KeratoconusNCT03990506
Photorefractive Intrastromal Crosslinking (PiXL) for the Treatment of Progressive Keratoconus
A study testing Epi-on PiXL and Epi-Off PiXL in people with Keratoconus and Corneal Crosslinking, run by Umeå University at 1 site in Sweden.
Trial summary
The purpose of this study is to evaluate the efficacy, safety and postoperative ocular discomfort by comparing individually customized Photorefractive intrastromal crosslinking (PiXL) for progressive Keratoconus. Read more about this study
- Who is it for?
- Ages 18 to 35 years
- Conditions the study is for
- Keratoconus, Corneal Crosslinking, Corneal Biomechanics
- What is being tested?
- Epi-on PiXL and Epi-Off PiXL
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteSweden
- Study dates
- 2 Apr 2019to 24 Jan 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 planned for corneal crosslinking.
- Progressive keratoconus documented with a consistent decrease of best corrected visual acuity with no other explanation, an unquestionable historical progression, or a progression documented with the Pentacam Scheimpflug camera with at least 2 of the following: progressive anterior and/or posterior corneal steepening and/or progressive corneal thinning and/or increased rate of corneal thickness change from the periphery to the center.
- A keratoconus diagnosis based on abnormal posterior elevation, abnormal corneal thickness distribution and clinical noninflammatory corneal thinning using the "Belin/Ambrósio enhanced ectasia" measurements of the Pentacam Scheimpflug camera.
- Minimum corneal thickness of 400 µm at the thinnest point before epithelial removal.
- 18-35 years of age
- No ocular abnormalities except keratoconus
- No previous ocular surgery
- No cognitive insufficiency interfering with the informed consent.
Who cannot join
- Age under 18 or over 35
- Any corneal abnormalities except keratoconus
- Pregnancy or lactation
- Previous ocular surgery
- Cognitive insufficiency
Trial locations and contacts
1 site in 1 country.
Sweden1 site
Department of Clinical Sciences/Ophthalmology, Umeå University
Umeå, 901 85
About this study
Official title: Comparison of Epi-off and Epi-on Photorefractive Intrastromal Crosslinking (PiXL) for Progressive Keratoconus
The purpose of this study is to evaluate the efficacy, safety and postoperative ocular discomfort by comparing individually customized Photorefractive intrastromal crosslinking (PiXL) for progressive Keratoconus. The study compares two different protocols, PiXL with corneal epithelium debridement (Epi-off) and PiXL without epithelium debridement in high oxygen environment (Epi-on), with the hypothesis that Epi-on gives less postoperative ocular discomfort.
Read the detailed description
The study is designed as a prospective, single-masked intraindividually comparing randomized clinical trial involving participants of both genders aged 18-35 years with Keratoconus planned for routine corneal crosslinking at the Department of Ophthalmology, Umeå University Hospital, Umeå, Sweden. The study includes 32 participants with bilateral Keratoconus, receiving Epi-off PiXL (n=32) in one eye and Epi-on PiXL in high oxygen environment (n=32) in the fellow eye. The participants are randomized to epi-on PiXL utilizing block randomization with a sample size of 16 in each block; 16 right eyes and 16 left eyes. All participants are informed about the procedures before consenting to participate in the study.
At baseline, before treatment, each eye is examined with slit-lamp microscopy, subjective refraction, determination of uncorrected (UCVA), low contrast visual acuity at 2.5 percentage contrast and 10 percentage contrast and best corrected (BSCVA) visual acuities using the LogMAR fast protocol and intraocular pressure (IOP) using Goldmann applanation tonometry. Under standardized, mesopic light conditions each eye is evaluated by keratometry readings and central corneal thickness using Schemipflug camera measurements, Pentacam HR® (Oculus, Inc. Lynnwood, WA).
Endothelial cellcount is assessed (SP-2000P, Topcon, Inc) and total ocular wavefront is measured with iTrace (Tracey Technologies, Inc.).
