Clinical and molecular analysis of Stargardt disease with preserved foveal structure and function

Am J Ophthalmol. 2013 Sep;156(3):487-501.e1. doi: 10.1016/j.ajo.2013.05.003.


Purpose: To describe a cohort of patients with Stargardt disease who show a foveal-sparing phenotype.

Design: Retrospective case series.

Methods: The foveal-sparing phenotype was defined as foveal preservation on autofluorescence imaging, despite a retinopathy otherwise consistent with Stargardt disease. Forty such individuals were ascertained and a full ophthalmic examination was undertaken. Following mutation screening of ABCA4, the molecular findings were compared with those of patients with Stargardt disease but no foveal sparing.

Results: The median age of onset and age at examination of 40 patients with the foveal-sparing phenotype were 43.5 and 46.5 years. The median logMAR visual acuity was 0.18. Twenty-two patients (22/40, 55%) had patchy parafoveal atrophy and flecks; 8 (20%) had numerous flecks at the posterior pole without atrophy; 7 (17.5%) had mottled retinal pigment epithelial changes; 2 (5%) had multiple atrophic lesions, extending beyond the arcades; and 1 (2.5%) had a bull's-eye appearance. The median central foveal thickness assessed with spectral-domain optical coherence tomographic images was 183.0 μm (n = 33), with outer retinal tubulation observed in 15 (45%). Twenty-two of 33 subjects (67%) had electrophysiological evidence of macular dysfunction without generalized retinal dysfunction. Disease-causing variants were found in 31 patients (31/40, 78%). There was a higher prevalence of the variant p.Arg2030Gln in the cohort with foveal sparing compared to the group with foveal atrophy (6.45% vs 1.07%).

Conclusions: The distinct clinical and molecular characteristics of patients with the foveal-sparing phenotype are described. The presence of 2 distinct phenotypes of Stargardt disease (foveal sparing and foveal atrophy) suggests that there may be more than 1 disease mechanism in ABCA4 retinopathy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Adult
  • Age of Onset
  • Aged
  • DNA Mutational Analysis
  • Electrophysiology
  • Female
  • Fluorescein Angiography
  • Fovea Centralis / anatomy & histology*
  • Fovea Centralis / physiology*
  • Humans
  • Macular Degeneration / congenital*
  • Macular Degeneration / genetics
  • Macular Degeneration / physiopathology
  • Male
  • Middle Aged
  • Phenotype
  • Photography
  • Polymerase Chain Reaction
  • Retrospective Studies
  • Stargardt Disease
  • Tomography, Optical Coherence
  • Visual Acuity / physiology


  • ABCA4 protein, human
  • ATP-Binding Cassette Transporters