Corneal Crosslinking Treatment Study

Study Overview
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Brief Summary
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Three different protocols for inducing corneal crosslinks in subjets with progressive keratoconus will be evaluated in this randomised clinical study.

Detailed Description
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Riboflavin does not penetrate the intact corneal epithelium. Corneal cross linking (CXL) is typically performed using the so-called Dresden protocol. The Dresden protocol states 30 minutes of UVA-radiation (3mW/cm2) but a 10 minute irradiation protocol (9mW/cm2) is frequently used. Both of the protocols involve mechanical removal of the epithelium over the central 8 mm of the corneal surface. The first days after treatment therefore involves some degree of pain, often intense, and the presence of a healing epithelial defect may be associated with development of infiltrates in the cornea. A number of approaches have been evaluated in order to promote riboflavin penetration through the intact epithelium, of which iontophoresis appears most promising. Keratoconic corneas are thin at the cone location and sometimes it is difficult to maintain the safety margin of 400 microns during corneal crosslinking. Instead of using isotonic standard riboflavin, a swelling effect of the cornea can be obtained by using hypotonic riboflavin. However, the latter has been indicated as less effective in the process of inducing cross links. Eighty-one of 81 patients of various degrees of keratoconus will be randomised to one of the following groups: 1) CXL (UVA 9mW/cm2) using isotonic riboflavin, or 2) CXL (UVA 9mW/cm2) using hypotonic riboflavin or 3) Iontophoresis with Ricrolin with following CXL (UVA 9mW/cm2). Hypothesis: i) CXL with hypotonic riboflavin or CXL with Ricrolin administered by iontophoresis or CXL with isotonic riboflavin is non-inferior compared to standard CXL with isotonic riboflavin. ii) The morphological structure post-CXL in the three different groups will be similar without any significant differences.

Official Title
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Prospective Randomised Corneal Crosslinking Study

Conditions
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Progressive Keratoconus

Intervention / Treatment
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* Procedure: Corneal crosslinking: CXL (UVA 9mW/cm2)
* Drug: Isotonic riboflavin
* Drug: Hypotonic riboflavin
* Procedure: Iontophoresis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Progress in keratoconic eye. We define progress as an increase in Kmax of 1.0 diopter in 1 year or 0.5 diopter in 6 months. This increase in Kmax will be accepted as progression if concomitant changes tomographic parameters. Exclusion Criteria: Concurrent ocular infection or corneal disease other than keratoconus. Pregnancy. Treatment with Isotretinoin.

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
Interventional Model Description: Prospective randomized interventional clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Isotonic riboflavin<br>CXL (UVA 9mW/cm2) treatment using isotonic riboflavin | Procedure: Corneal crosslinking: CXL (UVA 9mW/cm2)<br>* CXL treatment with UVA-radiation (9mW/cm2) with a 10 minute irradiation protocol.<br>Drug: Isotonic riboflavin<br>* CXL protocol with isotonic riboflavin<br>|
| Active Comparator: Hypotonic riboflavin<br>CXL (UVA 9mW/cm2) using hypotonic riboflavin | Procedure: Corneal crosslinking: CXL (UVA 9mW/cm2)<br>* CXL treatment with UVA-radiation (9mW/cm2) with a 10 minute irradiation protocol.<br>Drug: Hypotonic riboflavin<br>* CXL protocol with hypotonic riboflavin<br>|
| Active Comparator: Iontophoresis<br>Iontophoresis with Ricrolin with following CXL (UVA 9mW/cm2). | Procedure: Corneal crosslinking: CXL (UVA 9mW/cm2)<br>* CXL treatment with UVA-radiation (9mW/cm2) with a 10 minute irradiation protocol.<br>Procedure: Iontophoresis<br>* CXL protocol with iontophoresis and ricrolin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative change in visual acuity | Uncorrected visual acuity (UCVA) and best spectacle corrected visual acuity (BSCVA) | Patients will be evaluated 1, 6, 12 and 24 months after treatment. | 
| Postoperative change in Kmax | Maximum corneal steepness | Patients will be evaluated 1, 6, 12 and 24 months after treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative change in astigmatism | Corneal astigmatism | Patients will be evaluated 1, 6, 12 and 24 months after treatment. | 
| postoperative change in corneal nerve cell density | Corneal nerve cell density will be evaluated using confocal microscopy | Confocal microscopy will be performed at 6 and 12 months. | 
| Postoperative change in Keratocyte cell density | Keratocyte cell density will be evaluated using confocal microscopy | Confocal microscopy will be performed at 6 and 12 months. | 
| Postoperative change in endothelial cell count | Endothelial cell count will be evaluated using confocal microscopy | Confocal microscopy will be performed at 6 and 12 months. | 
| Postoperative change in demarcation lines | Identification of the demarcation lines with confocal microscopy will help establishing how deep was the effect of the CXL treatment. | Confocal microscopy will be performed at 6 and 12 months. | 
| Postoperative change in the corneal thickness during CXL treatment | Corneal pachymetry is the process of measuring the thickness of the cornea | Corneal pachymetry will be evaluated before and then every 5 minutes during 30 minutes under CXL treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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corneal crosslinking