title: A longitudinal study of stargardt disease: clinical and electrophysiologic assessment, progression, and genotype correlations.
abstract: OBJECTIVE
  To investigate the clinical and electrophysiologic natural history of Stargardt disease and correlate with the genotype.
  
  
  METHODS
  Cohort study of 59 patients.
  
  
  METHODS
  Clinical history, examination, and electrophysiologic assessment were undertaken in a longitudinal survey. Patients were classified into 3 groups based on electrophysiologic findings, as previously published: Group 1 had dysfunction confined to the macula; Group 2 had macular and generalized cone system dysfunction; and Group 3 had macular and both generalized cone and rod system dysfunction. At baseline, there were 27 patients in Group 1, 17 in Group 2, and 15 in Group 3. Amplitude reduction of >50% in the relevant electroretinogram (ERG) component or a peak time shift of >3 ms for the 30 Hz flicker ERG or bright flash a-wave was considered clinically significant ERG deterioration. Molecular screening of ABCA4 was undertaken.
  
  
  RESULTS
  The mean age at baseline was 31.7 years, with the mean follow-up interval being 10.5 years. A total of 22% of patients from Group 1 showed ERG group transition during follow-up, with 11% progressing to Group 2 and 11% to Group 3. Forty-seven percent of patients in Group 2 progressed to Group 3. There was clinically significant ERG deterioration in 54% of all subjects: 22% of Group 1, 65% of Group 2, and 100% of Group 3. At least 1 disease-causing ABCA4 variant was identified in 47 patients.
  
  
  CONCLUSIONS
  All patients with initial rod ERG involvement demonstrated clinically significant electrophysiologic deterioration; only 20% of patients with normal full-field ERGs at baseline showed clinically significant progression. Such data assist counseling by providing more accurate prognostic information and are also highly relevant in the design, patient selection, and monitoring of potential therapeutic interventions.
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: Alice E
authors.initials: AE
authors.lastname: Davidson
authors.forename: Donna S
authors.initials: DS
authors.lastname: Mackay
authors.forename: Chris R
authors.initials: CR
authors.lastname: Hogg
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.forename: Kazushige
authors.initials: K
authors.lastname: Tsunoda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
authors.forename: Catey
authors.initials: C
authors.lastname: Bunce
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Robson
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Webster
authors.forename: Graham E
authors.initials: GE
authors.lastname: Holder
authors.forename: Michel
authors.initials: M
authors.lastname: Michaelides
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D003623:Dark Adaptation; D018450:Disease Progression; D004596:Electroretinography; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D006801:Humans; D008268:Macular Degeneration / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010775:Photic Stimulation; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology*; D000080362:Stargardt Disease; D014792:Visual Acuity / Q000502:physiology; D055815:Young Adult
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters