今日の臨床サポート 今日の臨床サポート

著者: 坂井潤一 坂井眼科

監修: 沖波聡 倉敷中央病院眼科

著者校正/監修レビュー済:2023/01/25
患者向け説明資料

改訂のポイント:
  1. ぶどう膜診療ガイドライン2019に準拠するよう改訂を行った。

概要・推奨   

  1. ぶどう膜炎は虹彩炎、毛様体炎、脈絡膜炎の総称であるが、それらが単独で生じることは少なく、さらに隣接する網膜や硝子体にまで炎症が及んでいることも多い。
  1. 主な自覚症状として、充血、眼痛、霧視、羞明、飛蚊症があり、他覚所見として、毛様充血、角膜後面沈着物、前房内細胞浸潤、前房蓄膿、虹彩結節、虹彩萎縮、虹彩後癒着、隅角結節、虹彩前癒着(隅角)、硝子体混濁、網膜血管炎、網膜出血、網膜滲出斑、黄斑浮腫、視神経乳頭の発赤・腫脹などがみられる。
  1. 診察に当たっては、眼科検査機器を駆使してなるべく多くの情報を集めることが確定診断につながる。
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。
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病態・疫学・診察 

疾患情報  
  1. ぶどう膜炎は虹彩炎、毛様体炎、脈絡膜炎の総称であるが、それらが単独で生じることは少なく、さらに隣接する網膜や硝子体にまで炎症が及んでいることも多い。ときには炎症の主座が網膜のこともあり、内眼炎あるいは眼内炎症(intraocular inflammation)と呼んだほうが適切という意見が主流となりつつある。しかし、一般的にはぶどう膜炎(uveitis)という用語が定着しており、現在も広く用いられている。ぶどう膜炎は眼所見や成因により30種類以上の疾患単位に分けられる。
  1. 主な自覚症状として、充血、眼痛、霧視、羞明、飛蚊症があり、他覚所見として、毛様充血、角膜後面沈着物、前房内細胞浸潤、前房蓄膿、虹彩結節、虹彩萎縮、虹彩後癒着、隅角結節、虹彩前癒着(隅角)、硝子体混濁、網膜血管炎、網膜出血、網膜滲出斑、黄斑浮腫、視神経乳頭の発赤・腫脹などがみられる。
  1. ぶどう膜炎はその炎症部位から前部、中間部、後部、そして汎ぶどう膜炎に分類され、また炎症所見の性状から肉芽腫性、非肉芽腫性ぶどう膜炎に分けられる。ぶどう膜炎の成因には種々の感染病原体、炎症性全身疾患が関与していると考えられている。特徴的な眼所見や臨床検査結果などにより成因による分類ができた時点で診断が確定する。しかし、約30%の症例は分類不能(同定不能)とされる。
  1. ぶどう膜炎の解剖学分類:表<図表>
  1. ぶどう膜炎の分類:表<図表>
  1. ぶどう膜炎の種類:表<図表>
  1. 発症年齢、性差、出身地、また生活習慣(食事の嗜好、ペット飼育の有無、海外渡航歴、性交渉など)に特徴のあるぶどう膜炎があり、これらに関する問診が確定診断の糸口になる場合もある。
  1. ぶどう膜炎の全眼科疾患に占める頻度は、大学病院で約2%とされる。治療に用いるステロイド薬の副作用もあいまって白内障、緑内障の合併頻度が高く、また黄斑変性を残す例も多く、中途失明の主要な原因となっている。
問診・診察のポイント  
問診:
  1. 問診は2回行う。

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最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
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文献 

Hiroshi Takase, Annabelle A Okada, Hiroshi Goto, Nobuhisa Mizuki, Kenichi Namba, Nobuyuki Ohguro, Koh-Hei Sonoda, Makoto Tomita, Hiroshi Keino, Takeshi Kezuka, Reo Kubono, Kazuomi Mizuuchi, Etsuko Shibuya, Hiroyuki Takahashi, Ryoji Yanai, Manabu Mochizuki
Development and validation of new diagnostic criteria for acute retinal necrosis.
Jpn J Ophthalmol. 2015 Jan;59(1):14-20. doi: 10.1007/s10384-014-0362-0. Epub 2014 Dec 10.
Abstract/Text PURPOSE: The purposes of this study are to develop and validate new diagnostic criteria for acute retinal necrosis (ARN) based on the ocular findings, clinical course, and virologic testing of intraocular fluids.
SUBJECTS AND METHODS: The Japanese ARN Study Group, comprising 8 uveitis specialists and 1 statistician, was formed to develop new diagnostic criteria for ARN. The criteria used a combination of clinical features consistent with ARN including 6 early-stage ocular findings ([1a] anterior chamber cells or mutton-fat keratic precipitates; [1b] yellow-white lesion(s) in the peripheral retina [granular or patchy in the early stage, then gradually merging]; [1c] retinal arteritis; [1d] hyperemia of the optic disc; [1e] inflammatory vitreous opacities; and [1f] elevated intraocular pressure), 5 clinical courses ([2a] rapid expansion of the retinal lesion(s) circumferentially, [2b] development of retinal breaks or retinal detachment, [2c] retinal vascular occlusion, [2d] optic atrophy, and [2e] response to antiviral agents), and the results of virologic testing of intraocular fluids by means of either polymerase chain reaction or the Goldmann-Witmer coefficient for herpes simplex virus or varicella zoster virus. Various combinations of findings were analyzed to maximize the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The criteria were then used to retrospectively analyze patients who had been diagnosed as having ARN or control uveitis. Patients were followed at 1 of 7 tertiary uveitis clinics between 2009 and 2011.
RESULTS: Analysis of the data allowed delineation of 2 levels of diagnosis: "virus-confirmed ARN" (defined as the presence of both early-stage ocular findings 1a and 1b, the presence of any 1 of the 5 clinical courses, and a positive virologic test result) and "virus-unconfirmed ARN" (defined as the presence of 4 of 6 early-stage ocular findings including 1a and 1b, presence of any 2 of the 5 clinical courses, and a negative virologic test result, or when virologic testing had not been performed). The new diagnostic criteria were applied to 45 patients with ARN and 409 patients with control uveitis, resulting in a sensitivity of 0.89, a specificity of 1.00, a PPV of 1.00, and an NPV of 0.99.
CONCLUSIONS: New diagnostic criteria for ARN were developed and found to achieve high statistical values.

