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Purpose: Keratoconus is a non-inflammatory disease characterized by progressive thinning of the central cornea. There are indications for an autosomal dominant heredity. Our purpose was to find correlations between gene expression and structural changes in extracellular matrix components., Methods: Stromal RNA (keratoconus and comparison) was isolated from corneas, transformed to cRNA and analysed using biochips (Affymetrix). Structural investigations were performed by laser scanning and transmission electron microscopy., Results: In keratoconus corneas there was an upregulation of different extracellular matrix components (collagen XV, metalloproteases) and a down-regulation of collagen IV (alpha1, alpha3) and versican. The morphological changes correlated to genetic obtained data. The orthogonal arrangement of the collagen fibrills (anteriorly and central) was altered in the collagen matrix of keratoconus corneas., Conclusions: The changes point on deregulation of the matrix arrangement. The interest in the cause of the disease is focused on the interfibrillar arrangement, the interaction between collagen and proteoglucanes.