Clinicopathological correlation analysis of (lymph) angiogenesis and corneal graft rejection

PURPOSE To investigate the relationship of (lymph) angiogenesis and survival time of human cornea grafts. METHODS This was a case series study. A total of 250 patients requiring a second keratoplasty were screened according to our inclusion criteria: 1) only cases with primary non-inflamed cornea diseases were included; and 2) all primary diseased cornea specimens from the first corneal transplantation were confirmed not to have hemangiogenesis or lymphangiogenesis. The included patients were analyzed retrospectively and followed up for the survival time of the first and second grafts. Blood vessel content (BVC) and lymphatic vessel content (LVC) were assessed in the primary diseased cornea; first rejected grafts (including BVC(1) and LVC(1)) and second rejected grafts (including BVC(2) and LVC(2)) were assessed by immunohistochemistry. The survival times of the first (STG(1)) and second (STG(2)) rejected corneal grafts were calculated and the relationship between human corneal (lymph) angiogenesis and STG was statistically analyzed. RESULTS After screening, only 23 patients (23 eyes) were included. Their primary cornea diseases were non-inflamed, including keratoconus (n=14), leukoma (n=5), and Fuchs endothelial dystrophy (n=4). The mean duration of follow up was 36 months after the second keratoplasty. In all, 55 cornea specimens from different times following penetrating keratoplasty were collected and examined, including 23 primary non-inflamed corneas (without angiogenesis), 23 first rejected corneal grafts (all with hemangiogenesis, but only six cases with blown lymphatic vessels), and nine rejected corneal grafts (including six cases identified with lymphangiogenesis in the first rejection, all with lymphangiogenesis and hemangiogenesis). Based on our statistical analysis, STG(1) was correlated with LVC(1) but not with BVC(1) or (LVC(1)+BVC(1)), while STG(2) was correlated with (LVC(1)+LVC(2)), LVC(1), LVC(2), (LVC(2)+BVC(2)) and (LVC(1)+BVC(1)) but not with BVC(1) or BVC(2). CONCLUSIONS The survival time of human cornea grafts is related to both lymphangiogenesis and hemangiogenesis. Lymphangiogenesis only occurred in some rejected cases, but it seems to be a signal of poor prognosis for the new allograft.