PMID 25492579
D A Jabs, J T Rosenbaum, C S Foster, G N Holland, G J Jaffe, J S Louie, R B Nussenblatt, E R Stiehm, H Tessler, R N Van Gelder, S M Whitcup, D Yocum
Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel.
Am J Ophthalmol. 2000 Oct;130(4):492-513.
Abstract/Text PURPOSE: To provide recommendations for the use of immunosuppressive drugs in the treatment of patients with ocular inflammatory disorders.
PARTICIPANTS: A 12-person panel of physicians with expertise in ophthalmologic, pediatric, and rheumatologic disease, in research, and in the use of immunosuppressive drugs in patient care.
EVIDENCE: Published clinical study results. Recommendations were rated according to the quality and strength of available evidence.
PROCESS: The panel was convened in September of 1999 and met regularly through May 2000. Subgroups of the panel summarized and presented available information on specific topics to the full panel; recommendations and ratings were determined by group consensus.
CONCLUSIONS: Although corticosteroids represent one of the mainstays in the management of patients with ocular inflammation, in many patients, the severity of the disease, the presence of corticosteroid side effects, or the requirement for doses of systemic corticosteroids highly likely to result in corticosteroid complications supports the rationale for immunosuppressive drugs (for example, antimetabolites, T-cell inhibitors, and alkylating agents) being used in the management of these patients. Because of the potential for side effects, treatment must be individualized and regular monitoring performed. With careful use of immunosuppressive drugs for treatment of ocular inflammatory disorders, many patients will benefit from them either with better control of the ocular inflammation or with a decrease in corticosteroid side effects.

PMID 11024423
R Oktay Kaçmaz, John H Kempen, Craig Newcomb, Ebenezer Daniel, Sapna Gangaputra, Robert B Nussenblatt, James T Rosenbaum, Eric B Suhler, Jennifer E Thorne, Douglas A Jabs, Grace A Levy-Clarke, C Stephen Foster
Cyclosporine for ocular inflammatory diseases.
Ophthalmology. 2010 Mar;117(3):576-84. doi: 10.1016/j.ophtha.2009.08.010. Epub 2010 Jan 19.
Abstract/Text PURPOSE: To evaluate the clinical outcomes of cyclosporine treatment for noninfectious ocular inflammation.
DESIGN: Retrospective cohort study.
PARTICIPANTS: A total of 373 patients with noninfectious ocular inflammation managed at 4 tertiary ocular inflammation clinics in the United States observed to use cyclosporine as a single noncorticosteroid immunosuppressive agent to their treatment regimen, between 1979 and 2007 inclusive.
METHODS: Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics, including dosage of cyclosporine and main outcome measures, were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers.
MAIN OUTCOME MEASURES: Control of inflammation, sustained control after reducing corticosteroid dosages, and discontinuation of therapy because of toxicity.
RESULTS: Of the 373 patients (681 eyes) initiating cyclosporine monotherapy, 33.4% by 6 months and 51.9% by 1 year gained sustained, complete control of inflammation over at least 2 visits spanning at least 28 days. Approximately 25% more improved to a level of slight inflammatory activity by each of these time points. Corticosteroid-sparing success (completely controlled inflammation for at least 28 days with prednisone < or = 10 mg/day) was achieved by 22.1% by 6 months and 36.1% within 1 year. Toxicity led to discontinuation of therapy within 1 year by 10.7% of the population. Patients aged more than 55 years were more than 3-fold more likely to discontinue therapy because of toxicity than patients aged 18 to 39 years. Doses of 151 to 250 mg/day tended to be more successful than lower doses and were not associated with a higher discontinuation for toxicity rate; higher doses did not seem to offer a therapeutic advantage.
CONCLUSIONS: Cyclosporine, with corticosteroid therapy as indicated, was modestly effective for controlling ocular inflammation. Our data support a preference for cyclosporine adult dosing between 151 and 250 mg/day. Although cyclosporine was tolerated by the majority of patients, toxicity was more frequent with increasing age; alternative agents may be preferred for patients aged more than 55 years.

Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
PMID 20031223
Glenn J Jaffe, Andrew D Dick, Antoine P Brézin, Quan Dong Nguyen, Jennifer E Thorne, Philippe Kestelyn, Talin Barisani-Asenbauer, Pablo Franco, Arnd Heiligenhaus, David Scales, David S Chu, Anne Camez, Nisha V Kwatra, Alexandra P Song, Martina Kron, Samir Tari, Eric B Suhler
Adalimumab in Patients with Active Noninfectious Uveitis.
N Engl J Med. 2016 Sep 8;375(10):932-43. doi: 10.1056/NEJMoa1509852.
Abstract/Text BACKGROUND: Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis.
METHODS: This multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported.
RESULTS: The median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P<0.001). Outcomes with regard to three secondary end points (change in anterior chamber cell grade, change in vitreous haze grade, and change in best corrected visual acuity) were significantly better in the adalimumab group than in the placebo group. Adverse events and serious adverse events were reported more frequently among patients who received adalimumab (1052.4 vs. 971.7 adverse events and 28.8 vs. 13.6 serious adverse events per 100 person-years).
CONCLUSIONS: In our trial, adalimumab was found to be associated with a lower risk of uveitic flare or visual impairment and with more adverse events and serious adverse events than was placebo. (Funded by AbbVie; VISUAL I ClinicalTrials.gov number, NCT01138657 .).

PMID 27602665
Quan Dong Nguyen, Pauline T Merrill, Glenn J Jaffe, Andrew D Dick, Shree Kumar Kurup, John Sheppard, Ariel Schlaen, Carlos Pavesio, Luca Cimino, Joachim Van Calster, Anne A Camez, Nisha V Kwatra, Alexandra P Song, Martina Kron, Samir Tari, Antoine P Brézin
Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial.
Lancet. 2016 Sep 17;388(10050):1183-92. doi: 10.1016/S0140-6736(16)31339-3. Epub 2016 Aug 16.
Abstract/Text BACKGROUND: Non-infectious uveitis is a potentially sight-threatening ocular disorder caused by chronic inflammation and its complications. Therapeutic success is limited by systemic adverse effects associated with long-term corticosteroid and immunomodulator use if topical medication is not sufficient to control the inflammation. We aimed to assess the efficacy and safety of adalimumab in patients with inactive, non-infectious uveitis controlled by systemic corticosteroids.
METHODS: We did this multicentre, double-masked, randomised, placebo-controlled phase 3 trial at 62 study sites in 21 countries in the USA, Canada, Europe, Israel, Australia, and Latin America. Patients (aged ≥18 years) with inactive, non-infectious intermediate, posterior, or panuveitic uveitis controlled by 10-35 mg/day of prednisone were randomly assigned (1:1), via an interactive voice and web response system with a block size of four, to receive either subcutaneous adalimumab (loading dose 80 mg; biweekly dose 40 mg) or placebo, with a mandatory prednisone taper from week 2. Randomisation was stratified by baseline immunosuppressant treatment. Sponsor personnel with direct oversight of the conduct and management of the study, investigators, study site personnel, and patients were masked to treatment allocation. The primary efficacy endpoint was time to treatment failure, a multicomponent endpoint encompassing new active inflammatory chorioretinal or inflammatory retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, and visual acuity. Analysis was done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov number NCT01124838.
FINDINGS: Between Aug 10, 2010, and May 14, 2015, we randomly assigned 229 patients to receive placebo (n=114) or adalimumab (n=115); 226 patients comprised the intention-to-treat population. Median follow-up time was 155 days (IQR 77-357) in the placebo group and 245 days (119-564) in the adalimumab group. Treatment failure occurred in 61 (55%) of 111 patients in the placebo group compared with 45 (39%) of 115 patients in the adalimumab group. Time to treatment failure was significantly improved in the adalimumab group compared with the placebo group (median not estimated [>18 months] vs 8·3 months; hazard ratio 0·57, 95% CI 0·39-0·84; p=0·004). The 40th percentile for time to treatment failure was 4·8 months in the placebo group and 10·2 months in the adalimumab group. No patients in either group had opportunistic infections (excluding oral candidiasis and tuberculosis). No malignancies were reported in the placebo group whereas one (1%) patient in the adalimumab group reported non-serious squamous cell carcinoma. The most common adverse events were arthralgia (12 [11%] patients in the placebo group and 27 [23%] patients in the adalimumab group), nasopharyngitis (16 [17%] and eight [16%] patients, respectively), and headache (17 [15%] patients in each group).
INTERPRETATION: Adalimumab significantly lowered the risk of uveitic flare or loss of visual acuity upon corticosteroid withdrawal in patients with inactive, non-infectious intermediate, posterior, or panuveitic uveitis controlled by systemic corticosteroids. No new safety signals were observed and the rate of adverse events was similar between groups. These findings suggest that adalimumab is well tolerated and could be an effective treatment option in this patient population. An open-label extension study (NCT01148225) is ongoing to provide long-term safety data for adalimumab in patients with non-infectious uveitis.
FUNDING: AbbVie.

