Collaborative Corneal Transplantation Studies (CCTS)
Collaborative Corneal Transplantation Studies (CCTS)
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.
Males and females age 10 years or older with two to four quadrants of corneal stroma
 vascularization or a history of allograft rejection in the eye considered for surgery were
 eligible for both studies in the CCTS.

 Patients must have been willing to participate in 3 years of followup. No one was eligible
 for the CCTS who had a condition that would greatly increase the risk of nonrejection graft
 failure, such as xerophthalmia or severe exposure keratopathy. Also excluded were patients
 with systemic diseases or with medication usage that might alter their immune response.