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Photorefractive Intrastromal Crosslinking (PiXL) for the Treatment of Progressive Keratoconus

Primary Purpose

Keratoconus, Corneal Crosslinking, Corneal Biomechanics

Status
Completed
Phase
Not Applicable
Locations
Sweden
Study Type
Interventional
Intervention
Epi-on PiXL
Epi-Off PiXL
Sponsored by
Umeå University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Keratoconus

Eligibility Criteria

18 Years - 35 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Age under 18 or over 35
  • Any corneal abnormalities except keratoconus
  • Pregnancy or lactation
  • Previous ocular surgery
  • Cognitive insufficiency

Sites / Locations

  • Department of Clinical Sciences/Ophthalmology, Umeå University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Epi-on PiXL

Epi-off PiXL

Arm Description

Photorefractive intrastromal corneal crosslinking without epithelium debridement during humidified high oxygen flow.

Photorefractive intrastromal corneal crosslinking with epithelium debridement.

Outcomes

Primary Outcome Measures

Maximal keratometry (Kmax)
Kmax assessed with the Pentacam HR Scheimpflug camera, Diopters.

Secondary Outcome Measures

Uncorrected distance visual acuity (UDVA)
Change from baseline in distance uncorrected visual acuity, LogMAR
Best corrected visual acuity (BCVA)
Change from baseline in distance best corrected visual acuity, LogMAR
Mean keratometry (Kmean)
Kmean (average) assessed with the Pentacam HR Scheimpflug camera, Diopters.
Subjective Ocular Discomfort Scores
Subjective Ocular Discomfort Scores, Visual Analog Score (0 (no discomfort) - 10 (maximum discomfort)) for each eye, mm.
Low contrast visual acuity (LCVA)
Change from baseline in low contrast visual acuities at 10 % and 2.5 % contrast, LogMAR
Manifest spherical equivalent (MRSE)
Change from baseline in spherical equivalent on subjective distance refraction, Diopters
Central corneal thickness (CCT)
Change from baseline in central corneal thickness assessed with Pentacam, Scheimpflug camera, μm.
Change from baseline in ocular wavefront aberrometry
Change from baseline in higher order aberrations assessed with iTrace, Root mean square.
Endothelial cell density (ECC)
Change from baseline in endothelial cell density, cells/mm2
Intraocular pressure (IOP)
Change from baseline in intraocular pressure assessed with Goldmann applanation tonometry, mmHg.

Full Information

First Posted
June 12, 2019
Last Updated
August 29, 2023
Sponsor
Umeå University
Collaborators
Glaukos Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT03990506
Brief Title
Photorefractive Intrastromal Crosslinking (PiXL) for the Treatment of Progressive Keratoconus
Official Title
Comparison of Epi-off and Epi-on Photorefractive Intrastromal Crosslinking (PiXL) for Progressive Keratoconus
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
April 2, 2019 (Actual)
Primary Completion Date
January 24, 2023 (Actual)
Study Completion Date
January 24, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Umeå University
Collaborators
Glaukos Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Keratoconus, Corneal Crosslinking, Corneal Biomechanics, Corneal Densitometry, Scheimpflug Photography, Corneal Disease, Eye Diseases

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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
Participant
Masking Description
The participants are not aware which eye will receive the Epi-off PiXL treatment and which eye will receive the Epi-on PiXL treatment.
Allocation
Randomized
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Epi-on PiXL
Arm Type
Experimental
Arm Description
Photorefractive intrastromal corneal crosslinking without epithelium debridement during humidified high oxygen flow.
Arm Title
Epi-off PiXL
Arm Type
Active Comparator
Arm Description
Photorefractive intrastromal corneal crosslinking with epithelium debridement.
Intervention Type
Procedure
Intervention Name(s)
Epi-on PiXL
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Epi-Off PiXL
Intervention Description
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.
Primary Outcome Measure Information:
Title
Maximal keratometry (Kmax)
Description
Kmax assessed with the Pentacam HR Scheimpflug camera, Diopters.
Time Frame
1 month, 3 months, 6 months, 12 months and 24 months after treatment
Secondary Outcome Measure Information:
Title
Uncorrected distance visual acuity (UDVA)
Description
Change from baseline in distance uncorrected visual acuity, LogMAR
Time Frame
1 month, 3 months, 6 months, 12 months and 24 months after treatment
Title
Best corrected visual acuity (BCVA)
Description
Change from baseline in distance best corrected visual acuity, LogMAR
Time Frame
1 month, 3 months, 6 months, 12 months and 24 months after treatment
Title
Mean keratometry (Kmean)
Description
Kmean (average) assessed with the Pentacam HR Scheimpflug camera, Diopters.
Time Frame
1 month, 3 months, 6 months, 12 months and 24 months after treatment
Title
Subjective Ocular Discomfort Scores
Description
Subjective Ocular Discomfort Scores, Visual Analog Score (0 (no discomfort) - 10 (maximum discomfort)) for each eye, mm.
Time Frame
4 hours, 8 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days and 7 days after treatment
Title
Low contrast visual acuity (LCVA)
Description
Change from baseline in low contrast visual acuities at 10 % and 2.5 % contrast, LogMAR
Time Frame
1 month, 3 months, 6 months, 12 months and 24 months after treatment
Title
Manifest spherical equivalent (MRSE)
Description
Change from baseline in spherical equivalent on subjective distance refraction, Diopters
Time Frame
1 month, 3 months, 6 months, 12 months and 24 months after treatment
Title
Central corneal thickness (CCT)
Description
Change from baseline in central corneal thickness assessed with Pentacam, Scheimpflug camera, μm.
Time Frame
1 month, 3 months, 6 months, 12 months and 24 months after treatment
Title
Change from baseline in ocular wavefront aberrometry
Description
Change from baseline in higher order aberrations assessed with iTrace, Root mean square.
Time Frame
1 month, 3 months, 6 months, 12 months and 24 months after treatment
Title
Endothelial cell density (ECC)
Description
Change from baseline in endothelial cell density, cells/mm2
Time Frame
24 months after treatment
Title
Intraocular pressure (IOP)
Description
Change from baseline in intraocular pressure assessed with Goldmann applanation tonometry, mmHg.
Time Frame
1 month, 3 months, 6 months, 12 months and 24 months after treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: Age under 18 or over 35 Any corneal abnormalities except keratoconus Pregnancy or lactation Previous ocular surgery Cognitive insufficiency
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anders Behndig, MD, PhD
Organizational Affiliation
Department of Clinical Sciences/Ophthalmology, Umeå University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Clinical Sciences/Ophthalmology, Umeå University
City
Umeå
ZIP/Postal Code
901 85
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
No

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Photorefractive Intrastromal Crosslinking (PiXL) for the Treatment of Progressive Keratoconus

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