Copyright © 2016 Elsevier Ltd. All rights reserved.
PMID 27542302
日本眼炎症学会TNF阻害薬使用検討委員会:非感染性ぶどう膜炎に対するTNF阻害薬使用指針および安全対策マニュアル(2016年版). 日眼会誌 2017. 121: 34-41.
Hiroshi Goto, Manabu Mochizuki, Kunihiko Yamaki, Satoshi Kotake, Masahiko Usui, Shigeaki Ohno
Epidemiological survey of intraocular inflammation in Japan.
Jpn J Ophthalmol. 2007 Jan-Feb;51(1):41-4. doi: 10.1007/s10384-006-0383-4. Epub 2007 Feb 9.
Abstract/Text PURPOSE: To report the frequency and trend of intraocular inflammation based on a survey of new ophthalmology patient visits to university hospitals throughout Japan during 2002.
METHODS: A questionnaire was sent to the departments of ophthalmology in 110 university hospitals nationwide to survey the total number of new patients who visited the outpatient clinics for the first time between 1 January and 31 December 2002, and also the number of patients diagnosed with intraocular inflammation during this period.
RESULTS: The surveys completed by 41 university hospitals were analyzed in this study. During 2002, a total of 151 299 new ophthalmological patients presented at the 41 institutions, and 3060 (2.2%) of the new patients were diagnosed as having intraocular inflammation. The most frequent intraocular inflammatory disease identified was sarcoidosis (13.3%), followed by Vogt-Koyanagi-Harada (VKH) disease (6.7%), Behçet disease (6.2%), bacterial endophthalmitis (3.8%), herpetic iridocyclitis (3.6%), diabetic iritis (1.6%), human leukocyte antigen-B27-associated uveitis (1.5%), acute retinal necrosis (1.3%), ocular toxoplasmosis (1.1%), ocular toxocariasis (1.1%), uveitis associated with human T lymphotropic virus-1 (also known as HAU) (1.1%), and others. Infectious intraocular inflammation accounted for 16% of all uveitis cases.
CONCLUSIONS: Through the collaboration of a large number of institutions, some aspects of the epidemiology of intraocular inflammation in Japan were elucidated. However, the disease concept and diagnostic criteria remain ambiguous for a considerable number of diseases within the spectrum of intraocular inflammation, and the possibility that such factors may bias the present findings cannot be denied. In the future, a prospective survey based on well-defined, common diagnostic criteria is required to obtain more precise epidemiological data.

(c) Japanese Ophthalmological Society 2007.
PMID 17295139
J-I Sakai, Y Usui, M Sakai, H Yokoi, H Goto
Clinical statistics of endogenous uveitis: comparison between general eye clinic and university hospital.
Int Ophthalmol. 2010 Jun;30(3):297-301. doi: 10.1007/s10792-009-9336-5. Epub 2010 Jan 8.
Abstract/Text We compared uveitis patients who attended a general eye clinic (n = 183) with those who attended the ophthalmology department of a university hospital (n = 550) to examine factors that affect the clinical statistics of uveitis outpatients. We observed that diabetic iritis and herpetic iritis were significantly more frequent in the clinic whereas Vogt-Koyanagi-Harada disease and Behcet's disease were significantly more common in the university hospital. Among the so-called three leading uveitis, Behcet's disease and Vogt-Koyanagi-Harada disease were relatively rare in the general clinic; they might be concentrated in the university hospital setting because these diseases require treatment at specialist hospitals. In addition, uveitis secondary to underlying diseases such as diabetic iritis and transient non-granulomatous iridocyclitis was generally not referred to specialist hospitals. These factors may account for the differences in disease frequencies observed between the two facilities.

PMID 20058050
Jun-Ichi Sakai, Yoshihiko Usui, Jun Suzuki, Takeshi Kezuka, Hiroshi Goto
Clinical features of anterior uveitis caused by three different herpes viruses.
Int Ophthalmol. 2019 Dec;39(12):2785-2795. doi: 10.1007/s10792-019-01125-5. Epub 2019 May 27.
Abstract/Text PURPOSE: To compare the clinical findings in patients with anterior uveitis (AU) caused by herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV).
METHODS: We retrospectively analyzed the clinical profiles of HSV-AU (14 patients), VZV sine herpete (ZSH-AU: 21 patients), and CMV-AU (17 patients) diagnosed by the detection of corresponding viral DNA in aqueous humor samples by polymerase chain reaction. Further, five patients with Posner-Schlossman (P-S) syndrome were selected as controls for CMV-AU.
RESULTS: Patients with CMV-AU were predominately male or older in age, and all cases were unilateral except for three patients with CMV-AU. Mutton-fat keratic precipitates (KPs) were found mostly in patients with HSV-AU and ZSH-AU. Severities of AU and viral load were the highest in ZSH-AU, followed by HSV-AU and CMV-AU. Iris atrophy was observed in HSV-AU (50%) and ZSH-AU (76%), with typical morphology of round type and sector type, respectively. In patients with CMV-AU, a ring-shaped KP was found in 53% patients, 76% of whom showed a decreased number of corneal endothelial cells. CMV was not detected in the aqueous humor of patients with typical P-S syndrome.
CONCLUSION: Clinical findings of HSV-AU and VZV-AU were similar; however, more inflammatory findings were observed in VZV-AU. Iris atrophy morphologically differed in HSV-AU and VZV-AU. Inflammatory findings in CMV-AU were mild, and clinical features of iritis differed from those of the two former groups. A difference in the etiology between CMV-AU and P-S syndrome was observed.

