Paul-Marie Bernard

Effect of factors unrelated to tissue matching on corneal transplant endothelial rejection.

We examined 348 consecutive adult recipients of a corneal transplant for clinical signs of an endothelial rejection episode in a single-center follow-up study. The variables studied included primary diagnosis, number of previous corneal transplants, previous transplant failures from rejection episodes, transplant size, recipient corneal vascularization, donor age, recipient age and sex, past blood transfusions, and number of pregnancies. Five important risk factors were identified: primary diagnosis of herpetic, interstitial, or traumatic keratitis; transplant size 8 mm and larger; more than one previous corneal transplant; recipients younger than 60 years of age; and the presence of recipient corneal vascularization. This information will serve eventually for analyzing the effect of donor recipient tissue matching on corneal transplant rejection.

Association between Corneal Allograft Reactions and HLA Compatibility

The purpose of this follow-up study is to measure the association between corneal allograft reactions and donor-recipient HLA-A and HLA-B compatibility. Four hundred thirty-eight consecutive adult recipients of corneal grafts with known donor-recipient HLA matching were observed for allograft reactions and failures. Most of the recipients under observation (91%) were well matched for HLA-DR. Of 438 recipients, 158 (36%) completed a 3-year follow-up. Three factors were associated with endothelial allograft reactions: 2 to 4+ corneal vascularization (relative risk, 2.2; P = 0.0006), two mismatched antigens at either the HLA-A or HLA-B locus (relative risk, 2.1; P = 0.0009), and recipient wound size of 8 mm or greater (relative risk, 1.5; P = 0.05). Unexpectedly, a strong association between endothelial allograft reactions and HLA-A or HLA-B incompatibility was found in low-risk recipients defined as unvascularized recipients of a small graft (relative risk, 3.2; P = 0.004). A larger sample size is required to determine if HLA matching offers a solution for recipients with corneal vascularization.

PRETRANSPLANT AND POSTTRANSPLANT ANTIBODIES IN HUMAN CORNEAL TRANSPLANTATION

The purpose of this study was to measure the association between antibody formation and endothelial corneal allograft reactions in 533 consecutive corneal graft recipients. The median follow-up time of these recipients was 732 days. Pretransplant panel-reactive antibodies were not found to be associated with endothelial corneal allograft reactions. Out of 533 recipients, 239 developed posttransplant antibodies during the course of this study. The formation of posttransplant antibodies was frequent in recipients with pretransplant antibodies and in HLA-A,-B-incompatible recipients. Posttransplant antibodies most often appeared within the first six months after transplantation whereas endothelial allograft reactions most often occurred later. Out of 65 recipients who developed PPRA and underwent an allograft reaction, 53 had a PPRA peak prior to, or at about the time of, the allograft reaction. Corneal allograft reaction events diagnosed during the second and third year after surgery were correlated with PPRA formation during the first year after grafting. The 36-month reaction-free survival rate of transplants was estimated at 72% in recipients with PPRA compared with 86% in recipients without PPRA (log rank P value = 0.002). Furthermore, posttransplant antibody formation altered the outcome of corneal allografts in both HLA-A and -B—compatible and -incompatible recipients. These findings suggest that posttransplant antibody development represents a high risk of endothelial corneal allograft reactions.

Comparison of prognosis for men with type 2 diabetes mellitus and men with cardiovascular disease

Background: People with type 2 diabetes mellitus are at high risk for cardiovascular disease. In some studies, the mortality rate among people with this condition has been equivalent to that among people with cardiovascular disease. We compared cardiovascular mortality between incident cases of diabetes and cardiovascular disease. Methods: The study population was part of a random sample of 4376 men from Quebec, Canada, aged 35 to 64 years, who did not have cardiovascular disease in 1974 and who were followed until 1998. Three groups of incident cases were identified: diabetes without cardiovascular disease, first cardiovascular event (myocardial infarction, unstable angina or stroke) without diabetes, and both cardiovascular disease and diabetes. These cases were age-matched to a control group without diabetes or cardiovascular disease. Results: During the 24-year follow-up period, new diabetes without cardiovascular disease was documented in 137 men. A first cardiovascular event without diabetes was documented in 527 men. Relative to the 627 controls, men with 1 of the 2 diseases of interest had higher cardiovascular mortality (age-adjusted relative risk [RR] 3.11, 95% confidence interval [CI] 1.96–4.92) for those with diabetes and 4.46 (95% CI 3.15–6.30) for those with cardiovascular disease). However, within the first 5 years after diagnosis, men with cardiovascular disease had higher cardiovascular mortality than men with diabetes (age-adjusted RR 2.03, 95% CI 1.01–4.08). Interpretation: Men with isolated type 2 diabetes and men with isolated cardiovascular disease had similar cardiovascular mortality rates several years after initial diagnosis of either condition. These findings reinforce the need to prevent and optimally manage diabetes and cardiovascular disease.