Imaging Biomarkers as Predictors of Visual Acuity in ABCA4 and PRPH2-Related Disease

Abstract

Purpose : Patients with ABCA4 and PRPH2-related diseases present with highly variable visual acuities and associated quality of life. Multiple subtypes of ABCA4 and PRPH2-related diseases with distinct phenotypes have been proposed, with visual prognosis being less thoroughly investigated. The present study aimed to identify imaging features to predict visual acuity among patients with these inherited retinal diseases.

Methods : Consecutive retrospective study of patients managed at an urban retina-based practice between 2016 and 2023. Patients with bi-allelic ABCA4 or PRPH2 molecular variants were included. Fundus autofluorescence and color photos were analyzed by 2 masked graders (KCF, CCW). Features noted on imaging included bone spicules, peripapillary sparing, flecks, bull’s-eye maculopathy, and chorioretinal atrophy (CRA). These imaging features were included in stepwise multiple regression models to predict logMAR best recorded visual acuity (BRVA) from chart review. This study was done under IRB approval according to the Declaration of Helsinki.

Results : 92 eyes from 46 patients were studied in the ABCA4 group model. Predictors of worse BRVA included peripapillary sparing, hypoautofluorescent macular CRA, and macular bone spicules in ABCA4 disease, while presence of macular flecks was associated with preserved vision (all p <0.01, R²=0.58). 44 eyes from 22 patients were studied in the PRPH2 group model. Macular bone spicules were associated with worse BRVA (p < 0.01), while bull’s-eye maculopathy and peripapillary sparing were associated with preserved vision (p <0.05, R²=0.46).

Conclusions : This study identified risk and protective factors for visual outcome in patients with ABCA4 retinopathies and PRPH2-related disease. In both groups, the presence of bone spicules in the macula were strongly associated with worse vision. Macular flecks were associated with better vision in the ABCA4 group while bull’s-eye maculopathy was associated with preserved vision in the PRPH2 group. Due to the exceeding variability in visual acuity and phenotype in these diseases, further multivariable analysis with larger, more diverse populations is warranted to further understand these potential prognostic indicators.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.