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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Comparison of Epi-off and Epi-on Photorefractive Intrastromal Crosslinking (PiXL) for Progressive Keratoconus

Conditions
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Keratoconus, Corneal Crosslinking, Corneal Biomechanics, Corneal Densitometry, Scheimpflug Photography, Corneal Disease, Eye Diseases

Intervention / Treatment
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* Procedure: Epi-on PiXL
* Procedure: Epi-Off PiXL


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epi-on PiXL<br>Photorefractive intrastromal corneal crosslinking without epithelium debridement during humidified high oxygen flow. | Procedure: Epi-on PiXL<br>* 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.<br>|
| Active Comparator: Epi-off PiXL<br>Photorefractive intrastromal corneal crosslinking with epithelium debridement. | Procedure: Epi-Off PiXL<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal keratometry (Kmax) | Kmax assessed with the Pentacam HR Scheimpflug camera, Diopters. | 1 month, 3 months, 6 months, 12 months and 24 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Uncorrected distance visual acuity (UDVA) | Change from baseline in distance uncorrected visual acuity, LogMAR | 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 | 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. | 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. | 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 | 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 | 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. | 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. | 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 | 24 months after treatment | 
| Intraocular pressure (IOP) | Change from baseline in intraocular pressure assessed with Goldmann applanation tonometry, mmHg. | 1 month, 3 months, 6 months, 12 months and 24 months after treatment |