Genetic testing could help predict progression of Fuchs endothelial corneal dystrophy, a common age-related cause of visual loss.

FECD is a common inherited eye condition that primarily affects the cornea, the clear front part of the eye. It is one of the leading causes of vision loss as people age and is the most common reason for corneal transplants in high-income countries. FECD affects the corneal endothelial cells (CECs), which form a layer responsible for controlling fluid balance in the cornea. When these cells are lost more quickly than usual in people with FECD, the cornea becomes swollen and cloudy, leading to blurred vision.

This research builds on the team’s earlier research linking the severity of the disease to the number of copies of a repetitive DNA sequence called CTG18.1. The study examined the role of this key genetic risk factor (CTG18.1) alongside a broader polygenic risk score, which captures the combined effect of many smaller genetic factors. Together, these helped predict disease progression in 589 patients with FECD.

Gene therapies targeting CTG18.1 are in development, offering an alternative to the traditional reliance on cornea transplant surgery treatment pathway overshadowed by a global shortage of donor corneas and rising demand due to an ageing population.

Shane (Siyin) Liu, NIHR Academic Clinical Lecturer

“Fuchs dystrophy is one of the leading reasons for corneal transplantation, yet patients can experience very different disease courses, even when carrying the same major genetic mutation. Our study found that combining this high-impact mutation with thousands of smaller genetic differences across the genome improves prediction of disease progression. In the future, genetic testing may help identify patients at greatest risk of vision-threatening progression earlier, supporting more personalised monitoring and bringing us a step closer to truly personalised medicine in ophthalmology.”