KeratoconusTransPRKCXLNCT02208089
Simultaneous TransPRK and Corneal Collagen Cross-Linking
A study testing Transepithelial Photorefractive Keratectomy (TransPRK) and Corneal Collagen Cross-Linking (CXL) in people with Keratoconus, run by Bruce Allan at 1 site in United Kingdom.
Trial summary
Young patients with keratoconus face two problems: disease progression and corneal shape irregularity leading to poor vision even in spectacles. Corneal collagen cross-linking (CXL) is a new treatment designed to halt disease progression in keratoconus. Read more about this study
- Who is it for?
- Ages 18 to 35 years
- Conditions the study is for
- Keratoconus
- What is being tested?
- Transepithelial Photorefractive Keratectomy (TransPRK) and Corneal Collagen Cross-Linking (CXL)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Aug 2014to Jul 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patients with progressive stage II or III keratoconus
- CDVA < 0.00 logMAR or subjective problems with spectacle corrected visual quality (ghost images or light scatter symptoms)
Who cannot join
- Active ocular surface disease
- Minimum corneal thickness <390µm (leaving 325µm residual stromal thickness after transPTK - in line with minimum thickness recommendations for the study CXL protocol)
- Vulnerable groups (patients whose capacity for giving informed consent to participate in the trial may be impaired)
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Moorfields Eye Hospital NHS Foundation Trust, 162 City Road
London, EC1V 2PD
About this study
Official title: A Prospective Trial of Simultaneous Combined Transepithelial Photorefractive Keratectomy and Corneal Collagen Cross-linking for Keratoconus
Young patients with keratoconus face two problems: disease progression and corneal shape irregularity leading to poor vision even in spectacles.
Corneal collagen cross-linking (CXL) is a new treatment designed to halt disease progression in keratoconus. The aim is to stiffen the cornea thereby preventing further shape deterioration.
Read more
Topography or wavefront guided transepithelial photorefractive keratectomy (transPRK) uses the excimer laser (the laser used to correct sight in 'laser eye surgery') to reduce corneal shape irregularity in early stage keratoconus, reducing dependence on contact lenses.
In transPRK, the corneal skin layer is removed in a well controlled, no touch procedure, preparing the cornea for CXL. Performing both treatments simultaneously (combining both procedures in one operation) may offer several advantages over performing CXL first then waiting for corneal shape to stabilise before performing transPRK. In particular, visual rehabilitation may be faster. This study aims to evaluate visual recovery after simultaneous CXL and transPRK in progressive early stage keratoconus. Visual recovery in these patients will be compared with results for a similar group of patients with early stage keratoconus who have already been treated with CXL alone.
Read the detailed description
Features which distinguish this trial from previous trials of combined photorefractive keratectomy (PRK) and corneal collagen cross-linking (CXL) are: a rapid, pulsed light, CXL protocol; and a treatment programming algorithm for PRK designed to target higher order aberrations only with no compensatory additional laser corneal tissue removal.
Excimer laser treatment will be performed with the Schwind Amaris 750S laser (www.eye-tech-solutions.com). Unique features of this system utilised here include:
- Pre-programmed transepithelial ablation - laser removal of the minimum area of corneal epithelium required for PRK promoting more rapid recovery than conventional methods (20% alcohol application and manual epithelial removal). An 8mm diameter ablation zone will be applied throughout.
- Enhanced algorithms for minimal laser tissue removal - in this trial, the investigators are targeting higher order aberrations only (coma in particular) with the aim of improving spectacle corrected visual acuity without regard to the predicted spherocylindrical outcome. Unlike other current excimer laser platforms, Schwind Amaris treatment programming software allows treatment for irregular astigmatism without additional compensatory laser tissue removal to correct the spherocylindrical change induced by treatment of higher order aberrations. Higher order aberrations can also be treated selectively. The investigators will use an algorithm step that targets only aberrations (up to 6th order Zernike polynomials) with a value greater than 2 standard deviations from the population mean in normative data. These treatment planning steps allow the laser to create a large diameter treatment with minimal treatment depth.
Laser epithelial removal alone (transPTK at depth 55µm) removes a maximum 65µm of tissue in the corneal periphery. For patients with 390µm at the thinnest point, transPTK will therefore leave above 325µm residual stromal thickness prior to CXL. This is in line with recommendations for minimum stromal thickness after epithelial removal in the CXL protocol used here. Limited stromal reshaping is achieved in this simple embodiment of transPRK for keratoconus by taking advantage of the masking effect of the corneal epithelium, which tends to be thinnest over the cone apex. Where the thinnest point is greater than 390µm, further reductions in corneal shape irregularity can be produced by adding either wavefront or topography guided additional stromal ablation using custom programming on the Schwind Amaris laser. Ocular wavefront (aberrometry) guided smoothing will be used for patients with a 5.5mm or larger pupil at scanning and a consistent scan sequence (3 scans within 0.5 dioptre (D) spherical equivalent refraction). Corneal wavefront (topography) guided smoothing will be used for patients with ocular wavefront scans which do not meet these criteria. In all cases, a minimum corneal stromal thickness prior to CXL of 325µm will be preserved.
Immediately after PRK, corneal collagen cross-linking will be performed using the following protocol
Riboflavin soak: 10 minutes total soak time; application of 0.1% riboflavin preparation (VibeX Rapid - www.avedro.com) each 2 minutes with gentle balanced salt solution irrigation to remove excess riboflavin prior to UV light exposure.
UV light exposure: Total treatment time 8 minutes (370nm wavelength; 30mW/cm2 irradiance; 4 minutes total UV exposure time, pulsed 1.5 seconds on 1.5 seconds off; Avedro KXL I light source)
Mitomycin C will not be used. A bandage contact lens will be applied at the end of treatment and a standard post photorefractive keratectomy topical and systemic drug treatment regimen will be used in every case with initial clinical review 1 week after surgery.
- Conditions
- Keratoconus
- Being tested
- Transepithelial Photorefractive Keratectomy (TransPRK), Corneal Collagen Cross-Linking (CXL)
- Keywords
- Keratoconus, Corneal collagen cross-linking, Photorefractive keratectomy
- Medical subject headings
- Keratoconus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transepithelial Photorefractive Keratectomy (TransPRK)Procedure or surgery
Also called Corneal surface excimer laser treatment
Aberrometry or topography guided transepithelial photorefractive keratectomy (TransPRK) using the Schwind Amaris 750s excimer laser (www.eye-tech-solutions.com), an 8mm treatment diameter, and a tissue saving algorithm targeting selected higher order aberrations only. TransPRK will be followed immediately by corneal collagen cross-linking (CXL).
Corneal Collagen Cross-Linking (CXL)Procedure or surgery
Also called Rapid corneal collagen cross-linking
Riboflavin soak: 10 minutes total soak time; application of 0.1% riboflavin preparation (VibeX Rapid - www.avedro.com) each 2 minutes with gentle balanced salt solution irrigation to remove excess riboflavin prior to UV light exposure.
