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

NCT04811924 | Terminated Phase 2

• 1 other identifier: CXLMMC2020
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Keratoconus

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (3)

• Clinical haze grade

  1 month, 3 months, 6 months, 12 months and 18 months post-operation.

• Glare

  1 month, 3 months, 6 months, 12 months and 18 months post-operation.

• Higher-order aberrations

  1 month, 3 months, 6 months, 12 months and 18 months post-operation.

Study Arms (2)

CXL with MMC

ACTIVE COMPARATOR

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.

CXL without MMC

PLACEBO COMPARATOR

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

Interventions

Application of 0.02% MMC over 60 seconds post corneal crosslinking. DRUG

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.

CXL with MMC

Corneal crosslinking without the application of 0.02% MMC DRUG

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.

CXL without MMC

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Hôpital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

MeSH Terms

Conditions

Keratoconus

Condition Hierarchy (Ancestors)

Corneal Diseases; Eye Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The study will be double blinded from the patients and the researchers. An external pharmacy will be responsible for preparing the investigational product (IP) in an open manner, which will be transferred to the research pharmacy of the CIUSSS de l'Est-de-l'Île-de-Montréal. The research pharmacy will label and dispense the IP in a blinded manner for study team on the day of treatment and according to the randomization list provided by the study team.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized double blinded prospective clinical trial

Study Record Dates

• First Submitted: February 22, 2021
• First Posted: March 23, 2021
• Study Start: July 26, 2021
• Primary Completion: February 22, 2023
• Study Completion: February 22, 2023
• Last Updated: February 28, 2023

Record last verified: 2023-02

Locations

CA (1)