Press Release Announcing Results

Cornea Donor Study (CDS)

The Cornea Donor Study (CDS) is a prospective cohort study with the following objectives:

• To determine whether the graft-failure rate over a 5-year follow-up period following corneal transplantation is the same when using corneal tissue from donors older than 65 years of age compared with tissue from younger donors.
• To assess the relationship between donor/recipient ABO blood type compatibility and graft failure due to rejection.
• To assess corneal endothelial cell density as an indicator of the health of the cornea and as a surrogate outcome measure (in an optional ancillary study).

The importance of the CDS and its rationale are supported by the following:

1. Although the supply of donor tissue may be sufficient to satisfy the current level of need in the U.S. for patients requiring corneal transplants, the future donor pool may decrease due to:
   • elimination of tissues because of increasingly mandated serologic testing
   • a decrease in younger donors due to improved automotive safety laws
   • a projected decrease in suitable donors due to the steady increase in refractive surgery.
   The change in practice that will have the greatest, cost-effective impact in increasing the donor pool is to expand the use of corneal tissue from older donors. This change in practice could expand the donor pool by 20-35 percent.
2. The scientific literature on the suitability of older donor tissue for corneal transplantation is limited and inconclusive. Most of the available relevant data are retrospective and uncontrolled. However, the weight of current evidence suggests that transplants using older donor tissue have similar success rates to those using younger donor tissue when endothelial cell counts of the donor tissue are comparable. Despite this, many surgeons decline the use of older tissue on the basis of the lack of suitability. In other parts of the world, this bias against older donor tissue does not exist and donor age is not considered an important factor in assigning corneal tissue to a recipient.
3. The international demand for suitable donor tissue is grossly unmet. If this study demonstrates that older donor tissue is as suitable as younger tissue, the impact internationally will be great.
4. Despite the common performance of corneal transplantation, there are limited longitudinal data for even a five-year follow-up period. The study will help to fill this void by providing data on graft survival rates in general and the prognostic importance of various recipient factors as well as other donor factors.
5. The need for the ABO compatibility substudy stems from the Collaborative Corneal Transplant Study’s (CCTS) finding that ABO blood type compatibility reduced the risk of graft failure. Because this was an unexpected secondary finding in the CCTS, corroboration of this finding in a second study is needed.
6. The Specular Microscopy Ancillary Study will provide additional support for the overall results of the CDS. If the CDS demonstrates that graft survival is equivalent between older and younger donor tissue, some corneal surgeons may still have concern that older tissue will not fare as well with longer duration of follow-up. If it can be demonstrated that endothelial cell loss in clear grafts after five years is also equivalent, then the results and clinical impact of the CDS will be strengthened. Alternatively, if the graft failure rates at five years are comparable, but the surviving grafts from older donor age tissue have greater endothelial cell loss than grafts from younger tissue, then the importance of longer follow-up for the study cohort will be apparent.

The study enrolled 1,101 patients. A donor cornea meeting the following criteria will be assigned to the patient by a participating eye bank:

• donor age 10 to 75 years
endothelial cell count 2300 to 3300
• tissue quality very good to excellent
• death to preservation time <12 hrs if body refrigerated or eyes on ice and <8 hrs if not
• death to surgery time <5 days

Patients must be in the age range of 40 to 80 years, with corneal disease associated with endothelial dysfunction, including pseudophakic corneal edema, Fuchs’ dystrophy, posterior polymorphous dystrophy, endothelial failure from another cause, interstitial keratitis (non-herpetic), or perforating corneal injury.

No longer recruiting. Comments: Completed. Patient enrollment ended on July 31, 2002 with 1,101 patients enrolled.

Ongoing. Comments: Ongoing.

The 5-year cumulative probability of graft survival was 86% in both the <66.0 donor age group and the ≥66.0 donor age group (difference = 0%, upper limit of 1-sided 95% confidence interval = 4%). In a statistical model with donor age as a continuous variable, there was no significant relationship between donor age and outcome (P = 0.11). Three graft failures were due to primary donor failure, 8 to uncorrectable refractive error, 48 to graft rejection, 46 to endothelial decompensation (23 of which had a prior, resolved episode of probable or definite graft rejection), and 30 to other causes. Distributions of the causes of graft failure did not differ between donor age groups.

Five-year graft survivals for cornea transplants at moderate risk for failure are similar using corneas from donors ≥ 66.0 years and donors < 66.0. Surgeons and patients now have evidence that corneas comparable in quality to those used in this study from donors through age 75 are suitable for transplantation.

Specular Microsopy Ancilliary Study Results

Endothelial cell loss is substantial in the 5 years after corneal transplantation. There is a slight association between cell loss and donor age. This finding emphasizes the importance of longer-term follow-up with this cohort to determine if this relationship affects graft survival.