The rise-time of the rod-driven electroretinogram a-wave measured in over 200 twins: association with age and estimation of heritability

Abstract

Purpose : The electroretinogram (ERG) response to bright flashes delivered in the dark is driven largely by rod photoreceptors. It has been suggested that the time taken for the a-wave to rise from 10% to 90% of the peak amplitude (termed here the 10-90% rise-time, RT10-90) yields a quantitative measure of rod sensitivity. We investigated associations of this parameter with age and explored heritability in a twin study.

Methods : Healthy adult volunteers from the TwinsUK cohort based at St Thomas’ Hospital in London underwent dark-adapted and light-adapted ERG recordings using conductive fibre electrodes following mydriasis. As part of the protocol, white xenon flashes (67 photopic cd m^-2 s) were delivered in the dark and then later in the presence of a rod-saturating blue background (1.0 photopic and 30 scotopic cd m^-2). Subtraction of the latter responses (derived from the cone system) from the former responses (derived from the rod and cone system) yielded the estimated dark-adapted rod system response. RT10-90 measurements were extracted made from these derived responses. We quantified coefficients of intra-pair correlation for monozygotic (MZ) and dizygotic (DZ) twin pairs, and estimated heritability using structural equation modelling. The correlation with age was calculated also.

Results : Recordings were obtained from 208 participants (59 MZ and 45 DZ pairs). Mean (SD) age was 62.8 (10.8) years for the whole cohort. 93% were female. Mean (SD) RT10-90 for the derived rod responses was 3.8 (0.5) ms, with a median of 3.7 ms. The parameter was correlated positively with age (correlation coefficient 0.46). Coefficients of intra-pair correlation were 0.49 and 0.19 for MZ and DZ pairs respectively. Age-adjusted heritability was estimated to be 0.48 (95% CI 0.23-0.66).

Conclusions : The 10-90% rise-time parameter showed a moderate positive correlation with age, indicating that rod system sensitivity declines with age. This might reflect pre-retinal optical factors as well as potential changes at the level of the photoreceptors. The intra-pair correlation was higher for MZ than DZ twins, indicating that genetic factors contribute to the variance of this parameter, and our point estimate of heritability was 48%.

This is a 2021 ARVO Annual Meeting abstract.