： 10.4103/sjopt.sjopt_204_22

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Adis  

Introduction: This study investigated the effect of rebamipide on discrepancies in the power and axis of astigmatism between two intra-patient keratometric measurements in patients with dry eyes. Methods: Fifty-eight dry eyes (with a short tear breakup time [TBUT] of less than 5 s) were analyzed. Patients with dry eye were treated with 2% rebamipide ophthalmic suspension (group R) or Mytear® artificial tear ophthalmic solution (group M) for 4 weeks. TBUT and corneal higher-order aberrations (HOAs) were evaluated at baseline and 4 weeks after treatment. Astigmatism power and axis were measured twice during both evaluations, at 5-min intervals. Baseline and post-treatment measurements were compared. Changes in TBUT and HOAs, and intra-patient discrepancies in astigmatism power and axis measurements were evaluated. Results: HOAs showed significant positive correlations with intra-patient differences in astigmatism power and axis (P &lt
0.001). At the 4-week post-treatment follow-up, TBUT increased, and HOAs and astigmatism power and axis discrepancies decreased in a significant number of patients in group R (P &lt
0.001). In group M, only differences in astigmatism power decreased in a significant number of cases (P = 0.005). The degree of change in the intra-patient difference in astigmatism power between the two post-treatment keratometric measurements was significantly greater in group R than in group M (P &lt
0.001). In group R, baseline HOAs exhibited a significant positive correlation with changes in HOAs and intra-patient differences in astigmatism power (both P &lt
0.001). In group M, baseline HOAs were only significantly correlated with changes in intra-patient differences in astigmatism power (P = 0.030). Conclusion: In dry eyes with short TBUTs, rebamipide significantly improved the corneal surface condition and significantly reduced intra-patient discrepancies in astigmatism power and axis measurements. Rebamipide may improve the accuracy of intraocular lens (IOL) power calculations in dry eyes, particularly when toric IOLs are implanted.

DOI： 10.1007/s40123-021-00368-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Adis  

Introduction: Understanding the relationship between postoperative intraocular lens (IOL) shift and refractive change is crucial for the accuracy of predicted postoperative refraction (PPR). We assessed the relationships between different IOL fixation methods, haptic designs, and several metrics. Methods: Single-center, open-label study which included 69 eyes. We preoperatively measured the anterior chamber depth (ACD), lens thickness (LT), axial length (AL), and PPR. AcrySof IQ (n = 27) and FineVision (n = 24) were fixed in the bag, and FEMTIS (n = 18) was fixed in capsulorhexis. At 1 day, 1 week, and 1 month postoperatively, we checked the IOL position and refraction and compared the IOL shift, refraction change, and the margin of error of the predicted PPR (PR-PPR difference). We also analyzed the correlation between postoperative and preoperative variables. Results: FEMTIS showed the highest stability in terms of IOL shift and refraction. The in-the-bag-fixated IOLs showed a significant forward shift between 1 day and 1 week postoperatively. There were significant differences in the PR-PPR difference between the IOLs. ACD and AL showed significant positive correlations, and LT showed a significant negative correlation with IOL shift and change in PR between 1 day and 1 week, but not between 1 week and 1 month postoperatively. Conclusion: The relationship between postoperative IOL shift and refraction change varied according to IOLs with different haptic types. Capsulorhexis fixation may be more stable than in-the-bag fixation. Furthermore, preoperative ACD, LT, and AL may be useful factors to predict IOL shift, change in PR, and to a lesser extent the degree of the margin of error in clinical practice. Our findings may improve the accuracy of PPR and refractive outcomes.

DOI： 10.1007/s40123-021-00390-x

Scopus

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

<title>Abstract</title><sec>
<title>Background</title>
We hypothesized that Behçet’s disease (BD) consists of several clinical subtypes with different severity, resulting in heterogeneity of the disease. Here, we conducted a study to identify clinical clusters of BD.


</sec><sec>
<title>Methods</title>
A total of 657 patients registered in the Yokohama City University (YCU) regional BD registry between 1990 and 2018, as well as 6754 patients who were initially registered in the Japanese Ministry of Health, Labour and Welfare (MHLW) database between 2003 and 2014, were investigated. The YCU registry data regarding the clinical manifestations of BD, human leukocyte antigen (HLA) status, treatments, and hospitalizations were analyzed first, followed by similar analyses of the MHLW for validation. A hierarchical cluster analysis was independently performed in both patient groups.


</sec><sec>
<title>Results</title>
A hierarchical cluster analysis determined five independent clinical clusters in the YCU cohort. Individual counterparts of the YCU clusters were confirmed in the MHLW registry. Recent phenotypical evolutions of BD in Japan, such as increased gastrointestinal (GI) involvement, reduced complete type according to the Japan Criteria, and reduced HLA-B51 positivity were associated with chronologically changing proportions of the clinical clusters.


</sec><sec>
<title>Conclusions</title>
In this study, we identified independent clinical clusters among BD patients in Japan and found that the proportion of each cluster varied over time. We propose five independent clusters namely “mucocutaneous”, “mucocutaneous with arthritis”, “neuro”, “GI”, and “eye.”


</sec>

DOI： 10.1186/s13075-020-02406-6

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その他リンク： http://link.springer.com/article/10.1186/s13075-020-02406-6/fulltext.html

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: This study aimed to determine the clinical efficacy of apremilast for oral ulcers, extra-oral manifestations, and overall disease activity in patients with Behçet's disease (BD). METHODS: A systematic literature search was performed in PubMed, EMBASE, Cochrane Library, and Web of Science Core Collection. Studies assessing the treatment effects of apremilast in BD were included. The odds ratios (ORs) of being symptom free for individual manifestations and mean difference (MD) of Behçet's Disease Current Activity Form (BDCAF) scores were calculated with 95% confidence intervals (CIs) at 12 and 24 weeks using a random-model meta-analysis. RESULTS: Of 259 screened articles, eight were included. After 12 weeks of apremilast treatment the OR of symptom-free was as followings: oral ulcers, 45.76 (95% CI, 13.23-158.31); genital ulcers, 4.56 (95% CI, 2.47-8.44); erythema nodosum, 3.59 (95% CI, 1.11-11.61); pseudofolliculitis, 2.81 (95% CI, 1.29-6.15); and arthritis, 3.55 (95% CI, 1.71-7.40). Furthermore, BDCAF scores at 12 weeks were significantly reduced (MD=-1.38; -1.78 to -0.99). However, the proportion of oral-ulcer free patients increased at 24 weeks (OR=14.88; 4.81 to 46.07). CONCLUSION: The currently accumulated data indicates an improvement in mucocutaneous and articular symptoms by short-term apremilast treatment in patients with BD.

DOI： 10.1093/mr/roab098

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Churchill Livingstone  

Treatment options for acquired blepharoptosis include levator resection, levator aponeurosis advancement (LAA), Müller's muscle-conjunctival resection (MMCR), and frontalis suspension. Previously, we reported a technique called external Müller's muscle tucking (EMMT) using the Müller's muscle as a power source. In this study, we compare LAA with EMMT and evaluate the recurrence and reoperation rates. LAA was performed on 96 eyelids in 51 patients. The average follow-up period was 12.2 months, recurrence occurred in four eyelids (4.2%) of three patients, and reoperation was required in one eyelid of one patient (2.0%). EMMT was performed on 94 eyelids in 51 patients, the mean follow-up period was 10.5 months, recurrence occurred in 14 eyelids (15%) of 10 patients, and reoperation was required in three eyelids of two patients (3.9%). A comparison of LAA and EMMT recurrence showed that EMMT was associated with a significantly higher recurrence rate (P = 0.0021). The causes of EMMT recurrence included thinning and fatty degeneration of Müller's muscles, necrosis of ligated Müller's muscles, and less postoperative scar formation. There was no correlation between EMMT recurrence and the severity of the blepharoptosis.

DOI： 10.1016/j.bjps.2021.03.086

Scopus

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Although infliximab (IFX) decreases the risk of blindness due to refractory uveitis in patients with Behçet's disease (BD), there are no standard criteria for IFX switching or withdrawal. To evaluate the effect of IFX switching in patients with BD in long-term remission, a prospective, single-arm intervention trial was conducted, switching from IFX to cyclosporine A (CYA). STUDY DESIGN: A prospective open-label study. METHODS: Eligible patients met the following criteria: administration of IFX without concomitant immunosuppressants for more than 5 years with no episodes of ocular attacks, no retinal vasculitis on fluorescein fundus angiography, negative C-reactive protein in serum, and no extraocular lesions at the time of IFX withdrawal. CYA 5 mg/kg/day was administered from 6 weeks after IFX withdrawal. The primary outcome was the rate of readministration of tumor necrosis factor inhibitors at 1 year after IFX withdrawal. RESULTS: Three of 45 BD patients treated with IFX for refractory uveitis were included in the study. At 1 year after withdrawal of IFX, no patient had experienced any ocular attacks or needed readministation of IFX. However, extraocular lesions, such as recurrent oral ulcers, folliculitis, and recurrent fevers, occurred in all patients. Liver or renal dysfunction, which may have been caused by CYA, was also observed in all patients. CONCLUSIONS: Although no ocular attacks were observed for at least 1 year after IFX withdrawal, this prospective study indicates that IFX withdrawal should be considered carefully, even for patients in long term remission of ocular and extraocular lesions.

DOI： 10.1007/s10384-021-00872-2

PubMed

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記述言語：日本語   出版者・発行元：(公社)日本眼科手術学会  

目的:眼瞼下垂手術後の角膜乱視軸の変化量について検討する。対象と方法:2018年1月〜2020年6月に、横浜桜木町眼科で眼瞼下垂手術を施行した症例を診療録から後ろ向きに調査した。手術前および術後2ヵ月で角膜トポグラフィーによる角膜形状解析が可能であった眼瞼下垂症例を対象とした。術前に角膜形状に影響を及ぼすハードコンタクト装用者や角膜疾患のある症例は除外した。角膜乱視変化量はCravy法を用いて軸乱視量で検討した。結果:対象は423例709眼瞼(両側286例、片側137例)であった。内訳として、下垂の程度別では軽度135眼瞼、中等度292眼瞼、重度282眼瞼であった。術式別では挙筋腱膜前転法59眼瞼、Mueller筋タッキング337眼瞼、Mueller筋タッキングと挙筋腱膜前転法の併施313眼瞼であった。全症例の角膜乱視変化量の平均±標準偏差は、0.15±0.46D(-1.09〜2.78D)であり、軽度0.07±0.35D、中等度0.11±0.42D、重度0.22±0.53Dで、重度は軽度および中等度より有意に直乱視化した(p=0.013、p=0.017)。術式では挙筋腱膜前転法0.05D±0.40D、Mueller筋タッキング0.11±0.42D、Mueller筋タッキングと挙筋腱膜前転法の併施0.20±0.50Dで、Mueller筋タッキングと挙筋腱膜前転法の併施は挙筋腱膜前転法単独およびMueller筋タッキング単独より有意に直乱視化した(p=0.041、p=0.046)。結論:眼瞼下垂術後2ヵ月の平均惹起角膜乱視は少ないが、下垂が重度な症例および挙筋前転の多いMueller筋タッキングと挙筋腱膜前転法の併施例では有意な直乱視化が認められた。(著者抄録)

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：日本語   出版者・発行元：(株)日本医事新報社  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01024&link_issn=&doc_id=20210701010007&doc_link_id=%2Faf9mdcla%2F2021%2F005071%2F009%2F0028b0032%26dl%3D3&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faf9mdcla%2F2021%2F005071%2F009%2F0028b0032%26dl%3D3&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_4.gif

記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

<title>Abstract</title>
<sec>
<title>Objectives</title>
No large-scale registration study has comprehensively evaluated the activities of daily living (ADL) in patients with Behçet's disease (BD).


</sec>
<sec>
<title>Methods</title>
The Japanese government provided us with a dataset of confirmed or suspected BD cases derived from ongoing national registration. ADL were categorized and analyzed into four categories in patients who satisfied the international criteria for BD.


</sec>
<sec>
<title>Results</title>
Data from 2960 patients (men, 38.9%; women, 61.1%; median age 39 years) were assessed. While 1767 patients (59.7%) had normal ADL, the others had impaired ADL comprising: limited but not assisted, 1058 (35.7%); partially assisted, 116 (3.9%); and fully assisted, 19 (0.6%). Logistic regression analysis showed that chronic ocular lesions (odds ratio (OR) 1.85, 95% confidence interval (CI) 1.46–2.35, p&amp;lt; 0.001), paralysis (OR 2.51, 95% CI 1.58–3.97, p&amp;lt; 0.001), psychosis (OR 3.16, 95% CI 2.02–4.95, p&amp;lt; 0.001), and arthritis (OR 1.69, 95% CI 1.44–1.99, p&amp;lt; 0.001) led to the risk of impaired ADL (not normal ADL). Chronic ocular lesions (OR 3.61, 95% CI 2.27–5.72, p&amp;lt; 0.001), paralysis (OR 3.43, 95% CI 1.87–6.30, p&amp;lt; 0.001), and psychosis (OR 3.60, 95% CI 2.00–6.50, p&amp;lt; 0.001) were related to the requirement of physical assistance (partially or fully assisted), although arthritis (OR 1.39, 95% CI 0.93–2.06, p= 0.108) was not a significant factor in this model.


</sec>
<sec>
<title>Conclusion</title>
Ocular lesion, neurological manifestations, and arthritis affected ADL. Patients with ocular lesion or neurological manifestations more frequently required physical assistance.


</sec>

DOI： 10.1093/rheumatology/keab499

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Adenovirus infections are a major cause of epidemic keratoconjunctivitis (EKC), which can lead to corneal subepithelial infiltrates and multifocal corneal opacity. In the current study, we investigated the use of an E1/E3-deleted adenovirus serotype 5 (Ad5) vector as a vaccine administered intramuscularly (IM) or intranasally (IN) against subsequent challenges with a luciferase-expressing Ad5 (Ad5-Luci) vector via eyedrop. We evaluated the adaptive immune response to Ad5 vector vaccination and confirmed a robust polyfunctional CD8 T cell response in splenic cells. Neutralizing Ad5 antibodies were also measured in the sera of vaccinated mice as well as Ad5 antibody in the eye wash solutions. Upon challenge with Ad5-Luci vector 8 weeks post the primary immunization, transduction was significantly reduced by > 70% in the vaccinated mice, which was slightly better in IM- vs. that in IN-vaccinated animals. Resistance to subsequent challenge was observed 10 months post primary IM vaccination, with sustained reduction up to 60% in the Ad5-Luci vector transduction. Passive immunization of naive mice with antisera from IM to vaccinated mice subsequently challenged with the Ad5-Luci vector resulted in approximately 40% loss in transduction efficiency. Furthermore, the mice that received IM immunization with or without CD8 T cell depletion showed > 40% and 70% reductions, respectively, in Ad8 genomic copies after Ad8 topical challenge. We conclude that Ad-vector vaccination successfully induced an adaptive immune response that prevented subsequent Ad transduction in the cornea and conjunctiva-associated tissues in a mouse model of adenovirus keratoconjunctivitis, and that both cellular and humoral immunity play an important role in preventing Ad transduction.

DOI： 10.1016/j.vaccine.2021.05.010

PubMed

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記述言語：日本語   出版者・発行元：(株)日本臨床社  

厚生労働省ベーチェット病研究班ホームページにおける質問の患者背景および内容について解析した。2009年11月28日〜2018年11月26日に患者から送信された総計375件の質問(相談)を集計した。性別では女性の方が多く、年齢の内訳は7〜86歳(平均38.1歳)で30〜40歳にピークがみられた。罹病期間は5年以内の件数が106件/163件で65%を占めており、相談内容については診断148件(36.2%)、治療137件(33.5%)が主で、その他には病院紹介依頼、妊娠に関する相談などが含まれ、複数の相談も寄せられていた。また、相談内容には特殊型病変も多く72件/375件(19.2%)の相談内容が含まれていた。内訳は腸管ベーチェット病(BD)31例、神経BD 29例、血管BD 9例、神経・血管BD 3例であり、特殊型の相談の場合は複数回の相談が増加傾向にあった。

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01205&link_issn=&doc_id=20210603150022&doc_link_id=%2Fag6niria%2F2021%2F007906%2F022%2F0925b0930%26dl%3D3&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fag6niria%2F2021%2F007906%2F022%2F0925b0930%26dl%3D3&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_4.gif

記述言語：日本語   出版者・発行元：(株)日本臨床社  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01205&link_issn=&doc_id=20210603150002&doc_link_id=%2Fag6niria%2F2021%2F007906%2F002%2F0800-0804%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fag6niria%2F2021%2F007906%2F002%2F0800-0804%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Pseudomonas aeruginosa (P. aeruginosa) infection is one of the major causes of keratitis. However, effective prophylactic and therapeutic vaccines against P. aeruginosa keratitis have yet to be developed. In this study, we explored the use of P. aeruginosa membrane vesicles (MVs) as a prophylactic vaccine as well as the use of immune sera derived from P. aeruginosa MV-immunized animals as a treatment for P. aeruginosa corneal infections in C57BL/6 mice. METHODS: C57BL/6 mice were intramuscularly immunized with P. aeruginosa MVs; the mouse corneas were then scarified and topically infected with several P. aeruginosa strains, followed by determination of corneal clinical score and corneal bacterial load. Next, immune sera derived from P. aeruginosa MV-immunized ICR mice were administered intraperitoneally to naïve C57BL/6 mice, followed by topical P. aeruginosa challenge. Finally, the immune sera were also used as a topical treatment in the mice with established P. aeruginosa corneal infections. RESULTS: P. aeruginosa-specific IgG and IgA antibodies induced by intramuscular immunization were detected not only in the sera but also in the eye-wash solution. Both active and passive immunization significantly inhibited P. aeruginosa corneal infection. Finally, topical treatment with immune sera in the mice with established P. aeruginosa corneal infections notably decreased the corneal clinical score and corneal bacterial load. CONCLUSIONS: P. aeruginosa keratitis can be attenuated by vaccination of P. aeruginosa MVs and topical application of P. aeruginosa MV-specific immune sera.

DOI： 10.1016/j.vaccine.2021.04.035

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Guidelines and systematic reviews frequently warn of inhaled corticosteroid (ICS)-induced glaucoma. However, most of the published studies deny it. METHODS: We performed a systematic review of randomized, cohort, nested-case control, cross-sectional studies by using Meta-analyses of Observational Studies in Epidemiology statement. Four major databases, PubMed, EMBASE, Cochrane Search Manager, and the Web of Science Core Collection as well as meta-analysis were used. Studies comparing incidence, prevalence and intraocular pressure (IOP) between patients who were treated with and without ICSs were included. A random-model meta-analysis was performed using the inverse variance method. RESULTS: Out of 623 studies screened, 18 with 31,665 subjects were finally included. No significant difference between the 2 groups was observed for crude glaucoma incidence (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.86-1.04; P = 0.26; I² = 0%; P for heterogeneity = 0.57) as a primary endpoint, adjusted glaucoma incidence (OR, 0.90; 95% CI, 0.65-1.24; P = 0.64), crude prevalence (OR, 1.82; 95% CI, 0.23-14.19; P = 0.57), adjusted prevalence (OR, 1.22; 95% CI, 0.50-2.96; P = 0.66), IOP change during ICS treatment (mean difference [MD] +0.01 mmHg; 95% CI, -0.19-0.20; P = 0.95), and single measurement IOP (MD +0.37 mmHg; 95% CI, -0.24-0.97; P = 0.23). Time-to-event analysis for glaucoma development as one of the secondary endpoints (adjusted hazard ratio, 0.52; 95% CI, 0.28-0.96) suggested a reverse association between ICS and glaucoma. CONCLUSIONS: The ophthalmological side effects of ICSs, such as glaucoma and intraocular hypertension, should not be exaggerated. TRIAL REGISTRATION: University Hospital Medical Information Network Center Clinical Trial Registry Identifier: UMIN000040351.

