Strauss Rupert W, Muñoz Beatriz, Ho Alexander, Jha Anamika, Michaelides Michel, Cideciyan Artur V, Audo Isabelle, Birch David G, Hariri Amir H, Nittala Muneeswar G, Sadda SriniVas, West Sheila, Scholl Hendrik P N
Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland.
Moorfields Eye Hospital National Health Service Foundation Trust, London, England.
JAMA Ophthalmol. 2017 Nov 1;135(11):1232-1241. doi: 10.1001/jamaophthalmol.2017.4152.
Sensitive outcome measures for disease progression are needed for treatment trials of Stargardt disease.
To describe the yearly progression rate of atrophic lesions in the retrospective Progression of Stargardt Disease study.
DESIGN, SETTING, AND PARTICIPANTS: A multicenter retrospective cohort study was conducted at tertiary referral centers in the United States and Europe. A total of 251 patients aged 6 years or older at baseline, harboring disease-causing variants in ABCA4 (OMIM 601691), enrolled in the study from 9 centers between August 2, 2013, and December 12, 2014; of these patients, 215 had at least 2 gradable fundus autofluorescence images with atrophic lesion(s) present in at least 1 eye.
Areas of definitely decreased autofluorescence (DDAF) and questionably decreased autofluorescence were quantified by a reading center. Progression rates were estimated from linear mixed models with time as the independent variable.
Yearly rate of progression using the growth of atrophic lesions measured by fundus autofluorescence.
A total of 251 participants (458 study eyes) were enrolled. Images from 386 eyes of 215 participants (126 females and 89 males; mean [SD] age, 29.9 [14.7] years; mean [SD] age of onset of symptoms, 21.9 [13.3] years) showed atrophic lesions present on at least 2 visits and were graded for 2 (156 eyes), 3 (174 eyes), or 4 (57 eyes) visits. A subset of 224 eyes (123 female participants and 101 male participants; mean [SD] age, 33.0 [15.1] years) had areas of DDAF present on at least 2 visits; these eyes were included in the estimation of the progression of the area of DDAF. At the first visit, DDAF was present in 224 eyes (58.0%), with a mean (SD) lesion size of 2.2 (2.7) mm2. The total mean (SD) area of decreased autofluorescence (DDAF and questionably decreased autofluorescence) at first visit was 2.6 (2.8) mm2. Mean progression of DDAF was 0.51 mm2/y (95% CI, 0.42-0.61 mm2/y), and of total decreased fundus autofluorescence was 0.35 mm2/y (95% CI, 0.28-0.43 mm2/y). Rates of progression depended on the initial size of the lesion.
In Stargardt disease with DDAF lesions, fundus autofluorescence may serve as a monitoring tool for interventional clinical trials that aim to slow disease progression. Rates of progression depended mainly on initial lesion size.
斯塔加特病的治疗试验需要针对疾病进展的敏感结局指标。
在斯塔加特病进展的回顾性研究中描述萎缩性病变的年进展率。
设计、设置和参与者：在美国和欧洲的三级转诊中心进行了一项多中心回顾性队列研究。共有251名基线年龄在6岁及以上、携带ABCA4（OMIM 601691）致病变异的患者，于2013年8月2日至2014年12月12日期间从9个中心纳入研究；这些患者中，215名至少有2张可分级的眼底自发荧光图像，且至少一只眼中存在萎缩性病变。
由一个阅片中心对明确降低的自发荧光（DDAF）区域和可疑降低的自发荧光区域进行量化。进展率通过以时间为自变量的线性混合模型进行估计。
使用眼底自发荧光测量的萎缩性病变生长情况来计算年进展率。
共纳入251名参与者（458只研究眼）。215名参与者（126名女性和89名男性；平均[标准差]年龄，29.9[14.7]岁；症状发作的平均[标准差]年龄，21.9[13.3]岁）的386只眼的图像显示萎缩性病变在至少2次就诊时出现，并针对2次（156只眼）、3次（174只眼）或4次（57只眼）就诊进行了分级。一部分224只眼（123名女性参与者和101名男性参与者；平均[标准差]年龄，33.0[15.1]岁）在至少2次就诊时存在DDAF区域；这些眼被纳入DDAF区域进展情况的估计。在首次就诊时，224只眼（58.0%）存在DDAF，平均（标准差）病变大小为2.2（2.7）mm²。首次就诊时自发荧光降低（DDAF和可疑降低的自发荧光）的总平均（标准差）面积为2.6（2.8）mm²。DDAF的平均进展为0.51mm²/年（95%CI，0.42 - 0.61mm²/年），眼底自发荧光降低的总体平均进展为0.35mm²/年（95%CI，0.28 - 0.43mm²/年）。进展率取决于病变的初始大小。
在患有DDAF病变的斯塔加特病中，眼底自发荧光可作为旨在减缓疾病进展的干预性临床试验的监测工具。进展率主要取决于初始病变大小。
