Abstract
Purpose :
Abnormalities of retinal structure (by imaging)1 and function (by the electroretinogram ERG photopic negative response, PhNR)2 have been previously described in Stargardt’s disease related to ABCA4 gene mutations (STDG-ABCA4). This study aimed to evaluate in STDG/ABCA4 patients the PhNR as a function of disease duration and gene mutation severity, and the longitudinal changes in PhNR.
Methods :
Sixty patients (25 males, 35 females, mean age 32, SD 13) with an STDG phenotype, bi-allelic ABCA4 variants verified (whenever possible) by segregation analysis, and no concomitant ocular or systemic disorders were evaluated. Disease duration was estimated based on age at disease onset. All patients had multimodal imaging with spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF). Longitudinal PhNR changes were evaluated in a sub-group of 20 patients with at least three repeated evaluations including imaging and electroretinogram (ERG), over a median follow-up of 4.5 years (range 3-7). The cone ERG b-wave and PhNR were recorded and measured according to a published protocol.
Results :
Thirty-three patients had a severe mutation (group 1), as determined by ACMG, while the remaining had a milder mutation (group 2). In group 1, but not group 2 patients, both b-wave and PhNR amplitude were negatively correlated with disease duration (r= -0.66, slope -0.21). In 19/60 patients, PhNR was reduced below normal while the b-wave was normal. Both b-wave and PhNR amplitudes were weakly correlated with FAF area (r = 0.20), but PhNR loss correlated with loss of inner retinal thickness (r = 0.55). In the follow-up study, PhNR amplitude was more frequently deteriorated than b-wave, i.e. the PhNR amplitude declined in 8/20 patients, and the b-wave in 2/20.
Conclusions :
PhNR amplitude declined significantly as a function of disease duration in STDG/ABCA4, indicating progressive functional abnormalities of the inner retina. It is unclear how the observed ERG changes impact on visual function and the natural history of the disease.
1 Huang WC, Cideciyan AV, Roman AJ et al Invest Ophthalmol Vis Sci. 2014 Mar 20;55(3):1810-22.
2Abed E, Placidi G, Campagna F, et al Clin Exp Ophthalmol. 2018 Jul;46(5):519-530.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.