蕪城 俊克

＜文献概要＞目的:近年,わが国におけるトキソプラズマ網脈絡膜炎の多数例での報告は少ない。近年のわが国における活動性のトキソプラズマ網脈絡膜炎の臨床像を明らかにすることを目的として検討を行った。対象と方法:2000年1月〜2019年3月に東京大学医学部附属病院眼科を受診し活動性のトキソプラズマ網脈絡膜炎と診断された患者13例14眼について,鬼木の分類に従って先天性・後天性に分類し,臨床像を検討した。結果:片眼例が12例,両眼例が1例であった。黄斑部病変が7眼,周辺部病変が7眼にみられた。先天性トキソプラズマ症は2例2眼で,平均発症年齢は17.5歳,2眼とも黄斑部病変であった。後天性症例は8例9眼で平均発症年齢は44.9歳,黄斑部病変4眼,周辺部病変5眼であった。不明例は3例3眼で平均発症年齢は61.0歳,3例とも周辺部病変であった。全例でアセチルスピラマイシン投与が行われ,7例でプレドニゾロン内服が併用された。経過中に再燃が4例でみられ,黄斑部型症例が3例,周辺部型症例が1例であった。結論:近年のトキソプラズマ網膜症は両眼性が少なく,先天性より後天性症例が多く,後天性症例で周辺型が半分以上を占めた。アセチルスピラマイシン治療は,安全で多くの症例で有効であった。

Purpose: To investigate the clinical features and visual outcome of young Japanese patients with uveitis.Methods: Patients younger than 18 years who presented with uveitis at the University of Tokyo Hospital between 2000 and 2018 were retrospectively reviewed.Results: The study comprised 98 patients whose mean age was 12.3 ± 3.8 years. Anterior uveitis was present in 52.0%, panuveitis in 37.8%, and posterior uveitis in 10.2%. The most common diagnosis was juvenile chronic iridocyclitis (JCI) (29.6%) followed by tubulointerstitial nephritis and uveitis syndrome (4.1%) and neuroretinitis (4.1%). Thirty-nine patients received systemic anti-inflammatory treatment. Among all subjects, 56% presented with ocular complications and 20% underwent ocular surgery. Visual acuity of 20/200 or less was observed in 6.2%. The common causes of decreased vision were hypotony, serous retinal detachment, and pupil disorder.Conclusions: JCI was the most common diagnosis. Hypotony, serous retinal detachment, and pupil disorder can lead to visual loss.

Purpose: To compare standard fluorescein angiography (FA) and ultra-wide-field (UWF) FA in evaluating sarcoid uveitis activity using the scoring system adopted by the Angiography Scoring for Uveitis Working Group (ASUWG).Methods: Standard and UWF FA images of 36 eyes with sarcoid uveitis were acquired on the same day. Three graders independently graded 72 FA images using the ASUWG scoring system. We evaluated inter-observer variability using the intra-class correlation coefficient (ICC) and compared scores of each angiographic sign.Results: The ICC was 0.77 for standard FA and 0.87 for UWF FA, with respective total scores of 12.0 and 14.6. UWF FA had higher scores than standard FA for optic disc hyperfluorescence, posterior retinal vascular staining and/or leakage, and peripheral capillary leakage.Conclusions: The scores for UWF FA had a higher ICC than those for standard FA in evaluating sarcoid uveitis. Peripheral capillary leakage scores were particularly high for UWF FA.

＜文献概要＞目的:Chronic Retinal Necrosis(CRN)患者の臨床像について検討する。対象と方法:2012年3月〜2015年12月に東京大学医学部附属病院眼科ぶどう膜炎外来を受診したCRN患者3例の臨床像を後ろ向きに検討した。結果:症例は65歳女性,66歳女性,67歳男性で,2例は片眼性,1例は両眼性であった。経過観察期間はそれぞれ47ヵ月,15ヵ月,66ヵ月であった。免疫不全因子は免疫抑制薬内服中1例,糖尿病1例であった。HIV感染例は認めなかった。全例前房水PCR検査でサイトメガロウイルスDNAが陽性であった。全例に白色小型角膜後面沈着物,硝子体混濁,網膜動脈白鞘化,網膜動静脈炎,網膜出血を認めた。網膜滲出斑は2例に認めた。治療としてガンシクロビル硝子体注射(3例),バルガンシクロビル内服(2例)などの抗ウイルス療法を施行した。全例に網膜無灌流領域を認め,1例に網膜光凝固を施行した。最終観察時の矯正視力は全例1.0以上であった。結論:CRNの3例を経験した。抗ウイルス療法を終了するまで長期間要する症例もあったが,視力予後は良好であった。ウイルス性を疑う閉塞性網膜血管炎に対しては,治療最初期に眼内液PCR検査とぶどう膜炎精査を施行したうえで適切な抗ウイルス治療を行う必要がある。CRN患者に対しては,抗ウイルス療法だけではなく,網膜無灌流領域の確認と治療を行い,新生血管発生の予防に努めなければならない。

ぶどう膜炎の病態は動物疾患モデルを用いた研究などにより理解は進み,その成果はtumor necrosis factor(TNF)阻害薬などの新しい治療薬に応用されているが,依然として不明な点も多い.眼炎症性疾患であるBehcet病(以下,ベーチェット病),網膜血管炎,眼内リンパ腫に対して,その病態解明と新規治療法の開発に向けた我々の研究を報告する.1.ベーチェット病の臨床像とリンパ球を活性化するHLA関連抗原の解析 ベーチェット病ぶどう膜炎は内因性ぶどう膜炎の中でも最も重篤なぶどう膜炎である.我々は新しいベーチェット病ぶどう膜炎の活動性評価法としてBehcet's disease ocular attack score 24(BOS24)を作成し,視力変化と有意に相関することを示した.一方,ヒト白血球抗原(HLA)はリンパ球への抗原提示に必要な分子で,ベーチェット病ぶどう膜炎ではHLA-B*5101またはA*2601陽性症例が約8割を占める.我々はHLA-A*2601を持つ症例は,視力予後不良例が多いことを報告した.またHLA-B*51のポケット構造と結合力の高いアミノ酸配列を三次元的分子力学シミュレーションにより選定する方法を考案し,ベーチェット病患者リンパ球との反応性が報告されている既知の抗原における親和性の高いアミノ酸配列を推定した.それらのペプチドはベーチェット病患者の末梢血リンパ球の増殖を有意に促進した.HLAと抗原ペプチドの親和性がリンパ球の活性化に直接関与する可能性が示唆された.2.ぶどう膜炎における網膜血管炎の新しい理解 網膜血管炎はぶどう膜炎やさまざまな網膜疾患でみられ,フルオレセイン蛍光眼底造影(FA)での画像所見上,動脈炎,静脈炎,毛細血管炎に分類される.我々はさまざまなぶどう膜炎疾患のFA画像を検討し,感染性ぶどう膜炎では非感染性ぶどう膜炎と比べて網膜動脈炎および動静脈閉塞が高率にみられることを見出した.この機序を明らかにするために,活動期のさまざまなぶどう膜炎疾患の硝子体液中の炎症性サイトカインを網羅的に検討した.ぶどう膜炎疾患では共通してTNF-αやケモカインが上昇しており,眼内リンパ腫ではinterleukin(IL)-10,急性網膜壊死ではinterferon(IFN)-α2,細菌性眼内炎ではIL-6,IL-17A,顆粒球コロニー刺激因子(G-CSF)が特異的に上昇していた.ぶどう膜炎の原因疾患によって硝子体液中の炎症性サイトカインの発現パターンに特徴がみられることが明らかとなった.3.眼内リンパ腫の診断と治療 近年,ぶどう膜炎に占める眼内リンパ腫の割合は増加しており,他のぶどう膜炎疾患と誤診されやすく,脳中枢神経系病変を来しやすいため生命予後の不良な疾患である.本疾患の明確な診断基準および標準治療は未だ確立していない.我々は,眼内原発リンパ腫に対し,メトトレキサート硝子体内注射,全身化学療法,予防的低線量全脳照射を組み合わせた治療の前向き研究を行い,本疾患の生命予後を改善し,脳再発を抑制できることを示した.一方,二次性眼内リンパ腫は眼・脳中枢神経系以外の臓器を原発としたリンパ腫が眼内に進展した状態である.二次性眼内リンパ腫の臨床像および治療成績を後ろ向きに検討したところ,さまざまな治療にもかかわらず再燃を繰り返し,きわめて予後不良であることが明らかとなった.眼内リンパ腫,特に二次性眼内リンパ腫に対する新たな治療法の確立が急務である.(著者抄録)

