Pathophysiology of Keratoconus

Keratoconus is an enigma. A lot is known about changes that occur in keratoconus corneas but whether these are the cause, the effect, or a part of a self-perpetuating cycle is unclear. Eye rubbing appears as a consistent etiological factor in many reports. Atopy, allergy, connective tissue disorders, and several syndromes with gene disorders are important associations. Enzymatic degradation of the stromal collagen and ground substance with increased expression of matrix metalloproteinase (MMP)-1 and MMP-9; oxidative stress evidenced by reduced levels of superoxide dismutase, catalase, and glutathione peroxidase; and inflammation with expression of interleukin (IL)-1, IL-4, IL-5, IL-6, and tumor necrosis factor (TNF)-α are all involved in the pathogenesis. Structural and biochemical changes affect all layers of the cornea from epithelium to endothelium. Stromal collagen is primarily affected structurally and biochemically. Redistribution, degradation, and lysis of collagen fibrils occurs, which changes the compactness and resilience of the tissue. Elastin degradation in the pre-Descemet layer has recently been recognized as part of the pathophysiology of keratoconus. Alterations in cell morphology and density, and major changes in the form of thickening and tortuosity of corneal stromal nerves and attrition of the sub-basal nerve plexus are significant features. Biomechanical changes probably result from the changes described earlier and in turn induce further biochemical changes driving progression of keratoconus. Acute hydrops, a common occurrence in advance keratoconus, is immediately preceded by acute rupture of the Descemet membrane (DM) and the pre-Descemet layer together and not just of the DM.