Corneal dystrophies and genetics in the International Committee for Classification of Corneal Dystrophies era: a review

Abstract

Many of the corneal dystrophies have now been genetically characterized, and a system was established in 2008 by The International Committee for Classification of Corneal Dystrophies (IC3D) in an attempt to standardize the nomenclature. IC3D provided a classification system whereby all dystrophies can be categorized on the basis of the underlying genetic knowledge. Since that time, further work has established even more phenotypic and allelic heterogeneity than anticipated, particular for Fuchs endothelial corneal dystrophy and posterior polymorphous dystrophy. Using genome-wide association studies, a number of genes are now implicated both in normal corneal quantitative traits, such as central corneal thickness, as well as in disease. There is also a trend towards functional characterization of the genetic variants involved to elucidate the pathophysiology of these entities. This review article will provide an overview of the knowledge to date, with an emphasis on findings since the IC3D classification was published in 2008.

Mutations in Collagen, Type XVII, Alpha 1 (COL17A1) Cause Epithelial Recurrent Erosion Dystrophy (ERED)

“…In general, three phases were apparent in our ERED‐like patients of northern Swedish origin; a first phase with recurrent erosions, pain and photophobia during childhood, a second phase starting in the higher teens or 20s with alleviated symptoms and, finally a third phase after the 40s with disturbed vision and decreased visual acuity on the tested charts. It is likely that other families with a similar phenotype of development of recurrent corneal erosion in the first decade with the subsequent development of subepithelial scaring may also have mutations in this gene [Yee et al., ; Hammar et al., ; Hammar et al., ; Vincent ]. We recommend that COL17A1 should be tested for all superficial CDs of unknown genetic cause [Feder et al., ].…”

Dermochondrocorneal dystrophy (Francois syndrome) in a Mexican patient and literature review

“…This characterization has demonstrated genetic and allelic heterogeneity. For example TGFBI has been found mutated in Thiel–Behnke corneal dystrophy (OMIM 602082), Classic Lattice corneal dystrophy (OMIM 122220), Granular corneal dystrophy type 1 (OMIM 121900), Granular corneal dystrophy type 2 (OMIM 607541), and Reis–Bücklers Granular corneal dystrophy type 3 (OMIM 608470) [Vincent, ]). Most of the CDs do not present systemic manifestations, but there is a few with extraocular abnormalities.…”

Regenerative Cell Therapy for Corneal Endothelium

“…A subset of corneal blindness is the consequence of significant, irreversible HCEC loss. Of these, the two most common causes are trauma, most frequently related to eye surgery [16,17], and genetic disorders such as Fuchs dystrophy [18,19]. Fuchs dystrophy is a late-onset, slowly progressive, bilateral genetic disorder characterized by abnormal corneal endothelial cells, the presence of guttae, and corneal thickening.…”