• This article reviews the genetic classification of corneal dystrophies, with an emphasis on findings since the International Committee for Classification of Corneal Dystrophies (IC3D) classification was published in 2008.

    The author explains that many of the corneal dystrophies have now been genetically characterized. IC3D established a system in 2008 intended to standardize the nomenclature. In this system, all dystrophies can be categorized based on underlying genetic knowledge:

    • A category 1 dystrophy is one that is well-defined, in which the gene has been mapped and identified and the specific mutations in that gene are known.
    • Category 2 is reserved for those dystrophies in which a specific chromosomal locus (or loci) has been mapped but the underlying gene is not yet identified.
    • Category 3 is for well-characterized and well-defined dystrophies for which no linkage/loci have yet been elucidated.
    • Category 4 is for all other dystrophies, including suspected new or previously documented corneal dystrophy.

    Since IC3D was created, further work has established even more phenotypic and allelic heterogeneity than anticipated, particularly for Fuchs’ endothelial corneal dystrophy and posterior polymorphous dystrophy. Genome-wide association studies have implicated a number of genes both in normal corneal quantitative traits, such as central corneal thickness, and in disease.

    The author concludes that the current tools of next-generation sequencing, bioinformatics analysis and genetic variation databases should lead the way to more rapid identification of novel genetic mechanisms, particularly for those dystrophies for which linkage has already been established.