Photorefractive Intrastromal Corneal Crosslinking as a Treatment for Low Grade Myopia

Comparison of a 4-mm Ring Shaped and 3.5-mm Ring Shaped PiXL Protocol for Low Grade Myopia

To assess the improvement in refractive error and the corneal endothelial safety with a customized corneal crosslinking treatment regimen for low grade myopia. The study compares two treatment protocols, a 4.0-mm central ring-shaped zone with a 3.5-mm central ring-shaped zone in high oxygen environment without corneal epithelial debridement.

Study Overview

• Status: Completed
• Conditions: Eye Diseases; Refractive Errors; Myopia; Corneal Crosslinking
• Intervention / Treatment: Procedure: 4.0 mm treatment; Procedure: 3.5 mm treatment

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 27 participants with a myopia of -0.5 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 4.0 mm treatment zone in one eye and PiXL 3.5 mm treatment zone in the other, which is masked to the participant. For myopia <0.75D, 10 J/cm^2 is used and for higher levels of myopia 15J/cm^2 is used. Throughout the treatment, humidified oxygen is continuously delivered around the eye using an oxygen mask to achieve an oxygen concentration of ≥95 percentage. All participants are informed about the procedures and provide oral and written consent before inclusion in the study.

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 and 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): 27
• 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: Yes
• 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 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
Active Comparator: 4.0 mm zone; PiXL treatment with UV irradiation in a central 4.0-mm ring-shaped zone of the cornea. The area consist of three rings with a central 2-mm zone that is left untreated. The energy is higher towards the periphery of the ring-shaped area, reaching its maximum at 2-mm from the corneal centre. Pulsed UV-light, 1s on / 1s off; 30mW. For myopia of less than 0.75D, 10 J/cm2 is used, for higher levels of myopia 15J/cm2 is used.	Procedure: 4.0 mm treatment; PiXL treatment with UV irradiation in a central 4.0-mm ring-shaped zone of the cornea.
Experimental: 3.5 mm zone; PiXL treatment with UV irradiation in a central ring-shaped 3.5-mm zone of the cornea, 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. Pulsed UV-light, 0.5s on / 1s off; 45mW. For myopia of less than 0.75D, a maximum of 10 J/cm2 is used, for higher levels of myopia a maximum of 15J/cm2 is used.	Procedure: 3.5 mm treatment; PiXL treatment with UV irradiation in a central 3.5-mm ring-shaped zone of the cornea.

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, 12 and 24 months after treatment
Change from baseline in spherical equivalent	Change from baseline in spherical equivalent on subjective distance refraction	1, 3, 6, 12 and 24 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 and 24 months after treatment
Change from baseline in best corrected visual acuity	Change from baseline in best spectacle corrected distance visual acuity	1, 3, 6, 12 and 24 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): January 22, 2018
• Primary Completion (Actual): October 15, 2020
• Study Completion (Actual): October 15, 2020

Study Registration Dates

• First Submitted: June 12, 2019
• First Submitted That Met QC Criteria: June 12, 2019
• First Posted (Actual): June 17, 2019

Study Record Updates

• Last Update Posted (Actual): December 10, 2020
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Refractive Errors; Eye Diseases; Myopia
• Other Study ID Numbers: PiXLMYOP-II

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