Clinical trial NCT05847387: The Viability Control of Human Endothelial Cells Before Keratoplasty (V-CHECK) Study
Official title: Preoperative Surgeon Evaluation of Corneal Endothelial Status: the Viability Control of Human Endothelial Cells Before Keratoplasty (V-CHECK) Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Corneal Transplant Failure
Corneal Endothelial Cell Loss
Keywords: Keratoplasty
Corneal endothelium
Eye Banking
Lead sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Sponsor class: OTHER
First posted: 2023-05-06
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Consecutive patients undergoing keratoplasty at participating referral cornea clinics

Brief 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.

Detailed 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providing the tissue and tissue quality as assessed independently by a cornea surgeon performing the transplantation (unpublished data).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.

Eligibility criteria: 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

Primary outcomes:
measure: Trypan Blue Positive Areas (TBPA) percentage and Donor mortality
timeFrame: Preoperative
Secondary outcomes:
measure: Correlation of TBPA to declared endothelial cell density (dECD)
timeFrame: Preoperative
measure: Correlation of TBPA to declared endothelial mortality on corneal folds
timeFrame: Preoperative
measure: Final ECD
timeFrame: 1 year after enrollment
measure: Rate of endothelial cell loss
timeFrame: 1 year after enrollment
measure: Incidence of endothelial graft failure
timeFrame: 1 year after enrollment
measure: Relative risk of endothelial graft failure associated with TBPA
timeFrame: Preoperative
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: Antwerp University Hospital
city: Cologne
country: Germany
facility: Department of Ophthalmology, University of Cologne
city: Münster
country: Germany
facility: Münster University Hospital
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
state: BS
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna
city: Catanzaro
country: Italy
facility: Department of Medical and Surgical Sciences, University Magna Græcia
city: Roma
country: Italy
facility: Department of Experimental Medicine, Tor Vergata School of Medicine and Surgery
city: Venice
country: Italy
facility: Fondazione Banca degli Occhi del Veneto
city: Vicenza
country: Italy
facility: San Bortolo Hospital
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
Study officials:
affiliation: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
name: Vito Romano, MD
role: PRINCIPAL_INVESTIGATOR
References: