A Review of Keratoconus Cross-Linking Treatment Methods

Corneal collagen cross-linking (CXL) is a therapeutic intervention that utilizes riboflavin photochemical activation with ultraviolet-A (UV-A) light to induce covalent cross-links within the stromal corneal fibers, effectively increasing corneal biomechanical stability and halting the progressive ectasia. The method was introduced in the late 1990s in Germany at the University of Dresden. The cross-linking method using the Avedro system (Waltham, MA, USA) was approved by the US Food and Drug Administration (FDA) on 18 April 2016, based on three prospective, multicenter, randomized clinical trials for keratoconus and other corneal ectasias. Recent innovations in CXL include a range of new treatment protocols and methods, which have been introduced to further enhance the clinical effectiveness, efficiency, and safety of CXL. These modifications encompass approaches like transepithelial or epithelium-on CXL (TE-CXL or epi-on CXL), accelerated CXL (ACXL), pulsed CXL (PL-CXL), transepithelial iontophoresis-assisted crosslinking (I-CXL), diluted alcohol and iontophoresis-assisted corneal cross-linking (DAI-CXL), slit-lamp CXL, and CXL plus (combined) methods. This review synthesizes findings on currently used modifications of the cross-linking method, the effectiveness, and directions of development of this currently dominant surgical method of treating corneal ectasia. This review concentrates on the long-term follow-up data, based on publications ranging from 1998 up to 2023.