title: Quantitative Fundus Autofluorescence and Optical Coherence Tomography in ABCA4 Carriers.
abstract: OBJECTIVE
  To assess whether carriers of ABCA4 mutations have increased RPE lipofuscin levels based on quantitative fundus autofluorescence (qAF) and whether spectral-domain optical coherence tomography (SD-OCT) reveals structural abnormalities in this cohort.
  
  
  METHODS
  Seventy-five individuals who are heterozygous for ABCA4 mutations (mean age, 47.3 years; range, 9-82 years) were recruited as family members of affected patients from 46 unrelated families. For comparison, 57 affected family members with biallelic ABCA4 mutations (mean age, 23.4 years; range, 6-67 years) and two noncarrier siblings were also enrolled. Autofluorescence images (30°, 488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference. The gray levels (GLs) of each image were calibrated to the reference, zero GL, magnification, and normative optical media density to yield qAF. Horizontal SD-OCT scans through the fovea were obtained and the thicknesses of the outer retinal layers were measured.
  
  
  RESULTS
  In 60 of 65 carriers of ABCA4 mutations (age range, 9-60), qAF levels were within normal limits (95% confidence level) observed for healthy noncarrier subjects, while qAF levels of affected family members were significantly increased. Perifoveal fleck-like abnormalities were observed in fundus AF images in four carriers, and corresponding changes were detected in the outer retinal layers in SD-OCT scans. Thicknesses of the outer retinal layers were within the normal range.
  
  
  CONCLUSIONS
  With few exceptions, individuals heterozygous for ABCA4 mutations and between the ages of 9 and 60 years do not present with elevated qAF. In a small number of carriers, perifoveal fleck-like changes were visible.
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States.
authors.forename: Tobias
authors.initials: T
authors.lastname: Duncker
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States.
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Stein
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States.
authors.forename: Winston
authors.initials: W
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States 2Department of Pathology and Cell Biology, Columbia University, New York, New York, United States.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Tsang
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States.
authors.forename: Jana
authors.initials: J
authors.lastname: Zernant
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States.
authors.forename: Srilaxmi
authors.initials: S
authors.lastname: Bearelly
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States 3Department of Psychology, Columbia University, New York, New York, United States.
authors.forename: Donald C
authors.initials: DC
authors.lastname: Hood
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States.
authors.forename: Vivienne C
authors.initials: VC
authors.lastname: Greenstein
authors.affiliation: Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: François C
authors.initials: FC
authors.lastname: Delori
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States 2Department of Pathology and Cell Biology, Columbia University, New York, New York, United States.
authors.forename: Rando
authors.initials: R
authors.lastname: Allikmets
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States 2Department of Pathology and Cell Biology, Columbia University, New York, New York, United States.
authors.forename: Janet R
authors.initials: JR
authors.lastname: Sparrow
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005451:Fluorescein Angiography / Q000379:methods*; D005654:Fundus Oculi; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000473:pathology*; D012374:Rod Cell Outer Segment; D041623:Tomography, Optical Coherence / Q000379:methods*; D055815:Young Adult
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; D004247:DNA