DOI： 10.4168/aair.2021.13.3.435

PubMed

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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)

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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)

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01049&link_issn=&doc_id=20210419580003&doc_link_id=%2Fdz1nigan%2F2021%2F012504%2F002%2F0415-0424%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdz1nigan%2F2021%2F012504%2F002%2F0415-0424%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The threat of the current coronavirus disease pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is accelerating the development of potential vaccines. Candidate vaccines have been generated using existing technologies that have been applied for developing vaccines against other infectious diseases. Two new types of platforms, mRNA- and viral vector-based vaccines, have been gaining attention owing to the rapid advancement in their methodologies. In clinical trials, setting appropriate immunological endpoints plays a key role in evaluating the efficacy and safety of candidate vaccines. Updated information about immunological features from individuals who have or have not been exposed to SARS-CoV-2 continues to guide effective vaccine development strategies. This review highlights key strategies for generating candidate SARS-CoV-2 vaccines and considerations for vaccine development and clinical trials.

DOI： 10.1016/j.vaccine.2020.11.054

PubMed

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記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞●ベーチェット病では,特徴的な眼炎症のエピソードや所見ならびに眼外症状から診断に結びつける。●前房蓄膿を呈するぶどう膜炎はさまざまであり,ベーチェット病ではさらさらとした前房蓄膿が特徴的である。●ベーチェット病の治療の基本は,眼炎症発作の速やかな消炎とその予防である。

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01537&link_issn=&doc_id=20210108070008&doc_link_id=10.11477%2Fmf.1410213875&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1410213875&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Uveitis is a generic term for inflammation of the uvea, which includes the iris, ciliary body, and choroid. Prevalence of underlying non-infectious uveitis varies by race and region and is a major cause of legal blindness in developed countries. Although the etiology remains unclear, the involvement of both genetic and environmental factors is considered important for the onset of many forms of non-infectious uveitis. Major histocompatibility complex (MHC) genes, which play a major role in human immune response, have been reported to be strongly associated as genetic risk factors in several forms of non-infectious uveitis. Behçet's disease, acute anterior uveitis (AAU), and chorioretinopathy are strongly correlated with MHC class I-specific alleles. Moreover, sarcoidosis and Vogt-Koyanagi-Harada (VKH) disease are associated with MHC class II-specific alleles. These correlations can help immunogenetically classify the immune pathway involved in each form of non-infectious uveitis. Genetic studies, including recent genome-wide association studies, have identified several susceptibility genes apart from those in the MHC region. These genetic findings help define the common or specific pathogenesis of ocular inflammatory diseases by comparing the susceptibility genes of each form of non-infectious uveitis. Interestingly, genome-wide association of the interleukin (IL)23R region has been identified in many of the major forms of non-infectious uveitis, such as Behçet's disease, ocular sarcoidosis, VKH disease, and AAU. The interleukin-23 (IL-23) receptor, encoded by IL23R, is expressed on the cell surface of Th17 cells. IL-23 is involved in the homeostasis of Th17 cells and the production of IL-17, which is an inflammatory cytokine, indicating that a Th17 immune response is a common key in the pathogenesis of non-infectious uveitis. Based on the findings from the immunogenetics of non-infectious uveitis, a personalized treatment approach based on the patient's genetic make-up is expected.

DOI： 10.3389/fimmu.2021.640473

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Dove Medical Press Ltd  

Purpose: Halos are a chief source of patient dissatisfaction after multifocal intraocular lens (IOL) implantation. The primary purpose of this study was to investigate the influence of age, postoperative refraction, and pre-and postoperative pupil size on postoperative halo size with a trifocal diffractive IOL (AcrySof IQ PanOptix) and extended depth-of-focus (EDOF) IOL (TECNIS Symfony) to determine whether these factors could predict postoperative halo size. Patients and Methods: This single-center, open-label study conducted between October 2018 and April 2020 in Yokosuka, Japan included 160 patients: 80 with PanOptix and 80 with Symfony IOLs. Size and intensity of the halos were examined binocularly using a computer-based simulator (Eyeland Design Network GmbH) and scored from 0 (minimum) to 10 (maximum) at 1, 3, and 6 months postoperatively, along with the change in each variable for both IOLs. The respective correlations of halo size with age, postoperative refraction, pre-and postoperative pupil size, and discomfort level due to the halo were also investigated 6 months postoperatively. Results: Halo size and intensity were significantly mitigated between 1, 3, and 6 months postoperatively. Throughout the observation period, halo size was significantly larger with PanOptix than with Symphony (P &lt
0.05), and halo intensity was significantly higher with Symphony than with PanOptix (P &lt
0.05). The pre-and postoperative pupil size correlated positively with halo size, while age and postoperative refraction were negatively correlated, for both IOLs. Conclusion: Understanding the features and predictive preoperative factors of halos in different types of multifocal IOLs may be useful in improving patient satisfaction.

DOI： 10.2147/OPTH.S327660

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nature Research  

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213)
others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.

DOI： 10.1038/s42003-020-0802-y

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記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞目的:サイトメガロウイルス網膜炎(CMVR)は通常,後天性免疫不全症候群(AIDS)や免疫抑制療法中の免疫低下状態の患者に発症する。CMVRの晩期合併症のうち網膜剥離は重篤な視機能障害の原因となる。今回,横浜市立大学附属病院において診断されたCMVR 20例の臨床像を検討した。方法:2009〜2018年にCMVRと診断された20症例27眼につき,患者背景,基礎疾患,眼合併症,治療,視力予後などを診療録より後ろ向きに調査した。結果:発症時平均年齢は60.2±10.1歳,男女比は13:7。PCRにより14例(70%)にCMVゲノムが検出された。HIV/AIDS 3例(15%)のほか,悪性リンパ腫,関節リウマチ,白血病などに対する免疫抑制療法中の患者に発症した。眼合併症として裂孔原性網膜剥離7例8眼(29.6%),硝子体出血4例4眼(14.8%),網膜裂孔2例2眼と白内障の進行2例2眼(いずれも7.4%)がみられた。治療として,15例に抗ウイルス薬の全身投与,4例に抗ウイルス薬の硝子体注射,7例8眼に硝子体手術,2例2眼に網膜光凝固術を行った。27眼中9眼(33.3%)が最終視力0.1未満であり,網膜剥離合併症例で視力予後が悪かった。結論:CMVR後の網膜剥離を予防するためには網膜炎に対する適切な治療に加え,定期的な眼底検査を施行することが重要である。

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01537&link_issn=&doc_id=20201202100022&doc_link_id=10.11477%2Fmf.1410213860&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1410213860&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

掲載種別：研究論文（学術雑誌）   出版者・発行元：Informa UK Limited  

DOI： 10.1080/14397595.2020.1830504

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記述言語：英語   掲載種別：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.

DOI： 10.1080/09273948.2020.1789179

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Lippincott Williams and Wilkins  

Purpose: The aim of this study was to compare the influence of pupil dilation on power calculation formulas for third-(Hoffer Q, SRK/T) and fourth-(Haigis, Holladay3) generation intraocular lens (IOL) between monofocal and multifocal IOLs. Design: Retrospective, comparative study. Methods: We analyzed 280 eyes (162 monofocal, 118 multifocal
mean patient age: 72.9 7.7 years
41.25% male). Anterior chamber depth (ACD) and lens thickness (LT) were measured. Predicted postoperative refraction (PPR) and recommended IOL power were calculated using third-A nd fourth-generation formulas pre-A nd post-dilation. We evaluated the mean absolute change (MAC) in PPR, change in recommended IOL power per formula, and mean change in ACD and LT between preand post-dilation, for both monofocal and multifocal IOLs. Results: ACD and LT showed significant changes post-dilation. The MAC in PPR was significantly higher with fourth-generation formulas than that with third-generation formulas, for both IOLs, and more so for multifocal IOLs. For both IOLs, the PPR change correlated positively with ACD changes, but negatively with LT changes, for fourth-generation formulas. Multifocals correlated significantly stronger with LT than monofocals. When using fourth-generation formulas post-dilation, the recommended IOL power changed more frequently in multifocals than in monofocals, although not significantly. Conclusions: Pupil dilation did not influence third-generation formula calculations for both IOL types, but did affect PPR and recommended IOL power when using fourth-generation formulas, and more so for multifocals. Considering pupil dilation effects on monofocal and multifocal parameters is vital for accurate IOL calculation

DOI： 10.1097/APO.0000000000000310

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記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞緒言:遺伝子検査により診断され,2歳時にTNF阻害薬であるアダリムマブを導入することができたBlau症候群の1例を報告する。症例:3歳1ヵ月,女児。生後7ヵ月で原因不明の周期性発熱,および慢性炎症により他院小児科および眼科を受診した。眼科受診時に両眼の虹彩結節および視神経乳頭浮腫を認めたため,精査加療目的で当院を紹介され受診となった。父親にも関節炎,周期性発熱,ぶどう膜炎,および視神経乳頭浮腫がみられたため,遺伝子検査を実施した。父娘ともにNOD2 pArg587Cys hetero(R587C)のミスセンス変異が認められ,Blau症候群と診断された。その後,患児の視神経乳頭浮腫は軽減したが,虹彩後癒着は抗炎症薬点眼および散瞳薬点眼を使用しても徐々に進行した。また,周期性発熱,CRP高値などの全身所見に改善傾向がないため,2歳2ヵ月でアダリムマブ導入となった。導入後は眼所見,全身所見ともに落ち着いている。結論:Blau症候群は常染色体優性遺伝形式をとる全身性肉芽腫性炎症性疾患である。本症例は2歳でアダリムマブを導入したが,視力予後は不良な疾患であるため,今後も注意深い経過観察が必要である。

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Oncoprotein E6 of high-risk human papillomavirus (HPV) plays a critical role in inducing cell immortalization and malignancy. E6 downregulates caspase-dependent pathway through the degradation of p53. However, the effect of HPV E6 on other pathways is still under investigation. In the present study, we found that HPV E6 directly binds to all three forms (precursor, mature, and apoptotic) of apoptosis-inducing factor (AIF) and co-localizes with apoptotic AIF. This binding induced MG132-sensitive reduction of AIF expression in the presence of E6 derived from HPV16 (16E6), a cancer-causing type of HPV. Conversely, E6 derived from a non-cancer-causing type of HPV, HPV6 (6E6), did not reduce the levels of AIF despite its interaction with AIF. Flow cytometric analysis revealed that 16E6, but not 6E6, suppressed apoptotic AIF-induced chromatin degradation (an indicator of caspase-independent apoptosis) and staurosporine (STS, a protein kinase inhibitor)-induced apoptosis. AIF knockdown reduced STS-induced apoptosis in both of 16E6-expressing and 6E6-expressing cells; however, the reduction in 16E6-expressing cells was lower than that in 6E6-expressing cells. These findings indicate that 16E6, but not 6E6, blocks AIF-mediated apoptosis, and that AIF may represent a novel therapeutic target for HPV-induced cervical cancer.

DOI： 10.1038/s41598-020-71134-3

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記述言語：英語   掲載種別：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.

DOI： 10.1038/s42003-020-01185-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Keratoconus is a common ocular disorder that causes progressive corneal thinning and is the leading indication for corneal transplantation. Central corneal thickness (CCT) is a highly heritable characteristic that is associated with keratoconus. In this two-stage genome-wide association study (GWAS) of CCT, we identified a locus for CCT, namely STON2 rs2371597 (P = 2.32 × 10-13), and confirmed a significant association between STON2 rs2371597 and keratoconus development (P = 0.041). Additionally, strong STON2 expression was observed in mouse corneal epithelial basal cells. We also identified SMAD3 rs12913547 as a susceptibility locus for keratoconus development using predictive analysis with IBM's Watson question answering computer system (P = 0.001). Further GWAS analyses combined with Watson could effectively reveal detailed pathways underlying keratoconus development.

DOI： 10.1038/s42003-020-01137-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BioMed Central  

Background: Despite the surge in the number of cataract surgeries, there is limited information available regarding the influence of pupil dilation on predicted postoperative refraction and its comparison with recommended various intraocular lens power calculated using the different parameters. We used three different IOL power calculation formulas: Barrett Universal II (Barrett) (5-variable formula), Haigis (3-variable formula), and SRK/T (2-variable formula), in order to investigate the potential effect of pupil dilation on the predicted postoperative refraction (PPR) and recommended intraocular lens (IOL) power calculation. Methods: This retrospective study included 150 eyes. All variables were measured and calculated using a ZEISS IOL Master 700. The following variables were measured before and after dilation: anterior chamber depth (ACD), lens thickness (LT), white-to-white (WTW). PPR and recommended IOL power were calculated by Barrett, Haigis, and SRK/T IOL calculation formulas. The change in each variable before and after dilation, and the correlations between all changes were analyzed using the Wilcoxon signed-rank test and the Spearman's rank-order correlation test, respectively. Results: The mean absolute change (MAC) in PPR before and after dilation was found to be highest in the Barrett formula. Significant differences were found between each MAC (P &lt
0.0001). Significant changes were observed before and after dilation in ACD and LT (P &lt
0.0001), but not in WTW. Using the Barrett and Haigis formulas, there was a significant positive correlation between the change in PPR and change in ACD (P &lt
0.0001), and a negative correlation between change in PPR and change in LT (P &lt
0.0001). The correlations were strongest with the Barret formula followed by the Haigis, particularly in terms of LT. Changes in PPR determined by the Barrett formula also demonstrated a significant positive correlation with changes in WTW (P = 0.022). The recommended IOL power determined using Barrett and Haigis changed before and after dilation in 23.3 and 19.3% cases respectively, while SRK/T showed no change. Conclusions: In terms of PPR and recommended IOL power, pupil dilation influenced mostly the Barrett formula. Given the stronger correlation between the changes in PPR when using Barrett and the changes in ACD, LT, and WTW, changes in ACD, LT, and WTW significantly affect how dilation influences the Barrett formula. Determining how dilation influences each formula and other variables is key to improving the accuracy of IOL calculations.

DOI： 10.1186/s12886-020-01571-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Behçet's disease (BD) is an intractable systemic inflammatory disease characterized by four main symptoms: oral and genital ulcers and ocular and cutaneous involvement. The Japanese diagnostic criteria of BD classify intestinal BD as a specific disease type. Volcano-shaped ulcers in the ileocecum are a typical finding of intestinal BD, and punched-out ulcers can be observed in the intestine or esophagus. Tumor necrosis factor inhibitors were first approved for the treatment of intestinal BD in Japan and have been used as standard therapy. In 2007 and 2014, the Japan consensus statement for the diagnosis and management of intestinal BD was established. Recently, evidence-based JSBD (Japanese Society for BD) Clinical Practice Guidelines for BD (Japanese edition) were published, and the section on intestinal BD was planned to be published in English. Twenty-eight important clinical questions (CQs) for diagnosis (CQs 1-6), prognosis (CQ 7), monitoring and treatment goals (CQs 8-11), medical management and general statement (CQs 12-13), medical treatment (CQs 14-22), and surgical treatment (CQs 23-25) of BD and some specific situations (CQs 26-28) were selected as unified consensus by the members of committee. The statements and comments were made following a search of published scientific evidence. Subsequently, the levels of recommendation were evaluated based on clinical practice guidelines in the Medical Information Network Distribution Service. The degree of agreement was calculated using anonymous voting. We also determined algorithms for diagnostic and therapeutic approaches for intestinal BD. The present guidelines will facilitate decision making in clinical practice.

DOI： 10.1007/s00535-020-01690-y

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記述言語：日本語   出版者・発行元：金原出版(株)  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J00293&link_issn=&doc_id=20200629080003&doc_link_id=10.18888%2Fga.0000001692&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fga.0000001692&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞目的:難治性眼サルコイドーシスに対しアダリムマブ(ADA)投与中に肺病変の悪化がみられ,パラドキシカルリアクションが考えられた1例を報告する。症例:27歳,男性。両前眼部に炎症はなく,右眼底に広範囲におよぶ閉塞性血管炎を認め,全身検査および経気管支肺生検にてサルコイドーシスと組織学的に診断された。両眼底の無灌流領域に対し網膜光凝固術を施行したが,右眼に硝子体出血を生じ,プレドニゾロン(PSL)40mg/日の内服を開始した。その後,右眼網膜剥離を認めたため,硝子体手術および超音波水晶体乳化吸引術を施行した。術後2週間でADAを導入し,PSLを漸減,半年後に右眼内レンズ2次挿入術を施行した。PSL中止後,眼炎症の再燃はなかったが,呼吸器症状が出現した。胸部画像にて肺病変の悪化が認められ,ADAのパラドキシカルリアクションの可能性が考えられた。ADA継続のままPSL 25mg/日を開始したところ,肺病変は改善した。結論:既存治療で効果不十分なサルコイドーシスに対しADAは新たな治療の選択肢であるが,パラドキシカルリアクションによるサルコイドーシス悪化がみられる可能性もあるため,全身状態にも注意し,その悪化時には適切な対処が必要である。

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01537&link_issn=&doc_id=20200603070018&doc_link_id=10.11477%2Fmf.1410213588&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1410213588&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To identify novel susceptibility loci for high myopia. DESIGN: Genome-wide association study (GWAS) followed by replication and meta-analysis. PARTICIPANTS: A total of 14 096 samples from East and Southeast Asian populations (2549 patients with high myopia and 11 547 healthy controls). METHODS: We performed a GWAS in 3269 Japanese individuals (1668 with high myopia and 1601 control participants), followed by replication analysis in a total of 10 827 additional samples (881 with high myopia and 9946 control participants) from Japan, Singapore, and Taiwan. To confirm the biological role of the identified loci in the pathogenesis of high myopia, we performed functional annotation and Gene Ontology (GO) analyses. MAIN OUTCOME MEASURES: We evaluated the association of single nucleotide polymorphisms with high myopia and GO terms enriched among genes identified in the current study. RESULTS: We identified 9 loci with genome-wide significance (P < 5.0 × 10-8). Three loci were previously reported myopia-related loci (ZC3H11B on 1q41, GJD2 on 15q14, and RASGRF1 on 15q25.1), and the other 6 were novel (HIVEP3 on 1p34.2, NFASC/CNTN2 on 1q32.1, CNTN4/CNTN6 on 3p26.3, FRMD4B on 3p14.1, LINC02418 on 12q24.33, and AKAP13 on 15q25.3). The GO analysis revealed a significant role of the nervous system related to synaptic signaling, neuronal development, and Ras/Rho signaling in the pathogenesis of high myopia. CONCLUSIONS: The current study identified 6 novel loci associated with high myopia and demonstrated an important role of the nervous system in the disease pathogenesis. Our findings give new insight into the genetic factors underlying myopia, including high myopia, by connecting previous findings and allowing for a clarified interpretation of the cause and pathophysiologic features of myopia at the molecular level.

DOI： 10.1016/j.ophtha.2020.05.014

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

＜文献概要＞ベーチェット病は原因不明の全身性炎症疾患であり,遺伝的素因を有する個体に何らかの環境要因が関与することにより発症すると考えられている。最も強固な遺伝要因がHLA-B*51であることから,MHCクラスIを中心とする獲得免疫異常が注目されてきた。一方,臨床では発作性にみられる好中球優位の炎症など自己炎症疾患としての側面も併せ持つ。それを裏付けるように,自然免疫に関わる感受性遺伝子も数多く同定されており,さまざまな免疫系が複雑に絡まり病態を構築していることが明らかとなった。また,環境要因として病原体の存在が考えられているが,生体防御や口腔・腸管細菌叢に関する知見も得られてきており環境要因の解明も期待される。

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01750&link_issn=&doc_id=20200512150014&doc_link_id=%2Fai1phmdl%2F2020%2F003804%2F013%2F0061-0066%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai1phmdl%2F2020%2F003804%2F013%2F0061-0066%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: To evaluate the efficacy of a mydriatic agent for posterior synechiae after phacoemulsification and intraocular lens (IOL) implantation followed by Descemet membrane endothelial keratoplasty (staged DMEK). METHODS: In this prospective study, the outcomes of DMEK with or without mydriasis (0.5% tropicamide and 0.5% phenylephrine hydrochloride [Mydrin-P; Santen, Osaka, Japan]) after the DMEK procedure were analyzed. Patients underwent IOL implantation approximately 4 weeks before DMEK. Six months after DMEK, the iris posterior synechiae severity score was evaluated based on the extent of posterior synechiae affecting the eight areas (45° each) of the pupillary rim (posterior synechiae score; grades 0-8). Best spectacle-corrected visual acuity, central corneal thickness, endothelial cell density, axial length, and the amount of air at the end of the surgery were also evaluated. RESULTS: Fifteen eyes of 15 patients (mydriatic: n=8, control: n=7) were eligible for inclusion. Iris posterior synechiae were detected in all seven eyes (100.0%) in the control group, whereas they were noted in two eyes in the mydriatic group (25%). The mean iris posterior synechiae score was 0.69±1.20 in the mydriatic group and was significantly lower than that in the control group (4.57±0.90; P<0.001). There was no significant difference in other clinical factors. Although the incidence and scores of posterior synechiae in the control group were higher, the incidence was significantly reduced with the use of a mydriatic agent (in the mydriatic group). CONCLUSIONS: Use of a mydriatic agent is an effective measure to prevent postoperative synechiae after DMEK.

DOI： 10.1097/ICL.0000000000000616

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In the current study, we present guidelines for the diagnosis and treatment of the mucocutaneous lesions of Behçet's disease, which is a chronic inflammatory disease characterized by the involvement of various organs, including mucocutaneous, ocular, vascular, intestinal and central nervous system lesions. It is often identified in the Middle East Mediterranean to East Asia region. Skin manifestations include erythema nodosum, papulopustular lesions and thrombophlebitis, and mucosal manifestations include oral and genital ulcers. These mucocutaneous lesions are characteristically the first signs of Behçet's disease and are important to be recognized for the early diagnosis of the disease. Moreover, these manifestations also recur and persist over the long-term course of the disease. The management of mucocutaneous lesions is important to prevent recurrence. We developed consensus guidelines that provide recommendations for general practitioners and dermatologists and physicians on the management of the mucocutaneous lesions of Behçet's disease.

DOI： 10.1111/1346-8138.15207

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: How HLA-A26 modulates Behçet's disease (BD) ocular lesions such as iridocyclitis and retinochorioiditis has not been scrutinized.Methods: Ministry of Health, Labour and Welfare of Japan provided us a database of BD patients who were registered from 2003 to 2014. We selected patients who satisfied International Criteria for BD and whose data for HLA-A26 was available.Results: Eligible 557 patients consisting of 238 men (42.7%) and 319 women (57.3%), whose median age was 38 years old (interquartile range 29-47) were analyzed. Prevalence of general ocular lesions, iridocyclitis, retinochorioiditis, and chronic lesions were 43.1%, 30.7%, 34.1%, and 17.4%, respectively. The prevalence of ocular lesions was higher among HLA-A26 carriers compared to that among HLA-A26 non-carriers with odds ratio (OR) of 2.5 (95% confidence interval (95% CI) 1.8-3.5, p < .001) for general ocular lesions, OR of 2.5 (95% CI 1.7-3.6, p < .001) for iridocyclitis, OR of 2.8 (95% CI 1.9-4.0, p < .001) for retinochorioiditis, and OR of 2.7 (95% CI 1.7-4.3, p < .001) for 'chronic ocular lesion following iridocyclitis or retinochorioiditis'. The HLA-A26 had a similar impact on ocular lesions between HLA-B51 positive and negative cases (Breslow-Day test, p > .05). However, the HLA-A26 had a larger impact on iridocyclitis for men compared to women (Breslow-Day test, p = .040). The male HLA-A26 carriers had higher risk of iridocyclitis with OR of 3.4 (95% CI 2.0-5.9, p < .001), while the OR for women was 1.5 (95% CI 0.9-2.6, p = .146).Conclusion: HLA-A26 carriers had higher risk for iridocyclitis and retinochorioiditis. However, the impact was more prominent for men.

DOI： 10.1080/14397595.2019.1705538

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1080/24725625.2019.1649857

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記述言語：英語  

BACKGROUND: Behçet's disease (BD) is a chronic multi-systemic vasculitis with a considerable prevalence in Asian countries. There are many genes associated with a higher risk of developing BD, one of which is endoplasmic reticulum aminopeptidase-1 (ERAP1). In this study, we aimed to investigate the interactions of ERAP1 single nucleotide polymorphisms (SNPs) using a novel data mining method called Model-based multifactor dimensionality reduction (MB-MDR). METHODS: We have included 748 BD patients and 776 healthy controls. A peripheral blood sample was collected, and eleven SNPs were assessed. Furthermore, we have applied the MB-MDR method to evaluate the interactions of ERAP1 gene polymorphisms. RESULTS: The TT genotype of rs1065407 had a synergistic effect on BD susceptibility, considering the significant main effect. In the second order of interactions, CC genotype of rs2287987 and GG genotype of rs1065407 had the most prominent synergistic effect (β = 12.74). The mentioned genotypes also had significant interactions with CC genotype of rs26653 and TT genotype of rs30187 in the third-order (β = 12.74 and β = 12.73, respectively). CONCLUSION: To the best of our knowledge, this is the first study investigating the interaction of a particular gene's SNPs in BD patients by applying a novel data mining method. However, future studies investigating the interactions of various genes could clarify this issue.

DOI： 10.1371/journal.pone.0227997

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

Introduction : We report a case of Blau syndrome in a 2-year-old girl diagnosed based on genetic testing and treated with adalimumab, tumor necrosis factor inhibitors. Case • The patient was a girl aged 3 years and 1 month. Seven months after her birth, she had visited a pediatrist and an ophthalmologist in another hospital because of recurrent episodes of fever and chronic inflammation. Her eyes showed iris nodules and optic disc edema, and she was referred to our hospital. Her father had a history of arthritis, recurrent episodes of fever, uveitis, and optic disc edema. Genetic testing showed a missense mutation, pArg587Cys hetero (R587C) of her and her father's NOD2 gene, leading to the diagnosis of Blau syndrome. Subsequently, the optic disc edema of the patient reduced, but the posterior synechia gradually progressed, despite the use of anti-inflammatory and mydriatic drops. Her systemic findings, including recurrent episodes of fever and elevated C-reactive protein levels, had shown no improvement. Treatment with adalimumab was introduced when the patient was aged 2 years and 2 months. Ocular and other systemic findings improved with the treatment. Conclusion Blau syndrome is a systemic granulomatous inflammatory disorder with an autoso-mal-dominant inheritance. In this case, treatment with adalimumab was introduced at the age of 2 years.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Dove Medical Press Ltd  

A 68-year-old man with senile cataract underwent femtosecond laser-assisted cataract surgery (FLACS) in his left eye. Only anterior capsulotomy and lens fragmentation were planned with a femtosecond laser. Docking of the patient interface and anterior capsulotomy were completed without any complications. During the lens fragmentation process, the patient could not resist the temptation to squeeze his eyes shut, which caused excessive pressure from the eyelids. As the procedure proceeded, a bubble was formed at the edge of the patient interface and became increasingly larger. In addition, wrinkles in the conjunctiva were observed. As the lens fragmentation was approaching the final stage, the surgeon was reluctant to release the foot pedal to stop the laser emission. Finally, the patient interface lost adhesion to the cornea. Owing to the high repetition rate of the laser, the laser beam slipped into the corneal layers. Under an operating microscope, a grid-pattern laser beam trace was observed in the peripheral part of the cornea. As posterior capsule rupture occurred during the lens removal process, IOL insertion was no longer a suitable option. Therefore, scleral fixation of the implanted intraocular lens was performed without any unexpected events. One year postoperatively, the laser beam trace in the corneal layers could still be identified by slit-lamp examination. Nonetheless, since the laser beam trace was limited to the peripheral part of the cornea, and there was no damage to the central cornea, the visual acuity was 20/20. FLACS has significant benefits, especially in challenging cases of cataract surgery, and has well-established built-in safeguards for complications. However, this case study indicates the possibility of a suction break during laser emission and the preoperative risk factors. It demonstrates that recognizing the signs of suction break is necessary to avoid misplacement of the laser beam on the corneal layers.

DOI： 10.2147/IMCRJ.S280403

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Dove Medical Press Ltd  

Posterior capsule opacification (PCO) is the most common cause of deterioration of vision and contrast sensitivity and glare after cataract surgery. Neodymium (Nd): yttrium aluminum garnet (YAG) laser capsulotomy is an effective and standard procedure to treat these symptoms. The incidence rate of PCO requiring Nd:YAG laser treatment varies and depends on published studies, ranging from 2.2% to 10.0%. Although Nd:YAG laser treatment is largely safe, it still has complications, such as transient increase of intraocular pressure, anterior uveitis, intraocular lenses pitting, cystoid macula edema, endophthalmitis, and retinal detachment. We encountered a rare complication related to Nd:YAG laser treatment, where the laser accidentally hits the cornea. This occurred because the PCO was mistaken for the corneal layers during the laser procedure. This report presents the 3-year post-treatment process, and the findings herein may help raise the awareness of the possibi-lity of this rare complication and provide measures for its treatment.

DOI： 10.2147/IMCRJ.S271669

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Angiotensin-converting enzyme (ACE) is conventionally used as a biomarker in the diagnosis of uveitis associated with sarcoidosis, but its sensitivity is relatively low. In this study, we investigated whether serum soluble interleukin-2 receptor (sIL-2R) is also useful as a diagnostic marker, in addition to ACE, in the detection of uveitis associated with sarcoidosis. PATIENTS AND METHODS: Data were analyzed from 126 patients with uveitis (52 sarcoidosis and 74 non-sarcoid uveitis) and 12 with primary intraocular lymphoma (PIOL) who had their serum sIL-2R and ACE levels measured. RESULTS: Serum sIL-2R level was elevated in 69.2% of patients with sarcoid uveitis, 5.4% of those with non-sarcoid uveitis, and 16.7% of those with PIOL. The sensitivity and specificity of an elevated sIL-2R level for the detection of sarcoidosis were 69.2% and 93.0%, respectively. In contrast, serum ACE levels were elevated only in patients with sarcoid uveitis, with a sensitivity of 44.2% and specificity of 100%. Furthermore, serum sIL-2R and/or ACE level was elevated in 75.0% of patients with sarcoid uveitis, which is higher than those who had elevated serum ACE level only (44.2%, P = 0.0025). The sensitivity and specificity of elevated sIL-2R and/or ACE in detecting sarcoid uveitis were 75.0% and 93.0%, respectively. The PPV was 0.87, and the NPV was 0.86. CONCLUSION: Compared with the sensitivity of serum ACE levels alone, combined measurement of both serum sIL-2R and ACE levels improves sensitivity in the detection of uveitis associated with sarcoidosis. Nevertheless, serum ACE alone remains useful thanks to its high specificity in the differentiation of uveitis patients, with sarcoidosis from those without sarcoidosis.

DOI： 10.2147/OPTH.S264595

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記述言語：英語   掲載種別：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.

DOI： 10.1371/journal.pone.0233464

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objectives: To scrutinize the influence of HLA-B51 to each clinical manifestation of patients with Behçet's disease (BD) using a database of the Ministry of Health, Labour and Welfare of Japan. Methods: The database of newly registered patients with BD was obtained from the Japanese Ministry of Health, Labour and Welfare. Patients who met International Criteria for Behçet's Disease (ICBD) and had data for HLA-B51 were selected and analyzed. Results: Among the 3044 analyzable cases, 1334 (43.8%) were men and 1710 (56.2%) were women; the median age was 38 years (IQR 29-48). HLA-B51 was positive for 1334 (44.5%). Prevalence of selected manifestations was 98.5% for oral ulceration, 85.5% for skin lesion, 42.1% for ocular lesion, 69.1% for genital ulceration, and 29.0% for gastrointestinal symptom. HLA-B51-positive patients had higher risk for ocular lesion (OR 1.59, 95%CI: 1.37-1.84; p < .001) and lower risk for genital ulceration (OR 0.72, 95%CI: 0.62-0.84; p < .001) and gastrointestinal symptom (OR 0.65, 95%CI: 0.55-0.77; p < .001). No significant difference was observed for other organ involvement; oral ulceration, skin lesion, positive pathergy test, arthritis, epididymitis, vascular lesion, or neurological manifestation. Subgroup analyses revealed that HLA-B51 was not related to genital ulceration in the cases with an ICBD score of 6 or higher and that HLA-B51 tended to more largely affect the risk of three manifestations for men compared to that for women. Conclusion: HLA-B51 positive is a risk factor for ocular lesion and vice versa for genital ulceration and gastrointestinal symptoms in patients with Japanese BD.

DOI： 10.1080/14397595.2019.1649103

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Clinical data of patients with entro-, vasculo-, and neuro-variant possible Behçet's disease (BD) based on Japanese criteria has not yet comprehensively reported. Methods: This ongoing nation-wide registration has been carried out by the Japanese Ministry of Health, Labour and Welfare. The Ministry asked physicians who diagnosed a patient with confirmed or possible BD to register the patient data by filling out a registration form. The Ministry provided us with the dataset after unlinkable anonymization. We analyzed 2003-2014 database generated from the early stage new cases. Results: Among the 7950 analyzable cases, 694 (8.7%) had variant-type possible BD without satisfying complete/incomplete criteria. Of the 694 patients, 479, 46, and 169 had entero-, vasculo-, and neuro-variant possible BD, respectively. Out of these 694 patients, 35 (5.0%) and 154 (22.2%) satisfied the International Study Group criteria and the International Criteria of BD, respectively. Entero-variant possible patients rarely (1.8%) had ocular lesions. Patients with vasculo-variant possible BD were featured by low genital ulceration risk (6.8%) and frequent positive HLA-B51 (60.0%). Neuro-variant possible BD was featured by high median age at registration (48 year). Vasculo- (69.6%) and neuro-variant (68.6%) BD patients showed clear male dominance. Epididymitis was very rare among variant-type possible BD men. Conclusion: We analyzed 694 early-stage variant-type possible BD cases. We believe the data from our study will contribute to further international discussion regarding BD diagnostic criteria and clarification of the clinical presentations of the Japanese variant-type possible BD patients.

DOI： 10.1080/14397595.2018.1494501

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: To evaluate the clinical outcomes and features of Descemet's membrane endothelial keratoplasty (DMEK) for eyes with pseudoexfoliation syndrome (PEX). METHODS: In this retrospective study, 37 DMEK cases were reviewed from available medical records. Patients who exhibited endothelial dysfunction derived from PEX or Fuchs endothelial corneal dystrophy (FECD) and successfully underwent cataract surgery about four weeks before DMEK were enrolled. The best spectacle-corrected visual acuity (BSCVA), central corneal thickness (CCT), endothelial cell density (ECD), and incidence of intra-operative/post-operative complications of DMEK were analyzed. RESULTS: This study included 14 eyes of 14 patients (PEX: n = 6, FECD: n = 8). There was no primary graft failure. In the PEX group, BSCVA improved from 0.67 ± 0.28 at the preoperative point to 0.43 ± 0.14 at 1 month, 0.27 ± 0.10 at 3 months, and 0.19 ± 0.08 at 6 months after DMEK. The donor corneal ECD was 2704 ± 225 cells/mm2 at the preoperative point and decreased to 1691 ± 498 cells/mm2 at 1 month, 1425 ± 366 cells/mm2 at 3 months, and 1281 ± 340 cells/mm2 (52.7 ± 11.7% less than ECD of the donor graft) at 6 months after DMEK. None of the patients required rebubbling. When compared with the FECD group, no statistical difference was observed in CCT (p = 0.821); BSCVA (p = 0.001) and the reduction rate of ECD (p = 0.010) were relatively worse. CONCLUSIONS: DMEK is effective for the treatment of endothelial dysfunction due to PEX.

DOI： 10.1186/s12886-019-1130-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The strongest genetic risk factor of Behçet's disease (BD) is HLA-B*51. Our group previously reported that HLA-A*26 is independently associated with the risk of the onset of BD apart from HLA-B*51. Here, we re-evaluated the association between HLA-A*26 and BD in the Japanese population. We also performed a comprehensive literature search and meta-analyzed the extracted published data concerning the relationship between HLA-A*26 and BD to estimate the odds ratio (OR) of HLA-A*26 to BD. In this study, we genotyped 611 Japanese BD patients and 2,955 unrelated ethnically matched healthy controls. Genotyping results showed that the phenotype frequency of HLA-A*26 was higher in BD patients than in controls (OR = 2.12, 95% CI: 1.75-2.56). Furthermore, within the HLA-B*51-negative populations, the phenotype frequency of HLA-A*26 was significantly higher in BD patients than in controls (OR = 3.10, 95% CI: 2.43-3.95). Results obtained from meta-analysis combined with our data showed that the modified OR of HLA-A*26 became 1.80 (95% CI:1.58-2.06), whereas within the HLA-B*51-negative population, the modified OR became 4.02 (95% CI: 2.29-7.05). A subgroup analysis arranged by the geographical regions showed HLA-A*26 is in fact associated with the onset of BD in Northeast Asia (OR = 2.11, 95% CI: 1.75-2.56), but not in the Middle East or in Europe.

DOI： 10.1038/s41598-019-40824-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

DOI： 10.1097/MD.0000000000014668

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: This study aimed to identify patients with high-probability of ocular involvement of Behçet's disease (BD). METHODS: The Japanese Ministry of Health, Labour and Welfare provided dataset of ongoing nationwide BD registration project. A patient who had confirmed BD and who was suspected to have BD was registered. We mainly analyzed newly registered patients who had the data for all demographic and diagnostic parameters regardless of fulfilment of any diagnostic criteria. RESULTS: Among 3213 patients with confirmed or possible BD, 1382 (43.0%) were men and 1831 (57.0%) were women with a median age of 38 years (interquartile range (IQR) 30-49 years). The median duration between onset and registration was 0 year (IQR 0-3). A binomial multivariable logistic regression analysis revealed that being female (odds ratio (OR) 0.63, 95% confidence interval (CI) 0.53-0.75, p < .001), duration since onset (OR 1.33 per 10 years, 95% CI 1.18-1.51, p < .001), genital ulceration (OR 0.28, 95% CI 0.23-0.34, p < .001), and gastrointestinal symptoms (OR 0.36, 95% CI 0.30-0.44, p < .001) were related to the ocular lesion. Analyses based on data of 2800 patients who satisfied International criteria of BD, age-, sex-, duration-based subgroup analyses, analyses targeting iridocyclitis and retino-uveitis, and analysis including patients with missing data confirmed that the four factors were associated with the probability of eye involvement. CONCLUSION: The ocular involvement did not accompany with genital ulcer or gastrointestinal symptoms at the early stage of BD.

DOI： 10.1080/14397595.2018.1457424

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: To investigate whether variants in the ARMC9 gene encoding KU-MEL-1 are associated with Vogt-Koyanagi-Harada (VKH) disease in a Japanese population. Methods: We recruited 380 Japanese patients with VKH disease and 744 Japanese healthy controls to genotype seven single-nucleotide polymorphisms (SNPs) in ARMC9. We also performed imputation analysis of the ARMC9 region and 195 imputed SNPs were included in the statistical analysis. Results: We observed an increased frequency of the A allele of rs28690417 in patients compared with controls (P = 0.0097, odds ratio (OR) = 1.46). The A allele had a dominant effect on VKH disease risk (P = 0.011, OR = 1.51). However, these significant differences disappeared after Bonferroni correction (corrected P > 0.05). The remaining 201 SNPs did not show any significant association with disease risk. Conclusions: Our study suggests that ARMC9 variants do not play a critical role in the development of VKH disease.

