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Leopoldo Spadea, Emanuele Tonti, Enzo Maria Vingolo Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy Abstract: Collagen cross-linking (CXL) is a relatively new conservative approach for progressive corneal ectasia, which is able to strengthen corneal tissue reforming new covalent bonds. Subjective and objective results following this method seem to be promising. In recent years, newer CXL protocols have been developed to perform more effective and less invasive procedures. The increasing diffusion of CXL in the corneal ectatic disease has increased the need to have actual indices regarding the efficacy of the treatment. Evaluation of demarcation line (DL), a transition zone between the cross-linked anterior corneal stroma and the untreated posterior corneal stroma, is considered a measurement of the depth of CXL treatment into the stroma. Some evidence in the literature emphasize that DL could be a measure of effectiveness of the CXL. On the contrary, some authors believe that the “the deeper, the better” principle is rather a simplistic approach for interpreting the clinical importance of the corneal stromal DL. Keywords: corneal cross-linking, demarcation line, keratoconus, ultraviolet A