gms | German Medical Science

It is widely believed that genetics, the environment, and the cellular mechanism all play a role in KC [1], [2]. However, the exact contribution of each of the above to the etiology of KC is unknown. It is almost certain that KC is a multifactorial disease and the onset is still a mystery. KC has its onset at puberty and it can progress until the third or fourth decade of life; however, it can arrest at any point [3,50]. While multiple reports have associated KC with other disorders, it is more commonly seen as an isolated condition. The most common disorders associated with KC are Down syndrome and Leber’s congenital amaurosis [3]. Rabinowitz’s 1998 review discussed these studies [4]. In some cases, KC appears to have a familial association. However, in a study at the Cedars-Sinai Medicine Center, authors found that 99% of the 300 KC patients had no association with genetic diseases.

In terms of sex preference of the disease, it seems to affect both male and female. In fact, female or male dominance is unclear based on data reported from various studies. Some studies report a preponderance of men over women and others report the exact opposite [5]. It is known, however, that higher numbers of KC disorders are seen in the South Asian region.

One of the most common associations of KC is eye rubbing [6]. This environmental cause was first introduced by Ridley who discovered the relationship between KC and atopic disease [7]. In Ridley’s study, more that 70% of KC patients vigorously rubbed their eyes. Further support of this theory was provided by subsequent studies. Other environmental factors include poorly fit contact lenses and allergies [8]. The relationship between KC and contact lenses or allergies is still questioned by scientists and further studies are needed. In both cases, however, eye rubbing is a possible confounder.

Cellular dysfunction and biochemical abnormalities are almost certain to play a role in KC onset as well as progression. Various authors have suggested abnormalities in collagen fibers within the cornea and their cross-linking. Others have reported abnormalities in proteoglycans and proteoglycan metabolism of the cornea [9], [10]. One recent discovery is the abnormal processing of superoxide radicals in KC corneas and the involvement of oxidative stress in KC [11]. This is now linked to the quality of tears and the disruption on collagen structure due to the creation of harmful byproducts of cell metabolism.

Overall, there are many potential candidates for the onset and progression of the KC disease. These candidates (genetic, environmental, cellular, or other factors) may be acting alone or in combination, leading to a vision threatening condition.