Flicker electroretinogram peak times in over 1600 adult twins: distribution of times, associations with age and heritability

Abstract

Purpose : Cone photoreceptors drive both central and peripheral vision in most lighting conditions encountered during daily activities. Panretinal cone-driven responses can be measured using the light-adapted flicker electroretinogram (ERG). We analysed flicker ERG peak times recorded from over 1600 healthy adult twins to explore the distribution, association with age and heritability.

Methods : Participants were recruited from the TwinsUK cohort and underwent undilated photopic 28.3 Hz flicker ERG recordings (RETeval system with Sensor Strip skin electrodes, LKC technologies, Gaithersburg, MD). The device measured pupil diameter and adjusted stimulus strength to provide retinal illuminance (85 Td s white flicker; 850 Td white background) equivalent to the international standard. ERG peak times were averaged from both eyes. The distribution of responses and relationships with age were explored. Coefficients of intrapair correlation were calculated for monozygotic (MZ) and dizygotic (DZ) pairs as well as formal estimation of heritability by structural equation modelling.

Results : Recordings were obtained from 1594 participants (mean (SD) age 53.2 (16.5) years; 84% female). Mean (SD) peak time was 25.7 (1.3) ms (median 25.4 ms). The distribution deviated significantly from normality (Kolmogorov-Smirnov test p<0.0001). Following subtraction of a constant from each peak time, the reciprocal yielded a normal distribution (Kolmogorov-Smirnov p=1). Peak times showed significant positive correlation with age (Spearman correlation coefficient 0.54, p<0.0001). The increase with age was not linear; an expression by which the rate of change with age increased for older ages described the data mor closely than a simple linear fit. The participants included 675 full twin pairs (444 MZ and 231 DZ pairs). Coefficients of intra-pair correlation were 0.81 and 0.44 for MZ and DZ pairs respectively. Our estimate of heritability was 0.75 (95% CI, 0.70-0.78).

Conclusions : Peak times were not normally distributed, but their transformation to a normal distribution after taking the reciprocal (following subtraction of a constant time) might be consistent with some rate of signal processing being normally distributed. The relationship with age was not linear but showed a greater slope for older age groups. Approximately 75% of the variance in peak times could be attributable to genetic factors.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.