DOI： 10.1080/09273948.2018.1523438

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記述言語：英語  

Zonulopathy is a major concern if found during cataract surgery as it can cause further complications. Such complications may occur during continuous curvilinear capsulorhexis (CCC), lens fragmentation and intraocular lens (IOL) implantation. Femtosecond laser-assisted cataract surgery (FLACS) devices, such as the LenSX (Alcon Laboratories) are advantageous because they can detect the area and largest point of zonulopathy via anterior segment optical coherent tomography (AS-OCT) before the manual part of the procedure. CCC and lens fragmentation can also minimize further zonular stress. A symmetrical CCC is ideal for IOL implantation in the sulcus with optic capture. In the present study, we did not detect significant zonular dehiscence preoperatively in either of the eyes of our 68-year-old patient when using AS-OCT (CASIA2 Tomey). However, LenSx AS-OCT revealed zonular dehiscence in both eyes, perioperatively. We created CCC and lens fragmentation without causing stress to the zonules. In the subsequent manual part of procedure, we found zonular dehiscence in the same area as indicated by LenSx AS-OCT, which extended to approximately 200° in the right eye and 180° in the left. After lens fragmentation by LenSx, we successfully removed the lens without further zonular dialysis. However, zonular dialysis (>180°) in the right eye was too large to insert an IOL, either in the capsule or the sulcus. Therefore, we performed scleral IOL implantation. In the left eye, we avoided using capsular tension ring (CTR) for IOL placement to avoid further iatrogenic damage to the zonule. Instead, an IOL was inserted into the sulcus with optic capture to reduce the possibility of further stress to the zonula and phimosis. Post-surgically, the patient regained good eyesight in both eyes. This case illustrates the advantages of FLACS in addressing zonulopathy. The consistent creation of CCC and lens fragmentation by FLACS may increase success rates, even in unexpectedly challenging cases.

DOI： 10.2147/IMCRJ.S189367

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The recently emerged pachychoroid concept has changed the understanding of age-related macular degeneration (AMD), which is a major cause of blindness; recent studies attributed AMD in part to pachychoroid disease central serous chorioretinopathy (CSC), suggesting the importance of elucidating the CSC pathogenesis. Our large genome-wide association study followed by validation studies in three independent Japanese and European cohorts, consisting of 1546 CSC samples and 13,029 controls, identified two novel CSC susceptibility loci: TNFRSF10A-LOC389641 and near GATA5 (rs13278062, odds ratio = 1.35, P = 1.26 × 10-13; rs6061548, odds ratio = 1.63, P = 5.36 × 10-15). A T allele at TNFRSF10A-LOC389641 rs13278062, a risk allele for CSC, is known to be a risk allele for AMD. This study not only identified new susceptibility genes for CSC, but also improves the understanding of the pathogenesis of AMD.

DOI： 10.1038/s42003-019-0712-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: Lattice degeneration of the retina is a vitreoretinal disorder characterized by a visible fundus lesion that predisposes the patient to retinal detachment. It has been suggested that collagen type II alpha 1 (COL2A1) gene variants may contribute to the development of disorders associated with retinal detachment. Here we investigated whether COL2A1 gene variants were associated with the risk of lattice degeneration of the retina. Methods: We recruited 634 Japanese patients with lattice degeneration of the retina and 1694 Japanese healthy controls. We genotyped 13 tagging single-nucleotide polymorphisms (SNPs) in COL2A1. We also performed imputation analysis to evaluate the potential association of un-genotyped COL2A1 SNPs, involving the imputation of 65 SNPs. Results: Two intronic SNPs-rs1793954 and rs1635533-were significantly associated with lattice degeneration of the retina. The SNP rs1793954 showed the strongest association, with its C allele carrying an increased disease risk (p = 0.0016, corrected p = 0.021, OR = 1.25). The rs1793954 and rs1635533 SNPs were in strong linkage disequilibrium with each other (r2 = 0.99), and conditional analysis revealed that rs1793954 could account for the association between rs1635533 and the disease. Conclusions: Our results suggested that COL2A1 gene variants may contribute to the development of lattice degeneration of the retina. Further genetic and functional analyses of COL2A1 variants are needed to clarify the present findings.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Report global adalimumab safety and efficacy outcomes in patients with non-infectious uveitis. METHODS: Adults with non-infectious intermediate, posterior, or panuveitis were randomized 1:1 to receive placebo or adalimumab in the VISUAL I (active uveitis) or VISUAL II (inactive uveitis) trials. Integrated global and Japan substudy results are reported. The primary endpoint was time to treatment failure (TF). RESULTS: In the integrated studies, TF risk was significantly reduced (hazard ratio [95% CI]) with adalimumab versus placebo (VISUAL I: HR = 0.56 [0.40-0.76], p < 0.001; VISUAL II: HR = 0.52 [0.37-0.74], p < 0.001). In Japan substudies, no consistent trends were observed between groups (VISUAL I: HR = 1.20 [0.41-3.54]; VISUAL II: HR = 0.45 [0.20-1.03]). Adverse event rates were similar between treatment groups in both studies (854 to 1063 events/100 participant-years). CONCLUSIONS: Adalimumab lowered time to TF versus placebo in the integrated population; no consistent trends were observed in Japan substudies. Safety results were consistent between studies.

DOI： 10.1080/09273948.2018.1491605

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Takayasu arteritis (TAK) is a systemic vasculitis with severe complications that affects the aorta and its large branches. HLA-B*52 is an established susceptibility locus to TAK. To date, there are still only a limited number of reports concerning non-HLA susceptibility loci to TAK. We conducted a genome-wide association study (GWAS) and a follow-up study in a total of 633 TAK cases and 5,928 controls. A total of 510,879 SNPs were genotyped, and 5,875,450 SNPs were imputed together with HLA-B*52. Functional annotation of significant loci, enhancer enrichment, and pathway analyses were conducted. We identified four unreported significant loci, namely rs2322599, rs103294, rs17133698, and rs1713450, in PTK2B, LILRA3/LILRB2, DUSP22, and KLHL33, respectively. Two additional significant loci unreported in non-European GWAS were identified, namely HSPA6/FCGR3A and chr21q.22. We found that a single variant associated with the expression of MICB, a ligand for natural killer (NK) cell receptor, could explain the entire association with the HLA-B region. Rs2322599 is strongly associated with the expression of PTK2B Rs103294 risk allele in LILRA3/LILRB2 is known to be a tagging SNP for the deletion of LILRA3, a soluble receptor of HLA class I molecules. We found a significant epistasis effect between HLA-B*52 and rs103294 (P = 1.2 × 10-3). Enhancer enrichment analysis and pathway analysis suggested the involvement of NK cells (P = 8.8 × 10-5, enhancer enrichment). In conclusion, four unreported TAK susceptibility loci and an epistasis effect between LILRA3 and HLA-B*52 were identified. HLA and non-HLA regions suggested a critical role for NK cells in TAK.

DOI： 10.1073/pnas.1808850115

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記述言語：英語  

Behçet's Disease (BD) pathogenesis remains unclear, but some genetic loci and environmental factors are proposed to play a role. Here, we investigate the association of the endoplasmic reticulum aminopeptidase-1 (ERAP1) gene variants and HLA-B*51 with BD susceptibility and clinical manifestations in Iranian patients. In the study, 748 BD patients and 776 healthy individuals were included. The MGB-TaqMan Allelic Discrimination method was used to genotype 10 common missense single nucleotide polymorphisms (SNPs) and one intronic SNP in the ERAP1 gene region. We found no significant association between the 11 SNPs and BD in allelic and genotypic association tests. However, rs30187 showed the strongest association with BD in the recessive genotype model of the risk T allele in HLA-B*51 carriers. Although this became insignificant after correcting for multiple comparisons, the homozygous rs30187 risk allele genotype (TT) increased disease susceptibility in HLA-B*51 carriers in epistasis analysis, and the rs30187 TT recessive genotype showed a significant association with risk of cardiac involvement in the all patients and articular involvements in HLA-B*51 positive patients. Our findings suggest that gene-gene interactions between HLA-B*51 and ERAP1 variants is important for BD development, however, ERAP1 variants which interact with HLA-B*51 may differ among disease phenotypes or populations.

DOI： 10.1038/s41598-018-35700-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Sarcoidosis is a major cause of granulomatous uveitis but rarely manifests as multiple choroidal granulomas. This report describes the use of enhanced depth imaging optical coherence tomography (EDI-OCT) to visualize changes occurring in multiple choroidal granulomas during treatment. METHODS: The patient was a 36-year-old Japanese man with histopathologically confirmed sarcoidosis, who was examined using EDI-OCT and showed multiple yellowish-white subretinal lesions in the peripapillary region and the arcade of the right eye. RESULTS: EDI-OCT revealed homogeneous hyporeflective choroidal lesions with choriocapillaris thinning, consistent with a diagnosis of choroidal granulomas. Subretinal fluid adjacent to one of the peripapillary choroidal lesions was also apparent. EDI-OCT during oral prednisolone administration revealed a decrease in lesion size at as early as 3 weeks and complete resolution of the lesions after 6 months of treatment. However, 2 months after prednisolone discontinuation, EDI-OCT revealed recurrence of choroidal granulomas in the peripapillary region and the arcade of the right eye. After injection of triamcinolone acetonide into the posterior sub-Tenon's capsule (sub-Tenon's injection), EDI-OCT demonstrated a reduction in granuloma lesion size within 3 months of the injection. CONCLUSION: EDI-OCT allowed detailed morphologic visualization of the choroidal granulomas caused by sarcoidosis. This imaging technique was useful for monitoring changes in granuloma size in response to steroid administration and for early detection of recurrence. Injection of triamcinolone acetonide into the posterior sub-Tenon's capsule was as effective as oral prednisolone for the treatment of choroidal granulomas.

DOI： 10.1007/s10792-017-0720-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To evaluate the frequency and severity of iris posterior synechiae after Descemet membrane endothelial keratoplasty (DMEK) and to investigate possible causes of iris posterior synechiae. METHODS: Twenty-three eyes were investigated in 20 Asian patients who underwent DMEK 1 month after phacoemulsification and intraocular lens implantation surgery. A preexisting iris damage score was defined by iris damage and classified into 5 grades. Six months after DMEK, the iris posterior synechiae severity score was evaluated based on the extent of posterior synechiae, according to every 45 degrees of the pupillary rim (posterior synechiae score, 0-8). Correlations were analyzed between the posterior synechiae score and preexisting factors (preexisting iris damage score, axial length [AXL], anterior chamber depth, and anterior chamber volume, both before and after cataract surgery). RESULTS: Iris posterior synechiae appeared in 20 of 23 eyes (87.0%). Best spectacle-corrected visual acuity significantly improved at 6 months after DMEK (P < 0.001). Endothelial cell density was 1596 ± 530 cells/mm (P < 0.001); loss of cell density was 37.8 ± 19.9% at 6 months. Single regression analysis showed that the onset of iris posterior synechiae was correlated with the preexisting iris damage score (P = 0.006, r = 0.55), AXL (P < 0.001, r = -0.71), anterior chamber depth (P < 0.001, r = -0.70), and anterior chamber volume before cataract surgery (P < 0.001, r = -0.79). CONCLUSIONS: Iris posterior synechiae after DMEK frequently appeared in Asian eyes with shorter AXLs or a damaged iris.

DOI： 10.1097/ICO.0000000000001698

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記述言語：英語  

BACKGROUND: Neurosarcoidosis is a rare complication, and cranial neuropathy is the most frequent manifestation of this disease. However, few cohesive reports have discussed multiple cranial neuropathies in Japanese patients with sarcoidosis. The present report discusses the case of a patient with sarcoid uveitis and multiple neurological findings. We further review relevant literature regarding Japanese patients with multiple cranial nerve palsies published within the past 34 years (from January 1982 to December 2016). CASE PRESENTATION: We report findings associated with the case of a 56-year-old Japanese woman with granulomatous pan-uveitis who was later diagnosed as having sarcoidosis by skin and transbronchial lung biopsies. She presented right-sided Bell's palsy and was treated with orally administered prednisolone. However, while prednisolone was tapered, she developed facial (VII) and vagus (X) nerve palsies, followed by brain parenchyma lesions, which were not associated with any additional neurological symptoms. Furthermore, she exhibited increased intraocular pressure in her right eye, and she underwent trabeculectomy. Our review of the literature revealed that 64 Japanese patients with sarcoidosis experienced multiple cranial nerve palsies between 1982 and 2016. The most commonly affected cranial nerves were the facial (VII) (73.4%) and glossopharyngeal/vagus (IX/X) nerves (48.4%). Palsies of two distinct cranial nerves were found in 40.6% of the patients, followed by palsies of three (23.4%) and four (18.8%) nerves. Almost all patients (98.3%) received systemic steroid therapy, and total or partial remission was achieved in almost all patients (96.5%). CONCLUSIONS: According to the literature, patients with multiple cranial nerve palsies associated with sarcoidosis respond well to orally administered steroid therapy. However, our findings suggest that careful follow-up is necessary for patients with neurosarcoidosis due to potential aggravation of neuropathy.

DOI： 10.1186/s13256-018-1842-5

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

Purpose: To report changes in circumpapillary retinal nerve fiber thickness in optic neuritis in cases positive and negative for anti-aquaporin-4 autoantibody. Cases and IVIethod: This retrospective study was made on 27 eyes of 24 cases with optic neuritis. The series comprised 6 male and 21 female eyes. The age averaged 53 years. Anti-aquaporin-4 autoantibody was positive in 6 eyes and negative in 21 eyes. The cases were evaluated regarding visual acuity and circumpapillary retinal nerve fiber thickness for 6 months after start of treatment. Results: Circumpapillary retinal nerve fiber thickness started to decrease 2 weeks after start of treatment in eyes positive for anti-aquaporin-4 autoantibody. The decrease was significandy greater than in autoan-tibody-negative ones. Visual acuity improved throughout the course of treatment up to 6 months after start of treatment. There was no difference between autoantibody-positive and -negative eyes. Conclusion: Decrease in circumpapillary retinal nerve fiber thickness in optic neuritis was greater in eyes positive for anti-aquaporin-4 autoantibody than in negative ones.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

Purpose: To present an epidemiological survey of uveitis in children and adolescents at Yokohama City University Hospital. Cases and Method: This retrospective study included patients under the age of 19 years who visited to our hospital and were diagnosed with uveitis between April 2011 and March 2015. In total, we studied 63 cases for determining the clinical features and causes of the disease. Results: The mean age of the patients at the first visit was 13.1 ± 4.7 years (under 15 years: 60.3 %). There was a predominance of females (65.1%), and bilateral (65.1%) and non-granulomatous uveitis (65.1%). Anterior uveitis was observed in 50.8% patients and panuveitis in 42.9% patients. Systemic associations were found in 27.0% patients. Juvenile idiopathic arthritis (JIA) was the most common medical condition (12.7%), followed by chronic iridocyclitis in young girls (CIC) (7.9%) and tubulointerstitial nephritis and uveitis syndrome (6.3%). Unclassified cases were seen in 50.8% patients. Ocular complications were observed in 46.0% patients, including macular edema/degeneration (23.8%), optic disc hyperemia/edema (22.2%), cataract (20.6%), increased intraocular pressure/glaucoma (19.0%) and band keratopathy (11.1%). Systemic treatments were required in 36.5% of cases. 9.5% of cases underwent intraocular surgery, all of which were cataract extraction. Conclusion: Females, bilateral and anterior uveitis were prevalent in children and adolescents. Juvenile chronic iridocyclitis (JIA and CIC) were frequent.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

Purpose: To report 4 cases of Vogt-Koyanagi-Harada (VKH) disease who showed resistance or recurrence of the disease and who were brought under control by combined treatment of systemic cyclosporine and corticosteroid. Cases: The series comprised 3 males and one female. They were aged 43, 49, 57 and 73 years respectively. All the cases were initially treated by pulsed corticosteroid therapy. One case resolved after 3 courses of pulsed corticosteroid. One case failed to resolve. Two cases showed signs of recurrence. All the 4 cases resolved after additional cyclosporine. One of the 4 cases showed recurrence after tapering of cyclospsorine due to renal problems. Ocular findings were brought under control by increased dosage of corticosteroid. Conclusion: Ocular manifestations in 4 cases of VKH disease, that showed resistance to or dependence on corticosteroid, resolved after combined use of cyclosporine and corticosteroid.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nature Publishing Group  

Refractive errors, including myopia, are the most frequent eye disorders worldwide and an increasingly common cause of blindness. This genome-wide association meta-analysis in 160,420 participants and replication in 95,505 participants increased the number of established independent signals from 37 to 161 and showed high genetic correlation between Europeans and Asians (&gt
0.78). Expression experiments and comprehensive in silico analyses identified retinal cell physiology and light processing as prominent mechanisms, and also identified functional contributions to refractive-error development in all cell types of the neurosensory retina, retinal pigment epithelium, vascular endothelium and extracellular matrix. Newly identified genes implicate novel mechanisms such as rod-and-cone bipolar synaptic neurotransmission, anterior-segment morphology and angiogenesis. Thirty-one loci resided in or near regions transcribing small RNAs, thus suggesting a role for post-transcriptional regulation. Our results support the notion that refractive errors are caused by a light-dependent retina-to-sclera signaling cascade and delineate potential pathobiological molecular drivers.

DOI： 10.1038/s41588-018-0127-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Graft insertion into the anterior chamber is one of the most important procedures for successful Descemet membrane endothelial keratoplasty (DMEK). Especially in eyes with fragile zonular fibers and a shallow anterior chamber, smooth graft insertion tends to become more difficult. Ophthalmic viscoelastic devices (OVDs) can usually help to retain the space in the anterior chamber and to improve the safety of manipulations during various ophthalmic surgeries. Therefore, we postulated that graft insertion into the anterior chamber could be improved by their use. The purpose of this study is to investigate the availability and efficacy of OVDs during graft insertion in DMEK surgery.A total of 11 eyes of 9 patients with bullous keratopathy who underwent DMEK were retrospectively analyzed. The cause of bullous keratopathy was corneal endothelial decompensation following laser iridotomy in all eyes. We used low viscous dispersive OVD (Opegan) to maintain the anterior chamber depth during graft insertion in all of the eyes.The graft insertion was uneventful in all of the eyes. The inserted graft was attached to the back surface of the cornea. However, 2 eyes needed rebubbling, and after rebubbling, all of the 2 grafts completely attached to the back surface of the cornea. The best spectacle-corrected visual acuity significantly improved 6 months after surgery (P < .001) and the central corneal thickness significantly decreased (P < .001).The use of OVD facilitates safer graft insertion during DMEK, and subsequently prevents endothelial cell loss, which leads to a successful procedure.

DOI： 10.1097/MD.0000000000011245

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記述言語：英語  

Purpose: To evaluate the influence of pupil dilation on predicted postoperative refraction (PPR) and recommended intraocular lens (IOL) power to obtain target postoperative refraction calculated by using the third- and fourth-generation IOL power calculation formulas with a new optical biometer. Methods: This retrospective study included 162 eyes with cataract that underwent uneventful phacoemulsification with IOL implantation. PPR, recommended IOL power, anterior chamber depth (ACD), and lens thickness (LT) were measured pre- and post-pupil dilation. The change in PPR detected by using third-generation (Hoffer Q and SRK/T) and fourth-generation formulas (Haigis and Holladay 2) and the changes in ACD and LT were evaluated pre- and postdilation. The influence of dilation on the recommended IOL power calculated by each formula was analyzed. Result: ACD and LT significantly changed from pre- to postdilation. The mean absolute change in PPR between pre- and postdilation was significantly higher for fourth-generation formulas compared with third-generation formulas. The change in PPR between pre- and postdilation showed a significantly positive correlation with change in ACD and a significantly negative correlation with change in LT with fourth-generation formulas, but not with third-generation formulas. The discrepancy rate of recommended IOL power between pre- and postdilation calculated by fourth-generation formulas was significantly higher than that calculated by third-generation formulas. Conclusion: ACD and LT significantly changed by dilation. PPR and recommended IOL power significantly changed more by dilation when using fourth-generation formulas compared with third-generation formulas. Given the significant correlations of the change in PPR (between the pre- and postdilation) in the fourth-generation formulas and the changes in ACD and LT, the latter changes may be key in influencing dilation in the fourth-generation power calculation. Knowledge of the influence of dilation on fourth-generation formulas could help improve IOL calculation.

