Journal article
Combined cSLO-OCT imaging as a tool in preclinical ocular toxicity testing: A comparison to standard in-vivo and pathology methods.
- Soukup P 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. Electronic address: petr.soukup@uzh.ch.
- Lenz B Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Grenzacherstrasse 124, Basel 4070, Switzerland. Electronic address: barbara.lenz@roche.com.
- Altmann B Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Grenzacherstrasse 124, Basel 4070, Switzerland.
- Badillo S Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Grenzacherstrasse 124, Basel 4070, Switzerland. Electronic address: solveig.badillo@roche.com.
- Atzpodien EA Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Grenzacherstrasse 124, Basel 4070, Switzerland. Electronic address: elke-astrid.atzpodien@roche.com.
- Pot SA Ophthalmology Section, Equine Department, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, Zurich 8057, Switzerland. Electronic address: spot@vetclinics.uzh.ch.
- 2020-05-16
Published in:
- Journal of pharmacological and toxicological methods. - 2020
Confocal scanning laser ophthalmoscopy
Fundus examination
Histopathology
Methods
Non-invasive
Optical coherence tomography
Rat
Reduction
Retinal pigment epithelium
Retinal toxicity
English
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.
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.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1016/j.vascn.2020.106873
- PMID 32413488
- Persistent URL
- https://sonar.ch/global/documents/47697
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