PMID 31134426
Hiroshi Takase, Reo Kubono, Yukiko Terada, Ayano Imai, Shoko Fukuda, Makoto Tomita, Masaru Miyanaga, Koju Kamoi, Sunao Sugita, Kazunori Miyata, Manabu Mochizuki
Comparison of the ocular characteristics of anterior uveitis caused by herpes simplex virus, varicella-zoster virus, and cytomegalovirus.
Jpn J Ophthalmol. 2014 Nov;58(6):473-82. doi: 10.1007/s10384-014-0340-6. Epub 2014 Aug 16.
Abstract/Text PURPOSE: To compare the clinical characteristics of anterior uveitis (AU) caused by herpes simplex virus (HSV), varicella-zoster virus (VZV), or cytomegalovirus (CMV).
METHODS: The medical records were reviewed of 46 patients whose diagnoses were based on their clinical characteristics [e.g., unilateral involvement, presence of keratic precipitates (KPs), and elevation of intraocular pressure (IOP)] and on PCR detection of herpes virus DNA in the aqueous humor. The demographics, chief complaints, and clinical characteristics of the three types of herpetic AU were compared.
RESULTS: Of the 46 patients with AU, eight had HSV-AU, 20 had VZV-AU, and 18 had CMV-AU. HSV-AU and VZV-AU shared common features, i.e., a relatively acute disease process and the presence of large KPs. Among the three groups of patients, the characteristic features of those with VZV-AU were severe intraocular inflammation, as shown by severe aqueous flare, highest viral load in the aqueous humor, and presence of segmental iris atrophy. In comparison, patients with CMV-AU had the mildest intraocular inflammation, lowest corneal endothelial cell density, and highest IOP.
CONCLUSIONS: Although the AU caused by each of the three types of herpes viruses has a number of common features, each disease also has distinct features that should facilitate an accurate diagnosis.

PMID 25124341
Yukiko Terada, Toshikatsu Kaburaki, Hiroshi Takase, Hiroshi Goto, Satoko Nakano, Yoshitsugu Inoue, Kazuichi Maruyama, Kazunori Miyata, Kenichi Namba, Koh-Hei Sonoda, Yutaka Kaneko, Jiro Numaga, Masaya Fukushima, Noe Horiguchi, Mitsunao Ide, Fumie Ehara, Dai Miyazaki, Eiichi Hasegawa, Manabu Mochizuki
Distinguishing Features of Anterior Uveitis Caused by Herpes Simplex Virus, Varicella-Zoster Virus, and Cytomegalovirus.
Am J Ophthalmol. 2021 Jul;227:191-200. doi: 10.1016/j.ajo.2021.03.020. Epub 2021 Mar 25.
Abstract/Text PURPOSE: To determine distinguishing features of the clinical characteristics of anterior uveitis (AU) caused by herpes simplex virus (HSV), varicella-zoster virus (VZV), and cytomegalovirus (CMV).
DESIGN: Retrospective, multicenter case series.
METHODS: Consecutive patients with herpetic AU examined at 11 tertiary centers in Japan between January 2012 and December 2017 and who were followed for ≥3 months were evaluated. Diagnosis was made by polymerase chain reaction (PCR) for HSV, VZV, or CMV in the aqueous humor, or classical signs of herpes zoster ophthalmicus.
RESULTS: This study enrolled 259 herpetic AU patients, including PCR-proven HSV-AU (30 patients), VZV-AU (50), and CMV-AU (147), and herpes zoster ophthalmicus (32). All HSV-AU and VZV-AU patients were unilateral, while 3% of CMV-AU patients were bilateral. Most HSV-AU and VZV-AU patients were sudden onset with an acute clinical course, while CMV-AU had a more insidious onset and chronic course. There were no significant differences for all surveyed symptoms, signs, and complications between HSV-AU and VZV-AU. However, significant differences were detected for many items between CMV-AU and the other two herpetic AU types. Ocular hyperemia and pain, blurring of vision, ciliary injection, medium-to-large keratic precipitates (KPs), cells and flare in the anterior chamber, and posterior synechia significantly more often occurred in HSV-AU and VZV-AU vs CMV-AU. In contrast, small KPs, coin-shaped KPs, diffuse iris atrophy, elevated intraocular pressure, and glaucoma surgery were significantly more frequent in CMV-AU vs HSV-AU and VZV-AU.
CONCLUSION: This multicenter, retrospective study identified distinguishing features of HSV-AU, VZV-AU, and CMV-AU.

Copyright © 2021 Elsevier Inc. All rights reserved.
PMID 33773985
J Taylor-Wiedeman, J G Sissons, L K Borysiewicz, J H Sinclair
Monocytes are a major site of persistence of human cytomegalovirus in peripheral blood mononuclear cells.
J Gen Virol. 1991 Sep;72 ( Pt 9):2059-64. doi: 10.1099/0022-1317-72-9-2059.
Abstract/Text We have used the nested polymerase chain reaction (PCR) combined with fluorescence-activated cell sorting to define sites of latency of human cytomegalovirus (HCMV) in the peripheral blood of healthy subjects. Peripheral blood mononuclear (PBM) cells were separated into T cell or non-T cell populations and monocytes, and were then analysed by PCR for the presence of HCMV DNA. In five of six seropositive subjects, HCMV was found predominantly in the non-T cell population. Further analysis suggested that the virus was present in adherent cells and CD14+ cells. In three of nine seronegative subjects we could demonstrate HCMV DNA, which we do not believe was due to contamination, reproducibly by PCR. In one of these seronegative subjects, HCMV DNA was present predominantly in the non-T cell fraction of PBM cells. No HCMV DNA was detectable in the remaining six seronegative subjects. We conclude that, within the PBM cells of normal asymptomatic seropositive and some seronegative subjects, HCMV is present predominantly in the monocyte fraction. In addition, the detection of HCMV sequences in seronegative subjects may indicate that infection with HCMV is more widespread than conventional seroepidemiology suggests.

