PiXL as a Treatment for Low Grade Myopia

Evaluation of a Reduced Photorefractive Intrastromal Corneal Crosslinking Illumination Protocol. A Randomized Controlled Trial.

To assess the improvement in myopia with phototherapeutic intrastromal corneal collagen cross-linking (PiXL) without epithelial debridement (epi-on) in high oxygen environment for low grade myopia. The study compares two 3.5-mm central ring-shaped zone protocols; 10 min illumination time vs 16:40 min illumination time.

Study Overview

• Status: Active, not recruiting
• Conditions: Refractive Errors; Myopia
• Intervention / Treatment: Procedure: PiXL

Detailed Description

The study design is a prospective, single-masked intraindividually comparing randomized controlled trial, conducted at the Department of Clinical Sciences / Ophthalmology, Umeå University Hospital, Umeå, Sweden. The study includes healthy men and women with low grade myopia, aged between 18-35 years and involves 25 participants with a myopia of -0.50 to -2.5 diopters (D) and astigmatism of ≤0.75D. All participants are treated with phototherapeutic intrastromal corneal collagen cross-linking (PiXL) without epithelial debridement (epi-on), after topical riboflavin. Both eyes are treated and 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. Throughout the treatment, humidified oxygen is continuously delivered around the eye using an oxygen mask to achieve an oxygen concentration of ≥95 percentage. Prior to inclusion all participants are informed about the procedures and provide oral and written informed consent.

At baseline, each eye is examined with slit-lamp microscopy, subjective refraction, determination of uncorrected (UCVA), low contrast visual acuity at 2.5 percentage 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, central corneal thickness and after treatment also the depth of demarcation lines, extracted from Schemipflug camera measurements, Pentacam HR® (Oculus, Inc. Lynnwood, WA). Central corneal endothelial photographs are taken with the Topcon SP-2000P specular microscope (Topcon Europe B.V., Capelle a/d Ijssel, the Netherlands), from which the corneal endothelial cell count is manually calculated from a cluster of 25 cells from each photograph. Total ocular wavefront is measured with iTrace (Tracey Technologies, Inc.).

All the above mentioned examinations are reassessed at 1, 3, 6 and 12 months after treatment. At 1 day and 1 week after treatment, solely UCVA, Auto refractor measurements, slit-lamp examination and a subjective comparison of discomfort and visual performance in each eye are evaluated.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Umeå, Sweden, 90185
    • Umea University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes

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 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: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Protocol A; PiXL treatment with pulsed UV illumination (1.0 sec on /0.8 sec off) in high oxygen in a central ring-shaped 3.5-mm zone of the cornea and total illumination time of 10 min. The area consist of three rings with a central 1.5-mm zone that is left untreated. The illumination area consists of three rings, where the outer and inner ring are thinner than the middle ring. The maximum energy is distributed in the middle ring.	Procedure: PiXL; Phototherapeutic intrastromal corneal collagen cross-linking (PiXL) performed in a high-oxygen environment without corneal epithelial debridement, for treatment of low grade myopia.
Active Comparator: Protocol B; PiXL treatment with pulsed (0.5 sec on / 1 sec off) UV illumination in high oxygen in a central ring-shaped 3.5-mm zone of the cornea and total illumination time of 16:40 min. The area consist of three rings with a central 1.5-mm zone that is left untreated. The illumination area consists of three rings, where the outer and inner ring are thinner than the middle ring. The maximum energy is distributed in the middle ring.	Procedure: PiXL; Phototherapeutic intrastromal corneal collagen cross-linking (PiXL) performed in a high-oxygen environment without corneal epithelial debridement, for treatment of low grade myopia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Uncorrected distance visual acuity (UDVA)	Change from baseline in UDVA (logMAR)	1, 3, 6 and 12 months after treatment.
Manifest Refractive Spherical Equivalent	Change from baseline in MRSE (Diopters)	1, 3, 6 and 12 months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best spectacle corrected visual acuity (BSCVA)	Change from baseline in BSCVA (logMAR)	1, 3, 6 and 12 months after treatment
Endothelial cell density (ECC)	Change from baseline in ECC (cells/mm^2)	1, 3, 6 and 12 months after treatment
Low contrast visual acuity at 10% and 2.5% (LCVA)	Change from baseline in LCVA 10 % and 2.5% (logMAR)	1, 3, 6 and 12 months after treatment

Collaborators and Investigators

• Sponsor: Umeå University
• Collaborators: Glaukos Corporation
• Investigators: Principal Investigator: Anders Behndig, MD, PhD, Umea University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2019
• Primary Completion (Estimated): June 17, 2024
• Study Completion (Estimated): June 17, 2024

Study Registration Dates

• First Submitted: December 9, 2020
• First Submitted That Met QC Criteria: December 9, 2020
• First Posted (Actual): December 10, 2020

Study Record Updates

• Last Update Posted (Estimated): December 20, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

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

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