The Viability Control of Human Endothelial Cells Before Keratoplasty (V-CHECK) Study

Corneal Endothelial Cell Loss Clinical Trial

— V-CHECK  

Official title:

Preoperative Surgeon Evaluation of Corneal Endothelial Status: the Viability Control of Human Endothelial Cells Before Keratoplasty (V-CHECK) Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05847387
• Other study ID #: VC1
• Status: Recruiting
• Start date: December 1, 2023
• Est. completion date: September 30, 2025

Study information

• Verified date: February 2024
• Source: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
• Contact: Matteo Airaldi, MD
• Phone: +390303995847
• Email: matteo.airaldi[@]unibs.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this international cohort study is to validate a new method for preoperative assessment of endothelial viability in donor corneal tissues for transplantation, and to correlate endothelial health as assessed by the surgical team to functional and structural long-term outcomes in the cohort of patients receiving them.

Description:

The corneal endothelium is responsible for preserving corneal transparency by maintaining a dynamic equilibrium of corneal stromal hydration. Corneal Endothelial Cells (CECs) health is approximated by evaluating the Endothelial Cell Density (ECD) of corneal tissues though specular biomicroscopy. ECD is a key determinant of long-term tissue survival after corneal transplantation, as corneal graft function is directly dependent on the number of viable CECs. However, ECD represents only an estimation of total corneal endothelial health and is a suboptimal proxy for future endothelial failure. In the current chain of supply of donor corneal tissues, no independent evaluation of endothelial cell viability by the surgical team tasked with transplanting the donor corneal tissue is anticipated. The investigators have previously shown a poor correlation between ECD declared by the eye bank providing the tissue and tissue quality as assessed independently by a cornea surgeon performing the transplantation (unpublished data). In this study, the investigators describe a simple method to independently evaluate the overall endothelial viability of donor corneal tissue which can be adopted both by eye banks before shipment and by the corneal surgeons before transplantation in the operating theatre. This method uses basic image analysis to assess the extent of endothelial cell death and/or denuded endothelial areas with the use of Trypan Blue, a vital dye commonly employed during corneal transplantation. Endothelial cell loss is visualized and quantified as Trypan Blue Positive Areas (TBPA). The primary objective of this study is to quantify the extent of TBPA in the operating theatre before corneal transplantation and correlate it to overall donor mortality declared by the eye bank. Secondary objectives include the assessment of the correlation of TBPA with declared ECD and CECs mortality, on folds, as well as the longitudinal analysis of endothelial cell loss as a function of time from surgery and initial TBPA over a follow-up of 12 months, final ECD, incidence of graft failure, and risk of graft failure attributable to preoperative TBPA.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 135
• Est. completion date: September 30, 2025
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age older than 18 years old
• Planned corneal transplantation: perforating keratoplasty (PK), Descemet stripping automated endothelial keratoplasty (DSAEK), ultra-thin DSAEK (UT-DSAEK) or Descemet membrane endothelial keratoplasty (DMEK)
• Indication for corneal transplantation (low-moderate risk of rejection): keratoconus, Fuchs endothelial dystrophy
• Ability to provide written informed consent.

Exclusion Criteria:

• Prior corneal transplantation
• Planned preloaded DSAEK or preloaded DMEK
• Planned keratoplasty not involving corneal endothelium transplantation (i.e., superficial/deep anterior lamellar keratoplasty)
• Evidence of concurrent microbial keratitis
• Evidence of non-infectious or autoimmune keratitis
• Impending or frank corneal perforation
• Uncontrolled, elevated intraocular pressure (IOP)- Previous glaucoma surgery
• Acute or chronic inflammatory/infectious anterior segment uveitis
• Presence of an anterior chamber intraocular lens (IOL) for phakic or aphakic purposes

Related Conditions & MeSH terms

• Corneal Endothelial Cell Loss
• Corneal Transplant Failure

Intervention

Diagnostic Test:
• V-Check
Preoperative analysis of endothelial tissue staining with vital dye (Trypan Blue 0.05%) and image analysis to identify the percentage of Trypan Blue Positive Areas, corresponding to dead endothelial cells and/or denuded areas of endothelium, in tissues destined to keratoplasty

Locations

Country	Name	City	State
Belgium	Antwerp University Hospital	Edegem
Germany	Department of Ophthalmology, University of Cologne	Cologne
Germany	Münster University Hospital	Münster
Italy	IRCCS Azienda Ospedaliero-Universitaria di Bologna	Bologna
Italy	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia	Brescia	BS
Italy	Department of Medical and Surgical Sciences, University Magna Græcia	Catanzaro
Italy	Department of Experimental Medicine, Tor Vergata School of Medicine and Surgery	Roma
Italy	Fondazione Banca degli Occhi del Veneto	Venice
Italy	San Bortolo Hospital	Vicenza
Netherlands	Maastricht University Medical Center	Maastricht
Spain	Hospital Regional Universitario de Málaga	Málaga
United Kingdom	Royal Liverpool University Hospital	Liverpool

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Countries where clinical trial is conducted

Belgium,  Germany,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Trypan Blue Positive Areas (TBPA) percentage and Donor mortality	The comparison of the endothelial mortality of included donor corneas measured preoperatively (TBPA) and the overall endothelial mortality as declared by the eye bank providing the tissue	Preoperative
Secondary	Correlation of TBPA to declared endothelial cell density (dECD)	Spearman's rank correlation coefficient of TBPA and declared Endothelial Cell Density (dECD) as provided by the Eye Bank supplying the tissue	Preoperative
Secondary	Correlation of TBPA to declared endothelial mortality on corneal folds	Spearman's rank correlation coefficient of TBPA and declared Endothelial Cell mortality on corneal folds as provided by the Eye Bank supplying the tissue	Preoperative
Secondary	Final ECD	Final ECD of transplanted corneas at 12 months	1 year after enrollment
Secondary	Rate of endothelial cell loss	Rate of change of ECD over the course of the entire follow-up	1 year after enrollment
Secondary	Incidence of endothelial graft failure	The occurrence of clinically definite corneal edema and/or need for endothelial keratoplasty due to endothelial failure	1 year after enrollment
Secondary	Relative risk of endothelial graft failure associated with TBPA	Calculation through a proportional hazard model of the relative risk of endothelial graft failure attributable to preoperatively measured TBPA	Preoperative