KERALINK
Research type
Research Study
Full title
Corneal cross-linking versus standard care in children with keratoconus, a randomised, multicentre, observer-masked trial of efficacy and safety
IRAS ID
186776
Contact name
Vicky McCudden
Contact email
Sponsor organisation
Comprehensive Clinical Trials Unit at UCL
Eudract number
2016-001460-11
Duration of Study in the UK
2 years, 1 months, 31 days
Research summary
Research Summary:
Keratoconus is a long-term eye disorder characterised by the thinning and bulging of the normally round cornea into a cone-like shape that causes progressive distortion of vision. In advanced cases, corneal replacement by a transplant is needed. Corneal collagen cross-linking (CXL) is a procedure that involves the removal of the surface layer of the cornea (epithelium-off CXL), the administration of riboflavin (vitamin B2) eye drops and exposure of the cornea to UV light. CXL is a new treatment that is believed to stop keratoconus from getting worse, by increasing stiffness of the cornea and arresting progression. Keratoconus usually affects both eyes (although often asymmetrically) and in most cases starts in teens. It is often more advanced if diagnosed in childhood, and subsequently progresses faster.
The aim is to study the efficacy and safety of epithelium-off CXL in children with keratoconus, and to compare it to standard care with provision of glasses and/or contact lenses as required for best vision. Sixty eligible children aged 10-16 years with mild to moderate keratoconus will be randomised to participate in the study. The trial will be conducted in three secondary care NHS clinics in England: Moorfields Eye Hospital NHS Foundation Trust, the Royal Liverpool & Broadgreen University Hospitals NHS Trusts and Sheffield Teaching Hospital NHS Foundation Trust. In the intervention arm, the corneal epithelium will be removed, riboflavin eye drops administered, and one or both eyes exposed to UV light. Participants will be followed up at 3-monthly visits for 18 months, and those with unconfirmed progression at the 18 month visit will have an additional 21 month visit to confirm progression. The primary outcome measures of the study are whether cross-linking is efficacious and safe in patients under 17 years.Summary of Results:
Keratoconus is a long-term disorder causing increasing steepening and thinning of the cornea, the clear front wall of the eye. It leads to progressive distortion of vision. In most cases keratoconus starts during the teenage years and stops progressing when people are about 30 years old. It is often more severe if it starts in childhood. It can progress quite quickly to a stage that good vision cannot be achieved by standard care (wearing glasses and contact lenses) and a transplant operation becomes necessary. Recently, a new surgical intervention involving the removal of the surface layer of the cornea (‘epithelium-off’), the administration of eye drops, and the application of ultraviolet light has become available. The procedure can be performed under local anaesthesia in most patients. It is called corneal cross-linking. It is believed to stop keratoconus progression by increasing the stiffness of the cornea, but previous research has been of poor quality.
KERALINK was a high-quality randomised trial to see if the new treatment really works. Young people with confirmed keratoconus progression in one or both eyes were randomly allocated to the new treatment in addition to standard care, or to standard care alone. In total, 60 young people aged 10–16 years participated (30 allocated to the new treatment and 30 allocated to standard care alone).
Participants were followed up for 18 months. The primary outcome was the degree of distortion of the cornea at 18 months. Other outcomes included vision, need for glasses, and contact lenses, quality of life, and safety. We found significantly less distortion in eyes receiving the new treatment. This shows that the new treatment is effective in preventing disease progression. Participants allocated to the new treatment group also had better vision and were less likely to need to wear glasses or contact lenses, and there were no treatment-related complications.While the main KERALINK study was completed with negligible losses to follow-up at 18 months, the KERALINK Long-term study achieved this objective only in part, limited by numbers of participants lost to follow-up. In large part this was due to interference with study visit arrangements by the Covid-19 pandemic, which commenced just prior to the completion of 18-month follow-up for the main study. There was additional loss to follow-up due to the majority of participants, initially recruited in the 14–16-year age group, leaving home for higher education during the later years of follow-up.
There are two general conclusions. First, that the benefit of corneal cross-linking was sustained over 4-year follow-up, with progression found in very few corneal cross-linking-treated study eyes. Second, that progression of keratoconus was found in an increasing proportion of study eyes randomised to Standard Care and followed for this period. In those followed to 48 months, the great majority of study eyes treated by corneal cross-linking remained stable whereas progression was found in 60% of study eyes in the Standard Care group. This benefit is of not just statistical, but also clinical significance as it meets the protocol definition of progression and change in visual ability in an eye.REC name
London - Brent Research Ethics Committee
REC reference
16/LO/0913
Date of REC Opinion
30 Jun 2016
REC opinion
Further Information Favourable Opinion