title: Quantitative fundus autofluorescence in recessive Stargardt disease.
abstract: OBJECTIVE
  To quantify fundus autofluorescence (qAF) in patients with recessive Stargardt disease (STGD1).
  
  
  METHODS
  A total of 42 STGD1 patients (ages: 7-52 years) with at least one confirmed disease-associated ABCA4 mutation were studied. Fundus AF images (488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for variable laser power and detector sensitivity. The gray levels (GLs) of each image were calibrated to the reference, zero GL, magnification, and normative optical media density to yield qAF. Texture factor (TF) was calculated to characterize inhomogeneities in the AF image and patients were assigned to the phenotypes of Fishman I through III.
  
  
  RESULTS
  Quantified fundus autofluorescence in 36 of 42 patients and TF in 27 of 42 patients were above normal limits for age. Young patients exhibited the relatively highest qAF, with levels up to 8-fold higher than healthy eyes. Quantified fundus autofluorescence and TF were higher in Fishman II and III than Fishman I, who had higher qAF and TF than healthy eyes. Patients carrying the G1916E mutation had lower qAF and TF than most other patients, even in the presence of a second allele associated with severe disease.
  
  
  CONCLUSIONS
  Quantified fundus autofluorescence is an indirect approach to measuring RPE lipofuscin in vivo. We report that ABCA4 mutations cause significantly elevated qAF, consistent with previous reports indicating that increased RPE lipofuscin is a hallmark of STGD1. Even when qualitative differences in fundus AF images are not evident, qAF can elucidate phenotypic variation. Quantified fundus autofluorescence will serve to establish genotype-phenotype correlations and as an outcome measure in clinical trials.
authors.affiliation: Department of Ophthalmology and Columbia University, New York, New York, United States.
authors.forename: Tomas R
authors.initials: TR
authors.lastname: Burke
authors.forename: Tobias
authors.initials: T
authors.lastname: Duncker
authors.forename: Russell L
authors.initials: RL
authors.lastname: Woods
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Greenberg
authors.forename: Jana
authors.initials: J
authors.lastname: Zernant
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Tsang
authors.forename: R Theodore
authors.initials: RT
authors.lastname: Smith
authors.forename: Rando
authors.initials: R
authors.lastname: Allikmets
authors.forename: Janet R
authors.initials: JR
authors.lastname: Sparrow
authors.forename: François C
authors.initials: FC
authors.lastname: Delori
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005453:Fluorescence; D005654:Fundus Oculi; D006801:Humans; D008062:Lipofuscin; D008268:Macular Degeneration / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009887:Ophthalmoscopy / Q000379:methods*; D011446:Prospective Studies; D015203:Reproducibility of Results; D055213:Retinal Pigment Epithelium / Q000473:pathology*; D000080362:Stargardt Disease; D055815:Young Adult
chemical_list: D008062:Lipofuscin
keywords: ABCA4; lipofuscin; quantitative fundus autofluorescence; recessive Stargardt disease; retinal pigment epithelium; scanning laser ophthalmoscope