Study links new gender and genetic factors to Fuchs Endothelial Corneal Dystrophy

Figure. Slit-scanning in vivo confocal microscopy images of the corneal endothelium: A (left) demonstrates a healthy control cornea: Image of a normal corneal endothelium, showing a uniform hexagonal cell pattern with consistent cell density and no visible guttae or abnormalities (white solid arrowhead). B (right) shows FECD: Increased confluency of guttata, illustrating a more extensive presence of these structures. Images courtesy UCL/NIHR Moorfields Biomedical Research Centre.

New research from the UK indicates that genetic and demographic factors, including gender, contribute to Fuchs Endothelial Corneal Dystrophy (FECD). The large-scale study was led by the University College London (UCL) Institute of Ophthalmology and supported by National Institute for Health and Care Research (NIHR) Moorfields Biomedical Research Centre, and was published in JAMA Ophthalmology.

The study included 894 patients with FECD, the largest cohort to date. According to a press release from the NIHR, Moorfields and UCL, patients are more likely to develop FECD if they have an alteration in the TCF4 gene. The severity of FECD is linked to a DNA sequence called CTG18.1, and the number of copies present in a patient’s genetic information.

The authors wrote that patients who were of European and South Asian descent exhibited high incidences of the CTG sequence repeat. These patients were likely to have 50 or more copies of the CTG repeat in their DNA. Further, women were more likely to have FECD, and the gender disparity was larger among patients without the CTG18.1 expansion. The authors said that this indicates gender-specific factors may contribute to development of the disease.

“We are thrilled to share these findings, which represent a significant step forward in our understanding of FECD,” said Alice Davidson, PhD, a Professor of Molecular Genetics at the UCL Institute of Ophthalmology and lead investigator of the study. “By uncovering the critical role of the CTG18.1 repeat expansion in the TCF4 gene, particularly its impact on disease risk and severity in the context of demographic factors, we are paving the way for more personalised approaches to treatment. Our study not only broadens our understanding of the genetic drivers of FECD across diverse populations but also underscores the importance of integrating genetic testing into clinical care.”

FECD is an inherited disorder, which, primarily affects the cornea and is a leading cause of age-related vision loss. In low-income countries, FECD is the most common reason for corneal transplants. This study suggests that further investigation should explore genetic aspects of FECD and how demographic factors may impact the disease pathology and treatment. These findings could support gene therapies targeting CTG18.1 that are currently in development.

Reference

1. Large Scale Study Uncovers Demographic and Sex Factors Behind Genetic Cause of Age-Related Visual Loss. Press release. NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology. Published 10 March, 2025. Accessed 12 March, 2025.