A study looking at a comparison between surgical procedure conceived to increase the stiffness of cornea and standard care (glasses) in children with Keratoconus

ISRCTN ISRCTN17303768
DOI https://doi.org/10.1186/ISRCTN17303768
EudraCT/CTIS number 2016-001460-11
Secondary identifying numbers 32332
Submission date
02/11/2016
Registration date
10/11/2016
Last edited
21/01/2025
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Eye Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English Summary

Background and study aims
Keratoconus is an eye condition in which the normally round dome-shaped clear window of the eye (cornea) becomes thinner and changes shape over time, leading to poor vision. Symptoms of keratoconus generally begin in late teenage years or early twenties but they can start at any age. If it is spotted during childhood, it is often more advanced and worsens more quickly. Patients with a suspected or confirmed diagnosis of keratoconus are usually referred to hospital clinics immediately or when they first go to get glasses. In advanced cases, a transplant surgery to replace the affected cornea is needed. Corneal collagen cross-linking (CXL) is a procedure that involves the removal of the surface layer of the cornea, 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 stopping progression. The aim is to study the efficacy and safety of (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.

Who can participate?
Children aged between 10 and 16 years with mild to moderate keratoconus

What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group continue to receive normal care, which involved being given glasses or contact lenses to correct their vision. Those in the second group undergo the CXL procedure. This involves having the area numbed (local anaesthetic) or being put to sleep (general anaesthetic) for the operation, in which the surface layer of the cornea is removed, vitamin B2 eye drops applied and ultraviolet light shone on the eye. Participants in both groups have their eyes examined at the start of the study and then every three months for 18 months in order to assess progression of their condition.

What are the possible benefits and risks of participating?
It is not known whether there will be any benefits involved with participating. There is a risk that some patients treated with CXL will experience pain in the treated eye 1-2 days after the procedure. There is always a risk when having surgery, most of the time these are very mild (such as feeling nauseous, tired or dizzy from the anaesthetic).

Where is the study run from?
1. Moorfields Eye Hospital (UK)
2. Royal Hallamshire Hospital (UK)
3. Royal Liverpool Hospital (UK)

When is the study starting and how long is it expected to run for?
September 2015 to December 2022 (updated 23/10/2020, previously: February 2019)

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Dr Haripriya Tumuluri
ctu.keralink@ucl.ac.uk

Study website

Contact information

Mrs Lisa French
Public

Comprehensive Clinical Trials Unit
Institute of Clinical Trials and Methodology
University College London
90 High Holborn
London
WC1V 6LJ
United Kingdom

Phone +44 (0)20 3108 9777
Email ctu.keralink@ucl.ac.uk

Study information

Study designRandomised; Interventional; Design type: Treatment, Drug
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Other
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleCorneal cross-linking versus standard care in children with keratoconus, a randomised, multicentre, observer-masked trial of efficacy and safety
Study acronymKERALINK
Study hypothesisThe aim of KERALINK is to establish clear evidence on whether CXL is efficacious in stabilising the progression of keratoconus and safe in children and young patients between the age of 10 and 16 years.
Ethics approval(s)London-Brent Research Ethics Committee, 30/06/2016, ref: 16/LO/0913
ConditionSpecialty: Ophthalmology, Primary sub-specialty: Other; UKCRC code/ Disease: Eye/ Disorders of sclera, cornea, iris and ciliary body
InterventionParticipants are randomised into one of two groups in a 1:1 ratio using computer generated treatment group allocation

Intervention group: Participants receive cross-linking in one or both eyes (according to whether progression is confirmed in one eye or both eyes), under general or local anaesthesia as applicable, followed by standard management. Following removal of corneal epithelium and administration of riboflavin drops, ultraviolet light will be administered according to standardised parameters of 10mW/cm2 for a 5.4J/cm2 total energy dose.

Control group: Participants receive standard management alone, including refraction testing with provision of glasses and/or specialist contact lens fitting. Glasses or contact lenses to be provided for one or both eyes as required for best corrected visual acuity. Those patients who develop advanced disease and poor spectacle- and lens-corrected visual acuity during the course of the trial will be offered corneal transplantation.

Follow up for all participants takes place at every 3 months and involves examination of the study eye using Corneal Topography, Refraction and Corneal Ultrasound techniques.
Intervention typeOther
Primary outcome measureCurrent primary outcome measure as of 23/10/2020:
Keratoconus progression is assessed by measuring K2 by Pentacam at baseline, 18 months, and 48 months

Previous primary outcome measure as of 31/01/2019:
Keratoconus progression is assessed by measuring K2 by Pentacam at baseline and 18 months.

