Meta-analysis Finds Modified CXL Safe, Effective in Thin Corneas

A literature review identified hypotonic riboflavin as the most common CXL protocol modification tailored for thin corneas, though various other methods were used. The modified procedure was found to safely and effectively treat keratoconus patients with corneas thinner than 400µm, though further research will be needed to determine which surgical approaches are safest and most effective for this population.  Photo: Alia Cappellani, OD, and Nate Lighthizer, OD. Click image to enlarge. It is typically recommended that patients who undergo standard corneal collagen crosslinking (CXL) have a stromal thickness of at least 400µm. In recent years, however, modified CXL protocols designed for thinner corneas—some of which show promise in treating patients with thicknesses as low as 200μm—have shown improvements in visual and anatomical results, though the existing evidence regarding their safety and effectiveness is still insufficient, and treatment guidelines are not well-defined. To address this knowledge gap, a study published recently in American Journal of Ophthalmology systematically evaluated the literature on the safety and efficacy of CXL protocols in patients with keratoconus and thin corneas (thinnest point <400μm, with or without epithelium). A total of 29 studies published between 2011 and 2024 were analyzed, comprising data from 470 eyes. Two studies used the conventional (Dresden) CXL protocol without modifications, while the most common modification used in the other studies was hypotonic riboflavin to swell the corneal stroma. Other modifications included dextran as a chromophore carrier in isotonic riboflavin solutions, accelerated UVA exposure (less than 30 minutes), riboflavin-soaked contact lenses prior to UVA application, customized epithelial debridement (preserving a central island above the thinnest region), epi-on CXL, lenticules to enhance stromal thickness and, finally, Iontophoresis for riboflavin penetration.The results demonstrated significant clinical improvements in keratoconus patients with thin corneas following CXL treatment. Specifically, the maximum corneal curvature (Kmax) exhibited an average flattening of -1.40D at the 12-month mark, and corrected distance visual acuity improved by -0.09 logMAR units on average. Regarding safety outcomes, the study reported no major complications associated with the CXL procedure, and mild postoperative adverse events, such as subepithelial haze, resolved within a few months. Moreover, minimal changes were observed in endothelial cell density and corneal thickness post-treatment. In reviewing these findings, the authors contend that “CXL was generally safe and effective for treating progressive keratoconus in patients with corneal thickness under 400µm,” resulting in reduced corneal curvature and refractive error, as well as corresponding improvements in visual function. They noted, “Additional work is required to ascertain which modifications are the safest and most effective, and to determine updated minimum stromal thickness thresholds for each approach.”Click here for the journal source. Mohammadi F, McGuinness MB, Mustafa MZ, et al. Effectiveness and safety of cross-linking in keratoconus patients with corneal thickness >400µm: A systematic review and meta-analysis. Am J Ophthalmol. September 26, 2025. [Epub ahead of print].  This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.