Corneal dystrophies

Abstract

The term corneal dystrophy embraces a heterogenous group of bilateral genetically determined non-inflammatory corneal diseases that are restricted to the cornea. The designation is imprecise but remains in vogue because of its clinical value. Clinically, the corneal dystrophies can be divided into three groups based on the sole or predominant anatomical location of the abnormalities. Some affect primarily the corneal epithelium and its basement membrane or Bowman layer and the superficial corneal stroma (anterior corneal dystrophies), the corneal stroma (stromal corneal dystrophies), or Descemet membrane and the corneal endothelium (posterior corneal dystrophies). Most corneal dystrophies have no systemic manifestations and present with variable shaped corneal opacities in a clear or cloudy cornea and they affect visual acuity to different degrees. Corneal dystrophies may have a simple autosomal dominant, autosomal recessive or X-linked recessive Mendelian mode of inheritance. Different corneal dystrophies are caused by mutations in the CHST6, KRT3, KRT12, PIP5K3, SLC4A11, TACSTD2, TGFBI, and UBIAD1 genes. Knowledge about the responsible genetic mutations responsible for these disorders has led to a better understanding of their basic defect and to molecular tests for their precise diagnosis. Genes for other corneal dystrophies have been mapped to specific chromosomal loci, but have not yet been identified. As clinical manifestations widely vary with the different entities, corneal dystrophies should be suspected when corneal transparency is lost or corneal opacities occur spontaneously, particularly in both corneas, and especially in the presence of a positive family history or in the offspring of consanguineous parents. Main differential diagnoses include various causes of monoclonal gammopathy, lecithin-cholesterol-acyltransferase deficiency, Fabry disease, cystinosis, tyrosine transaminase deficiency, systemic lysosomal storage diseases (mucopolysaccharidoses, lipidoses, mucolipidoses), and several skin diseases (X-linked ichthyosis, keratosis follicularis spinolosa decalvans). The management of the corneal dystrophies varies with the specific disease. Some are treated medically or with methods that excise or ablate the abnormal corneal tissue, such as deep lamellar endothelial keratoplasty (DLEK) and phototherapeutic keratectomy (PTK). Other less debilitating or asymptomatic dystrophies do not warrant treatment. The prognosis varies from minimal effect on the vision to corneal blindness, with marked phenotypic variability.

The zebrafish eye—a paradigm for investigating human ocular genetics

“…6 A number of genes associated with human corneal dystrophies encode proteins which are expressed in the zebrafish cornea including tgfb1, keratin 3, and corneal keratan sulfate proteoglycan. 50 Importantly, some human corneal dystrophy-linked genes show conserved expression in the zebrafish cornea, including the François-Neetens fleck corneal dystrophygene PIP5K3. 51 The human gene Keratocan (KERA) encodes a corneal small leucine-rich proteoglycan which is essential in maintaining corneal transparency.…”

Corneal endothelium: developmental strategies for regeneration

“…This is a significant number considering that the annual number of corneal transplants in the United States is more than 32 000. 61 This disease is characterized by the presence of deposits on and thickening of Descemet's membrane, as well as changes in the shape, and size of the endothelial cells. The cornea progressively and slowly becomes opaque, causing blurred vision.…”

Macular corneal dystrophy and associated corneal thinning

“…1 Corneal thinning is an important clinical feature of MCD. 2 MCD is caused by mutations within the CHST6 gene and is a rare disorder.…”

“…1 CHST6 encodes the enzyme carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 6 that catalyzes the transfer of a sulfate group to the GlcNAc residues of keratan sulfate, and disease-causing mutations result in abnormal deposition of glycosaminoglycans in corneal stroma, keratocytes, Descemet membrane, and the corneal endothelium. 1,3 Keratoconus is a complex disorder characterized by bilateral thinning and ectasia of the cornea. It has a strong genetic component and the prevalence is estimated to be between 29 and 229 per 100 000 depending on the population studied.…”