Risk factors for corneal allograft rejection: intermediate results of a prospective normal-risk keratoplasty study

PURPOSE: To analyze the incidence of and possible risk factors for endothelial corneal allograft rejection in a well-defined population following penetrating normal-risk keratoplasty. METHODS: Since 1996 a longitudinal prospective study has been conducted to analyze the results of normal-risk penetrating keratoplasty. All patients underwent a standardized protocol of follow-up treatment and examinations in our institution. Diagnosis of corneal endothelial rejection was based on slit-lamp biomicroscopy and laser flare photometry. Data were analyzed using a proportional hazard model for censored data (Cox model), and Kaplan-Meier survival curves. The following parameters were analyzed: age, gender, atopic dermatitis, dry eye symptoms of the recipient; surgeon, graft diameter, post-mortem time, storage time and graft preservation method; and duration of postoperative epithelial defects. RESULTS: Between 1996 and May 2001, 397 patients were recruited and followed with a median follow-up of 18 months. Episodes of endothelial graft rejection were observed in 22 patients (5.5%; 18 eyes with acute diffuse episodes and 4 eyes with chronic focal rejection episodes). In addition, 12 eyes (3%) showed isolated small keratic precipitates ("graft rejection suspects"). All but one graft regained clarity after topical and systemic steroid treatment. Most episodes occurred 11-18 months postoperatively. The percentage of grafts without any episode of endothelial allograft rejection was 95% after 12 months, 89% after 18 months, and 86.5% after 24 months. The following factors were associated with graft rejection: atopic dermatitis (P=0.021), clinically manifest tear insufficiency (P=0.007), and short duration of graft storage (P=0.008). No significant correlation was detected for the remainder of the analyzed factors (P>0.05). CONCLUSION: The incidence of episodes of corneal endothelial allograft rejection following normal-risk keratoplasty was 13.5% within the first two postoperative years. However, the frequency of irreversible immunologic graft failure (3 per thousand) was lower than reported in the literature. Patients should be regularly followed up for at least 18 months postoperatively. Patients with underlying atopic dermatitis or dry eyes should receive special ophthalmological care.