title: A longitudinal study of Stargardt disease: quantitative assessment of fundus autofluorescence, progression, and genotype correlations.
abstract: OBJECTIVE
  We characterized subtypes of fundus autofluorescence (AF) and the progression of retinal atrophy, and correlated these findings with genotype in Stargardt disease.
  
  
  METHODS
  Full clinical examination and AF imaging was undertaken in 68 patients with Stargardt disease. The baseline data were compared to those at follow-up. Patients were classified into three AF subtypes: type 1 had a localized low signal at the fovea surrounded by a homogeneous background, type 2 had a localized low signal at the macula surrounded by a heterogeneous background with numerous foci of abnormal signal, and type 3 had multiple low signal areas at the posterior pole with a heterogeneous background. At baseline, there were 19 patients with type 1, 41 with type 2, and 8 with type 3 disease. The areas of reduced AF signal were measured and rate of atrophy enlargement (RAE) was calculated as the difference of the atrophy size over time (mm²) divided by the follow-up interval (years). Molecular screening of ABCA4 was undertaken.
  
  
  RESULTS
  The mean follow-up interval was 9.1 years. A total of 42% cases with type 1 disease progressed to type 2, and 12% with type 2 progressed to type 3. The RAE (mm²/y) based upon baseline AF subtypes was significantly different; 0.06 in type 1, 0.67 in type 2, and 4.37 in type 3. ABCA4 variants were identified in 57 patients. There was a significant association between AF subtype and genotype.
  
  
  CONCLUSIONS
  The AF pattern at baseline influences the enlargement of atrophy over time and has genetic correlates. These data are likely to assist in the provision of counseling on prognosis in Stargardt disease and be valuable for future clinical trials.
authors.affiliation: University College London Institute of Ophthalmology, London, United Kingdom.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Fujinami
authors.forename: Noemi
authors.initials: N
authors.lastname: Lois
authors.forename: Rajarshi
authors.initials: R
authors.lastname: Mukherjee
authors.forename: Vikki A
authors.initials: VA
authors.lastname: McBain
authors.forename: Kazushige
authors.initials: K
authors.lastname: Tsunoda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.forename: Fred W
authors.initials: FW
authors.lastname: Fitzke
authors.forename: Catey
authors.initials: C
authors.lastname: Bunce
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Webster
authors.forename: Michel
authors.initials: M
authors.lastname: Michaelides
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography / Q000379:methods*; D005500:Follow-Up Studies; D005654:Fundus Oculi; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009887:Ophthalmoscopy; D055213:Retinal Pigment Epithelium / Q000473:pathology*; D000080362:Stargardt Disease; D055815:Young Adult
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; D004247:DNA
keywords: ABCA4; Stargardt; autofluorescence