Standard Corneal Collagen Cross-linking (CXL) versus Accelerated Cross-linking (ACXL)

Keratonconus is a bilateral, non-inflammatory, corneal ectasia that can cause progressive thinning and protrusion of the cornea, requiring changes in spectacle or contact lens prescriptions.  Ultimately, progressive keratoconus can lead to corneal scarring, vision unable to be corrected by spectacles or contact lenses, and possibly requiring a corneal transplant surgery.   Corneal collagen cross-linking (CXL) has been proven to halt the progression of keratoconus.  The initial protocol for CXL treatment was called the Dresden protocol, named after the university where it was first developed. This protocol requires a patient to lie still for just over an hour: a few minutes to remove the epithelium, 30 minutes for the riboflavin soak time, and 30 minutes for the ultraviolet light exposure (3 mW/cm2).  Investigators have looked into reducing the length of the treatment by increasing the intensity of the light exposure (9 or 18 mW/cm2), thereby maintaining the same total energy applied to the cornea (5.4 J/cm2).  Several studies have tried to compare this “accelerated” cross-linking (ACXL) protocol to the standard Dresden protocol.

A recent prospective interventional study performed at the Department of Ophthalmology and Visual Sciences, at Chinese University of Hong Kong, looked at these two cross-linking protocols. The purpose of the study was to compare both clinical and topographic effects between the standard CXL (3 mW/cm2 for 30 minutes) and ACXL (18 mW/cm2 for 5 minutes) protocols in progressive keratoconus. The treatment protocols were designed to provide equivalent energy exposures and use the same formulation of riboflavin to address potential confounding variables in prior comparative studies of CXL and ACXL. Only patients with progressive keratoconus were included in the study, with the diagnosis based on corneal topography, clinical signs, and refractive error measurements.  Patients were followed for 1 year after their cross-linking procedures. 

The results of the study showed that standard CXL and ACXL were both successful in stopping the progression of keratoconus.  Both groups also showed a significant improvement in their visual acuity, both corrected (with spectacles or contact lenses) and uncorrected visual acuities.  Other studies have also showed some similar improvements after cross-linking.  Many think this is due to an improved or more regular shape of the corneal after cross-linking. The patients who had standard CXL showed some corneal flattening compared to baseline measurements.  ACXL did not show a significant flattening compared to the baseline measurements.  There were no problems or side effects of the treatment detected during the study. 

This study and others like it, are important to determine how well an increased strength of light and reduced surgical time impact the outcome of treatment.  Patients and surgeons alike, would be very happy to have a reduced surgical time, as long as the effect of treatment were similar. The results of this study show that both standard CXL and ACXL (18 mW/cm2 for 5 minutes) are effective in stabilising progressive keratoconus at 1 year. 

Study details are available on the Nature website:

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