HMN 2025: What is the new genetic risk for severe macular degeneration

A new study published in Nature Communications reveals the specific genetic factors linked to the presence of reticular pseudodrusen—deposits that drive vision loss and are found on the retina of up to 60% of people with advanced age-related macular degeneration (AMD).

The research, led by the Center for Eye Research Australia, WEHI and the University of Melbourne, offers a promising new target for treatments aimed at the most severe forms of AMD, including geographic atrophy.

AMD is a leading cause of irreversible blindness in people over 50 worldwide, resulting from the death of light-sensing cells in the macula, the part of the retina needed for central vision.

Globally, more than 196 million people have AMD. In its early stages, it is difficult to predict who is most at risk of vision loss and when treatment should begin. Current therapies can only slow disease progression once significant damage has occurred.

Key genetic findings and implications

The Australian team led a large international study which, for the first time, pinpointed a key difference in genetic changes in the group with reticular pseudodrusen—finding a strong link with genetic variations on Chromosome 10 but no link to other well-known AMD gene changes on Chromosome 1.

Eye scans of people with this genetic variation also revealed a thinner retina, a finding that warrants further investigation.

Study co-lead Professor Robyn Guymer AM, from the Center for Eye Research Australia, said the results highlight that AMD is not a single disease but a group of related conditions potentially requiring tailored treatment approaches.

“Reticular pseudodrusen deposits, visible in eye scans, have been linked to worse visual function and poorer treatment outcomes,” she said.

“Our research has now identified which of the genetic changes appear to be driving this more serious form of AMD. This discovery provides a crucial lead for developing new drugs that target these changes—potentially preventing vision loss before it begins.”

Expert perspectives and future directions

Co-lead Professor Melanie Bahlo AM from WEHI said this was the first genome-wide analysis of the genetic drivers behind reticular pseudodrusen.

“In 2005, researchers first linked changes on Chromosome 1 including the complement factor H (CFH) gene, part of the immune system, to AMD,” she said. “Recently, new treatments targeting these changes have shown modest success in slowing down the disease.

“Our study is the first to suggest that reticular pseudodrusen deposits are driven by pathways associated with Chromosome 10 but not by the well-known AMD-related genes on Chromosome 1.

“This is a significant finding. It demonstrates the need to explore how genetic changes on Chromosome 10 affect retinal structure and to develop therapies that go beyond complement factor to targeting to prevent sight-threatening deposits on the retina.”

Provided by
Centre for Eye Research Australia

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