Transepithelial Corneal Cross-linking Using Iontophoresis

Study Overview
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Brief Summary
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The purpose of the present Randomized Clinical Trial (RCT) is to compare the efficacy and safety of transepithelial corneal cross-linking using iontophoresis (T-ionto CL) to treat progressive keratoconus in comparison with standard cross-linking (standard CL).

Detailed Description
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Keratoconus is a progressive corneal ectatic disease causing visual impairment by inducing irregular astigmatism and corneal opacity. This disorder typically begins during the second decade of life and, in severe forms, may need a corneal transplantation. Corneal cross-linking with riboflavin and UV-A is a procedure intended to halt keratoconus progression. It generates additional chemical bonds between stromal proteins in order to stiffen the corneal tissue. Standard CL includes epithelial removal and stroma soaking with dextran-enriched 0.1% riboflavin solution for 30 minutes before being exposed to ultraviolet-A radiation using a 3mW/cm2 lamp for 30 minutes. Epithelial debridement exposes the cornea to a risk of side effects, such as pain for the first two post-operative days, temporary loss of visual acuity during the first three months, and serious complications, such as infection and stromal opacity due to corneal scarring. Iontophoresis is a non invasive technique in which a weak electric current is used to enhance the penetration of hypotonic 0.1% riboflavin-5-phosphate solution into the corneal stroma through the intact epithelium. After iontophoresis, the corneal tissue is irradiated using a 10 mW/cm2 for 9 minutes (T-ionto CL). From previous experimental work (Lombardo M. et al. JCRS 2014 and JCRS 2015), the investigators provided evidence that T-ionto CL increases the stiffness of human corneas with results almost comparable with standard CL. The new procedure holds the promise to be as effective as the standard procedure while minimizing all the related risks. It is object of the present clinical trial to randomize patients with progressive keratoconus to T-ionto CL and standard CL and compare efficacy and safety of treatments.

Official Title
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Randomized Clinical Trial Comparing Transepithelial Corneal Cross-linking Using Iontophoresis and Standard Corneal Cross-linking for the Treatment of Keratoconus

Conditions
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Progressive Keratoconus

Intervention / Treatment
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* Device: Cross-linking with iontophoresis
* Device: Standard corneal cross-linking


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of progressive keratoconus Exclusion Criteria: Anterior corneal curvature steeper than 61 D; central corneal thickness <400 um corneal scarring; descemetocele; history of herpetic keratitis; Concomitant eye diseases; Inflammatory eye diseases; Glaucoma; Cataract; Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 46 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
Interventional Model Description: Consecutive patients were randomized, using block randomization model, in one of the arm
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cross-linking with iontophoresis<br>Transepithelial cross-linking by using iontophoresis to administer riboflavin into the corneal stroma | Device: Cross-linking with iontophoresis<br>* The procedure involves a constant current source and two electrodes. The active electrode is a bath tube, which includes a stainless steel grid, placed into the cup at a minimal distance from the cornea. The reservoir is filled with dextran-free, hypotonic riboflavin-5-phosphate solution. The generator applies a constant current of 1mA for a preset period of 5 min. After the riboflavin administration by iontophoresis, the cornea is irradiated using a UVA lamp of 10mW/cm2 for 9 minutes.<br>* Other names: Ricrolin+;|
| Active Comparator: Standard corneal cross-linking<br>Standard corneal cross-linking includes de-epithelialization and stromal soaking by applying drops of riboflavin | Device: Standard corneal cross-linking<br>* In the standard CL, the epithelium is mechanically removed. Then, a solution of riboflavin is instilled each minute for 30 minutes. Corneas are irradiated using a UVA lamp of 3mW/cm2 for 30 minutes.<br>* Other names: Ricrolin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| K-max | Measuring maximum keratometry (K-max), measured in diopters (D), derived from computerized videokeratography. | Changes from baseline in Kmax at 12 months | 
| Corneal Endothelial Cell Density | Endothelial cell density (ECD) will be evaluated using specular microscopy | Changes from baseline in ECD at 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optical Aberrations | Optical aberrations of the eye will be measured using dynamic skyascopy. Corneal wavefront aberration will be measured using Placido disk topographer and Scheimpflug tomographer. | Changes from baseline at 12 months. | 
| Visual Acuity | Visual acuity tested using ETDRS | Changes from baseline at 12 months. | 
| Contrast Sensitivity | Contrast sensitivity tested using Pelli-Robson chart | Changes from baseline at 12 months. | 
| Central Retinal Thickness | Central retinal thickness (1 mm ETDRS map) will be measured before and after CXL procedures | Changes from baseline at 12 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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corneal cross-linking, transepithelial corneal cross-linking, iontophoresis, progressive keratoconus