Full-field ERG as a predictor of the natural course of ABCA4-associated retinal degenerations

PURPOSE: To assess retinal function in combination with the retinal structure in ABCA4-associated retinal degenerations. Moreover, to evaluate the possibility of predicting the natural course of these disorders. METHODS: 34 patients with Stargardt disease or cone rod dystrophy carrying confirmed mutations in ABCA4 were selected from our retinitis pigmentosa (RP) register. Sequence analysis of the entire coding region of the ABCA4 gene was performed. The patients were subdivided into three groups based on their most recent visual fields. Group 1 included ten patients with central scotomas within 10°, group 2 included 19 patients with larger central scotomas of 10–35°, and group 3 included five patients with mere temporal residues. The patients underwent slit-lamp and fundus examinations, visual acuity testing, optical coherence tomography (OCT), fundus photography (color, red-free, and autofluorescence (AF) images), full-field electroretinography (ffERG), and multifocal electroretinography (mERG). FfERG and mERG results were analyzed statistically. Total rod and cone function, as well as macular function, was compared between the three groups and of each group to a normal material. In 23 patients who had undergone ffERG on a previous occasion, the 30 Hz flicker implicit time (IT) from the first visit was also analyzed. RESULTS: The ffERG statistics revealed significant differences between the groups regarding cone and rod function with group 1 showing the highest amplitudes and the shortest ITs while group 3 demonstrated the lowest amplitudes and the most delayed ITs. When compared to controls, group 1 did not show any significant changes while groups 2 and 3 demonstrated reduced amplitudes and delayed 30 Hz ITs. Regarding estimation of the natural course, identical results of the 30 Hz IT were encountered for the groups also at the first visit early in the course of disease. Comparison of the mERGs showed significant differences with group 1 demonstrating the highest amplitudes and group 3 the lowest for all rings but rings 2 and 3 in the right eye for which the amplitudes were the second highest. The mERGs for each group were also compared to controls showing reduced mERG amplitudes for all rings in all groups, except group 1, left eye. OCT showed macular attenuation in all patients. Evaluation of the inner and outer photoreceptor junction (IS/OS) morphology revealed alterations related to macular function measured with mERG in all eyes. Eight patients in group 1 showed foveal IS/OS junction loss, one had foveal IS/OS junction disorganization, and one had IS/OS loss also beyond the fovea. In group 2, one patient had IS/OS junction loss confined to the fovea, and the rest showed total loss of IS/OS junctions. Group 3 was devoid of IS/OS junctions. Concerning the AF images, group 1 showed small areas of absent AF in the macula, peripapillary sparing, and flecks of increased and reduced AF in the posterior pole. In group 2, the central areas of absent AF were larger. Flecks of reduced AF were the most dominant and reached beyond the posterior pole. Seven of 19 patients had peripapillary sparing. In group 3, large confluent areas of reduced AF were found in the posterior pole and beyond with small areas of increased AF in the far periphery. No peripapillary sparing was seen. CONCLUSIONS: The current study demonstrates a significant difference in total retinal function, as well as macular function, between patients with ABCA4-associated retinal degeneration and a different degree of visual field defects with gradual deterioration of function along with increased visual field constriction. Likewise, the morphological changes, including the deviant AF pattern and loss of IS/OS junctions, that were related to macular function measured with mERG worsened with the degree of visual field defects. Moreover, in these groups of patients with ABCA4-associated retinal degenerations, full-field cone 30 Hz flicker IT seems to be a predictor of the natural course of the disease also on long-term follow-up.