June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Retinal pigment epithelium (RPE) pigmentary changes are associated with progression from early to advanced age-related macular degeneration (AMD) independent of CFH and ARMS2 risk genotypes.
Author Affiliations & Notes
  • William K Scott
    Hussman Institute for Human Genomics, University of Miami, Miami, Florida, United States
  • Susan H. Slifer
    Hussman Institute for Human Genomics, University of Miami, Miami, Florida, United States
  • Jacob K. Welch
    Hussman Institute for Human Genomics, University of Miami, Miami, Florida, United States
  • Stephen G Schwartz
    Bascom Palmer Eye Institute, University of Miami, Naples, Florida, United States
  • Jaclyn L Kovach
    Bascom Palmer Eye Institute, University of Miami, Naples, Florida, United States
  • Srinivas Sadda
    Doheny Eye Institute, Los Angeles, California, United States
  • Muneeswar G. Nittala
    Doheny Eye Institute, Los Angeles, California, United States
  • Jonathan L Haines
    Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, United States
  • Margaret A Pericak-Vance
    Hussman Institute for Human Genomics, University of Miami, Miami, Florida, United States
  • Footnotes
    Commercial Relationships   William Scott, None; Susan Slifer, None; Jacob Welch, None; Stephen Schwartz, None; Jaclyn Kovach, None; Srinivas Sadda, None; Muneeswar Nittala, None; Jonathan Haines, None; Margaret Pericak-Vance, None
  • Footnotes
    Support  NIH Grant EY012118, BrightFocus Foundation Grant M2018112
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 4189. doi:
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      William K Scott, Susan H. Slifer, Jacob K. Welch, Stephen G Schwartz, Jaclyn L Kovach, Srinivas Sadda, Muneeswar G. Nittala, Jonathan L Haines, Margaret A Pericak-Vance; Retinal pigment epithelium (RPE) pigmentary changes are associated with progression from early to advanced age-related macular degeneration (AMD) independent of CFH and ARMS2 risk genotypes.. Invest. Ophthalmol. Vis. Sci. 2020;61(7):4189.

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

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Abstract

Purpose : Studies of progression from early to advanced AMD (either geographic atrophy, GA, or choroidal neovascularization, CNV) have focused separately on genetic factors or ocular pathology. Drusen size, area and volume and presence of RPE pigmentary abnormalities are consistently associated with progression. Studies examining risk factors for progression should consider joint effects of genetic factors and baseline ocular pathology.

Methods : We studied 354 European-descended individuals with >=1 year of follow-up and >=1 eye with early AMD at baseline examination. Mean age at baseline was 77.1 years (range: 57–92); 60% of subjects were women. Fundus photograph evaluation used a modified AREDS clinical staging and noted presence of pseudodrusen, RPE detachment, and RPE hyper- or hypo-pigmentation. Genome-wide array genotyping and imputation determined risk alleles at CFH and ARMS2. Cox proportional hazards regression models assessed association of AREDS grade, baseline ocular pathology, and genotypes with time to progression from early to advanced AMD in each eye. Covariates included baseline grade, sex, age at baseline, and a random effect for correlation between paired eyes.

Results : Significantly shorter time of progression to advanced AMD was detected in eyes with intermediate AMD (hazard ratio (HR)=4.61, p=0.03), RPE hyperpigmentation (HR=4.71, p=1.4 x 10-9) or hypopigmentation (HR=6.8, p=6.9 x 10-7). Pseudodrusen and RPE detachment were not significantly associated. The association of RPE pigmentation with progression was not altered by CFH (rs10922109) or ARMS2 (rs3750846) risk alleles, and neither locus was associated with progression time or with hyper- or hypo-pigmentation. Results were similar when considering progression to GA and CNV separately.

Conclusions : These results support prior findings of increased risk (and shorter time to progression) for eyes with large or frequent small drusen and eyes with RPE pigmentation changes (regardless of drusen size and number). RPE pigmentation changes are useful indicators of individuals at increased risk of progression, and statistical models of progression to advanced AMD should incorporate both genetic factors and ocular traits measured by fundus photography and optical coherence tomography.

This is a 2020 ARVO Annual Meeting abstract.

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