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Purpose: To report the 4-year outcomes of transepithelial accelerated corneal collagen crosslinking (TE-ACXL) in the treatment of eyes with progressive keratoconus (KC). Methods: Eyes of patients who underwent TE-ACXL (6mW/cm2 for 15 minutes) for progressive KC and presented 48 months of follow-up were included. Corrected distance visual acuity (CDVA), keratometry measurements (Kmax, maximum keratometry, Kmean, mean keratometry and Astg, corneal astigmatism), thinnest corneal thickness (PachyMin), and topographic, and tomographic indices (specifically the posterior radius of curvature from the 3.0 mm centered on the thinnest point of the cornea (PRC), and the D-index) were analysed preoperatively and every 12 months after TE-ACXL, up to 48 months. Progression after TE-ACXL was considered when eyes presented ≥ 1 criteria: (1) increase of ≥ 1D in Kmax or increase of ≥ 0.75D in Kmean or increase of ≥ 1D in Astg; (2) reduction of ≥ 0.085 mm in PRC; (3) decrease ≥ 5% in PachyMin. Results: 41 eyes from 30 patients were included, with a mean age at crosslinking of 20.90± 4.69 years. There was a significant increase in Kmean (+0.64± 1.04 D, p< 0.001; +0.98 ± 1.49 D, p< 0.001; +1.27± 2.01 D, p< 0.001; +1.13± 2.00 D, p=0.006) and a significant decrease in PRC throughout follow-up (− 0.12± 0.22, p=0.002; − 0.15± 0.24, p< 0.001; − 0.17± 0.43, p=0.021; − 0.16± 0.43, p=0.027). PachyMin decreased significantly at 36 and 48 months (− 8.50± 15.93 μm, p=0.004; − 7.82± 18.37, p=0.033). According to our progression criteria, there was a major progression rate throughout follow-up (57.1%, 61.1%, 58.8%, and 67.9%, respectively). Surgery and follow-up were uneventful in all subjects. Eleven eyes (26.8%) required further procedures, ≥ 36 months after the initial TE-ACXL, due to persistent progressive disease. Conclusion: TE-ACXL proved to be a safe therapeutic option for progressive KC. However, its efficacy is deemed unsatisfactory, as a notable proportion of affected eyes may continue to advance within a 4-year timeframe, necessitating additional procedures to halt the disease's course. [ABSTRACT FROM AUTHOR]