Plain English Summary
Background and study aims
Keratoconus is an eye condition that involves thinning of the cornea and bulging. This irregular corneal shape results in reduced vision. This condition affects both eyes although often affects one eye more than the other. It usually occurs around puberty continuing until middle age. It affects about 1 in 1750 individuals, occurring in all ethnic groups and equally affects men and women. Riboflavin/ultraviolet corneal collagen cross-linkage (CXL) appears to be the first treatment that stabilizes the cornea and stops the progression of keratoconus. The standard treatment involves removing the central corneal skin, applying vitamin B2 drops, which soak into the substance of the cornea, and then shining ultraviolet light onto the cornea. This treatment has been shown to increase the strength of the cornea by cross-linking the molecules within it. Iontophoresis has been used routinely for many decades to allow certain drugs to penetrate the skin and eye without the need for injections and has been shown to be effective in allowing riboflavin to enter the cornea without the need to remove the corneal skin. This may speed up recovery after the operation, and reduce pain and the risk of infection and scarring. The aim of this study is to compare the effectiveness of an epithelium-on (trans-epithelial) technique with the standard epithelium-off procedure.
Who can participate?
Adults with mild to moderate bilateral keratoconus with no corneal scarring, evidence of disease progression in both eyes within the past 1-2 years, and with no other eye disease or previous eye surgery, can participate in this study.
What does the study involve?
Patients will undergo a routine eye examination to find out the extent of keratoconus and then after full consent undergo cross-linking treatment to both eyes, with one eye randomly allocated to the standard epithelium-off treatment and the other eye undergoing trans-epithelial (epithelium-on) treatment. After the surgery patients will be asked to fill out a questionnaire regarding the amount of pain they experienced during the first 5 days after surgery. Patients will be examined at 1 week after the treatment and four more times in the year after the procedures. The second eye will be treated within 3-4 months of the first eye.
What are the possible benefits and risks of participating?
The benefits are that it may halt the progression of keratoconus in up to 90% of cases as well as improve the overall corneal shape in the majority of eyes. Risks are few but removal of the corneal epithelium in the standard epithelium-off technique results in significant post-operative pain and increases the rare risks of post-operative infection and scarring. The epithelium-on technique should reduce pain after the operation and speed up recovery as well as possibly reduce the small risks of infection and scarring. However, it is unknown whether the epithelium-on technique will be as effective in halting keratoconus progression as the epithelium-off technique.
Where is the study run from?
St Thomas Hospital, London, UK.
When is the study starting and how long is it expected to run for?
The study is expected to start in January 2014 and finish by January 2016.
Who is funding the study?
The study has been funded by the Eye Hope Charity (UK).
Who is the main contact?
Dr David P.S. OBrart
david.obrart@gstt.nhs.uk
Trial website
Contact information
Type
Scientific
Primary contact
Dr David O'Brart
ORCID ID
Contact details
Department of Ophthalmology
St Thomas Hospital
London
SE1 7EH
United Kingdom
davidobrart@aol.com
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
IRAS Project ID: 133912
Study information
Scientific title
A randomized, bilateral, controlled, prospective study to investigate the efficacy of trans-epithelial riboflavin/ultraviolet A corneal collagen cross-linking using iontophoresis to halt the progression of keratoconus
Acronym
Study hypothesis
Trans-epithelial riboflavin/ultraviolet A corneal collagen cross-linking using iontophoresis is as efficaceous as the standard epithelium off technique to halt the progression of keratoconus.
Ethics approval
NRES Committee London - City Road & Hampstead, REC ref: 13/LO/1895
Study design
Randomized bilateral prospective study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Keratoconus, post-refractive surgery ectasia
Intervention
Patients will be recruited from the corneal clinics at Guy's and St Thomas' NHS Trust. All patients will have bilateral keratoconus or post-laser refractive surgery iatrogenic keratoconus. Patients will have a history of progression or documented progression of keratoconus over the preceding 2 years. Patients will be fully counselled as to the rationale and experimental nature of the study. Patients will undergo a full pre-operative examination including refraction, corneal topography and tomography (scans of corneal shape), pachymetry (measurements of corneal thickness) and endothelial (cells on the inner layer of the cornea that help maintain its transparency) cell counts. All of these tests are part of the routine work-up for this procedure.
Patients will be randomized to receive trans-epithelial cross-linking to one eye or epithelium-off cross-linking treatments to the other. Patients will be offered treatment of both eyes within 3-4 months. The optometrist performing pre- and post-operative measurements will be observer masked as to which eye received which treatment. Patients will be asked to grade their experiences of pain using a visual analogue score of 0 to 10 every 6 hours for 5 days following surgery. Patients will be examined at 1 day, 1 week, 1, 3, 6 and 12 months.
Intervention type
Drug
Phase
Not Applicable
Drug names
Riboflavin
Primary outcome measures
1. Stability of refractive error (diopters)
2. Topograhic simulated keratometry (diopters) (corneal curvature)
3. Corneal pachymetry (micrometers)
4. Visual acuity (logMar) at 12 months compared to pre-operative values
These parameters will be measured pre-operatively and at 3, 6 and 12 months.
Secondary outcome measures
1. Visual analogue pain scores will be documented for 5 days after surgery. Patients will be asked to grade the pain they are experiencing every 6 hours after surgery from 0 (no pain) to 10 (worse pain they have ever had) for 5 days following surgery.
2. Complications if present will be documented at 1 week and 1, 3, 6 and 12 months after surgery.
Overall trial start date
01/01/2014
Overall trial end date
01/01/2016
Reason abandoned
Eligibility
Participant 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
2. Grade I-III keratoconus (3 mm keratometry less than 55 diopters, cone apex power less than 70 diopters, central pachymetry greater than 400 um)
3. Age over 18 years
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
30
Participant exclusion criteria
1. Advanced keratoconus (3 mm keratometry greater than 55 diopters, cone apex power greater than 70 diopters, central pachymetry less than 400 um)
2. Pregnancy
3. Corneal scarring
4. Co-existant ocular pathology other than keratoconus
5. Age less than 18 years
Recruitment start date
01/01/2014
Recruitment end date
01/01/2016
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Department of Ophthalmology
London
SE1 7EH
United Kingdom
Sponsor information
Organisation
Guy's & St Thomas' Foundation NHS Trust (UK)
Sponsor details
c/o Karen Ignatian
R&D Department
16th Floor
Tower Wing
Great Maze Pond
London
SE1 9RT
United Kingdom
karen.ignatian@gstt.nhs.uk
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Charity
Funder name
Eye Hope Charity (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary