Corneal crosslinking to treat adults and children with keratoconus

Health Technology Wales
Record ID 32018000670
Authors' objectives: HTW researchers searched for and appraised evidence on the clinical and cost effectiveness of CXL in people with progressive keratoconus. Evidence on CXL procedures that involve removing the corneal epithelium (to allow eye drops to penetrate the cornea) during the procedure (known as ‘epithelium-off’ CXL) was considered. This is an updated version of an appraisal. HTW originally issued Guidance on this topic in February 2018.
Authors' results and conclusions: Two systematic reviews of randomised controlled trials provided evidence on outcomes after CXL compared to no treatment. The results suggest keratoconus progression is less likely after CXL than in untreated eyes at 18 or 36 months. The same sources of evidence suggest that 12 months after treatment, CXL-treated eyes have improvements in maximum keratometry (Kmax, a measurement of corneal curvature frequently used as an indicator of disease progression) and visual acuity compared to untreated eyes. These results suggest that in addition to changes in disease progression, CXL may reduce distortion of the cornea and thereby improve vision, although the design of the studies and reliability of the evidence means these conclusions should be interpreted cautiously. Evidence on outcomes beyond 36 months (the maximum follow-up time used in the randomised controlled trials) was assessed using observational studies. These reported rates of progression ranging from 0 to 20% in adults and 0 to 25% in children following CXL treatment, with follow up times ranging from 3 to 10 or more years. The majority of observational studies also reported that mean improvements in Kmax and visual acuity after CXL were sustained in the long term. An economic analysis developed by HTW to consider the cost-effectiveness of CXL in the UK NHS setting found CXL to be more effective but more costly than standard care. Whether CXL can be considered cost-effective in cost per QALY terms was found to be heavily dependent upon the assumption around the duration of treatment effect with CXL. In the base case, where it was assumed that patients would progress as if untreated after 10 years, CXL was not found to be cost-effective at a threshold of £20,000 per QALY. However, threshold analysis showed that CXL became cost-effective at £20,000 per QALY, with a CXL treatment effect duration of 14 years or more.
Authors' recomendations: The evidence supports the routine adoption of corneal cross-linking (CXL) for children and adults with progressive keratoconus. Compared to standard care, CXL slows disease progression and may improve visual acuity. It may also reduce or delay the need for corneal transplantation. Economic modelling suggests that CXL is cost effective on the basis of an assumed sustained clinical benefit for at least 14 years.
Authors' methods: The Evidence Appraisal Report is based on a literature search (strategy available on request) for published clinical and economic evidence on the health technology of interest. It is not a full systematic review but aims to identify the best available evidence on the health technology of interest. Researchers critically evaluate and synthesise this evidence. We include the following clinical evidence in order of priority: systematic reviews; randomised trials; non-randomised trials. We only include evidence for “lower priority” evidence where outcomes are not reported by a “higher priority” source. We also search for economic evaluations or original research that can form the basis of an assessment of costs/cost comparison. We carry out various levels of economic evaluation, according to the evidence that is available to inform this.
Authors' identified further reserach: HTW recommends the acquisition of real-world data to capture long-term outcomes (including patient-reported outcomes measures) in people who have CXL for keratoconus.
Project Status: Completed
Year Published: 2021
English language abstract: An English language summary is available
Publication Type: Rapid Review
Country: Wales, United Kingdom
MeSH Terms
  • Keratoconus
  • Cross-Linking Reagents
  • Keratoconus
  • Corneal cross-linking
  • Adults
  • Children
Organisation Name: Health Technology Wales
Contact Address: Life Sciences Hub Wales 3 Assembly Square Cardiff CF10 4PL
Contact Name: Susan Myles, PhD
Contact Email:
Copyright: Health Technology Wales
This is a bibliographic record of a published health technology assessment from a member of INAHTA or other HTA producer. No evaluation of the quality of this assessment has been made for the HTA database.