• National Eye Institute
    Retina/Vitreous

    A collaborative study by researchers from 16 international sites has shed light on the mysterious underlying biology of Fuchs corneal dystrophy with the identification of 3 new causative gene regions.

    After analyzing genomic data from 2,075 Fuchs patients and 3,342 healthy subjects, the team found associations between the disorder and novel variants in the genes KANK4, LAMC1 and ATP1B1. The findings, published in Nature Communications, also confirm the link of a previously suspected fourth locus at the gene TCF4.

    “The identification of these genes paves the way for the development of a test to identify individuals who are at risk of getting Fuchs dystrophy, and also for the development of drugs to slow disease progression or to potentially delay or prevent it from occurring,” said George A. McKie, DVM, PhD, director of the National Eye Institute’s cornea research program, which helped fund the study.

    The authors also discovered that LAMC1 variants confer a significantly elevated risk of Fuchs dystrophy among women, while TCF4 variants confer a greater risk in men, challenging the prior definition of Fuchs as an autosomal dominant disorder.

    Fuchs patients show accelerated corneal endothelium cell death, resulting in progressively worsening edema in the central or stromal layer of the cornea. There are no current therapies other than palliative symptom management. Advanced disease typically necessitates a corneal transplant.

    According to one of the study’s lead authors, Sudha K. Iyengar, PhD, of Case Western Reserve University, together the 4 loci predict the risk of an individual developing Fuchs dystrophy with an accuracy of about 78%.

    “Considering that there is currently no clinical screening tool other than family history, this is a significant advance for development of molecular diagnostic tests,” said Dr. Iyengar.

    Future research from the group will investigate how these genes contribute to the functioning of corneal endothelium cells.