TOPIC: This review evaluates the effectiveness and safety of combining cPRK with CXL versus CXL alone in improving visual outcomes for patients with progressive keratoconus. DESIGN: Systematic Review and Meta-Analysis CLINICAL RELEVANCE: Keratoconus leads to vision loss and affects quality of life. While CXL is the current standard for halting progression, it does not correct the visual impairment. This review explores whether adding cPRK to CXL offers better visual outcomes while maintaining the same safety, potentially refining treatment approaches. METHODS: A systematic search of MEDLINE, PubMed, Cochrane Library and EMBASE was conducted through September 2024, following PRISMA guidelines. The initial study design aimed to include randomized controlled trials (RCTs) as well as comparative non-randomized prospective or retrospective studies evaluating CXL+cPRK versus CXL alone, with a minimum follow-up of six months. However, only non-randomized studies were retrieved. As a result, all included studies were assessed for the risk of bias using the ROBINS-I tool. The primary outcomes were uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA). Secondary outcomes included refraction, corneal structure, and higher-order aberrations (HOA). Meta-analysis was performed using standardized mean differences (SMD) with 95% confidence intervals (CI), and heterogeneity was assessed using a random-effects model where necessary. Sensitivity analysis was conducted using a leave-one-out approach to assess the robustness of the results. This study is registered in the PROSPERO database (CRD42024594757). RESULTS: Eight non-randomized studies involving 731 eyes from 706 patients were analyzed. Compared to CXL alone, the combination of CXL+cPRK significantly improved post-operative UDVA (SMD = -0.39, 95% CI: -0.69 to -0.08, P = 0.01) and CDVA (SMD = -0.57, 95% CI: -0.96 to -0.18, P =0.004), while also reducing refractive cylinder error. Additionally, CXL+cPRK led to reductions in coma, total HOA, coma-like aberrations, mean keratometry (KM), and central corneal thickness (CCT). No significant differences were observed between the groups in endothelial cell count (ECC). The rate of postoperative ectasia progression was comparable between both groups. All included studies exhibited at least one ROBINS-I domain at high risk of bias, particularly related to confounding. The heterogeneity observed in this analysis was primarily attributed to differences in surgical techniques, patient selection criteria, and study designs across the included studies. CONCLUSIONS: Customized PRK combined with CXL provides superior postoperative visual acuity (UDVA, CDVA) and visual quality compared to CXL alone while maintaining the same corneal stability in the management of progressive keratoconus. Only non-randomized studies could be retrieved for the purpose of the study.