Ocular discomfort is subjectively evaluated in each eye by a specific visual analogous rating scale at 4h, 8h 24h and thereafter daily up to 1 week postoperatively.
All the above mentioned examinations are repeated at 1, 3, 6, 12 and 24 months after treatment. At 1 day and 1 week after treatment, solely UCVA, Auto-refractor measurements and slit-lamp examination are evaluated.
- Conditions
- Keratoconus, Corneal Crosslinking, Corneal Biomechanics, Corneal Densitometry, Scheimpflug Photography, Corneal Disease
- Being tested
- Epi-on PiXL, Epi-Off PiXL
- Medical subject headings
- Keratoconus, Corneal Diseases, Eye Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Epi-on PiXLProcedure or surgery
Photorefractive intrastromal crosslinking (PiXL) After local anaesthetics, the cornea is soaked in Riboflavin by repeated topical application during 10 minutes. For masking purposes, epithelial debridement is simulated by moving a scraping instrument in front of the cornea. A Riboflavin soaked sponge is used to lightly disrupt the epithelium tight junctions, without epithelium debridement. The cornea is illuminated with PiXL under 16:40 minutes during continuously delivery of humidified high oxygen via specific oxygen goggles. The UV-dosage is individually customized based upon Kmax; < 45D, 7.2J/cm2; 45-50D, 10J/cm2; > 50D, 15 J/cm2.
Epi-Off PiXLProcedure or surgery
Photorefractive intrastromal crosslinking (PiXL) After local anaesthetics, the corneal epithelium is debrided and the cornea is soaked in Riboflavin by repeated topical application during 10 minutes. The cornea is then illuminated with individually customized topography-guided PiXL under 16:40 minutes. The UV-dosage is individually customized based upon Kmax; < 45D, 7.2J/cm2; 45-50D, 10J/cm2; > 50D, 15 J/cm2.
| Study group | Role | What they receive |
|---|---|---|
| Epi-on PiXL | Experimental | Photorefractive intrastromal corneal crosslinking without epithelium debridement during humidified high oxygen flow. Receives: Procedure: Epi-on PiXL |
| Epi-off PiXL | Active comparator | Photorefractive intrastromal corneal crosslinking with epithelium debridement. Receives: Procedure: Epi-Off PiXL |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal keratometry (Kmax)
Kmax assessed with the Pentacam HR Scheimpflug camera, Diopters.
Measured: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
Secondary outcomes (10)
Uncorrected distance visual acuity (UDVA)
Change from baseline in distance uncorrected visual acuity, LogMAR
Measured: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
Best corrected visual acuity (BCVA)
Change from baseline in distance best corrected visual acuity, LogMAR
Measured: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
Mean keratometry (Kmean)
Kmean (average) assessed with the Pentacam HR Scheimpflug camera, Diopters.
Measured: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
Subjective Ocular Discomfort Scores
Subjective Ocular Discomfort Scores, Visual Analog Score (0 (no discomfort) - 10 (maximum discomfort)) for each eye, mm.
Measured: 4 hours, 8 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days and 7 days after treatment
Low contrast visual acuity (LCVA)
Change from baseline in low contrast visual acuities at 10 % and 2.5 % contrast, LogMAR
Measured: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
Manifest spherical equivalent (MRSE)
Change from baseline in spherical equivalent on subjective distance refraction, Diopters
Measured: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
Central corneal thickness (CCT)
Change from baseline in central corneal thickness assessed with Pentacam, Scheimpflug camera, μm.
Measured: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
Change from baseline in ocular wavefront aberrometry
Change from baseline in higher order aberrations assessed with iTrace, Root mean square.
Measured: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
Endothelial cell density (ECC)
Change from baseline in endothelial cell density, cells/mm2
Measured: 24 months after treatment
Intraocular pressure (IOP)
Change from baseline in intraocular pressure assessed with Goldmann applanation tonometry, mmHg.
