The KERALINK trial of corneal cross-linking for progressive keratoconus in children. Methodology and baseline patient characteristics

Abstract

Purpose : The Keralink trial tests the hypothesis that corneal cross-linking (CXL) reduces the progression of keratoconus compared to standard care with spectacles or contact lenses in patients under 17 years.

Methods : The trial is a prospective randomized, observer-masked, multicentre trial for progressive keratoconus in patients aged 10-16 years. Treatment arms are: (i) treatment with epithelium-off CXL in one or both eyes according to whether progression was uni- or bilateral, and (ii) standard care with spectacles or contact lenses as necessary for best corrected visual acuity (VA). To differentiate true progression from measurement artefact, eligibility was defined by an increase from baseline in the steepest corneal meridian (K₂) of >1.5D between two examinations separated by 3 or more months using topography. The eye with the more advanced keratoconus was the study eye for the primary analysis. The CXL procedure included epithelium removal and a 5.4J/cm² total energy dose of UV light. Participants are followed 3-monthly for 18 months by corneal topography, VA, refraction, apical corneal pachymetry and quality of life questionnaires. The primary trial outcome measure is between-group difference in K₂ at 18 months adjusted for K₂ at baseline examination. Secondary outcomes are the effect of CXL on (i) keratoconus progression, (ii) time to keratoconus progression, (iii) VA, (iv) refraction and (v) apical corneal thickness. The analysis of the primary outcome will be performed using a linear mixed model fitted to all K₂ values recorded.

Results : Sixty patients with progressive keratoconus in one or both eyes were prospectively recruited at five UK centres from October 2016 to September 2018, 30 randomized to each arm. Median age at randomization was 15 years (interquartile range 14-16). Of the 60 patients randomized, 43 were male, 21 were of Indian/Pakistani/Bangladeshi ethnicity and 16 had allergic eye disease. There were no adverse effects of CXL. Follow-up will complete in March 2020.

Conclusions : This is the first randomised trial to evaluate the efficacy of CXL in keratoconus in children. The trial will provide robust evidence on whether CXL arrests keratoconus progression in a higher or lower proportion of young patients than reported in adults, and whether the effect of treatment is sustained for a shorter or longer post-treatment period than in adults.

This is a 2020 ARVO Annual Meeting abstract.