Microvolt Cone Electroretinography in Type 1 and 2 Usher Syndrome

Abstract

Purpose: Psychophysical cone-mediated function and its decay have been previously evaluated in Usher syndrome (USH) type 1 and 2. The cone electroretinogram (ERG) typically has poor signal-to-noise ratio early in the course of the disease and has thus been studied less frequently. We used a method of recording microvolt level photopic ERG to evaluate small cone ERG in USH1 and USH2 patients.

Methods: USH1 (n = 18) or USH2 (n = 25) patients (age range: 8-68 years) were included in the study, along with normal subjects (n = 12). Molecular identification was available for 32/43 patients with results pending for the rest. Subgroups of USH1(n = 9) and USH2 (n = 9) patients underwent 2-4 follow-up examinations at 2-8 year intervals. Ganzfeld 32 Hz photopic ERGs were elicited and recorded according to a technique, termed “cycle-by-cycle” (IOVS 39:146; 1998). This technique is valuable in recordings of poor signal-to-noise ratio since amplitude and timing phase of the response fundamental harmonic to each individual stimulus flash is isolated by Discrete Fourier Transform to estimate signal statistical uncertainty. ISCEV standard 30 Hz flicker ERG was recorded at the same visit.

Results: Cone ERGs from USH1 and USH2 patients showed both amplitude losses and phase delays (p < 0.01), compared to control values. However, USH 1C patients did not show a delay in response phase (i.e. response timing). In both USH1 and USH2 patients, and independent of genotype, log ERG amplitudes decreased with disease duration at a similar rate (-0.012 log unit/year). However, the ERG phase did not show progressive changes over time. ISCEV standard responses were not recordable in 7/43 patients.

Conclusions: Cone function evaluated by cycle-by-cycle ERG shows a decline, in both USH1 and USH2, comparable to that determined psychophysically. Abnormalities in the ERG timing phase can be found in most genetic USH subtypes, reflecting a common mechanism of cone dysfunction. Our results point to the value of cycle-by-cycle ERG as a more dependable cone function test (as compared to ISCEV standard flicker response); we recommend it as an outcome measure in future trials involving USH patients.

Keywords: 696 retinal degenerations: hereditary • 509 electroretinography: clinical