Measured: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2019
- Study start2 Apr 2019
- Primary completion24 Jan 2023
- Study completion24 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for KeratoconusStudies of the same condition, open and under way.
- More trials run by Umeå UniversityThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, single-masked intraindividually comparing randomized controlled trial. Participants will be randomized to receive Epi-off PiXL in one eye and Epi-on PiXL in the other, which is masked to the participant. The participant can choose to treat in eye at a time or both eyes during the same visit.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Umeå University
- Sponsor type
- University, hospital or other
- Collaborators
- Glaukos Corporation
- Responsible party
- Principal investigator, Anders Behndig, Umeå University
- Investigators
- Anders Behndig, MD, PhD, Principal investigator, Department of Clinical Sciences/Ophthalmology, Umeå University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03990506
- Sponsor's protocol ID
- PiXLKC-I
- Status last verified
- Aug 2023
- First submitted
- 12 Jun 2019
- Last updated
- 1 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Epi-off and Epi-on Photorefractive Intrastromal Crosslinking (PiXL) for Progressive Keratoconus
- ClinicalTrials.gov ID
- NCT03990506
- Acronym / sponsor ID
- PiXLKC-I
- Conditions
- Keratoconus, Corneal Crosslinking, Corneal Biomechanics, Corneal Densitometry, Scheimpflug Photography, Corneal Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Umeå UniversityUniversity, hospital or other
- Collaborators
- Glaukos Corporation
- Study start
- 2 Apr 2019 (actual)
- Primary completion
- 24 Jan 2023 (actual)
- Study completion
- 24 Jan 2023 (actual)
- First posted
- 19 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy, safety and postoperative ocular discomfort by comparing individually customized Photorefractive intrastromal crosslinking (PiXL) for progressive Keratoconus. The study compares two different protocols, PiXL with corneal epithelium debridement (Epi-off) and PiXL without epithelium debridement in high oxygen environment (Epi-on), with the hypothesis that Epi-on gives less postoperative ocular discomfort.
Detailed description
The study is designed as a prospective, single-masked intraindividually comparing randomized clinical trial involving participants of both genders aged 18-35 years with Keratoconus planned for routine corneal crosslinking at the Department of Ophthalmology, Umeå University Hospital, Umeå, Sweden. The study includes 32 participants with bilateral Keratoconus, receiving Epi-off PiXL (n=32) in one eye and Epi-on PiXL in high oxygen environment (n=32) in the fellow eye. The participants are randomized to epi-on PiXL utilizing block randomization with a sample size of 16 in each block; 16 right eyes and 16 left eyes. All participants are informed about the procedures before consenting to participate in the study.
At baseline, before treatment, each eye is examined with slit-lamp microscopy, subjective refraction, determination of uncorrected (UCVA), low contrast visual acuity at 2.5 percentage contrast and 10 percentage contrast and best corrected (BSCVA) visual acuities using the LogMAR fast protocol and intraocular pressure (IOP) using Goldmann applanation tonometry. Under standardized, mesopic light conditions each eye is evaluated by keratometry readings and central corneal thickness using Schemipflug camera measurements, Pentacam HR® (Oculus, Inc. Lynnwood, WA).
Endothelial cellcount is assessed (SP-2000P, Topcon, Inc) and total ocular wavefront is measured with iTrace (Tracey Technologies, Inc.).
Ocular discomfort is subjectively evaluated in each eye by a specific visual analogous rating scale at 4h, 8h 24h and thereafter daily up to 1 week postoperatively.
All the above mentioned examinations are repeated at 1, 3, 6, 12 and 24 months after treatment. At 1 day and 1 week after treatment, solely UCVA, Auto-refractor measurements and slit-lamp examination are evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Prospective, single-masked intraindividually comparing randomized controlled trial. Participants will be randomized to receive Epi-off PiXL in one eye and Epi-on PiXL in the other, which is masked to the participant. The participant can choose to treat in eye at a time or both eyes during the same visit.
| Arm | Type | Receives |
|---|---|---|
| Epi-on PiXL | Experimental | Procedure: Epi-on PiXLPhotorefractive intrastromal corneal crosslinking without epithelium debridement during humidified high oxygen flow. |
| Epi-off PiXL | Active comparator | Procedure: Epi-Off PiXLPhotorefractive intrastromal corneal crosslinking with epithelium debridement. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Patients planned for corneal crosslinking.
