Failed allogeneic corneal lenticules show fibrosis and identity loss without dominant T cell rejection

Failed allogeneic corneal stromal lenticules showed progressive opacity and fibrotic integration failure in six explants from three patients. Scar-matrix production and loss of corneal identity were observed without a dominant T cell rejection program. The explants differed from eight unimplanted donor controls in terms of scar-matrix, transparency, and corneal-identity programs.

Calibrated immune programs and repertoire reconstruction distinguished the explants from canonical adaptive rejection. Exchange initially reduced interface reflectivity, but recurrent opacity and corneal steepening with declining uncorrected acuity were seen in two and one patient, respectively. In non-scarring rabbit repair, corneal identity moved toward the uninjured state, despite increasing similarity to the explant-derived expression signature.

Tacrolimus and rapamycin suppressed canonical rejection but moved identity in opposite directions. Resveratrol reduced scar-associated programs, increased identity, and improved graft appearance. These findings establish classic-rejection activity and tissue integration as separable axes, suggesting that treatment of failed lenticules should focus on controlling stromal remodeling and preserving corneal identity.