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Study looking at the effectiveness of collagen crosslinking (CXL) in children is now recruiting.

Posted: Mon 17 Oct 2016 1:08 pm
by Anne Klepacz
While there have been a number of studies demonstrating the effectiveness of CXL in adults and the procedure has been approved by NICE for use in the NHS, much less is known about the effectiveness of CXL in children. Up till now, there has been no ‘randomised’ trial in young patients (a randomised trial compares the results in people receiving CXL with those receiving standard care of spectacles or contact lenses). So news that a multi-centre study has now received funding and is recruiting patients is very welcome.
Although the study is being done in London, Sheffield and Liverpool, young people 16 and under with a confirmed diagnosis of keratoconus can be referred from other hospitals, optometrists and GPs. The chief investigator, Mr Frank Larkin writes -

The Keralink trial has been designed to investigate efficacy and safety of the established technique of CXL in the paediatric age group. This is a trial funded by the National Institute for Health Research, in which patients aged 16 or less with progressive keratoconus in one or both eyes will be randomised to receive either CXL or standard care with spectacles and/or contact lenses. The trial will directly address these questions: (i) what is the efficacy of CXL in the early stage of keratoconus in children? (ii) If effective, what is the duration of CXL benefit, particularly in young patients? (iii) Is there a measurable improvement in quality of life following CXL? Funding for 21 month follow-up is in place in the first instance, although the Keralink team will seek funding for longer follow-up of recruited patients.

The trial will commence recruitment in October 2016 and be conducted in Moorfields Eye Hospital in London, St. Paul’s Eye Unit in Liverpool and the Royal Hallamshire Hospital in Sheffield. The chief investigator is Mr Frank Larkin at Moorfields, assisted by consultant colleagues Mr Stephen Tuft (also Moorfields), Mr Matthew Edwards and Mr Mathew Raynor (Sheffield) and Prof Colin Willoughby (Liverpool). Further information about the trial will be made available to parents and patients, and assistance with travel costs will be available once recruited to the trial. For further information please contact Mr Larkin c/o Judy.Carpenter@moorfields.nhs.uk

Re: Study looking at the effectiveness of collagen crosslinking (CXL) in children is now recruiting.

Posted: Thu 16 Feb 2017 2:39 pm
by Anne Klepacz
Just a reminder that this trial is still recruiting young people

Re: Study looking at the effectiveness of collagen crosslinking (CXL) in children is now recruiting.

Posted: Sat 25 Mar 2017 12:18 pm
by Anne Klepacz
Our guest speaker at the AGM held recently was Mr Frank Larkin. This is a summary of the talk he gave.
Study of the effectiveness of corneal collagen crosslinking (CXL) in young people aged 10-16

Mr Larkin began his talk by outlining the background to this research study (the Keralink trial) which is currently recruiting young patients.
The challenge of KC in young patients is that, in general, KC diagnosed in those early years is more like to progress further and be more severe. Given that KC tends to stabilise naturally after the age of 30 or so, KC diagnosed in children has more time to progress. Mr Larkin quoted a French study which showed that KC in children was often more advanced at the time of diagnosis than KC diagnosed in adults. He also quoted a 1994 study carried out at Moorfields by Mr Stephen Tuft. One of the findings from that study was that the time from diagnosis to corneal transplant was shorter in the patients under 18 when first seen at Moorfields than in those 18 and over. Data from the NHS Blood and Transplant show that 52% of all corneal transplants carried out in the 8-15 age group are for keratoconus.

Before the introduction of CXL, standard care for keratoconus was spectacles, contact lenses when spectacles cannot adequately correct the vision, and corneal transplantation for advanced KC where contact lenses can no longer correct the vision. CXL is designed to halt KC progression and involves removing the epithelium (the top layer of the cornea), administering riboflavin drops for 20 mins followed by UVA light pulsed on/off for 8 minutes. (Timings and protocols vary between different centres offering the procedure). After the procedure, a bandage contact lens is worn for a few days and eye drops are needed to prevent infection.
CXL became available on the NHS at Moorfields in 2012. Since that time, there has been a steady increase of young patients being offered the procedure at Moorfields – 3 in 2012 and around 40 in 2016. The majority have been aged 15 or 16 but the figures include some patients as young as 10. CXL is a safe procedure, but a possible complication is keratitis caused by infection, which can be reversed but leaves a visually significant scar. Patients with allergic disorders (asthma, eczema, hay fever) are more at risk of infection as allergic disease alters the bacteria population on the skin and surface of the eye.
Guidance on the provision of CXL on the NHS issued by NICE in 2013 said that a high quality randomised controlled trial in children was needed. The Keralink trial has been set up to answer the questions - is CXL effective and for how long, and is it safe in children. Current one year post CXL data from Moorfields for stabilisation of KC is c.90% in adults, but much lower in young patients.

Keralink Study

Those eligible for the study are children and young people aged 10 to 16 with progressive KC in one or both eyes (as measured by Pentacam scans at least 3 months apart). Not eligible for the study are youngsters who have corneal scarring, have a corneal apex thickness of less than 400 microns or K max (corneal curvature) of more than 62 dioptres or have other corneal conditions as well as KC. The study also excludes any rigid contact lens wearers who are not able to leave their contact lenses out for 7 days before a topography measurement (i.e. cope with glasses only for 7 days) and Down’s syndrome patients with KC (because KC tends to be different in these patients).

Those taking part in the study are randomly assigned to either the group that will have CXL treatment or to the group receiving ‘standard care’ i.e. spectacles or contact lenses, this second group being the ‘control’ group for the study. The optometrists carrying out the Pentacam scans will not know which group a child is in.

The main outcome measure of the study is the Pentacam scan i.e. measuring any changes in corneal curvature in both groups. Secondary outcome measures are progression of KC, best corrected visual acuity (BCVA), refraction, apical corneal thickness and quality of life (as measured by questionnaires). All patients in the study are followed up every 3 months for 18 months (although the hope is that funding will eventually be available for longer follow up).

Mr Larkin stressed the significance of this study, which is the first randomised trial of CXL in children in the world, and its importance in view of the recent large increase in diagnosis and referrals from community optometrists of children with KC. Challenges for the trial are that parents’ preconceived belief in the effectiveness of CXL could hinder recruitment to the trial (although so far no eligible families have declined to participate in the study) and the possibility that some children in the standard care group might show significant progression of KC during the study. Ethical considerations mean these will be looked at individually to see if further treatment should be offered.

One question this study is not looking at is whether CXL should be performed at the point of diagnosis, without confirmation that KC is progressing. Mr Larkin’s view is that it shouldn’t, as some patients even in this age group have spontaneous stabilisation without any intervention, and, as mentioned above, CXL is not safe in all patients.

The Keralink trial is being funded by the National Institute for Health Research (NIHR) and is happening in three centres – Moorfields, St Paul’s Eye Unit in Liverpool and the Royal Hallamshire Hospital in Sheffield though children for the study need not already be patients of those hospitals. Recruitment to the study will be continuing throughout 2017. More information can be obtained by contacting keralink@moorfields.nhs.uk

Re: Study looking at the effectiveness of collagen crosslinking (CXL) in children is now recruiting.

Posted: Wed 06 Sep 2017 1:15 pm
by Anne Klepacz
A further update - the study continues to recruit young people aged 10-17. Another hospital is joining the study, at Newport in South Wales.