Age-related changes in ERG and genotype-phenotype comparison in patients with achromatopsia.

Abstract

Purpose : To assess age-related ERG variability in individuals with achromatopsia (ACHM) and to examine possible genotype-phenotype differences.

Methods : Sixty individuals with ACHM (age range 10-75 years; median 29 years) were examined in the Electrophysiology department of Moorfields Eye Hospital. All underwent full-field ERG testing incorporating the International-standard ERG protocol. The majority had undergone genetic testing and were found to have disease-causing variants in CNGB3 (N=21), CNGA3 (N=11), PDE6C (N=6) or ATF6 (N=2). Additional cases were included according to clinical and ERG criteria but without a genetic diagnosis (N=20). The main dark-adapted (DA) and light-adapted (LA) full-field ERG parameters were compared with those in an unaffected control group (N=140; age range 10-79 years; median 48 years).

Results : The DA 0.01 (dim flash) ERGs were within normal limits and showed age-related decline indistinguishable from the control group across 6 decades. The mean DA 10 (strong flash) ERG a- and b-waves were significantly smaller than in the control group (p<0.05), by 26% and 22% respectively. There were similar age-related reductions of DA10 ERG a-wave amplitudes in the control and ACHM groups. There were no significant differences in DA ERG amplitudes between different genotypes and genetically unresolved cases. The LA 30Hz ERGs were undetectable except in three cases, with severely delayed residual responses. The LA3 (single flash cone) ERGs were undetectable in most but a minority had detectable markedly abnormal waveforms, including those associated with PDE6C (n=6) and ATF6 variants.

Conclusions : The scotopic dim flash (DA 0.01) ERG amplitudes in cases of ACHM are indistinguishable from controls, consistent with normal rod function and rod system stimulus selectivity. The strong flash (DA 10) ERG a-and b-wave mean amplitudes are significantly reduced, irrespective of genotype, in keeping with a loss of the DA cone system contribution. The normal DA dim flash rod ERGs suggest additional DA blue flash ERGs may be superfluous in ERG protocols that aim to characterize rod system function.The data show age-related ERG changes in ACHM, pertinent to studies that aim to test efficacy of potential new treatments.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.