Effect of Pupil Size on Fixed-Luminance Flicker Full-Field Electroretinogram Magnitude

Abstract

Purpose Diopsys ® NOVA fixed-luminance flicker full-field electroretinogram (ffERG) device is a potential adjunct to conventional flicker ffERG testing for assessing cone cell function. Magnitude of measured electrical response is known to vary with pupil size in conventional ffERG testing. The index study characterizes the relationship between magnitude of measured electrical activity and pupil size, both pupil diameter and pupil area, for this device. Methods Seventeen patients (34 eyes) with no known ocular diseases were enrolled in the study. Electrophysiologic function of cone cells was evaluated using fixed-luminance flicker ffERG before and after dilation. Linear regression models, with inter-eye correlations controlled as fixed-effects, were used to characterize the effect of pupil dilation on the magnitude of the measured responses. Results Mean age of study patients was 33.5 (standard deviation 7.4 years), and 35.3% of the subjects were female. Mean value of electrical response magnitude was 10.07±2.79µV before dilation and 15.30±4.08µV after dilation. The correlations of ERG magnitude with pupil diameter and with pupil area were not significant for either dilated or undilated eyes considered separately but were highly significant (p<0.001) for dilated and undilated eyes considered in aggregate. ERG magnitude tended to increase by 1.08 µV for every 1 mm increase in pupillary diameter. Conclusion An increase in pupil size, both pupil diameter and pupil area, is significantly associated with an increase in flicker ffERG magnitude recorded by the Diopsys device, suggesting that pupil size should be measured and considered when making clinical judgments based on the flicker ffERGs recorded by the device, and that pupil size-specific reference ranges could improve the clinical utility of the device.

Spontaneous Fluctuations in Pupil Size Shape Retinal Responses to Visual Stimuli

“…however, the retina is also in a slightly stronger state of adaptation, which decreases the strength of the response; these two counteracting forces cancel each other out, in our case even almost perfectly. As a result, the amplitude of the first ERG component becomes invariant to changes in pupil size, at least within the range of naturally occurring fluctuations and within the range of stimulus intensities tested here (see Gonzalez et al, 2004;Mobasserian et al, 2022 for studies using pharmacological manipulations of pupil size). Functionally, this may be one of many processes that contribute to brightness constancy, and more specifically brightness constancy with respect to natural fluctuations in pupil size.…”

“…Gonzalez et al, 2004; Robson et al, 2018). However, ERG studies have generally compared very large differences in pupil size (several mm) by contrasting pharmacologically dilated pupils with either pharmacologically constricted pupils (Gonzalez et al, 2004) or natural (untreated) pupils (Mobasserian et al, 2022). Importantly, such pharmacologically induced changes in pupil size also affect subjective brightness perception (Sulutvedt et al, 2021) in a way that naturally occurring fluctuations in pupil size do not (Wardhani et al, 2022); therefore, it is unclear how relevant such large pupil-size changes are to natural visual perception.…”

“…Whether smaller changes in pupil size (±1 mm), which in part reflect spontaneous fluctuations in arousal (Lowenstein et al, 1963; Mathôt et al, 2015; Reimer et al, 2014), similarly affect ERG amplitude is currently unclear. One study found that individual differences in pupil size do not correlate with individual differences in ERG amplitude (Mobasserian et al, 2022). However, to our knowledge, no study has looked at whether ERG amplitude is affected by spontaneous fluctuations in pupil size.…”

“…pupils (Mobasserian et al, 2022). Importantly, such pharmacologically induced changes in pupil size also affect subjective brightness perception (Sulutvedt et al, 2021) in a way that naturally occurring fluctuations in pupil size do not (Wardhani et al, 2022); therefore, it is unclear how relevant such large pupil-size changes are to natural visual perception.…”