Quantitative Fundus Autofluorescence and Genetic Associations in Macular, Cone, and Cone-Rod Dystrophies
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Quantitative Fundus Autofluorescence and Genetic Associations in Macular, Cone, and Cone-Rod Dystrophies. / Gliem, Martin; Müller, Philipp L; Birtel, Johannes; Herrmann, Philipp; McGuinness, Myra B; Holz, Frank G; Charbel Issa, Peter.
in: OPHTHALMOL RETINA, Jahrgang 4, Nr. 7, 07.2020, S. 737-749.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Quantitative Fundus Autofluorescence and Genetic Associations in Macular, Cone, and Cone-Rod Dystrophies
AU - Gliem, Martin
AU - Müller, Philipp L
AU - Birtel, Johannes
AU - Herrmann, Philipp
AU - McGuinness, Myra B
AU - Holz, Frank G
AU - Charbel Issa, Peter
N1 - Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
PY - 2020/7
Y1 - 2020/7
N2 - PURPOSE: To investigate quantitatively lipofuscin-associated fundus autofluorescence in patients with macular and cone/cone-rod dystrophies (MD/CCRDs).DESIGN: Prospective, single-center, case-control study.PARTICIPANTS: Two hundred thirty patients with MD/CCRDs who had undergone genetic testing and 110 control participants without any eye disease.METHODS: Participants were examined using quantitative fundus autofluorescence (qAF) imaging with a modified confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference (modified Spectralis HRA-OCT; Heidelberg Engineering, Heidelberg, Germany). Mean qAF values were obtained by averaging measurements from an 8-segment ring centered on the fovea (qAF8) and compared with controls.MAIN OUTCOME MEASURES: The qAF8 levels.RESULTS: Elevated qAF8 values were a frequent finding (n = 105 [45%]) and associated with ABCA4 (n = 73 [70%]), PRPH2 (n = 9 [9%]), CERKL (n = 3 [3%]), PROM1 (n = 2 [2%]), CRX (n = 1 [1%]), and CDHR1 (n = 1 [1%]) mutations. Reduced qAF8 values were rare (n = 15 [7%]) and found predominantly among patients with MERTK (n = 3 [20%]) and RDH5 (n = 2 [13%]) mutations. Patients with normal qAF8 values (n = 110 [48%]) showed high genotypic heterogeneity. For various genes including ABCA4, PRPH2, CDHR1, and PROM1, higher qAF8 measures were associated with specific phenotypes and genotypes. For instance, qAF8 values were normal in PRPH2-related central areolar chorioretinal dystrophy but increased in PRPH2-related Stargardt-like retinopathy. Accordingly, high qAF8 levels were associated with specific genetic causes and mutation detection rates in characteristic but genetically heterogenous clinical phenotypes, such as a Stargardt-like flecked fundus, bull's eye maculopathy, or pattern dystrophy. In genetically unsolved cases (16 with elevated, 35 with normal, 7 with reduced qAF values), qAF8 was used to support or reject ambiguous results of genetic testing, to suggest underlying pathogenic pathways, and to predict disease in otherwise healthy participants.CONCLUSIONS: Quantitative fundus autofluorescence imaging revealed characteristic qAF levels in association with certain gene mutations and in participants without detected mutations. These findings indicate that qAF may facilitate differential diagnostics of MD/CCRDs and may offer novel pathogenetic insights that may be of particular value for the assessment of future treatment approaches.
AB - PURPOSE: To investigate quantitatively lipofuscin-associated fundus autofluorescence in patients with macular and cone/cone-rod dystrophies (MD/CCRDs).DESIGN: Prospective, single-center, case-control study.PARTICIPANTS: Two hundred thirty patients with MD/CCRDs who had undergone genetic testing and 110 control participants without any eye disease.METHODS: Participants were examined using quantitative fundus autofluorescence (qAF) imaging with a modified confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference (modified Spectralis HRA-OCT; Heidelberg Engineering, Heidelberg, Germany). Mean qAF values were obtained by averaging measurements from an 8-segment ring centered on the fovea (qAF8) and compared with controls.MAIN OUTCOME MEASURES: The qAF8 levels.RESULTS: Elevated qAF8 values were a frequent finding (n = 105 [45%]) and associated with ABCA4 (n = 73 [70%]), PRPH2 (n = 9 [9%]), CERKL (n = 3 [3%]), PROM1 (n = 2 [2%]), CRX (n = 1 [1%]), and CDHR1 (n = 1 [1%]) mutations. Reduced qAF8 values were rare (n = 15 [7%]) and found predominantly among patients with MERTK (n = 3 [20%]) and RDH5 (n = 2 [13%]) mutations. Patients with normal qAF8 values (n = 110 [48%]) showed high genotypic heterogeneity. For various genes including ABCA4, PRPH2, CDHR1, and PROM1, higher qAF8 measures were associated with specific phenotypes and genotypes. For instance, qAF8 values were normal in PRPH2-related central areolar chorioretinal dystrophy but increased in PRPH2-related Stargardt-like retinopathy. Accordingly, high qAF8 levels were associated with specific genetic causes and mutation detection rates in characteristic but genetically heterogenous clinical phenotypes, such as a Stargardt-like flecked fundus, bull's eye maculopathy, or pattern dystrophy. In genetically unsolved cases (16 with elevated, 35 with normal, 7 with reduced qAF values), qAF8 was used to support or reject ambiguous results of genetic testing, to suggest underlying pathogenic pathways, and to predict disease in otherwise healthy participants.CONCLUSIONS: Quantitative fundus autofluorescence imaging revealed characteristic qAF levels in association with certain gene mutations and in participants without detected mutations. These findings indicate that qAF may facilitate differential diagnostics of MD/CCRDs and may offer novel pathogenetic insights that may be of particular value for the assessment of future treatment approaches.
KW - Adolescent
KW - Adult
KW - Case-Control Studies
KW - Child
KW - Cone-Rod Dystrophies/genetics
KW - Cross-Sectional Studies
KW - DNA/genetics
KW - DNA Mutational Analysis
KW - Eye Proteins/genetics
KW - Female
KW - Fluorescein Angiography/methods
KW - Fundus Oculi
KW - Humans
KW - Male
KW - Middle Aged
KW - Mutation
KW - Ophthalmoscopy/methods
KW - Pedigree
KW - Prospective Studies
KW - Retinal Cone Photoreceptor Cells/pathology
KW - Retinal Pigment Epithelium/pathology
KW - Tomography, Optical Coherence/methods
KW - Young Adult
U2 - 10.1016/j.oret.2020.02.009
DO - 10.1016/j.oret.2020.02.009
M3 - SCORING: Journal article
C2 - 32646556
VL - 4
SP - 737
EP - 749
JO - OPHTHALMOL RETINA
JF - OPHTHALMOL RETINA
SN - 2468-6530
IS - 7
ER -