今日の臨床サポート

Vogt-小柳-原田病

著者: 岩橋千春 近畿大学病院 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:2021/07/14
参考ガイドライン:
  1. 日本眼科炎症学会ぶどう膜炎診療ガイドライン作成委員会:ぶどう膜炎診療ガイドライン、日本眼科学会雑誌 第123巻、第6号
患者向け説明資料

概要・推奨   

  1. 原田病の診断に髄液検査が必要か否かという問題は、いまだ結論は出ていない。髄膜刺激症状や耳鳴りといった全身症状がない場合には施行することが推奨されている(推奨度2)
  1. 原田病の視力予後はおおむね良好といわれているが、炎症の遷延化に伴い網膜変性を生じた場合や再燃を繰り返す場合には視力低下を来すこともあり、速やかな消炎が治療の目標となる。そのためには、発症早期に十分なステロイド薬の全身投与が推奨されている(推奨度2)
  1. 原田病では病初期に大量のステロイド薬を全身投与することが推奨されているため、ステロイドパルス治療が選択されることもまれではない(推奨度2)
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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。閲覧にはご契約が必要となります。閲覧にはご
  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。閲
  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。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。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
  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。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。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
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、林太祐、渡邉裕次、井ノ口岳洋、梅田将光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。
※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、実際の保険適用の査定において保険適用及び保険適用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用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:
岩橋千春 : 特に申告事項無し[2021年]
監修:沖波聡 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行い、難治症例に対する治療について加筆修正を行った。

病態・疫学・診察

疾患情報  
  1. Vogt-小柳-原田病(以下、原田病)は、サルコイドーシス(眼科)ベーチェット病(眼科)と並んで、わが国では頻度の高いぶどう膜炎である。
  1. 急性期の臨床像としては、全身では髄膜刺激症状や難聴、眼所見としては後極部を中心に漿液性剝離を伴った両眼性炎症を認める。
  1. 眼所見としては、ほかに乳頭浮腫型、前眼部型があり、これらでは診断に苦慮することがある。
  1. 後期には脱色素症状(白髪、皮膚の白斑、夕焼け状眼底など)や脱毛を伴うことが多い。そのため、原田病はメラノサイトを標的とした自己免疫疾患と考えられている。
  1. 治療は、ステロイド薬の全身投与を病初期にしっかり行うことが重要である。
 
原田病後期の眼底所見

発症3カ月後。両眼に夕焼け状眼底を認める。

出典

img1:  大黒伸行先生ご提供
 
 
問診・診察のポイント  
  1. 頭痛・耳鳴り・感冒様症状などの前駆症状の有無を問診で確認する。

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文献 

著者: R W Read, G N Holland, N A Rao, K F Tabbara, S Ohno, L Arellanes-Garcia, P Pivetti-Pezzi, H H Tessler, M Usui
雑誌名: Am J Ophthalmol. 2001 May;131(5):647-52.
Abstract/Text PURPOSE: To present revised criteria for the diagnosis of Vogt-Koyanagi-Harada disease, a chronic, bilateral, granulomatous ocular and multisystem inflammatory condition of unknown cause.
METHODS: Diagnostic criteria and nomenclature were subjects of discussion at the First International Workshop on Vogt-Koyanagi-Harada Disease on October 19-21, 1999, at the University of California, Los Angeles, Conference Center, Lake Arrowhead, California. A committee appointed by the workshop participants was charged with drafting revised criteria for Vogt-Koyanagi-Harada disease, based on discussions held during the conference. This article is the consensus committee report.
RESULTS: New criteria, taking into account the multisystem nature of Vogt-Koyanagi-Harada disease, with allowance for the different ocular findings present in the early and late stages of the disease, were formulated and agreed upon by the committee. These criteria are based on additional knowledge and experience of experts in the field and are believed to reflect disease features more fully than previously published criteria.
CONCLUSIONS: The revised definition of Vogt-Koyanagi-Harada disease, with expanded diagnostic criteria, will facilitate performance of studies involving homogeneous populations of patients, at various stages of disease, that address unanswered questions regarding treatment and disease mechanisms.

PMID 11336942  Am J Ophthalmol. 2001 May;131(5):647-52.
著者: S M Islam, J Numaga, K Matsuki, Y Fujino, H Maeda, K Masuda
雑誌名: Invest Ophthalmol Vis Sci. 1994 Feb;35(2):752-6.
Abstract/Text PURPOSE: To investigate the difference, if any, in the immunogenetic backgrounds between two clinical subtypes of Vogt-Koyanagi-Harada disease (VKH).
METHODS: HLA-DR4 gene variations were investigated in 46 Japanese patients, 28 with the prolonged type and 18 with the nonprolonged type of VKH. HLA-DR4 genes were amplified with polymerase chain reaction (PCR) and then analyzed for its variation with single-strand conformation polymorphism (SSCP) and restriction fragment length polymorphism (RFLP) methods.
RESULTS: Significant differences were found in the DR4 gene variation in the two clinical subtypes. All the patients with the prolonged type had either the DRB1*0405 or DRB1*0410 variant, whereas 39% of the patients with the nonprolonged type had neither of them. This difference in frequency was statistically highly significant (P = 0.00059, Pc = 0.0041). DRB1*0405 was also more frequent in the prolonged type (93%) than in the nonprolonged type (56%) (P = 0.0044, Pc " 0.030). In the prolonged type, relative risk was highest for DRB1*0405/0410 (128), whereas in the nonprolonged type it was highest for DR4 (8.6).
CONCLUSION: This preliminary study showed that DR4 gene variants differed significantly between the two subtypes of VKH, suggesting that the clinical course of VKH is determined partly by the patient's HLA-DR gene variation.

PMID 7906684  Invest Ophthalmol Vis Sci. 1994 Feb;35(2):752-6.
著者: Masaru Miyanaga, Tatushi Kawaguchi, Kentaro Shimizu, Kazunori Miyata, Manabu Mochizuki
雑誌名: Int Ophthalmol. 2007 Apr-Jun;27(2-3):183-8. doi: 10.1007/s10792-007-9076-3. Epub 2007 May 3.
Abstract/Text PURPOSE: To evaluate the importance of early cerebrospinal fluid (CSF)-guided diagnosis and early high-dose corticosteroid therapy on the complications and visual prognosis of Vogt-Koyanagi-Harada (VKH) disease.
PATIENTS AND METHODS: Charts from patients with VKH disease who had been seen at Tokyo Medical and Dental University Hospital and Miyata Eye Hospital between 1994 and 2002 were retrospectively reviewed. The patients were classified into two groups. The first group (group A) consisted of patients who had received a full work-up including CSF examination and corticosteroid pulse therapy at the acute ophthalmic stage of disease. The second group (group B) consisted of patients who were referred to us by local ophthalmologists long after the disease onset, had not had a CSF examination and had been treated with low-dose systemic corticosteroids or topical corticosteroid therapy. The ocular complications, systemic complications and visual prognosis were compared between the two groups.
RESULTS: Twenty-two patients were included in group A and ten patients in group B. The initial diagnosis at the acute ophthalmic stage had been VKH disease in all patients of group A, while, in group B, the diagnosis was idiopathic uveitis in six patients (60%) initially. Frequency of recurrent uveitis and integumentary symptoms were significantly lower in group A. Intensity of sunset glow fundus was significantly more severe in group B. All eyes in group A obtained a final visual acuity of 0.8 or better, whereas 11 eyes (55%) in group B were below this level.
CONCLUSIONS: The results indicate that early diagnosis, helped by CSF examination and early high-dose corticosteroid therapy, decreased the complication rate and improved the visual prognosis.

PMID 17476572  Int Ophthalmol. 2007 Apr-Jun;27(2-3):183-8. doi: 10.100・・・
著者: Julie H Tsai, Somsiri Sukavatcharin, Narsing A Rao
雑誌名: Int Ophthalmol. 2007 Apr-Jun;27(2-3):189-94. doi: 10.1007/s10792-007-9044-y. Epub 2007 Mar 6.
Abstract/Text PURPOSE: To determine the significance of lumbar puncture in diagnosis of Vogt-Koyanagi-Harada disease (VKH).
METHOD: A retrospective analysis was conducted on 116 consecutive patients diagnosed with VKH. Two additional patients who presented with acute VKH were included in the analysis. Demographic characteristics, including gender, age, and ethnicity, were extracted from the medical record. The stage of disease at presentation was documented. Pertinent laboratory results and diagnostic procedures such as lumbar puncture, fluorescein angiography, and echography that contributed to the diagnosis of VKH were collected.
RESULTS: Lumbar puncture results for 10 patients were available. Eight of these patients presented with pleocytosis consistent with a diagnosis of VKH. Clinical features and fluorescein angiography confirmed the diagnosis in these patients. Both of the patients who did not exhibit cerebrospinal fluid (CSF) pleocytosis presented with headache, vision loss, and bilateral uveitis. Fluorescein angiography disclosed multiple foci of leakage at the retinal pigment epithelium level with accumulation of dye under the retina and disc leakage, confirming diagnosis of VKH.
CONCLUSION: The utility of lumbar puncture as a diagnostic criterion for VKH should be re-evaluated given that clinical features and fluorescein angiography alone often support the diagnosis. The inherent risks and complications associated with the procedure must prompt the clinician to reserve this evaluation for atypical presentations.

