June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Prediction of AMD Progression Within Eye-Specific Baseline Severity Scales, and Attributable Fraction for Modifiable Factors and a Genetic Risk Score
Author Affiliations & Notes
  • Rafael Widjajahakim
    Dept. of Ophthalmology and Visual Sciences, University of Massachusetts Medical School, Worcester, Massachusetts, United States
  • Bernard Rosner
    Channing Division of Network Medicine, Harvard Medical School, Boston, Massachusetts, United States
  • Johanna M Seddon
    Dept. of Ophthalmology and Visual Sciences, University of Massachusetts Medical School, Worcester, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Rafael Widjajahakim, None; Bernard Rosner, None; Johanna Seddon, Gemini Therapeutics, Inc. (I)
  • Footnotes
    Support  NIH R01-EY011309; R01-EY028602; R01-EY022445; American Macular Degeneration Foundation, Northampton, MA. USA; The Macular Degeneration Center of Excellence, University of Massachusetts Medical School, Department of Ophthalmology and Visual Sciences, Worcester, MA, USA
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 325. doi:
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      Rafael Widjajahakim, Bernard Rosner, Johanna M Seddon; Prediction of AMD Progression Within Eye-Specific Baseline Severity Scales, and Attributable Fraction for Modifiable Factors and a Genetic Risk Score. Invest. Ophthalmol. Vis. Sci. 2021;62(8):325.

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

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Abstract

Purpose : To determine modifiable and genetic factors associated with progression to advanced age-related macular degeneration (AMD) for eyes with different baseline severity scales, and to assess population attributable fraction of these factors.

Methods : An eye that progressed was defined as a transition from no AMD or non-advanced AMD (AREDS severity scales 1-8) to any advanced AMD (scales ≥9) at 2 consecutive visits during 12 years of follow up. Eight genetic variants were associated with progression, adjusting for age, sex, education, smoking history, BMI, baseline severity scale, and AREDS treatment. A Genetic Risk Score (GRS) was calculated. Kaplan-Meier survival curves were constructed for the impact of GRS and smoking on rate of progression within categories of the baseline AMD scales, and population attributable fractions were calculated for specific factors.

Results : Among 5421 eyes, 948 progressed to advanced AMD. Genetic variants associated with progression included genes in the complement, immune, inflammatory, lipid, extracellular matrix, DNA repair and protein binding pathways. Eyes from subjects with GRS in the upper tertile had three times higher risk of progression than the lowest tertile (HR=3.03, 95% CI: 2.31-3.97) (Fig. 1). For overall advanced AMD, as well as the neovascular and atrophic subtypes, there was a strong effect for GRS among eyes with baseline intermediate level severity scales 6-8, while the differences were smaller among eyes starting with severity scales 1-5. As shown in Fig. 2, for eyes among past smokers with baseline severity scale 8, the 12 year probability of progression was 55% for GRS 1 vs. 90% for GRS 3, while among current smokers, the corresponding progression rates were 80% vs. > 95%. Calculation of population attributable fraction showed that the percent of disease prevented if smoking and body weight behaviors changed to past or never smoking and BMI < 25, was about 15%. In a similar calculation, if GRS tertiles changed from higher levels to the lowest risk, the percent prevented would be 37%, holding severity scale constant.

Conclusions : Carriers with higher GRS have higher risk of progression for eyes with the same level of baseline severity scale, and smoking further increases risk. Changing to healthier behaviors could reduce risk of progression from non-advanced to advanced stages of AMD.

This is a 2021 ARVO Annual Meeting abstract.

 

 

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