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

Not Applicable

Completed

• Conditions: Keratoconus; Corneal Biomechanics; Eye Diseases; Corneal Crosslinking; Corneal Densitometry; Scheimpflug Photography; Corneal Disease
• Interventions: Procedure: Epi-Off PiXL; Procedure: Epi-on PiXL

• Registration Number: NCT03990506
• Lead Sponsor: Umeå University

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.

Study Timeline

• Study Start: 2019-04-02
• Study First Submitted: 2019-06-12
• Study First Submitted QC: 2019-06-15
• Study First Posted: 2019-06-19
• Primary Completion: 2023-01-24
• Study Completion: 2023-01-24
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-29
• Last Update Posted: 2023-09-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Epi-off PiXL	Epi-Off PiXL	Photorefractive intrastromal corneal crosslinking with epithelium debridement.
Epi-on PiXL	Epi-on PiXL	Photorefractive intrastromal corneal crosslinking without epithelium debridement during humidified high oxygen flow.

Primary Outcome Measures

Name	Time	Method
Maximal keratometry (Kmax)	1 month, 3 months, 6 months, 12 months and 24 months after treatment	Kmax assessed with the Pentacam HR Scheimpflug camera, Diopters.

Secondary Outcome Measures

Name	Time	Method
Endothelial cell density (ECC)	24 months after treatment	Change from baseline in endothelial cell density, cells/mm2
Intraocular pressure (IOP)	1 month, 3 months, 6 months, 12 months and 24 months after treatment	Change from baseline in intraocular pressure assessed with Goldmann applanation tonometry, mmHg.
Uncorrected distance visual acuity (UDVA)	1 month, 3 months, 6 months, 12 months and 24 months after treatment	Change from baseline in distance uncorrected visual acuity, LogMAR
Mean keratometry (Kmean)	1 month, 3 months, 6 months, 12 months and 24 months after treatment	Kmean (average) assessed with the Pentacam HR Scheimpflug camera, Diopters.
Subjective Ocular Discomfort Scores	4 hours, 8 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days and 7 days after treatment	Subjective Ocular Discomfort Scores, Visual Analog Score (0 (no discomfort) - 10 (maximum discomfort)) for each eye, mm.
Manifest spherical equivalent (MRSE)	1 month, 3 months, 6 months, 12 months and 24 months after treatment	Change from baseline in spherical equivalent on subjective distance refraction, Diopters
Change from baseline in ocular wavefront aberrometry	1 month, 3 months, 6 months, 12 months and 24 months after treatment	Change from baseline in higher order aberrations assessed with iTrace, Root mean square.
Best corrected visual acuity (BCVA)	1 month, 3 months, 6 months, 12 months and 24 months after treatment	Change from baseline in distance best corrected visual acuity, LogMAR
Low contrast visual acuity (LCVA)	1 month, 3 months, 6 months, 12 months and 24 months after treatment	Change from baseline in low contrast visual acuities at 10 % and 2.5 % contrast, LogMAR
Central corneal thickness (CCT)	1 month, 3 months, 6 months, 12 months and 24 months after treatment	Change from baseline in central corneal thickness assessed with Pentacam, Scheimpflug camera, μm.

Trial Locations

Locations (1)

Department of Clinical Sciences/Ophthalmology, Umeå University; 🇸🇪 Umeå, Sweden