PMID 17340216  Int Ophthalmol. 2007 Apr-Jun;27(2-3):189-94. doi: 10.10・・・
著者: Abdullah S Al-Kharashi, Hassan Aldibhi, Hamad Al-Fraykh, Dustan Kangave, Ahmed M Abu El-Asrar
雑誌名: Int Ophthalmol. 2007 Apr-Jun;27(2-3):201-10. doi: 10.1007/s10792-007-9062-9. Epub 2007 Apr 14.
Abstract/Text PURPOSE: To identify prognostic factors for final visual outcome, development of complications, and recurrent inflammation in patients with Vogt-Koyanagi-Harada (VKH) disease.
METHODS: All patients diagnosed with acute uveitis associated with VKH disease at the King Khaled Eye Specialist Hospital and King Abdulaziz University Hospital between January 1999 and February 2004 were reviewed. Data collected included age, gender, initial and final visual acuities, clinical findings at presentation, interval between onset of disease and starting treatment, treatment received, complications, number of recurrences, extraocular manifestations, and duration of follow-up period.
RESULTS: Sixty-eight patients were identified. There were 51 (75%) females and 17 (25%) males with a mean age of 25.04 +/- 10.28 years (range 7-55 years). The mean follow-up period was 34.4 +/- 20.1 months (range 8-62 months). The following factors were significantly associated with final visual acuity of 20/20 by univariate analysis: good initial visual acuity of better than 20/200 (p = 0.0415), absence of posterior synechiae of the iris at presentation (p = 0.0106), use of systemic corticosteroids for longer than nine months (p = 0.0479), slow tapering of systemic corticosteroids (p = 0.0024), absence of complications (p < 0.001), and absence of extraocular manifestations (p = 0.0124). Logistic regression analysis identified the use of systemic corticosteroids for longer than nine months to be associated with final visual acuity of 20/20 [odds ratio = 3.4; 95% confidence interval (CI) = 1.14-10.1]. The following factors were significantly associated with the development of complications by univariate analysis: age older than 18 years (p = 0.0161), initial visual acuity of 20/200 or worse (p = 0.0011), and presence of posterior synechiae of the iris at presentation (p = 0.0453). Factors identified after logistic regression analyses were age older than 18 years (odds ratio = 3.3; 95% CI = 1.33-8.17), and presence of posterior synechiae of the iris at presentation (odds ratio = 3.42; 9% CI = 1.38-8.47). Initial visual acuity of better than 20/200 was significantly associated with a lower risk of developing complications (odds ratio = 0.283; 95% CI = 0.129-0.629). The following factors were significantly associated with recurrent inflammation of three times or more by univariate analysis: initial visual acuity of 20/200 or worse (p = 0.0179), anterior chamber reaction of more than 2+ at presentation (p < 0.001), rapid tapering of systemic corticosteroids (p < 0.001), and development of extraocular manifestations (p = 0.0277).
CONCLUSIONS: Clinical findings at presentation, duration and method of tapering of systemic corticosteroids, and development of extraocular manifestations are significantly associated with final visual acuity, development of ocular complications, and recurrent inflammation. The development of ocular complications was significantly associated with a worse final visual acuity.

PMID 17435968  Int Ophthalmol. 2007 Apr-Jun;27(2-3):201-10. doi: 10.10・・・
著者: Russell W Read, Fei Yu, Massimo Accorinti, Bahram Bodaghi, Soon-Phaik Chee, Christine Fardeau, Hiroshi Goto, Gary N Holland, Hidetoshi Kawashima, Eri Kojima, Phuc Lehoang, Claire Lemaitre, Annabelle A Okada, Paola Pivetti-Pezzi, Antonio Secchi, Robert F See, Khalid F Tabbara, Masahiko Usui, Narsing A Rao
雑誌名: Am J Ophthalmol. 2006 Jul;142(1):119-24. doi: 10.1016/j.ajo.2006.02.049.
Abstract/Text PURPOSE: To compare the effect on outcomes of the route of administration of corticosteroids in acute Vogt-Koyanagi-Harada disease.
DESIGN: Retrospective comparative interventional case series.
METHODS:
SETTINGS: Nine international uveitis specialty clinics.
STUDY POPULATION: Forty-eight patients presenting over a three-year period to a study center with acute Vogt-Koyanagi-Harada disease.
INTERVENTION: Initial treatment with corticosteroid either orally (Oral only group) or intravenously followed by an oral taper (IV+Oral group).
MAIN OUTCOME MEASURES: Change in visual acuity with treatment; development of ocular complications, including visually significant cataract, choroidal neovascularization, subretinal fibrosis, fundus pigment migration, nummular hypopigmented lesions, and diffuse fundus depigmentation; use of immunosuppressive therapy.
RESULTS: The Oral only group comprised 15 patients (31%) and the IV+Oral group 33 patients (69%). Median follow-up was 15 months. There was no difference in duration of follow-up between groups (P = .234). There was no difference in the change in visual acuity between groups, adjusting for initial visual acuity (P = .402). There were no differences in the rates of development of visually significant cataract, fundus pigmentary changes, or in the rate of use of subsequent immunosuppressive therapy between treatment groups. No patients developed choroidal neovascularization or subretinal fibrosis over the study period.
CONCLUSIONS: Route of administration of corticosteroid had no detectable effect on change in visual acuity nor on the development of visually significant complications over the study period. Prospective trials are necessary to address speed of resolution and definitively answer outcome questions.

