From the Department of Ophthalmology, Medical University Graz (R.W.S.), Graz, Austria; Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, University College London (R.W.S., K.F., M.M.), London, United Kingdom; Department of Ophthalmology, Kepler University Clinic (R.W.S.), Linz, Austria; Institute of Clinical and Molecular Ophthalmology Basel (IOB) (R.W.S., H.P.N.S.), Basel, Switzerland.
Doheny Eye Institute, David Geffen School of Medicine at University of California Los Angeles (A.H., A.J., S.S., M.I.), California, USA.
Am J Ophthalmol. 2023 Jun;250:157-170. doi: 10.1016/j.ajo.2023.02.003. Epub 2023 Feb 9.
To estimate the progression rate of atrophic lesions in Stargardt disease derived from fundus autofluorescence (FAF).
International, multicenter, prospective cohort study.
A total of 259 participants aged ≥6 years with disease-causing variants in the ABCA4 gene were enrolled from 9 centers and followed over a 24-month period. FAF images were obtained every 6 months, and areas of definitely decreased autofluorescence (DDAF) and decreased autofluorescence (DAF) were quantified. Progression rates were estimated from linear mixed models with time as the independent variable.
A total of 488 study eyes of 259 participants (88.8% with both eyes) were enrolled and images from 432 eyes were followed for 24 months. The overall estimated progression of DDAF was 0.74 mm/y (95% CI 0.64-0.85, P < .0001) and that of DAF was 0.64 mm/y (95% CI 0.57-0.71) over a 24-month period in univariate analysis. Growth rates were strongly dependent on baseline lesion area. After square root transformation, the DDAF growth rate was not dependent on baseline lesion radius (P = .11), whereas the DAF growth rate was dependent (P < .0001). Genotype was not found to significantly impact the growth rate of DDAF or DAF lesions.
FAF may serve as a convenient monitoring tool and suitable end point for interventional clinical trials that aim to slow disease progression. DDAF and DAF lesion sizes at baseline are strong predicting factors for lesion area growth and can be partially accounted for by square root transformation.
从眼底自发荧光（FAF）估计斯塔加特病萎缩病变的进展速度。
国际多中心前瞻性队列研究。
共招募了 9 个中心的 259 名年龄≥6 岁且携带 ABCA4 基因突变的患者，随访 24 个月。每 6 个月进行一次 FAF 图像采集，并对明确减少的自发荧光（DDAF）和减少的自发荧光（DAF）区域进行量化。使用线性混合模型，以时间为自变量，估计进展率。
共纳入了 259 名患者的 488 只研究眼（88.8%的患者双眼均被纳入），其中 432 只眼的图像随访了 24 个月。在单变量分析中，DDAF 的总体估计进展速度为 0.74mm/y（95%CI 0.64-0.85，P<.0001），DAF 的进展速度为 0.64mm/y（95%CI 0.57-0.71）。在未校正分析中，基线病变面积强烈影响增长率。经平方根转换后，DDAF 的增长率与基线病变半径无关（P=.11），而 DAF 的增长率则依赖于（P<.0001）。未发现基因型对 DDAF 或 DAF 病变的增长率有显著影响。
FAF 可能成为一种方便的监测工具和合适的终点，适用于旨在减缓疾病进展的干预性临床试验。基线时 DDAF 和 DAF 病变大小是病变面积增长的强有力预测因素，可部分通过平方根转换来解释。
