Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom; Department of Ophthalmology, University of Bonn, Bonn, Germany; Center for Rare Diseases, University of Bonn, Bonn, Germany.
BioQuant, University of Heidelberg, Heidelberg, Germany.
Am J Ophthalmol. 2020 May;213:134-144. doi: 10.1016/j.ajo.2020.01.013. Epub 2020 Jan 24.
To investigate the prognostic value of demographic, functional, and imaging parameters on retinal pigment epithelium (RPE) atrophy progression secondary to maternally inherited diabetes and deafness (MIDD) and to evaluate the application of these factors in clinical trial design.
Retrospective observational case series.
Thirty-five eyes of 20 patients (age range, 24.9-75.9 years) with genetically proven MIDD and demarcated RPE atrophy on serial fundus autofluorescence (AF) images were included. Lesion size and shape-descriptive parameters were longitudinally determined by 2 independent readers. A linear mixed-effect model was used to predict the lesion enlargement rate based on baseline variables. Sample size calculations were performed to model the power in a simulated interventional study.
The mean follow-up time was 4.27 years. The mean progression rate of RPE atrophy was 2.33 mm/year, revealing a dependence on baseline lesion size (+0.04 [0.02-0.07] mm/year/mm, P < .001), which was absent after square root transformation. The fovea was preserved in the majority of patients during the observation time. In the case of foveal involvement, the loss of visual acuity lagged behind central RPE atrophy in AF images. Sex, age, and number of atrophic foci predicted future progression rates with a cross-validated mean absolute error of 0.13 mm/year and to reduce the required sample size for simulated interventional trials.
Progressive RPE atrophy could be traced in all eyes using AF imaging. Shape-descriptive factors and patients' baseline characteristics had significant prognostic value, guiding appropriate subject selection and sample size in future interventional trial design.
研究人口统计学、功能和影像学参数对母系遗传性糖尿病和耳聋（MIDD）继发的视网膜色素上皮（RPE）萎缩进展的预后价值，并评估这些因素在临床试验设计中的应用。
回顾性观察性病例系列。
纳入 35 只眼 20 例（年龄 24.9-75.9 岁）患者，这些患者均经基因证实患有 MIDD ，并在眼底自发荧光（AF）图像的系列检查中出现边界清晰的 RPE 萎缩。由 2 名独立的读者对病变大小和形态描述性参数进行纵向测定。采用线性混合效应模型根据基线变量预测病变扩大率。进行样本量计算以模拟干预研究中的功效。
平均随访时间为 4.27 年。RPE 萎缩的平均进展速度为 2.33mm/年，显示出与基线病变大小的依赖性（+0.04[0.02-0.07]mm/年/mm，P<.001），但在平方根转换后则不存在这种依赖性。在观察期间，大多数患者的黄斑保持完好。在黄斑受累的情况下，视力丧失滞后于 AF 图像中中心 RPE 萎缩。性别、年龄和萎缩病灶数量可以预测未来的进展速度，经交叉验证的平均绝对误差为 0.13mm/年，并减少模拟干预试验所需的样本量。
使用 AF 成像可以追踪所有眼睛的进行性 RPE 萎缩。形态描述性因素和患者的基线特征具有重要的预后价值，可指导未来干预试验设计中的适当患者选择和样本量。
