Dropless penetrating keratoplasty: immunosuppression by a subconjunctival dexamethasone implant, pilot tolerance and safety study

Abstract

AbstractPurposePenetrating keratoplasty (PK) remains the first technic of corneal transplantation worldwide and rejection a common cause of graft failure. Its prevention has been based for decades on repeated instillation of steroid eye drops (dexamethasone, prednisolone, rimexolone). Nevertheless, the overall survival of corneal transplants, all indications combined, is lower than that of some organ transplants. Both compliance and the discontinuous nature of the eye drops may be involved. The improvement of immunosuppression could avoid numerous graft failures. In a rabbit model of PK, we previously demonstrated that a subconjunctival dexamethasone implant (Ozurdex) was well tolerated and prevented rejection as efficiently as steroid eye drops trice daily during the first 5‐6 weeks. We then designed a clinical trial to first investigate the tolerance and safety of subconjunctival Ozurdex after PK.MethodsSingle centre, phase II non‐randomized tolerance and safety pilot study on 14 patients (NCT02834260). Designed to analyze the risk of increased intraocular pressure (IOP, primary endpoint at month 1), possible discomfort, resorption time, and collect initial efficacy data. The implant was injected at the 12 o'clock position, 5 mm from the limbus, at the end of PK, in order to deliver dexamethasone immediately. A steroid eye drop relay was planned at the time of complete resorption of the implant. Patients were monitored at regular intervals during 12 months: IOP, discomfort and redness scores, implant status, rejection episode, endothelial cell density, and central corneal thickness by OCT. An independent adverse event committee gave its opinion after the first patient, then at regular intervals.ResultsNo increase in IOP, no adverse event related to the implant was observed. The average duration of resorption was 6 weeks. The therapeutic relay with dexamethasone eye drops was uneventful.ConclusionsHis is the first proof of concept that dropless immunosuppression is possible after penetrating keratoplasty. Ozurdex, chosen here because it was the only ophthalmological steroid implant marketed in France, obviously resorbs too quickly, but this work paves the way for the use of other implants that release a steroid or another immunosuppressive agent in the very long term.