title: Spontaneously occurring fundus findings observed using confocal scanning laser ophthalmoscopy in wild type Sprague Dawley rats.
abstract: OBJECTIVE
  Non-invasive in vivo imaging is an increasingly used component of pre-clinical research. However, to reliably interpret data, it may be necessary to identify and document pre-existent findings prior to initiating long-term or intensive protocols, particularly where toxicity or efficacy is under investigation. Here we report here spontaneously occurring findings from the Sprague Dawley (SD) rat eye using multi-modal confocal scanning laser ophthalmoscopy (cSLO).
  
  
  METHODS
  As part of ongoing studies, with the goal of excluding animals with abnormalities from further investigation, a total of 165 wild type SD rats (312 eyes) were assessed using cSLO imaging at baseline prior to initiating experiments to detect, describe, and determine the prevalence of spontaneous fundus findings.
  
  
  RESULTS
  Using fundus autofluorescence (FAF) as the primary screening modality, over 30% of analyzed eyes possessed some fundus finding that differed from the normal composite reference image. Unexpectedly, 100% of eyes demonstrated a diffuse hyperfluorescent region in the posterior pole that was ultimately considered normal, and formed part of the reference. Evaluated by three independent reviewers, five groups of FAF abnormalities were defined, based primarily on shape and size of the lesion. Of these, the most extensive lesions were further analyzed using infrared reflectance (IR) and red free (RF) imaging. White light and autofluorescent microscopy of excised tissue confirmed that the extensive lesions were derived from abnormalities in both the isolated retina and posterior eyecups.
  
  
  CONCLUSIONS
  Given the newly described hyperfluorescent glow that appears in all eyes, and the high basal rate of spontaneous lesions in the outbred SD rat, we suggest that investigators be aware of the variants of normal, and that baseline in vivo screening be considered prior to initiating intensive or expensive investigation.
authors.affiliation: Keenan Research Centre for Biomedical Science, St Michael's Hospital, 209 Victoria Street, Toronto, ON, Canada, M5B 1W8.
authors.forename: Rahul
authors.initials: R
authors.lastname: Joshi
authors.affiliation: University of Toronto, Department of Laboratory Medicine and Pathobiology, 1 King's College Circle, Toronto, ON, Canada, M5S 1A8; University of Toronto, Department of Ophthalmology and Vision Sciences, 340 College Street, Toronto, ON, Canada, M5T 3A9; Keenan Research Centre for Biomedical Science, St Michael's Hospital, 209 Victoria Street, Toronto, ON, Canada, M5B 1W8.
authors.forename: Natalie
authors.initials: N
authors.lastname: Pankova
authors.affiliation: Keenan Research Centre for Biomedical Science, St Michael's Hospital, 209 Victoria Street, Toronto, ON, Canada, M5B 1W8.
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
authors.affiliation: University of Toronto, Department of Laboratory Medicine and Pathobiology, 1 King's College Circle, Toronto, ON, Canada, M5S 1A8; Keenan Research Centre for Biomedical Science, St Michael's Hospital, 209 Victoria Street, Toronto, ON, Canada, M5B 1W8.
authors.forename: David Sung Hyeon
authors.initials: DS
authors.lastname: Baek
authors.affiliation: Keenan Research Centre for Biomedical Science, St Michael's Hospital, 209 Victoria Street, Toronto, ON, Canada, M5B 1W8.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Keenan Research Centre for Biomedical Science, St Michael's Hospital, 209 Victoria Street, Toronto, ON, Canada, M5B 1W8.
authors.forename: Matthew
authors.initials: M
authors.lastname: Reyad
authors.affiliation: University of Toronto, Department of Laboratory Medicine and Pathobiology, 1 King's College Circle, Toronto, ON, Canada, M5S 1A8; University of Toronto, Department of Ophthalmology and Vision Sciences, 340 College Street, Toronto, ON, Canada, M5T 3A9; Keenan Research Centre for Biomedical Science, St Michael's Hospital, 209 Victoria Street, Toronto, ON, Canada, M5B 1W8; Department of Ophthalmology, St. Michael's Hospital, 30 Bond Street, Toronto, ON, Canada, M5B 1W8; Biomedical Engineering, McMaster University, 1280 Main Street West, Hamilton, ON, Canada, L8S 4K1. Electronic address: boyds@smh.ca.
authors.forename: Shelley R
authors.initials: SR
authors.lastname: Boyd
mesh_terms: D000818:Animals; D005453:Fluorescence; D005654:Fundus Oculi; D018613:Microscopy, Confocal; D015588:Observer Variation; D009887:Ophthalmoscopy / Q000379:methods*; D010641:Phenotype; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012160:Retina / Q000473:pathology*; D012164:Retinal Diseases / Q000473:pathology*
keywords: Baseline abnormality; In vivo optical imaging; Retinal toxicity; Spontaneous lesion