Collaborative
Corneal Transplantation Studies
To determine whether
histocompatibility matching of corneal transplant donors and
recipients can reduce the incidence of graft rejection in high-risk
patients.
Approximately 20
percent of corneal transplant patients, about 6,000 per year,
face donor tissue rejection at rates of up to 60 percent because
of corneal vascularization or prior graft rejection. Histocompatibility
antigen matching and/or crossmatching may have offered these
patients an improved chance for successful outcome.
The Collaborative
Corneal Transplantation Studies Group conducted two controlled,
double-masked studies addressing distinct scientific questions
about donor-recipient histocompatibility matching. The Crossmatch
Study was a randomized study assessing the effectiveness
of crossmatching in preventing graft rejection among high-risk
patients with lymphocytotoxic antibodies. The Antigen Matching
Study was a prospective, double-masked, observational study
of the effectiveness of HLA-A, -B, and -DR donor-recipient matching
in high-risk patients who had no lymphocytotoxic antibodies.
Six clinical centers recruited high-risk patients and collaborated
with their local eye banking and organ procurement agencies
in procuring donor corneal tissue. For each of the two studies,
a total of 400 patients were sought. Blood samples from each
enrolled patient were sent to the local CCTS tissue typing laboratory
for HLA typing, and serum samples were sent to the Central Laboratory
to be screened for preformed lymphocytotoxic antibodies. Depending
on the results of the testing, patients were entered into the
Crossmatch Study or the Antigen Matching Study.
As corneal donors became available, donor blood samples were
HLA typed at the local laboratories and crossmatched against
all CCTS patients who awaited transplantation. Results of the
testing were entered in a national, 24-hour computerized allocation
system operated by the United Network for Organ Sharing (UNOS).
Patients in the Crossmatch Study received a cornea from either
a positively crossmatched donor or a negatively crossmatched
donor. Patients in the Antigen Matching Study received a cornea
with 0 to 6 matched antigens.
Transplant patients were followed intensively during the first
months after surgery. The number of clinic visits was tapered
to 2 during the third and final year of followup, resulting
in a total of 17 postoperative visits. Irreversible failure
of the corneal allograft due to all causes was the primary outcome
variable in both studies. Allograft reaction episodes, irreversible
failure due to rejection, and visual acuity were secondary outcome
variables.
Researchers report
that donor-recipient tissue typing had no significant long-term
effect on the success of corneal transplantation in more than
400 patients at high risk for rejection.
The Collaborative Corneal Transplantation Studies (CCTS) suggested
instead that matching patient and donor blood types (ABO compatibility),
a test that is not currently standard practice in corneal transplantation,
might be effective in improving patient outcome. Treating patients
with high-dose topical steroid therapy for several months after
surgery may have improved transplant survival in this study.
After 3 years of patient followup, CCTS researchers found that
people who received corneal transplants with well-matched antigens
did not fare significantly better than those with a poor match.
Each patient group had similar rates of initial immune reactions,
graft rejection, and graft failure due to rejection or other
causes. The researchers also noted that CCTS patients who were
compatible with the donor’s blood type had a better outcome
than unmatched patients.
The CCTS also reported a 65 percent rate of graft survival at
its 3-year mark--higher than the usual average of about 50 percent
in high-risk patients. The study’s high success rate might be
due to rigorous high-dose steroid therapy given to control the
patients’ immune reaction to the donor cornea several months
after surgery.
The most important conclusion to be drawn from the CCTS is that
high-dose, postoperative topical steroids, good patient compliance
with a self-administered steroid regimen, and close patient
followup are the keys to successful corneal transplantation
in high-risk individuals.
Data from the CCTS indicate that matching patient and donor
blood types combined with treating patients with high-dose topical
steroids after surgery may be potentially more effective in
improving high-risk corneal transplantation. These two inexpensive
strategies are considerably more economical than the more expensive
donor-recipient tissue typing. These findings provide clinicians
with solid information on managing patients at high-risk for
graft failure, while keeping health care costs to a minimum.
Last Updated: 10/21/99
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