PMID 1654370
G N Holland
Standard diagnostic criteria for the acute retinal necrosis syndrome. Executive Committee of the American Uveitis Society.
Am J Ophthalmol. 1994 May 15;117(5):663-7.
Abstract/Text
PMID 8172275
坂井潤一、臼井嘉彦. 急性網膜壊死とその類縁疾患. 臨床眼科. 2008 62: 130-137.
D J Forster, P U Dugel, G T Frangieh, P E Liggett, N A Rao
Rapidly progressive outer retinal necrosis in the acquired immunodeficiency syndrome.
Am J Ophthalmol. 1990 Oct 15;110(4):341-8.
Abstract/Text Two patients, both seropositive for the human immunodeficiency virus, developed rapidly progressive retinal necrosis associated with a systemic herpes zoster infection. The retinitis in these patients was characterized by primary involvement of the outer retina, with sparing of the inner retina and retinal vasculature until late in the disease process; a rapidly progressive course; poor response to intravenous acyclovir; and development of rhegmatogenous retinal detachment. In one of the patients, the retinitis was initially multifocal. Electron microscopy of a retinal biopsy specimen from one of the patients demonstrated virus particles consistent with a herpesvirus, and polymerase chain reaction disclosed herpesvirus in a retinal biopsy specimen of the other patient. This entity may represent a distinct form of acute retinal necrosis that is seen in immunocompromised individuals.

PMID 2220967
M Kashiwase, T Sata, Y Yamauchi, H Minoda, N Usui, T Iwasaki, T Kurata, M Usui
Progressive outer retinal necrosis caused by herpes simplex virus type 1 in a patient with acquired immunodeficiency syndrome.
Ophthalmology. 2000 Apr;107(4):790-4.
Abstract/Text OBJECTIVE/BACKGROUND: To identify the etiologic agent of rapidly progressive outer retinal necrosis (PORN) in a 32-year-old man with acquired immunodeficiency syndrome (AIDS), who had retinitis developed from cytomegalovirus (CMV). Multiple yellowish spots appeared in the deep retina without evidence of intraocular inflammation or retinal vasculitis, diagnosed clinically as PORN. Death occurred after failure of multiple organs.
DESIGN: Case report.
METHODS: Both globes were taken at autopsy, fixed in formalin, and examined histopathologically and immunohistochemically to identify causative agents in the retinal lesions.
MAIN OUTCOME MEASURE: Immunohistochemistry.
RESULTS: All layers of the retina were severely damaged and contained focal calcification. Cytomegalic inclusion bodies were found in cells in the damaged retina of the right eye. Immunohistochemical studies for herpesviruses revealed the presence of CMV antigens in the right retina at the posterior pole and herpes simplex virus type 1 (HSV-1)-specific antigen in the periphery of both retinas. No varicella-zoster virus (VZV) antigen was detected in either retina.
CONCLUSIONS: PORN has been described as a variant of necrotizing herpetic retinopathy, occurring particularly in patients with AIDS. Although the etiologic agent has been reported to be VZV, HSV-1 can be an etiologic agent.

PMID 10768344
E A Roig-Melo, T A Macky, M L Heredia-Elizondo, D V Alfaro
Progressive outer retinal necrosis syndrome: successful treatment with a new combination of antiviral drugs.
Eur J Ophthalmol. 2001 Apr-Jun;11(2):200-2.
Abstract/Text PURPOSE: To describe a case of progressive outer retinal necrosis syndrome, successfully treated with a new combination of antiviral drugs.
METHODS: The patient was treated with a combined therapy of antiviral drugs that includes: intravenous acyclovir 10 mg/kg, three intravitreal injections of foscarnet (1200 microg) and a ganciclovir implant in the right eye.
RESULTS: The progressive outer retinal necrosis appeared to response dramatically with the combination of antiviral agents used over a period of 2 weeks with a final visual acuity of 20/80 at 3 months of follow up.
CONCLUSIONS: Intravitreal foscarnet combined with i.v. acyclovir and ganciclovir implant may represent an effective alternative treatment for PORN.

PMID 11456028
D Salmon-Ceron
Cytomegalovirus infection: the point in 2001.
HIV Med. 2001 Oct;2(4):255-9.
Abstract/Text The incidence of cytomegalovirus (CMV) disease, one of the most prevalent opportunistic infections in HIV-infected persons in the early 1990s, has decreased by more than 80% since the introduction of highly active antiretroviral therapy (HAART). The rare cases of CMV disease still observed in Western countries occur mainly in profoundly immunosuppressed patients who have failed to respond to HAART. A new finding is the occasional occurrence of inflammatory retinitis in some patients on HAART with a history of healed retinitis. New tools for CMV detection have become available recently, including use of polymerase chain reaction (PCR) to detect CMV DNA from plasma. It has been possible to redefine, in the HAART period, patients at risk for CMV disease as those who have a low CD4 cell count as well as a blood marker of CMV blood dissemination (plasma CMV DNAaemia or high pp65 antigenaemia). Besides the classical therapeutic approach using ganciclovir (GCV), foscarnet and cidofovir, development of valganciclovir (VGCV), an orally administered prodrug of GCV, appears promising. There is evidence to suggest that it is as effective as intravenous GCV for the treatment of CMV retinitis, and it is currently being studied as a pre-emptive therapy in patients at high risk for CMV disease. Finally, patients with inactive CMV retinitis receiving HAART and with stable immune reconstitution may be able to discontinue maintenance therapy provided a regular ophthalmological and virological surveillance is maintained.

PMID 11737406
Jennifer E Thorne, Douglas A Jabs, John H Kempen, Janet T Holbrook, Charles Nichols, Curtis L Meinert, Studies of Ocular Complications of AIDS Research Group
Incidence of and risk factors for visual acuity loss among patients with AIDS and cytomegalovirus retinitis in the era of highly active antiretroviral therapy.
Ophthalmology. 2006 Aug;113(8):1432-40. doi: 10.1016/j.ophtha.2006.03.021. Epub 2006 Jun 12.
Abstract/Text PURPOSE: To describe the incidence of and risk factors for visual acuity loss among patients with AIDS and cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART).
DESIGN: Multicenter prospective observational study.
PARTICIPANTS: Three hundred seventy-nine patients with AIDS and CMV retinitis (494 eyes).
METHODS: Follow-up every 3 months with medical history, ophthalmologic examination, and laboratory testing.
MAIN OUTCOME MEASURES: Incidence of visual acuity loss to 20/50 or worse, to 20/200 or worse, and of doubling of the visual angle in eyes affected with CMV retinitis.
RESULTS: Among the 494 eyes with CMV retinitis, the baseline frequencies of visual acuity loss to 20/50 or worse and to 20/200 or worse were 29% and 15%, respectively. Over a median follow-up period of 3.1 years, the incidences of visual acuity loss to 20/50 or worse, to 20/200 or worse, and of doubling of the visual angle were 0.10/eye-year (EY), 0.06/EY, and 0.13/EY, respectively. Immune recovery was associated with a 42% reduction in vision loss to 20/50 or worse and with a 61% reduction in vision loss to 20/200 or worse after adjusting for confounding. Of the patients with immune recovery at baseline, 17% had immune recovery uveitis (IRU). In these patients, the incidence rate of 20/50 or worse vision was similar to that observed in patients without immune recovery (0.17/EY vs. 0.16/EY), but the incidence of 20/200 or worse vision was similar to that observed among patients with immune recovery (0.04/EY vs. 0.04/EY).
CONCLUSIONS: Cytomegalovirus retinitis is associated with a substantial risk of incident vision loss in the era of HAART. Those who have HAART-induced immune recovery have approximately 50% lower risk of visual acuity loss. Presence of IRU at baseline attenuated the protective effect of immune recovery for moderate vision loss but not for blindness.

PMID 16766032
G M Behrens, D Meyer, M Stoll, R E Schmidt
Immune reconstitution syndromes in human immuno-deficiency virus infection following effective antiretroviral therapy.
Immunobiology. 2000 Aug;202(2):186-93. doi: 10.1016/S0171-2985(00)80065-0.
Abstract/Text Effective antiretroviral therapy leads to rapid decrease in plasma HIV-1 RNA, frequently followed by an increase in CD4 T-helper cell counts. The improvement of immune function during highly active antiretroviral therapy has important impact on natural history of AIDS-related opportunistic disorders. Here we describe cases of unusual clinical inflammatory syndromes in CMV retinitis, hepatitis C, and atypical mycobacteriosis in HIV-1 infected patients associated with the initiation of antiretroviral therapy. Pathogenetic implications and therapeutic management of these new immunopathologic syndromes are discussed.

