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

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.

Study Overview

• Status: Terminated
• Conditions: Keratoconus
• Intervention / Treatment: Drug: Application of 0.02% MMC over 60 seconds post corneal crosslinking.; Drug: Corneal crosslinking without the application of 0.02% MMC

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dorline Sokoundjou; Phone Number: 7114 514-252-3400; Email: bfv2.hmr@ssss.gouv.qc.ca

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H1T 2M4
      • Hopital Maisonneuve-Rosemont

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CXL with MMC; 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.; 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.
Placebo Comparator: CXL without MMC; 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; 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.

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Ciusss de L'Est de l'Île de Montréal

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2021
• Primary Completion (Actual): February 22, 2023
• Study Completion (Actual): February 22, 2023

Study Registration Dates

• First Submitted: February 22, 2021
• First Submitted That Met QC Criteria: March 22, 2021
• First Posted (Actual): March 23, 2021

Study Record Updates

• Last Update Posted (Estimate): February 28, 2023
• Last Update Submitted That Met QC Criteria: February 27, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Keratoconus
• Other Study ID Numbers: CXLMMC2020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No