PURPOSE: To clarify the prevalence of secondary glaucoma (SG) and its speed of progression in patients with herpes simplex virus (HSV)-anterior uveitis (AU), varicella zoster virus (VZV)-AU, and cytomegalovirus (CMV)-AU. METHODS: In total, 170 patients with herpetic AU were enrolled in this retrospective observational case series. Patients with visual field (VF) defects and glaucomatous disc abnormalities were diagnosed with SG. Moreover, the speed of SG progression was defined as decreasing mean deviation (MD) values per year. SG prevalence and annual MD-value decrease were compared among the three types of herpetic AU. RESULTS: SG prevalence was 16%, 9%, and 72% in patients with HSV-AU, VZV-AU, and CMV-AU, respectively. Patients with CMV-AU had the highest SG prevalence (odds ratio = 3.15; 95% confidence interval = 1.15-8.65; P < 0.05). Furthermore, the annual MD-value change was significantly higher in SG caused by CMV-AU than in that caused by HSV/VZV-AU (-2.6 ± 2.4 dB/year and -0.45 ± 0.54 dB/year, respectively; P < 0.05). CONCLUSIONS: Our results demonstrated that patients with CMV-AU may have a higher risk and faster speed of progression of SG than patients with HSV/VZV-AU. Therefore, clinicians should monitor glaucoma onset and VF-defect progression in patients with CMV-AU.

PURPOSE: Retinal vasculitis and occlusive changes are important signs of posterior uveitis and are possible diagnostic markers for uveitis. However, the frequency of arteritis and phlebitis in various uveitis entities, including infectious uveitis (IU) and non-infectious uveitis (NIU), have not been systematically investigated. STUDY DESIGN: Retrospective. METHODS: We investigated the frequency of retinal vascular inflammatory and occlusive changes in patients with IU and NIU. The study included 283 patients with intermediate, posterior, or pan-uveitis who were diagnosed with IU (presumed tuberculous uveitis, acute retinal necrosis, cytomegalovirus retinitis, human T-cell lymphotropic virus type 1-associated uveitis, toxoplasmic retinitis, syphilitic uveitis, rubella virus-associated uveitis, fungal endophthalmitis, and bacterial endophthalmitis) or NIU (sarcoidosis, Behçet's disease, Vogt-Koyanagi-Harada disease, human leukocyte antigen-B27-associated uveitis, systemic lupus erythematosus retinopathy, psoriatic uveitis, rheumatoid arthritis/collagen disease-associated uveitis, multiple sclerosis-associated uveitis, and sympathetic ophthalmia). All patients underwent fluorescein angiography (FA) and color photography examinations of the fundus. Presence of inflammatory and occlusive changes was determined by FA images. RESULTS: Significantly higher positive ratios of phlebitis, vein sheathing, vein occlusion, arteritis, artery sheathing, artery occlusion, and avascular areas were observed in the IU group than in the NIU group (p < 0.05). Notably, the discrepancy between IU and NIU was prominent with regard to retinal arterial changes (arteritis [57.9% vs 11.2%], inflammatory artery sheathing [33.7% vs 0%], and artery occlusion [22.1% vs 3.7%], respectively; p < 0.0001). CONCLUSION: Findings of vasculitis and occlusion, especially in retinal arteries, in FA strongly suggest an infectious origin of active uveitis.

Treatment of uveitis is complicated because of its multiple aetiologies and elevation of various inflammatory mediators. To determine the mediators that are elevated in the vitreous humor according to the aetiology of the uveitis, we examined the concentrations of 21 inflammatory cytokines, 7 chemokines, and 5 colony-stimulating/growth factors in vitreous samples from 57 eyes with uveitis associated with intraocular lymphoma (IOL, n = 13), sarcoidosis (n = 15), acute retinal necrosis (ARN, n = 13), or bacterial endophthalmitis (BE, n = 16). Samples from eyes with idiopathic epiretinal membrane (n = 15), which is not associated with uveitis, were examined as controls. Heat map analysis demonstrated that the patterns of inflammatory mediators in the vitreous humor in eyes with uveitis were disease-specific. Pairwise comparisons between the 5 diseases showed specific elevation of interferon-α2 in ARN and interleukin (IL)-6, IL-17A, and granulocyte-colony stimulating factor in BE. Pairwise comparisons between IOL, ARN, and BE revealed that levels of IL-10 in IOL, RANTES (regulated on activation, normal T cell expressed and secreted) in ARN, and IL-22 in BE were significantly higher than those in the other 2 types of uveitis. These mediators are likely to be involved in the immunopathology of specific types of uveitis and may be useful biomarkers.

