The Effect of Mitomycin C on Corneal Haze and Scarring After Corneal Crosslinking in Keratoconus Patients

Study Overview
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Brief Summary
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Corneal crosslinking (Crosslinking, CXL) is a treatment offered for the stabilization of early corneal ectatic disorders such as keratoconus. Although CXL is an excellent treatment option to stabilize early ectatic corneas, complications include corneal haze, sterile infiltrate, endothelial cell toxicity, treatment failure and stromal scarring. Corneal haze is a common finding in almost all CXL patients and may decrease visual quality. The effect of 0.02% mitomycin C (MMC) for 2 minutes on corneal haze and scarring in refractive surgery is well established in the literature with many clinical studies confirming its effectiveness. Although the pattern of corneal haze after CXL appears to be different from the haze pattern seen following refractive procedures, both processes are thought to be caused by an inflammatory response. The investigators postulate that MMC can reduce post-CXL haze and scars when using the optimal concentration and duration of exposure.

Official Title
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The Effect of Mitomycin C on Corneal Haze and Scarring After Corneal Crosslinking in Keratoconus Patients

Conditions
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Keratoconus

Intervention / Treatment
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* Drug: Application of 0.02% MMC over 60 seconds post corneal crosslinking.
* Drug: Corneal crosslinking without the application of 0.02% MMC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients from both genders with confirmed keratoconus with evidence of clinical and topographic progression. Patients with the diagnosis of other ectatic disorders such as post refractive surgery ectasia with evidence of clinical and topographic progression. Exclusion Criteria: Patients who are pregnant Patients who are breast-feeding Patients who have allergy to MMC Patients with other corneal conditions such as limbal stem cell deficiency (LSCD) Patients with peripheral marginal keratitis Patients with history of corneal melting Patients with history of HSV/VZV keratitis Patients with history of hydrops

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized double blinded prospective clinical trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CXL with MMC<br>Patients who have undergone corneal cross-linking (CXL) with the application of Mitomycin C (MMC). | Drug: Application of 0.02% MMC over 60 seconds post corneal crosslinking.<br>* Topical application of 0.02% MMC on the surface of the cornea post CXL. The surface of the eye is washed thoroughly with Balanced Salt Solution (BSS) over 1 minute after MMC application.<br>|
| Placebo Comparator: CXL without MMC<br>Patients who have undergone corneal cross-linking (CXL) without the application of Mitomycin C (MMC). | Drug: Corneal crosslinking without the application of 0.02% MMC<br>* Topical application of placebo on the surface of the cornea post CXL. The surface of the eye is washed thoroughly with Balanced Salt Solution (BSS) over 1 minute after placebo application.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corneal haze/scarring | Corneal haze or scarring will be measured by densitometry. Densitometry values obtained from Scheimpflug images (software 70722, Pentacam HR, Oculus, Germany) will inform backward light scattered reflected by the cornea and therefore reflect the amount of stromal haze, and expressed as grayscale units (GSU), defining the backscattered light in a 0 to 100 scale in concentric zones. A 6mm central zone will be used for the analysis and compartmentalized in: anterior 160 microns depth (epithelium, bowman and anterior stroma), posterior 60 microns depth (endothelium, Descemet and posterior stroma) and the layer in between. | 1 month post-operation | 
| Corneal haze/scarring | Corneal haze or scarring will be measured by densitometry. Densitometry values obtained from Scheimpflug images (software 70722, Pentacam HR, Oculus, Germany) will inform backward light scattered reflected by the cornea and therefore reflect the amount of stromal haze, and expressed as grayscale units (GSU), defining the backscattered light in a 0 to 100 scale in concentric zones. A 6mm central zone will be used for the analysis and compartmentalized in: anterior 160 microns depth (epithelium, bowman and anterior stroma), posterior 60 microns depth (endothelium, Descemet and posterior stroma) and the layer in between. | 3 months post-operation | 
| Corneal haze/scarring | Corneal haze or scarring will be measured by densitometry. Densitometry values obtained from Scheimpflug images (software 70722, Pentacam HR, Oculus, Germany) will inform backward light scattered reflected by the cornea and therefore reflect the amount of stromal haze, and expressed as grayscale units (GSU), defining the backscattered light in a 0 to 100 scale in concentric zones. A 6mm central zone will be used for the analysis and compartmentalized in: anterior 160 microns depth (epithelium, bowman and anterior stroma), posterior 60 microns depth (endothelium, Descemet and posterior stroma) and the layer in between. | 6 months post-operation | 
| Corneal haze/scarring | Corneal haze or scarring will be measured by densitometry. Densitometry values obtained from Scheimpflug images (software 70722, Pentacam HR, Oculus, Germany) will inform backward light scattered reflected by the cornea and therefore reflect the amount of stromal haze, and expressed as grayscale units (GSU), defining the backscattered light in a 0 to 100 scale in concentric zones. A 6mm central zone will be used for the analysis and compartmentalized in: anterior 160 microns depth (epithelium, bowman and anterior stroma), posterior 60 microns depth (endothelium, Descemet and posterior stroma) and the layer in between. | 12 months post-operation | 
| Corneal haze/scarring | Corneal haze or scarring will be measured by densitometry. Densitometry values obtained from Scheimpflug images (software 70722, Pentacam HR, Oculus, Germany) will inform backward light scattered reflected by the cornea and therefore reflect the amount of stromal haze, and expressed as grayscale units (GSU), defining the backscattered light in a 0 to 100 scale in concentric zones. A 6mm central zone will be used for the analysis and compartmentalized in: anterior 160 microns depth (epithelium, bowman and anterior stroma), posterior 60 microns depth (endothelium, Descemet and posterior stroma) and the layer in between. | 18 months post-operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical haze grade | Using slit lamp exam as established in the literature on a scale (the slit lamp clinical haze/scar density grade) ranging from 0 (minimum value) to 4 (maximum value); which means the higher the score, the worse the stromal haze/density is. | 1 month, 3 months, 6 months, 12 months and 18 months post-operation. | 
| Glare | This will be measured in the treated eye and reported as the logarithm of the straylight parameter. | 1 month, 3 months, 6 months, 12 months and 18 months post-operation. | 
| Higher-order aberrations | Higher-order aberrations (OPDScan wavefront analyzer, Gamagori, Japan) will be expressed as Zernike polynomials through the sixth order over a 6 mm diameter optical zone. HOA will allow further assessment of the optical quality of the eye. | 1 month, 3 months, 6 months, 12 months and 18 months post-operation. |