Fuchs Corneal Dystrophy

Fuchs corneal dystrophy (FCD) is a hereditary, progressive disease of the posterior cornea which results in excrescences of Descemet membrane, endothelial cell loss, corneal edema, and, in late stages, bullous keratopathy. Structural changes are noted principally in Descemet membrane and the endothelium, with thickening of Descemet membrane, loss of barrier function, and increased corneal hydration, although secondary effects occur throughout all layers. Multiple chromosomal loci and, more recently, causal genetic mutations have been identified for this complex disorder, including in TCF8, SLC4A11, LOXHD1, and AGBL1. A trinucleotide repeat in TCF4 correlates strongly with disease status and interacts in common pathways with previously identified genes. Dysregulation of pathways involving oxidative stress and apoptosis, epithelial-to-mesenchymal transition, microRNA, mitochondrial genes, and unfolded protein response has been implicated in FCD pathogenesis.