Clinical and Molecular Analysis of Stargardt Macular Dystrophy with Preserved Foveal Structure and Function

Abstract

Purpose: : To describe a subset of patients with Stargardt disease (STGD) who maintain foveal structure and function despite para-foveal atrophy of the retinal pigment epithelium (RPE).

Methods: : Fundus autofluorescence (AF) images of 402 affected patients were surveyed. 18 were selected on the basis of apparent normal foveal AF. All 18 underwent comprehensive ophthalmic examinations, of which 10 underwent ABCA4 screening. International-standard pattern and full-field electroretinograms (PERG; ERG) were recorded in 34/36 eyes and spectral-domain optical coherence tomography (SD-OCT) in 20/36.

Results: : The mean age at presentation was 43.7 years (30 to 62). At the most recent examination, mean visual acuity (VA) was 0.34 LogMAR (-0.10 to 3.00) at mean age 51.2 years (33 to 68). Fundus examination showed bilateral para-foveal atrophy, with foveal sparing, surrounded by flecks in 15/18 patients; one additional patient had unilateral foveal sparing. 2/18 had bilateral macular flecks without atrophy. SD-OCT imaging identified normal foveal structure in 10/20 eyes, relatively preserved foveal thickness with absence of the junction between photoreceptor inner and outer segments in 6/20 and foveal thinning in 4/20. PERGs were normal in 4/34, subnormal or showed residual responses in 17/34 and were undetectable in 13/34. Likely disease-causative variants in ABCA4 were identified in 9/10 patients.

Conclusions: : STGD usually presents with loss of VA and early structural abnormalities of the foveal neurosensory retina. We have ascertained a small cohort of patients who have maintained a normal neurosensory foveal structure over time; in keeping with previous reports of retained central vision in a minority of patients with STGD. The underlying ABCA4 mutations are not obviously different to typical patients with STGD. There may therefore be two distinct mechanisms in which ABCA4 dysfunction causes macular disease. This is an important consideration when selecting patients for future therapeutic trials.

Keywords: retinal degenerations: hereditary • electroretinography: clinical • macula/fovea