Analysis of retinal sublayer thicknesses and rates of change in ABCA4-associated Stargardt disease

S Scott Whitmore,Adam P Deluca,Elizabeth L Geary,Ian C Han,Justine L Cheng,D Brice Critser,Jeremy M Hoffmann,Edwin M Stone,Christopher R Fortenbach

doi:10.1038/s41598-020-73645-5

Abstract

Stargardt disease, the most common inherited macular dystrophy, is characterized by vision loss due to central retinal atrophy. Although clinical trials for Stargardt are currently underway, the disease is typically slowly progressive, and objective, imaging-based biomarkers are critically needed. In this retrospective, observational study, we characterize the thicknesses of individual retinal sublayers by macular optical coherence tomography (OCT) in a large cohort of patients with molecularly-confirmed, ABCA4-associated Stargardt disease (STGD1) relative to normal controls. Automated segmentation of retinal sublayers was performed with manual correction as needed, and thicknesses in various macular regions were compared using mixed effects models. Relative to controls (42 eyes, 40 patients), STGD1 patients (107 eyes, 63 patients) had slight thickening of the nerve fiber layer and retinal pigment epithelium-Bruch’s membrane, with thinning in other sublayers, especially the outer nuclear layer (ONL) (p < 0.0015). When comparing the rate of retinal sublayer thickness change over time (mean follow-up 3.9 years for STGD1, 2.5 years for controls), STGD1 retinas thinned faster than controls in the outer retina (ONL to photoreceptor outer segments). OCT-based retinal sublayer thickness measurements are feasible in STGD1 patients and may provide objective measures of disease progression or treatment response.

Highlights

Stargardt disease, the most common inherited macular dystrophy, is characterized by vision loss due to central retinal atrophy
Most imagingbased studies of progression in STGD1 have assessed the area of retinal pigment epithelium (RPE) loss, which is readily measured using en face fundus autofluorescence (FAF) imaging[9,11,12,13,14,15]
For the STGD1 group, included patients were younger at baseline than excluded STGD1 patients, and mean visual acuity was better for included eyes than those we excluded (Fig. 3)

Summary

Introduction

The most common inherited macular dystrophy, is characterized by vision loss due to central retinal atrophy. Clinical trials for Stargardt are currently underway, the disease is typically slowly progressive, and objective, imaging-based biomarkers are critically needed. In this retrospective, observational study, we characterize the thicknesses of individual retinal sublayers by macular optical coherence tomography (OCT) in a large cohort of patients with molecularly-confirmed, ABCA4-associated Stargardt disease (STGD1) relative to normal controls. Few studies to date have quantified the degree of OCT-based retinal thinning in STGD1 or attempted to assess the rate of retinal thickness change over time[20,21]. We evaluate retinal sublayer changes as measured by OCT in a large cohort of patients with molecularly-confirmed ABCA4-associated Stargardt disease. We describe regional differences in retinal thickness change based on macular zones and quantify the rate of change for various retinal sublayers over time

Methods

Results

Conclusion