AIMS: To investigate susceptible human leukocyte antigen (HLA) alleles and their associations with clinical features in Thai patients with Behçet's disease (BD). METHOD: Eighteen HLA-A and 36 HLA-B alleles were determined in 42 Thai BD patients and 99 healthy controls (HCs) by reverse line blot assay, and reconfirmed by MICRO SSP assay. RESULTS: The BD patients had significantly higher allele frequency (AF) of HLA-B*51 than the HCs (13.10% vs 5.05%, P = .025). The AF of HLA-A*26, -A*26:01 and -B*51:01 also was higher and almost reached statistical significance (5.59% vs 1.52%, P = .054, 5.95% vs 1.52%, P = .054 and 10.71% vs 4.04%, P = .051, respectively). However, the BD patients had significantly higher AF of either HLA-A*26:01 or -B*51:01 (16.67% vs 5.56%, P = .005), or -A*26:01 or -B*51X (19.05% vs 6.56%, P = .003). The AF of HLA-B*51:01 and -B*51X increased significantly in -A*26:01 non-carrier BD patients (12.16% vs 4.17%, P = .024 and 14.86% vs 5.21%, P = .019, respectively); and that of HLA-A*26:01 was significantly higher in -B*51X non-carrier BD patients (7.58% vs 1.67%, P = .034). HLA-B*51:01 associated significantly with the presence of posterior uveitis and visual impairment (18.18% vs 2.50%, P = .031 for both conditions). HLA-B*51:01 was not observed in BD patients with gastrointestinal involvement or arthritis. Furthermore, the AF of HLA-B*51:01 was significantly higher in HLA-A*26:01 non-carrier BD patients without arthritis (17.30% vs 0%, P = .050). CONCLUSION: HLA-B*51:01 was a susceptible allele for Thai BD patients, and associated with posterior uveitis and visual impairment. HLA-A*26:01 was another susceptible allele in HLA-B*51X non-carrier patients. The protective effect of HLA-B*51:01 on arthritis needs further investigation.

Department of Ophthalmology, Tokyo Metropolitan Geriatric Hospital Purpose I To report clinical features of 13 cases with toxoplasmic retinochoroiditis. Cases " We observed 13 cases of toxoplasmic retinochoroiditis during 19 years through 2019 at University of Tokyo Hospital. The series comprised 9 males and 4 females. It was unilateral in 12 cases and bilateral in one. It was congenital in 2 cases, acquired in 9 eyes of 8 cases, and was uncertain in 3 cases. Age of onset was 17.5 years, 44.9 years, and 61.1 years respectively. Only the macula was involved in congenital cases. The macula was involved in 4 and the peripheral fundus was involved in 5 of acquired cases. Only the peripheral fundus was involved in uncertain cases. All cases were treated by peroral ace-tylspiramycin. Seven cases received, additionally, prednisolone. Recurrence occurred in 4 cases, including 3 cases of macular and one case of peripheral involvement.Conclusion ' Toxoplasmic retinochoroiditis in the present series was characterized by unilateral involvement, preponderance of acquired than congenital origin, and more frequent involvement of peripheral fundus in acquired cases. Systemic treatment with acetylspiramycin was safe and effective in the majority of cases.

Purpose: To report 3 patients with chronic retinal necrosis and cytomegalovirus infection. Cases: The cases were 2 females aged 65 and 66 years, and one male aged 67 years. Two were unilaterally and one was bilaterally affected. One had diabetes mellitus and one had been treated by immunosuppressive drugs for hepatitis C. No case was positive for HIV. Findings and Clinical Course: All the affected eyes showed keratic precipitates, vitreous opacity, retinal artery occlusion, retinal vasculitis, and retinal hemorrhage. Polymerase chain reaction was positive for cytomegalovirus-DNA in aqueous humor in all the eyes. All the cases were treated by antiviral therapy including intravitreal ganciclovir. Two cases were treated by oral valganciclovir. Nonperfusion retinal area was present in all the eyes and were treated by photocoagulation. Cases were followed up for 15 to 66 months, average 47 months. Best-corrected visual acuity was 1.0 or better in all the eyes at the end of follow-up. Conclusion: Visual outcome was favorable in all the 3 cases of chronic retinal necrosis and cytomegalovirus infection. Laser photocoagulation appeared to be beneficial to nonperfused retinal areas.

Purpose: We investigated clinical characteristics of ocular Behçet's disease (BD) patients treated in the 1990s and the 2000s.Methods: We retrospectively examined records of 68 newly arrived patients with ocular BD followed for more than 4 months during the 2000s and compared to those of 107 patients during the 1990s. Patient profiles, ocular and systemic symptoms, frequency of ocular attacks, BD ocular attack score 24-6 months (BOS24-6M), best-corrected visual acuity (BCVA), and immunomodulatory treatment were noted.Results: Clinical characteristics in the 2000s showed increases in iridocyclitis type, intestinal-, vasculo-, and neuro-BD cases, oral corticosteroid, methotrexate, and infliximab therapy usage, cataract and glaucoma surgery, and pseudophakia, and decreases in BOS24-6M and cyclophosphamide usage. BCVA of 20/30 or better at the final visit was slightly increased in the 2000s.Conclusions: Milder ocular BD tendency was seen in cases in the 2000s, whereas the incidence of special type of BD might be increasing.

Recently developed technologies have revealed that the genomes of many organisms produce transcripts that do not encode proteins. These are called non-coding RNAs. Long non-coding RNAs (lncRNAs) are important regulators of the expression of their target genes at the levels of transcription, translation, and degradation. Multiple studies have demonstrated a role for lncRNAs in various biological responses, including pathogenic infection. Upon pathogenic infection, the expression levels of lncRNAs are dynamically altered, suggesting that lncRNAs are involved in the host immune response or propagation of pathogens. In this review, we focused on host lncRNAs that are involved in pathogenic infection. Some host lncRNAs act as host defense molecules to prevent pathogenic proliferation, while others are utilized by the pathogen to enhance the propagation of pathogens.

PURPOSE: To investigate the clinical features of patients with ocular inflammation associated with relapsing polychondritis in Japan. METHODS: Ocular findings, systemic symptoms, and therapies were analysed retrospectively. RESULTS: Nine of 11 patients had scleritis (diffuse scleritis: six patients, posterior scleritis: two patients, episcleritis: one patient) and two patients had anterior uveitis. All cases were bilateral, and ten patients experienced recurrent episodes. Auricular chondritis was the most common systemic symptom. Ten patients were administered systemic steroids, and five patients were administered other immunosuppressive medications for severe systemic symptoms. At their last visit, none of the patients had decreased visual acuity that resulted from relapsing polychondritis-associated ocular inflammation. CONCLUSIONS: Ocular inflammation is often bilateral and recurring. Patients with ocular inflammation must be questioned regarding systemic symptoms so that the signs of relapsing polychondritis are not overlooked. Early diagnosis and prompt, appropriate treatment are important because relapsing polychondritis is a potentially lethal disease.

