Advanced Cross Linking for Low-grade Myopia (PiXLO2)

Non-invasive Phototherapeutic Intrastromal Corneal Collagen Crosslinking (PiXL) for Low-grade Myopia

To evaluate the improvement in myopic refractive error and the corneal endothelial safety with a corneal crosslinking treatment regimen for mild myopia. The treatment involves a 4-mm central treatment zone in high oxygen environment without corneal epithelial debridement.

Study Overview

• Status: Completed
• Conditions: Myopia; Corneal Crosslinking
• Intervention / Treatment: Procedure: PiXL

Detailed Description

The study is designed as a prospective, single-masked intraindividually comparing randomized controlled trial involving healthy volunteers ≥18 years of age of both genders with mild myopia, performed at the Department of Clinical Sciences / Ophthalmology, Umeå University Hospital, Umeå, Sweden. The study involves 23 persons with a myopia of -0.5 to -2.5 diopters (D) and astigmatism of ≤0.75 D. All participants are treated with phototherapeutic intrastromal corneal collagen cross-linking (PiXL) without epithelial debridement (epi-on), after topical riboflavin. For myopia of less than 1.0D, 10 J/cm2 will be used, for higher levels of myopia 15J/cm2 will be used, and the treatment involves continuous delivery of oxygen around the eye using an oxygen mask to achieve an oxygen concentration of ≥90% during treatment. Participants will be randomized to receive ultraviolet (UV) light according to PiXL Protocol A in one eye and PiXL Protocol B in the other, which is masked to the participant. Both eyes will be treated during the same visit.

Protocol A: UV irradiation in a central 4 mm homogenous zone of the cornea. Protocol B: UV irradiation in a central ring-shaped 4 mm area of the cornea. Patients are randomized utilizing a computer list of unique random numbers between 1 and 23; an even number will be treated with a homogeneous zone in the right eye; an uneven number with a homogeneous zone in the left eye. All patients are informed about the procedures and provide oral and written consent before inclusion in the study.

At baseline, before treatment, each eye is evaluated with slit-lamp examination, subjective refraction, determination of uncorrected (UCVA) and best corrected (BSCVA) visual acuities using the LogMAR fast protocol and intraocular pressure (IOP) using Goldmann applanation tonometry. Each eye is photographed using the "25 pictures" program with the Pentacam HR® (Oculus, Inc. Lynnwood, WA) under standardized, mesopic light conditions. Keratometry readings, central corneal thickness and the average corneal densitometry values (corneal light backscatter), expressed as standardized gray scale units, GSU) is determined with the Pentacam HR®. Central corneal endothelial photographs are taken with the Topcon SP-2000P specular microscope (Topcon Europe B.V., Capelle a/d Ijssel, the Netherlands), and the corneal endothelial cell count is calculated from a cluster of 25 cells from each photograph.

All the above mentioned investigations are repeated at 1, 3, 6,12 and 24 months after the treatment. At 1 week after treatment, UCVA is registered and a slit-lamp examination, a subjective comparison of discomfort and visual performance in each eye and an autorefractometer measurement are performed. One day after treatment the latter 3 examinations are performed.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Umeå, Sweden, 901 85
    • Department of Clinical Sciences/Ophthalmology, Umeå University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Spherical equivalent on distance subjective refraction between -0.50D and -2.50D.
• Astigmatism ≤ 0.75D
• Stable myopia. Maximum change in refraction of 0.50D in the last 2 years.
• Best corrected visual acuity of at least 0.00 logMAR (ETDRS chart).
• Thinnest pachymetry reading ≥ 440 μm.
• No previous ocular surgery.
• No cognitive insufficiency interfering with the informed consent.

Exclusion Criteria:

• History of or current ocular condition, disease, surgery or medication with ocular effects that could affect the outcomes of the treatment.
• Allergy to any substance or device used in the study.
• Cognitive insufficiency interfering with the informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PiXL Protocol A; PiXL treatment with UV irradiation in a central 4 mm homogenous zone of the cornea. For myopia of less than 1.0D, 10 J/cm2 will be used, for higher levels of myopia 15J/cm2 will be used.	Procedure: PiXL; Phototherapeutic intrastromal corneal collagen cross-linking (PiXL) performed in a high-oxygen environment without corneal epithelial debridement, for treatment of mild myopia.
Active Comparator: PiXL Protocol B; PiXL treatment with UV irradiation in a central ring-shaped 4-mm area of the cornea. A central 2-mm zone is left untreated, and the energy is higher towards the periphery of the ring-shaped area, reaching its maximum at 2 mm from the corneal centre. For myopia of less than 1.0D, a maximum of 10 J/cm2 will be used, for higher levels of myopia a maximum of 15J/cm2 will be used.	Procedure: PiXL; Phototherapeutic intrastromal corneal collagen cross-linking (PiXL) performed in a high-oxygen environment without corneal epithelial debridement, for treatment of mild myopia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in uncorrected visual acuity	Change from baseline in distance uncorrected visual acuity	1, 3, 6 and 12 months after treatment
Change from baseline in spherical equivalent	Change from baseline in spherical equivalent on subjective distance refraction	1, 3, 6 and 12 months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in corneal endothelial cell density	Change from baseline in central corneal endothelial cell density	12 months after treatment

Collaborators and Investigators

• Sponsor: Umeå University
• Collaborators: Glaukos Corporation
• Investigators: Principal Investigator: Anders Behndig, MD, PhD, Department of Clinical Sciences/Ophthalmology, Umeå University, Umeå, Sweden

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2016
• Primary Completion (Actual): October 31, 2020
• Study Completion (Actual): November 30, 2020

Study Registration Dates

• First Submitted: June 20, 2017
• First Submitted That Met QC Criteria: June 22, 2017
• First Posted (Actual): June 23, 2017

Study Record Updates

• Last Update Posted (Actual): December 11, 2020
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Myopia; corneal Crosslinking
• Additional Relevant MeSH Terms: Eye Diseases; Refractive Errors; Myopia
• Other Study ID Numbers: PiXLMYOP-I

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No