Abstract
Purpose :
To determine associations between macular drusen parameters derived from an automatic OCT algorithm, age-related macular degeneration (AMD) stage and genetic variants.
Methods :
Eyes classified with early and intermediate AMD with OCT imaging among participants with genetic data were selected (n=239 eyes). Drusen area and volume measurements were estimated using the Zeiss Cirrus advanced retinal pigment epithelium (RPE) analysis algorithm in a 5mm diameter zone centered on the fovea (perifoveal region). Ten common single nucleotide polymorphisms (SNPs) associated with AMD were evaluated: CFH Y402H: rs1061170, CFH: rs1410996, ARMS2 A69S: rs10490924, CFB: rs541862, C3 R102G: rs2230119, COL8A1: rs13095226, RAD51B: rs8017304, ABCA1: rs1883025, LIPC: rs10468017, CETP: rs3764261. Associations between drusen measurements and genetic variants were calculated using generalized estimating equations and linear mixed models adjusting for age, sex, smoking, BMI, and education. Additional analyses were performed for the two most consistently associated genetic variants.
Results :
No gene variants were consistently associated with drusen area and volume less than the median in the perifoveal region compared to eyes with no measurable drusen (Table 1). CFH: rs1410996 and ARMS2 A69S: rs10490924 were consistently associated with drusen area and volume ≥ median (Table 1). When analyzed in a linear mixed model, CFH homozygous risk was associated with significantly greater adjusted means of drusen area and volume when compared to the homozygous non-risk genotype (p=0.028; p=0.023 respectively). Results were consistent when one gene was adjusted for the other in a bivariate model, with significant trends for higher means with more risk alleles for both CFH: rs1410996 and ARMS2 A69S: rs10490924 (Table 2).
Conclusions :
CFH and ARMS2 genetic variants commonly associated with advanced AMD are associated with higher drusen burden in eyes with early and intermediate AMD, as determined by the automatic RPE algorithm using OCT. Further characterization of drusen morphology and other sub-phenotypes may lead to identification of biomarkers that could serve as early anatomic endpoints for clinical trials.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.