Full-field electroretinogram in autism spectrum disorder

Paul A. Constable, Sebastian B. Gaigg, Dermot M. Bowler, Herbert Jägle, Dorothy A. Thompson

To explore early findings that individuals with autism spectrum disorder (ASD) have reduced scotopic ERG b-wave amplitudes. Light-adapted (LA) and dark-adapted (DA) ERGs were produced by a range of flash strengths that included and extended the ISCEV standard from two subject groups: a high-functioning ASD group N = 11 and a Control group N = 15 for DA and N = 14 for LA ERGs who were matched for mean age and range. Flash strengths ranged from DA -4.0 to 2.3 log phot cd s m(-2) and LA -0.5 to 1.0 log phot cd s m(-2), and Naka-Rushton curves were fitted to DA b-wave amplitude over the first growth limb (-4.0 to -1.0 log phot cd s m(-2)). The derived parameters (V max, K m and n) were compared between groups. Scotopic 15-Hz flicker ERGs (14.93 Hz) were recorded to 10 flash strengths presented in ascending order from -3.0 to 0.5 log Td s to assess the slow and fast rod pathways, respectively. LA 30-Hz flicker ERGs, oscillatory potentials (OPs) and the responses to prolonged 120-ms ON-OFF stimuli were also recorded. The ISCEV LA b-wave amplitude produced by 0.5 log phot cd s m(-2) was lower in the ASD group (p < 0.001). Repeated measures ANOVA for the LA b-wave amplitude series forming the photopic hill was significantly (p = 0.01) different between groups. No group differences were observed for the distributions of the time to peaks of LA a-wave, b-wave or the photopic negative responses (phNR) (p > 0.08) to the single flash stimuli, but there was a significant difference in the distribution for the LA b-wave amplitudes (corrected p = 0.006). The prolonged 120-ms ON responses were smaller in the ASD group (corrected p = 0.003), but the OFF response amplitude (p > 0.6) and ON and OFF times to peaks (p > 0.4) were similar between groups. The LA OPs showed an earlier bifurcation of OP2 in the younger ASD participants; however, no other differences were apparent in the OPs or 30-Hz flicker waveforms. DA b-wave amplitudes fell below the control 5th centile of the controls for some individuals including four ASD participants (36 %) at the 1.5 log phot cd s m(-2) flash strength and two (18 %) ASD participants at the lower -2 log phot cd s m(-2) flash strength. However, across the 13 flash strengths, there were no significant group differences for b-wave amplitude's growth (repeated measures ANOVA p = 0.83). Nor were there any significant differences between the groups for the Naka-Rushton parameters (p > 0.09). No group differences were observed in the 15-Hz scotopic flicker phase or amplitude (p > 0.1), DA ERG a-wave amplitude or time to peak (p > 26). The DA b-wave time to peak at 0.5 log phot cd s m(-2) was longer in the ASD group (p = 0.04). Under LA conditions, the b-wave is reduced across the ASD group, along with the ON response of the prolonged flash ERG. Some ASD individuals also show subnormal DA ERG b-wave amplitudes. These exploratory findings suggest there is altered cone-ON bipolar signalling in ASD.