Abstract PURPOSE: To analyze corneal confocal microscopy changes after combined photorefractive keratectomy (PRK) plus the cross linking (CXL) procedure. DESIGN: Prospective interventional case series. METHODS: At the Department of Basic Medical Sciences, Neuroscience, and Sense Organs of the University of Bari, Bari, Italy, 17 eyes of 17 patients with progressive keratoconus underwent confocal microscopy examination before and after 1, 3, 6, 12, 18, and 48 months following PRK plus the CXL procedure. The main outcome measures were mean superficial epithelial cell density; mean basal epithelial cell density; mean anterior, mid and posterior keratocyte density; qualitative analysis of stromal backscatter; sub-basal and stromal nerve density parameters; and mean endothelial cell density. RESULTS: During the 4-year follow-up, the mean superficial epithelial cell density, mean basal epithelial cell density and mean endothelial cell density remained unchanged (P > 0.05). The anterior mid-stromal keratocyte density showed a significant decrease (P