Kinetics of Heterogeneous Background in Stargardt's Disease over Time.

Eduardo Rodríguez-Bocanegra,Lucía Lee Ferraro,Marc Biarnés,Manuel Dominik Fischer,Jordi Monés,Míriam Garcia

doi:10.3390/life12030381

Abstract

Stargardt’s disease (STGD1) is caused by mutations in the ABCA4 gene. Different lesions characterised by decreased autofluorescence levels are found in fundus autofluorescence (FAF) from STGD1 patients and could be used as outcome indicators for disease progression. We investigated the fate of foci with reduced autofluorescence (FRA) within the heterogeneous background of STGD1 patients using FAF imaging. Genetically confirmed STGD1 patients presenting heterogeneous background autofluorescence on high-quality FAF images at a minimum of two visits at least 12 months apart were chosen. A grid centred on the fovea was used to define five different zones. Within each zone, five FRA were randomly selected for each eye. The eccentricity of foci was determined at different time points for each patient. Analysis of 175 randomly chosen FRA showed consistent centrifugal displacement over time, most notably in eyes showing areas with definitely decreased autofluorescence. Interestingly, FRA did not leave an area of hypo-autofluorescence on FAF in locations where they were previously located. These findings may help to better understand STGD1 progression, improve FAF interpretation, and shed light on the nature of heterogeneous background.

Highlights

The purpose of this study is to investigate the fate of foci with reduced autofluorescence (FRA) within the heterogeneous background of STGD1 patients over time using
We found that the observed displacement of FRA was always directed away from the foveal avascular zone (FAZ), i.e., in a centrifugal direction
The lesions we describe meet the definition of foci with reduced autofluoThe lesions we describe meet the definition of foci with reduced autofluorescence (FRA) in terms of fundus autofluorescence (FAF) intensity and topographic distribution within the heterrescence (FRA) in terms of FAF intensity and topographic distribution within the hetogeneous background, as defined in the ProgStar study [9]

Summary

Introduction

One of the most common forms of juvenile macular degeneration is Stargardt’s disease (STGD1; OMIM 248200), with an estimated prevalence of 1:10.000 [1]. This autosomal recessive macular dystrophy is caused by mutations in the ABCA4 gene, and it usually manifests in childhood or adolescence with progressive loss of central vision leading to legal blindness [2,3]. The reason lies in the fact that protein ABCA4 deficiency causes an increased accumulation of lipofuscin components (bisretinoid fluorophores) in the photoreceptor outer segment disc membranes [4]. As a result of outer segment disc separation and phagocytosis by the retinal pigment epithelium (RPE), lipofuscin accumulation increases in the RPE and eventually leads to cell death and macular atrophy [5]. The best approach to track the progression of the disease and which endpoints to use to assess iations

Objectives

Methods

Results

Conclusion