What Role Do Genetics Play in Age-Related Macular Degeneration?

Steffen Schmitz-Valckenberg, MD, explains the close association between disease progression and uncovered risk alleles.

Data presented last week showed a pair of previously identified genetic high-risk loci for age-related macular degeneration (AMD) are closely associated with the biological mechanisms that drive disease burden in patients with the retina disease.

The findings from Steffen Schmitz-Valckenberg, MD, of the Department of Ophthalmology & Visual Sciences at the John A. Moran Eye Center and Steele Center for Translational Medicine at the University of Utah, showed prevalence of Chr1 and Chr10 were linked to patient risk of late-stage disease and visual acuity loss—both independently and in combination.

In an interview with HCPLive, Schmitz-Valckenberg discussed the brief history of genomic research that has gone into AMD, the leading cause of irreversible vision loss in the US. As he explained it, experts are only 2 decades removed from the “major discovery” of Chr1 and Chr10 as risk alleles linked to AMD.

“But during the last 15 years, there’s still kind of a missing link between the genetics and the manifestation and progression of the disease—between the patient and his genetic fingerprint,” Schmitz-Valckenberg said.

While further research is warranted by the discoveries made by his team, Schmitz-Valckenberg stressed the necessity and value of genomic research into AMD: about 70% of the chronic condition is driven by genetics, he explained, yet the field only plays a “minor role” in shaping modern clinical trial designs and outcomes.

“This is something which I think is difficult to understand, and also may be a major reason why we’re still struggling to identify an effective treatment in AMD beyond the anti-VEGF approaches,” he said. “There is no treatment yet available for the main pathway of AMD.”

The study, “Progression of Age-Related Macular Degeneration Among Individuals Homozygous for Risk Alleles on Chromosome 1 (CFH-CFHR5) or Chromosome 10 (ARMS2/HTRA1) or Both,” was published online in JAMA Ophthalmology.