PMID 16815259  Am J Ophthalmol. 2006 Jul;142(1):119-24. doi: 10.1016/j・・・
著者: Emiko Yamanaka, Nobuyuki Ohguro, Shuji Yamamoto, Yayoi Nakagawa, Yoshiko Imoto, Yasuo Tano
雑誌名: Am J Ophthalmol. 2002 Sep;134(3):454-6.
Abstract/Text PURPOSE: To evaluate the rapid effects of pulse corticosteroid therapy on the serous retinal detachment found at the acute phase of Vogt-Koyanagi-Harada disease.
DESIGN: Interventional case series.
METHODS: Nine Japanese patients determined to be at the acute phase of Vogt-Koyanagi-Harada disease with serous retinal detachment were treated with pulse corticosteroid therapy. Optical coherence tomography was used to follow the resolution of the retinal detachment.
RESULTS: Optical coherence tomography images showed a marked decrease in the retinal detachment immediately after the first intravenous injection of corticosteroid and subsequent resolution.
CONCLUSION: The rapid improvement of serous retinal detachment associated with Vogt-Koyanagi-Harada disease following pulse corticosteroid therapy supports an early therapeutic mechanism related to improved permeability of capillaries and permeability of the blood-retinal barrier rather than an anti-inflammatory or immunosuppressive action.

PMID 12208266  Am J Ophthalmol. 2002 Sep;134(3):454-6.
著者: S R Nowilaty, M Bouhaimed, Photodynamic Therapy Study Group
雑誌名: Br J Ophthalmol. 2006 Aug;90(8):982-6. doi: 10.1136/bjo.2006.091538. Epub 2006 May 10.
Abstract/Text AIM: To assess the effects of photodynamic therapy (PDT) with verteporfin in the treatment of subfoveal choroidal neovascularisation (CNV) secondary to Vogt-Koyanagi-Harada disease (VKH).
METHODS: Six eyes of six patients with VKH who developed subfoveal CNV underwent standard PDT. Repeated treatments were performed at 3 month intervals for persistent leakage. Charts and angiographic data were analysed retrospectively.
RESULTS: Age of patients ranged between 17 years and 27 years. Five CNV lesions were recent and classic (greatest lesion diameter was 1100-3100 microm). One CNV was chronic and partially scarred. Mean visual acuity (VA) at presentation was 20/200. Five patients had more than 1 year of follow up. In five eyes there was active inflammation and CNV. Of these eyes, the first three required one PDT each. The final CNV scar was smaller/stable with improvement of VA in two eyes. The third developed a larger CNV scar with loss of two lines of VA. Submacular fibrosis developed in all three. In the fourth eye, mild CNV leakage persisted after one PDT but hazy media precluded a second PDT. At 18 months the CNV scar and VA were stable. The fifth case, with mild inflammation, required three PDT. The CNV leakage became minimal, the lesion became smaller, and VA improved significantly. The sixth eye with CNV had no inflammation and needed two PDT sessions to halt the CNV leakage. The final lesion was smaller and vision was stable. There were no PDT related complications in our series.
CONCLUSION: Photodynamic therapy with verteporfin appears to be a safe and viable treatment option for subfoveal CNV secondary to VKH. It offers a chance for stabilisation or even improvement of vision. Further study is warranted.

PMID 16687455  Br J Ophthalmol. 2006 Aug;90(8):982-6. doi: 10.1136/bjo・・・
著者: Lihteh Wu, Teodoro Evans, Mario Saravia, Ariel Schlaen, Cristobal Couto
雑誌名: Jpn J Ophthalmol. 2009 Jan;53(1):57-60. doi: 10.1007/s10384-008-0600-4. Epub 2009 Jan 30.
Abstract/Text BACKGROUND: Vogt-Koyanagi-Harada (VKH) syndrome is characterized by bilateral diffuse uveitis associated with auditory, neurological, and cutaneous signs and symptoms. VKH syndrome is a cell-mediated autoimmune disease against melanocytes. Choroidal neovascularization (CNV) occurs in 15% of VKH patients and is associated with poor visual prognosis.
CASES: We report on two patients with VKH syndrome and CNV that were treated with intravitreal bevacizumab.
OBSERVATIONS: One of the VKH patients also had an extrafoveal CNV membrane and underwent multiple intravitreal injections of bevacizumab in combination with laser photocoagulation, with subsequent improvement in visual acuity. The second had a subfoveal CNV that responded to a single intravitreal injection of bevacizumab.
CONCLUSION: Intravitreal bevacizumab may be a useful drug to treat CNV in eyes with VKH syndrome.

