Corneal Collagen Crosslinking to Increase the Resistance of the Support Graft of the KPro Type I Against Corneal Melting

Corneal Melting in Boston Keratoprosthesis Type I Clinical Trial

— CXL-KPro  

Official title:

Corneal Collagen Crosslinking to Increase the Resistance of the Graft Used as a Support for the Boston Keratoprosthesis Type I Against Corneal Melting

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03041883
• Other study ID #: CE14.362
• Status: Recruiting
• Phase: N/A
• Start date: January 4, 2017
• Est. completion date: January 2025

Study information

• Verified date: April 2024
• Source: Centre hospitalier de l'Université de Montréal (CHUM)
• Contact: Marie-Catherine Tessier
• Phone: 514-890-8000
• Email: marie-catherine.tessier.chum[@]ssss.gouv.qc.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to demonstrate the safety and efficacy of the corneal collagen crosslinking with riboflavin and ultraviolet A in aim to increase the resistance of the graft used as a support for the Boston keratoprosthesis (KPro) type I against corneal melting (keratolysis or sterile necrosis).

Description:

The Boston type 1 keratoprosthesis (KPro) is an artificial cornea that restores the clarity of the visual axis. It is indicated in patients for whom conventional corneal transplantation offers a very low probability of success. Several innovations have led to improved outcomes following implantation of a KPro. However, retention of the KPro varies between 83 and 100% in the most recent series. The extrusion of the KPro is usually caused by the melting of the corneal tissue (keratolysis or sterile necrosis) used as a support.

This corneal melting is mediated by enzymes from the class of the matrix metalloproteinases (MMP). Several different types of insults may lead to an excess of these enzymes. Chronic inflammation of the ocular surface is undoubtedly the best recognized risk factor. Indeed, autoimmune diseases such as Stevens-Johnson syndrome, Lyell syndrome (toxic epidermal necrolysis, TENS) and mucous membrane pemphigoid, has the highest rate of corneal melting post KPro. Moreover, the development of a retroprosthetic membrane has recently been recognized as a risk factor for melting. Furthermore, the dryness of the corneal epithelium, due to insufficient tear production or an alteration of the blink reflex of the eye, can also lead to an overexpression of MMP. Finally, infectious keratitis can lead to significant thinning of the corneal tissue, even once the infectious process is resolved.

Corneal collagen cross-linking is a technique approved by Health Canada for strengthening the biomechanical properties of the cornea. The crosslinked corneas become more resistant to collagenase and other MMP. The use of a crosslinked corneal graft as a support for the KPro is an interesting approach to the prevention of corneal melting.

A prospective, randomized, controlled and double-blind study will be conducted with patients receiving a Kpro at the Centre Hospitalier de l'Université de Montréal. Forty patients will be randomized into two groups, half will receive KPro in a crosslinked graft-support, while the other half will receive a usual graft-support. Patients will be met by their surgeon to discuss the risks, benefits of the KPro type I and alternatives treatments. Patients accepting KPro surgery, will be informed of the nature and course of the study and will be offered to participate in the study. The Eye bank of Canada will manage the randomization and maintain the codes identifying the crosslinked corneas from the untreated corneas, keeping both the surgeon and the patient blinded. Randomization will be done through a free application (http://www.randomizer.org/form.htm). A series of 10 numbers will be generated. Even numbers indicate crosslinked corneas and odd numbers indicate non-crosslinked corneas. The order of the digits will increase as for each subject is enrolled in the study. The procedure for corneal collagen crosslinking will be performed at the Eye Bank of Canada in a similar procedure to the treatment for keratoconus. Under sterile conditions, the corneo-scleral button will be inspected to meet the standard of care. If the patient is randomized to the crosslinked group, then the cornea will be treated with crosslinking as described further. If the patient is randomized the control group, the cornea will not be treated with crosslink but will be deepithelialized and soaked with riboflavin drops as described further.

The surgeon will receive the graft and operate according to the standard procedure. The KPro surgery and postoperative care will be performed in the standard way and thus will be the same for both study groups. Postoperative follow will be held at 1 day, 1 week, 2 weeks, 1 month and 3 months and will continue subsequently every 2-4 months depending on the judgment of the surgeon. These visits will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination. In particular, the presence of corneal melting, leakage of aqueous humor, corneal infection and extrusion will be noted. Meanwhile, an imaging allowing quantification of the thickness of the cornea graft-support (optical coherence tomography anterior segment) will be performed at least once during the first three months postoperative. This imaging will be repeated at 1, 2 and 5 years.

The prevalence of various complications (melting, leak, infection, extrusion) will be compared between the two groups with the Fischer exact test. Also, the time between surgery and the occurrence of complications will be compared using the Student t test. Finally, survival analysis of Kaplan-Meier will be performed for 1) the occurrence of corneal melting and 2) maintaining a visual acuity greater than 20/200.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Candidate for KPro type I

• Capacity to give written consent

• Ability to be followed for the duration of the study

Exclusion Criteria:

• Participation in another interventional study

• Failure to wear a therapeutic contact lens due to abnormalities of the eyelids.