UV light exposure: Total treatment time 8 minutes (370nm wavelength; 30mW/cm2 irradiance; 4 minutes total UV exposure time, pulsed 1.5 seconds on 1.5 seconds off; Avedro KXL I light source)
| Study group | Role | What they receive |
|---|---|---|
| TransPRKCXL | Experimental | Simultaneous combined transepithelial photorefractive keratectomy (TransPRK) and corneal collagen cross-linking (CXL) Receives: Procedure: Transepithelial Photorefractive Keratectomy (TransPRK); Procedure: Corneal Collagen Cross-Linking (CXL) |
| CXL only | Active comparator | Corneal collagen cross-linking (CXL) using the same protocol without transepithelial photorefractive keratectomy Receives: Procedure: Corneal Collagen Cross-Linking (CXL) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in LogMAR Corrected Distance Visual Acuity (CDVA)
Change in spectacle corrected logarithm minimum angle of resolution (LogMAR) distance visual acuity recorded in a 4m testing lane in photopic lighting conditions between baseline measurement and final review at 24 months (note that negative change = better vision; 0.1 logMAR units = 1 line on the test chart)
Measured: Preoperative vs 24 months
Secondary outcomes (4)
Clinically Significant Visual Gain
Number of participants with gain of ≥2 lines (≥0.20 logMAR units) corrected distance visual acuity (CDVA) on a standard 5 letter per line EDTRS visual acuity testing chart
Measured: Preoperative vs 24 months postoperative
Clinically Significant Visual Loss
Number of participants with loss of ≥2 lines (≥0.20 LogMAR units) corrected distance visual acuity (CDVA)
Measured: preoperative vs 24 months postoperative
Change in Kmax - Maximum Local Anterior Corneal Surface Curvature on Tomography Map
Pentacam (www.oculus.de) measure: Maximum local curvature (Kmax). Reduction in dioptric value = corneal flattening
Measured: Preoperative vs 24 months postoperative
Progression Rate
The number of participants with possible keratoconus disease progression after treatment defined by a ≥1.5D increase in Kmax, anterior and posterior K2 (maximum local corneal curvature, maximum anterior and posterior meridional corneal curvature) measured using a Pentacam HD corneal tomographer (www.oculus.de).
Measured: 6 months postoperative - 24 months postoperative
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2014 (estimated)
- Study startAug 2014
- Primary completionJul 2016
- Study completionJul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for KeratoconusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Interventional case series with matched historical controls
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bruce Allan
- Sponsor type
- University, hospital or other
- Collaborators
- Moorfields Eye Hospital NHS Foundation Trust
- Responsible party
- Sponsor-investigator, Bruce Allan, Moorfields Eye Hospital NHS Foundation Trust
- Investigators
- Bruce D Allan, MD FRCOphth, Principal investigator, Moorfields Eye Hospital NHS Foundation TrustDan M Gore, FRCOphth, Principal investigator, Moorfields Eye Hospital NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02208089
- Sponsor's protocol ID
- ALLB1018
- Acronym
- TransPRKCXL
- Status last verified
- Sep 2018
- First submitted
- 25 Jul 2014
- Last updated
- 8 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Gore DM, Shortt AJ, Allan BD. New clinical pathways for keratoconus. Eye (Lond). 2013 Mar;27(3):329-39. doi: 10.1038/eye.2012.257. Epub 2012 Dec 21.
PubMed 23258309Kanellopoulos AJ, Asimellis G. Keratoconus management: long-term stability of topography-guided normalization combined with high-fluence CXL stabilization (the Athens Protocol). J Refract Surg. 2014 Feb;30(2):88-93. doi: 10.3928/1081597X-20140120-03.
PubMed 24763473
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Trial of Simultaneous Combined Transepithelial Photorefractive Keratectomy and Corneal Collagen Cross-linking for Keratoconus
- ClinicalTrials.gov ID
- NCT02208089
- Acronym / sponsor ID
- TransPRKCXL / ALLB1018
- Conditions
- Keratoconus
- Keywords
- Keratoconus, Corneal collagen cross-linking, Photorefractive keratectomy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Bruce AllanUniversity, hospital or other
- Collaborators
- Moorfields Eye Hospital NHS Foundation Trust
- Study start
- Aug 2014
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 4 Aug 2014 (estimated)
- Results
- Posted 8 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Young patients with keratoconus face two problems: disease progression and corneal shape irregularity leading to poor vision even in spectacles.
Corneal collagen cross-linking (CXL) is a new treatment designed to halt disease progression in keratoconus. The aim is to stiffen the cornea thereby preventing further shape deterioration.
Topography or wavefront guided transepithelial photorefractive keratectomy (transPRK) uses the excimer laser (the laser used to correct sight in 'laser eye surgery') to reduce corneal shape irregularity in early stage keratoconus, reducing dependence on contact lenses.
