Cone Photoreceptor Dysfunction in Early-Stage Diabetic Retinopathy: Association Between the Activation Phase of Cone Phototransduction and the Flicker Electroretinogram

PURPOSE: To define the nature and extent of cone photoreceptor abnormalities in diabetic individuals who have mild or no retinopathy by assessing the activation phase of cone phototransduction and the flicker ERG in these individuals. METHODS: Light-adapted single-flash and flicker ERGs were recorded from 20 diabetic individuals who have no clinically apparent retinopathy (NDR), 20 diabetic individuals who have mild nonproliferative diabetic retinopathy (NPDR), and 20 nondiabetic, age-equivalent controls. A-waves elicited by flashes of different retinal illuminance were fit with a delayed Gaussian model to derive R(mp3) (maximum amplitude of the massed photoreceptor response) and S (phototransduction sensitivity). Fundamental amplitude and phase of ERGs elicited by full-field sinusoidal flicker were obtained across a frequency range of 6 to 100 Hz. RESULTS: ANVOA indicated that both diabetic groups had significant S losses compared with the controls, whereas mean R(mp3) did not differ significantly among the groups. ANOVA also indicated significantly reduced flicker ERG amplitude for frequencies ≥56 Hz for both diabetic groups compared with the controls. Flicker ERG timing (phase) did not differ significantly among the groups. Log R(mp3) + log S was significantly correlated with the patients' high-frequency (62.5 Hz) flicker ERG amplitude loss (r = 0.69, P < 0.001). CONCLUSIONS: The delayed Gaussian a-wave model is useful for characterizing abnormalities in the activation phase of cone phototransduction and can help explain flicker ERG abnormalities in early-stage diabetic retinopathy. Reduced cone sensitivity and attenuated high-frequency flicker ERGs provide evidence for impaired cone function in these individuals.