Elevation of preoperative recipient aqueous cytokine levels in eyes with primary graft failure after corneal transplantation

Purpose: Primary graft failure after corneal transplantation is caused by dysfunction of corneal endothelial cells. Recently, we demonstrated that preoperative recipients' aqueous cytokine levels are associated with rapid corneal endothelial cell loss after corneal transplantation. In the present study, we evaluated the preoperative inflammatory cytokine levels in the aqueous humor (AqH) of eyes with primary graft failure following corneal transplantation. Methods: Among the prospective consecutive case series (273 eyes), this study included patients who developed primary graft failure (eight eyes) and patients who underwent corneal transplantation for the treatment of bullous keratopathy (108 eyes) or cataract surgery (30 eyes). AqH samples were collected at the beginning of each surgery. The levels of the cytokines (interleukin [IL]-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, interferon [IFN]-gamma, monocyte chemotactic protein [MCP]-1, E-selectin, P-selectin, and soluble intercellular adhesion molecule [sICAM]-1) in the AqH were measured with multiplex beads immunoassay. Results: In eyes with primary graft failure, the preoperative levels of aqueous protein (4.6-fold), interleukin (IL)-6 (179-fold), IL-17A (7.1-fold), MCP-1 (2.6-fold), IFN-gamma (4.3-fold), E-selectin (2.3-fold), P-selectin (2.0-fold), and sICAM-1 (5.5-fold) were statistically significantly higher compared to the cataract controls (p<0.0021). There was no primary graft failure among the recipients who received corneal grafts of fellow eyes from the same donors. Conclusions: Preoperative levels of AqH cytokines, such as IL-6, IL-17A, MCP-1, IFN-gamma, and sICAM-1, increased in eyes with primary graft failure after corneal transplantation. These cytokine levels could be prognostic biomarkers to predict primary graft failure after corneal transplantation.