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

Study Overview
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Brief Summary
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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.

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

Conditions
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Keratoconus

Intervention / Treatment
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* Procedure: iontophoresis of riboflavin
* Procedure: epithelium-off
* Procedure: Corneal collagen crosslinking
* Device: galvanizator, Potok-1
* Drug: Dextralink
* Drug: Riboflavin 0,1%
* Device: UFalink


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard epithelium-off CXL<br>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<br> <br> Procedure: Corneal collagen crosslinking<br>* 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.<br>Drug: Dextralink<br>* Riboflavin 0,1% + Dextran T-500<br>Device: UFalink<br>* device for UVA irradiation - providing UVA light - 370 nm, 3 mW/cm2<br>|
| Experimental: Transepithelial CXL via iontophoresis of riboflavin<br>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: iontophoresis of riboflavin<br> <br> Procedure: Corneal collagen crosslinking<br>* 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.<br>Device: galvanizator, Potok-1<br>* Device for providing iontophoresis procedure<br>Drug: Riboflavin 0,1%<br> <br> Device: UFalink<br>* device for UVA irradiation - providing UVA light - 370 nm, 3 mW/cm2<br>|

What is the study measuring?
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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 |
| --- | --- | --- |
| Corneal thickness, μm, as measured by OCT tomography | Using optical coherence tomography to estimate the pachymetry changes | 2 years | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Collagen crosslinking (CXL), Standard corneal crosslinking (CXL), Transepithelial CXL, Iontophoresis, Riboflavin