The pathophysiology of how keratoconus develops and progresses is not well understood. Genetic factors appear to be multifactorial and are considered fundamental to the etiology and progression of keratoconus. However, the underlying molecular and/or genetic abnormalities are unknown.

Keratoconus has been linked with systemic conditions such as atopic disease, genetic conditions such as trisomy 21 and Turner’s syndrome, and various connective tissue disorders, as well as with eye rubbing, rigid contact lens wear and ocular trauma. Keratoconic corneas also have an accumulation of cytotoxic by-products from the nitric oxide and lipid peroxidation pathways, abnormal antioxidant enzymes, and increased levels of mitochondrial DNA damage. These findings suggest that ongoing oxidative stress contribute to keratoconus.