Combined cSLO-OCT imaging as a tool in preclinical ocular toxicity testing: A comparison to standard in-vivo and pathology methods.

ABSTRACT

INTRODUCTION: 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). METHODS: 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. RESULTS: 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. DISCUSSION: 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.