AIMS: International criteria for the diagnosis of ocular sarcoidosis (OS) was established by the first International Workshop on Ocular Sarcoidosis (IWOS) and validations studies revealed certain limitations of the criteria. To overcome the limitations, revised IWOS criteria was established in an international meeting. This manuscript was aimed at reporting the revised IWOS criteria. METHODS: A consensus workshop was carried out to discuss and revise the IWOS criteria. The workshop was held on 27 April 2017, in Nusa Dua, Bali, Indonesia. Prior to the workshop, a questionnaire proposing revised criteria and consisting of one item for differential diagnosis, seven items for ocular clinical signs, 10 items for systemic investigations and three categories of diagnostic criteria was circulated to 30 uveitis specialists. Questionnaire items with over 75% support were taken as consensus agreement; items with below 50% support were taken as consensus disagreement and items with 50%-75% support were discussed at the workshop. Of the latter items, those supported by two-thirds majority in the workshop were taken as consensus agreement. RESULTS: The survey and subsequent workshop reached consensus agreements of the revised criteria for the diagnosis of OS as follows: (1) other causes of granulomatous uveitis must be ruled out; (2) seven intraocular clinical signs suggestive of OS; (3) eight results of systemic investigations in suspected OS and (4) three categories of diagnostic criteria depending on biopsy results and combination of intraocular signs and results of systemic investigations. CONCLUSIONS: Revised IWOS criteria were proposed by a consensus workshop.

Purpose: To clarify the relationship between fluorescein angiography (FA) leakage after infliximab therapy and ocular attack relapse in patients with ocular Behçet's disease (BD). Methods: Patients with ocular BD were divided into two groups based on the presence (Group 1) or absence (Group 2) of ocular attacks after IFX therapy. FA leakage was evaluated by FA score in each of the optic discs, macula, large retinal vessels, and capillary vessels. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the relationship between FA score after IFX therapy and ocular attack relapse. Results: The areas under the curves obtained from the ROC curve of optic disc score and capillary vessels score after IFX therapy were 0.867 (95% confidence interval [CI]: 0.788-0.946) and 0.788 (95% CI: 0.649-0.927), respectively. Conclusions: FA leakage in the optic disc and capillary vessels after IFX therapy was strongly related to ocular attack relapse.

This study aimed to clarify the association between the retinal leakage site on fluorescein angiography (FA) and subfoveal choroidal thickness (SCT) measured using enhanced depth imaging optical coherence tomography (EDI-OCT). Twenty-two patients with Behçet's uveitis were retrospectively selected in this study. They underwent EDI-OCT and FA in both the active and convalescent phases. The associations of the changes between the active and convalescent phases in SCT and in FA leakage in various retinal areas (total retina, peripheral retina, macula, and optic disc) were examined. The changing rates of SCT between the two investigated phases were significantly associated with the changes in total FA leakage scores (y = 1.79X+ 11.7, r2 = 0.210, p < 0.05). Furthermore, the changes in FA leakage scores in the macula were correlated with the changing rates in SCT (y = 3.72X+ 13.9, r2 = 0.219, p < 0.05). By contrast, there were no significant associations between the changes in SCT and those in leakage from the peripheral retina or the optic disc on FA. These findings demonstrate that SCT may reflect macular vasculitis as determined using FA, and SCT measurement could be a non-invasive method to investigate inflammation near the macula in Behçet's uveitis.

Purpose: To report a case of syphilitic uveitis that simulated central serous chorioretinopathy. Cese: A 56-year-old male presented with central scotoma in the right eye. He had been treated with photocoagulation for central serous chorioretinopathy in the left eye 2 years before. Findings and Clinical Course: Best-corrected visual acuity (BCVA) was 1.2 in either eye. The right eye showed a yellowish lesion that was identified as serous retinal detachment by optical coherence tomography (OCT). Serous retinal detachment resolved 2 weeks later but BCVA decreased to 0.15. The vitreous body in the right eye showed signs of uveitis. Both eyes showed hyperemia of optic disc and retinal vasculitis. Rapid plasma reagin and Treponema pallidum hemagglutination assay were positive and were suggestive of syphilitic uveitis. He received intravenous benzylpenicillin for 2 weeks followed by peroral amoxicillin for 2 weeks. The fundus lesion in both eyes gradually disappeared. BCVA was 1.2 right and 0.8 left after 3 weeks of treatment. Conclusion: The observed findings in the left eye appears to be acute suphilitic posterior placoid chorioretinitis (ASPPC) that simulated central serous chorioretinopathy.

＜文献概要＞目的:中心性漿液性脈絡網膜症(CSC)との鑑別を要した,梅毒性ぶどう膜炎の1例を報告する。症例:患者は56歳,男性。左眼のCSCに対して光凝固術の既往がある。2年後に右眼に中心暗点を自覚し来院した。右眼黄斑部に黄白色病変とOCTでその部位に一致した滲出性網膜剥離(ERD)を認め,CSCが疑われた。2週間後には黄斑部のERDは消失したが,矯正視力が0.2から0.15と低下していた。右眼硝子体セル1+,右優位の視神経乳頭発赤がみられ,蛍光眼底造影検査で両眼視神経乳頭過蛍光と網膜血管炎を認めた。血液検査で梅毒血清反応(RPR)は32倍,トレポネーマ抗体は陽性が判明し,梅毒性ぶどう膜炎と診断した。髄液細胞数の増加もあり,神経梅毒の合併が考えられた。左眼にも黄斑部に黄白色病変が出現し,急性梅毒性後部脈絡網膜炎(ASPPC)と診断した。駆梅療法としてベンジルペニシリン2,400万単位/日を2週間持続点滴の後,アモキシシリン750mg/日を2週間内服した。視神経乳頭発赤は軽快し,左眼のASPPCも消失した。治療開始6ヵ月後にはRPRは2倍まで低下した。結論:梅毒性ぶどう膜炎の初期では前房内炎症を認めないこともあり,CSCとの鑑別が困難なことがある。視神経乳頭発赤やOCTでの網膜外層の異常,および蛍光眼底造影での網膜血管炎所見は梅毒性ぶどう膜炎を疑う所見であると考えられた。

Background: Adalimumab, a human anti-tumor necrosis factor-ɑ monoclonal antibody, was recently reported to be effective in lowering the risk of recurrence of noninfectious uveitis. This is the first case series of adalimumab administrations for relentless placoid chorioretinitis (RPC) patients. Case Presentation: We report 2 cases of RPC where successful treatments were achieved with adalimumab. A 34-year-old woman developed conjunctival hyperemia, mild iridocyclitis, and multiple atrophic retinal lesions, along with exudative changes that were widespread from the posterior pole to peripheral retina in both eyes. The diagnosis of RPC was made based on the characteristic recurrences of choroiditis despite systemic corticosteroid and cyclosporine. Adalimumab therapy was introduced to the patient, and thereafter no recurrence was observed while tapering the immunosuppressive agents. The second case was a 22-year-old man with visual deterioration in both eyes who exhibited widespread multiple chorioretinal atrophic lesions. We diagnosed the case as RPC based on characteristic clinical findings and recurring chorioretinitis during tapering of systemic corticosteroids. Adalimumab therapy was administrated, and immunosuppressant dosage was successfully reduced without any recurrences. Conclusions: In the current two RPC cases, adalimumab was quite effective and useful to reduce the dosages of systemic immunosuppressants. Further study is necessary to confirm the effectiveness of adalimumab in RPC patients.