PMID 19184312  Jpn J Ophthalmol. 2009 Jan;53(1):57-60. doi: 10.1007/s1・・・
著者: R D Fechtner, A S Khouri, T J Zimmerman, J Bullock, R Feldman, P Kulkarni, A J Michael, T Realini, R Warwar
雑誌名: Am J Ophthalmol. 1998 Jul;126(1):37-41.
Abstract/Text PURPOSE: To report the association of anterior uveitis with the use of latanoprost.
METHODS: We studied four patients with complicated open-angle glaucoma who had anterior uveitis associated with the use of latanoprost. The uveitis was unilateral and occurred only in the eye receiving latanoprost in three patients. In one patient, latanoprost was used in both eyes, and the uveitis was bilateral. Four of five eyes had a history of prior inflammation and/or prior incisional surgery. All patients were rechallenged with the drug.
RESULTS: The uveitis improved after cessation of latanoprost with or without topical corticosteroids. It recurred after rechallenging with latanoprost in all eyes.
CONCLUSION: There is a possible association between latanoprost and anterior uveitis. Topical prostaglandin analogs may be relatively contraindicated in patients with a history of uveitis or prior ocular surgery. This association may also be possible in eyes that have not had previous uveitis or incisional surgery.

PMID 9683147  Am J Ophthalmol. 1998 Jul;126(1):37-41.
著者: R E Warwar, J D Bullock, D Ballal
雑誌名: Ophthalmology. 1998 Feb;105(2):263-8.
Abstract/Text OBJECTIVE: This study aimed to investigate the incidence of cystoid macular edema and anterior uveitis associated with the use of latanoprost.
DESIGN: A retrospective review of patients treated with latanoprost in the authors' practice between September 1, 1996, and August 1, 1997, was performed.
PARTICIPANTS: Ninety-four patients and 163 eyes were studied.
INTERVENTION: Patients presenting with signs and symptoms of ocular inflammation while receiving latanoprost were noted, and their response to the discontinuation of the drug was recorded.
MAIN OUTCOME MEASURES: The presence and degree of anterior uveitis and cystoid macular edema were measured.
RESULTS: Six (6.4%) of 94 patients (8 [4.9%] of 163 eyes) had anterior uveitis develop, and 2 (2.1%) of 94 patients (2 [1.2%] of 163 eyes) had cystoid macular edema develop while being treated with latanoprost.
CONCLUSION: Although latanoprost is an effective ocular-hypotensive agent, the authors' experience with the drug has shown a significant incidence of anterior uveitis and cystoid macular edema. To the authors' knowledge, this is the first study to report the incidence of both cystoid macular edema and anterior uveitis associated with latanoprost therapy. Treating physicians should be aware of these potential complicating side effects of latanoprost.

PMID 9479285  Ophthalmology. 1998 Feb;105(2):263-8.
著者: S Saccà, A Pascotto, C Siniscalchi, M Rolando
雑誌名: J Ocul Pharmacol Ther. 2001 Apr;17(2):107-13. doi: 10.1089/10807680151125393.
Abstract/Text The purpose of this study was to report paradoxical reaction on the intraocular pressure after treatment with latanoprost in 3 cases of uveitic glaucoma. Serial clinical examinations of intraocular pressure by means of daily tonometric curves were performed in three patients with uveitic glaucoma before and after the beginning of latanoprost therapy. All measurements were performed by two doctors, but every patient's IOP was always measured by the same doctor. Adverse reactions, such as increased intraocular pressure and recurrence of inflammation, were noted to occur 7 to 16 days after rechallenging with topical latanoprost therapy for glaucoma in patients with history of uveitic glaucoma. The conclusion indicates that clinicians should be alerted to these possible complications of topical latanoprost therapy in uveitic glaucoma.

PMID 11324978  J Ocul Pharmacol Ther. 2001 Apr;17(2):107-13. doi: 10.1・・・
著者: C B Camras, A Alm, P Watson, J Stjernschantz
雑誌名: Ophthalmology. 1996 Nov;103(11):1916-24.
Abstract/Text PURPOSE: To determine efficacy and safety of latanoprost, a prostaglandin analog for glaucoma, during 1 year of treatment.
METHODS: After baseline measurements, 0.005% latanoprost was topically applied once daily for 12 months in patients from Scandinavia, the United Kingdom, and the United States who had elevated intraocular pressure (IOP). Diagnoses included ocular hypertension, chronic open-angle glaucoma, exfoliation syndrome, and pigment dispersion syndrome. Treatment was masked for the first 6 months and open-label during the second 6 months.
RESULTS: Of the 272 patients initially enrolled, withdrawals were due to inadequate IOP control (1%), increased iris pigmentation (5%), other ocular problems (3%), systemic medical problems (3%), and nonmedical reasons (14%). Latanoprost significantly (P < 0.0001) reduced diumal IOP from 25.3 +/- 3.0 mmHg (mean +/- standard deviation) at baseline to 17.4 +/- 2.7 mmHg (32% reduction) at 12 months in the 198 patients who completed 1 year of treatment. The IOP reduction was maintained at a consistent level throughout the 12 months without evidence of drift, and was not affected by sex, age, race, or eye color. Overall, latanoprost caused a possible or definite increase in iris pigmentation in 12% of the 272 patients, all of whom had multicolored irides at baseline. One half of these patients with increased pigmentation withdrew before completing 1 year of therapy. Visual field, optic disc cupping, visual acuity, refractive error, conjunctival hyperemia, aqueous flare, anterior chamber cellular response, lens examination, blood pressure, heart rate, blood tests, and urinalysis were not appreciably altered.
CONCLUSION: Latanoprost safely and effectively reduces IOP for 1 year in patients of diverse nationalities, providing further evidence for its usefulness in chronic glaucoma therapy.

