The cascade hypothesis of keratoconus

Cont Lens Anterior Eye. 2003 Sep;26(3):139-46. doi: 10.1016/S1367-0484(03)00022-5.


Keratoconus, a non-inflammatory thinning of the cornea, is a leading indication for corneal transplantation. For its causation, we propose a "Cascade Hypothesis" stating that keratoconus corneas have abnormal or defective enzymes in the lipid peroxidation and/or nitric oxide pathways leading to oxidative damage. The accumulation of oxidative, cytotoxic by-products causes an alteration of various corneal proteins, triggering a cascade of events, (i.e. apoptosis, altered signaling pathways, increased enzyme activities, fibrosis). This hypothesis is supported by biochemical, immunohistochemical and molecular data presented in this review. Based upon this evidence, one can speculate that keratoconus patients should minimize their exposure to oxidative stress. Protective steps should include wearing ultraviolet (UV) protection (in the contact lenses and/or sunglasses), minimizing the mechanical trauma (eye rubbing, poorly fit contact lenses) and keeping eyes comfortable with artificial tears, non-steroidal anti-inflammatory drugs and/or allergy medications.