Both nature and nurture are factors for developing advanced age-related macular degeneration (AMD) and vision loss, according to findings published in Investigative Ophthalmology & Visual Science. The team also identified risk factors that may hasten the disease’s progression by up to 12 years.

There are genetic, demographic, and environmental variables that can predict who is more likely to progress to advanced AMD, according to researchers. However, the age at which patients progress from nonadvanced to advanced AMD varies, even among those with the same baseline macular pathology.

The Massachusetts-based investigators conducted longitudinal analyses to determine the behavioral and genetic factors associated with incidence and age of progression to advanced AMD, geographic atrophy (GA), and neovascular disease (NV). Analyses were conducted among the 5421 eyes of 2976 participants with nonadvanced AMD at baseline (mean age of 68.8 years ± 5.0 years), 56.1% women). Researchers confirmed progression based on 2 consecutive visits on the AMD severity scale. The team performed separate analyses for progression and age of progression and adjusted for correlation between eyes, demographic and behavioral covariates, baseline severity scale, and genetic variants.


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Higher genetic risk scores (GRS) — including 8 genetic variants — were associated with a higher rate of progression to advanced AMD within each baseline severity scale, especially for the highest risk intermediate level AMD category. A history of smoking further increased this risk. When looking at the age when progression to advanced disease occurred, researchers found that smoking reduced the age of onset by 3.9 years (P <.001), and higher body mass index (BMI) led to earlier onset by 1.7 years (P =.003). The team noted similar results for GA and NV. The genetic variants associated with earlier age of progression were CFH R1201C (4.3 years), C3 K155Q (2.15 years), and ARMS2/HTRA1 (0.8 years per allele).

The team concluded that combined, rare variants, smoking, and higher BMI could lead to as much as 11.5 additional years of disease and treatment burden. Following a healthy lifestyle could reduce risk and perhaps stave off visual impairment.

Limitations of this study include the use of baseline data as predictors of subsequent progression. Additionally, fundus photography was used to determine the severity scale and time of progression to advanced AMD. However, researchers note that optical coherence tomography or machine learning methods could improve the precision of these markers. 

Disclosure: One study author declared an affiliation with the biotech or pharmaceutical industries. Please see the original reference for a full list of authors’ disclosures.

Reference

Seddon JM, Widjajahakim R, Rosner B. Rare and common genetic variants, smoking, and body mass index: progression and earlier age of developing advanced age-related macular degeneration. Invest Ophthalmol Vis Sci. 2020;61(14):32. doi:10.1167/iovs.61.14.32