{Reference Type}: Journal Article {Title}: Case for Epithelium-Off Corneal Cross-linking. {Author}: Dupps WJ; {Journal}: Cornea {Volume}: 41 {Issue}: 10 {Year}: Oct 2022 1 {Factor}: 3.152 {DOI}: 10.1097/ICO.0000000000003044 {Abstract}: UNASSIGNED: The question of whether the epithelium should be removed in corneal cross-linking (CXL) in the treatment of keratoconus and other corneal ectatic disorders remains controversial. The motivation for epithelium-on CXL methods, which are not yet FDA approved and vary greatly in methodology, is to reduce the risk of vision-threatening complications related to debridement. However, as discussed in this counterpoint piece, most high-level evidence suggests that removal of the epithelium facilitates greater crosslinking effectiveness as measured by primary clinical outcome metrics such as topographic flattening and stabilization of disease. Furthermore, quality evidence is still lacking for a significant reduction in rates of infectious keratitis or loss of vision that can be attributed to debridement-related complications. In the absence of comparative effectiveness trials or long-term follow-up studies that show otherwise, the FDA-approved epi-off protocol is still the standard-bearer for safe and effective stabilization of corneal ectatic disease.