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Margaret E Collins; Visual Evoked Potentials as an Extension of Electroretinography in Non-Clinical Ocular Toxicity Studies. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5123.
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Electroretinography (ERG) has been used to assess retinal function and identify changes that may be associated with ocular toxicity during the conduct of nonclinical studies. Routine ERGs consist of measuring retinal responses to a series of light stimuli, with the ISCEV standards for ERG generally being used. However, ERGs only assess electrical impulse generation and transmission to the level of the retinal ganglion cell (RGC) and are not affected by loss of RGC function. Visual evoked potential (VEP) assesses impulse generation at the level of the visual cortex. The combination of ERGs and VEPs can give a full picture of visual impairment if there are test article-related effects on vision.
Cynomolgus monkeys were assessed via ERG and VEP measurements. All measurements were conducted using the LKS UTAS E-3000 Visual Electrodiagnostic System. ERGs were measured in accordance with ISCEV standards. To mimic the effect of reduced rod/cone function, a second round of ERGs were collected immediately following the first set of flicker measurements. Following ERG assessment, pattern and flash VEPs were measured by placing reference, ground and recording electrodes on the scalp. All data were analyzed by measuring amplitude and latency of waveforms.
Ophthalmic findings that were clearly limited to the retina upon ophthalmoscopy produced alterations in ERG responses, but not in VEPs. When a second round of ERGs were collected immediately after the flicker assessment (i.e. in the absence of dark adaptation), reduced amplitude was noted for most parameters. Animals noted as having reduced vision based on behavior without the presence of findings during ophthalmoscopy variably showed either alterations in ERG and/or VEP responses, or no alterations in response. Due to the nature of pattern VEPs, which require directed focusing by the subject, flash VEPs were less variable than pattern VEPs.
While ERGs remain the primary assessment of retinal function in nonclinical ocular toxicity studies, VEPs can provide an additional assessment. In some cases, VEPs may be more appropriate. The nature of the test article effect should be taken into account when determining the most appropriate method for elucidating the cause of vision changes in non-human primates
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