Corneal Melting after Crosslinking: A Systematic Literature Review

Abstract

The crosslinking (CXL) has established itself as a fundamental treatment for stabilizing keratoconus; however, serious complications such as corneal melting represent significant challenges to its safety. Therefore, this systematic review aimed to elucidate the occurrence of post-CXL corneal melting and relate it to relevant technical and clinical parameters. To this end, this research followed the PRISMA guidelines and was conducted between January and March 2025, searching the PubMed, Scopus, Web of Science, SciELO, BVS, and Google Scholar databases. Fifteen studies were selected after rigorous screening based on predefined inclusion and exclusion criteria. The extracted data included CXL protocols, previous pachymetry values, time of melting occurrence, and clinical management. After analyzing this study, it was revealed that corneas with pachymetry below 400 µm presented a significantly increased risk of melting, particularly when subjected to accelerated (FAST) or adapted (sub-400) protocols; furthermore, the Dresden protocol demonstrated greater safety, while technical variants with hypoosmolar riboflavin showed a high potential for complications. Moreover, the time interval for the onset of melting showed a bimodal distribution: most cases occurred in the first few weeks post-procedure, but reports documented late occurrence, with cases appearing between 5 and 12 years after CXL. Therefore, it was identified that additional factors, such as systemic comorbidities (diabetes) and individual inflammatory response, modulated the risk and chronology of the complication. Therefore, it is concluded that post-CXL corneal melting, although rare, has an increased occurrence in thin corneas subjected to modified protocols, requiring prolonged clinical monitoring. Furthermore, careful candidate selection based on preoperative pachymetry and appropriate protocol is fundamental to minimizing this devastating complication, making the development of evidence-based clinical guidelines imperative to optimize the risk-benefit ratio of the procedure.