Combined cSLO-OCT imaging as a tool in preclinical ocular toxicity testing: A comparison to standard in-vivo and pathology methods.
Confocal scanning laser ophthalmoscopy
Fundus examination
Histopathology
Methods
Non-invasive
Optical coherence tomography
Rat
Reduction
Retinal pigment epithelium
Retinal toxicity
Journal
Journal of pharmacological and toxicological methods
ISSN: 1873-488X
Titre abrégé: J Pharmacol Toxicol Methods
Pays: United States
ID NLM: 9206091
Informations de publication
Date de publication:
Historique:
received:
18
04
2019
revised:
11
12
2019
accepted:
07
05
2020
pubmed:
16
5
2020
medline:
29
5
2021
entrez:
16
5
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32413488
pii: S1056-8719(20)30202-1
doi: 10.1016/j.vascn.2020.106873
pii:
doi:
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
106873Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest This study was supported by and carried out at Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland: PS, BL, BA, SB, EAA (employees). SAP none. Authors declare no conflict of interest.