Keratoconus is a cone-like ectasia of the cornea, which affects both eyes, that degenerates, with consequent central or paracentral thinning of the stroma and irregular astigmatism. The diffusion of Keratoconus in general population is quite high. The cause of Keratoconus is unknown, but it seems it is due to enzymatic changes in corneal epithelium. Because it is a degenerative process, at the beginning it is possible to correct myopia or regular astigmatism with glasses, but when the error is higher it is necessary to apply hard contact lenses. In all patient affected by Keratoconus there is a reduction of cross-links in the corneal collagen fibers. Collagen is a protein organized in fiber, which are involved in limiting the tissue deformation and in preventing mechanical brakes. There are different types of Cross-Linking to treat Keratoconus; one of them is Photochemical Cross-linking, which, with Riboflavin as a photo sensitizer, and applying on it UV irradiation at a determined wavelength, induces free radicals reactions and increase cross-links fibers. The goal of Transepithelial treatment is to obtain mechanical X-Linking of collagen fiber networks of the corneal stroma without side effects. The news is represented by the possibility of realizing cross-linking keeping the epithelium unaltered. This natural barrier protects the cornea but it is not an impermeable status: it is an osmotic membrane through which riboflavin can penetrate to the cornea.