DOI： 10.2147/OPTH.S172846

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記述言語：英語  

At present, only one design is available for trifocal intraocular lens (IOL); unfortunately, this particular design is not suitable for implantation in the sulcus with optic capture when posterior capsule rupture (PCR) occurs. Although three-piece bifocal IOLs can be implanted in the sulcus, this form of IOL can be vulnerable to tilt and decentration, thus causing aberration and photopic phenomena, such as halos and glares. However, visual axis centered optic capture using femtosecond laser-assisted cataract surgery (FLACS) is able to manage such complex operations. In the present study, we implanted a three-piece +4.0 D bifocal IOL into the sulcus of a patient who experienced PCR using optic capture and FLACS following the straightforward implantation of a one-piece trifocal IOL in the other eye. Defocus curves showed that the weakness of the trifocal IOL (nearest distances) was compensated for by the strength of the +4.0 D bifocal IOL, whereas the weakness of the +4.0 D bifocal IOL (middle distance) was compensated for by the strength of the trifocal IOL. Therefore, this combination provided the patient with a wider range of depth of focus. The contrast sensitivity in both eyes was within the normal range. Photopic phenomena were comparable with the bilateral implantation of the trifocal IOL. Anterior segment optical coherence tomography showed that tilt and decentration in the trifocal IOL implanted in the bag was significantly higher than the +4.0 D bifocal IOL implanted in the visual axis centered optic capture. This case showed that the intraindividual implantation of a single-piece trifocal IOL in the bag and a three-piece +4.0 D bifocal IOL in the sulcus, using a combination of optic capture and FLACS, is promising particularly in cases of PCR and can provide a wider range of vision without losing visual quality.

DOI： 10.2147/IMCRJ.S176095

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective: This report aimed to scrutinize the prevalence of Behçet's disease (BD)-related clinical manifestations based on age- and sex-specific subgroups using a Japanese nationwide registration database. Methods: The database of newly registered BD was obtained from the Japanese Ministry of Health, Labour and Welfare. Patients who met the International Criteria for Behçet's Disease were selected and analysed. Results: Among 6627 International Criteria for Behçet's Disease cases, 2651 (40.0%) were men and 3976 (60.0%) were women with a median age of 39 years (interquartile range: 31-50 years). Ocular lesion was more common in male [odds ratio (male: female) 2.64 (95% CI: 2.35, 2.95, P < 0.001)] and genital ulceration was more common in female (odds ratio = 0.29, 95% CI: 0.25, 0.32, P < 0.001). Ocular lesion (P < 0.001), arthritis (P < 0.001) and vascular lesions (P < 0.001) were more frequently observed in elderly registered patients. Contrarily, genital ulceration (P < 0.001), epididymitis of males (P = 0.023) and oral ulceration (P = 0.003) were more common in younger patients. Simultaneous assessment of sex and age revealed that male predominance of ocular involvement was found in the young adult generation, but not in patients over 70 year of age. A female predominance of genital ulcer was prominently observed in patients 20-59 year of age; however, the sex difference was not found in patients over 60 years of age. Sensitivity analysis using International Study Group criteria replicated the results. Conclusion: We showed that clinical phenotype in early phase of BD was different depending on onset age and sex.

DOI： 10.1093/rheumatology/kex285

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To describe a simple technique that uses posterior chandelier illumination during Descemet membrane endothelial keratoplasty in cases of severe bullous keratopathy (BK). METHODS: Five eyes of 4 patients with advanced BK undergoing Descemet membrane endothelial keratoplasty were retrospectively analyzed. The pupil of the host eye was not treated with mydriatic or miotic agents. The chandelier illuminator was inserted transconjunctivally into the vitreous cavity from the pars plana. RESULTS: In all eyes, BK was secondary to laser iridotomy, which was performed for prevention or treatment of angle closure glaucoma. The implanted graft was clearly confirmed in the anterior chamber using activated chandelier illumination. The graft was immediately attached to the host cornea, with eventual healing of BK in all eyes. No complication involving insertion or removal of the 25-gauge trocar and the chandelier illuminator was observed. No vision-threatening complication was observed in any of the 5 eyes. CONCLUSIONS: The chandelier illuminator provided good visibility of the anterior chamber and enhanced the safety of surgery by preventing formation of an inverted graft.

DOI： 10.1097/ICO.0000000000001254

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Neuro-Behçet's disease (NBD) is subcategorized into parenchymal-NBD (P-NBD) and non-parenchymal-NBD types. Recently, P-NBD has been further subdivided into acute P-NBD (A-P-NBD) and chronic progressive P-NBD (CP-P-NBD). Although an increasing number of studies have reported the various clinical features of A-P-NBD and CP-P-NBD over the last two decades, there was a considerable inconsistency. Two investigators systematically searched four electrical databases to detect studies that provided sufficient data to assess the specific characteristics of A-P-NBD and CP-P-NBD. All meta-analysis was carried out by employing the random-model generic inverse variance method. We included 11 reports consisted of 184 A-P-NBD patients and 114 CP-P-NBD patients. While fever (42% for A-P-NBD, 5% for CP-P-NBD, p < 0.001, I2 = 93%) was more frequently observed in A-P-NBD cases; sphincter disturbances (9%, 34%, P = 0.005, I2 = 87%), ataxia (16%, 57%, P < 0.001, I2 = 92%), dementia (7%, 61%, P < 0.001, I2 = 97%), confusion (5%, 18%, P = 0.04, I2 = 76%), brain stem atrophy on MRI (4%, 75%, P < 0.001, I2 = 98%), and abnormal MRI findings in cerebellum (7%, 54%, P = 0.02, I2 = 81%) were more common in CP-P-NBD. Cerebrospinal fluid cell count (94/mm3, 11/mm3, P = 0.009, I2 = 85%) was higher in A-P-NBD cases. We demonstrated that A-P-NBD and CP-P-NBD had clearly different clinical features and believe that these data will help future studies investigating P-NBD.

DOI： 10.1038/s41598-017-09938-z

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記述言語：英語  

DOI： 10.1007/s10792-016-0321-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41598-017-00877-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/ng.3786

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記述言語：英語   出版者・発行元：TAYLOR & FRANCIS INC  

DOI： 10.3109/13816810.2016.1145698

Web of Science

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記述言語：英語  

DOI： 10.3109/09273948.2015.1136422

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Introduction: Maintaining the correct orientation of the donor graft is important during Descemet's membrane endothelial keratoplasty (DMEK). We describe a new method of marking the donor graft prior to DMEK. Methods: Twelve eyes of 10 patients with bullous keratopathy who underwent DMEK were retrospectively analysed. Donor discs were created by stripping the endothelium-Descemet's membrane layer from corneoscleral buttons. Four semicircular marks, two 1.0 mm and two 1.5 mm in diameter, were created at the edge of the donor disc. The small and large marks were paired. Each donor graft was inserted into the anterior chamber, unfolded and attached to the posterior corneal stroma with an air bubble. Results: The inserted grafts were all appropriately orientated when attached to the back surfaces of the corneas. The two pairs of asymmetric marks afforded valuable guidance. Even when the graft was partially folded or decentred, and one pair of marks was obscured, the other pair was always visible to indicate graft orientation. Best spectacle-corrected visual acuity improved significantly in all patients (p<0.001). Compared with the preoperative endothelial cell density of the donor graft, that of the corneal endothelium had decreased 44.0%±10.0% by 6 months after surgery. Conclusions: Two pairs of asymmetrical semicircular marks placed on the edge of the donor graft allowed appropriate graft orientation during DMEK.

DOI： 10.1136/bmjophth-2017-000080

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: The crystallin beta A4 (CRYBA4) gene variant, rs2009066, was previously reported to be associated with high myopia in a southern Chinese population. In the present study, we investigated whether CRYBA4 variants were associated with high myopia in a Japanese population. Methods: We recruited 1,063 Japanese patients with high myopia (spherical equivalent [SE] ≤-9.00 D in both eyes) and 1,009 healthy Japanese subjects (SE >-1.00 D). We genotyped rs2009066 and three tagging single-nucleotide polymorphisms (SNPs), rs16982456, rs2071861, and rs4276, in the CRYBA4 region. Results: We did not find any significant association between these four SNPs and high myopia in an allele analysis. However, rs2009066 and rs2071861, which were in strong linkage disequilibrium (LD; r2=0.86), showed a marginal association with high myopia in the recessive genotype model of risk alleles (rs2009066 G allele: P=0.032, odds ratio [OR] =1.31; rs2071861 A allele: P=0.037, OR =1.31). Nevertheless, this association became insignificant after correcting for multiple testing (Pc >0.05). Conclusion: This study showed no significant association between CRYBA4 variants and high myopia in a Japanese population. Our findings did not correspond with a previous study. Further genetic studies with other populations are needed to elucidate a potential contribution of the CRYBA4 region in the development of high myopia.

DOI： 10.2147/OPTH.S146038

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記述言語：英語  

DOI： 10.1111/1346-8138.13251

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3109/13816810.2015.1028649

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nature Publishing Group  

Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4
P = 6.3E-04).

DOI： 10.1038/srep25853

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10384-016-0441-5

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記述言語：英語  

DOI： 10.1038/ncomms11008

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2147/OPTH.S104761

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：DOVE MEDICAL PRESS LTD  

Components of fish roe possess antioxidant and antiaging activities, making them potentially very beneficial natural resources. Here, we investigated chum salmon eggs (CSEs) as a source of active ingredients, including vitamins, unsaturated fatty acids, and proteins. We incubated human dermal fibroblast cultures for 48 hours with high and low concentrations of CSE extracts and analyzed changes in gene expression. Cells treated with CSE extract showed concentration-dependent upregulation of collagen type I genes and of multiple antioxidative genes, including OXR1, TXNRD1, and PRDX family genes. We further conducted in silico phylogenetic footprinting analysis of promoter regions. These results suggested that transcription factors such as acute myeloid leukemia-1a and cyclic adenosine monophosphate response element-binding protein may be involved in the observed upregulation of antioxidative genes. Our results support the idea that CSEs are strong candidate sources of antioxidant materials and cosmeceutically effective ingredients.

DOI： 10.2147/CIA.S102092

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2147/CIA.S102092

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記述言語：英語  

DOI： 10.1371/journal.pone.0160392

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語  

DOI： 10.1038/ejhg.2014.288

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.bbi.2015.05.003

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記述言語：日本語   掲載種別：研究論文（国際会議プロシーディングス）   出版者・発行元：Igaku-Shoin Ltd  

Purpose: To report a case of sarcoidosis who showed pulmonary and heart lesions with multiple choroidal granuloma. Case: An 80-year-old female was referred to us for uveitis since 9 months before. She had received implantation of pace maker for severe atrioventricular block 2 years before. Findings: Visual acuity was 1.2 in either eye. The right eye showed slight opacity in the aqueous. Both eyes showed vitreous opacity and multiple nodules in and posterior to the retina. Optical coherence tomography showed elevated choroidal and intraretinal nodules. Systemic examinations showed pulmonary and heart lesions leading to the diagnosis of sarcoidosis. Peroral prednisolone was followed by resolution of retinal and choroidal granuloma 3 months later. Conclusion: This case illustrates that sarcoidosis may underlie in a female of advanced age in the presence of atrioventricular block and choroidal granuloma.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

Purpose: To report a case who was initially suspected of sarcoidosis due to bilateral hilar lymphadenopathy and who was finally diagnosed with malignant lymphoma by brain biopsy. Case: A 69-year-old male presented with bilateral blurring of vision left. Corrected visual acuity was 0.7 right and 0.6 left The right eye showed signs of anterior uveitis. Both eyes showed vitreous opacity. Computed tomography showed bilateral hilar lymphadenopathy and swelling of lymphnodes in the mediastinum. The findings were suggestive of sarcoidosis. Magnetic resonance imaging showed intracranial lesions 3 months later. Brain biopsy led to the diagnosis of diffuse large B-cell lymphoma. Treatment with massive dosis of methotrexate was followed by improved brain and ocular lesions for 5 months until present Conclusion: The present case illustrates that malignant lymphoma may manifest symptoms simulating ocular sarcoidosis.

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記述言語：英語  

DOI： 10.1038/ejhg.2014.158

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/ncomms7689

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10067-013-2442-9

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記述言語：英語  

For the purpose of investigating Behcet&#039;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&#039;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

DOI： 10.1007/s10067-013-2442-9

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記述言語：英語   掲載種別：論文集(書籍)内論文   出版者・発行元：Springer Japan  

The etiology of Behçet’s disease (BD) is still unclear, but currently some external environmental factors are thought to trigger BD in individuals with a particular genetic background. It is well established that BD is strongly associated with the human leukocyte antigen (HLA) class I allele, HLA-B51, in many different ethnic groups, indicating that the HLA-B51 allele is one of the genetic factors underlying BD. However, the presence of HLA-B51 -negative BD patients suggests that other genetic and/or environmental factors also play important roles in the development of BD. Several genes have been recently identified as susceptibility factors for the development of BD, especially with the help of genome-wide association studies. Those fi ndings provide new insights into the genetic tendency underlying BD by connecting classically known findings and allow for clearer interpretation of the etiology and pathophysiology of BD at the molecular level. Thus, findings from genetic studies can provide useful clinical information and open the door to the development of more accurate and reliable diagnostic and treatment approaches for BD.

DOI： 10.1007/978-4-431-54487-6_3

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記述言語：英語  

DOI： 10.1007/s10384-014-0362-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2147/OPTH.S95167

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3109/09273948.2014.981547

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記述言語：日本語   出版者・発行元：日本サルコイドーシス/肉芽腫性疾患学会  

【目的】今回、サルコイドーシス(サ症)診断基準の全身検査項 目に、血清可溶性 IL-2 受容体(s IL-2R)が加わった。血清 s IL-2R はサ症の他、悪性リンパ腫や膠原病、結核などでも上昇すること が知られている。我々は、ぶどう膜炎患者における血清 s IL-2R 測定が、サ症鑑別・診断に有用か否かを検討した。 【対象・方法】2014 年 8 月から 2015 年 5 月までに当院眼科外来 を受診し、確定診断がついたサ症 43 例、眼内悪性リンパ腫 10 例、 サ症以外の原因の明らかなぶどう膜炎 48 例について、ERISA 法 にて血清 s IL-2R を測定した。 【結果】血清 s IL-2R (Cut-Off 値:534U/ml)はサ症では 31 例 (72.1%、平均値:913.7 U/ml)、眼内悪性リンパ腫では 2 例(20%、 平均値:521 U/ml)、サ症以外のぶどう膜炎では 3 例(6.3%)に上 昇が見られた。サ症における血清 s IL-2R の感度は 72.1%、特異 度は 91.4%であった。 【結論】眼内悪性リンパ腫との鑑別を考慮に入れる必要はあるが、 血清 s IL-2R 測定は、サ症に伴うぶどう膜炎を鑑別・診断するた めに有用であると考えられた。

DOI： 10.7878/jjsogd.35.Suppl1_50-2

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記述言語：英語  

DOI： 10.3980/j.issn.2222-3959.2015.01.01

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ophtha.2014.04.042

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記述言語：英語  

DOI： 10.1007/s10792-013-9878-4

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記述言語：英語  

DOI： 10.1111/aos.12349

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記述言語：英語  

DOI： 10.1007/s00417-014-2616-4

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記述言語：英語  

DOI： 10.1007/s00417-014-2597-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10384-013-0294-0

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記述言語：英語   掲載種別：論文集(書籍)内論文   出版者・発行元：Springer Nature  

Although the etiology of Behçet’s disease (BD) remains uncertain, genetic and environmental factors likely both play an important role in BD development. BD is strongly associated with the human leukocyte antigen (HLA) class I allele, HLA-B*51, in many different ethnic groups. However, the presence of HLA-B*51-negative BD patients suggests that other genetic and/or environmental factors are also important in the development of BD. Several genetic variations have been recently identified as susceptibility factors for the development of BD, especially with the help of genome-wide association studies. Those findings provide new insights into the etiology and pathophysiology of BD allowing for a clearer interpretation the molecular level, and translation of those genetic findings may lead to development of more accurate diagnostic tools and more effective treatment approaches for BD.

DOI： 10.1007/978-88-470-5477-6_4

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

Purpose: To report the outcome of vitreous biopsy for uveitis during vitrectomy with and without irrigation. Cases and Method: This study was made on 16 eyes of 12 cases who received vitreous biopsy during the past 6 months. The series comprised 11 male and 5 female eyes. The age averaged 69±11 years. Vitreous sample was obtained first without and later with irrigation. Findings: Level of IL-6 was higher in 10 eyes sampled without irrigation and was higher in 6 eyes with irrigation. Level of IL-10 could be evaluated in 4 eyes. It was higher in one sample obtained without and in 3 samples obtained with irrigation. Ratio of 11-10 and IL-6 was 1.0 or over in all the 4 eyes. There was no difference in the cytological diagnosis between samples obtained with and without irrigation. Conclusion: There was no difference in the outcome of vitreous biopsy obtained with and without irrigation.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

Purpose : To report imaging analyses of retinal ganglion cell layer (RGCL) thinning followed by retinal nerve fiber layer (RNFL) thinning in patients with history of malignancy. Subjects and Methods : This study was made on 184 eyes of 92 patients with history of malignancy, included gastric, esophageal, liver, colon, and kidney cancer, etc. The findings were compared with those in 68 eyes of 34 patients with normal tension glaucoma and 58 eyes of 29 healthy controls. The imaging analyses apparatus was 3D OCT-2000. Results : The significance maps showed RGCL thinning in 96.3% of patients with malignancy. The RNFL thickness around the disc showed thinning in 58.3% of patients with malignancy. Average values of RGCL thickness showed significant thinning (p&lt
0.001) compared with healthy control. Conclusion : The cancer nonspecific thinning of RGCL followed by RNFL in patients with history of malignancy was observed.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

Purpose: To report a case of Vogt-Koyanagi-Harada (VKH) disease with bilateral rubeosis iridis that received pulsed corticosteroid therapy. Case: A 24-year-old male was referred to us for inflammation in the anterior chamber with rubeosis in both eyes. He had had hyperemia and blurring since 2 months before. Findings: Corrected visual acuity was 0.3 right and 0.8 left. Pleocytosis was present in the cerebrospinal humor. He showed hearing difficulty. He was diagnosed with VKH disease and received pulsed corticosteroid therapy. Rubeosis iridis disappeared and visual acuity improved to 1.5 in either eye 8 months later. Conclusion: This case illustrates that VKH disease is a possibility when intense sign of anterior inflammation is present in uveitis.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

Purpose: To report the outcome of trabeculectomy for glaucoma in 3 cases of Behget disease. Cases: All were males and were aged 30, 39 and 44 years respectively. Behget disease had been diagnosed 14 months, 8 years and 14 years before. Ocular hypertension was present unilaterally in all the cases. Trabeculectomy with adjunct use of mitomycin C was performed after systemic infliximab for 3 months, 30 months, and 2 weeks respectively. Results: Intraocular pressure (IOP) in the affected eye was 42 mmHg, 27 mmHg and 35 mmHg respectively. IOP decreased after surgery and has been maintained under 14 mmHg for 4 years until present. There has been no recurrence of intraocular inflammation nor infection. Conclusion: Trabeculectomy was effective in 3 eyes of Behget disease after introduction of systemic infliximab therapy.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

Purpose: To report a case of sarcoidosis with ocular and multiple cranial nerve involvement. Case: A 34-year-old female presented with blurring in the right eye since one month before. She had also anosmia, dysphagia and impaired taste. Findings: Corrected visual acuity was 1.2 right and 1.5 left. The right eye showed signs of anterior uveitis. Both eyes showed peripheral anterior synechia and retinal periphlebitis. X-ray studies showed hypertrophy of pulmonary hilar lymph nodes. Transtracheal biopsy of the lungs led to the diagnosis of sarcoidosis. One month after her initial visit, she developed signs of cranial nerve palsy involving trigeminal, facial, glossopharyngeal and vagal nerves. She was treated by pulsed therapy of methylprednisolone. Anosmia started to improve the third day followed by improved fundus findings. Palsy of cranial nerves recovered 10 months after start of treatment. She has been doing well for 8 months until present. Conclusion: Pulsed corticosteroid therapy was followed by improvement of ocular and nerve findings as manifestation of sarcoidosis.

