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PURPOSE Identification of potential predictive factors for keratoconus progression after treatment by accelerated Cross-linking (A-CXL) SECONDARY OBJECTIVES: Evaluation of clinical and topographic outcomes for two years following accelerated cross-linking treatment for progressive keratoconus including: best spectacle corrected visual acuity (BSCVA), thinnest pachymetry, maximum keratometry (Kmax), cylinder. STUDY Prospective, interventional, monocentric study. SITE: Metz-Thionville Regional Medical Center, Lorraine University, Mercy Hospital, Metz, France. PATIENTS AND METHODS We included 82 eyes of 60 patients between March 2014 and June 2016 who underwent accelerated corneal cross-linking (A-CXL) with epithelial debridement for progressive keratoconus, with a minimum follow-up of 2 years. A complete clinical evaluation and corneal topography were performed before cross-linking, and subsequently at 6, 12 and 24 months post-procedure. The following parameters were monitored during follow-up: best spectacle corrected visual acuity (BSCVA), minimal pachymetry, maximum keratometry (Kmax), mean anterior and posterior curvatures, maximum posterior curvature, presence of optical aberrations, subdivided into spherical aberration, coma, astigmatism, higher order optical aberrations and residual optical aberrations. After a 2-year follow-up, two groups, defined as "responders" and "non-responders" to treatment, were separated for analysis, and their initial characteristics were compared. RESULTS Data for 82 eyes of 60 patients with progressive keratoconus with a mean age of 24±7 years were studied. Fourteen eyes (17.1%) showed signs of progression after treatment by A-CXL (non-responders), and 68 eyes (82.9%) showed stabilization of the disease (responders). Characteristics of non-responding eyes after A-CXL included a younger mean age (20±5 vs. 25±7 years) (P=0.04) and a lower initial mean BCVA for non-responders of 0.44±0.16 logMAR vs. 0.29±0.19 logMAR (P=0.03). Non-responders also had a higher mean maximal posterior curvature (AKB) of -10.84±1.72D vs. -9.46± 1.12D (P=0.03). They also showed more higher order optical aberrations (3.84±1.72D vs. 2.4±1.02D; P=0.01), including coma (3.85±1.81D vs. 2.1±1.01D; P=0.03) and more residual aberrations than responders (1.05±0.44D vs. 0.45±0.6D; P=0.005). No significant differences were found between responders and non-responders for the other parameters in our study. CONCLUSION Eyes with progressive keratoconus who did not respond to A-CXL treatment were the most aggressive cases in the youngest patients, with highest maximum corneal curvatures and most pronounced optical aberrations. These patients should be informed in advance of the high risk of non-response to A-CXL treatment, and of the potential need for additional treatment in the future.