July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Associations between Perifoveal Drusen Burden and Genetic Risk in Eyes with Early or Intermediate Age-Related Macular Degeneration
Author Affiliations & Notes
  • Rafael Widjajahakim
    Ophthalmology and Visual Sciences, Macular Degeneration Center of Excellence, University of Massachusetts Medical School, Worcester, Massachusetts, United States
  • James Dossett
    Tufts University School of Medicine, Boston, Massachusetts, United States
  • Bernard Rosner
    Channing Division of Network Medicine, Harvard Medical School, Boston, Massachusetts, United States
  • Johanna M Seddon
    Ophthalmology and Visual Sciences, Macular Degeneration Center of Excellence, University of Massachusetts Medical School, Worcester, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Rafael Widjajahakim, None; James Dossett, None; Bernard Rosner, None; Johanna Seddon, Gemini Therapeutics, Inc (E)
  • Footnotes
    Support  NIH Grant R01 EY0011309, International Retinal Research Foundation (IRRF), The American Macular Degeneration Foundation (AMDF)
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1164. doi:
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    • Get Citation

      Rafael Widjajahakim, James Dossett, Bernard Rosner, Johanna M Seddon; Associations between Perifoveal Drusen Burden and Genetic Risk in Eyes with Early or Intermediate Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1164.

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      © ARVO (1962-2015); The Authors (2016-present)

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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.

 

 

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