PMID 8942890  Ophthalmology. 1996 Nov;103(11):1916-24.
著者: Albert Alm, John Schoenfelder, Jacquie McDermott
雑誌名: Arch Ophthalmol. 2004 Jul;122(7):957-65. doi: 10.1001/archopht.122.7.957.
Abstract/Text OBJECTIVE: To evaluate the 5-year safety and efficacy of adjunctive 0.005% latanoprost once daily.
METHODS: Patients with primary open-angle or exfoliation glaucoma who completed a 3-year, open-label, uncontrolled, prospective trial could enter a 2-year extension phase. High-resolution color photographs of irides were taken at baseline and at 14 subsequent visits. Photographs were assessed for change in iris pigmentation compared with baseline. Intraocular pressures and adverse events were recorded.
MAIN OUTCOME MEASURE: Development and progression of increased iris pigmentation over 5 years.
RESULTS: Of the 519 original patients, 380 enrolled in the extension phase with approximately 89% having an eye color known to be susceptible to color change. After 5 years, most patients had no increase in iris pigmentation, but certain colored irides exhibited notably greater susceptibility than others. For those whose irides did change, onset occurred during the first 8 months in 74% and during the first 24 months in 94%. No patient developed an increase in pigmentation after month 36; the rate of progression decreased over time. Adverse event profiles were similar for patients with and without increased pigmentation. The overall mean intraocular pressure reduction from baseline of 25% was sustained with no need for change in intraocular pressure-lowering treatment in 70% of the eyes.
CONCLUSION: Latanoprost therapy is safe and well tolerated for long-term treatment of open-angle glaucoma.

PMID 15249358  Arch Ophthalmol. 2004 Jul;122(7):957-65. doi: 10.1001/a・・・
著者: 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
雑誌名: 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  Am J Ophthalmol. 2000 Oct;130(4):492-513.
著者: Christine Fardeau, Thi Ha Chau Tran, Badra Gharbi, Nathalie Cassoux, Bahram Bodaghi, Phuc LeHoang
雑誌名: Int Ophthalmol. 2007 Apr-Jun;27(2-3):163-72. doi: 10.1007/s10792-006-9024-7. Epub 2007 Feb 2.
Abstract/Text OBJECTIVE: To report features of retinal fluorescein (FA) and indocyanine green (ICGA) angiography and optical coherence tomography (OCT) at successive stages of Vogt-Koyanagi-Harada (VKH) disease.
METHODS: FA and ICGA were systematically performed in cases of VKH disease, at admission, 1 month later, and at the end of the follow-up. In addition, the most recent patients underwent OCT. In the follow-up, the clinical evolution and extent of treatment were related to the angiographic and tomographic features.
RESULTS: FA and ICGA showed a diffuse delayed choroidal perfusion, including a delayed arterial, choriocapillar, and venous filling. This delayed choroidal perfusion involved the posterior pole and the hole periphery. The classically described serous retinal detachments were slowly filled from numerous pin points that could correspond to leakage through areas of damaged retinal pigment epithelium due to the choroidal ischemia. An uneven background choroidal fluorescence visible at the mid phase of ICGA was the result of multiple hypofluorescent round lesions in the choroidal stroma. Choroidal folds appeared hypofluorescent in FA and hyperfluorescent in ICGA. Some of these angiographic findings were present at the very early neurologic stage of the disease. Moreover, under treatment, a persisting altered choroidal perfusion could increase the incidence of retinal detachment relapses.
DISCUSSION: Various pathological conditions are characterized by choroidal involvement and serous retinal detachment. Angiographical findings may be helpful in the diagnosis.
CONCLUSION: FA coupled with ICGA can be an useful tool in the early diagnosis of VKH disease as well as during the tapering of immunosuppressive drugs.

