Cornea Preservation Time, Endothelial Cell Density, Endothelial Keratoplasty, Transplant Success
Conditions
Keywords
cornea, transplant, preservation, endothelial keratoplasty
Brief summary
The purpose of this study is to determine if the 3-year graft failure rate following endothelial keratoplasty performed with donor corneas with a preservation time of 8 to 14 days is non-inferior to the failure rate when donor corneas with a preservation time of 7 or fewer days are used.
Detailed description
When the donor cornea is removed from the person who died, it is prepared for transplantation by an eye bank. The donor cornea is placed into a liquid that helps preserve the cornea until it is transplanted. The Food and Drug Administration (FDA) has approved storage of the cornea in this liquid for up to 14 days before the transplant. The purpose of this study is to see if the length of time the donor cornea is kept in the preservation liquid before the transplant affects the likelihood of the transplant being successful. We will follow participants for 3 years after transplant to see if there are any differences in transplant success or in the number of transplanted endothelial cells (the layer of cells that line the undersurface of the cornea) on the corneas that were preserved for 7 days or less compared to those preserved between 8 and 14 days. We have no reason to believe that there is any greater risk for transplant failure with either preservation time group.
Interventions
BIOLOGICALCornea tissue transplant
Cornea tissue preserved 0 to 7 days
Sponsors
National Eye Institute (NEI)
Jaeb Center for Health Research
Case Western Reserve University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
Study Participant Eligibility Criteria * Study Participant Inclusion Criteria 1. Age range 30-\<91 years with minimum life expectancy of at least 3 years. 2. Willingness to return for follow-up study visits at 1 day, 1 week, 1 month, 6 months, 1 year, 2 years and 3 years. 3. Fluent in English or Spanish. * Study Participant
Exclusion criteria
1) Decisionally and/or cognitively impaired Study Eye Eligibility Criteria * Study Eye Inclusion Criteria 1. Endothelial keratoplasty (EK) is scheduled between 10 and 60 days after enrollment * The 10-day requirement relates to the need to be able to randomly assign the eye to either intervention group. * The 60-day requirement relates to the need to have current eligibility and enrollment data at the time of surgery. If surgery is postponed to \>60 days after the initial enrollment visit, a new Baseline Visit and eligibility assessment will have to be performed. 2. Presence of a condition related to endothelial dysfunction which will be treated by EK. * Eligible indications for EK include: * Presence of Fuchs endothelial corneal dystrophy (FECD) meeting at least one of the following: * Phakic FECD * Phakic FECD with cataract * Triple procedure including EK for FECD, cataract extraction and posterior chamber intraocular lens implantation (IOL) is allowed * Aphakic FECD * Pseudophakic FECD with posterior capsule supported, suture-fixated, or sulcus-supported posterior chamber IOL * Aphakic or pseudophakic corneal edema with posterior capsule supported, suture-fixated, or sulcus-supported posterior chamber IOL without FECD * Study Eye
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Eyes With Corneal Graft Failure Within 3 Years of Surgery | Study eye will be assessed for this outcome for 3 years following surgery | Graft failure, defined as the occurrence of one of the following within 3 years of surgery: * Regrafting of the study eye for any reason * Cornea which remains cloudy without clearing, according to the following: 1. cloudy cornea on the first postoperative day which does not clear within 8 weeks OR 2. cloudy cornea which was initially clear postoperatively but becomes and remains cloudy for 3 months without clearing. |
| Endothelial Cell Density (ECD) | 3 years from surgery | Endothelial cell density at 3 years from surgery, conditional on graft survival at 3 years from surgery. |
Countries
United States
Participant flow
Pre-assignment details
Randomization was at eye level. When both eyes of a participant were included, the eye undergoing surgery 1st was assigned randomly to a PT group and the 2nd eye to the other group. 2 eyes had their assigned donor corneas inadvertently switched, and resulted in 1 of these participants receiving both study eyes from 8-14d group.
Participants by arm
| Arm | Count |
|---|---|
| Preservation Time Group 1 Subjects in this arm will receive cornea tissue preserved for up to 7 days prior to transplant.
Cornea tissue transplant: Cornea tissue preserved either 7 or less days or 8 to 14 days. | 675 |
| Preservation Time Group 1 Subjects in this arm will receive cornea tissue preserved for up to 7 days prior to transplant.
Cornea tissue transplant: Cornea tissue preserved either 7 or less days or 8 to 14 days. | 675 |
| Preservation Time Group 2 Subjects in this arm will receive cornea tissue preserved for 8 to 14 days prior to transplant.
Cornea tissue transplant: Cornea tissue preserved either 7 or less days or 8 to 14 days. | 654 |
| Preservation Time Group 2 Subjects in this arm will receive cornea tissue preserved for 8 to 14 days prior to transplant.
