A recently developed composite risk score model appeared more effective at anticipating progression than the model with more than 30 genetic variants known to be related to prevalent AMD. Photo: Getty Images; Anna Bedwell, OD. Click image to enlarge.

Identifying subtypes of early AMD that pose higher risk of progression to the vision-threatening forms of the disease could lead to earlier intervention, more frequent monitoring and reduced burden of visual loss. Genetic screening has been attempted in the past but the polygenic nature of AMD has made its clinical value questionable. Researchers in Massachusetts developed a composite risk score that included family history, non-genetic factors and the most predictive genetic variants, and demonstrated that it was able to separate high and low risk of progression among eyes with the same baseline AMD severity group. The team found that a family history of AMD conferred additional important information in risk prediction even after adjusting for genetic susceptibility and other factors.

The prospective, longitudinal cohort study, published in American Journal of Ophthalmology, classified 4,910 eyes with non-advanced AMD at baseline in AREDS were classified using the AREDS severity scale. Among them, 863 progressed to advanced AMD over 12 years. Baseline AMD severity scale and status of the fellow eye were important predictors; genes provided additional discrimination. The researchers wrote in their paper that, “These results could inform physicians who conduct assessment of presence and degree of macular degeneration, and provide guidance to obtain family history of disease since it relates to subsequent progression to more advanced stages of the disease.”       

Family history of AMD also independently predicted progression after accounting for genetic and other covariates: one family member vs. none (hazard ratio; HR= 1.21); ≥ two family members vs. none (HR= 1.55). The team also suggested that the importance of family history could be explained in part by other shared environmental or lifestyle factors among families or other unknown genetic variants.

A composite risk score calculated using beta estimates of non-genetic and significant genetic factors predicted progression to advanced AMD (HR= 5.57, 90th vs. 10th percentile), providing superior fit vs. other models with only ocular or non-genetic variables.

“The composite risk score including genetic factors could be useful for clinical management to identify individuals who are more likely to progress to advanced stages of AMD, who could then be advised to have more frequent follow-up appointments,” they concluded.

An online risk calculator is being developed to implement these methods. The research team hopes that this free resource will enable the user to obtain an AMD risk score both with and without genetic information, with additional discrimination if genetic variants are included.