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

Recruiting
Conditions
Corneal Transplant Failure
Corneal Endothelial Cell Loss
Interventions
Diagnostic Test: V-Check
Registration Number
NCT05847387
Lead Sponsor
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
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providing the tissue and tissue quality as assessed independently by a cornea surgeon performing the transplantation (unpublished data).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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
135
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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Keratoplasty groupV-CheckPatients undergoing keratoplasty and their respective donor tissue
Primary Outcome Measures
NameTimeMethod
Trypan Blue Positive Areas (TBPA) percentage and Donor mortalityPreoperative

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

Secondary Outcome Measures
NameTimeMethod
Final ECD1 year after enrollment

Final ECD of transplanted corneas at 12 months

Correlation of TBPA to declared endothelial mortality on corneal foldsPreoperative

Spearman's rank correlation coefficient of TBPA and declared Endothelial Cell mortality on corneal folds as provided by the Eye Bank supplying the tissue

Correlation of TBPA to declared endothelial cell density (dECD)Preoperative

Spearman's rank correlation coefficient of TBPA and declared Endothelial Cell Density (dECD) as provided by the Eye Bank supplying the tissue

Relative risk of endothelial graft failure associated with TBPAPreoperative

Calculation through a proportional hazard model of the relative risk of endothelial graft failure attributable to preoperatively measured TBPA

Rate of endothelial cell loss1 year after enrollment

Rate of change of ECD over the course of the entire follow-up

Incidence of endothelial graft failure1 year after enrollment

The occurrence of clinically definite corneal edema and/or need for endothelial keratoplasty due to endothelial failure

Trial Locations

Locations (12)

Department of Ophthalmology, University of Cologne

🇩🇪

Cologne, Germany

Maastricht University Medical Center

🇳🇱

Maastricht, Netherlands

IRCCS Azienda Ospedaliero-Universitaria di Bologna

🇮🇹

Bologna, Italy

Hospital Regional Universitario de Málaga

🇪🇸

Málaga, Spain

Department of Medical and Surgical Sciences, University Magna Græcia

🇮🇹

Catanzaro, Italy

Department of Experimental Medicine, Tor Vergata School of Medicine and Surgery

🇮🇹

Roma, Italy

San Bortolo Hospital

🇮🇹

Vicenza, Italy

Münster University Hospital

🇩🇪

Münster, Germany

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

🇮🇹

Brescia, BS, Italy

Fondazione Banca degli Occhi del Veneto

🇮🇹

Venice, Italy

Antwerp University Hospital

🇧🇪

Edegem, Belgium

Royal Liverpool University Hospital

🇬🇧

Liverpool, United Kingdom

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