Cornea tissue transplant: Cornea tissue preserved either 7 or less days or 8 to 14 days. | 655 |
| Total | 2,659 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Censored (severe event unrelated to PT) | 1 | 1 |
| Overall Study | Death | 20 | 32 |
| Overall Study | Exclude prior to study | 32 | 44 |
| Overall Study | Failure - Not regrafted | 2 | 6 |
| Overall Study | Failure - Regrafted | 28 | 43 |
| Overall Study | Lost to Follow-up | 53 | 48 |
| Overall Study | Withdrawal by Subject | 18 | 17 |
Baseline characteristics
| Characteristic | Preservation Time Group 2 | Total | Preservation Time Group 1 |
|---|---|---|---|
| Age, Continuous | 70 years | 70 years | 70 years |
| Central subepithelial/stromal scarring present (not affect postoperative stromal clarity assessment) | 48 eyes | 85 eyes | 37 eyes |
| Corneal Dystrophy other than FECD (Fuchs endothelial corneal dystrophy)) EBMD (epithelial basement membrane dystrophy) | 29 eyes | 67 eyes | 38 eyes |
| Corneal Dystrophy other than FECD (Fuchs endothelial corneal dystrophy)) Keratoconus | 0 eyes | 1 eyes | 1 eyes |
| Corneal Dystrophy other than FECD (Fuchs endothelial corneal dystrophy)) No | 623 eyes | 1253 eyes | 630 eyes |
| Corneal Dystrophy other than FECD (Fuchs endothelial corneal dystrophy)) Other | 3 eyes | 9 eyes | 6 eyes |
| Current cigarette smoker | 45 eyes | 90 eyes | 45 eyes |
| Diagnosis Aphakic corneal edema without FECD | 2 eyes | 2 eyes | 0 eyes |
| Diagnosis Fuchs endothelial corneal dystrophy (FECD) | 624 eyes | 1255 eyes | 631 eyes |
| Diagnosis Pseudophakic corneal edema without FECD | 29 eyes | 73 eyes | 44 eyes |
| Glaucoma medication currently being used | 54 eyes | 99 eyes | 45 eyes |
| History of Diabetes | 126 eyes | 242 eyes | 116 eyes |
| Intraocular pressure (IOP) | 15 mm Hg | 15 mm Hg | 15 mm Hg |
| Peripheral anterior synechiae present (nongonioscopic) | 2 eyes | 6 eyes | 4 eyes |
| Postoperative lens status Phakic | 6 eyes | 10 eyes | 4 eyes |
| Postoperative lens status Pseudophakic posterior chamber intraocular lens | 649 eyes | 1320 eyes | 671 eyes |
| Preoperative lens status Aphakic | 2 eyes | 2 eyes | 0 eyes |
| Preoperative lens status Phakic | 351 eyes | 692 eyes | 341 eyes |
| Preoperative lens status Pseudophakic posterior chamber intraocular lens | 302 eyes | 636 eyes | 334 eyes |
| Prior glaucoma surgery | 13 eyes | 31 eyes | 18 eyes |
| Race/Ethnicity, Customized African American | 21 eyes | 47 eyes | 26 eyes |
| Race/Ethnicity, Customized American India or Alaskan Native | 2 eyes | 3 eyes | 1 eyes |
| Race/Ethnicity, Customized Asian | 5 eyes | 12 eyes | 7 eyes |
| Race/Ethnicity, Customized Hispanic or Latino | 25 eyes | 44 eyes | 19 eyes |
| Race/Ethnicity, Customized More than 1 race | 3 eyes | 9 eyes | 6 eyes |
| Race/Ethnicity, Customized Unknown or not reported | 5 eyes | 8 eyes | 3 eyes |
| Race/Ethnicity, Customized White | 594 eyes | 1207 eyes | 613 eyes |
| Received any immunizations or vaccinations in last 3 mo | 81 eyes | 173 eyes | 92 eyes |
| Sex: Female, Male Female | 392 eyes | 801 eyes | 409 eyes |
| Sex: Female, Male Male | 263 eyes | 529 eyes | 266 eyes |
| Stromal corneal vessels present (but not visually significant) | 1 eyes | 5 eyes | 4 eyes |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 20 / 675 | 32 / 654 |
| other Total, other adverse events | 0 / 675 | 0 / 654 |
| serious Total, serious adverse events | 1 / 675 | 2 / 654 |
Outcome results
Primary
Endothelial Cell Density (ECD)
Endothelial cell density at 3 years from surgery, conditional on graft survival at 3 years from surgery.
Time frame: 3 years from surgery
Population: Eyes with graft success and a gradable image at 3 year (945 eyes of 769 unique participants)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Preservation Time Group 1 | Endothelial Cell Density (ECD) | 1722 Cells per square millimeter | Standard Deviation 626 |
| Preservation Time Group 2 | Endothelial Cell Density (ECD) | 1642 Cells per square millimeter | Standard Deviation 631 |
p-value: 0.0395% CI: [8, 138]Mixed Models Analysis
Primary
Number of Eyes With Corneal Graft Failure Within 3 Years of Surgery
Graft failure, defined as the occurrence of one of the following within 3 years of surgery: * Regrafting of the study eye for any reason * Cornea which remains cloudy without clearing, according to the following: 1. cloudy cornea on the first postoperative day which does not clear within 8 weeks OR 2. cloudy cornea which was initially clear postoperatively but becomes and remains cloudy for 3 months without clearing.
Time frame: Study eye will be assessed for this outcome for 3 years following surgery
Population: Analyzed number of eyes in each group (Overall 1090 unique participants)
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Preservation Time Group 1 | Number of Eyes With Corneal Graft Failure Within 3 Years of Surgery | 30 Eyes |
| Preservation Time Group 2 | Number of Eyes With Corneal Graft Failure Within 3 Years of Surgery | 49 Eyes |
p-value: 0.0295% CI: [1.09, 2.71]Regression, Cox