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Causes of Keratoconus

A family history of keratoconus has been established in some cases. Most researchers believe that multiple, complex factors are required for the development of keratoconus including both genetic and environmental factors.

With the advent of videokeratography to assess family members, however, pedigrees have been analysed. These studies show corneal changes consistent with keratoconus in some family members, which suggest an autosomal dominant pattern of inheritance.

Keratoconus may be associated with wide variety of systemic and ocular conditions.

Systemic associations:

  • Atopy (a genetic predisposition to develop an allergic reaction): Eye rubbing seen in systemic atopy may play a role in the development of keratoconus.
  • Down syndrome (Trisomy 21): In Down syndrome (Trisomy 21), frequency of acute hydrops is higher, perhaps because of eye rubbing and/or these patients are treated infrequently with keratoplasty and their disease is allowed to progress further.
  • Ehlers-Danlos syndrome.
  • Marfan syndrome.

Ocular associations:

  • Retinitis pigmentosa.
  • Retinopathy of prematurity.
  • Fuchs’ corneal endothelial dystrophy.
  • Posterior polymorphous dystrophy.

Contributory factors such as:

  1. Enzyme abnormalities in corneal epithelium: Enzyme abnormalities such as increased expression of lysosomal enzymes (catalase and cathepsin) and decreased levels of inhibitors of proteolytic enzymes (tissue inhibitor matrix metalloproteinases), may play a role in corneal stromal degradation.
  2. Differentially expressed corneal epithelium: Differentially expressed corneal epithelium between keratoconus and myopes (as controls) in both genetic expression and protein expression.
  3. Molecular defect: Molecular defect producing unusual absence of water channel protein aquaporin 5 in keratoconus as compared to normal corneal epithelium.
  4. Gelatinolytic activity: Gelatinolytic activity in stroma has been described, which may be due to decreased function of enzyme inhibitors.
  5. Abnormalities in corneal collagen and its cross-linking: Abnormalities in corneal collagen and its cross-linking may be the cause of keratoconus.
  6. Hard contact lens wear.
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