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

Study Overview
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Brief Summary
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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
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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providing the tissue and tissue quality as assessed independently by a cornea surgeon performing the transplantation (unpublished data).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.

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

Conditions
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Corneal Transplant Failure, Corneal Endothelial Cell Loss

Intervention / Treatment
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* Diagnostic Test: V-Check


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Keratoplasty group<br>Patients undergoing keratoplasty and their respective donor tissue | Diagnostic Test: V-Check<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| Final ECD | Final ECD of transplanted corneas at 12 months | 1 year after enrollment | 
| Rate of endothelial cell loss | Rate of change of ECD over the course of the entire follow-up | 1 year after enrollment | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Keratoplasty, Corneal endothelium, Eye Banking