PMID- 25283059 OWN - NLM STAT- MEDLINE DCOM- 20150414 LR - 20211021 IS - 1549-4713 (Electronic) IS - 0161-6420 (Print) IS - 0161-6420 (Linking) VI - 122 IP - 2 DP - 2015 Feb TI - Quantitative fundus autofluorescence distinguishes ABCA4-associated and non-ABCA4-associated bull's-eye maculopathy. PG - 345-55 LID - S0161-6420(14)00755-6 [pii] LID - 10.1016/j.ophtha.2014.08.017 [doi] AB - PURPOSE: 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. DESIGN: Prospective cross-sectional study at an academic referral center. SUBJECTS: 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 degrees , 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 degrees to 9 degrees 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. MAIN OUTCOME MEASURES: 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. CI - Copyright (c) 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. FAU - Duncker, Tobias AU - Duncker T AD - Department of Ophthalmology, Columbia University, New York, New York. FAU - Tsang, Stephen H AU - Tsang SH AD - Department of Ophthalmology, Columbia University, New York, New York; Department of Pathology and Cell Biology, Columbia University, New York, New York. FAU - Lee, Winston AU - Lee W AD - Department of Ophthalmology, Columbia University, New York, New York. FAU - Zernant, Jana AU - Zernant J AD - Department of Ophthalmology, Columbia University, New York, New York. FAU - Allikmets, Rando AU - Allikmets R AD - Department of Ophthalmology, Columbia University, New York, New York; Department of Pathology and Cell Biology, Columbia University, New York, New York. FAU - Delori, Francois C AU - Delori FC AD - Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts. FAU - Sparrow, Janet R AU - Sparrow JR AD - 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. LA - eng GR - R01 EY024091/EY/NEI NIH HHS/United States GR - R01 EY015520/EY/NEI NIH HHS/United States GR - R01 EY018213/EY/NEI NIH HHS/United States GR - EY015520/EY/NEI NIH HHS/United States GR - P30EY019007/EY/NEI NIH HHS/United States GR - EY024091/EY/NEI NIH HHS/United States GR - R24 EY019861/EY/NEI NIH HHS/United States GR - P30 EY019007/EY/NEI NIH HHS/United States GR - EY019861/EY/NEI NIH HHS/United States GR - EY021163/EY/NEI NIH HHS/United States GR - R01 EY021163/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20141003 PL - United States TA - Ophthalmology JT - Ophthalmology JID - 7802443 RN - 0 (ABCA4 protein, human) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Lipofuscin) RN - Macular dystrophy, concentric annular SB - IM MH - ATP-Binding Cassette Transporters/*genetics MH - Adolescent MH - Adult MH - Child MH - Cross-Sectional Studies MH - DNA Mutational Analysis MH - Female MH - *Fluorescein Angiography MH - Humans MH - Lipofuscin/metabolism MH - Macular Degeneration/*diagnosis/*genetics/metabolism MH - Male MH - Middle Aged MH - Prospective Studies MH - Retinal Pigment Epithelium/metabolism MH - Tomography, Optical Coherence MH - Young Adult PMC - PMC4306619 MID - NIHMS633369 EDAT- 2014/10/07 06:00 MHDA- 2015/04/15 06:00 PMCR- 2016/02/01 CRDT- 2014/10/07 06:00 PHST- 2014/05/14 00:00 [received] PHST- 2014/06/26 00:00 [revised] PHST- 2014/08/06 00:00 [accepted] PHST- 2014/10/07 06:00 [entrez] PHST- 2014/10/07 06:00 [pubmed] PHST- 2015/04/15 06:00 [medline] PHST- 2016/02/01 00:00 [pmc-release] AID - S0161-6420(14)00755-6 [pii] AID - 10.1016/j.ophtha.2014.08.017 [doi] PST - ppublish SO - Ophthalmology. 2015 Feb;122(2):345-55. doi: 10.1016/j.ophtha.2014.08.017. Epub 2014 Oct 3.