Kempen John H, Altaweel Michael M, Holbrook Janet T, Sugar Elizabeth A, Thorne Jennifer E, Jabs Douglas A
Department of Ophthalmology, Massachusetts Eye and Ear, Boston3The Discovery Eye Center, MyungSung Christian Medical Center and MyungSung Medical School, Addis Ababa, Ethiopia.
Fundus Photograph Reading Center, Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison.
JAMA. 2017 May 16;317(19):1993-2005. doi: 10.1001/jama.2017.5103.
A randomized clinical trial comparing fluocinolone acetonide implant vs systemic corticosteroids and immunosuppression for treatment of severe noninfectious intermediate, posterior, and panuveitides did not result in a significant difference in visual acuity at 2 and 4.5 years; longer-term outcomes are not known.
To compare the association between intravitreous fluocinolone acetonide implant vs systemic therapy and long-term visual and other outcomes in patients with uveitis.
DESIGN, SETTING, AND PARTICIPANTS: Nonprespecified 7-year observational follow-up of the Multicenter Uveitis Steroid Treatment (MUST) randomized clinical trial comparing the alternative treatments. Follow-up was conducted in tertiary uveitis subspecialty practices in the United States (21), the United Kingdom (1), and Australia (1). Of 255 patients 13 years or older with intermediate, posterior, or panuveitis (active within ≤60 days) enrolled in the MUST trial between December 6, 2005, and December 9, 2008, 215 consented to ongoing follow-up through at least 7 years postrandomization (last visit, February 10, 2016).
Participants had been randomized to receive a surgically placed intravitreous fluocinolone acetonide implant or systemic corticosteroids supplemented by immunosuppression. When both eyes required treatment, both eyes were treated.
Primary outcome was change from baseline in best-corrected visual acuity in uveitic eyes (5 letters = 1 visual acuity chart line; potential range of change in letters read, -121 to +101; minimal clinically important difference, 7 letters), analyzed by treatment assignment accounting for nonindependence of eyes when patients had 2 uveitic eyes. Secondary outcomes included potential systemic toxicities of corticosteroid and immunosuppressive therapy and death.
Seven-year data were obtained for 161 uveitic eyes (70% of 90 patients assigned to implant) and 167 uveitic eyes (71% of 90 patients assigned to systemic therapy) (77% female; median age at enrollment, 48 [interquartile range, 36-56] years). Change in mean visual acuity from baseline (implant, 61.7; systemic therapy, 65.0) through 7 years (implant, 55.8; systemic therapy, 66.2) favored systemic therapy by 7.2 (95% CI, 2.1-12) letters. Among protocol-specified, prospectively collected systemic adverse outcomes, the cumulative 7-year incidence in the implant and systemic therapy groups, respectively, was less than 10%, with the exceptions of hyperlipidemia (6.1% vs 11.2%), hypertension (9.8% vs 18.4%), osteopenia (41.5% vs 43.1%), fractures (11.3% vs 18.6%), hospitalization (47.6% vs 42.3%), and antibiotic-treated infection (57.4% vs 72.3%).
In 7-year extended follow-up of a randomized trial of patients with severe intermediate, posterior, or panuveitis, those randomized to receive systemic therapy had better visual acuity than those randomized to receive intravitreous fluocinolone acetonide implants. Study interpretation is limited by loss to follow-up.
clinicaltrials.gov Identifier: NCT00132691.
一项比较氟轻松醋酸酯植入物与全身用皮质类固醇及免疫抑制疗法治疗严重非感染性中间葡萄膜炎、后葡萄膜炎和全葡萄膜炎的随机临床试验，在2年和4.5年时视力未出现显著差异；长期结果未知。
比较玻璃体内注射氟轻松醋酸酯植入物与全身治疗对葡萄膜炎患者长期视力及其他结果的影响。
设计、地点和参与者：对多中心葡萄膜炎类固醇治疗（MUST）随机临床试验进行非预先设定的7年观察性随访，比较替代治疗方法。随访在美国（21个）、英国（1个）和澳大利亚（1个）的三级葡萄膜炎专科进行。在2005年12月6日至2008年12月9日期间纳入MUST试验的255例13岁及以上患有中间葡萄膜炎、后葡萄膜炎或全葡萄膜炎（≤60天内活动）的患者中，215例同意在随机分组后至少随访7年（最后一次随访时间为2016年2月10日）。
参与者被随机分配接受手术植入玻璃体内氟轻松醋酸酯植入物或全身用皮质类固醇并辅以免疫抑制治疗。当双眼均需治疗时，双眼都进行治疗。
主要结局是葡萄膜炎患眼最佳矫正视力相对于基线的变化（5个字母 = 视力表1行；字母阅读变化的潜在范围为 -121至 +101；最小临床重要差异为7个字母），按治疗分组进行分析，同时考虑患者双眼受累时双眼的非独立性。次要结局包括皮质类固醇和免疫抑制治疗的潜在全身毒性以及死亡。
获得了161只葡萄膜炎患眼（分配至植入物组的90例患者中的70%）和167只葡萄膜炎患眼（分配至全身治疗组的90例患者中的71%）的7年数据（77%为女性；入组时的中位年龄为48岁[四分位间距为36 - 56岁]）。从基线到7年时平均视力的变化（植入物组，61.7；全身治疗组，65.0）（植入物组，55.8；全身治疗组，66.2）显示全身治疗组比植入物组高7.2个字母（95%置信区间，2.1 - 12）。在方案规定的、前瞻性收集的全身不良结局中，植入物组和全身治疗组7年累计发生率分别低于10%，但高脂血症（6.1%对11.2%）、高血压（9.8%对18.4%）、骨质减少（41.5%对43.1%）、骨折（11.3%对18.6%）、住院（47.6%对42.3%）以及接受抗生素治疗的感染（57.4%对72.3%）除外。
在对严重中间葡萄膜炎、后葡萄膜炎或全葡萄膜炎患者的随机试验进行7年延长随访中，随机接受全身治疗的患者视力优于随机接受玻璃体内氟轻松醋酸酯植入物治疗的患者。研究解读因失访而受限。
clinicaltrials.gov标识符：NCT00132691。
