L- and M-cone-driven electroretinograms in Stargardt's macular dystrophy-fundus flavimaculatus

PURPOSE. TO study the dynamics of the long (L) and middle (M)-wavelength-se nsitive cone-driven pathways and their interactions in patients with Starga rdt's macular dystrophy-fundus flavimaculatus (SMD-FF) and to correlate the m with other clinical parameters and individual genotypes. METHODS. Forty-seven patients with SMD-FF participated in the study. In add ition to standard 30-Hz flicker electroretinograms (30-Hz fERG), ERG respon ses were measured to stimuli that modulated exclusively the L or the M cone s (L/M cones) or the two simultaneously. Blood samples were screened for mu tations in the 50 exons of the ABCA4 gene. RESULTS. Patients with SMD-FF did not show a decrease in the mean L/M-cone- driven ERG sensitivity, but there was a significant increase in the interin dividual variability. The mean L-/M-cone weighting ratio was normal. Howeve r, the L-cone-driven ERG was significantly phase delayed, whereas the M-con e-driven ERG was significantly phase advanced. These phase changes were sig nificantly correlated with disease duration. The amplitude and implicit tim e of the standard 30-Hz fERG both correlated significantly with the L/M-con e-driven ERG sensitivity and with the phase difference between the L/M-cone -driven ERGs, indicating the complex origin of the standard 30-Hz fERG. Pro bable disease-associated mutations in the ABCA4 gene were found in 40 of 45 patients, suggesting that they form a genetically fairly uniform SMD-FF st udy group. There was no correlation between the genotype and the L/M-cone-d riven ERGs. CONCLUSIONS. The changes in L/M-cone-driven ERG sensitivity and phase possi bly represent two independent disease processes. The phase changes are simi lar to those found in patients with retinitis pigmentosa and possibly are a general feature of retinal dystrophies.