Everett Kinsey lecture. The elusive causes of keratoconus: a working hypothesis.

Purpose: Keratoconus is a diseasethat has been recognized clinically for many years. However, it is only more recently that a better understanding has been achieved in the area of keratoconus pathogenesis. The purpose of this paper is to summarize the completed research, review ongoing studies, and present a hypothesis for keratoconus pathology.

Methods: We used immunochemistry and molecular techniques to characterize keratoconus corneas.

Results and conclusions: Our hypothesis attempts to incorporate many of the recognized biochemical and molecular abnormalities found in the keratoconus corneas. Our hypothesis states: 1) there is abnormal processing of the free radicals and superoxides within the keratoconus corneas; 2) there is a build-up of destructive aldehydes or peroxynitrites within the corneas; 3) the cells that are damaged irreversibly undergo the process of apoptosis; and 4) the cells that are damaged reversibly undergo wound healing or repair. As part of the wound healing process, various degradative enzymes and wound healing factors are upregulated, which leads to focal areas of corneal thinning and fibrosis. Future studies will be directed to testthis working hypothesis and determine if these theories are valid.