• Written By:
    Cornea/External Disease, Refractive Mgmt/Intervention

    Review of: The Independent Effect of Various Cross-Linking Treatment Modalities on Treatment Effectiveness in Keratoconus

    Godefrooij D, Roohé S, Soeters N, et al. Cornea, January 2020

    This prospective study investigated 1-year outcomes of various corneal crosslinking (CXL) techniques for treating progressive keratoconus.

    Study design

    Investigators included 670 eyes of 461 patients who underwent CXL. Eight combinations of CXL modalities were assessed, including 2 different CXL techniques (transepithelial or epithelium-off), 7 riboflavin formulations and 2 ultraviolet-A protocols (conventional 3 mW/cm2 or accelerated 9 mW/cm2). Patients treated using the Dresden protocol were used as the reference group.

    Primary outcomes were maximum keratometry and mean keratometry 1 year after treatment. Secondary outcomes were uncorrected and corrected distance visual acuity, manifest refractive spherical equivalent, and corneal thickness 1 year after treatment.


    The authors found 4 treatment modalities with a higher likelihood of having increased maximum and mean keratometry values at 1 year after treatment compared with the reference group: transepithelial CXL (TE-CXL; P=0.001), 1 riboflavin formulation (Meran; P = 0.02), and both accelerated protocols (Vibex Rapid; P<0.001 and Collagex; P<0.001).

    Patients who underwent standard CXL with Meran had poorer postoperative CDVA than the reference group (P=0.04). Patients who underwent standard CXL with Innocross-R were the only group with significant changes in MRSE (+1.0 D; P=0.03). The remaining visual outcomes, manifest refractive spherical equivalent and corneal thickness were similar among the treatment modalities. Infections were rare (1.6%); however, re-treatment was required for 33.3% of cases that underwent TE-CXL.


    During follow-up, keratoconus progression was defined as an increase in keratometry of 0.1 D, rather than the conventional definition of 1.0 D. This increases sensitivity while decreasing specificity of the results. There were significant differences in the size of the various groups, which ranged from 13 to 253—the results obtained from relatively smaller groups should be interpreted with caution. Likewise, conclusions regarding accelerated cross-linking are limited as many different accelerated protocols such as pulsed-light CXL or other UVA intensities were not included.

    Clinical significance

    In this study, TE-CXL, Meran riboflavin and accelerated irradiation protocols appeared to be associated with reduced efficacy in controlling keratoconus progression. One-third of cases treated using TE-CXL eventually required retreatment.