PMID 10993293
M P Karavellas, S P Azen, J C MacDonald, C L Shufelt, C Y Lowder, D J Plummer, B Glasgow, F J Torriani, W R Freeman
Immune recovery vitritis and uveitis in AIDS: clinical predictors, sequelae, and treatment outcomes.
Retina. 2001;21(1):1-9.
Abstract/Text PURPOSE: To determine 1) clinical predictors of an inflammatory syndrome associated with cytomegalovirus (CMV) retinitis (immune recovery vitritis or uveitis [IRV or IRU]); 2) clinical sequelae of IRV; and 3) the effect of corticosteroid treatment on visual acuity.
METHODS: A cohort study from the AIDS Ocular Research Unit of the University of California, San Diego, and a case series from the Cleveland Clinic consisted of patients who had acquired immunodeficiency syndrome and inactive CMV retinitis who responded to highly active antiretroviral therapy (HAART) with CD4 T-lymphocyte levels >60 cells/mm3. The cohort was followed for a median of 13.5 months following increase in CD4 count. The authors studied the occurrence of IRV, defined as symptomatic (vision decrease and/or floaters) vitritis of 1+ or greater severity associated with inactive CMV retinitis. Macular edema or epiretinal membrane formation was determined by clinical examination and fluorescein angiography. Five eyes were treated with sub-Tenon corticosteroid injections.
RESULTS: In the cohort study, 19 (63%) of 30 HAART responders developed IRV (26 eyes). The clinical spectrum of inflammation included vitritis, papillitis, macular edema, and epiretinal membranes. Eyes with CMV surface area >30% of the retina were at the highest risk (relative risk = 4.5) of developing IRV (P = 0.03). During follow-up, inflammation persisted without treatment for a median of 20 weeks and 14 patients (16 eyes) developed macular changes. Treatment resulted in vision improvement without reactivation of retinitis. Histology and immunohistochemistry of associated epiretinal membranes showed evidence of chronic inflammation with a predominant T-lymphocyte cell population. In the case series, 3 (38%) of 8 HAART responders developed IRV (4 eyes). All four eyes were treated and resulted in visual acuity improvement of one line.
CONCLUSIONS: Symptomatic IRV or IRU develops in a significant number of patients with CMV retinitis following successful HAART. Eyes with CMV surface area >30% of the retina are at the greatest risk. Eyes with IRV respond favorably to antiinflammatory therapy without reactivation of retinitis. Immune recovery vitritis may be the result of an immunologic reaction to latent CMV antigens in the eye in which T-lymphocytes play a role.

PMID 11217922
Jolanda D F de Groot-Mijnes, Lenneke de Visser, Aniki Rothova, Margje Schuller, Anton M van Loon, Annemarie J L Weersink
Rubella virus is associated with fuchs heterochromic iridocyclitis.
Am J Ophthalmol. 2006 Jan;141(1):212-214. doi: 10.1016/j.ajo.2005.07.078.
Abstract/Text PURPOSE: To determine whether rubella virus (RV) is involved in the pathogenesis of Fuchs heterochromic iridocyclitis (FHI).
DESIGN: Retrospective patient-controlled study.
METHODS: Intraocular immunoglobulin G production against RV, herpes simplex virus (HSV), varicella zoster virus (VZV), and Toxoplasma gondii was determined in the aqueous humor of 14 patients with FHI, 13 control subjects with herpetic uveitis anterior, and 19 control subjects with ocular toxoplasmosis by calculation of the Goldmann-Witmer coefficient (GWC).
RESULTS: All patients and control subjects were seropositive for RV. Intraocular antibody production (GWC >3) against RV was found in 13 of 14 patients (93%) with FHI. Intraocular antibody production against HSV, VZV, or T gondii was not detected. None of the control subjects with herpetic uveitis anterior or with toxoplasma chorioretinitis had a positive GWC for rubella virus (P < .0001, Fisher exact test).
CONCLUSION: Rubella virus, but not HSV, VZV, or T gondii, is associated with FHI.

PMID 16387009
J L Smith
Ocular Lyme borreliosis--1991.
Int Ophthalmol Clin. 1991 Fall;31(4):17-38.
Abstract/Text
PMID 1743893
鬼木信乃夫:トキソプラズマ性網脈絡幕炎86症例についての臨床的考察. 臨眼 1968 22:137-148.
J L Lyons, J T Rosenbaum
Uveitis associated with inflammatory bowel disease compared with uveitis associated with spondyloarthropathy.
Arch Ophthalmol. 1997 Jan;115(1):61-4.
Abstract/Text BACKGROUND: Inflammatory bowel disease (IBD) and spondyloarthropathy (SA) such as Reiter syndrome may be characterized by diarrhea, arthritis, stomatitis, and uveitis.
OBJECTIVE: To determine if the characteristics of the eye disease could help distinguish these 2 diagnoses.
DESIGN: Seventeen patients with uveitis and IBD referred to a university clinic were compared retrospectively with 89 patients with uveitis and SA referred to the same clinic.
RESULTS: Twelve (80%) of the 15 patients with evaluable IBD had Crohn disease. In marked contrast to patients with SA, patients with IBD were usually female (82%). Whereas uveitis with SA was predominantly anterior, unilateral, sudden in onset, and limited in duration, patients with IBD frequently had uveitis that was bilateral, posterior, insidious in onset, and/or chronic in duration. Results for 89% of the patients with SA who underwent HLA-B27 typing were positive, compared with only 46% of such patients with IBD. Episcleritis, scleritis, and glaucoma were more common among patients with IBD. Arthritis did not easily distinguish the 2 groups, as 13 (76%) of the patients with IBD had a history of joint disease. In 10 (59%) of the patients with IBD, the diagnosis of uveitis preceded that of IBD.
CONCLUSION: The hallmarks of uveitis can often distinguish SA and IBD.

PMID 9006426
岡部智子、松本直、岡島行伸、渡辺博、杤久保哲男、坂井潤一.:リファブチンによるぶどう膜炎の1例. あたらしい眼科31:599-603,2014.
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、渡邉裕次、井ノ口岳洋、梅田将光および日本医科大学多摩永山病院 副薬剤部長 林太祐による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
坂井潤一 : 特に申告事項無し[2025年]
監修:沖波聡 : 特に申告事項無し[2025年]

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