Pas Jeroen A A H, Li Catherina H Z, Van den Broeck Filip, Dhooge Patty P A, De Zaeytijd Julie, Collin Rob W J, Leroy Bart P, Hoyng Carel B
Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands.
Invest Ophthalmol Vis Sci. 2025 Apr 1;66(4):76. doi: 10.1167/iovs.66.4.76.
The purpose of this study was to assess the natural course of the retinal atrophy growth rate in patients with Stargardt disease (STGD1) with particular mutations in ABCA4, which may be eligible for mutation-specific therapy.
Fundus autofluorescence images (Heidelberg Spectralis) were gathered from 221 patients (436 eyes) in two centers: Radboud UMC and Ghent University Hospital. The area of definitely decreased autofluorescence and total decreased autofluorescence was measured using the Heidelberg RegionFinder software tool. Square root transformation was used to correct for two-dimensional growth. A mixed model was used to determine the atrophy growth rates. Atrophy growth rates were calculated for all eyes and were categorized into subgroups based on ABCA4 mutations potentially suitable for mutation-specific therapy (c.4539+2001G>A; c.5461-10T>C; c.5882G>A; c.768G>T), or subgroups based on age of onset.
The mean square root-transformed growth rate of atrophy was 0.1446 mm/year (95% CI, 0.1382-0.1510 mm/year) for definitely decreased autofluorescence and 0.1459 mm/year (95% CI, 0.1402-0.1515 mm/year) for total decreased autofluorescence. Definitely decreased autofluorescence square root-transformed atrophy growth was slower in patients heterozygous for c.5882G>A (0.0821 mm/year) and c.4539+2001G>A (0.0686 mm/year) than c.768G>T (0.1299 mm/year) and c.5461-10T>C (0.1565 mm/year). Eyes of patients with late-onset STGD1 had the fastest atrophy growth (0.1782 mm/year), compared with eyes of patients with early-onset STGD1 (0.1655 mm/year) and patients with intermediate-onset STGD1 (0.1269 mm/year).
Atrophy growth rates vary among subgroups of patients with STGD1, depending on both specific mutations and age of onset. This pattern may have implications for the design of clinical trials for mutation-specific therapies.
本研究旨在评估患有特定ABCA4突变的斯塔加特病（STGD1）患者视网膜萎缩生长速率的自然病程，这些患者可能符合针对特定突变的治疗条件。
从拉德堡大学医学中心（Radboud UMC）和根特大学医院这两个中心的221名患者（436只眼）收集眼底自发荧光图像（海德堡Spectralis）。使用海德堡RegionFinder软件工具测量明确降低的自发荧光区域和总的降低的自发荧光区域。采用平方根变换来校正二维生长。使用混合模型确定萎缩生长速率。计算所有眼睛的萎缩生长速率，并根据可能适用于针对特定突变治疗的ABCA4突变（c.4539 + 2001G>A；c.5461 - 10T>C；c.5882G>A；c.768G>T）或根据发病年龄将其分为亚组。
对于明确降低的自发荧光，萎缩的平均平方根变换生长速率为0.1446毫米/年（95%置信区间，0.1382 - 0.1510毫米/年），对于总的降低的自发荧光，为0.1459毫米/年（95%置信区间，0.1402 - 0.1515毫米/年）。对于c.5882G>A（0.0821毫米/年）和c.4539 + 2001G>A（0.0686毫米/年）杂合子患者，明确降低的自发荧光平方根变换后的萎缩生长比c.768G>T（0.1299毫米/年）和c.5461 - 10T>C（0.1565毫米/年）患者慢。晚发性STGD1患者的眼睛萎缩生长最快（0.1782毫米/年），相比之下，早发性STGD1患者的眼睛（0.1655毫米/年）和中间发病型STGD1患者的眼睛（0.1269毫米/年）。
STGD1患者亚组之间的萎缩生长速率有所不同，这取决于特定突变和发病年龄。这种模式可能对针对特定突变治疗的临床试验设计有影响。
