TY - JOUR
T1 - Progression of geographic atrophy and genotype in age-related macular degeneration
AU - Klein, Michael L.
AU - Ferris, Frederick L.
AU - Francis, Peter J.
AU - Lindblad, Anne S.
AU - Chew, Emily Y.
AU - Hamon, Sara C.
AU - Ott, Jurg
N1 - Funding Information:
Supported by contracts and grants from the National Eye Institute, National Institutes of Health , Bethesda, Maryland, R01-EY12203 (MLK), China NSFC grant 30730057 (JO), grants to the Casey Eye Institute, Oregon Health & Science University from Research to Prevent Blindness , New York, New York (PJF, MLK), the Foundation Fighting Blindness , Owings Mills, Maryland (PJF), and the Casey Eye Institute Macular Degeneration Fund (MLK and PJF). The authors have no proprietary interest in any materials or products discussed herein. No authors have any financial/conflicting interests to disclose.
PY - 2010
Y1 - 2010
N2 - Purpose: We sought to determine whether genotype is associated with rate of growth of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD). Design: Prospective analysis of participants in a randomized controlled clinical trial. Participants: We included 114 eyes of 114 participants in the Age-Related Eye Disease Study (AREDS). Methods: Fundus photographs from AREDS participants with GA from whom a DNA specimen had been obtained and serial photographs had been taken over a minimum of 2 years were evaluated for progression as determined by change in cumulative area of GA. All fundus photographs were scanned, digitized, and centrally graded longitudinally for area of GA. The relationship of GA progression with previously identified genetic variants associated with AMD was assessed. Main Outcome Measures: Genotype frequencies and change in cumulative area of GA. Results: The mean growth rate of GA for the 114 eyes was 1.79 mm2/year (range, 0.17-4.76). No association between growth rate and genotype was present for variants in the CFH, C2, C3, APOE, and TLR3 genes. For the single nucleotide polymorphism rs10490924 in LOC387715/ARMS2, there was a significant association of GA growth rate, both adjusted and unadjusted for initial lesion size, with the homozygous risk genotype as compared with the homozygous nonrisk genotype (unadjusted P = 0.002; Bonferroni-corrected P = 0.014) and for allelic association (Bonferroni-corrected P value = 0.011). Analyses of other measures of GA progression (progression to central GA from extrafoveal GA and development of bilateral GA in those initially with unilateral GA) showed no statistically significant association between progression and the LOC387715/ARMS2/HTRA1 genotype. Conclusions: Growth rates of GA calculated from digitized serial fundus photographs showed no association with variants in the CFH, C2, C3, APOE, or TLR3 genes. There was a nominally significant association with the LOC387715/ARMS2/HTRA1 genotype, although this finding was not supported by analyses of secondary measures of GA progression. Replication in other populations is needed to establish the existence of an association. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.
AB - Purpose: We sought to determine whether genotype is associated with rate of growth of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD). Design: Prospective analysis of participants in a randomized controlled clinical trial. Participants: We included 114 eyes of 114 participants in the Age-Related Eye Disease Study (AREDS). Methods: Fundus photographs from AREDS participants with GA from whom a DNA specimen had been obtained and serial photographs had been taken over a minimum of 2 years were evaluated for progression as determined by change in cumulative area of GA. All fundus photographs were scanned, digitized, and centrally graded longitudinally for area of GA. The relationship of GA progression with previously identified genetic variants associated with AMD was assessed. Main Outcome Measures: Genotype frequencies and change in cumulative area of GA. Results: The mean growth rate of GA for the 114 eyes was 1.79 mm2/year (range, 0.17-4.76). No association between growth rate and genotype was present for variants in the CFH, C2, C3, APOE, and TLR3 genes. For the single nucleotide polymorphism rs10490924 in LOC387715/ARMS2, there was a significant association of GA growth rate, both adjusted and unadjusted for initial lesion size, with the homozygous risk genotype as compared with the homozygous nonrisk genotype (unadjusted P = 0.002; Bonferroni-corrected P = 0.014) and for allelic association (Bonferroni-corrected P value = 0.011). Analyses of other measures of GA progression (progression to central GA from extrafoveal GA and development of bilateral GA in those initially with unilateral GA) showed no statistically significant association between progression and the LOC387715/ARMS2/HTRA1 genotype. Conclusions: Growth rates of GA calculated from digitized serial fundus photographs showed no association with variants in the CFH, C2, C3, APOE, or TLR3 genes. There was a nominally significant association with the LOC387715/ARMS2/HTRA1 genotype, although this finding was not supported by analyses of secondary measures of GA progression. Replication in other populations is needed to establish the existence of an association. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.
UR - http://www.scopus.com/inward/record.url?scp=77955469874&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955469874&partnerID=8YFLogxK
U2 - 10.1016/j.ophtha.2009.12.012
DO - 10.1016/j.ophtha.2009.12.012
M3 - Article
C2 - 20381870
AN - SCOPUS:77955469874
SN - 0161-6420
VL - 117
SP - 1554-1559.e1
JO - Ophthalmology
JF - Ophthalmology
IS - 8
ER -