The Cornea Donor Study (CDS) was designed as a prospective cohort study with the following
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 alternate outcome measure (in an optional Specular Microscopy Ancillary Study).
The study enrolled 1101 subjects with a corneal disease considered to be at moderate risk
for failure (principally Fuchs' dystrophy and pseudophakic corneal edema). A donor cornea
meeting the following criteria was assigned to the subject by one of 43 participating eye
- 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
- death to surgery time <5 days
The cornea surgeon (investigator) and patient were masked to donor age and characteristics
of the donor cornea. Preoperative management, surgical technique, and postoperative care,
including prescription of medications, were provided according to each investigator's
customary routine. The follow-up visit schedule for the initial six months was left to each
investigator's discretion and after this time the minimum follow-up visit schedule included
a visit between six and 12 months and then one visit every 12 months through five years.
The primary study outcome was graft survival at five years. The definition of graft
failure, based on the definition used in Collaborative Corneal Transplantation Studies, was
a regraft or, in the absence of regraft, a cloudy cornea in which there was loss of central
graft clarity sufficient to compromise vision for a minimum of three consecutive months.
Follow-up in the initial phase of the study continued for five years unless the patient had
a regraft of the study eye.
For the ABO compatibility study, the ABO blood type of both the donor and recipient were
determined in order to compare the rate of graft failure for ABO-compatible cases with the
rate for ABO-incompatible cases.
For the Specular Microscopy Ancillary Study, endothelial cell counts were determined from
specular images by a central reading center, and the relationship of the cell counts to
donor age were assessed. In the initial phase of the study, specular images were obtained
at 6 months, and then annually through five years post-transplant.
Five-year follow up was completed in November 2007. The 5-year cumulative probability of
success was 86%: 86% in the <66.0 year donor age group and 86% in the >=66.0 year donor age
group (difference = 0%, upper limit of one-sided 95% confidence interval = 4%). Adjusting
for baseline endothelial cell density had no appreciable effect on these results. In a
statistical model with donor age as a continuous variable, there was not a 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, and 30 to other causes. At least one probable or definite graft
rejection episode preceded graft failure in 23 of the 46 failures attributed to endothelial
decompensation (4 definite and 19 probable) and in 18 of the 30 failures attributed to other
causes (4 definite and 14 probable). The distribution of causes of failure between the
donor age groups did not substantially differ.
Although the 5-year results indicated no difference in the success rate of moderate-risk
transplants according to donor age, results from the SMAS indicated that among the
successful cases, there was a slight association between donor age and endothelial cell
loss, with the cell loss after 5 years being slightly lower in corneas from younger donors
(r adjusted for baseline endothelial cell density = -0.19, 95% confidence interval -0.29 to
-0.08). Whether this slight association between cell loss and donor age is of clinical
importance is not known. Of perhaps even greater importance, however, was the finding that
irrespective of donor age, endothelial cell loss was substantial over the first five years
after transplant even when the graft had been successful. Half of the successful cases
experienced a cell loss of 70% or more, and at five years more than half had an endothelial
cell density <800 cells/mm2.
The CDS will continue and patients will be followed annually through 2012 in order to to
determine the overall 10-year survival rate for moderate risk grafts and to determine
whether the graft-failure rate is related to donor age. Additional objectives include
determining the value of endothelial cell density in predicting graft failure and evaluating
donor and recipient characteristics that may be predictive of late graft failure. All CDS
subjects who are active at the 5-year exam are eligible for the extended follow-up phase.
As part of the Specular Microscopy Ancillary Study, follow-up images will be obtained during
the extended follow-up phase at 7-8 years and again at 10-years. The same procedures used
during the first 5 years will be followed for the grading of the 7-8 year and 10-year
- Patients must be in the age range of 40 to 80 years.
- Patients 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.