Fuchs endothelial corneal dystrophy

Abstract

Fuchs endothelial corneal dystrophy (FECD) is characterized by progressive loss of corneal endothelial cells, thickening of Descement's membrane and deposition of extracellular matrix in the form of guttae. When the number of endothelial cells becomes critically low, the cornea swells and causes loss of vision. The clinical course of FECD usually spans 10-20 years. Corneal transplantation is currently the only modality used to restore vision. Over the last several decades genetic studies have detected several genes, as well as areas of chromosomal loci associated with the disease. Proteomic studies have given rise to several hypotheses regarding the pathogenesis of FECD. This review expands upon the recent findings from proteomic and genetic studies and builds upon recent advances in understanding the causes of this common corneal disorder.

Figure 1

Pathogenesis of FECD. Genetic and environmental factors lead to corneal endothelial cell loss, resulting in corneal edema and blurring of vision. Some characteristic histological findings are endothelial cell morphological changes, thickened Descemet’s membrane, and guttae formation.

Figure 2

Specular microscopy of a patient with FECD. Arrowheads point to the variability observed in corneal endothelial cell size (polymegathism) and shape (pleomorphism). Stars represent guttae.

Figure 3

Ultrastructure of Descemet’s membrane of a normal cornea (A), and late-onset (B) and early-onset (C) FECD. Scale bar: 2 μm. (Reprinted with permission from Gottsch JD, et al.46)

Figure 4

Colocalization of clusterin (red) and TGFβIp (green) in FECD-affected endothelium. Endothelial cell nuclei (blue) cluster around a gutta (A). Schematic representation of guttae formation and gradual accumulation of clusterin (CLU) and TGFβIp or keratoepithelin (KE) in Descemet’s membrane (B).