Keratoconus: is it a Non-inflammatory Disease?

Keratoconus has been recognized and investigated for more than 150 years (1). Historically, ophthalmologists have described keratoconus as a bilateral, progressive, non-inflammatory disorder of the cornea that is associated with corneal steepening and thinning (1,2). The Global Panel on Keratoconus and Ectatic Diseases recently stated that ‘abnormal posterior ectasia, abnormal corneal thickness distribution and clinical noninflammatory corneal thinning are mandatory findings to diagnose keratoconus (3).’ Nevertheless, it is well established that keratoconus is characterized by a marked degradation of the corneal extracellular matrix involving inflammatory features such as increased levels of matrix metallopeptidase 9 (MMP-9), interleukin 6 (IL6), and tumor necrosis factor alpha (TNF-αa), as well as increased oxidative stress (4,5). Moreover, patients with keratoconus have increased levels of inflammatory mediators in their tears, as shown in numerous studies (4-7). The role of inflammation induced by eye rubbing, wearing contact lenses, and ultraviolet irradiation, is another aspect of the inflammatory nature of keratoconus (4). Eye rubbing is a proven risk factor for the development and progression of keratoconus, and it involves several pathways, including the stimulation of inflammation (8-9). The complex interactions between genetic predisposition and environmental trigger factors, (such as eye rubbing and wearing contact lenses) in the development of keratoconus probably represents the key to understanding the role of inflammation in the pathophysiology of keratoconus (10).