In transPRK, the corneal skin layer is removed in a well controlled, no touch procedure, preparing the cornea for CXL. Performing both treatments simultaneously (combining both procedures in one operation) may offer several advantages over performing CXL first then waiting for corneal shape to stabilise before performing transPRK. In particular, visual rehabilitation may be faster. This study aims to evaluate visual recovery after simultaneous CXL and transPRK in progressive early stage keratoconus. Visual recovery in these patients will be compared with results for a similar group of patients with early stage keratoconus who have already been treated with CXL alone.
Detailed description
Features which distinguish this trial from previous trials of combined photorefractive keratectomy (PRK) and corneal collagen cross-linking (CXL) are: a rapid, pulsed light, CXL protocol; and a treatment programming algorithm for PRK designed to target higher order aberrations only with no compensatory additional laser corneal tissue removal.
Excimer laser treatment will be performed with the Schwind Amaris 750S laser (www.eye-tech-solutions.com). Unique features of this system utilised here include:
- Pre-programmed transepithelial ablation - laser removal of the minimum area of corneal epithelium required for PRK promoting more rapid recovery than conventional methods (20% alcohol application and manual epithelial removal). An 8mm diameter ablation zone will be applied throughout.
- Enhanced algorithms for minimal laser tissue removal - in this trial, the investigators are targeting higher order aberrations only (coma in particular) with the aim of improving spectacle corrected visual acuity without regard to the predicted spherocylindrical outcome. Unlike other current excimer laser platforms, Schwind Amaris treatment programming software allows treatment for irregular astigmatism without additional compensatory laser tissue removal to correct the spherocylindrical change induced by treatment of higher order aberrations. Higher order aberrations can also be treated selectively. The investigators will use an algorithm step that targets only aberrations (up to 6th order Zernike polynomials) with a value greater than 2 standard deviations from the population mean in normative data. These treatment planning steps allow the laser to create a large diameter treatment with minimal treatment depth.
Laser epithelial removal alone (transPTK at depth 55µm) removes a maximum 65µm of tissue in the corneal periphery. For patients with 390µm at the thinnest point, transPTK will therefore leave above 325µm residual stromal thickness prior to CXL. This is in line with recommendations for minimum stromal thickness after epithelial removal in the CXL protocol used here. Limited stromal reshaping is achieved in this simple embodiment of transPRK for keratoconus by taking advantage of the masking effect of the corneal epithelium, which tends to be thinnest over the cone apex. Where the thinnest point is greater than 390µm, further reductions in corneal shape irregularity can be produced by adding either wavefront or topography guided additional stromal ablation using custom programming on the Schwind Amaris laser. Ocular wavefront (aberrometry) guided smoothing will be used for patients with a 5.5mm or larger pupil at scanning and a consistent scan sequence (3 scans within 0.5 dioptre (D) spherical equivalent refraction). Corneal wavefront (topography) guided smoothing will be used for patients with ocular wavefront scans which do not meet these criteria. In all cases, a minimum corneal stromal thickness prior to CXL of 325µm will be preserved.
Immediately after PRK, corneal collagen cross-linking will be performed using the following protocol
Riboflavin soak: 10 minutes total soak time; application of 0.1% riboflavin preparation (VibeX Rapid - www.avedro.com) each 2 minutes with gentle balanced salt solution irrigation to remove excess riboflavin prior to UV light exposure.
UV light exposure: Total treatment time 8 minutes (370nm wavelength; 30mW/cm2 irradiance; 4 minutes total UV exposure time, pulsed 1.5 seconds on 1.5 seconds off; Avedro KXL I light source)
Mitomycin C will not be used. A bandage contact lens will be applied at the end of treatment and a standard post photorefractive keratectomy topical and systemic drug treatment regimen will be used in every case with initial clinical review 1 week after surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Interventional case series with matched historical controls
| Arm | Type | Receives |
|---|---|---|
| TransPRKCXL | Experimental | Procedure: Transepithelial Photorefractive Keratectomy (TransPRK), Procedure: Corneal Collagen Cross-Linking (CXL)Simultaneous combined transepithelial photorefractive keratectomy (TransPRK) and corneal collagen cross-linking (CXL) |
| CXL only | Active comparator | Procedure: Corneal Collagen Cross-Linking (CXL)Corneal collagen cross-linking (CXL) using the same protocol without transepithelial photorefractive keratectomy |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Patients with progressive stage II or III keratoconus
- CDVA < 0.00 logMAR or subjective problems with spectacle corrected visual quality (ghost images or light scatter symptoms)
Key exclusion criteria (3 listed)
- Active ocular surface disease
- Minimum corneal thickness <390µm (leaving 325µm residual stromal thickness after transPTK - in line with minimum thickness recommendations for the study CXL protocol)
- Vulnerable groups (patients whose capacity for giving informed consent to participate in the trial may be impaired)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transepithelial Photorefractive Keratectomy (TransPRK)Also: Corneal surface excimer laser treatmentAberrometry or topography guided transepithelial photorefractive keratectomy (TransPRK) using the Schwind Amaris 750s excimer laser (www.eye-tech-solutions.com), an 8mm treatment diameter, and a tissue saving algorithm targeting selected higher order aberrations only. TransPRK will be followed immediately by corneal collagen cross-linking (CXL). | Procedure or surgery | TransPRKCXL |
| Corneal Collagen Cross-Linking (CXL)Also: Rapid corneal collagen cross-linkingRiboflavin soak: 10 minutes total soak time; application of 0.1% riboflavin preparation (VibeX Rapid - www.avedro.com) each 2 minutes with gentle balanced salt solution irrigation to remove excess riboflavin prior to UV light exposure. UV light exposure: Total treatment time 8 minutes (370nm wavelength; 30mW/cm2 irradiance; 4 minutes total UV exposure time, pulsed 1.5 seconds on 1.5 seconds off; Avedro KXL I light source) | Procedure or surgery | CXL only, TransPRKCXL |
Primary outcome
Change in LogMAR Corrected Distance Visual Acuity (CDVA)
Time frame: Preoperative vs 24 months
Change in spectacle corrected logarithm minimum angle of resolution (LogMAR) distance visual acuity recorded in a 4m testing lane in photopic lighting conditions between baseline measurement and final review at 24 months (note that negative change = better vision; 0.1 logMAR units = 1 line on the test chart)
4 secondary outcomes
Clinically Significant Visual Gain
Time frame: Preoperative vs 24 months postoperative
Clinically Significant Visual Loss
Time frame: preoperative vs 24 months postoperative
Change in Kmax - Maximum Local Anterior Corneal Surface Curvature on Tomography Map
Time frame: Preoperative vs 24 months postoperative
Progression Rate
Time frame: 6 months postoperative - 24 months postoperative
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23258309Gore DM, Shortt AJ, Allan BD. New clinical pathways for keratoconus. Eye (Lond). 2013 Mar;27(3):329-39. doi: 10.1038/eye.2012.257. Epub 2012 Dec 21.
- Background: PubMed 24763473Kanellopoulos AJ, Asimellis G. Keratoconus management: long-term stability of topography-guided normalization combined with high-fluence CXL stabilization (the Athens Protocol). J Refract Surg. 2014 Feb;30(2):88-93. doi: 10.3928/1081597X-20140120-03.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruce D Allan, MD FRCOphth principal investigator
Moorfields Eye Hospital NHS Foundation Trust
Dan M Gore, FRCOphth principal investigator
Moorfields Eye Hospital NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transepithelial Photorefractive Keratectomy (TransPRK) and Corneal Collagen Cross-Linking (CXL) in people with Keratoconus, run by Bruce Allan at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in LogMAR Corrected Distance Visual Acuity (CDVA) (time frame: Preoperative vs 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02208089, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2019.