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

A 73-year-old female with a past medical history of breast cancer, who 10 years earlier experienced complete remission, complained of bilateral visual field disturbances and photopsia, 2 months prior. Tumour recurrence and metastatic lesions were not found during the medical examination, but antibodies against recoverin were detected in her serum. Despite immunosuppressive treatment with prednisolone and plasmapheresis, rapid and diffuse degeneration of the patient's photoreceptors and deterioration of her visual field were observed. This is a rare case of cancer-associated retinopathy with a long interval (10 years) between the diagnosis of the malignancy and visual loss.

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.

Uveitis is a sight-threatening disease. Up to 35% of patients may have impaired vision. Inflammation of the uvea tissue has more than 60 etiologies. Previous reports have shown that 20-40% of uveitis cases were noninfectious. Some of them may be associated with systemic rheumatological and autoimmune diseases but some may affect the eyes only. The epidemiology and clinical situations of some specific uveitis entities vary worldwide because they are influenced by genetic, ethnic, environmental, and socioeconomic factors. The Asia-Pacific region comprises more than 30 countries. Epidemiology and patterns of uveitis vary greatly in this region. However, some uveitis entities, such as Behcet's disease, sarcoidosis, and Vogt-Koyanagi-Harada disease, are more common in this region. Many studies on the epidemiology, risk factors, and immune pathogenesis of this disease have been conducted. In this article, we review the epidemiology of noninfectious uveitis and special situations of these three uveitis entities in the Asia-Pacific region.

Purpose: To report a case of acute retinal necrosis (ARN) caused by varicella-zoster virus (VZV) in an elderly patient with ocular sarcoidosis after oral corticosteroid indication. Methods: Retrospective case report. Results: A 75-year-old male with a past history of ocular sarcoidosis came with blurred left vision. Ocular findings in the left eye were consistent with ocular sarcoidosis, while no inflammation in the right eye. On day 14, intraocular inflammation in the left eye resolved by topical corticosteroid, but inflammatory cells were found in the right eye. Suspecting recurrence of ocular sarcoidosis, systemic corticosteroid was initiated. On day 21, inflammation worsened, and the presence of extended yellowish white peripheral retinal lesion in the right eye suggested ARN. Polymerase chain reaction (PCR) testing using ocular fluid detected 3.0 × 107 copies/ml of VZV DNA. Conclusions: In the case of poor response to immunosuppressive therapy in elderly uveitis, infection including ARN should be considered. Immediate PCR testing for pathogen screening is required.

Several proteins have been proposed as candidate auto-antigens in the pathogenesis of Behçet's disease (BD). In this study, we aimed to confirm the cellular responses to candidate peptide autoantigens with high affinity for the HLA-B*51:01 molecule using computerized binding predictions and molecular dynamics simulations. We identified two new candidate peptides (HSP65PD, derived from heat shock protein-65, and B51PD, derived from HLA-B*51:01) with high-affinity to the HLA-B*51:01 binding pocket using the Immune Epitope Database for Major Histocompatibility Complex-I Binding Prediction and molecular dynamics simulations. The peptide-induced proliferation of lymphocytes from patients with BD, sarcoidosis, Vogt-Koyanagi-Harada disease (VKH) with panuveitis, systemic scleroderma (SSc) without uveitis, and healthy controls (HC) was investigated using the bromodeoxyuridine assay. The proliferative response of leukocytes to HSP65PD was significantly higher in BD (SI 1.92 ± 0.65) than that in sarcoidosis (SI 1.38 ± 0.46), VKH (SI 1.40 ± 0.33), SSc (SI 1.32 ± 0.31), and HC (SI 1.27 ± 0.28) (P = 0.0004, P = 0.0007, P < 0.0001, P < 0.0001, respectively, Mann-Whitney's U-test). The proliferative response of leukocytes to B51PD was also higher in BD than that in sarcoidosis, VKH, SSc without uveitis, and HC, whereas no significant differences were observed among the five groups in response to a control peptide derived from topoisomerase 1. A significantly higher response to HPS65PD and B51PD was observed in the HLA-B*51:01-positive patients with BD than in the HLA-B*51:01-negative patients. In conclusion, two peptides that had high affinity to HLA-B*51:01 in computerized binding prediction showed significantly higher response in HLA-B*51:01-positive patients with BD, indicating the usefulness of computerized simulations for identifying autoreactive peptides to HLAs.

BACKGROUND: The distribution of uveitis varies with genetic, ethnic, geographic, environmental, and lifestyle factors. Epidemiological information about the patterns of uveitis is useful when an ophthalmologist considers the diagnosis of uveitis. Therefore, it is important to identify the causes of uveitis over the years in different regions. The purposes of this study were to characterize the uveitis patients who first arrived at the University of Tokyo Hospital in 2013-2015, and to analyze the changes in the patterns of uveitis from 2004 to 2012 to 2013-2015. METHODS: We retrospectively identified 750 newly arrived patients with uveitis who visited the Uveitis Clinic in the University of Tokyo Hospital between January 2013 and December 2015, using clinical records. We extracted data on patient age, sex, diagnosis, anatomic location of inflammation, laboratory test results of blood and urine, and chest X-ray and fluorescein fundus angiography findings for each patient. In addition, we compared these data with those from 2004 to 2012 to analyze the changes in the patterns of uveitis. RESULTS: A definite diagnosis was established in 445 patients (59.3%). The most common diagnoses were herpetic iridocyclitis (7.5%), sarcoidosis (6.1%), Behçet's disease (4.4%), Vogt-Koyanagi-Harada disease (4.1%), and intraocular lymphoma (4.1%). The most frequent unclassified type of uveitis was suspected sarcoidosis (22.3%). Analysis of the changes in the patterns of uveitis in the central Tokyo area from 2004 to 2012 to 2013-2015 revealed notable increasing trends of herpetic iridocyclitis and intraocular lymphoma, and increasing trends of bacterial endophthalmitis, fungal endophthalmitis, and juvenile chronic iridocyclitis. In contrast, the frequency of sarcoidosis, Behçet's disease, and Vogt-Koyanagi-Harada disease decreased. CONCLUSIONS: The patterns of uveitis changed considerably from 2004 to 2012 to 2013-2015. Continuous investigations about the epidemiology of uveitis are needed to diagnose uveitis more accurately.

RATIONALE: Chronic uveitis with immunosuppressive agents could develop chronic herpetic retinitis with varicella-zoster virus (VZV) or herpes simplex virus (HSV). Ocular Epstein-Barr virus (EBV) infection develops uveitis and vitritis, but the clinical feature of EBV retinitis is not typical as a viral retinitis. EBV retinitis is rare, and only a few cases of EBV retinitis have been reported. Herein, we describe a case of retinitis with EBV and VZV which were the primary viruses verified by multiplex polymerase chain reaction (PCR). PATIENT CONCERNS: A 75-year-old woman suffered from sudden visual loss in the left eye. She had been diagnosed with rheumatoid arthritis. At presentation, visual acuity (VA) was 20/400 in the left eye. Slit lamp examination disclosed fine white keratic precipitates with infiltrating cells and dense vitreous opacities in the anterior segment and vitreous. Fundus photographs showed multifocal chorioretinal scars in macula and peripheral retina, and granular lesions surrounding arcade vessels. DIAGNOSES: Ocular toxoplasmosis was primarily suspected. INTERVENTIONS: However, serological test showed negative of toxoplasmosis. Therefore, a diagnostic and therapeutic vitrectomy was performed. Vitreous fluid sample was used for multiplex PCR for detection of human herpesvirus (HHV) -1 to -8, toxoplasmosis and toxocariasis. OUTCOMES: Multiplex PCR detected 5.8 × 10 copies/mL of EBV-deoxyribonucleic acid (DNA), and 3.6 × 10 copies/mL of VZV-DNA in the sample. Therefore, we could diagnose the unidentified panuveitis a retinitis associated with double infection of EBV and VZV. At 85 days after the vitrectomy, VA of the left eye recovered to be 20/16. LESSONS: Elderly patients under immunosuppression may be susceptible to develop retinitis associated with infection of multiple HHVs, and multiplex PCR is an excellent tool to diagnose an unidentified panuveitis resembling this case.

PURPOSE: To evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. DESIGN: Phase 3, open-label, multicenter clinical trial extension (VISUAL III). PARTICIPANTS: Adults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF. METHODS: Patients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 through 78. MAIN OUTCOME MEASURES: Disease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff. RESULTS: Of 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65%) patients had active uveitis; 60% (145/242, NRI) achieved quiescence at week 78, and 66% (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35%) patients had inactive uveitis; 74% (96/129, NRI) achieved quiescence at week 78, and 93% (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR; left and right eyes; as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5-1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials. CONCLUSIONS: Patients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified.

PURPOSE: To investigate the clinical characteristics of Japanese patients with scleritis STUDY DESIGN: Retrospective study METHODS: The clinical records of 123 patients with scleritis, who presented to the University of Tokyo Hospital between January, 2004 and December, 2015, were retrospectively reviewed. RESULTS: The cohort comprised 55 men and 68 women (mean age, 57.8±16.4 years), of which 76 showed anterior diffuse scleritis, 17 showed anterior nodular scleritis, 10 showed anterior necrotizing scleritis, and 20 showed posterior scleritis. The underlying etiology was identified in 39 patients. Autoimmune diseases were present in 32 patients, including eight with rheumatoid arthritis, seven with antineutrophil cytoplasmic antibody-associated vascular disease, and six with relapsing polychondritis. Ocular hypertension was the most common ocular complication (41%), followed by anterior chamber cells (38%). Fifty-three percent of patients required systemic immunosuppressive medication. Systemic corticosteroids were the most commonly used medication (45%), followed by methotrexate (11%). A, decrease in vision was observed in one-third of patients with anterior necrotizing scleritis or posterior scleritis, of which secondary glaucoma and optic neuritis were the major causes. CONCLUSION: Autoimmune diseases were present in 26% of patients. One-third of patients with anterior necrotizing scleritis or posterior scleritis experienced decreased vision, mostly due to secondary glaucoma and optic neuritis. Therefore, controlling intraocular pressure by methods such as administration of steroid-sparing immunosuppressive medication and appropriate treatment for posterior scleritis are essential for scleritis treatment.

BACKGROUND: Fuchs' uveitis (FU) is occasionarlly complicated with heavy vitreous opacity. We have performed vitrectomy procedures to remove vitreous opacity in affected patients as part of differential diagnosis for primary vitreoretinal lymphoma (PVRL). CASE PRESENTATION: We retrospectively reviewed the clinical records of five patients who first visited the Uveitis Clinic of the University of Tokyo Hospital between 2009 and 2013, were diagnosed with FU and underwent a vitrectomy for removal of dense vitreous opacity. All were diagnosed as FU by ocular findings and elevation of Goldmann-Witmer coefficient (GWC) value for the rubella virus (RV) antibody. In examinations of the vitreous body, cytological diagnosis, elevation of IL-10/IL-6 ratio, and the kappa/lambda ratio in flow cytometry findings were negative in all cases, whereas monoclonal immunoglobulin heavy chain (IgH) gene rearrangement was positive in 4 cases and negative in 1 case. CONCLUSIONS: Although monoclonal IgH gene rearrangement is thought to be a reliable biomarker for PVRL, a high percentage of vitreous specimens from our FU patients showed pseudo-positive results. Ophthalmologists must take care regarding possible pseudo-positive findings when performing differential diagnosis between FU and PVRL. Combinations of results of cytological diagnosis, IL-10/IL-6 ratio, kappa/lambda ratio, and IgH gene rearrangement may be necessary for a definitive diagnosis of PVRL and differentiation from FU.

Candida lusitaniae is an uncommon cause of candidiasis in humans. Ocular manifestations of C. lusitaniae infection have not been reported. C. lusitaniae is either intrinsically resistant to amphotericin B or can acquire such resistance. We describe a case of bilateral endophthalmitis due to C. lusitaniae bloodstream infection in a liver transplant patient with rectal cancer. The patient suffered fungemia and endophthalmitis and was treated with liposomal amphotericin B. The isolate was identified as C. lusitaniae by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, the system based on biochemical tests, and sequencing of the internal transcribed spacer region. The minimal inhibitory concentrations were 0.06 μg/mL for amphotericin B and 2.0 μg/mL for fluconazole. Repeat blood cultures were negative and the endophthalmitis improved following treatment with liposomal amphotericin B. However, the treatment was changed to fluconazole due to nephrotoxicity. No recurrence occurred after completion of treatment.

Vitreous opacity (VO) is a common feature of intermediate uveitis, posterior uveitis, and panuveitis. Fundus observation is critical for determining the etiology of uveitis, however, is often interfered with VO. In these clinical settings, vitrectomy contributes to a correct diagnosis and guides alternative management strategies. The purpose of this study was to evaluate the diagnostic yield and surgical outcome of vitrectomy in uveitic patients with VO and compare the visual outcome between infectious and noninfectious uveitis. Forty-five eyes with uveitis-associated VO underwent diagnostic and therapeutic vitrectomy, and etiological diagnosis of uveitis was confirmed in 34 of 45 eyes (75.6%). The diagnoses were infectious uveitis in 13 eyes (28.9%), noninfectious uveitis in 21 eyes (46.7%), and unidentified uveitis in 11 eyes (24.4%). Visual acuity (VA) improvement rates at 6 months after surgery were 69.2%, 76.2%, and 90.9% in the infectious, noninfectious, and unidentified uveitis groups, with no significant difference among 3 groups. Significant decrease in inflammation score after vitrectomy was observed only in the infectious uveitis group. This study demonstrated that diagnostic vitrectomy for inflammatory eyes with VO of unknown etiology was effective in infectious and noninfectious uveitis, and the therapeutic effect of VA improvement was observed in both types of uveitis.

