Corneal Cross-Linking for Keratoconus

(EVOKE Trial)

Overseen By Joseph B Ciolino, MD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Joseph B. Ciolino, MD

Must not be taking: Antibiotics

Disqualifiers: Stevens-Johnson syndrome, Ocular pemphigoid, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: Surgery day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two types of corneal transplants for individuals with keratoconus, a condition where the cornea thins and becomes cone-shaped, causing vision problems. One group will receive donor corneas strengthened with a process called cross-linking before the transplant, while the other group will receive regular donor corneas. The goal is to determine which method better stabilizes the cornea and improves vision. This trial suits adults with keratoconus who need a corneal transplant and have not had one before. As an unphased trial, it provides an opportunity to explore innovative treatment options for keratoconus.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are currently being treated with antibiotics or have a history of certain conditions like Stevens-Johnson syndrome, you may not be eligible to participate.

What prior data suggests that ex vivo corneal cross-linking of donor keratoplasty tissue is safe?

Research has shown that corneal cross-linking is generally safe for individuals with keratoconus, a condition where the cornea weakens and becomes misshapen. This procedure strengthens the cornea, potentially improving vision. The FDA has approved this treatment for those with worsening keratoconus and corneal ectasia, where the cornea thins and weakens after certain eye surgeries.

While specific data on the safety of ex vivo cross-linking (performed before cornea transplantation) is not yet available, this technique aims to stabilize the cornea beforehand. It relies on the same principles as the approved procedure for living corneas, suggesting potential safety.

Studies have demonstrated that cross-linking can reduce issues like astigmatism, which affects light focus in the eye, and may improve vision. Overall, current evidence supports the safety of similar procedures, though specific safety data for this exact treatment is still being collected. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the ex vivo corneal cross-linking of donor keratoplasty tissue because it introduces a new technique in preparing corneal tissue for transplantation. Unlike standard keratoplasty procedures, which use untreated donor tissue, this method strengthens the donor corneal tissue before transplantation by cross-linking collagen fibers. This potentially enhances the durability and longevity of the graft, reducing the risk of complications like graft failure or the progression of keratoconus. By fortifying the corneal structure in advance, this innovative approach aims to improve overall outcomes for patients with keratoconus.

What evidence suggests that ex vivo corneal cross-linking is effective for keratoconus?

Research has shown that corneal cross-linking effectively stabilizes the cornea in people with keratoconus, a condition where the cornea thins and bulges. Studies have found that this procedure helps maintain vision and significantly reduces astigmatism, which occurs when the cornea isn't perfectly round, causing blurry vision. In this trial, one arm will involve ex vivo cross-linking of donor corneal tissue before keratoplasty, while the control arm will use non-cross-linked donor corneal tissue. Previous studies demonstrated that repeating the cross-linking procedure over 12 months kept keratoconus stable in all patients without major issues. Another study found that cross-linking reduced corneal swelling in a lab model that imitates real-life conditions. Overall, cross-linking offers a promising way to improve outcomes for people with keratoconus. ^{1 2 6 7 8}

Who Is on the Research Team?

Joseph Ciolino, MD

Principal Investigator

Massachusetts Eye and Ear

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-50 with keratoconus requiring corneal transplantation, who haven't had a previous transplant or cross-linking, and have no history of certain eye conditions or systemic diseases. Participants must consent to study requirements and avoid additional corneal procedures during the study.

Inclusion Criteria

Willing and able to provide written informed consent.

Willing and able to comply with study assessments for the full duration of the study.

I agree not to undergo any additional eye surgeries during the study.

Exclusion Criteria

You are currently participating in another medical study or trial at the same time.

Pregnancy (positive pregnancy test) or lactating

I have had surgery for glaucoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants undergo corneal transplantation with either cross-linked or non-cross-linked donor tissue

Surgery day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after surgery with visits at 1 Day, 1 Week, 1 Month, 6 Months, 1 Year, 1.5 Years, 2 Years, and 2.5 Years post-surgery

130 weeks

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ex Vivo Corneal Cross-Linking of Donor Keratoplasty Tissue

Trial Overview The trial tests if using donor corneas treated with Riboflavin and UV light (cross-linking) before transplant can improve vision and reduce astigmatism in keratoconus patients compared to transplants without this treatment.

How Is the Trial Designed?

Group I: Ex vivo cross linking of donor corneal tissue Experimental Treatment 1 Intervention

Treatment Arm: The donor corneal tissue used in the PK or DALK procedures will previously undergo ex vivo crosslinking.

Group II: Non-cross-linked donor corneal tissue for keratoplasty Placebo Group 1 Intervention

Control Arm: The donor corneal tissue used in the PK or DALK procedures will not previously undergo ex vivo crosslinking.

Who Is Running the Clinical Trial?

Joseph B. Ciolino, MD

Lead Sponsor

Trials

4

Recruited

340+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12413346/

Clinical Outcomes of Repeated Corneal Crosslinking for ... Repeated accelerated CXL stabilized keratoconus in all 26 eyes over 12 months, while no major complications were observed. What has been learned ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04584125?term=RIBOFLAVIN%205'-PHOSPHATE&rank=9

A Randomized Clinical Trial of Ex Vivo Corneal Cross ... This randomized clinical trial will assess corneal astigmatism and visual outcomes in participants who have undergone corneal transplantation for ...

3. ophthalmologyscience.org ophthalmologyscience.org/article/S2666-9145(25)00114-9/fulltext

Clinical Efficacy of Ex Vivo Cross-Linking on ... Corneal crosslinking ameliorates the extent of corneal oedema in subsequent acute keratoconus in an ex vivo model

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11898512/

Long-Term Outcomes in Crosslinking Therapy for Patients ... CXL treatment is an important treatment method in the treatment of keratoconus, preserving visual functions, significantly reducing the severity of astigmatism.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2452403419300032

Five years outcomes after corneal cross-linking for ... The aim of this large prospective study was to evaluate the five year outcomes of CXL and to extract possible pre-operative parameters to predict the outcome ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2666914525001149

Clinical Efficacy of Ex Vivo Cross-Linking on ... These results suggest that ex vivo CXL of donor tissue may be a particularly promising option to improve the survival rates of keratoplasties that are defined ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12206266/

Repeated corneal crosslinking for progressive keratoconus This review summarises the existing data on repeated CXL after primary failure, emphasising on clinical efficacy and safety.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04584125?tab=history

Record History | NCT04584125 A Randomized Clinical Trial of Ex Vivo Corneal Cross-Linking of Donor Keratoplasty Tissue for Keratoconus Used for Keratoplasty in Keratoconus Patients (EVOKE).