PMID 17273903  Int Ophthalmol. 2007 Apr-Jun;27(2-3):163-72. doi: 10.10・・・
著者: Lourdes Arellanes-García, Moisés Hernández-Barrios, Jans Fromow-Guerra, Pedro Cervantes-Fanning
雑誌名: Int Ophthalmol. 2007 Apr-Jun;27(2-3):155-61. doi: 10.1007/s10792-006-9027-4. Epub 2007 Jan 26.
Abstract/Text PURPOSE: To report the fluorescein fundus angiographic (FFA) findings in the different clinical stages of Vogt-Koyanagi-Harada (VKH) patients.
METHODS: Retrospective, transversal and descriptive study. All patients underwent FFA at least in one occasion. Patients with incomplete clinical files or a deficient FFA were excluded. We divided the patients in four groups, depending on their clinical stage at the time of the study: acute uveitic stage, chronic uveitis stage, convalescent stage and recurrence stage. We correlated the frequency and statistical significance of eleven angiographic patterns with their corresponding clinical stages.
RESULTS: The files of 60 patients were reviewed. Most common findings in the acute uveitis stage were: disseminated spotted choroidal hyperfluorescence and choroidal hypofluorescence. In the chronic uveitic stage: spotted hyper and hypofluorescence and optic disc hyperfluorescence. In the convalescent stage: spotted hyper and hypofluorescence and blockage of choroidal fluorescence. Retinal vasculitis was found more frequently than in previous reports. A reticular hypofluorescent pattern with no clinical correlation was found.
CONCLUSIONS: The angiographic findings of VKH syndrome change as the disease progress along different clinical stages. Recognition of those different patterns helps the clinician to diagnose the disease during all its stages.

PMID 17253110  Int Ophthalmol. 2007 Apr-Jun;27(2-3):155-61. doi: 10.10・・・
著者: Carl P Herbort, Alessandro Mantovani, Nadia Bouchenaki
雑誌名: Int Ophthalmol. 2007 Apr-Jun;27(2-3):173-82. doi: 10.1007/s10792-007-9060-y. Epub 2007 Apr 25.
Abstract/Text PURPOSE: Firstly, to give a review of characteristic indocyanine green angiographic (ICGA) signs in Vogt-Koyanagi-Harada (VKH) disease and, secondly, to determine the utility of ICG angiography in the assessment and follow-up of choroidal inflammatory activity during initial high-dose inflammation suppressive therapy and during the tapering of therapy.
METHODS: We have first reviewed characteristic ICGA signs in VKH. This is followed by a study of four patients with an acute initial VKH uveitis episode who received regular initial and follow-up angiographic examinations for at least 9 months. Classical ICGA signs were recorded at onset and followed for at least 9 months and were correlated with treatment levels. The treatment consisted of high-dose oral corticosteroids (0.8-1.5 mg/kg) preceded by pulse intravenous methylprednisolone (500-1000 mg) for 3 days in hyperacute cases and followed by very slow tapering with the addition of an immunosuppressive agent in cases of insufficient response.
RESULTS: The major ICGA signs that were both consistently present and easy to record in the four VKH patients having an acute initial uveitis episode with a pre-treatment angiography and an angiographic follow-up for a minimum of 9 months include (1) early choroidal stromal vessel hyperfluorescence and leakage, (2) hypofluorescent dark dots, (3) fuzzy vascular pattern of large stromal vessels and (4) disc hyperfluorescence. All patients were treated with high-dose inflammation suppressive therapy: in two patients, within 14 and 21 days after initial symptoms, respectively, and in the other two patients, within 6 weeks. Hypofluorescent dark dots, the most constant and easily recordable sign, was very prominent in all cases at presentation. A 90% to complete resolution of dark dots was noted in all four patients after 4 months of therapy. The other three major angiographic signs, early choroidal stromal vessel hyperfluorescence and leakage, indistinct fuzzy vessels at the intermediate angiographic phase and disc hyperfluorescence resolved in all cases within 8 weeks or less of high-dose inflammation suppressive therapy. In three of the four patients, dark dots reappeared after a mean of 7.8 +/- 2.8 months after onset of therapy when the patients were under a mean corticosteroid dose of 13.2 +/- 6.3 mg per day without any significant clinical or fluorescein angiographic signs, indicating subclinical recurrence. An increase in the inflammation suppressive therapy again brought about angiographic resolution of choroidal subclinical disease in all cases.
CONCLUSION: Choroidal inflammation shown by ICG angiography can be suppressed completely by initial high-dose inflammation suppressive therapy. However, recurrent subclinical choroidal inflammation is detected at the end of the tapering period in a high proportion of cases. This indicates that, in the absence of an ICGA follow-up, undetected smoldering subclinical disease may persist, thereby explaining the frequently reported evolution towards sunset glow fundus despite an apparently controlled disease. This is a clear indication that VKH disease should be followed by ICG angiography and, in the case of choroidal subclinical reactivation, a reversal of therapy tapering and an extension of therapy duration should be considered.

