Paired-flash electroretinography: a new tool to examine rod function in patients with Stargardt disease

Previous studies have suggested that Stargardt patients display abnormally slow rod dark adaptation after adapting light that bleaches a substantial fraction of the visual pigment. However, relatively little is known about the recovery of rod responsiveness in this disease following weaker adapting light. In this study we applied a recently developed paired-flash electroretinographic (ERG) technique to investigate the effect of weak adapting light on rod photoreceptor activity, in normal subjects and in patients with Stargardt disease and an ABCA4 mutation. ERG a-wave responses to a bright probe flash in paired-flash trials were recorded from 6 normal subjects and 5 Stargardt/ABCA4 patients. In addition, the instantaneous amplitude-response function at defined times after the adapting light was investigated in three-flash trials. Under dark-adapted conditions, maximal peak amplitudes of the rod-mediated a-wave recorded from Stargardt patients were on average lower than those of normals. However, normalized dark-adapted amplitude-intensity functions exhibited similar sensitivity in both normals and patients. Furthermore, amplitude-intensity functions obtained from normals and patients following adapting light exhibited generally similar extents of desensitization. Despite reductions in average maximal a-wave amplitude in the Stargardt/ABCA4 patients, the recovery of rod flash sensitivity does not differ substantially from that of normals under the investigated experimental conditions.