Risk Factors for Progression of Graft Rejection to Graft Failure Following Penetrating Keratoplasty

To analyze the risk factors for graft failure in eyes with endothelial graft rejection following penetrating keratoplasty (PK). Single-center, retrospective study that included patients who underwent PK at Wills Eye Hospital (2007–2018) who later presented with endothelial graft rejection, defined as clinical appearance of keratic precipitates or anterior chamber reaction. Among patients with rejection across multiple grafts, only the first PK of the first eye with documented rejection was included. The primary outcome measures were progression to graft failure, defined as irreversible and visually significant stromal edema, haze, or scarring, and acute graft failure, defined as failure within 6 months of rejection. 296 eyes from 296 patients were included with mean age of 54.4 ± 21.3 years. Average follow-up duration was 4.5 ± 2.9 years and rejection occurred 16.2 ± 18.7 months after transplantation. The rate of graft failure was 45.9% and the rate of acute failure was 31.4%. Predictors of failure after rejection included history of systemic autoimmune disorders (OR = 8.99, 95% CI = 2.03–39.77, <i>p</i> = 0.004), prior glaucoma surgery (OR = 2.73, 95% CI = 1.05–7.11, <i>p</i> = 0.039), and postoperative lens status as aphakia (OR = 7.59, 95% CI = 1.00–57.52, <i>p</i> = 0.0497). Predictors of acute graft failure after rejection included history of systemic autoimmune disorders (OR = 4.69, 95% CI = 1.20–18.33, <i>p</i> = 0.026), active microbial infection (OR = 3.52, 95% CI = 1.69–7.31, <i>p</i> = 0.001), and prior glaucoma surgery (OR = 3.50, 95% CI = 1.42–8.62, <i>p</i> = 0.006). Systemic autoimmune disorders and prior glaucoma surgery predicted both overall and acute graft failure, suggesting more aggressive rejection episodes in these cohorts.