Abstract
The electroretinogram (ERG) is widely used to help diagnose and follow patients with genetic eye disease. It has also become an important outcome measure in clinical trials. Historically, the focus has been on the amplitude and implicit time of the b-wave, and much is known about the decline of b-wave amplitude with age in normal subjects, its inherent test-retest variability, and the natural history of b-wave decline in retinitis pigmentosa. We will review the relevant literature and show how this information is necessary before designing a clinical trial.
The same kind of information has not previously been available for the a-wave of the ERG. Following the elaboration of a computational model that relates the response to events in the phototransduction cascade, we showed that an equivalent model could be fit to the leading edge of the rod-only, and subsequently cone, a-wave. We will present normal cone and rod phototransduction parameters and their variation with age, evaluate progression in cone and rod parameters over time in a subset of patients with XLRP and compare the test-retest variability of these a-wave parameters with the variability in cone and rod b-wave measures.
The results suggest that phototransduction efficiency, as indexed by S, decreases with age for both cone and rod-only responses, while maximum cone and rod photoresponses (RmP3) remains constant. In patients with XLRP tested annually for four years, RmP3 for rods and, to a lesser extent for cones, declined with disease progression, while S remained stable. The test-retest variability in the a-wave RmP3 is lower than previously reported measures of the variability in b-wave peak-to-peak amplitude. We conclude that RmP3, rather than S, should be the outcome measure of choice when using the a-wave to follow photoreceptor function in prospective studies and/or treatment trials.