KERALINK

A Phase II Clinical Trial to establish Efficacy and Safety of cross-linking in children with Keratoconus

The National Institute of Health Research (NIHR) Efficacy and Mechanism Evaluation (EME) Programme is funding research on keratoconus patients to establish the safety and efficacy of crosslinking procedure in children aged 10 - 16 years. Keratoconus is characterised by thinning and distortion of the cornea that results in visual loss from complex refractive error and corneal opacification. The prevalence in Europe is rising with an estimated 50,000 affected individuals in the UK. Keratoconus is often more advanced if it is first diagnosed in childhood, rather than in adults, with faster subsequent disease progression.

Current treatments involve provision of glasses. If spectacle corrected visual acuity is poor, contact lens are provided and visual acuity is reviewed every 6 months. Those patients with advanced disease and poor spectacle and lens corrected visual acuity are offered corneal transplantation. The proposed cross linking procedure is conceived to increase the stiffness of the cornea and stop progression of keratoconus.

This phase II multi-centre; observer masked, randomised controlled trial compared cross-linking treatment with standard care to investigate efficacy and safety of epithelium-off cross-linking in the paediatric age group. 60 patients were enrolled and the final 18 month follow up visit took place in Q2 2020.  This data was published in Ophthalmology in April 2021.

Longer term follow up of this patient population is of wide interest and so additional funding has been secured from the NIHR to continue the follow up of the KERALINK patients to 48 months post randomisation.

ISRCTN: 17303768

Publications

• Daniel FP Larkin, Kashfia Chowdhury, Caroline J Doré, Catey Bunce, Jennifer M Burr, Emilia Caverly, Lisa French, Dimitra Kopsini, Anne Klepacz, Mathew Raynor, Matthew Edwards & Stephen J Tuft | Epithelium-off corneal cross-linking surgery compared with standard care in 10- to 16-year-olds with progressive keratoconus: the KERALINK RCT | Efficacy and Mechanism Evaluation Volume: 8, Issue: 15, Published in October 2021, https://doi.org/10.3310/eme08150

• Daniel F P Larkin, Kashfia Chowdhury, Jennifer M Burr, Mathew Raynor, Matthew Edwards, Stephen J Tuft, Catey Bunce, Emilia Caverly, Caroline Doré | EFFECT OF CORNEAL CROSS-LINKING vs STANDARD CARE ON KERATOCONUS PROGRESSION IN YOUNG PATIENTS: THE KERALINK RANDOMIZED CONTROLLED TRIAL | PMID: 33892046 | DOI: 10.1016/j.ophtha.2021.04.019

• Larkin F, Chowdhury K, Burr JE, Bunce C, Doré CJ. The KERALINK trial of corneal cross-linking for progressive keratoconus in children. Methodology and baseline patient characteristics. Annual meeting of the Association-for Research-in-Vision-and-Ophthalmology (ARVO) Investigative Ophthalmology and Visual Science 1 June 2020;61(7)

• Chowdhury K, Doré CJ, Bunce C, Larkin DFP. Corneal cross-linking versus standard care in children with keratoconus – a randomised, multicentre, observer-masked trial if efficacy and safety (KERALINK): a statistical analysis plan. Trials 2020;21:523.

• Chowdhury K, Doré CJ, Burr JM, Bunce C, Raynor M, Edwards M, Larkin DFP. A randomised, controlled, observer-masked trial of corneal cross-linking for progressive keratoconus in children: the KERALINK protocol. BMJ Open 2019;9:e028761.