Department of Ophthalmology and Visual Sciences
Eye Diseases | Ophthalmology
Purpose: The purpose of this study was to determine associations between macular drusen parameters derived from an automatic optical coherence tomography (OCT) algorithm, nonadvanced age-related macular degeneration (AMD) stage, and genetic variants.
Methods: Eyes classified as early or intermediate AMD with OCT imaging and genetic data were selected (n = 239 eyes). Drusen area and volume measurements were estimated using the Zeiss Cirrus advanced retinal pigment epithelium analysis algorithm in a perifoveal zone centered on the fovea. Associations between drusen measurements and common genetic variants in the complement and high-density lipoprotein (HDL) lipid pathways and the ARMS2/HTRA1 variant were calculated using generalized estimating equations and linear mixed models adjusting for age, sex, smoking, body mass index, and education.
Results: Drusen area > /= the median was independently associated with a higher number of risk alleles for CFH risk score and risk variants in C3 and ARMS2/HTRA1 compared with eyes with no measurable drusen. Similar results were obtained for drusen volume. When all genes were analyzed in the same model, only CFH score and ARMS2/HTRA1 were associated with drusen measurements. HDL pathway genes were not significantly related to drusen parameters. Nonadvanced AMD stages were associated with OCT-derived drusen area and volume.
Conclusions: Variants in CFH and ARMS2/HTRA1, commonly associated with advanced AMD, were independently associated with an increase in drusen burden determined by OCT in an allele dose dependent manner, in eyes with early and intermediate AMD. Biomarkers such as a quantitative classification of nonadvanced AMD and other OCT-derived subphenotypes could provide earlier anatomic endpoints for clinical trials and facilitate the development of new therapies for AMD.
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Copyright 2019 The Authors. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DOI of Published Version
Invest Ophthalmol Vis Sci. 2019 Oct 1;60(13):4469-4478. doi: 10.1167/iovs.19-27475. Link to article on publisher's site
Investigative ophthalmology and visual science
Seddon JM, Dossett JP, Widjajahakim R, Rosner B. (2019). Association Between Perifoveal Drusen Burden Determined by OCT and Genetic Risk in Early and Intermediate Age-Related Macular Degeneration. Open Access Articles. https://doi.org/10.1167/iovs.19-27475. Retrieved from https://escholarship.umassmed.edu/oapubs/4013
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.