Abstract
Purpose: :
To characterize inter-ocular and inter-subject variability in the scotopic electroretinogram (ERG) to a standard flash in rabbits and monkeys.
Methods: :
A total of 411 rabbits (290 pigmented, 121 albino) and 223 cynomolgus monkeys underwent ERG testing as part of baseline measures in pre-clinical studies. All animals were dark-adapted for at least 2 h prior to testing. Following immobilization with ketamine/xylazine and pupillary dilation, ERGs were recorded using monopolar JetTM contact lens electrodes referenced to a subdermal electrode. Temperature, sPO2, and heart rate were continuously monitored. Flash intensity was 2.7cd-s m-2. Amplitude and implicit times of the a- and b-waves and oscillatory potentials were scored using automated software routines. Data were log-transformed and fit with normal distributions. A Bland-Altman discrepancy analysis was used to examine inter-ocular differences (IOD) between the two species.
Results: :
In rabbits, log B-wave amplitudes were normally distributed (mean=2.24 +/- 0.142 (sd) log mcV, coefficient of variability (COV) of 6%); as were log A-wave amplitudes (mean=1.76 +/- 0.17 log mcV, COV 9%). There were no significant differences in B-wave amplitude between albino and pigmented strains. B-Wave amplitude was significantly larger in female relative to male rabbits. Log B-wave amplitudes were slightly larger in monkeys than in rabbits (mean=2.43 +/- 0.092. COV 4% log mcV; average log A-wave amplitude =2.13+/- 0.094 log mcV, COV 4%). No sex-related differences were noted in monkeys. The 95th percentile of the distribution of log B-Wave amplitude IODs was 7% in rabbits and 5% in monkeys. Inter-ocular limits of agreement (95%) were 15% in rabbits and 12% in monkeys with negligible bias.
Conclusions: :
These data provide normative values for ERG parameters in two species that are widely used in pre-clinical testing. IODs were similar despite different retinal anatomy and pupil size. High agreement was found between the eyes with a narrower range than that reported in human. These data will be useful for sample size determination in pre-clinical testing and in studies that use the fellow eye as a control.
Keywords: electroretinography: non-clinical • retina • ocular irritancy/toxicity testing