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This study was designed to assess feasibility and biocompatibility of a lamellar, nonperforating supraDescemetic Synthetic Cornea (sDSC) implanted in rabbit eyes after a corneal injury.Corneal vascularization and scarring was induced in the right eye of 15 rabbits by application of 1-heptanol and complete surgical removal of the limbus. An sDSC (7-mm diameter, 450-μm-thick optical zone, 100-μm-thick outer flange) was implanted after 45 ± 5 days. The keratoprostheses were implanted with their central optic part positioned on a completely exposed Descemet's membrane (DM) while the outer flange was located in deep stroma. Three different materials were tested: hydrophobic PMMA (n = 5) and hydrophilic HEMA-MMA (n = 5) and HEMA-NVP (n = 5) with a water content of 34% and 75%, respectively. The corneal surface was covered with a conjunctiva-Tenon flap. Central flap trephination was performed after 63 ± 7 days. DM vascularization and scarring was assessed and graded after flap opening and weekly thereafter.In all 15 consecutive cases implantation could be completed successfully without perforation of DM. Repair of the conjunctival flap had to be performed in five rabbits. Four months postoperatively, the flaps were opened. Four of five corneas (80%) with a PMMA implant and three of five (60%) with a HEMA-NVP75 implant had retained their original transparency. The others had developed significant neovascularization in the Descemet-sDSC optic interface. All corneas (100%) that received an sDSC made of HEMA-MMA34 displayed a completely clear DM without any vessels or scarring. DM was found firmly attached to the posterior surface of the optic.Implantation of a nonperforating synthetic cornea on top of an exposed DM is feasible. HEMA-MMA34 showed the most promising results. Because opening of the anterior chamber is not required, a lamellar supraDescemetic Synthetic Cornea would theoretically reduce some of the risks attributed to penetrating keratoprostheses.