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記述言語：英語  

DOI： 10.1007/s00417-013-2469-2

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記述言語：英語  

DOI： 10.1007/s00417-013-2419-z

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記述言語：英語  

DOI： 10.1136/annrheumdis-2011-200288

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WICHTIG EDITORE  

Purpose: Globe rupture is a serious condition. Despite advancements in vitrectomy, the postoperative prognosis for visual acuity remains poor in many cases. We conducted multiple regression analysis to identify preoperative factors associated with postoperative visual acuity.
Methods: Subjects comprised 24 patients with globe rupture in one eye who had 5 consecutive years of consultation and were followed up for 12 months or longer. Subjects comprised 13 males and 11 females with a mean age of 67.8 +/- 17.4 years. Our methods involved performing multiple regression analysis with age, preoperative visual acuity, scope of injury, number of surgeries, hyphema, vitreous hemorrhage, retinal detachment, and subchoroidal hemorrhage as explanatory variables, and postoperative visual acuity as the response variable.
Results: Preoperative visual acuity and scope of retinal detachment were explanatory factors found to correlate significantly with postoperative visual acuity after globe rupture.
Conclusions: Our results demonstrate that postoperative visual acuity can be predicted to some degree by preoperative visual acuity and the scope of retinal detachment.

DOI： 10.5301/ejo.5000252

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記述言語：英語  

DOI： 10.1007/s00417-012-2232-0

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記述言語：英語  

DOI： 10.1016/j.ajhg.2013.06.016

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3109/09273948.2012.756114

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記述言語：英語  

DOI： 10.1136/bjophthalmol-2012-302289

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Purpose: To report changes in refraction following lens removal with implantation of intraocular lens (IOL) in eyes with acute glaucomatous attack. Cases: This study was made on 14 eyes that received lens removal with implantation of intraocular lens (IOL) during acute glaucomatous attack in the past 3 years. The series comprised 4 males and 10 females. The age averaged 68 years. Results: Intraocular pressure averaged 52.5 mmHg before and 15.2 mmHg after surgery. Length of ocular axis averaged 22.3 ±0.77 mm. Corneal curvature, expressed as K1 and K2, averaged 7.72 mm and 7.49 mm respectively before, and 7.63 mm and 7.50 mm after surgery. The difference was not significant. No difference was present between target refraction before and actual one after surgery. Conclusion: There was no difference between target and actual refraction in eyes that received lens removal with IOL implantation during acute glaucomatous attack.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1073/pnas.1306352110

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記述言語：英語  

DOI： 10.3109/09273948.2012.747619

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/ng.2520

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記述言語：英語  

DOI： 10.1136/bjophthalmol-2012-302704

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10384-012-0211-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0074372

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記述言語：英語  

DOI： 10.1159/000354611

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2147/OPTH.S52726

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   掲載種別：研究論文（国際会議プロシーディングス）  

Purpose: To report the incidence of uveitis in patients aged 70 years or over in our institution over a 3-year period. Cases: This retrospective study was made on 111 cases of uveitis who were aged 70 years or over during 3 years through March 2012. A total of 646 cases of uveitis were seen during the same period. Results: Definitive diagnosis was made in 66 cases (60%), comprising sarcoidosis (15.3%), malignant lymphoma (5.6%), and Vogt-Koyanagi-Haada disease (4.5%). There was no case of Behçet disease. Out of 45 patients with unclassified uveitis, presumed sarcoidosis was the most frequent. Conclusion: Sarcoidosis was the most frequent followed by malignant lymphoma among entities of uveitis in patients over 70 years of age. This trend was the same as in patients throughout the ages.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nature Publishing Group  

The caveolin 1 to caveolin 2 (CAV1-CAV2) gene region on chromosome 7q31 has been reported to be associated with susceptibility to primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) in previous studies. We investigated whether genetic variants in the CAV1-CAV2 region are associated with NTG in Japanese patients. Two hundred and ninety-two Japanese patients with NTG and 352 Japanese healthy controls were recruited. We genotyped three single-nucleotide polymorphisms
that is, rs1052990, rs4236601, and rs7795356, in the CAV1-CAV2 gene region and assessed the allelic diversity among cases and controls. The frequency of the minor allele (G) of rs1052990 was significantly decreased in NTG cases compared with controls (P=0.014, OR=0.71), whereas NTG or POAG cases had a significantly higher frequency of the allele than controls in previous studies. Conversely, rs7795356 did not show any significant association with NTG cases, and rs4236601 was monomorphic in the Japanese study population. Our findings did not correspond with previous positive results, suggesting that CAV1-CAV2 variants studied in the present study are not important risk factors for NTG susceptibility in all populations. Further studies are needed to elucidate the possible contribution of the CAV1-CAV2 region to the development of glaucoma. © 2013 Macmillan Publishers Limited All rights reserved.

DOI： 10.1038/eye.2013.123

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記述言語：日本語   掲載種別：研究論文（国際会議プロシーディングス）  

Purpose: To report a case of choroidal malignant melanoma treated by diode laser irradiation. Case: A 48-year-old male presented with metamorphopsia since 10 days before. Findings: Corrected visual acuity was 1.5 in either eye. The left eye showed a dark-brown protrusion along the vascular arcade superior to the macula. The tumor was associated by serous retinal detachment. The left eye was diagnosed with choroidal malignant melanoma and was treated by irradiation of diode laser. Visual acuity decreased to 0.7 the following day and improved to 1.2 three weeks later. There has been no recurrence of retinal detachment for 7 months until present. Conclusion: Diode laser irradiation was effective for choroidal malignant melanoma associated with retinal detachment.

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記述言語：日本語   掲載種別：研究論文（国際会議プロシーディングス）  

Purpose: To report 4 cases of ocular injury m eyes with past history of penetrating keratoplasty. Cases: The present series comprised one male and 3 females. The age ranged from 51 to 81 years, average 71 years. Findings: Blunt trauma was the cause of injury in all the cases. Falling down was mainly involved. All the eyes showed rupture along the previous corneal wound. Visual acuity after injury was no light perception in 2 eyes, and light perception in 2 eyes. Final visual acuity was no light perception, light perception, 0.03 and 0.4 in one eye each. Visual acuity in the fellow eye was 0.1 in 2 eyes, 0.4 and 0.8 in one eye each. Conclusion: Due precaution is needed after penetrating keratoplasty, as the patients often have impaired vision or visual field in addition to fragile eyeglobe.

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記述言語：日本語   掲載種別：研究論文（国際会議プロシーディングス）  

Purpose: To present a review of primary intraocular lymphoma in our institution. Cases: This study was made on 6 cases who received diagnostic vitrectomy and were diagnosed with primary intraocular lymphoma at Yokohama City University Hospital during the past 38 months. Results: The series comprised 2 males and 4 females. Three cases were unilaterally and 3 were bilaterally affected. The age ranged from 62 to 82 years, average 73 years. They were followed up for 8 to 72 months. All the affected eyes showed dense vitreous opacity or retinal exudates. Ratio of IL-10 versus IL-6 ranged from 1.3 to 76.7. All the cases showed lymphoma of classlllb or below by biopsy. Three cases developed involvement of central nervous system (CNS) during the follow-up and resulted in fatal outcome. Two cases refused treatment and one case received intravitreal methotrexate. These 3 cases did not develop CNS involvement. Conclusion: Involvement of CNS results in fatal outcome in primary intraocular lymphoma. Ratio of IL-10 versus IL-6 was not an indicator of CNS involvement.

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記述言語：英語  

DOI： 10.1097/ICO.0b013e3182408bc7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1167/iovs.12-10491

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記述言語：英語  

DOI： 10.1177/1550059412445608

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記述言語：英語  

DOI： 10.1136/bjophthalmol-2011-300864

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記述言語：英語  

DOI： 10.1007/s00417-011-1921-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: Intraocular lymphoma is a rare disease with a poor prognosis. Early diagnosis and early treatment greatly influence the survival prognosis of this disease. This retrospective study aimed to clarify the clinical features of patients diagnosed with intraocular lymphoma, and the diagnostic significance of results from analysis of vitreous samples including cytology, cytokine measurements, and the IgH gene rearrangement test. Methods: We reviewed 217 patients with intraocular lymphoma diagnosed at 25 medical institutions in Japan. Together with clinical observation, cytological analysis, determination of the levels of cytokines, and/or detection of IgH gene rearrangements were conducted using vitreous fluid specimens. The results were studied in conjunction with clinical findings of intraocular lymphoma. Survival curves were estimated by use of the Kaplan-Meier method. Results: The subjects comprised 85 men and 132 women, with a mean age at first ophthalmological examination of 63.4 years. The mean observation period was 41.3 months. During the observation period, 69 patients had onset of lymphoma in one eye and 148 had onset in both eyes. Intraocular lymphoma with involvement of the central nervous system (CNS) was most common, found in 60.8% of the patients, whereas intraocular lymphoma without involvement of other organs was found in 28.1% of patients. With respect to onset patterns, 82.5% of patients developed primary ocular lesions whereas 16.1% developed primary CNS lesions preceding intraocular lymphoma. Blurred vision and ataxia were the most common ocular and extra-ocular symptoms that prompted patients to seek medical examination. Vitreous opacification was the most common ocular finding. The detection rates of malignant cytology, IL-10/IL-6 ratio greater than 1.0, and IgH gene rearrangements in vitreous specimens were 44.5, 91.7, and 80.6%, respectively, of patients tested. IL-10/IL- 6 ratio greater than 1.0 had the highest overall detection rate, and was extremely high (≥90%) in patients with or without vitreous opacification. The 5-year survival rate was 61.1%. Conclusion: Cytokine analysis of vitreous biopsy had the highest detection rate for intraocular lymphoma. This supplementary diagnostic test should be performed frequently to confirm a diagnosis of intraocular lymphoma. © Japanese Ophthalmological Society 2012.

DOI： 10.1007/s10384-012-0150-7

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記述言語：日本語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/hr.2012.41

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記述言語：英語  

DOI： 10.1093/rheumatology/ker444

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3109/09273948.2012.665124

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

As one of the leading causes of visual impairment and blindness, myopia poses a significant public health burden in Asia. The primary determinant of myopia is an elongated ocular axial length (AL). Here we report a meta-analysis of three genome-wide association studies on AL conducted in 1,860 Chinese adults, 929 Chinese children, and 2,155 Malay adults. We identified a genetic locus on chromosome 1q41 harboring the zinc-finger 11B pseudogene ZC3H11B showing genome-wide significant association with AL variation (rs4373767, beta = -0.16 mm per minor allele, P-meta = 2.69x10(-10)). The minor C allele of rs4373767 was also observed to significantly associate with decreased susceptibility to high myopia (per-allele odds ratio (OR) = 0.75, 95% CI: 0.68-0.84, P-meta = 4.38x10(-7)) in 1,118 highly myopic cases and 5,433 controls. ZC3H11B and two neighboring genes SLC30A10 and LYPLAL1 were expressed in the human neural retina, retinal pigment epithelium, and sclera. In an experimental myopia mouse model, we observed significant alterations to gene and protein expression in the retina and sclera of the unilateral induced myopic eyes for the murine genes ZC3H11A, SLC30A10, and LYPLAL1. This supports the likely role of genetic variants at chromosome 1q41 in influencing AL variation and high myopia.

DOI： 10.1371/journal.pgen.1002753

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記述言語：英語  

DOI： 10.1097/ICO.0b013e3181dc81d2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WICHTIG EDITORE  

PURPOSE. To report a case in which a nonselective cyclooxygenase (COX) inhibitor improved an exudative lesion in age-related macular degeneration.
METHODS/RESULTS. A 64-year-old man had a complaint of metamorphopsia in the left eye. Visual acuity was 0.5 in the left eye. Fluorescein angiography and indocyanine angiography showed juxtafoveal occult choroidal neovascularization (CNV) in the left eye, and pegaptanib sodium 0.3 mg was administered once every 6 weeks. After 4 months, visual acuity improved to 0.8. After 8 months follow-up, optical coherence tomography (OCT) showed subretinal fluid (SRF) and retinal pigment epithelium (RPE) irregularity. Visual acuity was 0.4. We recommended further pegaptanib sodium injections, but the patient did not consent to the treatment. Onset of cellulitis of the left toe occurred 1 week before the scheduled visit after 9 months. The patient was treated with loxoprofen sodium (nonselective COX inhibitor) and cefdinir for 7 days. At 2 weeks after onset of cellulitis, SRF had disappeared and OCT showed improvement of RPE irregularity.
CONCLUSIONS. A COX inhibitor had an effect on vascular permeability in CNV and may have improved exudative changes.

DOI： 10.5301/ejo.5000032

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記述言語：英語  

DOI： 10.1007/s00417-011-1800-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.exer.2011.12.021

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記述言語：英語  

DOI： 10.1016/j.exer.2011.12.021

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記述言語：英語  

DOI： 10.1016/j.bbrc.2012.01.033

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0039300

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記述言語：英語  

DOI： 10.1371/journal.pgen.1002753

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語  

DOI： 10.1097/ICU.0b013e32834bbd7e

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Purpose: To report a case of psoriatic uveitis that markedly responded to intravenous infliximab. Case: A 58-year-old male presented with anterior uveitis in both eyes since 3 years before. He had had iliosacral arthritis 28 years before. He had been diagnosed with psoriatic arthritis 11 years before. Findings: Both eyes showed anterior uveitis and were diagnosed with psoriatic uveitis. During the ensuing 14 years, the uveitis persisted despite instillation of corticosteroid and systemic cyclosporine. Cutaneous manifestations exacerbated 15 years after his initial visit. Intravenous infusion of infliximab was promptly followed by improvements of skin and ocular lesions. Conclusion: The present case illustrates that systemic infliximab may induce improvements in psoriasis and uveitis.

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記述言語：英語  

DOI： 10.3109/09273948.2011.553981

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記述言語：英語  

DOI： 10.1159/000329190

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語  

DOI： 10.1016/j.humimm.2010.12.007

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Juvenile idiopathic arthritis (JIA) is one of the most common forms of pediatric chronic arthritis. JIA is a clinically heterogeneous disease. Therefore, the genetic background of JIA may also be heterogeneous. The aim of this study was to investigate associations between human leukocyte antigen (HLA) and susceptibility to JIA and/or uveitis, which is one of the most devastating complications of JIA. A total of 106 Japanese articular JIA patients (67 with polyarthritis and 39 with oligoarthritis) and 678 healthy controls were genotyped for HLA-A, -B and -DRB1 by PCR-sequence-specific oligonucleotide probe methodology. HLA-A(*)02:06 was the risk factor for JIA accompanied by uveitis after adjustment for clinical factors (corrected P-value &lt; 0.001, odds ratio (OR) 11.7, 95% confidence interval (CI) 3.2-43.0). On the other hand, HLA-DRB1(*)04:05 was associated with polyarticular JIA (corrected P-value &lt; 0.001, OR 2.9, 95% CI 1.7-4.8). We found an association of HLA-A(*)02:06 with susceptibility to JIA accompanied by uveitis, which might be considered a separate clinical JIA entity. We also found an association between HLA-DRB1(*)04:05 and polyarticular JIA. Thus, clinical subtypes of

DOI： 10.1038/jhg.2010.159

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Juvenile idiopathic arthritis (JIA) is one of the most common forms of pediatric chronic arthritis. JIA is a clinically heterogeneous disease. Therefore, the genetic background of JIA may also be heterogeneous. The aim of this study was to investigate associations between human leukocyte antigen (HLA) and susceptibility to JIA and/or uveitis, which is one of the most devastating complications of JIA. A total of 106 Japanese articular JIA patients (67 with polyarthritis and 39 with oligoarthritis) and 678 healthy controls were genotyped for HLA-A, -B and -DRB1 by PCR-sequence-specific oligonucleotide probe methodology. HLA-A(*)02:06 was the risk factor for JIA accompanied by uveitis after adjustment for clinical factors (corrected P-value < 0.001, odds ratio (OR) 11.7, 95% confidence interval (CI) 3.2-43.0). On the other hand, HLA-DRB1(*)04:05 was associated with polyarticular JIA (corrected P-value < 0.001, OR 2.9, 95% CI 1.7-4.8). We found an association of HLA-A(*)02:06 with susceptibility to JIA accompanied by uveitis, which might be considered a separate clinical JIA entity. We also found an association between HLA-DRB1(*)04:05 and polyarticular JIA. Thus, clinical subtypes of JIA can be classified by the presence of the specific HLA alleles, HLA-A(*)02:06 and DRB1(*)04:05.

DOI： 10.1038/jhg.2010.159

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.bbrc.2010.09.088

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/ng.624

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記述言語：英語  

Behçet&#039;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&#039;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).

DOI： 10.1038/ng.624

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記述言語：英語  

DOI： 10.1016/j.ophtha.2009.12.001

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記述言語：英語  

DOI： 10.1136/ard.2009.108571

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語  

DOI： 10.1016/j.clinph.2009.12.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

This study explores the effect of priming rhesus monkeys with an Ad5/35 vector expressing simian immunodeficiency virus (SIV) gag and gp120, and then boosting the animals with an modified vaccinia virus Ankara (MVA) vector encoding the same antigens after a 2-month interval. The animals were intravenously challenged with 100 TCID50 of highly pathogenic SIVmac239 virus 2 months after the booster vaccination. The priming vaccination induced robust SIV-specific cell-mediated and humoral immune responses, and boosting further enhanced the cellular immunity. Vaccination reduced peak and long-term viral loads by 1-2 logs for a period of &gt;6 months, as reflected by a reduction in both the SIV RNA and DNA levels. Of considerable interest, the immunized monkeys did not suffer from loss of CD4 T cells, particularly central memory CD4 T cells. These results demonstrate that prophylactic vaccination with Ad5/35 followed by MVA reduces viral replication and prevents CD4 T-cell loss, and that these effects may decrease the likelihood of disease progression. Gene Therapy (2010) 17, 4-13; doi: 10.1038/gt.2009.122; published online 17 September 2009

DOI： 10.1038/gt.2009.122

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/ar3005

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/nm.2018

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JOURNAL HARD TISSUE BIOLOGY  

To evaluate the efficacy of tooth extraction wound protection made of atelocollagen sponge (TRE-641), we observed healing in tooth extraction sites filled with TRE-641 and those filled with a control material, oxide cellulose. Subjects were 11 beagle dogs, with a total of 22 extraction sites. Both maxillary lateral incisors were carefully removed, and extraction wounds were filled with TRE-641 on one side and with oxidized cellulose sponge as control on the other side. Wound healing was observed, and the animals were sacrificed at 7, 14, and 28 days after surgery. We compared extent of bone formation, hematoma, inflammation, and graft material remaining between the two groups. At 7 days, newly formed bone extending from the floor and wall of the socket bone were seen in the TRE-641. Hematoma and inflammation were observed in the oxide cellulose. At 14 days, a small amount of TRE-641 remained. In the oxide cellulose group, a small amount of hematoma remained. At 28 days, the extraction socket was filled with newly formed bone in both groups. TRE-641 produced acceptable early phase bone healing at the tooth extraction site with no remnant graft material with sufficient bone formation of the tooth extraction wound.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JOURNAL HARD TISSUE BIOLOGY  

The aim of this study was to reveal the efficacy of autogenous bone mixed with beta-TCP. The mixtured graft materials at the maxillary sinus floor were observed.
Sinus floor augmentation with autogenous bone and beta-TCP was performed at six sites in three patients. The grafted site was observed with computed tomography (CT) at one, six and twelve months. The height and Hounsfield units (HU) of graft tissues were calculated using SIMplant. Dental implant surgery was then performed.
The increasing height of graft tissue at one month was approximately 13 mm and showed 20 % reduction at twelve months. Approximately 10 mm bone height was gained before implant surgery. The mean HU at six months showed the bone level HU. The HU at one month was reduced at six months and slightly increased mainly at the center of graft tissue at twelve months. At implant surgery, initial stability was adequate.
The mixture of autogenous bone and beta-TCP played a sufficient role for sinus floor augmentation, and it could be possible to reduce bone harvesting by using beta-TCP.

