Cornea. 2009 May 30; Prasher P, Muftuoglu O, Hsiao ML, Bowman RW, Hogan RN, Mootha VVPURPOSE:: To report the clinical and histopathologic findings of 2 patients who developed epithelial downgrowth after Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS:: A 64-year-old woman (case 1) underwent DSAEK for corneal edema secondary to Fuchs endothelial dystrophy in left eye. However, the graft failed to attach, and a repeat DSAEK was performed 3 weeks later. After 4 months, the patient developed herpes simplex virus keratitis that resulted in anterior stromal scarring. A penetrating keratoplasty was performed 15 months after the initial DSAEK. Our second patient (case 2) was an 87-year-old female who underwent DSAEK for corneal edema secondary to Fuchs endothelial dystrophy in left eye. Six months later, she had an episode of graft rejection and developed secondary glaucoma. At 14 months postoperatively, a retrocorneal membrane was seen involving the temporal half of the endothelial surface of the graft. The retrocorneal membrane extended from the inferior thickened edge of the endothelial keratoplasty graft to the iris stromal surface. An Ahmed shunt implantation followed by repeat DSAEK were then performed. The excised corneal buttons were examined. RESULTS:: Histopathologic evaluation showed multilayered epithelium on the interface and attenuated endothelium in the endothelial graft in case 1. The host cornea showed diffuse stromal scarring. Case 2 showed multilayered epithelium with early cyst formation at the edge of the graft. The epithelium extended to involve the endothelial surface without involvement of interface surface. Significant scar formation was observed between the edge of the endothelial keratoplasty graft and thickened host Descemet membrane. Some pigmented cells were present within the epithelial downgrowth. The epithelium stained positively with cytokeratin A1/A3 in both cases. CONCLUSIONS:: Although rare, epithelial downgrowth can occur after DSAEK and can be associated with graft failure. Early recognition and surgical treatment of epithelial downgrowth is crucial in treating the complications of corneal decompensation and glaucoma.