Etiology-Specific Comparison of the Long-Term Clinical Outcome of Repeat Deep Anterior Lamellar Keratoplasty for Optical Indications.

PURPOSE: The aim of this study was to evaluate the etiology-specific clinical outcomes and complications of repeat deep anterior lamellar keratoplasty (DALK) after failed DALK. METHODS: This retrospective case study included 32 eyes of 27 patients who underwent repeat DALK of 450 cases of DALK performed for optical indications between 1997 and 2013. The patients were divided into 4 etiology-specific subgroups (the corneal dystrophy, ocular surface disease, stromal scar, and others) or those with or without limbal stem cell deficiency (LSCD). The clinical outcomes evaluated were graft survival, best-corrected visual acuity, endothelial cell density, and complications. RESULTS: The mean postoperative follow-up duration was 69.6 ± 54.8 months. The 1-, 3-, and 5-year overall graft survival rate were 76.7%, 57.5%, and 38.8% respectively. The graft survival rate was the highest in the corneal dystrophy group ( P = 0.0014) and was significantly ( P = 0.0010) higher in eyes without LSCD than in eyes with LSCD. There were no significant differences in the graft survival rates between the previous and current DALK groups. The postoperative best-corrected visual acuity of all subjects improved significantly. The postoperative endothelial cell density did not decrease after repeat DALK. There were no significant differences in the incidence of complications between patients with and without LSCD, except the incidence of persistent epithelial defects. CONCLUSIONS: Repeat DALK had favorable outcomes in all etiology-specific groups, whereas eyes with LSCD required careful assessment of the ocular surface to avoid graft failure due to persistent epithelial defects.

Pathological processes in aqueous humor due to iris atrophy predispose to early corneal graft failure in humans and mice.

Corneal endothelial cell (CEnC) loss after corneal transplantation is the major cause of graft failure and remains a clinically relevant challenge to overcome. Accumulated knowledge derived from long-term clinical outcomes suggested that elevated protein levels in the aqueous humor are associated with CEnC loss. However, the full spectrum of driver proteins and molecular processes remains to be determined. Here, we defined the somatic microenvironmental landscape and cellular response across human aqueous humor in samples with poor corneal transplantation clinical outcomes using multiomics analyses and clarified specific driver alterations, including complement activation and disturbed energy homeostasis. These driver alterations were also confirmed in aqueous humor from a novel murine model that spontaneously develops iris atrophy, leading to CEnC loss. The application of the integrative multiomics performed in human samples to the novel murine model will help the development of therapeutic modalities for patients with CEnC loss after corneal transplantation.