Department of Ophthalmology, University of Bonn, Ernst-Abbe-Str. 2, 53127, Bonn, Germany.
Center for Rare Diseases, University of Bonn, Bonn, Germany.
Sci Rep. 2021 Jan 14;11(1):1466. doi: 10.1038/s41598-020-80766-4.
Spatially-resolved retinal function can be measured by psychophysical testing like fundus-controlled perimetry (FCP or 'microperimetry'). It may serve as a performance outcome measure in emerging interventional clinical trials for macular diseases as requested by regulatory agencies. As FCP constitute laborious examinations, we have evaluated a machine-learning-based approach to predict spatially-resolved retinal function ('inferred sensitivity') based on microstructural imaging (obtained by spectral domain optical coherence tomography) and patient data in recessive Stargardt disease. Using nested cross-validation, prediction accuracies of (mean absolute error, MAE [95% CI]) 4.74 dB [4.48-4.99] were achieved. After additional inclusion of limited FCP data, the latter reached 3.89 dB [3.67-4.10] comparable to the test-retest MAE estimate of 3.51 dB [3.11-3.91]. Analysis of the permutation importance revealed, that the IS&OS and RPE thickness were the most important features for the prediction of retinal sensitivity. 'Inferred sensitivity', herein, enables to accurately estimate differential effects of retinal microstructure on spatially-resolved function in Stargardt disease, and might be used as quasi-functional surrogate marker for a refined and time-efficient investigation of possible functionally relevant treatment effects or disease progression.
空间分辨视网膜功能可通过眼底控制的视野检查（FCP 或“微视野检查”）等心理物理学测试进行测量。它可以作为新兴的黄斑疾病干预性临床试验的疗效评估指标，这也是监管机构的要求。由于 FCP 检查较为繁琐，我们评估了一种基于机器学习的方法，旨在根据微结构成像（通过光谱域光学相干断层扫描获得）和隐性斯塔加特病患者的数据来预测空间分辨视网膜功能（“推断的敏感性”）。使用嵌套交叉验证，（平均绝对误差，MAE [95%CI]）达到 4.74dB [4.48-4.99]的预测准确率。在进一步纳入有限的 FCP 数据后，后者达到 3.89dB [3.67-4.10]，与测试-重测 MAE 估计值 3.51dB [3.11-3.91]相当。置换重要性分析表明，IS&OS 和 RPE 厚度是预测视网膜敏感性的最重要特征。“推断的敏感性”可以准确估计斯塔加特病中视网膜微观结构对空间分辨功能的差异影响，并可能作为精细且高效的潜在功能相关治疗效果或疾病进展研究的准功能替代标志物。
