Background/aims To investigate the progression of quantitative autofluorescence (qAF) measures and the potential as clinical trial endpoint in ABCA4 -related retinopathy. Methods In this longitudinal monocentre study, 64 patients with ABCA4 -related retinopathy (age (mean±SD), 34.84±16.36 years) underwent serial retinal imaging, including optical coherence tomography (OCT) and qAF (488 nm excitation) imaging using a modified confocal scanning laser ophthalmoscope with a mean (±SD) review period of 20.32±10.90 months. A group of 110 healthy subjects served as controls. Retest variability, changes of qAF measures over time and its association with genotype and phenotype were analysed. Furthermore, individual prognostic feature importance was assessed, and sample size calculations for future interventional trials were performed. Results Compared with controls, qAF levels of patients were significantly elevated. The test–retest reliability revealed a 95% coefficient of repeatability of 20.37. During the observation time, young patients, patients with a mild phenotype (morphological and functional) and patients with mild mutations showed an absolute and relative increase in qAF values, while patients with advanced disease manifestation (morphological and functional), and homozygous mutations at adulthood revealed a decrease in qAF. Considering these parameters, required sample size and study duration could significantly be reduced. Conclusion Under standardised settings with elaborated conditions towards operators and analysis to counterbalance variability, qAF imaging might be reliable, suitable for quantifying disease progression and constitutes a potential clinical surrogate marker in ABCA4 -related retinopathy. Trial design based on patients’ baseline characteristics and genotype has the potential to provide benefits regarding required cohort size and absolute number of visits. Data are available upon reasonable request.

中文翻译：

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ABCA4 相关视网膜病变定量眼底自发荧光测量的进展、可靠性、预测参数和样本量计算


背景/目的 研究定量自发荧光 (qAF) 测量的进展以及作为 ABCA4 相关视网膜病变临床试验终点的潜力。方法 在这项纵向单中心研究中，64 名 ABCA4 相关视网膜病变患者（年龄（平均值±SD），34.84±16.36 岁）接受了系列视网膜成像，包括使用改良的光学相干断层扫描（OCT）和 qAF（488 nm 激发）成像。共焦扫描激光检眼镜，平均 (±SD) 审查期为 20.32±10.90 个月。一组 110 名健康受试者作为对照组。分析了重新测试的变异性、qAF 测量值随时间的变化及其与基因型和表型的关联。此外，还评估了个体预后特征的重要性，并计算了未来干预试验的样本量。结果与对照组相比，患者的qAF水平显着升高。重测可靠性显示 95% 的重复性系数为 20.37。观察期间，年轻患者、轻度表型（形态和功能）患者以及轻度突变患者的qAF值出现绝对和相对升高，而晚期疾病表现（形态和功能）患者以及成年期纯合突变患者显示 qAF 下降。考虑到这些参数，所需的样本量和研究持续时间可以显着减少。结论 在标准化设置下，对操作者有详细的条件并进行平衡变异性的分析，qAF 成像可能是可靠的，适合量化疾病进展，并构成 ABCA4 相关视网膜病变的潜在临床替代标志物。 基于患者基线特征和基因型的试验设计有可能在所需队列规模和绝对就诊次数方面带来益处。数据可根据合理要求提供。