Scientists Discover Why Some People Lose Vision Faster from Macular Degeneration

A groundbreaking genetic study has identified why some people with age-related macular degeneration (AMD) face faster vision loss than others. Researchers discovered that specific eye deposits called reticular pseudodrusen are controlled by different genes than typical AMD, explaining why current treatments work poorly for this aggressive subtype.

What Makes Some AMD Cases More Dangerous?

The key lies in mysterious ribbon-like deposits that appear in some people's eyes. While normal drusen (fatty deposits) sit beneath the retina's support layer, reticular pseudodrusen cluster above it in distinct patterns. People with these deposits face much higher risk of developing geographic atrophy, where retinal cells die off and create permanent blind spots.

Scientists analyzed DNA from three groups: people with AMD plus reticular pseudodrusen, people with AMD but no pseudodrusen, and healthy controls. The surprising finding? The two AMD groups showed completely different genetic patterns.

Why Current Treatments Fall Short?

The research team discovered that reticular pseudodrusen are driven by genetic variants on chromosome 10, specifically involving genes called ARMS2 and HTRA1. Meanwhile, typical AMD involves chromosome 1 genes that control immune system inflammation. This explains why new FDA-approved drugs targeting the immune system show only modest results.

• Chromosome 1 variants: Control immune inflammation in typical AMD cases
• Chromosome 10 variants: Drive reticular pseudodrusen formation and faster vision loss
• HTRA1-AS1 gene: A key player that affects other genes without making proteins directly

"Our data show that these deposits of reticular pseudodrusen, present in some but not all AMD cases, are driven by pathways associated with chromosome 10 and not by genetic risk in other AMD-related genes such as those on chromosome 1," said Dr. Robyn Guymer from the Centre for Eye Research Australia.

The chromosome 10 variants also caused measurably thinner retinas compared to healthy eyes, suggesting they directly damage retinal structure. This finding came from analyzing thousands of eye scans from the international Reticular Pseudodrusen Consortium.

What This Means for Future Treatments?

The discovery reinforces that AMD isn't one disease but multiple conditions requiring different approaches. Current complement-targeting drugs work by reducing immune system inflammation, but they can't address the chromosome 10 pathway driving reticular pseudodrusen.

"This study could help explain why drugs that target just the complement pathway have shown a minimal effect in slowing geographic atrophy," explained Dr. Anand Swaroop, chief of the Neurobiology Neurodegeneration and Repair Laboratory at the National Eye Institute.

The research, funded by the National Institutes of Health and Australia's National Health and Medical Research Council, involved an international collaboration. The findings were published in Nature Communications and represent years of work analyzing genetic data from AMD patients worldwide.

"This study reinforces that AMD is not one disease," said Dr. Emily Chew, who leads the National Eye Institute's Division of Epidemiology and Clinical Applications. "Our findings highlight that different treatment approaches will be needed for different AMD subtypes."