A 31-year-old woman developed bilateral painful red eyes. A slit-lamp examination revealed anterior diffuse scleritis. She had been diagnosed with palmoplantar pustulosis 2 years before. Further evaluation revealed hyperostosis of the sacroiliac joint and inflammation of the bilateral sternoclavicular joints and right sternocostal joint. Ultimately, she was diagnosed with SAPHO syndrome by rheumatologists after excluding other causative diseases. Scleritis associated with SAPHO syndrome is relatively uncommon. An identification of any systemic symptoms and early consultation with rheumatologists are key to making an early and correct diagnosis.

PURPOSE: We report three cases of ocular inflammation and polymyalgia rheumatica without concomitant giant-cell arteritis. METHODS: Report of three cases. RESULTS: Polymyalgia rheumatica onset was at a mean age of 66.7 years, and ocular inflammation, which developed 7-21 months later, was bilateral in all patients. Ocular inflammation presented as episcleritis, scleritis, or anterior uveitis, and it emerged during the tapering of low-dose prednisolone prescribed for polymyalgia rheumatica in all patients. Recurrence of ocular inflammation was observed in two patients. CONCLUSIONS: Ocular inflammation associated with polymyalgia rheumatica was often bilateral and occurred during steroid tapering. Although this presentation is relatively uncommon, polymyalgia rheumatica should be considered in the differential diagnosis of older patients presenting with ocular inflammation, especially those with proximal myalgia and elevated inflammatory markers.

Primary intraocular lymphoma (IOL) has a propensity for central nervous system (CNS) relapse within 2 years of initial diagnosis, affecting clinical outcome. To reduce CNS relapse, we performed the combination treatment protocols of intravitreal methotrexate injections, methotrexate-based systemic induction chemotherapy and consolidation high-dose cytarabine and reduced-dose whole brain radiation therapy (rdWBRT, 23·4 Gy) for B-cell primary IOL with or without newly diagnosed CNS involvement. All patients underwent longitudinal brain magnetic resonance imaging (MRI) and cognitive assessment for evaluation of treatment-induced leucoencephalopathy. Seventeen patients initiated and 16 completed the protocol treatment. CNS relapse occurred in 2 patients and intraocular relapse in 3. Four-year progression-free survival (PFS) was 74·9% and 4-year overall survival (OS) was 86·3%, with a median follow-up period of 48·9 months. Of 11 patients without CNS involvement, 1 had CNS relapse and 3 intraocular relapse, and 4-year PFS and OS was 72·7% and 88·9%, respectively. Although white matter abnormalities shown by MRI were significantly increased at 4 years after rdWBRT, only one patient developed mild cognitive impairment. The combination of intravitreal chemotherapy, prophylactic systemic chemotherapy and rdWBRT for primary IOL showed a potential to reduce CNS relapse rate and improved 4-year PFS and OS without increase of cognitive dysfunction.

目的:3施設における病型別の視神経炎の臨床像の違いについて検討する。対象および方法:視神経炎と診断された57例84眼を対象として、脳脊髄病変の有無および血液検査の結果から、特発性群、自己抗体陽性群、抗Aquaporin-4抗体陽性群(抗AQP4群)、多発性硬化症群(multiple sclerosis:MS群)の4群に病型分類した。病型ごとに性別、発症時年齢、罹患眼(両眼・片眼)、眼痛の有無、初診時のステロイド治療の有無、自己抗体の陽性率、再発率、再発頻度、経過中最低矯正視力、最終矯正視力を比較した。結果:MS群と抗AQP4群は女性が多かった。特発性群と自己免疫性群は眼痛が多く、抗AQP4群、MS群は眼痛が少なかった。抗AQP4群は他群に比べ経過中最低矯正視力、最終矯正視力ともに低かった。抗AQP4群は脳脊髄病変の有無によらず経過中最低矯正視力、最終矯正視力に差は認めなかった。結論:抗AQP4抗体陽性の場合、脳脊髄病変の有無にかかわらず、経過中最低矯正視力、最終矯正視力ともに、他の視神経炎に比べ不良であると考えられた。(著者抄録)

A 68-year-old male presented with blurred vision in both eyes. Ophthalmoscopy revealed bilateral prominent disc swelling and vitritis. No systematic neurological symptoms were observed. Magnetic resonance imaging revealed bilateral meningeal enhancement of the optic nerve. Small cell carcinoma was found, and antibodies against collapsing response-mediating protein-5 (CRMP-5) were detected in the serum. Ophthalmological manifestations disappeared during a decrease in tumour size with treatment for the malignancy. This case report describes this rare case of anti-CRMP-5 antibody-positive paraneoplastic perioptic neuritis without neurological symptoms, showing that prompt diagnosis and timely treatment of the underlying tumour are crucial to prevent increased levels of autoantibodies and irreversible damage to the nervous system.

PURPOSE: To investigate the frequency of conditions of newly arrived patients with uveitis from 2010 to 2012 and compare this frequency with that since 2004. METHODS: We retrospectively analyzed clinical records of patients who visited the outpatient clinic from January 2010 to December 2012, and compared them with those from 2004-2009. RESULTS: From 2010 to 2012, 695 new patients with uveitis visited Tokyo University Hospital, with a definite diagnosis made in 431 (62.0%). The most common diagnosis was scleritis (8.3%), followed by sarcoidosis (8.1%); herpetic iridocyclitis (5.5%); Behçet disease (4.6%); Vogt-Koyanagi-Harada disease (4.0%); acute anterior uveitis (3.7%); Posner-Schlossman syndrome (3.6%); intraocular malignant lymphoma (3.0%); and bacterial endophthalmitis (1.9%). The most frequent unclassified type of uveitis was sarcoidosis-suspected (14.8%). CONCLUSIONS: When compared with years 2004-2009, the present series showed an increasing trend of intraocular malignant lymphoma, bacterial endophthalmitis, and chronic iridocyclitis, and a notable increase in chronic iridocyclitis in young girls, with decreasing trends of scleritis and Vogt-Koyanagi-Harada disease.

BACKGROUND: In 2014, Pang et al. reported three cases with vitelliform submaculopathy as a preceding lesion of primary intraocular lymphoma (PIOL). Here, we report a case with an atypical presentation of PIOL who initially presented with vitelliform submaculopathy, vitreous haze and preripheral retinal focus. CASE PRESENTATION: A 73-year-old female initially visited another hospital with a chief complaint of acute reduced vision in the right eye. Funduscopic examination of the right eye showed a yellowish retinal lesion at the fovea with vitreous haze and retinal foci scattered in the peripheral region. Spectral-domain optic coherence tomography (SD-OCT) revealed a hyperreflective subretinal debris above the retinal pigment epithelium (RPE) at the fovea, suggesting vitelliform submaculopathy. Vitrectomy was performed to improve visualization of the retinal lesions and for examination of PIOL. Vitreous cytology was class III and cytokine analysis of vitreous fluid showed increased IL-10 and an IL-10/IL-6 ratio >1, suggesting PIOL. Thereafter, there was a sub-RPE infiltration of presumed lymphoma in the nasal retina, and PCR analysis of anterior chamber fluid indicated IgH gene rearrangement, leading to diagnosis of PIOL. Three months later, there was complete disappearance of the vitelliform submacular lesion, with resultant disruption and thinning of the outer retinal layers on SD-OCT images. CONCLUSIONS: Clinicians should be aware of atypical manifestations of PIOL such as vitelliform submaculopathy and peripheral retinal foci with vitreous haze. The patient's unusual funduscopic changes are findings that have not reported in patients with PIOL.