• Inability to give written consent

Contraindications to the KPro type I:

• Severe dryness with keratinization of the ocular surface

• Intraocular tumor

• Terminal glaucoma

• Inoperable retinal detachment

• Phthisis bulbi

Related Conditions & MeSH terms

• Corneal Melting in Boston Keratoprosthesis Type I
• Corneal Ulcer

Intervention

Procedure:
• Crosslinking with riboflavin of the corneal graft-support
Corneal graft support for the KPro will be crosslinked and used with the standard surgical technique
• De-epithelisation of the corneal graft support with instillation of riboflavin
Corneal graft-support will be de-epithelialized and soaked with riboflavin and then used with the standard surgical technique

Locations

Country	Name	City	State
Canada	Centre Hospitalier de l'Université de Montréal	Montreal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Centre hospitalier de l'Université de Montréal (CHUM)	Maisonneuve-Rosemont Hospital

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Examine whether the use of crosslinked cornea decreases the rate of corneal melting post-Kpro when compared to using a standard corneal button	This visit will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	1 day
Primary	Examine whether the use of crosslinked cornea decreases the rate of corneal melting post-Kpro when compared to using a standard corneal button	This visit will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	1 week
Primary	Examine whether the use of crosslinked cornea decreases the rate of corneal melting post-Kpro when compared to using a standard corneal button	This visit will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	2 weeks
Primary	Examine whether the use of crosslinked cornea decreases the rate of corneal melting post-Kpro when compared to using a standard corneal button	This visits will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	1 month
Primary	Examine whether the use of crosslinked cornea decreases the rate of corneal melting post-Kpro when compared to using a standard corneal button	An imaging allowing quantification of the thickness of the cornea graft-support (optical coherence tomography anterior segment) will be performed.	1 month
Primary	Examine whether the use of crosslinked cornea decreases the rate of corneal melting post-Kpro when compared to using a standard corneal button	This visit will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	3 months
Primary	Examine whether the use of crosslinked cornea decreases the rate of corneal melting post-Kpro when compared to using a standard corneal button	These visits will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	Every 2-4 months depending on the judgment of the surgeon for at least 5 years
Primary	Examine whether the use of crosslinked cornea decreases the rate of corneal melting post-Kpro when compared to using a standard corneal button	An imaging allowing quantification of the thickness of the cornea graft-support (optical coherence tomography anterior segment) will be performed.	1 year
Primary	Examine whether the use of crosslinked cornea decreases the rate of corneal melting post-Kpro when compared to using a standard corneal button	An imaging allowing quantification of the thickness of the cornea graft-support (optical coherence tomography anterior segment) will be performed.	2 years
Primary	Examine whether the use of crosslinked cornea decreases the rate of corneal melting post-Kpro when compared to using a standard corneal button	An imaging allowing quantification of the thickness of the cornea graft-support (optical coherence tomography anterior segment) will be performed.	5 years
Secondary	Comparison of the rates of infectious keratitis between the groups	This visit will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	1 day
Secondary	Comparison of the rates of infectious keratitis between the groups	This visit will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	1 week
Secondary	Comparison of the rates of infectious keratitis between the groups	This visit will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	2 weeks
Secondary	Comparison of the rates of infectious keratitis between the groups	This visit will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	1 month
Secondary	Comparison of the rates of infectious keratitis between the groups	This visits will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	3 months
Secondary	Comparison of the rates of infectious keratitis between the groups	These visits will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	Every to 2-4 months depending on the judgment of the surgeon for at least 5 years
Secondary	Comparison of the rates of extrusion of the KPro between the groups	This visit will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	1 day
Secondary	Comparison of the rates of extrusion of the KPro between the groups	This visit will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	1 week
Secondary	Comparison of the rates of extrusion of the KPro between the groups	This visit will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	2 weeks
Secondary	Comparison of the rates of extrusion of the KPro between the groups	This visit will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	1 month
Secondary	Comparison of the rates of extrusion of the KPro between the groups	This visit will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	3 months
Secondary	Comparison of the rates of extrusion of the KPro between the groups	These visits will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	Every to 2-4 months depending on the judgment of the surgeon for at least 5 years
Secondary	Comparison of the visual acuity between the groups	This visit will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	1 day
Secondary	Comparison of the visual acuity between the groups	This visit will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	1 week
Secondary	Comparison of the visual acuity between the groups	This visit will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	2 weeks
Secondary	Comparison of the visual acuity between the groups	This visit will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	1 month
Secondary	Comparison of the visual acuity between the groups	This visit will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	3 months
Secondary	Comparison of the visual acuity between the groups	This visit will include measurement of visual acuity and intraocular pressure and a full slit-lamp examination.	Every to 2-4 months depending on the judgment of the surgeon for at least 5 years