Abstract
Purpose :
A comprehensive characterization of ABCA4 retinopathies is currently missing. The aim of this study is to report the demographic, genotypic and imaging characteristics in its different phenotypes
Methods :
Observational, cross-sectional study. 66 patients with biallelic ABCA4 variants underwent: visual acuity (VA), color photograph, optical coherence tomography (OCT), fundus autofluorescence, OCT angiography. Clinical notes were reviewed for age at onset (AO), presenting symptoms and electrophysiology (ERG). Variants were classified as missense, nonsense, structural and splicing-site. Each eye was assigned to one phenotype based on AO, imaging and ERGs: cone dystrophy/bull’s eye maculopathy (CD, 20), cone-rod dystrophy (CRD, 6), Stargardt disease (SD, 14), late-onset SD (LO-SD, 19), fundus flavimaculatus (FF, 7). Images were analyzed for: peripapillary sparing, type of atrophy according to CAM reports, extension of definitely-decreased autofluorescence (DDAF), flecks, choroidal thickness, choriocapillaris flow deficit (CC-FlD).
Results :
CRD patients had younger AO (12±8 years) and worse VA (29±13 letters), while LO-SD had higher AO (59±9) and VA (62±23 letters)(p<0.01).CD and SD patients complained of central VA loss, whereas LO-SD and FF patients had paracentral scotomas or were asymptomatic.
Missense variants were more frequent in CD, structural in SD and splicing-site in CRD and LO-SD (all p<0.05). Peripapillary sparing was absent in 3 eyes with LO-SD (8%).CD typically had signs of cORA (100%), while CRD and SD eyes showed both cORA (71-100%) and cRORA (82-100%). All LO-SD patients had evidence of cRORA corresponding to larger areas of DDAF (all p<0.001). FF eyes had signs of iORA (100%). Differently from dot and pisciform flecks, resorbed flecks were significantly associated with CRD and LO-SD (p<0.01).
LO-SD had thinner choroid (179±69µm) and more CC-FlD (2.7±2.6 µm2)(p<0.01).
Conclusions :
Several outcome measures have been proposed for ABCA4 retinopathies (VA, outer retinal layers’ status and DDAF).
Our results highlight that its phenotypes differ for AO, visual function and OCT alterations. Moreover, although precise genotype-phenotype correlation remains complicated, we found some associations between phenotypes and certain types of variants. These findings should be considered when interpreting results in future clinical trials.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.