Standard Versus Transepithelial Corneal Crosslinking

Study Overview
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Brief Summary
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The gold standard corneal crosslinking (CXL) technique involves the initial step of epithelial removal, in order to achieve a sufficient treatment effect (meaning: stabilisation of progressive keratoconus (KC). Our aim is to evaluate the effects of transepithelial CXL (TE-CXL), whereby the epithelium is left intact and the cornea is instead treated by a solution composed of 0.1% riboflavin, combined with enhancers, after which standard CXL is performed. This solution seems to facilitate riboflavin penetration into the corneal stroma through the intact epithelium. The investigators expect to achieve a similar effect of TE-CXL with the advantage of a faster healing time and less risk of infections.

Official Title
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Standard Versus Transepithelial Corneal Crosslinking for Treatment of Progressive Keratoconus

Conditions
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Keratoconus

Intervention / Treatment
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* Procedure: Transepithelial versus epithelium-off CXL
* Drug: Ricrolin TE
* Drug: Isotonic riboflavin


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. For this research study, the inclusion parameters will be the same as mentioned above, with the following additional inclusion criteria: Documented progression of KC, as demonstrated by anterior segment imaging and/or corneal topography: o Defined an increase in maximal keratometry, steepest keratometry, mean keratometry or topographic cylinder value by ≥ 0.5 D over the previous 6 months and/or a decrease in thinnest pachymetry Documented progression of KC defined by increase in refractive cylinder of ≥ 0.5 D over the previous 6 months Exclusion Criteria: Presence of corneal scars. History of epithelial healing problems. Presence of previous ocular infection (such as herpes keratitis). Patients who are pregnant 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: epithelium off CXL<br>epithelium removal + 30 minute isotonic riboflavin eye drops (3 minute interval) + 30 minutes ultraviolet-A irradiation (riboflavin every 5 minutes) | Procedure: Transepithelial versus epithelium-off CXL<br>* A comparison of the CXL procedure with and without epithelium removal<br>* Other names: epithelium-on versus epithelium-ff corneal crosslinking;Drug: Isotonic riboflavin<br>* After epithelium removal, isotonic riboflavin was instilled during 30 minutes before ultraviolet-A irradiation<br>|
| Experimental: Ricrolin TE CXL<br>Ricrolin-TE eye drops for 15 minutes (2 minute interval) and 15 minute Ricrolin TE pooled on the cornea using a silicone ring + 30 minutes ultraviolet-A irradiation (Ricrolin TE every 5 minutes). | Procedure: Transepithelial versus epithelium-off CXL<br>* A comparison of the CXL procedure with and without epithelium removal<br>* Other names: epithelium-on versus epithelium-ff corneal crosslinking;Drug: Ricrolin TE<br>* Ricrolin TE was instilled during 30 minutes before ultraviolet-A irradiation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical stabilisation of keratoconus one year after CXL | Using a Scheimpflug device (Pentacam, Oculus), topography measurements are performed. Clinical stabilisation is defined as an increase of no more than 1 diopter of the maximum keratometry value over the preoperative maximum keratometry value. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complications, defined as epithelial healing problems and/or keratitis. | the incidence of epithelial healing problems after treatment will be recorded | 1 year |