AIMS: To investigate the ability of the Behçet's disease ocular attack score 24 (BOS24) scoring system to predict visual acuity (VA) in patients with ocular Behçet's disease. DESIGN: This is a retrospective study. METHODS: We included 91 eyes of 50 patients with ocular Behçet's disease (33 males, 17 females) who were referred to our hospital between 1986 and 2008 with >5 years follow-up. Total BOS24 scores over a 5-year period, BOS24-5Y, were calculated as the sum of BOS24 scores for each attack over the 5-year study period for each eye. Change in VA was defined as change in best-corrected visual acuity (BCVA) from the first remission to the last remission at the end of the target period. Factors related to change in VA (age, gender, BCVA at the first remission, total number of immunosuppressive medications and total number of ocular attacks during the 5-year period and BOS24-5Y) were evaluated using a linear mixed model. RESULTS: BCVA (logarithm of the minimal angle resolution) deteriorated from 0.16±0.30 (mean±SD) to 0.21±0.37 over the 5-year study period, but there was no statistical difference. The total number of ocular attacks during the 5-year period and BOS24-5Y scores were 10.0±7.9 and 36.8±40.8, respectively. Linear mixed-model analysis revealed that BOS24-5Y was the most important index for VA deterioration, followed by BCVA at the first remission. CONCLUSIONS: BOS24-5Y was found to be a significant positive prognostic index for VA deterioration in patients with ocular Behçet's disease.

経過中に急激な漿液性網膜剥離の進行を認めた眼内悪性リンパ腫の1例を経験した。症例は73歳、男性。中枢神経原発悪性リンパ腫に対してメトトレキサート大量療法を施行され、寛解していたが、3年後に右眼の視力低下を自覚。矯正視力は右眼指数弁、左眼1.0。初診から2週間後に右眼下方に胞状の漿液性網膜剥離が出現し、4週間後に全剥離となった。左眼の後極部にも漿液性網膜剥離を生じ、矯正視力は0.02に低下した。右眼生検の結果、硝子体細胞診class III、IL10は80,500pg/mlと高値を示し、中枢神経原発悪性リンパ腫の既往から、眼内悪性リンパ腫と診断した。メトトレキサート硝子体注射10回、メトトレキサートとデキサメサゾンの髄腔内注射3回施行し、両眼の漿液性網膜剥離は速やかに消失した。漿液性網膜剥離をみた場合には、眼内悪性リンパ腫の可能性を忘れてはならない。メトトレキサート硝子体注射はその治療に有効であった。(著者抄録)

OBJECTIVES: Behçet's disease (BD) is a systemic inflammatory disorder polarised to the Th1 and Th17 immune systems. Allergic diseases are polarised to the Th2 immune system. The aim of the present study is to investigate the prevalence of allergic diseases in patients who have BD. METHODS: The study involved a large-scale interview survey of Japanese patients with BD at 21 institutes of ophthalmology; 353 patients (255 males and 98 females) were recruited for this study. We analysed the history of allergic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), bronchial asthma (BA) and drug/food allergies (FA). RESULTS: Oral aphthous ulcers, ocular lesions, skin lesions, genital ulcers, arthritis, neurological lesions, intestinal lesions, deep vein thrombosis and epididymitis were reported in 95.8%, 98.6%, 72.5%, 44.8%, 13.9%, 6.8%, 6.2%, 3.7% and 1.4% of the patients, respectively. It was also reported that 73 patients (20.7%) had histories of allergic diseases: AD (5 cases, 1.4%), AR (36 cases, 10.2%), BA (19 cases, 5.4%) and FA (30 cases, 8.5%). This percentage was significantly lower than in a survey that Japan's Ministry of Health, Labour and Welfare conducted for healthy population (47.6%) (odds ratio = 0.29, 95% confidence interval = 0.22-0.38, p=4.9×10-22). Frequencies of posterior/pan-uveitis, relatively severe ocular findings, and visual prognosis were not affected by a history of allergic diseases in BD. CONCLUSIONS: Patients with BD had fewer complications from allergic diseases than did the entire population of Japan.

PURPOSE: To determine the involvement of sympathetic activity in choroidal neovascularization (CNV) using laser-induced CNV in a mouse model. METHODS: We investigated changes in the proportions of intraocular lymphocytes, granulocytes, and three macrophage subtypes (Ly6Chi, Ly6Cint, and Ly6Clo) after laser injury in mice using flow cytometry, and evaluated CNV lesion size in mice lacking inflammatory cells. Further, we evaluated the lesion size in mice administered the β3 receptor antagonist, splenic-denervated and splenectomized mice. We also assessed changes in the proportions of intraocular macrophages and peripheral blood monocytes in splenic-denervated and splenectomized mice. Lastly, lesion size was compared between splenic-denervated mice with or without adoptive transfer of macrophages following laser injury. After Ly5.1 mice spleen-derived Ly6Chi cells were transferred into Ly5.2 mice, the proportions of intraocular Ly5.1+Ly6Chi cells were compared. RESULTS: In WT mice, the proportion of CD4+ T cells recruited into the eye increased progressively from day 3 to day 7 after laser injury, whereas, intraocular CD8+ T cells did not change significantly. Proportions of B220+ cells, granulocytes, and two subtypes of intraocular macrophages (Ly6Chi and Ly6Clo) peaked at day 3 following laser injury. In contrast, Ly6Cint/loCD64+ subtype showed a significantly higher percentage at day 7 after laser injury. There were no differences in lesion size between CD4-/-or Rag2-/-mice and controls, whereas lesion size was significantly reduced in CCR2-/- mice and clodronate liposome-treated mice. CNV lesion area was significantly reduced in mice with β3 blocker treatment, splenic-denervated and splenectomized mice compared with controls. Intraocular Ly6Chi macrophages were also reduced by splenic denervation or splenectomy. Adoptive transfer of spleen-derived Ly6Chi cells increased the lesion size in splenic-denervated mice. Compared with controls, intraocular donor-derived Ly6Chi cells recruited into the eye were reduced in splenic-denervated and splenectomized mice. CONCLUSIONS: Although lymphocytes had little effect on CNV formation, Ly6Chi macrophages/monocytes exacerbated CNV in mice. Sympathetic activity might contribute to CNV via the recruitment of macrophages to the eye.