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RecruitingNCT06753916ExCrossVUpdated Sep 21, 2026

ExCrossV Multi Site Trial for Vascularized High Risk Keratoplasty

A Phase 2 interventional study of Corneal Donor Tissue with Cross Linking and Corneal Donor Tissue without Cross Linking in Corneal Transplant Failure, sponsored by Massachusetts Eye and Ear Infirmary. Recruiting at 12 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-21.

Sponsored by Massachusetts Eye and Ear Infirmary · Phase 2, Interventional, and Treatment

From the registry’s dates

  • Started Apr 2025; still recruiting 1 year 7 months later.
Phase
Phase 2
Study type
Interventional
Enrollment
96
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

  • Corneal Transplant Failure

Keywords

  • Keratoplasty
  • Cross Linking
03

In context

Lead sponsor

Massachusetts Eye and Ear Infirmary is the lead sponsor of 100 studies on the registry; 23 are open to participants now.

Of its 13 completed or terminated interventional studies of FDA-regulated products, 7 (54%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Age 18 and older
  • Willing and able to provide written
  • 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

Exclusion Criteria:

  • History of Stevens-Johnson syndrome or ocular pemphigoid
  • Ocular or periocular
  • Non-healing epithelial defect of at least 0.5x0.5 mm in host corneal bed lasting ≥6 weeks preoperatively
  • Uncontrolled glaucoma
  • Change in topical regimen within 14 days of transplantation
  • Use of systemic 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 (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.
Terms in these criteria, in plain language(5)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Single group
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
96 participants (estimated)

Study arms

  • 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

  • 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

Interventions

  • ProcedureCorneal 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.

    Also known as: Treatment

  • ProcedureCorneal 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.

    Also known as: Control

06

What researchers measure

Primary outcomes

  1. Determining the Primary Safety of Corneal Cross Linking

    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

    Time frame: 24 Months

Secondary outcomes

  1. Measure of the Frequency of Graft Failures though Corneal Cross Linking

    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.

    Time frame: 24 Months

  2. Measure of Time from Surgery to Overall Graft Failure for Corneal Cross Linking over 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).

    Time frame: 24 Months

  3. Measure of Time from Surgery to Graft Rejection for Corneal Cross Linking over 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.

    Time frame: 24 Months

  4. Measure of the Efficacy of Corneal Cross Linking Through Image Review

    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.

    Time frame: 24 Months

07

Study locations

8 of 12 sites recruiting
  • University of California Irvine - Gavin Herbert Eye Institute
    Irvine, California 92617, United States
    Not yet recruiting
    • Marjan Farid, MD · Principal investigator
  • The University of California Los Angeles - Doris Stein Eye Research Center
    Los Angeles, California 90095, United States
    Not yet recruiting
    • Anthony Aldave, MD · Principal investigator
  • University of California San Francisco - Wayne and Gladys Valley Center for Vision
    San Francisco, California 94158, United States
    Not yet recruiting
  • University of Miami - Bascom Palmer Eye Institute
    Miami, Florida 33136, United States
    Recruiting
  • Price Vision Group
    Indianapolis, Indiana 46260, United States
    Recruiting
    • Marianne Price, PhD · Contactmprice@cornea.org · 317-844-5530
    • Lauren Blisset · Contactlauren@cornea.org · (317) 814-2996
    • David Price, MD · Principal investigator
  • Kansas City Eye Clinic
    Overland Park, Kansas 66204, United States
    Recruiting
    • Megan Hefer, CCRP · Contactmhefter@kceyeclinic.com · 913-341-3100
    • Christopher Ketcherside, MD · Principal investigator
    • Megan Haghnegahdar, MD · Sub investigator
  • Mid-Atlantic Cornea Consultant
    Towson, Maryland 21204, United States
    Recruiting
    • Lauren West · Contactlwest@midatlanticcornea.com · 410-616-9952
    • Alexander Altman, MD · Principal investigator
    • Sudeep Pramanik, MD · Principal investigator
  • Massachusetts Eye and Ear
    Boston, Massachusetts 02114, United States
    Recruiting
  • University of Michigan - Kellogg Eye Center
    Ann Arbor, Michigan 48015, United States
    Recruiting
    • Lianne Shami, BS · Contactliannes@med.umich.edu · 734-647-8397
    • Shahzad Mian, MD · Principal investigator
  • Wake Forest Baptist Eye Center
    Bermuda Run, North Carolina 27006, United States
    Not yet recruiting
  • Duke University - Duke Eye Center
    Durham, North Carolina 27705, United States
    Recruiting
  • Cincinnati Eye Institute
    Cincinnati, Ohio 45242, United States
    Recruiting
    • Lee Stokes · Contactlstokes@cvphealth.com · 513-569-3213
    • Kavitha Sivaraman, MD · Principal investigator
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 21, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT06753916
Responsible party
Joseph B. Ciolino, MD (Associate Professor of Ophthalmology, Massachusetts Eye and Ear Infirmary) — Principal investigator
First posted
Dec 31, 2024
Start date
Apr 1, 2025
Primary completion
Jan 1, 2028 (estimated)
Completion
Jan 1, 2031 (estimated)
Last update
Sep 21, 2026

Study contacts

Michael Cheung, MSc, CCRP
Contact
mcheung0@meei.harvard.edu
6175736060
Nikolay Boychev, OD, PhD
Contact
Joseph Ciolino, MD
principal investigator · Massachusetts Eye and Ear

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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