title: Quantitative fundus autofluorescence distinguishes ABCA4-associated and non-ABCA4-associated bull's-eye maculopathy.
abstract: OBJECTIVE
  Quantitative fundus autofluorescence (qAF) and spectral-domain optical coherence tomography (SD OCT) were performed in patients with bull's-eye maculopathy (BEM) to identify phenotypic markers that can aid in the differentiation of ABCA4-associated and non-ABCA4-associated disease.
  
  
  METHODS
  Prospective cross-sectional study at an academic referral center.
  
  
  METHODS
  Thirty-seven BEM patients (age range, 8-60 years) were studied. All patients exhibited a localized macular lesion exhibiting a smooth contour and qualitatively normal-appearing surrounding retina without flecks. Control values consisted of previously published data from 277 healthy subjects (374 eyes; age range, 5-60 years) without a family history of retinal dystrophy.
  
  
  METHODS
  Autofluorescence (AF) images (30°, 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 grey levels (GLs) from 8 circularly arranged segments positioned at an eccentricity of approximately 7° to 9° in each image were calibrated to the reference (0 GL), magnification, and normative optical media density to yield qAF. In addition, horizontal SD OCT images through the fovea were obtained. All patients were screened for ABCA4 mutations using the ABCR600 microarray, next-generation sequencing, or both.
  
  
  METHODS
  Quantitative AF, correlations between AF and SD OCT, and genotyping for ABCA4 variants.
  
  
  RESULTS
  ABCA4 mutations were identified in 22 patients, who tended to be younger (mean age, 21.9±8.3 years) than patients without ABCA4 mutations (mean age, 42.1±14.9 years). Whereas phenotypic differences were not obvious on the basis of qualitative fundus AF and SD OCT imaging, with qAF, the 2 groups of patients were clearly distinguishable. In the ABCA4-positive group, 37 of 41 eyes (19 of 22 patients) had qAF8 of more than the 95% confidence interval for age. Conversely, in the ABCA4-negative group, 22 of 26 eyes (13 of 15 patients) had qAF8 within the normal range.
  
  
  CONCLUSIONS
  The qAF method can differentiate between ABCA4-associated and non-ABCA4-associated BEM and may guide clinical diagnosis and genetic testing.
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York.
authors.forename: Tobias
authors.initials: T
authors.lastname: Duncker
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York; Department of Pathology and Cell Biology, Columbia University, New York, New York.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Tsang
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York.
authors.forename: Winston
authors.initials: W
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York.
authors.forename: Jana
authors.initials: J
authors.lastname: Zernant
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York; Department of Pathology and Cell Biology, Columbia University, New York, New York.
authors.forename: Rando
authors.initials: R
authors.lastname: Allikmets
authors.affiliation: Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: François C
authors.initials: FC
authors.lastname: Delori
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York; Department of Pathology and Cell Biology, Columbia University, New York, New York. Electronic address: jrs88@columbia.edu.
authors.forename: Janet R
authors.initials: JR
authors.lastname: Sparrow
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002648:Child; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D008062:Lipofuscin / Q000378:metabolism; D008268:Macular Degeneration / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D041623:Tomography, Optical Coherence; D055815:Young Adult
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; D008062:Lipofuscin