- Progressive keratoconus documented with a consistent decrease of best corrected visual acuity with no other explanation, an unquestionable historical progression, or a progression documented with the Pentacam Scheimpflug camera with at least 2 of the following: progressive anterior and/or posterior corneal steepening and/or progressive corneal thinning and/or increased rate of corneal thickness change from the periphery to the center.
- A keratoconus diagnosis based on abnormal posterior elevation, abnormal corneal thickness distribution and clinical noninflammatory corneal thinning using the "Belin/Ambrósio enhanced ectasia" measurements of the Pentacam Scheimpflug camera.
- Minimum corneal thickness of 400 µm at the thinnest point before epithelial removal.
- 18-35 years of age
Key exclusion criteria (5 listed)
- Age under 18 or over 35
- Any corneal abnormalities except keratoconus
- Pregnancy or lactation
- Previous ocular surgery
- Cognitive insufficiency
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 |
|---|---|---|
| Epi-on PiXLPhotorefractive intrastromal crosslinking (PiXL) After local anaesthetics, the cornea is soaked in Riboflavin by repeated topical application during 10 minutes. For masking purposes, epithelial debridement is simulated by moving a scraping instrument in front of the cornea. A Riboflavin soaked sponge is used to lightly disrupt the epithelium tight junctions, without epithelium debridement. The cornea is illuminated with PiXL under 16:40 minutes during continuously delivery of humidified high oxygen via specific oxygen goggles. The UV-dosage is individually customized based upon Kmax; < 45D, 7.2J/cm2; 45-50D, 10J/cm2; > 50D, 15 J/cm2. | Procedure or surgery | Epi-on PiXL |
| Epi-Off PiXLPhotorefractive intrastromal crosslinking (PiXL) After local anaesthetics, the corneal epithelium is debrided and the cornea is soaked in Riboflavin by repeated topical application during 10 minutes. The cornea is then illuminated with individually customized topography-guided PiXL under 16:40 minutes. The UV-dosage is individually customized based upon Kmax; < 45D, 7.2J/cm2; 45-50D, 10J/cm2; > 50D, 15 J/cm2. | Procedure or surgery | Epi-off PiXL |
Primary outcome
Maximal keratometry (Kmax)
Time frame: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
Kmax assessed with the Pentacam HR Scheimpflug camera, Diopters.
10 secondary outcomes
Uncorrected distance visual acuity (UDVA)
Time frame: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
Best corrected visual acuity (BCVA)
Time frame: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
Mean keratometry (Kmean)
Time frame: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
Subjective Ocular Discomfort Scores
Time frame: 4 hours, 8 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days and 7 days after treatment
Low contrast visual acuity (LCVA)
Time frame: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
Manifest spherical equivalent (MRSE)
Time frame: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
Central corneal thickness (CCT)
Time frame: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
Change from baseline in ocular wavefront aberrometry
Time frame: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
Endothelial cell density (ECC)
Time frame: 24 months after treatment
Intraocular pressure (IOP)
Time frame: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2023.
- Individual participant dataSharing planned: No
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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.
Anders Behndig, MD, PhD principal investigator
Department of Clinical Sciences/Ophthalmology, Umeå University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Epi-on PiXL and Epi-Off PiXL in people with Keratoconus and Corneal Crosslinking, run by Umeå University at 1 site in Sweden.
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 8 inclusion and 5 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 1 Sep 2023. 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 Sweden. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximal keratometry (Kmax) (time frame: 1 month, 3 months, 6 months, 12 months and 24 months after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Sep 2023.