A randomized, bilateral, controlled, prospective study to investigate the efficacy of corneal shape customised versus standard whole central cornea riboflavin/ultraviolet A corneal collagen cross-linking
| ISRCTN | ISRCTN52187987 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN52187987 |
| Secondary identifying numbers | Version 1 |
- Submission date
- 14/01/2018
- Registration date
- 03/02/2018
- Last edited
- 25/07/2022
- Recruitment status
- Stopped
- Overall study status
- Stopped
- Condition category
- Eye Diseases
Plain English summary of protocol
Background and study aims
Keratoconus is an eye disease in which the cornea (the transparent dome at the front of the eye) thins and begins to bulge into a cone-like shape (known as ectasia), resulting in reduced and distorted vision. The condition affects both eyes (bilateral), often differently (asymmetrical), and usually starts around puberty and gets worse until the third or fourth decade of life. It affects about 1 in 500-1250 people, occurring in all ethnic groups and equally affects males and females. Riboflavin (vitamin B2)/ultraviolet A (UVA) (370nm) corneal collagen cross-linkage (CXL) is the first treatment which appears to halt the progression of keratoconus and other ectasias of the cornea. It involves removing the central corneal skin (epithelium), which grows back after a few days, applying vitamin B2 drops (Riboflavin), which soak into the substance of the cornea (stroma), and then shining ultraviolet light at 370nm onto the cornea. This has been shown to increase the strength of the cornea by cross-linking the protein molecules within it. In the standard technique ultraviolet (UV) light is shone at the central 9.0 mm of the corneal stroma, regardless of the position on the cornea of the bulging (known as the cone) and therefore the location of the weakened corneal tissue. In most cases this area is in the middle of the lower part of the cornea towards the side of the ear. This means that during the standard procedure both normal and abnormal tissue are irradiated. Interestingly, it has been found that better results tend to occur with more centrally located cones. This is perhaps because with centrally located cones, the conventional central (or axial) treatment is directed towards the site of the disease rather than the entire cornea. The aim of this study is to compare the effectiveness of tomography/topography orientated CXL, where the treatment is directed to the location of the main area of ectasia on the cornea (the cone), with the standard technique where the central 9.0 mm area of the cornea is treated regardless of the cone location. The location of the cone is determined by three-dimensional corneal imaging known as tomography using a simple, quick, painless no-touch device called the Pentacam (Oculus Inc, Arlington, Washington, USA). These measurements are entered into a programmable cross-linking UVA light emission system called the Mosaic™ (Avedro Inc, Waltham, USA). This allows patterned, precise, tomography-guided CXL with the delivery of more UV energy precisely at the location of maximal corneal bulging (ectasia) where the cornea is weakest. It is hoped that this targeted treatment will improve the outcomes of CXL by stopping progression of the condition and flattening the cone, resulting in improved corneal shape and better visual outcomes compared to the standard procedure.
Who can participate?
Patients aged over 18 with mild to moderate bilateral keratoconus
What does the study involve?
Participants undergo a routine eye examination to determine the precise degree of keratoconus and then undergo cross-linking treatment to both eyes, with one eye randomly allocated to the standard central treatment and the other eye undergoing tomography-guided treatment. The second eye is treated within 3-4 months of the first eye. Participants are examined at 1 week and 1, 3, 6, and 12 months after the procedures.
What are the possible benefits and risks of participating?
Corneal collagen cross linking has been shown to stop the progression of keratoconus in up to 95% of cases with up to 6-10 years follow-up as well as improve the overall corneal shape in most eyes. Complications are few, with sight-threatening complications, such as infection and scarring and the need for a corneal transplant, occurring in less than 1% and often eyes gaining in vision, although such improvements may take months/years to become apparent. It is hoped, although not proven, that tomography-guided treatment will result in improved outcomes of CXL not only in terms of stopping progression of the condition but also with improved flattening of the cone, which will result in improved corneal shape and better visual outcomes compared to the standard procedure.
Where is the study run from?
St Thomas’ Hospital (UK)
When is the study starting and how long is it expected to run for?
January 2018 to March 2021
Who is funding the study?
Eyehope charity (UK)
Who is the main contact?
