Incidence of Atrophic Lesions in Stargardt Disease in the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study Report No. 5
Incidence of Atrophic Lesions in Stargardt Disease in the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study Report No. 5
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DOI：
10.1001/jamaophthalmol.2017.1121
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发表时间：
2017-07-01
影响因子：
8.1
通讯作者：
Scholl, Hendrik P. N.
中科院分区：
文献类型：
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作者：
Strauss, Rupert W.;Munoz, Beatriz;Scholl, Hendrik P. N.
重要性 需要对疾病进展敏感的结果测量作为未来 Stargardt 病治疗试验的临床终点。 目的 通过眼底自发荧光成像检查 Stargardt 病患者视网膜色素上皮萎缩性病变的发生率。 设计、设置和参与者 在这项回顾性多中心队列研究中，基线时在欧洲三级转诊中心的 217 名 6 岁及以上患者，美国和英国的三磷酸腺苷（ATP）结合盒亚家族A成员4（ABCA4）基因携带致病变异并符合以下标准的患者入组：（1）最近就诊时至少1只眼睛有至少1个界限清楚的萎缩区域，最小直径为300μm，所有萎缩病变的总面积小于或等于12mm（2），并且(2) 至少 2 次就诊的眼底自发荧光图像，至少 2 次就诊之间间隔至少 6 个月。数据收集时间为2013年8月22日至2014年12月12日。数据分析时间为2015年3月15日至2017年1月31日。曝光图像由中央阅片中心的工作人员进行评估。概述并量化了明显减少的自发荧光（DDAF）和可疑减少的自发荧光（QDAF）区域。使用 Kaplan-Meier 生存曲线估计无病灶生存率。 主要结果和措施 通过眼底自发荧光确定萎缩性病变的发生率。 结果 217 名患者（平均 [SD] 年龄，21.8 [13.3] 岁；127 名女性 [57.5%]；148 名白人 [68.2%]）贡献了 390 只眼睛，平均（SD）随访时间为 3.9 (1.6) 年（范围：0.7-12.1 年）。在首次就诊时没有 DDAF 的眼睛中，出现 DDAF 病变的中位时间为 4.9 年（95% CI，4.3-5.6 年）。在没有 QDAF 的眼睛中，出现 QDAF 病变的中位时间为 6.3 年（95% CI，5.6-9.7 年）。与没有 DDAF 病变的眼睛相比，首次就诊时有 DDAF 病变的眼睛不太可能出现 QDAF 病变（风险比，0.19；95% CI，0.05-0.70；P = 0.01）。 结论和相关性 估计首次就诊时没有 DDAF 的眼睛中 50% 将在不到 5 年内出现病变，这表明发病率DDAF 的检测结果可以作为治疗试验的结果衡量标准。
IMPORTANCE Outcome measures that are sensitive to disease progression are needed as clinical end points for future treatment trials in Stargardt disease.OBJECTIVE To examine the incidence of atrophic lesions of the retinal pigment epithelium in patients with Stargardt disease as determined by fundus autofluorescence imaging.DESIGN, SETTING, AND PARTICIPANTS In this retrospective multicenter cohort study, 217 patients 6 years and older at baseline at tertiary referral centers in Europe, the United States, and the United Kingdom who were harboring disease-causing variants in the adenosine triphosphate (ATP)-binding cassette subfamily A member 4 (ABCA4) gene and who met the following criteria were enrolled: (1) at least 1 well-demarcated area of atrophy with a minimum diameter of 300 mu m, with the total area of all atrophic lesions being less than or equal to 12 mm(2) in at least 1 eye at the most recent visit, and (2) fundus autofluorescence images for at least 2 visits with a minimum of 6 months between at least 2 visits. Data were collected between August 22, 2013, and December 12, 2014. Data analysis was performed from March 15, 2015, through January 31, 2017.EXPOSURES Images were evaluated by staff at a central reading center. Areas of definitely decreased autofluorescence (DDAF) and questionably decreased autofluorescence (QDAF) were outlined and quantified. Lesion-free survival rates were estimated using Kaplan-Meier survival curves.MAIN OUTCOMES AND MEASURES Incidence of atrophic lesions as determined by fundus autofluorescence.RESULTS The 217 patients (mean [SD] age, 21.8 [13.3] years; 127 female [57.5%]; 148 white [68.2%]) contributed 390 eyes for which the mean (SD) follow-up time was 3.9 (1.6) years (range, 0.7-12.1 years). Among eyes without DDAF at first visit, the median time to develop a DDAF lesion was 4.9 years (95% CI, 4.3-5.6 years). Among eyes without QDAF, the median time to develop a QDAF lesion was 6.3 years (95% CI, 5.6-9.7 years). Eyes with a lesion of DDAF at the first visit were less likely to develop a QDAF lesion compared with eyes without a lesion of DDAF (hazard ratio, 0.19; 95% CI, 0.05-0.70; P = .01).CONCLUSIONS AND RELEVANCE An estimated 50% of the eyes without DDAF at first visit will develop the lesion in less than 5 years, suggesting that incidence of DDAF could serve as an outcome measure for treatment trials.