Late Acute Rejection After Allograft Limbal Stem Cell Transplantation: Evidence for Long-Term Donor Survival

Abstract

Purpose: To describe the clinical presentation and management of late (>3.0 years) acute graft rejection in keratolimbal allograft (KLAL) recipients.

Methods: This was a multicenter, retrospective observational case series. Six eyes of 6 patients with ocular surface transplant at a mean age of 36.2 years were seen at 3 tertiary referral centers for acute graft rejection between 2007 and 2013. Main outcome measures included strength of systemic immunosuppression (SI) at the time of rejection, time to rejection, and clinical presentation of rejection.

Results: Preoperative diagnoses included total limbal stem cell deficiency because of aniridia (n = 2) or chemical injury (n = 4). After an initially successful outcome, patients experienced late acute graft rejection at a mean time of 67.8 ± 24.1 months (range: 41-98) after KLAL while receiving suboptimal levels of SI because of medication taper (n = 5) or noncompliance (n = 1). Objective findings included an epithelial rejection line (n = 6), edema (n = 2), corneal epithelial irregularities (n = 2), and neovascularization (n = 1). Antirejection management consisted of topical corticosteroids (n = 6) and augmentation of SI therapy (n = 5).

Conclusions: These cases of late acute graft rejection in KLAL patients support the notion that allodonor cells can persist over the long run and remain at risk for immunologic rejection. It further underscores the fact that long-term success with KLAL may require extension of SI beyond the first few years, albeit at lower levels individualized to each patient.

Figure 1

Clinical characteristics of acute rejection: A, slit-lamp photograph from a 40-year-old woman with aniridia who presented with 6 weeks of decreased vision and increased discomfort and irritation 6 years after KLAL OS while non-compliant with her systemic immunosuppression regimen. Note the epithelial rejection line (white arrow). B, superior corneal neovascularization and conjunctivalization (white arrow). C, use of fluorescein staining to highlight the epithelial rejection line.

Figure 2

Case 6: A, preoperative slit-lamp photograph from a 37-year-old woman with aniridia demonstrating epithelial irregularity. B, a stable ocular surface at 2.5 years after keratolimbal allograft while on tacrolimus and mycophenolate mofetil. C, acute graft rejection 5.5 years after surgery evidenced by epithelial rejection line (white arrow). The patient had not received systemic immunosuppression for 2 years and had self-discontinued topical steroids one month prior to presentation. D, use of fluorescein staining to further highlight these findings.