Non-inferiority Trial of Iontophoretic Corneal Collagen Crosslinking (CXL) Compared to Standard Corneal Collagen Crosslinking in Progressive Keratoconus.

Study Overview
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Brief Summary
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The primary purpose of the protocol is to compare the current standard CXL with iontophoretic CXL to provide evidence in relation to the efficacy and safety in progressive keratoconus. Corneal collagen crosslinking (CXL) is the first surgical procedure that appears to halt the progression of keratoconus. In the current standard CXL, the central corneal epithelium must be debrided to efficiently permeate the corneal stroma with riboflavin. The epithelium debridement can cause severe pain, infection and stromal haze. The study hypothesis is that iontophorese CXL is as effective as standard CXL to stabilize a progressive keratoconus.

Detailed Description
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Keratoconus is a common bilateral progressive corneal ecstatic disease causing visual impairment by inducing irregular astigmatism and corneal opacities. This disorder typically begins during teenage years, progresses until the age of 30 to 40 years and, in severe forms, may need a corneal transplantation. CXL has changed the natural evolution of keratoconus. It creates links between collagen fibrils in order to rigidify the corneal stroma and slow down the progression of keratoconus. The corneal stroma is soaked with a riboflavin solution before being exposed to ultraviolet-A radiation. In the current standard CXL, the central corneal epithelium must be debrided to allow the penetration of riboflavin into the cornea with 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 riboflavin into the cornea. The iontophoresis technique could allow intrastromal riboflavin diffusion, while keeping the corneal epithelium on, combining the efficiency of the standard procedure without the side effects of epithelial debridement.

Official Title
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Non-inferiority Trial of Iontophoretic Corneal Collagen Crosslinking (CXL) Compared to Standard Corneal Collagen Crosslinking in Progressive Keratoconus.

Conditions
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Progressive Keratoconus

Intervention / Treatment
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* Device: Iontophoretic CXL
* Device: Standard CXL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old Corneal thickness ≥ 400 µm Progressive stage 1 to 3 keratoconus (Krumeich classification) Exclusion Criteria: Corneal thickness < 400µm Stage 4 keratoconus (Krumeich classification) Concomitant corneal disease History of corneal surgery

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 |
| --- | --- |
| Experimental: Iontophoretic CXL<br>The iontophoretic CXL involves a constant current source and two electrodes. The main electrode is a circular cup, with a surrounding annular suction ring to affix the device on the cornea during the procedure. The electrode itself is a stainless steel grid, placed into the cup at a minimal distance from the cornea. The reservoir is filled with riboflavin 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 by a UVA light for 3mW/cm2 during 30 minutes. | Device: Iontophoretic CXL<br> <br> |
| Active Comparator: Standard CXL<br>In the standard CXL, the epithelium is mechanically removed. Then, a solution of riboflavin is instilled each minute for 30 minutes. Corneas are irradiated by a UVA light for 3mW/cm2 during 30 minutes. | Device: Standard CXL<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The main outcome parameter is the non-inferiority of iontophoretic CXL compared to standard CXL in progressive keratoconus | Measuring maximum keratometry (K-max) derived from computerized videokeratography. | Outcome measure is assessed at 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of minimum keratometry | Measure assessed by tomographic measurement. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Progressive keratoconus, standard CXL, iontophoretic CXL, keratometry