Keratoconus is a degenerative thinning of the ECM of the cornea. The cornea is a specialized ECM-rich protective barrier tissue of the eye made up of collagens, glycoproteins, and proteoglycans, like lumican, keratocan, biglycan and decorin. In keratoconus the corneal ECM deteriorates, becomes thin and protrudes. Patients suffer from high astigmatism, scarring and progressive loss of vision. Keratoconus is managed by contact lens use and UV cross-linking of collagens (CXL) to temporarily strengthen the ECM connective tissue at the early stages. In advanced stages cornea-transplants are required, making keratoconus a leading cause for cornea-transplants worldwide. Although influenced by multiple environmental stressors, keratoconus has a strong genetic basis where multiple genetic variants individually or in combination are hypothesized to be causal.