Standard Corneal Collagen Crosslinking Versus Transepithelial Corneal Crosslinking by Iontophoresis of Riboflavin

Comparative Study of Results of Standard Corneal Collagen Crosslinking Versus Transepithelial Corneal Crosslinking by Iontophoresis of Riboflavin: a Randomized Control Trial

The standard CXL technique involves removal of the epithelium to enable riboflavin to penetrate into stromal tissue, to avoid epithelial debridement and increasing the patient's comfort and safety transepithelial corneal crosslinking (CXL) was suggested. Iontophoresis of riboflavin is one of approach for riboflavin impregnation.

In this study, the investigators compared the results of standard corneal crosslinking (CXL) and transepithelial CXL via iontophoresis of riboflavin after 24 months follow up.

Study Overview

• Status: Completed
• Conditions: Keratoconus
• Intervention / Treatment: Procedure: epithelium-off; Procedure: Corneal collagen crosslinking; Drug: Dextralink; Device: UFalink; Procedure: iontophoresis of riboflavin; Device: galvanizator, Potok-1; Drug: Riboflavin 0,1%

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Documented progressive KC (by Pentacam and/or corneal topography imaging).
• A clear central cornea.
• A minimal corneal thickness of ≥ 400 µm at the thinnest corneal location (Pentacam imaging).
• Minimal Snellen corrected distance visual acuity of ≥ 0.4.
• Patient age of ≥ 18 years.

Exclusion Criteria:

• Corneal scarring.
• History of epithelial healing problems.
• History or presence of ocular infection (such as herpes keratitis)
• Pregnancy and/or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard epithelium-off CXL; Removing the central 8-10mm of the epithelium and applying a riboflavin solution (0.1% riboflavin-5-phosphate and 20% dextran T-500) to the corneal surface 30 minutes before irradiation and at 5 minutes intervals during the course of a 30 minute exposure to 370 nm UVA with an irradiance of 3 mWcm-2 (UFalink, Russian Federation)	Procedure: epithelium-off; Procedure: Corneal collagen crosslinking; Standard surface UVA irradiation (370 nm, 3 mW/cm2; UFalink, Russian Federation) was then applied at a 5-cm distance for 30 minutes. During UVA exposure, hypotonic riboflavin drops were continued every 2 minutes.; Drug: Dextralink; Riboflavin 0,1% + Dextran T-500; Device: UFalink; device for UVA irradiation - providing UVA light - 370 nm, 3 mW/cm2
Experimental: Transepithelial CXL via iontophoresis of riboflavin; impregnation of the cornea with a riboflavin 0.1% hypotonic solution is performed by using an iontophoresis device (galvanizator; Potok-1, Russian Federation). The passive electrode (anode) was applied to the inferior part of the cervical vertebrae. The active electrode (cathode), a bath tube (glass or plastic - 10-12 ml) is applied to the open eye,then r the tube is taped to the skin of the orbital margins and filled with riboflavin 0.1%. The current intensity is initially 0.2 mA and then gradually increased to 1.0 mA at 0.2 mA for 1 minute at 10-second intervals increments to determine individual tolerance. The total time that the riboflavin administration is 10 minutes. Standard surface UVA irradiation (370 nm, 3 mW/cm2) using UFalink device, (Russian Federation) is then applied at a 5-cm distance for 30 minutes with continuing hypotonic riboflavin drops every 2 minutes	Procedure: Corneal collagen crosslinking; Standard surface UVA irradiation (370 nm, 3 mW/cm2; UFalink, Russian Federation) was then applied at a 5-cm distance for 30 minutes. During UVA exposure, hypotonic riboflavin drops were continued every 2 minutes.; Device: UFalink; device for UVA irradiation - providing UVA light - 370 nm, 3 mW/cm2; Procedure: iontophoresis of riboflavin; Device: galvanizator, Potok-1; Device for providing iontophoresis procedure; Drug: Riboflavin 0,1%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kmax, D	Using topography measurements, clinical stabilisation is defined as an increase of no more than 1 diopter of the maximum keratometry value over the preoperative maximum keratometry value	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual acuity as assessed by Decimal system	Decimal visual acuity assessed on a study later was converted to the logarithm of minimal angle of resolution (logMAR).	2 years
Corneal thickness, μm, as measured by OCT tomography	Using optical coherence tomography to estimate the pachymetry changes	2 years

Collaborators and Investigators

• Sponsor: Ufa Eye Research Institute
• Investigators: Study Chair: Mukharram Bikbov, Professor, Ufa Eye Research Institute

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: May 20, 2015
• First Submitted That Met QC Criteria: May 26, 2015
• First Posted (Estimate): May 29, 2015

Study Record Updates

• Last Update Posted (Estimate): May 29, 2015
• Last Update Submitted That Met QC Criteria: May 26, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Iontophoresis; Riboflavin; Collagen crosslinking (CXL); Standard corneal crosslinking (CXL); Transepithelial CXL
• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Keratoconus; Physiological Effects of Drugs; Photosensitizing Agents; Dermatologic Agents; Micronutrients; Vitamins; Vitamin B Complex; Riboflavin
• Other Study ID Numbers: TCXL-ionto