title: Clinical and molecular analysis of Stargardt disease with preserved foveal structure and function.
abstract: OBJECTIVE
  To describe a cohort of patients with Stargardt disease who show a foveal-sparing phenotype.
  
  
  METHODS
  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.
authors: University College London, Institute of Ophthalmology, London, United Kingdom; Moorfields Eye Hospital, London, United Kingdom; Laboratory of Visual Physiology, National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo, Japan; Department of Ophthalmology, Keio University, School of Medicine, Tokyo, Japan.
authors: Kaoru
authors: K
authors: Fujinami
authors: University College London, Institute of Ophthalmology, London, United Kingdom; Moorfields Eye Hospital, London, United Kingdom.
authors: Panagiotis I
authors: PI
authors: Sergouniotis
authors: University College London, Institute of Ophthalmology, London, United Kingdom; Moorfields Eye Hospital, London, United Kingdom.
authors: Alice E
authors: AE
authors: Davidson
authors: University College London, Institute of Ophthalmology, London, United Kingdom; Moorfields Eye Hospital, London, United Kingdom.
authors: Genevieve
authors: G
authors: Wright
authors: University College London, Institute of Ophthalmology, London, United Kingdom; Moorfields Eye Hospital, London, United Kingdom.
authors: Ravinder K
authors: RK
authors: Chana
authors: Laboratory of Visual Physiology, National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo, Japan.
authors: Kazushige
authors: K
authors: Tsunoda
authors: Department of Ophthalmology, Keio University, School of Medicine, Tokyo, Japan.
authors: Kazuo
authors: K
authors: Tsubota
authors: University College London, Institute of Ophthalmology, London, United Kingdom; Moorfields Eye Hospital, London, United Kingdom.
authors: Catherine A
authors: CA
authors: Egan
authors: University College London, Institute of Ophthalmology, London, United Kingdom; Moorfields Eye Hospital, London, United Kingdom.
authors: Anthony G
authors: AG
authors: Robson
authors: University College London, Institute of Ophthalmology, London, United Kingdom; Moorfields Eye Hospital, London, United Kingdom.
authors: Anthony T
authors: AT
authors: Moore
authors: University College London, Institute of Ophthalmology, London, United Kingdom; Moorfields Eye Hospital, London, United Kingdom.
authors: Graham E
authors: GE
authors: Holder
authors: University College London, Institute of Ophthalmology, London, United Kingdom; Moorfields Eye Hospital, London, United Kingdom.
authors: Michel
authors: M
authors: Michaelides
authors: University College London, Institute of Ophthalmology, London, United Kingdom; Moorfields Eye Hospital, London, United Kingdom. Electronic address: andrew.webster@ucl.ac.uk.
authors: Andrew R
authors: AR
authors: Webster
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D017668:Age of Onset; D000368:Aged; D004252:DNA Mutational Analysis; D004594:Electrophysiology; D005260:Female; D005451:Fluorescein Angiography; D005584:Fovea Centralis / Q000033:anatomy & histology* / Q000502:physiology*; D006801:Humans; D008268:Macular Degeneration / Q000151:congenital* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010781:Photography; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D000080362:Stargardt Disease; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters