Cornea Donor Study
Condition: Corneal Disease; Fuch's Dystrophy; Pseudophakic Corneal Edema
MeSH terms: Corneal Diseases; Corneal Edema; Fuchs' Endothelial Dystrophy
Study type: Interventional

Summary: 
      The Cornea Donor Study (CDS) was designed as 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 alternate outcome measure (in an optional Specular Microscopy Ancillary Study).
    

Detailed description: 
      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 banks:

        -  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

      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.

      Patients in the CDS continued in annual follow up 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 included 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
      were active at the 5-year exam were eligible for the extended follow-up phase.

      As part of the Specular Microscopy Ancillary Study, follow-up images were 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 were followed for the grading of the 7-8 year and 10-year images.
    

Intervention name(s): corneas assigned by donor age group
Intervention type(s): Other
Intervention description(s): A web-based computer program was used to select and assign a cornea by donor age group from those available at the eye bank that met the study eligibility criteria. The program randomly selected a cornea based on a two-level minimization procedure which attempted first to balance for each surgeon the number of corneas from donors >=66 and <66 years old and then, when possible, to balance among age subgroups of 10-35, 36-50, 51-65, 66-70, and 71-75 years. The assignment was made without regard to recipient age or any other subject characteristics.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: cornea transplant; corneal endothelial cell density; moderate risk corneal diseases; corneal transplantation