The National Eye Institute Prospective ABCA4 Retinopathy Natural History Study: Autofluorescence Imaging Analysis

Abstract

Purpose : The purpose of this study is to investigate the progression of atrophy in ABCA4 retinopathy using imaging techniques.

Methods : Forty nine patients carrying at least one ABCA4 mutation and clinical diagnosis of Stargardt disease or cone-rod dystrophy underwent comprehensive ophthalmic evaluations as part of a prospective ABCA4 retinopathy natural history protocol at the National Institutes of Health (NCT01736293). Color fundus photos, short-wavelength autofluorescence (SW-AF) (Heidelberg 488/500nm), and spectral domain-optical coherence tomography (SD-OCT) images were acquired and this data was used for analysis. Genotype-phenotype correlation analysis of the nature of mutations to the imaging findings was performed. One year follow-up data was compared to baseline visits.

Results : Of the forty nine patients that were enrolled in this study, to date, 29 patients had a complete data set spanning one year and were included in this analysis. Age at baseline examination ranged from 12 to 63 years and visual acuity ranged from 20/16 to 20/500. Discrete areas of hypo-autofluorescence on SW-AF were delineated using the Heidelberg Spectralis RegionFinder software and a within-session repeatability coefficient of 0.07 log mm2 was found. Seven patients (24%) were found to have progression in atrophy greater than the variability determined by the repeatability coefficient over this one year time span with a median rate of change of 0.114 log mm2 per year in one eye (30% per year). Age of the patients that progressed ranged from 16 to 61 years at baseline with visual acuity that remained essentially stable (range=20/16-20/250). Five of these seven patients that progressed had a phenotype of discrete central atrophy with surrounding flecks and atrophic lesions.

Conclusions : Fundus imaging, specifically autofluorescence has been instrumental in the diagnosis and monitoring of patients with Stargardt disease. One year, prospective data supports SW-AF as a reliable method to monitor change in patients with ABCA4 retinopathy. This study provides an opportunity to investigate the association between fundus autofluorescence changes in Stargardt disease with molecular genetics and other clinical findings that may be used as outcome variables in future trials.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.