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

216 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized clinical trial will assess corneal astigmatism and visual outcomes in participants who have undergone corneal transplantation for keratoconus with ex vivo cross-linked donor corneal tissue versus participants who have undergone corneal transplantation for keratoconus with non-cross-linked donor corneas. Crosslinking is a procedure that stabilizes the biomechanical properties of the cornea; as a result, the cornea stiffens. It has been shown that this procedure stabilizes the cornea of patients with keratoconus or corneal ectasias. The FDA currently approves crosslinking for patients with progressive keratoconus and corneal ectasia following refractive surgery. Ex vivo crosslinking of donor corneal tissue for patients with keratoconus undergoing PK or DALK could stabilize the cornea and reduce the risk of high astigmatism and improve vision in patient with 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 data supports the effectiveness of the treatment Ex Vivo Corneal Cross-Linking of Donor Keratoplasty Tissue for Keratoconus?

Research shows that corneal collagen cross-linking (CXL) can reduce the need for corneal transplants in keratoconus patients and stabilize the condition, suggesting its effectiveness. Additionally, studies indicate that accelerated CXL improves vision and corneal shape in progressive keratoconus, supporting the potential benefits of similar treatments. ^{1 2 3 4 5}

Is corneal cross-linking safe for humans?

Research shows that corneal cross-linking is generally safe for treating keratoconus, including in children. Different methods have been studied, and they all focus on safety and effectiveness. ^{2 6 7 8 9}

How is the treatment Ex Vivo Corneal Cross-Linking of Donor Keratoplasty Tissue different from other treatments for keratoconus?

This treatment is unique because it involves strengthening the cornea outside the body before transplanting it, which is different from traditional corneal cross-linking that is done directly on the patient's eye. ^{4 10 11 12 13}

Research Team

Joseph Ciolino, MD

Principal Investigator

Massachusetts Eye and Ear

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

References

1. United States pubmed.ncbi.nlm.nih.gov

Did Collagen Cross-Linking Reduce the Requirement for Corneal Transplantation in Keratoconus? The Canadian Experience. [2020]

2. France pubmed.ncbi.nlm.nih.gov

[High-irradiance accelerated corneal collagen crosslinking for the treatment of keratoconus: A retrospective study]. [2017]

3. Pakistan pubmed.ncbi.nlm.nih.gov

Visual and Topographical Outcomes Following Accelerated Trans-Epithelial Corneal Crosslinking in Progressive Keratoconus. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Measurement of In Vivo Biomechanical Changes Attributable to Epithelial Removal in Keratoconus Using a Noncontact Tonometer. [2021]

5. France pubmed.ncbi.nlm.nih.gov

Corneal collagen cross-linking in keratoconus -- long-term prospective study. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Analysis of the outcomes of three different cross-linking protocols for treatment of paediatric keratoconus: A multicentre randomized controlled trial. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Accelerated corneal crosslinking for treatment of progressive keratoconus in pediatric patients. [2022]

8. Pakistan pubmed.ncbi.nlm.nih.gov

Efficacy and safety of transepithelial collagen cross linking for progressive keratoconus. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical results with two different pharmaceutical preparations of riboflavin in corneal cross-linking: an 18-month follow up. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Predicting factors for the efficacy of cross-linking for keratoconus. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Corneal Cross-linking for Progressive Keratoconus: Up to 13 Years of Follow-up. [2021]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Epi-off-lenticule-on corneal collagen cross-linking in thin keratoconic corneas. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

Outcomes of Simultaneous and Sequential Cross-linking With Excimer Laser Surface Ablation in Keratoconus. [2019]