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DOI： 10.1097/IAE.0b013e3181a3b946

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1167/iovs.08-2530

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記述言語：英語  

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記述言語：英語  

DOI： 10.1093/rheumatology/kep077

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Beta-tricalcium phosphate (beta-TCP) was grafted into rat mandibular bone defects to assess its potential as a scaffold material for bone regeneration. For this purpose, beta-TCP (TCP), allogenic bone (Allograft), and allogenic bone combined with beta-TCP (Combined) were employed as graft materials. To the left side of the graft materials in the bone defects, platelet-rich plasma (PRP) was added. The rats were sacrificed at one, three, and five weeks. Bone formation rate (BFR), remaining beta-TCP rate (RTR), beta-TCP absorption rate (TAR), whole amount of beta-TCP (WTCP), and total rate of BFR and RTR (TBR) were measured. Combined showed equivalent BFR to Allograft at five weeks, and showed higher RTR at one week and higher BFR at five weeks than TCP. Combined with PRP showed higher TAR than that without PRP at three weeks. Therefore, combination with allogenic bone showed reduced beta-TCP absorption, hence enhancing the role of beta-TCP in bone regeneration. These findings suggested that beta-TCP is a better scaffold for bone regeneration if its early absorption is reduced when used in combination with an osteogenic material.

DOI： 10.4012/dmj.28.153

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記述言語：英語  

DOI： 10.1016/j.humimm.2008.10.014

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Purpose To ascertain and define the position of a potential disease susceptibility gene around D21S0083i prioritized during our previous whole genome case-control association analysis with 27158 microsatellite markers, in Japanese high-myopia patients.
Methods 520 high myopic patients and 520 healthy controls were genotyped using 39 SNPs distributed around D21S0083i on chromosome 21q22.3.
Results Only 1 SNP (rs2839471) of 39 SNPs was significant after correction for multiple testing (allele T: P = 0.00027, Pc = 0.01, OR = 1.684). The SNP ( rs2839471) did not reside in haplotype blocks constructed by the pair-wise linkage disequilibrium between the SNPs.
Conclusions The SNP ( rs2839471) is suggested to be located in the frequent recombinant region within UMODL1. Together this region might play a critical role for susceptibility to high myopia, and warrants further confirming studies and investigations as to the mechanisms by which UMODL1 may contribute to myopia.

DOI： 10.1038/eye.2008.152

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語  

DOI： 10.1097/ICB.0b013e31817f2e2e

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To describe vertical distraction osteogenesis of a scapular flap and removable lip support for oral rehabilitation after surgical creation of an ablative defect of the mandible. CASE REPORT: A 70-year-old man who was diagnosed with squamous cell carcinoma of the left lower gingiva underwent segmental mandibulectomy for tumor ablation and reconstruction with a scapular bone flap. To augment bone height of this flap, vertical distraction osteogenesis was performed. After denture fabrication, a removable lip support was placed between the implant-supported denture and the lower lip. RESULTS: The bone height of the scapular bone flap increased by 9 mm. Implants with adequate length could be placed in the distracted bone. The lip support was effective. Two years after masticatory loading, the implants remained stable. CONCLUSION: Vertical distraction osteogenesis of the scapular bone flap was suitable to facilitate postoperative functional and esthetic restoration after tumor resection. A removable lip support was also useful as a supplementary tool for oral rehabilitation.

DOI： 10.1016/j.tripleo.2008.05.048

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記述言語：英語  

Previously, we reported that phorbol 12-myristate 13-acetate (PMA)-activated protein kinase C (PKC) induced Rac1 activation in A172 glioblastoma cells. In this study, we investigated the mechanism of PMA-activated PKC-induced migration of glioblastoma cells by focusing on Rac1. PMA-induced formation of lamellipodia and focal complexes following migration were blocked by inhibiting Rac1 with small interfering RNA (siRNA), implicating Rac1 in PMA-induced glioblastoma cell migration. PMA-activated PKC induced phosphorylation of c-jun N-terminal kinase (JNK), one of the downstream effectors of Rac1. Immunohistochemical analysis showed that phosphorylated JNK was translocated to paxillin-containing focal complexes upon PMA stimulation and that Rac1 siRNA blocked these phenomena. These results suggest that phosphorylated JNK functions in cell migration and that JNK phosphorylation and translocation are mediated by Rac1. Furthermore, inhibition of Rac1 reduced phosphorylation of paxillin, a focal adhesion component and a downstream effector of JNK, at serine 178 (Ser178). Paxillin phosphorylation at this site has been shown to be involved in cell migration. Immunohistochemical analysis detected phosphorylation of paxillin (Ser178) in focal complexes upon PMA stimulation that was blocked by Rac1 siRNA. SP600125, a JNK inhibitor, also blocked PMA-induced phosphorylation of paxillin and aggregation of phosphorylated paxillin (Ser178) in focal complexes. In conclusion, paxillin is a critical downstream effector of Rac1 that may be involved in PMA-stimulated migration presumably by modulating the integrity of focal complex formation.

DOI： 10.3892/or_00000063

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1399-0039.2008.01111.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Toll-like receptor 4 (TLR4) is a transmembrane receptor that mediates immune responses to exogenous and endogenous ligands and interacts with heat shock proteins, which are reportedly involved in normal tension glaucoma (NTG). This study was undertaken to investigate whether TLR4 polymorphisms are associated with NTG. METHODS: Two hundred fifty Japanese patients with NTG and 318 Japanese healthy control subjects were recruited. Eight single-nucleotide polymorphisms (SNPs) in the TLR4 gene were genotyped, and allelic and phenotypic diversity was assessed between cases and control subjects. RESULTS: Strong linkage disequilibrium was observed among all SNPs (D' >or= 0.85), which were located in one haplotype block. With respect to allelic diversity, the minor allele of three SNPs (rs10759930, rs1927914, and rs7037117) carried a significantly increased risk of NTG. With regard to genotypic diversity, individuals with the minor allele of six SNPs (rs10759930, rs1927914, rs1927911, rs12377632, rs2149356, and rs7037117) had a 1.47- to 1.65-fold increased risk of NTG. rs7037117, located in the 3'-untranslated region of TLR4, was most strongly associated with NTG, and when incorporated into a haplotype with rs10759930, the strongest association was detected (P = 0.0038, P(c) = 0.0095). CONCLUSIONS: Multiple SNPs in the TLR4 gene are associated with the risk of NTG. This finding suggests that the ligands and/or cytokines involved in the TLR4 signaling network may be risk factors for the development of NTG.

DOI： 10.1167/iovs.07-1575

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：B M J PUBLISHING GROUP  

Aims: The aim of this study was to investigate the association between normal tension glaucoma and the candidate disease locus glaucoma 1, open angle, B (GLC1B) on chromosome 2. There are many reports describing the results of association or linkage studies for primary open angle glaucoma (POAG), with GLC1B as one of the loci associated with normal or moderately elevated intraocular pressure. However, there are few reports about the association of genes or defined genomic regions with normal tension glaucoma, which is the leading type of glaucoma in Japan. The GLC1B locus is hypothesized to be a causative region for normal tension glaucoma. Methods: Genomic DNA was extracted from whole blood of normal tension glaucoma (n= 143) and healthy controls (n= 103) of Japanese origin. Results: Fifteen microsatellite markers within and/or near to the GLC1B locus were genotyped, and their association with normal tension glaucoma was analysed. Two markers D2S2264 and D2S176 had significant positive associations. Conclusion: The D2S176 marker had the strongest significant association and it is located 24 kb from the nearest gene NCK2, which now becomes an important new candidate gene for future studies of its association with normal tension glaucoma.

DOI： 10.1136/bjo.2008.139980

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Corneal endothelial cell (CEC) transplantation should become clinically applicable in the near future. However, the immunologic changes after allo-CEC transplantation are poorly understood at present. We tried to establish a mouse model of allogeneic CEC transplantation for immunologic studies. METHODS: Benzalkonium chloride was injected into the anterior chamber of the eyes of recipient BALB/c mice to create bullous keratopathy. Full-thickness corneal transplantation was performed by using 4 types of corneas: BALB/c corneas (isograft group), BALB/c corneas denuded of CEC (no endothelium group), C3H/He mouse corneas (allograft group), and corneas reconstituted by seeding immortalized C3H/He mouse CECs onto BALB/c corneas denuded of endothelium (CEC allograft group). Eyes were observed with an operating microscope for 4 weeks after transplantation and were subjected to histologic examination and fluorescein microscopy. RESULTS: All corneal grafts were transparent in the isograft group (n = 12), whereas none of the grafts were clear by 4 weeks after transplantation in the no endothelium group (n = 13). Corneal grafts were transparent at 4 weeks in 75% of the CEC allograft group (n = 12). The histologic rejection rate was 0% in the CEC allograft group, which was significantly lower than in the allograft group (67%; n = 18; P < 0.01). CONCLUSIONS: We established a mouse allo-CEC transplantation model by using cultured cells. This model should be useful for studying the immunologic processes after CEC transplantation.

DOI： 10.1097/QAI.0b013e31815e722b

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

CARD15 was first identified as a susceptibility gene for Crohn&apos;s disease. More recently, CARD15 mutations were shown to be associated with the pediatric granulomatous inflammatory diseases, Blau syndrome and early-onset sarcoidosis (EOS). The aim of the present study was to evaluate whether CARD15 variants also play a role in patients with ordinary sarcoidosis other than EOS. We enrolled 135 Japanese sarcoidosis patients with uveitis as well as 95 healthy individuals and performed mutation analysis by direct sequencing of CARD15 exon 4. Direct DNA sequencing in the sarcoidosis patients showed eight CARD15 variants, including five novel mutations (13402C &gt; T, 13543C &gt; T, 13775C &gt; A, 13937G &gt; A, and 14079C &gt; T). Compared with healthy individuals, CARD15 mutations are not common in the Japanese patients with sarcoidosis. Based on the results, we examined the clinical manifestations in patients with sarcoidosis according to their CARD15 mutations. Sarcoidosis patients with these mutations have no specific clinical features with regard to course of the disease or disease severity. Our results indicate that in general, CARD15 mutations may not contribute to the risk of sarcoidosis.

DOI： 10.1111/j.1399-0039.2008.01043.x

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記述言語：英語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CHURCHILL LIVINGSTONE  

This paper describes a case of vertical distraction osteogenesis of a free vascularized osteocutaneous scapular flap in the reconstructed mandible before implant therapy. The patient was a 67-year-old woman with squamous cell carcinoma of the right lower gingiva. She underwent segmental mandibulectomy for tumor ablation and reconstruction with an osteocutaneous scapular flap. The distraction protocol, clinical course and implant therapy are presented. Through this procedure, the bone height of the scapular graft increased by 10 rum. Implants with adequate length could be placed in the distracted area. Two years after masticatory loading, the condition of these implants was stable. Vertical distraction osteogenesis of the scapular flap was considered effective when performed before implant therapy, to facilitate postoperative functional and esthetic restoration after tumor resection.

DOI： 10.1016/j.ijom.2008.01.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WICHTIG EDITORE  

PURPOSE. To report a spontaneous closure of a macular hole (MH) that was caused by a ruptured retinal arterial macroaneurysm (RAM).
METHODS. Observational case report. Clinical examinations and optical coherence tomographic (OCT) evaluations of the retina of a 73-year-old woman who developed a MH secondary to a ruptured RAM.
RESULTS. The first sign of a closure of the MH was the appearance of tissue bridging the MH in the OCT images. Later, OCT images showed a hyperreflective tissue, probably glial cells, that connected the bridging tissue to the RPE. Seven months after the first examination, the hyperreflective tissue was smaller and the shape of the foveal pit had recovered.
CONCLUSIONS. A spontaneous closure of a MH caused by a ruptured RAM can occur and surgical intervention was not necessary. The tissue bridging over the MH and the hyperreflective tissue connecting the bridging tissue to the RPE most likely were involved in the spontaneous MH closure.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS INC  

Purpose: To delineate features of ocular sarcoidosis. Methods: Comparison of the old and new Japanese guidelines for diagnosing ocular sarcoidosis by review of the medical records of 100 sarcoidosis patients and 147 patients with non-sarcoidosis uveitis. Results: The overall diagnostic sensitivity and specificity for the old guidelines were 80.0% and 45.6%; sensitivity and specificity for the new guidelines were 84.0% and 83.0%. Positive and negative predictive values and the likelihood ratios for a positive and negative test result improved. The new guidelines achieved more than 80% specificity for all categories. Conclusion: The new guidelines allow easier distinction of ocular sarcoidosis.

DOI： 10.1080/09273940802051100

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Purpose : We investigated whether or not use of the revised guidelines, Diagnostic Standard and Guidelines for Sarcoidosis 2006", resulted in improved diagnostic yield. Methods : We reviewed the medical records of 95 patients with suspected sarcoidosis diagnosed by the former guidelines retrospectively to see if they are diagnosed as having sarcoidosis when examined by revised guidelines. Results : Out of the 95 patients with "suspected sarcoidosis", 24(25.3%) were clinically diagnosed as sarcoidosis ("new clinically diagnosed sarcoidosis group"). They showed no difference in frequency of ocular findings compared with the 71patients who remained suspected sarcoidosis group. However, frequency systemic examination findings varied between the two groups. All the patients(100%) diagnosed as "new clinically diagnosed sarcoidosis group" turned out to be bilateral hilar lymphadenopathy (BHL) positive. Conclusions : The improved diagnostic yield was attributed to (l)addition of BHL to items of systemic examination findings that has been commonly implemented in ophthalmology providing high sensitivity and specificity, and (2) reduction of the condition requiring "3 or more items to be positive to "2 or more items to be positive .it was considered that the revised Diagnostic Standard and Guidelines for sarcoidosis has contributed to facilitate the diagnoses without increasing any burden on the part of patients.

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記述言語：英語   出版者・発行元：B M J PUBLISHING GROUP  

DOI： 10.1136/ard.2007.079871

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記述言語：英語  

Toll-like receptors (TLRs) mediate signaling that triggers activation of the innate immune system, whereas heme oxygenase (HO)-1 (an inducible heme-degrading enzyme that is induced by various stresses) suppresses inflammatory responses. We investigated the interaction between TLR and HO-1 in an inflammatory disorder, namely Behçet&#039;s disease.Thirty-three patients with Behçet&#039;s disease and 30 healthy control individuals were included in the study. Expression levels of HO-1, TLR2 and TLR4 mRNA were semiquantitatively analyzed using a real-time PCR technique, and HO-1 protein level was determined by immunoblotting in peripheral blood mononuclear cells (PBMCs) and polymorphonuclear leukocytes. In some experiments, cells were stimulated with lipopolysaccharide or heat shock protein-60; these proteins are known to be ligands for TLR2 and 4.Levels of expression of HO-1 mRNA were significantly reduced in PBMCs from patients with active Behçet&#039;s disease, whereas those of TLR4, but not TLR2, were increased in PBMCs, regardless of disease activity. Moreover, HO-1 expression in PBMCs from patients with Behçet&#039;s disease was repressed in the presence of either lipopolysaccharide or heat shock

DOI： 10.1186/ar2367

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/ar2367

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Ten subjects were asked to pay attention to green or to red, when each visual stimulus was presented as two small squares, one green and the other red. They were instructed to push a button with the right hand, when the attended color was on the right side, and to push a button with the left hand, when the attended color was on the left side. The P1/N1 peak-to-peak amplitudes of visual event-related potentials were significantly higher when subjects focused attention on green rather than on red. We assume that the attended color had the effect of modulating the P1/N1 components.

DOI： 10.1016/j.neulet.2007.09.075

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記述言語：日本語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Purpose: Behcet&apos;s disease (BD) is known to be associated with HLA-B*51 in many different ethnic groups. Recently, the major histocompatibility complex class I chain-related gene A (MICA), located near the HLA-B gene, has been proposed as a candidate gene for BD susceptibility in several ethnic groups. To compare the relative contribution of MICA polymorphisms and HLA-B*51 to BD in different ethnic groups, we studied MICA polymorphisms in Turkish BD patients.
Methods: Thirty-three Turkish BD patients and 65 healthy controls were enrolled for analysis of polymorphisms in the extracellular domains of MICA.
Results: The phenotype frequencies of MICA*009 were significantly higher in BD patients (75.8%) than in controls (29.2%) (P = 0.000015). HLA-B*51 was also significantly more frequent in BD patients (81.8%) than in controls (29.2%) (P = 0.0000007). A strong association existed between MICA*009 and HLA-B*51. To assess the confounding effect of MICA*009 on HLA-B*51, we performed a stratification analysis that showed that BD was distinctly associated only with HLA-B*51.
Conclusion: Our results indicate that the major susceptibility gene for BD is HLA-B*51 and that the association between MICA*009 and BD arises from a strong linkage disequilibrium with HLA-B*51. However, we suggest that MICA*009 likely elicits an immune effect secondary to BD. Jpn J Ophthalmol 2007;51: 431-436 (c) Japanese Ophthalmological Society 2007.

DOI： 10.1007/s10384-007-0473-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1399-0039.2007.00924.x

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記述言語：英語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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DOI： 10.1007/s00439-007-0388-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS INC  

The authors topically administered gatifloxacin (GFLX) into the eye before cataract surgery and measured the concentrations of this agent to determine its penetration into aqueous humor. Seventy-seven patients with age-related cataracts who underwent cataract surgery were enrolled in this study. They received 0.3% GFLX ophthalmic solution 4 times at 30-min intervals, beginning 2 h before surgery. Aqueous humor was aspirated from the anterior chamber and assayed for GFLX concentration using high-performance liquid chromatography. The mean intraoperative GFLX concentration in aqueous humor was 0.485 +/- 0.328 mu g/mL. GFLX level was 0.573 +/- 0.367 mu g/mL in elderly patients, at least 70 years of age, and was significantly higher than that (0.322 +/- 0.135 ug/mL) in the patients less than 70 years old. This concentration was close to or higher than the minimum inhibitory concentrations required to inhibit the growth of 90% of major pathogens of endophthalmitis (MIC90), such as Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcusfaecalis associated with poor prognosis, other than Staphylococcus epidermidis, Pseudomonas aerugi. nosa, and MRSA (methicillin-resistant S. aureus) in vitro. The GFLX concentrations found in aqueous humor samples were sufficient to kill bacteria other than S. epidermidis, P. aeruginosa, and MRSA in vitro.

DOI： 10.1080/09273940701346338

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語  

During the past decade, considerable efforts and resources have been devoted to elucidating the multiple genetic and environmental determinants responsible for hypertension and its associated cardiovascular diseases. The success of positional cloning, fine mapping, and linkage analysis based on whole-genome screening, however, has been limited in identifying multiple genetic determinants affecting diseases, suggesting that new research strategies for genome-wide typing may be helpful. Disease association (case-control) studies using microsatellite markers, distributed every 150 kb across the human genome, may have some advantages over linkage, candidate, and single nucleotide polymorphism typing methods in terms of statistical power and linkage disequilibrium for finding genomic regions harboring candidate disease genes, although it is not proven. We have carried out genome-wide mapping using 18,977 microsatellite markers in a Japanese population composed of 385 hypertensive patients and 385 normotensive control subjects. Pooled sample analysis was conducted in a 3-stage genomic screen of 3 independent case-control populations, and 54 markers were extracted from the original 18,977 microsatellite markers. As a final step, each single positive marker was confirmed by individual typing, and only 19 markers passed this test. We identified 19 allelic loci that were significantly different between the cases of essential hypertension and the controls.

