June 2020
Volume 61, Issue 7
ARVO Annual Meeting Abstract  |   June 2020
Genetic Susceptibility, Diet Quality and Two Step Progression in Drusen Size
Author Affiliations & Notes
  • Johanna M Seddon
    University of Massachusetts Medical School, Boston, Massachusetts, United States
  • Bernard Rosner
    Channing Division of Network Medicine, Harvard Medical School, Boston, Massachusetts, United States
  • Benedicte MJ Merle
    Bordeaux Population Health Research Center, team LEHA, Univ. Bordeaux, Inserm, Bordeaux, France
  • Footnotes
    Commercial Relationships   Johanna Seddon, Gemini Therapeutics, Inc (E), Laboratoires Théa (R); Bernard Rosner, None; Benedicte Merle, Bausch&Lomb (R), Laboratoires Théa (R), Synadiet (R)
  • Footnotes
    Support  NIH R01-EY011309, R01-EY028602, R01-EY022445, American Macular Degeneration Foundation, Northampton, MA, The Macular Degeneration Center of Excellence, University of Massachusetts Medical School, Department of Ophthalmology and Visual Sciences, Worcester, MA
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 2997. doi:
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      Johanna M Seddon, Bernard Rosner, Benedicte MJ Merle; Genetic Susceptibility, Diet Quality and Two Step Progression in Drusen Size. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2997.

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

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Purpose : Genetic susceptibility and modifiable factors including the Alternate Mediterranean Diet (aMeDi) are associated with rate of progression to advanced stages of AMD. (Merle B, Am J Clin Nut 2015; 102:1196-1206, Seddon J. IOVS 2017; 58: 6513-6528). In this study, we investigated the relationship of growth in drusen size in earlier stages of AMD with genetic susceptibility and the aMeDi.

Methods : Subjects in this analysis had complete ocular, genetic and dietary data with mean follow-up time of 10.2 years in the Age-Related Eye Disease database. Maximal drusen size was graded on an ordinal scale and 2 step progression was determined. A genetic risk score using variants associated with advanced AMD and derived from a stepwise regression model yielded 11 variants in 8 genes. Adherence to aMeDi was assessed using a 9-component score based on intake of vegetables, fruits, legumes, whole cereals, fish, meat, nuts, alcohol, and monounsaturated-to-saturated fatty acids ratio. Multivariate Cox proportional hazards models were used to assess associations between drusen growth and the genetic and nutritional variables.

Results : Among 3023 eligible eyes, 587 (19.4%) had drusen growth. In the stepwise selection, common and rare risk alleles for CFH Y402H, CFH rs1410996, CFH R1210C, C3 R102G, C3 K155Q, VEGF-A, ARMS2/HTRA1, TIMP3, NPLOC4, and HSPH1 variants were significantly associated with 2 step progression in drusen size, and the C2 E318D protective allele conferred decreased risk, adjusting for other covariates. Participants with a high genetic risk score had higher risk, (HR per 1 standard deviation increase = 1.64, 95% CI: 1.49-1.80; P<0.001), and subjects with a medium/high adherence to aMeDi score (4 to 9) tended to have a lower risk (HR 0.83, 95% CI: 0.68-0.99; P=0.049), adjusting for all covariates.

Conclusions : Genetic susceptibility involving the complement, immune and other biologic pathways was independently related to drusen growth, after adjusting for other AMD risk factors. A diet rich in healthful nutrient-rich foods including fruits, vegetables, legumes and fish, as in the Mediterranean diet, may reduce enlargement of drusen, the hallmark of early stages AMD. Knowledge of both nature and nurture -modifiable factors and genetic susceptibility-may identify subjects at higher risk of early disease progression who could benefit from preventive measures.

This is a 2020 ARVO Annual Meeting abstract.


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