Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Grenzacherstrasse 124, Basel 4070, Switzerland; Ophthalmology Section, Equine Department, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, Zurich 8057, Switzerland.
Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Grenzacherstrasse 124, Basel 4070, Switzerland.
J Pharmacol Toxicol Methods. 2020 Jul-Aug;104:106873. doi: 10.1016/j.vascn.2020.106873. Epub 2020 May 12.
Confocal scanning laser ophthalmoscopy and optical coherence tomography (cSLO-OCT) became available for human and animal ophthalmic examinations in recent years. The purpose of this study was to evaluate lesion detection and localization with cSLO-OCT imaging in an experimental outer retinal toxicity model and to compare cSLO-OCT to standard examination methods (indirect ophthalmoscopy (IO), fundus photography (FP) and central section histopathology).
A test compound was orally administered to albino rats (n = 4) for four weeks (part A) and to albino (n = 2) and pigmented (n = 2) rats for eight weeks (part B). Control animals received vehicle only. Retinal changes were documented using cSLO-OCT, IO, FP, angiography and histopathology. Retinal thicknesses were compared between groups using a mixed effects model.
All compound-treated animals developed progressive multifocal hyperreflective spot changes mostly confined to the retinal pigment epithelium. In study parts A and B, cSLO identified fundus lesions earlier than IO/FP in albino rats. In study part B, cSLO quantified fundus lesions more accurately than IO/FP in albino rats but no difference was seen in pigmented rats. Central section histopathology revealed no abnormalities in three out of four compound-treated animals in part B. Altogether, without cSLO-OCT, present fundus changes would have remained undetected in one of four compound-treated animals in both parts A and B.
Integration of combined cSLO-OCT imaging into toxicology study design can improve toxicity study readouts and facilitate longitudinal examination of single animals at multiple time points, leading to a reduction of experimental animal numbers.
近年来，共聚焦扫描激光检眼镜和光学相干断层扫描（cSLO-OCT）可用于人类和动物的眼科检查。本研究旨在评估在实验性视网膜外层毒性模型中使用 cSLO-OCT 成像进行病变检测和定位，并将 cSLO-OCT 与标准检查方法（间接检眼镜（IO）、眼底照相（FP）和中央切片组织病理学）进行比较。
在四周（A 部分）和八周（B 部分）中，向白化大鼠（n=4）口服给予测试化合物，向白化（n=2）和色素沉着（n=2）大鼠给予测试化合物。仅给予对照动物载体。使用 cSLO-OCT、IO、FP、血管造影和组织病理学记录视网膜变化。使用混合效应模型比较组间视网膜厚度。
所有接受化合物治疗的动物均出现进行性多灶性高反射斑点改变，主要局限于视网膜色素上皮。在 A 部分和 B 部分中，cSLO 在白化大鼠中比 IO/FP 更早地识别眼底病变。在 B 部分中，cSLO 在白化大鼠中比 IO/FP 更准确地量化眼底病变，但在色素沉着大鼠中未见差异。中央切片组织病理学显示，在 B 部分的四分之三的化合物处理动物中未发现异常。总之，如果没有 cSLO-OCT，在 A 部分和 B 部分的四分之一的化合物处理动物中，目前的眼底变化将在没有 cSLO-OCT 的情况下被遗漏。
将联合 cSLO-OCT 成像集成到毒理学研究设计中，可以提高毒理学研究结果，并促进对单个动物在多个时间点的纵向检查，从而减少实验动物数量。
