To investigate graft survival and rejection following sequential bilateral corneal transplantation.

Retrospective cohort study.

The study included patients with Fuchs endothelial dystrophy (FED), pseudophakic bullous keratopathy (PBK), or keratoconus who had undergone a penetrating keratoplasty (PK), endothelial keratoplasty (EK), or deep anterior lamellar keratoplasty (DALK) between 1999 and 2012. The main cohort included patients who had received a first transplant in both eyes for the same indication and a control cohort patients who had undergone a unilateral first corneal transplant. Main outcome measures were graft rejection or failure at 5 years.

A total of 11 822 patients were included, of whom 9335 had a unilateral and 2487 bilateral corneal transplantation. For patients with FED (P < .005) and KC (P = .03) but not PBK (P = .19), a transplant in the second eye was associated with a 50% reduction in risk of graft failure within 5 years in the first eye (FED: hazard ratio [HR] 0.47, 95% confidence interval [CI]: 0.34–0.64; KC: HR 0.50, 95% CI: 0.24–1.02). For FED this was dependent on the type of transplant (EK: HR 0.30, 95% CI: 0.17–0.52; PK: HR 0.61, 95% CI: 0.42–0.88). We found no association between a transplant in the second eye and a rejection episode in the first eye (KC P = .19, FED P = .39, PBK P = .19).

For FED and KC, a transplant in the second eye was associated with a reduced risk of graft failure in the first eye, independent of inter-transplant time. For FED this effect was pronounced following an EK in the first eye, where the risk of failure was reduced by 70%.