Prof. David P.S. O’Brart
Contact information
Scientific
Guy's and St Thomas' NHS Foundation Trust
London
SE1 7EH
United Kingdom
Study information
| Study design | Randomised controlled bilateral study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | A randomized, bilateral, controlled, prospective study to investigate the efficacy of tomography-orientated versus standard axial riboflavin/ultraviolet A corneal collagen cross-linking |
| Study objectives | The hypothesis is that the visual refractive and tomographic outcomes of tomography-orientated collagen cross-linking (CXL), where treatment is directed to the location of the cone, are superior to the standard technique where the central 8.0-9.0 mm is treated irrespective of the cone location. |
| Ethics approval(s) | Not provided at time of registration |
| Health condition(s) or problem(s) studied | Keratoconus, corneal ectasia |
| Intervention | Patients will undergo a routine eye examination to determine the precise degree of keratoconus and then after full consent as to the risks and benefits of the procedure undergo cross-linking treatment to both eyes with one eye randomized to the standard central treatment and one undergoing tomography-guided treatment (randomisation by shuffled envelope system by nurse not involved in the study kept under lock and key in theatre). Patients will be examined at 1 week and 1, 3, 6, and 12 months after the procedures. |
| Intervention type | Procedure/Surgery |
| Primary outcome measure | Change in: 1. Refractive error (diopters) 2. Topographic simulated keratometry (diopters) (corneal curvature) 3. Maximum keratometry (Kmax) 4. Posterior corneal curvature 5. Pentacam-derived keratoconus indices 6. Belin-Ambrosio enhanced ectasia scores 7. Corneal pachymetry (micrometers) 8. Visual acuity (logMar) Measured at baseline 6, 12 and 18 months |
| Secondary outcome measures | Stability in: 1. Refractive error (diopters) 2. Topographic simulated keratometry (diopters) (corneal curvature) 3. Maximum keratometry (Kmax) 4. Posterior corneal curvature 5. Pentacam-derived keratoconus indices 6. Belin-Ambrosio enhanced ectasia scores 7. Corneal pachymetry (micrometers) 8. Visual acuity (logMar) 9. Endothelial cell counts 10. Sight-threatening complications Measured at baseline 6, 12 and 18 months |
| Overall study start date | 01/01/2018 |
| Completion date | 31/03/2021 |
| Reason abandoned (if study stopped) | The study was terminated early without full recruitment because of restrictions following public health guidance ,the inability to recruit patients, and the limited time the topography guided cross-linking equipment was available to the study team. |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 36 |
| Total final enrolment | 34 |
| Key inclusion criteria | 1. Progressive keratoconus defined by an increase in refractive astigmatism, maximum keratometry, apex power of the cone by more than 1 diopter and/or a decrease in central corneal pachymetry by 10% in the preceding 2 years to 18 months 2. Grade I-III keratoconus (3mm keratometry less than 55 diopters, cone apex power less than 70 diopters, central pachymetry greater than 400um) 3. Age over 18 |
| Key exclusion criteria | 1. Advanced keratoconus (3mm keratometry greater than 55 diopters, cone apex power greater than 70 diopters, central pachymetry less than 400um) 2. Pregnancy 3. Corneal scarring 4. Co-existant ocular pathology other than keratoconus 5. Age less than 18 |
| Date of first enrolment | 01/03/2018 |
| Date of final enrolment | 31/03/2021 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
United Kingdom
Sponsor information
Hospital/treatment centre
Research and Development Department
16th Floor, Guy's Tower
London
SE1 9RT
England
United Kingdom
"ROR" |
https://ror.org/00j161312 |
|---|
Funders
Funder type
Charity
No information available
Results and Publications
| Intention to publish date | 31/12/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer reviewed journal and presentation of the data at national and international ophthalmic meetings. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. David O'Brart. Data will be anonymized and only refractive, keratometric, visual, pachymetry data and endothelial counts will be available. Individual patient data, scans etc will not be available for data protection reasons. Data will only be released to those conducting research with full ethical approval and in agreement with the ethics committee and department of research and development. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | 25/07/2022 | 25/07/2022 | No | No |
Additional files
Editorial Notes
25/07/2022: The basic results of this trial have been uploaded as an additional file.
15/07/2022: The study status has been changed to 'Stopped'. The study terminated early due to the COVID-19 pandemic and an inability to recruit patients because of lockdown measures and limited access to the research equipment required to complete the study. By the time the study closed 18 eyes were randomised into the tomography-orientated group (TG) and 16 eyes were randomised into the standard treatment (ST) group. These eyes have reached 15-month follow-up and data has been presented at national meetings. The intention to publish date was changed from 31/12/2021 to 31/12/2022.
05/06/2020: The following changes were made to the trial record:
1. Due to current public health guidance, recruitment for this study has been paused.
2. The recruitment end date and overall trial end date were changed from 31/03/2020 to 31/03/2021.
3. The intention to publish date was changed from 31/12/2019 to 31/12/2021.
18/10/2018: The recruitment end date was updated from 30/09/2018 to 31/03/2020.
