ExCrossV Multi Site Trial for Vascularized High Risk Keratoplasty (ExCrossV)

April 17, 2026 updated by: Joseph B. Ciolino, MD, Massachusetts Eye and Ear Infirmary

Multicenter Clinical Trial to Evaluate the Safety and Efficacy of Ex Vivo Corneal Cross-linking of Donor Corneal Tissue Used for Vascularized High-risk Keratoplasty

The main objective of this study is to determine the safety of Ex Vivo Cross Linking (CXL) of donor corneal tissue in participants who have undergone high-risk penetrating keratoplasty.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a randomized, double-masked, multi site clinical trial to determine the safety of Ex Vivo CXL of donor corneal tissue in 96 participants who have undergone high-risk penetrating keratoplasty.

Participants will be randomized to receive either a corneal tissue that has been untreated vs. a corneal tissue that has been treated with Photrexa® Viscous & Photrexa® and UV light. The tissue will be prepared by a Corneal Tissue Bank under Current-Good-Tissue-Practice (CGTP) and delivered to the respective institutions for transplantation. Participants will be monitored up to 24 months post-transplantation to assess for adverse events of the randomized tissue.

Study Type

Interventional

Enrollment (Estimated)

96

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Nikolay Boychev, OD, PhD

Study Locations

  • United States
    • California
      • Irvine, California, United States, 92617
        • Not yet recruiting
        • University of California Irvine - Gavin Herbert Eye Institute
        • Principal Investigator:
          • Marjan Farid, MD
      • Los Angeles, California, United States, 90095
        • Not yet recruiting
        • The University of California Los Angeles - Doris Stein Eye Research Center
        • Principal Investigator:
          • Anthony Aldave, MD
      • San Francisco, California, United States, 94158
        • Not yet recruiting
        • University of California San Francisco - Wayne and Gladys Valley Center for Vision
        • Contact:
        • Principal Investigator:
          • Julie Schallhorn, MD
    • Florida
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami - Bascom Palmer Eye Institute
        • Principal Investigator:
          • Guillermo Amescua, MD
        • Contact:
        • Contact:
    • Indiana
      • Indianapolis, Indiana, United States, 46260
        • Recruiting
        • Price Vision Group
        • Principal Investigator:
          • David Price, MD
        • Contact:
        • Contact:
    • Kansas
      • Overland Park, Kansas, United States, 66204
        • Recruiting
        • Kansas City Eye Clinic
        • Principal Investigator:
          • Christopher Ketcherside, MD
        • Sub-Investigator:
          • Megan Haghnegahdar, MD
        • Contact:
    • Maryland
      • Towson, Maryland, United States, 21204
        • Not yet recruiting
        • Mid-Atlantic Cornea Consultant
        • Principal Investigator:
          • Sudeep Pramanik, MD
        • Principal Investigator:
          • Alexander Altman, MD
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
    • Michigan
      • Ann Arbor, Michigan, United States, 48015
        • Recruiting
        • University of Michigan - Kellogg Eye Center
        • Principal Investigator:
          • Shahzad Mian, MD
        • Contact:
    • North Carolina
      • Bermuda Run, North Carolina, United States, 27006
        • Not yet recruiting
        • Wake Forest Baptist Eye Center
        • Principal Investigator:
          • Matthew Giegengack, MD
        • Contact:
      • Durham, North Carolina, United States, 27705
        • Recruiting
        • Duke University - Duke Eye Center
        • Principal Investigator:
          • Esen Akpek, MD
        • Contact:
        • Contact:
    • Ohio
      • Cincinnati, Ohio, United States, 45242
        • Recruiting
        • Cincinnati Eye Institute
        • Principal Investigator:
          • Kavitha Sivaraman, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Participants Receiving Treated Cross Linked Corneal Tissue
Participants in this group will receive tissue that has been treated with 0.1% riboflavin (Vitamin B2) and 20% dextran (Photrexa® viscous and Photrexa®) with UV light treatment. Participants will be monitored over a period of 24 months.
Procedure: Corneal Donor Tissue with Cross Linking
Participants are transplanted with corneal donor tissue that has been treated with 0.1% riboflavin (Vitamin B2) and 20% dextran (Photrexa® Viscous & Photrexa®) with UV light treatment.
Other Names:
  • Treatment
Placebo Comparator: Participants Receiving Untreated Cross Linked Corneal Tissue
Participants in this group will receive tissue that has has not been treated with 0.1% riboflavin (Vitamin B2) and 20% dextran (Photrexa® viscous and Photrexa®) without UV light treatment. Participants will be monitored over a period of 24 months.
Procedure: Corneal Donor Tissue without Cross Linking
Participants are transplanted with corneal donor tissue that has not been treated with the UV light and the 0.1% riboflavin (Vitamin B2) and 20% dextran (Photrexa® Viscous & Photrexa®) without UV light treatment, this is the control group.
Other Names:
  • Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determining the Primary Safety of Corneal Cross Linking
Time Frame: 24 Months

The occurrence of adverse events throughout study including:

  1. Ocular Safety per the incidences and severity of ocular adverse events during the study based on ophthalmic examination and participants' self-report.

  2. Short Term Safety Events (Post Surgery < 1 Month)

    • Post-Op Microbial Keratitis
    • Acute Rejection (Epithelial, Endothelial, Sub epithelial, or Mixed)

  3. Long Term Safety Events (Post Surgery > 1 Month)

    • Rejection (Epithelial, Endothelial, or Mixed)
    • Graft Failure
    • Ulcerative Keratitis
    • Persistent Epithelial Defect lasting more than 6 Weeks
24 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measure of the Frequency of Graft Failures though Corneal Cross Linking
Time Frame: 24 Months
To determine the efficacy of using cross linked tissue for the indicated keratoplasty for the prevention of corneal graft rejection and corneal neovascularization, by measuring the frequency of primary graft failures over 24 months.
24 Months
Measure of Time from Surgery to Overall Graft Failure for Corneal Cross Linking over 24 Months
Time Frame: 24 Months
The efficacy of using cross linked tissue for the indicated keratoplasty for the prevention of corneal graft rejection and corneal neovascularization, by measuring the time from surgery to overall graft failure (regardless of cause).
24 Months
Measure of Time from Surgery to Graft Rejection for Corneal Cross Linking over 24 Months
Time Frame: 24 Months
The efficacy of using cross linked tissue for the indicated keratoplasty for the prevention of corneal graft rejection and corneal neovascularization, by measuring the occurrence of any rejection episode. (Epithelial, Endothelia, Sub Epithelial, or Mixed) determined as either definite rejection, probably rejection, and possible rejection, from the time of surgery over 24 months.
24 Months
Measure of the Efficacy of Corneal Cross Linking Through Image Review
Time Frame: 24 Months

The efficacy of using cross linked tissue for the indicated keratoplasty for the prevention of corneal graft rejection and corneal neovascularization.

1. Corneal Neovascularization (CNV) measured and analyzed from slit-lamp photography.
24 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts Eye and Ear Infirmary

Investigators

  • Principal Investigator: Joseph Ciolino, MD, Massachusetts Eye and Ear

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2025

Primary Completion (Estimated)

January 1, 2028

Study Completion (Estimated)

January 1, 2031

Study Registration Dates

First Submitted

September 19, 2024

First Submitted That Met QC Criteria

December 20, 2024

First Posted (Actual)

December 31, 2024

Study Record Updates

Last Update Posted (Actual)

April 21, 2026

Last Update Submitted That Met QC Criteria

April 17, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023P002687

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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