Collagen Crosslinking for Keratoconus - a Randomized Controlled Clinical Trial

Study Overview
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Brief Summary
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The purpose of this study is to determine whether corneal collagen crosslinking is effective in the treatment of progressive keratoconus.

Detailed Description
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Keratoconus is a noninflammatory, asymmetrical, progressive corneal ectasia caused by biomechanical instability of the corneal stroma. Treatment modalities are primarily glasses or contact lenses. It has been estimated that one out of five patients will progress to such an extent that a corneal transplant is necessary to regain useful vision. Corneal collagen crosslinking (CXL) is a treatment modality that intends to halt progression of keratoconus. This study investigates the efficacy av CXL in stabilizing the cornea in keratoconus by means of a randomized controlled clinical trial. Participants are eligible for inclusion if progressive keratoconus is confirmed and the inclusion criteria are met. Follow-up after inclusion is at 1 week (treatment group), 1, 3, 6 and 12 months. Pre- and post-inclusion examinations include measurement of uncorrected distance visual acuity (UCDVA), best spectacle corrected distance visual acuity (BSCDVA), Scheimpflug-topography and slitlamp examination.

Official Title
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Collagen Crosslinking for Keratoconus - a Randomized Controlled Clinical Trial

Conditions
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Keratoconus

Intervention / Treatment
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* Device: Corneal Collagen Crosslinking


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Keratoconus diagnosis determined clinically and topographically (KISA%- index) Significant progression is defined as change (increase) of Kmax by at least 1D from baseline at 6 months and/or change (increase) of Sim-K-ast by at least 1D from baseline at 6 months. Kmax is defined as the steepest radius of curvature (either the maximum simulated K-reading or the maximum K-reading in the 3-mm zone or the 5-mm zone) of the anterior corneal surface that progressed the most during 6 months observation Ability to stop contact lens (rigid and soft) wear at least two weeks prior to next exam Signed written informed consent Exclusion Criteria: Age < 18 years Pregnancy Breast feeding History of corneal surgery History of ocular herpes simplex infection Minimal corneal thickness < 300 micrometers Recurrent corneal erosions Other corneal (e g endothelial) or conjunktival diseases Neurodermatitis Severe forms av atopic disease Collagenoses, autoimmune or other systemic disease Systemic treatment with high doses of steroids Severe scarring och striae of the cornea Relative exclusion criteria: Kmax > 58D Minimal corneal thickness < 400 micrometers (a modified CXL-treatment will be used swelling the cornea before UV-illumination treatment).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 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: Corneal Collagen Crosslinking<br>The keratokonic eye which progresses most is included and randomized. Significant progression is defined in the eligibility criteria section. If randomized to the treatment arm the cornea is treated with collagen crosslinking as described below. | Device: Corneal Collagen Crosslinking<br>* Keratoconic corneas that show significant progression as specified in the inclusion criteria section will receive one single treatment with CXL if randomized to the treatment arm. A treatment protocol based on 30 minutes dropping with riboflavin/dextran solution and 10 minutes UV-illumination treatment will be used.<br>* Other names: Innocross-R hypotonic riboflavin 0.1%;|
| No Intervention: Control group<br>The keratokonic eye which progresses most is included and randomized to either the treatment group (CXL) or the control group. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kmax | Kmax is defined as the steepest radius of curvature of the anterior corneal surface. It is measured by Scheimpflug-topography (Pentacam, Oculus Inc.). An increase of less than 1 diopter (D) from baseline at 12 months is defined as non-progression. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sim-K-astigmatism | Sim-K-astigmatism (Sim-K-ast) is defined as the absolute amount of anterior corneal astigmatism related to the Sim-Ks as measured by Scheimpflug-topography (Pentacam, Oculus Inc.). An increase of less than 1 D from baseline at 12 months is defined as non progression. | 12 months | 
| MRSE | Manifest Refractive Spherical Equivalent. The spherical equivalent is calculated by algebraic addition of the spherical power and half the cylindrical power of an eye. An eye with a specific spherical equivalent power has the closest overall effect to a given toric lens. A decrease of less than 0.5 D from baseline at 12 months is defined as non-progression. | 12 months | 
| UCDVA | UCDVA is defined as the uncorrected distance visual acuity measured with an Early Treatment of Diabetic Retinopathy Study (ETDRS)-chart and expressed in numbers of letters. A decrease of less than 5 letters (one line) from baseline at 12 months is defined as stable BCDVA. | 12 months | 
| BSCDVA | BSCDVA is defined as the the best spectacle corrected distance visual acuity measured with an ETDRS-chart and expressed in numbers of letters. A decrease of less than 5 letters (one line) from baseline at 12 months is defined as stable BCDVA. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Collagen crosslinking, Keratoconus