ExCrossV Multi Site Trial for Vascularized High Risk Keratoplasty

Inclusion Criteria:

* Age 18 and older
* Willing and able to provide written informed consent
* Willing and able to comply with study assessments for the full duration of the study
* Patients undergoing high-risk penetrating keratoplasty, defined as corneal neovascularization (NV) in 1 or more quadrants ≥2 mm from the limbus or extension of corneal NV to the graft-host junction in a previously failed graft
* Superficial vessels are defined as those within the anterior one-third of the cornea and deep vessels within the posterior two-thirds of the cornea (i.e., deep stroma).

Superficial CNV involving ≤2 quadrants (equivalent to ≤6 clock hours) without deep CNV are classified as mild. CNV with \>2 quadrants of superficial vessels (\>6 clock hours) or 1 quadrant of deep vessels (\>3 clock hours) as severe (36).

Exclusion Criteria:

* History of Stevens-Johnson syndrome or ocular pemphigoid
* Ocular or periocular malignancy
* Non-healing epithelial defect of at least 0.5x0.5 mm in host corneal bed lasting ≥6 weeks preoperatively
* Uncontrolled glaucoma
* Change in topical corticosteroid regimen within 14 days of transplantation
* Use of systemic immunosuppressive for indication other than corneal graft rejection
* Participation in another simultaneous medical investigation or trial
* Pregnancy (positive pregnancy test) or lactating
* Pre-menopausal women not using adequate contraception (Reliable intrauterine devices, hormonal contraception or a spermicide in combination with a barrier method)
* Ocular infection within 30 days prior to study entry.
* Presence of anterior chamber intraocular lens
* Active uveitis within 90 days prior to the study entry.
* No ocular surgery or procedure within 90 days prior to the study entry or concomitant to the study procedure.