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抗结核治疗的结核性葡萄膜炎患者的临床特征和结局:协作性眼结核研究(COTS)-1 报告。

Clinical Features and Outcomes of Patients With Tubercular Uveitis Treated With Antitubercular Therapy in the Collaborative Ocular Tuberculosis Study (COTS)-1.

机构信息

National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore

Moorfields Eye Hospital, National Health Service Foundation Trust, London, England

出版信息

JAMA Ophthalmol. 2017 Dec 1;135(12):1318-1327. doi: 10.1001/jamaophthalmol.2017.4485.

Abstract

IMPORTANCE

Eradication of systemic tuberculosis (TB) has been limited by neglected populations and the HIV pandemic. Whereas ocular TB often presents as uveitis without any prior evidence of systemic TB, the existing uncertainty in the diagnosis of TB uveitis may perpetuate missed opportunities to address systemic TB.

OBJECTIVE

To examine the clinical features of TB uveitis and the associations with response to antitubercular therapy (ATT).

DESIGN, SETTING, AND PARTICIPANTS: This retrospective multinational cohort study included patients from 25 ophthalmology referral centers diagnosed with TB uveitis and treated with ATT from January 1, 2004, through December 31, 2014, with a minimum follow-up of 1 year.

MAIN OUTCOMES AND MEASURES

Treatment failure, defined as a persistence or recurrence of inflammation within 6 months of completing ATT, inability to taper oral corticosteroids to less than 10 mg/d or topical corticosteroid drops to less than 2 drops daily, and/or recalcitrant inflammation necessitating corticosteroid-sparing immunosuppressive therapy.

RESULTS

A total of 801 patients (1272 eyes) were studied (mean [SD] age, 40.5 [14.8] years; 413 [51.6%] male and 388 [48.4%] female; 577 [73.6%] Asian). Most patients had no known history (498 of 661 [75.3%]) of systemic TB. Most patients had bilateral involvement (471 of 801 [58.8%]). Common clinical signs reported include vitreous haze (523 of 1153 [45.4%]), retinal vasculitis (374 of 874 [42.8%]), and choroidal involvement (419 of 651 [64.4%]). Treatment failure developed in 102 of the 801 patients (12.7%). On univariate regression analysis, the hazard ratios (HRs) associated with intermediate uveitis (HR, 2.21; 95% CI, 1.07-4.55; P = .03), anterior uveitis (HR, 2.68; 95% CI, 1.32-2.35; P = .006), and panuveitis (HR, 3.28; 95% CI, 1.89-5.67; P < .001) were significantly higher compared with posterior distribution. The presence of vitreous haze had a statistically significant association (HR, 1.95; 95% CI, 1.26-3.02; P = .003) compared with absence of vitreous haze. Bilaterality had an associated HR of 1.50 (95% CI, 0.96-2.35) compared with unilaterality (HR, 1 [reference]), although this finding was not statistically significant (P = .07). On multivariate Cox proportional hazards regression analysis, the presence of vitreous haze had an adjusted HR of 2.98 (95% CI, 1.50-5.94; P = .002), presence of snow banking had an adjusted HR of 3.71 (95% CI, 1.18-11.62; P = .02), and presence of choroidal involvement had an adjusted HR of 2.88 (95% CI, 1.22-6.78; P = .02).

CONCLUSIONS AND RELEVANCE

A low treatment failure rate occurred in patients with TB uveitis treated with ATT. Phenotypes and test results are studied whereby patients with panuveitis having vitreous and choroidal involvement had a higher risk of treatment failure. These findings are limited by retrospective methods. A prospectively derived composite clinical risk score might address this diagnostic uncertainty through holistic and standardized assessment of the combinations of clinical features and investigation results that may warrant diagnosis of TB uveitis and treatment with ATT.

摘要

重要性

系统性结核病(TB)的根除受到被忽视人群和 HIV 大流行的限制。虽然眼部 TB 通常表现为没有任何先前系统性 TB 证据的葡萄膜炎,但 TB 葡萄膜炎诊断中存在的不确定性可能会导致错失治疗系统性 TB 的机会。

目的

研究 TB 葡萄膜炎的临床特征及其与抗结核治疗(ATT)反应的相关性。

设计、地点和参与者:本回顾性多国队列研究纳入了 2004 年 1 月 1 日至 2014 年 12 月 31 日期间在 25 个眼科转诊中心被诊断为 TB 葡萄膜炎并接受 ATT 治疗的患者,随访时间至少为 1 年。

主要结局和测量

治疗失败定义为 ATT 完成后 6 个月内炎症持续或复发、无法将口服皮质类固醇减少至每天 10 毫克以下或局部皮质类固醇滴注减少至每天 2 滴以下、以及/或需要皮质类固醇保留免疫抑制治疗的顽固性炎症。

结果

共研究了 801 名患者(1272 只眼)(平均[SD]年龄 40.5[14.8]岁;413 名[51.6%]男性和 388 名[48.4%]女性;577 名[73.6%]亚洲人)。大多数患者没有已知的全身 TB 病史(661 例中的 498 例[75.3%])。大多数患者存在双侧受累(801 例中的 471 例[58.8%])。常见的临床体征包括玻璃体混浊(1153 例中的 523 例[45.4%])、视网膜血管炎(874 例中的 374 例[42.8%])和脉络膜受累(651 例中的 419 例[64.4%])。801 名患者中有 102 名(12.7%)发生治疗失败。在单变量回归分析中,中间葡萄膜炎(HR,2.21;95%CI,1.07-4.55;P=0.03)、前葡萄膜炎(HR,2.68;95%CI,1.32-2.35;P=0.006)和全葡萄膜炎(HR,3.28;95%CI,1.89-5.67;P<0.001)的风险比(HR)明显高于后分布。与无玻璃体混浊相比,玻璃体混浊的存在具有统计学意义的相关性(HR,1.95;95%CI,1.26-3.02;P=0.003)。双侧受累与单侧受累(HR,1[参考])相比,具有相关的 HR 为 1.50(95%CI,0.96-2.35),尽管这一发现没有统计学意义(P=0.07)。在多变量 Cox 比例风险回归分析中,玻璃体混浊的存在具有调整后的 HR 为 2.98(95%CI,1.50-5.94;P=0.002),雪堤的存在具有调整后的 HR 为 3.71(95%CI,1.18-11.62;P=0.02),脉络膜受累的存在具有调整后的 HR 为 2.88(95%CI,1.22-6.78;P=0.02)。

结论和相关性

接受 ATT 治疗的 TB 葡萄膜炎患者的治疗失败率较低。研究了表型和检测结果,发现全葡萄膜炎患者玻璃体和脉络膜受累的治疗失败风险更高。这些发现受到回顾性方法的限制。通过对可能需要 TB 葡萄膜炎诊断和 ATT 治疗的临床特征和检查结果的组合进行整体和标准化评估,可能会提出一种前瞻性的综合临床风险评分,以解决这种诊断不确定性。

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