Abstract
Purpose: To investigate the association of optical coherence tomography (OCT)-derived drusen measures in Amish age-related macular degeneration (AMD) patients with known loci for macular degeneration. Methods: Members of the Old Order Amish community in Pennsylvania ages 50 and older were assessed for drusen area, volume and regions of retinal pigment epithelium (RPE) atrophy using a Cirrus High-Definition OCT. Measurements were obtained in the macula region within a central circle (CC) of 3 mm in diameter and a surrounding perifoveal ring (PR) of 3 to 5 mm in diameter using the Cirrus OCT RPE analysis software. Other demographic information, including age, gender and smoking status, were collected. Study subjects were further genotyped to determine their risk for the AMD-associated SNPs in the SYN3, LIPC, ARMS2, C3, CFB, CETP, CFI and CFH genes using TaqMan genotyping assays. The association of genotypes with OCT measures were assessed using linear trend p-values calculated from univariate and multivariate generalized linear models. Results: 432 eyes were included in the analysis. Multivariate analysis (adjusted by age, gender and smoking status) confirmed the known significant association between AMD and macular drusen with the number of CFH risk alleles for the drusen area (the area increased 0.12 mm2 for a risk allele increase, p < 0.01), drusen volume (the volume increased 0.01 mm3 for a risk allele increase, p ≤ 0.05) and the area of RPE atrophy (the area increased 0.43 mm2 for a risk allele increase, p = 0.003). SYN3 risk allele G is significantly associated with larger area PR (the area increased 0.09 mm2 for a risk allele increase, p = 0.03) and larger drusen volume in the central circle (the volume increased 0.01 mm3 for a risk allele increase, p = 0.04). Conclusion: Among the genotyped SNPs tested, the CFH risk genotype appears to play a major role in determining the drusen phenotype in the Amish AMD population.
Highlights
Age-related macular degeneration (AMD) is a leading cause of vision loss and is influenced by genetic, environmental and dietary factors [1]
We describe the correlation of optical coherence tomography (OCT)-derived measures of drusen and retinal pigment epithelium (RPE) atrophy in an elderly Amish population with SNP genotypes in the complement-related genes: factor H (CFH), CFI, complement factor B region (CFB), CETP, C3, ARMS2, LIPC
To determine if there was an association among 3 genotypes of each SNP and drusen area/volume or area of RPE atrophy, the number of risk alleles for each genotype was counted as either 0, 1 or 2, and genotype association with each OCT measure from an eye was evaluated using tests of linear trend from generalized linear models with inter-eye correlation accounted for using generalized estimating equations (GEE)
Summary
Age-related macular degeneration (AMD) is a leading cause of vision loss and is influenced by genetic, environmental and dietary factors [1]. It is estimated that in the United States alone, the number of advanced AMD cases may reach up to three million by the year 2020 [2]. Clinical features of AMD include the death of photoreceptors and retinal pigment epithelium (RPE). Drusen are hallmark deposits associated with early AMD and considered to be a major risk factor for the progression of AMD [3,4,5]. The late stages of AMD are classically divided into two forms: non-neovascular (“dry”) AMD/atrophic. Several studies have identified a variety of potential risk factors associated with AMD [6]
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