PMID 17457515  Int Ophthalmol. 2007 Apr-Jun;27(2-3):173-82. doi: 10.10・・・
著者: Y Oshima, S Harino, Y Hara, Y Tano
雑誌名: Am J Ophthalmol. 1996 Jul;122(1):58-66.
Abstract/Text PURPOSE: To report the indocyanine green angiographic findings associated with Vogt-Koyanagi-Harada disease and compare them with fluorescein angiographic findings and monochromatic scanning laser images.
METHODS: In a prospective study, indocyanine green angiography, by scanning laser ophthalmoscopy or infrared fundus photography, was performed in ten consecutive patients (20 eyes) with Vogt-Koyanagi-Harada disease during the acute stage before and recovery stage after corticosteroid treatment. Findings were compared with fluorescein angiographic features and monochromatic scanning laser imaging.
RESULTS: During the acute stage of the disease, indocyanine green angiography disclosed a dark background in the early phase and multiple, non-uniform hypofluorescent lesions in the midphases. Lesions were more numerous and extensive than areas either of serous retinal detachment on monochromatic scanning laser imaging or of punctate hyperfluorescence on fluorescein angiography. During the recovery stage, the abnormal dark background on indocyanine green angiography at initial examination resolved, with choroidal vessels visible in all cases, but nonuniform hypofluorescent lesions persisted in most eyes. Fluorescein angiography disclosed hypofluorescent patchy areas, and confocal infrared laser imaging showed some bright reflective lesions in three patients with especially severe clinical symptoms. On final examination after an average of 17.7 months, both angiographies still disclosed abnormal findings in these three patients.
CONCLUSIONS: Indocyanine green angiographic findings suggest that choroidal inflammation may cause a transient choroidal circulatory disturbance during the acute stage of Vogt-Koyanagi-Harada disease. In more severe cases, this dysfunction may secondarily damage the retinal pigment epithelium.

PMID 8659599  Am J Ophthalmol. 1996 Jul;122(1):58-66.
著者: Marcela F Bordaberry
雑誌名: Curr Opin Ophthalmol. 2010 Nov;21(6):430-5. doi: 10.1097/ICU.0b013e32833eb78c.
Abstract/Text PURPOSE OF REVIEW: To review current advances in the diagnosis and therapy of Vogt-Koyanagi-Harada (VKH) disease.
RECENT FINDINGS: A new T-cell subset (Th17) may play an important role in the initiation and maintenance of inflammatory disease when stimulated by the interleukin (IL)-23, thus producing IL-17. Recent developments of new imaging techniques, such as high-resolution optical coherence tomography 3 scanner (OCT3), have allowed greater accuracy in VKH disease diagnosis. The OCT3 examinations have shown that cystoid spaces appear in the neurosensory layer (between the inner and outer segments of photoreceptors) and not in the subretinal space. This structural finding was also supported by functional studies with multifocal electroretinography that measured the photoreceptors activity. Antimetabolites (azathioprine, mycophenolate mofetil and methotrexate), T-cell inhibitors (cyclosporine and tacrolimus) and biologic agents, associated with the well known glucocorticosteroids therapy, showed good results in acute and chronic phases of the disease. Intravitreal triamcinolone and bevacizumab were reported to have encouraging results for progressive or stubborn cases of VKH disease.
SUMMARY: To uphold visual acuity, an early, fast and accurate diagnosis is necessary, followed by an aggressive and lengthy immunosuppressive treatment.

PMID 20829689  Curr Opin Ophthalmol. 2010 Nov;21(6):430-5. doi: 10.109・・・
著者: Cristóbal Couto, Ariel Schlaen, Mercedes Frick, Marina Khoury, Matilde Lopez, Erika Hurtado, Debra Goldstein
雑誌名: Ocul Immunol Inflamm. 2018;26(3):485-489. doi: 10.1080/09273948.2016.1236969. Epub 2016 Oct 24.
Abstract/Text PURPOSE: To evaluate the clinical outcome and safety of adalimumab in patients with Vogt-Koyanagi-Harada (VKH) disease.
METHODS: VKH patients treated with adalimumab seen at the University of Buenos Aires were reviewed. Main outcome measures were visual acuity, anterior segment inflammation, optic nerve inflammation (ONI), steroid sparing effect, number of immunosuppressives, and relapses.
RESULTS: In total, 14 VKH patients, mean age 23.07 ± 8 years; median of adalimumab treatment 10 months, were analyzed. At start of adalimumab treatment (baseline), median of corticosteroid dose was 20 mg and at 6 months, 4 mg. At baseline, 11 patients were on immunosuppressive treatment and at 6 months only four continued with immunosuppressive therapy. In the 28 eyes, the median of active inflammation was 2 at baseline and 0 after 6 months on adalimumab.
CONCLUSIONS: Treatment with adalimumab is an effective and safe option, reducing the need for oral corticosteroid and conventional immunosuppressive therapy.

PMID 27775450  Ocul Immunol Inflamm. 2018;26(3):485-489. doi: 10.1080/・・・

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