Fuchs endothelial corneal dystrophy: current perspectives on diagnostic pathology and genetics-Bowman Club Lecture

Abstract

Fuchs endothelial corneal dystrophy (FECD) was first described over a century ago. Since then, we have learnt much about its clinical manifestations, surgical and non-surgical treatment, microscopic appearance and pathogenesis. Over the past decade, significant advances have been made with respect to our understanding of FECD genetics. This progress now enables us to appreciate that FECD in fact describes multiple entities with distinct underlying genetic causes. For example, an early-onset and rare form of the disease has been attributed to missense mutations in the COL8A2 gene, whereas the vast majority of late-onset cases can be attributed to a non-coding repeat expansion within the TCF4 gene.FECD is one of the most common indications for corneal transplantation. In recent years, attention has turned to alternative treatment techniques that do not depend on donor tissue supply. The design and development of these non-surgical treatment approaches have benefited from increased knowledge of pathogenesis.This review will cover our current knowledge about the histology and genetics of FECD, and how combining these interdisciplinary approaches might may improve diagnostic accuracy and aid the development of therapeutics for this common and visually disabling disease.

Keywords: Cornea; Dystrophy; Genetics; Pathology.

Figure 1

Case 1, H&E stained section, ×10 objective magnification. In this case of histologically classic FECD, the epithelium is lifted off Bowman’s layer to form bullae (asterisks). The stroma is diffusely oedematous, with loss of its normal basketweave texture and reduction in the interlamellar spaces. Endothelial cells are flattened and only visible for short stretches (arrow). FECD, Fuchs endothelial corneal dystrophy.

Figure 2

Case 1, PAS stained section, ×10 objective magnification. There are epithelial bullae (asterisks). Additionally, the PAS stain highlights protrusions of basement membrane into the regenerated epithelium (black arrows). Descemet membrane is thickened. Buried guttae (white arrows) are covered by further basement membrane material, giving a fairly regular posterior contour. PAS, periodic acid-Schiff.

Figure 3

Case 1, PAS stained section, ×10 objective magnification. In this area, Descemet membrane bears large numbers of exophytic guttae (arrows). PAS, periodic acid-Schiff.

Figure 4

Case 2, PAS stained section, ×20 objective magnification. This is a clinically (not genetically) diagnosed case of FECD, which is histologically non-typical. There is marked thickening of Descemet membrane. Rather shallow, infrequent guttae (arrows) lie on top of a laminated zone. They are covered by a further thick layer with a distinctly different texture. FECD, Fuchs endothelial corneal dystrophy; PAS, periodic acid-Schiff.