The Pathophysiology of Keratoconus

PURPOSE: Keratoconus is a progressive disease characterized by changes in corneal shape, resulting in loss of visual function. There remains a lack of comprehensive understanding regarding its underlying pathophysiology. This review aims to bridge this gap by exploring structural failures and inflammatory processes involved in the etiology and progression of keratoconus. METHODS: A literature review was conducted using PubMed and Google Scholar databases, screening for articles published in English using the keyword combinations of "keratoconus" with "pathophysiology," "pathology," "metabolism," "inflammatory," "oxidative stress," "cytokines," "enzymes," "collagen," and "cornea." Articles published between January 1, 1970, and June 1, 2023, were queried and reviewed, with greater emphasis placed on more recent data. Fifty-six relevant studies were examined to develop a thorough review of the pathophysiological mechanisms at play in keratoconus. RESULTS: Biomechanical structural failures in the cornea seem to be the primary militating factors in keratoconus etiology and progression. These include disruptions in the arrangement in the collagen lamellae, a decrease in collagen levels, a decrease in natural collagen crosslinking, and changes in lysosomal enzyme activity. Immunologic changes have also been identified in keratoconus, challenging the traditional view of the condition as noninflammatory. Elevated levels of proinflammatory cytokines like IL-1b, IL-6, IL-17, and TNF-α have been observed, along with increased apoptosis of keratocytes. Increased oxidative stress leads to the activation of collagenase and gelatinase enzymes. CONCLUSIONS: Keratoconus is a complex condition influenced by both structural defects and inflammatory processes. Understanding these mechanisms can inform clinical management and potentially lead to more effective treatments.