Previous primary outcome measure:
Keratoconus progression is assessed by measuring Kmax by Pentacam at baseline and 18 months.
Secondary outcome measures1. Time to keratoconus progression is measured using Pentacam at baseline, post-treatment, 3, 6, 9, 12, 15 and 18 months
2. Uncorrected and best corrected visual acuity is measured using a Standard Eye Chart at baseline, post-treatment, 3, 6, 9, 12, 15 and 18 months
3. Refraction is measured using a Retinoscope at baseline, post-treatment, 3, 6, 9, 12, 15 and 18 months
4. Apical corneal thickness is measured using ultrasound at baseline, post-treatment, 3, 6, 9, 12, 15 and 18 months
5. Quality of life as assessed by using the CHU9D and CVAQC questionnaires at baseline, 6, 12 and 18 months
Overall study start date01/09/2015
Overall study end date31/12/2022

Eligibility

Participant type(s)Patient
Age groupChild
Lower age limit10 Years
Upper age limit16 Years
SexBoth
Target number of participantsPlanned Sample Size: 60; UK Sample Size: 60
Total final enrolment60
Participant inclusion criteriaCurrent inclusion criteria as of 31/01/2019:
1. Age 10-16 years
2. Keratoconus progression confirmed in one or both eyes by Pentacam corneal topography. Progression will be defined as an increase of at least 1.5 dioptres in K2 or Kmax on Pentacam corneal topography.
3. Provision of informed consent and willingness to complete the patient reported outcome measures
4. Willing to attend for follow up visits

Previous inclusion criteria:
1. Age 10-16 years
2. With keratoconus progression confirmed in one or both eyes by Pentacam cornealtopography. Progression will be defined as an increase of at least 1.5 dioptres in Kmax on corneal topography between two Pentacam examinations at least 3 months apart.
3. Provision of informed consent and willingness to complete the patient reported outcome measures
4. Willing to attend for follow up visits
Participant exclusion criteriaCurrent exclusion criteria as of 31/01/2019:
1. Advanced keratoconus as determined by apex corneal scarring
2. Apex corneal thickness <400 μm
3. Steepest corneal meridian (K2) >62 dioptres and maximum corneal curvature (Kmax) >70 dioptres on Pentacam topography at screening
4. Rigid contact lens wear in both eyes and unable to abstain for 7 days pre-examinations
5. Corneal comorbidity
6. Down’s syndrome
7. Any clinical condition which the investigator considers would make the patient unsuitable for the trial, including pregnancy
8. Participation in other clinical trials which would materially impact on the Keralink study

Previous exclusion criteria:
1. Advanced keratoconus as determined by apex corneal scarring
2. Apex corneal thickness 60 diopres
3. Rigid contact lens wear in both eyes and unable to abstain for 7days pre-examinations
4. Corneal co-morbidity
5. Down's syndrome
6. Any clinical condition which the investigator considers would make the patient unsuitable for the trial, including pregnancy
7. Participation in other clinical trials which would materially impact on the Keralink study
Recruitment start date28/10/2016
Recruitment end date26/09/2018

Locations

Countries of recruitment

  • England
  • United Kingdom
  • Wales

Study participating centres

Moorfields Eye Hospital
City Road
London
EC1V 2PD
United Kingdom
Royal Hallamshire Hospital
8 Beech Hill Road
Sheffield
S10 2SB
United Kingdom
Royal Liverpool Hospital
Prescot Street
Liverpool
Prescot St
United Kingdom
Royal Gwent Hospital
Cardiff Road
Newport
NP20 2UB
United Kingdom
Royal Manchester Eye Hospital
Oxford Road
Manchester
M13 9WL
United Kingdom

Sponsor information

University College London
University/education

Comprehensive Clinical Trials Unit
Gower Street
London
WC1E 6BT
England
United Kingdom

Website http://www.ucl.ac.uk/
ROR logo "ROR" https://ror.org/02jx3x895

Funders

Funder type

Government

National Institute for Health Research
Government organisation / National government
Alternative name(s)
National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Location
United Kingdom

Results and Publications

Intention to publish date31/10/2021
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryOther
Publication and dissemination planPlanned publication in a high-impact peer-reviewed journal
IPD sharing planThe datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Protocol article protocol 12/09/2019 23/10/2020 Yes No
Statistical Analysis Plan Statistical analysis plan 12/06/2020 23/10/2020 No No
Results article 21/04/2021 08/12/2022 Yes No
HRA research summary 28/06/2023 No No
Results article 01/10/2021 21/01/2025 Yes No

Editorial Notes

21/01/2025: Publication reference added.
08/12/2022: Publication reference added.
20/09/2021: Internal review.
23/10/2020: The following changes were made to the trial record:
1. The overall end date was changed from 31/10/2020 to 31/12/2022.
2. The total final enrolment was added
3. Publication reference added.
4. The publication and dissemination plan was added.
5. The trial website was added.
6. The primary outcome measure was changed.
7. The plain English summary was updated to reflect these changes.
31/01/2019: The following changes have been made:
1. Royal Gwent Hospital and Royal Manchester Eye Hospital have been added to the trial participating centres.
2. The public contact has been changed from Dr Haripriya Tumuluri to Mrs Lisa French.
3. The primary outcome measure has been changed.
4. The overall trial end date has been changed from 28/02/2019 to 31/10/2020.
5. The inclusion criteria have been changed.
6. The participant inclusion criteria: Age group has been changed from Adult to Child.
7. The recruitment end date has been changed from 31/03/2017 to 26/09/2018.
8. The intention to publish date has been changed from 28/02/2020 to 31/10/2021.
9. The participant exclusion criteria have been changed.
31/10/2017: Internal review.