DOI： 10.1161/01.HYP.0000257256.77680.02

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER TOKYO  

Purpose: To determine whether single-nucleotide polymorphisms (SNPs) within the transforming growth factor-beta 1 (TGF-beta 1) gene are associated with high myopia in Japanese. Previous studies have indicated that the gene expression products, regulators of the TGF-beta 1 gene, are involved in high myopia.
Methods: Genomic DNA samples were obtained from 330 Japanese patients with high myopia and 330 Japanese controls without high myopia who were chosen at random. SNPs were genotyped by the TaqMan system, using primer extension and polymerase chain reaction amplification.
Results: Ten SNPs were identified in the high-myopia patients and controls, with four of the ten SNPs having nonsynonymous changes. However, no statistical differences in the SNPs were detected between the high-myopia cases and the controls.
Conclusions: Sequence variants of the TGF-beta 1 gene were not associated significantly with high myopia, and further studies are needed to identify which genes are responsible for high myopia.

DOI： 10.1007/s10384-006-0417-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ASSOC RESEARCH VISION OPHTHALMOLOGY INC  

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.

DOI： 10.1167/iovs.06-0991

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/jmv.20779

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Purpose: To report three cases of pentrating corneal injury treated by primary insertion of intraocular lens (IOL). Cases: All were males aged 24, 29 and 55 years respectively. The injury was caused by a flying nail in 2 cases and by a piece of steel wire in the other. They were seen by us on day 1 or 2 of injury. All had penetrating corneal injury, ruptured anterior capsule, and traumatic cataract. Echography showed no abnormal findings in the 3 eyes. Best corrected visual acuity in the injured eye was 0.03, 0.5 and 0.5 respectively. The injured eye was treated by suture of corneal wound, phacoemulsification- aspiration, and IOL insertion. The power of IOL was calculated from data in the injured eye in 2 cases, and from those in the fellow eye in the other with extensive corneal wound. Results: There was no postoperative infection throughout. Final corrected visual acuity was 0.15, 0.5 and 1.2. Deviation of refraction from the calculated value was -0.35D, +0.2D and +0.1D respectively. Conclusion: Primary IOL insertion can be safe and effective for penetrating corneal injury with intract posterior capsule.

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記述言語：英語  

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.

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DOI： 10.1007/s00251-006-0155-9

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DOI： 10.1016/j.jdermsci.2006.05.010

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記述言語：英語  

DOI： 10.1038/sj.jid.5700203

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To increase the degree of specificity for nomenclature in the current "Guidelines for Diagnosis of Ocular Sarcoidosis" published in 1990 by the Diffuse Pulmonary Disease Research Committee of Japan. SUBJECTS AND METHODS: We reviewed the records of patients with uveitis from the Uveitis Clinic in the Department of Ophthalmology at Yokohama City University. Subjects were selected from the records of uveitis patients with histologically proven sarcoidosis (78), and others with non-sarcoidosis uveitis (81). We examined the sensitivity and specificity of suspected characteristics of ocular sarcoidosis in the current "Guidelines for Diagnosis of Ocular Sarcoidosis". RESULTS: The definition specificity was improved by changing anterior uveitis to granulomatous anterior uveitis, and by simplifying to cloudy mass (snowball, string of pearls) from the previous diffused/cloudy mass vitreous opacity (snowball, string of pearls), and also by changing from retinal peripheral vasculitis (in many cases retinal periphlebitis, also at times retinal peripheral arteritis) to retinal periphlebitis. CONCLUSION: This newly proposed "Guidelines for Diagnosis of Ocular Sarcoidosis" gives a much clearer definition of sarcoidosis, as well as improved nomenclature for specific categories of ocular symptoms.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING  

The present study represents the first four-digit allele genotyping of HLA-A and -B in Japanese Behcet's disease (BD) patients and controls using a new genotyping method (named the PCR-SSOP-Luminex method) to determine the association of certain HLA-A or -B alleles with BD. Peripheral blood lymphocytes were collected from 180 Japanese BD patients and 170 healthy controls. The genotype frequency of HLA-B*5101 was significantly increased in the patients (61.7%) as compared with the controls (15.9%) (Pc = 1 x 10(-16), OR = 8.5). When we recalculated the phenotype frequencies after excluding the HLA-B*51-positive patients and controls to account for the effects of the linkage disequilibrium and the abundance of the HLA-B*51 allele, the frequencies of HLA-A*2602 and HLA-B*3901 had a weak association in the patient group without HLA-B*51 as compared with the control group without HLA-B*51 (A*2602; Pc = 0.130, OR = 4.3, B*3901; Pc = 0.099, OR = 3.5). This study confirmed on the basis of using a new and more accurate genotyping method that Japanese BD patients have a strong primary association with HLA-B*5101. The significant increase of HLA-A*2602 and B*3901 in the patient group without HLA-B*51 suggests that these two alleles might also have some secondary influence on the onset of BD.

DOI： 10.1111/j.1399-0039.2006.00586.x

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We tested the current and newly proposed guidelines for the diagnosis of ocular sarcoidosis in 159 patients of uveitis seen during the foregoing 35 months. The series comprised 78 patients of histologically diagnosed sarcoidosis and 81 patients of other uveitis entities including 40 patients of Behçet disease and 21 patients of Vogt-Koyanagi-Harada disease. The current guidelines showed sensitivity of 84.6% and specificity of 38.3% for sarcoidosis. The newly proposed guidelines showed sensitivity of 83.3% and specificity of 60.5% for sarcoidosis by assuming 2 or more items for diagnostic criteria, and sensitivity of 69.2% and specificity of 87.7% by assuming 3 or more items for the criteria. The findings show that, if sensitivity is a major factor, a case may be diagnosed with sarcoidosis when 2 or more categories are fulfilled. If specificity is a major factor, a case may be diagnosed with sarcoidosis when 3 or more categories are fulfilled.

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記述言語：日本語   掲載種別：研究論文（国際会議プロシーディングス）  

We measured the power of accommodation after lens-preserving vitreous surgery in 10 eyes of 10 patients. The series comprised 8 eyes of rhegmatogenous retinal detachment and 2 eyes of diabetic retinopathy. Their age ranged from 28 to 41 years, average 36 years. The nuclear cataract was graded as G0 in 5 eyes and G1 in 5 eyes after Emery Little classification. Power of accommodation was measured using an polyaccommodometer. There was no progression in lens opacity during the follow-up period averaging 7.1 months after surgery. The postoperative power of accommodation averaged 7.6±3.7 diopters in operated eyes and 10.9±5.4 diopters in fellow eyes. The findings show that power of accommodation is preserved after vitreous surgery by short-term observation.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We have developed a new high-throughput, high-resolution genotyping method for the detection of alleles at the human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 loci by combining polymerase chain reaction (PCR) and sequence-specific oligonucleotide probes (SSOPs) protocols with the Luminex 100 xMAP flow cytometry dual-laser system to quantitate fluorescently labeled oligonucleotides attached to color-coded microbeads. In order to detect the HLA alleles with a frequency of more than 0.1% in the Japanese population, we created 48 oligonucleotide probes for the HLA-A locus, 61 for HLA-B, 34 for HLA-C, and 51 for HLA-DRB1. The accuracy of the PCR-SSOP-Luminex method was determined by comparing it to the nucleotide sequencing method after subcloning into the plasmid vector using 150 multinational control samples obtained from the International HLA DNA Exchange University of California Los Angeles. In addition, we performed the PCR-SSOP-Luminex method for HLA allele typing on DNA samples collected from 1,018 Japanese volunteers. Overall, the genotyping method exhibited an accuracy of 85.91% for HLA-A, 85.03% for HLA-B, 97.32% for HLA-C, and 90.67% for HLA-DRB1 using 150 control samples, and 100% for HLA-A and -C, 99.90% for HLA-B, and 99.95% for HLA-DRB1 in 1,018 Japanese samples. The PCR-SSOP-Luminex method provides a simple, accurate, and rapid approach toward multiplex genotyping of HLA alleles to the four-digit or higher level of resolution in the Japanese population. It takes only approximately 5 h from DNA extraction to the definition of HLA four-digit alleles at the HLA-A, HLA-B, HLA-C, and HLA-DRB1 loci for 96 samples when handled by a single typist.

DOI： 10.1007/s00251-005-0048-3

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記述言語：日本語   掲載種別：研究論文（国際会議プロシーディングス）  

We performed cataract surgery on 2 eyes with iris coloboma. Following phacoemulsification-aspiration and intraocular lens implantation, the defective iris was sutured using 10-0 polypropylene thread. Visual acuity improved after surgery in both cases. There was no change in visual field or corneal astigmatism. Both patients were satisfied with the cosmetic outcome. There were no complications throughout. The findings show that repair of colobomatous iris may be of value during cataract surgery.

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記述言語：英語  

DOI： 10.1097/01.ICL.0000152491.96155.B4

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記述言語：英語  

DOI： 10.1097/01.ICL.0000152490.39831.4D

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS INC  

Aims: We intravenously administered flomoxef sodium (FMOX) 120 minutes before cataract surgery, topically administered levofloxacin (LVFX) into the eyes four times at 30-minute intervals before surgery, and measured the aqueous humor concentrations of these agents to investigate their penetration into the aqueous humor and their efficacy in the prevention of postoperative endophthalmitis. Methods: Sixty-eight patients who underwent cataract surgery at the Department of Ophthalmology, Yokohama City University School of Medicine, or its affiliate, Kanazawa Hospital, Yokohama, were enrolled in this study. They received one or both of the following: 1.0 g FMOX via a 20-minute intravenous drip and LVFX ophthalmic solution applied four times at 30-minute intervals, both beginning two hours before the operation. Aqueous humor was aspirated from the anterior chamber and assayed for FMOX and LVFX concentrations using high-performance liquid chromatography ( HPLC). Results: The mean intraoperative FMOX and LVFX concentrations in the patients' aqueous humor were 1.21 +/- 0.63 mu g/ml and 0.69 +/- 0.47 mu g/ml, respectively. These concentrations sufficiently exceeded the MIC90 values against Staphylococcus epidermidis, S. aureus, and Propionibacterium acnes. Conclusions: The FMOX and LVFX concentrations in the aqueous humor sampling were adequate to kill bacteria in vitro. These drugs may have efficacy in the prevention of postoperative endophthalmitis in patients undergoing cataract surgery.

DOI： 10.1080/09273940590928607

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00535-004-1560-1

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記述言語：英語  

DOI： 10.1089/jop.2005.21.157

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記述言語：英語  

DOI： 10.1002/jmv.20295

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記述言語：英語  

DOI： 10.1016/j.exer.2004.09.010

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掲載種別：研究論文（学術雑誌）  

A 42-year-old female presented with blurring in her left eye since 2 weeks before. She had had herpes zoster 10 months before. Her husband had been dead for 4 years. Her corrected visual acuity was 1.2 in either eye. The left fundus showed diffuse retinal hemorrhages and exudates in the temporal periphery. Detection of cytomegalovirus (CMV) DNA in the aqueous humor led to the diagnosis of DNA retinitis. She showed decreased CD4+ T cells and anti-HIV antibody in the blood, leading to the diagnosis of AIDS. She was initially treated by systemic ganciclovir and later by highly active antiretroviral therapy (HAART). Recovery of CD4+ T cells was followed by immune recovery uveitis consisting of vitreous opacity and macular edema. Vitreous opacity healed spontaneously. Macular edema improved after retrobulbar injection of corticosteroid. There is a possibility that the activity of CMV retinitis at the start of HAART may be related to onset and severity of immune recovery uveitis.

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記述言語：英語  

DOI： 10.1016/j.jdermsci.2004.07.011

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: We examined the effects of the immunosuppressive neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) on rat endotoxin-induced uveitis, and to measure the expression of inflammatory cytokines and chemokines with and without the alpha-MSH treatment over the course of the disease. METHODS: We injected Lewis rats once with Salmonella typhimurium lipopolysaccharide (LPS) to induce uveitis. The rats were given intravenous injections of 250, 500 or 1000 microg of alpha-MSH. The eyes were examined over the next 24 h for inflammation. Aqueous humor was collected 6, 12 and 24 h after endotoxin injections and the number of infiltrating cells were counted in anterior chamber. In addition, we assayed the concentration of protein, nitric oxide, TNF-alpha, IL-6, MCP-1 and MIP-2. RESULTS: Rats injected with alpha-MSH showed a significant decrease in the number of infiltrating cells in anterior chamber. Moreover, alpha-MSH-treated rats with endotoxin-induced uveitis (EIU) showed significantly lower concentrations of protein, nitric oxide, proinflammatory cytokines and chemokines in their aqueous humor. Even the early stages of EIU were suppressed by the injection of alpha-MSH. CONCLUSIONS: Our results demonstrate that the immunosuppressive neuropeptide alpha-MSH inhibits the early induction events of endotoxin-induced inflammation in the eye; therefore, suppresses the subsequent infiltration of cells and intraocular production of inflammatory cytokines and chemokines in eyes. alpha-MSH has a possibility of being a therapeutic strategy for anterior uveitis.

DOI： 10.1016/j.intimp.2004.04.011

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記述言語：英語  

DOI： 10.1016/j.jdermsci.2003.12.004

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記述言語：英語  

DOI： 10.1016/S1044-7431(03)00220-3

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記述言語：英語  

DOI： 10.1167/iovs.03-0246

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記述言語：英語  

DOI： 10.1007/s00018-003-2333-3

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記述言語：英語  

DOI： 10.1167/iovs.02-0822

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL MUNKSGAARD  

Major histocompatibility complex (MHC) class I chain-related gene A and B (MICA and MICB) are located very close to HLA-B. MICA is reported to be strongly associated with Behcet's disease (BD), a multisysytemic inflammation disorder characterized by oral apthous ulcers, skin lesions and genital ulcers. These two molecules are highly conserved at the amino acid levels. To determine the function of MICB in vivo and the relationship between the expression of MICB and BD experimentally, we produced several transgenic mouse lines (termed CAG-MICB) expressing human MICB cDNA under a ubiquitous promoter. They exhibited a 50% increase in the number of white blood cells compared with their non-transgenic littermates and also exhibited a 10-20% reduction in body weight compared, with non-transgenic littermates. Exfoliation of the skin first appeared around 7 days after birth and disappeared after 2 weeks of age. This was repeatedly observed in the transgenic offspring of two independent CAG-MICB lines examined. Histopathological analysis of skin of young mice exhibiting skin abnormalities revealed hyperkeratosis of the epidermis and thickening of the granular layer with slight infiltration of inflammatory cells in the dermis without any vasculitis. Other remarkable abnormalities associated with BD have not been observed in the CAG-MICB lines. Furthermore, fluorescein angiography of eyes of the CAG-MICB lines was performed, but there were no marked changes of BD-related uveitis in the ocular fundus. These findings suggest that (i) MICB expression is related to temporary skin inflammation, and (ii) expression of MICB is not directly associated with BD.

DOI： 10.1034/j.1399-0039.2003.00014.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1034/j.1399-0039.2002.600506.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1034/j.1399-0039.2002.590207.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

To clarify the prevalence of open-angle glaucoma (OAG) and its relationship to refraction among a Japanese population with a broad range of ages including children and adolescents, an I-year epidemiological survey was conducted. The subjects of this study were 64,394 asymptomatic individuals who had attended the glasses and contact lens center in Yokohama, Japan from February 15, 1999 to February 14, 2000 and had been subjected to several optical examinations. The results of this study showed that the overall prevalence of OAG was 1.19% (1.14% for men, and 0.98% for women). Prevalence for children aged 6 to 14 of both sexes was approximately 0.5%. There were significant positive associations between the strength (diopter) of myopic refraction and OAG prevalence among all the examined subjects. (C) 2001 Elsevier Science Inc. All rights reserved.

DOI： 10.1016/S0895-4356(01)00388-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1034/j.1399-0039.2001.580306.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1034/j.1399-0039.2001.580202.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MUNKSGAARD INT PUBL LTD  

We previously reported a conserved haplotype of HLA B52-DR2 and a significantly high frequency of the major histocompatibility complex (MHC) class I chain-related gene A (MICA) transmembrane-short tandem repeat (TM-STR) 6 allele in Japanese patients with ulcerative colitis (UC). To examine the predominance of the MICA TM-STR 6 allele as a marker of the susceptibility to UC within the susceptible haplotype, the association of each allele with UC was estimated following stratification of the patients to control for any possible confounding effects of other alleles positively associated with UC. Sixty-four patients with UC and 236 unrelated healthy controls were included in this study. All subjects were Japanese. BLA-A, -B, -C, and -DR antigens were determined serologically. A triplet repeat polymorphism of the YWCA was determined by direct sequencing. To control for the effect of linkage disequilibrium, Mantel-Haenszel weighed odds ratios were calculated. Significantly higher phenotype frequencies of B52, WCA TM-STR 6, and DR2 were observed in patients with UC. Linkage disequilibria. among alleles associated with UC revealed that a B52 - MICA TM-STR 6 - DR2 haplotype was conserved in patients with UC, as in controls. When the association of HLA-1352 was estimated after patient stratification for the possible confounding effect of MICA TM-STR 6 or DR2, a strong significant association of B52 with UC was still observed. In contrast, no association with UC was observed for MICA TM-STR 6 or DR2, after stratification of the possible confounding effect of HLA-1352. These results imply that the significant increase in MICA TM-STR 6 in Japanese patients with UC is attributable to linkage disequilibrium with HLA-1352.

DOI： 10.1034/j.1399-0039.2001.580201.x

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DOI： 10.1034/j.1399-0039.2001.057005457.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：COLD SPRING HARBOR LAB PRESS  

Human chromosomes 1q21-q25, 6p21.3-22.2, 9q33-q34, and 19p13.1-p13.4 carry clusters of paralogous loci, to date best defined by the flagship 6p MHC region. They have presumably been created by two rounds of large-scale genomic duplications around the time of vertebrate emergence. Phylogenetically, the 1q21-25 region seems most closely related to the 6p21.3 MHC region, as it is only the MHC paralogous region that includes bona fide MHC class I genes, the CD1 and MR1 loci. Here, to clarify the genomic structure of this model MHC paralogous region as well as to gain insight into the evolutionary dynamics of the entire quadriplication process, a detailed analysis of a critical 1.7 megabase (Mb) region was performed. To this end, a composite, deep, YAC, BAG, and PAC contig encompassing all five CD1 genes and linking the centromeric +P5 locus to the telomeric KRTC7 locus was constructed. Within this contig a 1.1-Mb BAC and PAC core segment joining CD1D to FCER1A was fully sequenced and thoroughly analyzed. This led to the mapping of a total of 41 genes (12 expressed genes, 12 possibly expressed genes, and 17 pseudogenes), among which 31 were novel. The latter include 20 olfactory receptor (OR) genes, 9 of which are potentially expressed. Importantly, CD1, SPTA1, OR, and FCER1A belong to multigene families, which have paralogues in the other three regions. Furthermore, it is noteworthy that 12 of the 13 expressed genes in the 1q21-q22 region around the CD1 loci are immunologically relevant. In addition to CD1A-E, these include SPTA1, MNDA, IFI-16, AIM2, BL1A, FY and FCER1A. This functional convergence of structurally unrelated genes is reminiscent of the 6p MHC region, and perhaps represents the emergence of yet another antigen presentation gene cluster, in this case dedicated to lipid/glycolipid antigens rather than antigen-derived peptides.

DOI： 10.1101/gr.175801