Cone Responses in Usher Syndrome Types 1 and 2 by Microvolt Electroretinography

Purpose:Progressive decline of psychophysical cone-mediated measures has been reported in type 1 (USH1) and type 2 (USH2) Usher syndrome. Conventional cone electroretinogram (ERG) responses in USH demonstrate poor signal-to-noise ratio. We evaluated cone signals in USH1 and USH2 by recording microvolt level cycle-by-cycle ERG (CxC). Methods:Responses of molecularly genotyped USH1 (n = 18) or USH2 (n = 24) subjects (age range: 15-69 years) were compared with those of controls (n = 12). A subset of USH1 (n = 9) and USH2 (n = 9) subjects was examined two to four times over 2 to 8 years. Photopic CxC ERG and conventional 30-Hz flicker ERG were recorded on the same visits. Results:USH subjects showed considerable cone flicker ERG amplitude losses and timing phase delays (p < 0.01) compared with controls. USH1 and USH2 had similar rates of progressive logarithmic ERG amplitude decline with disease duration (-0.012 log μV/year). Of interest, ERG phase delays did not progress over time. Two USH1C subjects retained normal response timing despite reduced amplitudes. The CxC ERG method provided reliable responses in all subjects, whereas conventional ERG was undetectable in 7 of 42 subjects. Conclusions:CxC ERG showed progressive loss of amplitude in both USH1 and USH2 subjects, comparable to that reported with psychophysical measures. USH subjects showed abnormal ERG response latency, but this changed less than amplitude with time. In USH syndrome, CxC ERG is more sensitive than conventional ERG and warrants consideration as an outcome measure in USH treatment trials.