Corneal Collagen Cross-Linking Techniques for Keratoconus

Overseen By Jasmine Ly, OD

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Center for Sight, Sacramento, CA

Disqualifiers: Corneal transplant, Prior CXL, Pregnancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the best way to strengthen the cornea (the clear front part of the eye) in individuals with keratoconus, a condition where the cornea becomes thin and cone-shaped, or similar disorders. Researchers are comparing two methods: Epi-ON, where the outer layer of the cornea remains intact, and Epi-OFF, where it is removed before treatment. The goal is to determine which method is safer and more effective. This trial suits those diagnosed with keratoconus or similar corneal conditions who have experienced issues like corneal thinning or scarring. Participants should be willing to try either treatment method and adhere to the study schedule. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both Epi-OFF and Epi-ON corneal collagen cross-linking (CXL) treatments have been studied for their safety in people with keratoconus. Epi-OFF CXL involves removing the outer layer of the cornea, while Epi-ON keeps it intact.

For Epi-OFF, studies have found it effective and generally safe over time. One study reported no severe complications, such as corneal infections or scars, after treatment. However, removing the outer layer increases the risk of infection and slows recovery compared to Epi-ON.

Epi-ON offers better patient comfort and quicker recovery since the outer layer of the eye remains intact. This method reduces the risk of infection and is generally well-tolerated, with fewer side effects reported.

Both treatments continue to be studied, but current research suggests they are safe options for managing keratoconus, each with its own pros and cons regarding recovery and comfort. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these corneal collagen cross-linking techniques for keratoconus because they offer innovative approaches to treating this eye condition. Unlike traditional methods such as the standard Epi-OFF procedure, which requires removing the corneal epithelium, the Epi-ON treatment allows for the treatment without this step, potentially reducing discomfort and recovery time. Both Epi-ON and Epi-OFF techniques utilize Ricrolin+ as a riboflavin formulation and the VEGA UV-A system for irradiation, which are cutting-edge tools in enhancing the corneal structure. By comparing these methods, researchers hope to find more patient-friendly and effective options for managing keratoconus.

What evidence suggests that this trial's treatments could be effective for keratoconus?

This trial will compare Epi-OFF and Epi-ON CXL treatments for managing keratoconus. Research has shown that Epi-OFF CXL effectively stops the disease from worsening, though it may cause more discomfort, such as pain and slower healing. In contrast, Epi-ON CXL is gentler, maintaining corneal thickness and improving vision with fewer side effects. Studies have found that Epi-ON CXL can also effectively slow the progression of keratoconus. Both treatments in this trial use the Ricrolin+ riboflavin and VEGA UV-A system, which have been proven safe and effective. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals at least 12 years old with keratoconus or other corneal ectatic disorders. Participants must provide consent, have specific topography map changes, and be willing to use birth control if applicable. Those with prior CXL treatment, corneal transplants, certain ocular conditions, allergies to study materials, or inadequate corneal thickness are excluded.

Inclusion Criteria

I have been diagnosed with keratoconus or a similar eye condition.

If female and capable of becoming pregnant, must not be lactating or pregnant and must agree to use a medically acceptable form of birth control for at least one week prior to the treatment visit and to continue for one month following treatment

Presence of central or inferior steepening on the topography map

Exclusion Criteria

Study eye keratoconus severity is classified as being normal or atypical normal based on the OPD-Scan III keratoconus classification indices

A known contraindication, sensitivity, or allergy to the test article or its components or to study medications

A specific eye treatment technique cannot be used on me, as per my doctor's advice.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Epi-ON or Epi-OFF corneal collagen cross-linking treatment

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Multiple visits at Baseline, 6 Months, and 12 Months

What Are the Treatments Tested in This Trial?

Interventions

• Epi-OFF
• Epi-ON
• Ricrolin+
• VEGA UV-A system

Trial Overview The study compares two techniques of Corneal Collagen Cross-Linking (CXL) treatments for strengthening the cornea: Epi-OFF (removal of the outer layer of the cornea) and Epi-ON (outer layer left intact), both using Ricrolin+ and VEGA UV-A system in a randomized design.

How Is the Trial Designed?

Group I: Epi-ON CXL Active Control 2 Interventions

The Epi-OFF treatment will be performed with removal of the corneal epithelium before the first dose of riboflavin is administered. Ricrolin+ will be used as the riboflavin formulation for the pre-treatment and irradiation steps of the Epi-OFF treatments. The VEGA UV-A light will be used during the irradiation steps of the Epi-OFF treatment.

Group II: Epi-OFF CXL Active Control 2 Interventions

The Epi-ON treatment will be performed without removal of the corneal epithelium. Ricrolin+will be used as the riboflavin formulation for the pre-treatment and irradiation steps of the Epi-ON treatments. The VEGA UV-A light will be used during the irradiation steps of the Epi-ON treatment.

Who Is Running the Clinical Trial?

Center for Sight, Sacramento, CA

Lead Sponsor

Trials

1

Recruited

550+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6087595/

Epi-Off versus Epi-On Corneal Collagen Cross-Linking in ... CXL epi-on technique is preferable to CXL epi-off since it preserves the corneal thickness and improves visual acuity, also reducing the postoperative ocular ...

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

Clinical Outcomes of Repeated Corneal Crosslinking for ... This study aims to evaluate the efficacy and safety of repeated corneal cross-linking (CXL) in patients with progressive keratoconus who have ...

3. aaojournal.org aaojournal.org/article/S0161-6420(24)00282-3/fulltext

Safety and Efficacy of Epithelium-Off Corneal Collagen ... The most commonly reported risks of CXL include pain, infection, delayed epithelial healing, stromal haze, photophobia, and treatment failure.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT07194538

One-Year Outcomes After Conventional vs Accelerated Epi ... The study population comprises consecutive patients with progressive keratoconus managed with standard-of-care, epi-off corneal collagen cross- ...

5. eyewiki.org eyewiki.org/Techniques_for_Corneal_Collagen_Crosslinking:_Epi-off_vs_Epi-on

Techniques for Corneal Collagen Crosslinking: Epi-off vs ... Data for accelerated epi-on CXL is limited but shows promising results. Several studies have shown it to be effective in halting progression of ectasia but ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40357455/

Efficacy and Safety of Epi-On vs Epi-Off Corneal Cross ... This review compares two CXL methods, epithelium-on (epi-on) and epithelium-off (epi-off), to assess their safety and effectiveness for managing corneal ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11142646/

Conventional Epithelial-Off Corneal Crosslinking in Patients ... Our objective here was thus to evaluate the safety and 10-year outcomes of conventional epi-off CXL for the treatment of progressive KC for the ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03598634

Epi Off Versus Epi on Corneal Collagen Cross-linking in ... The aim of the study is to evaluate two different techniques of cross linking: standard epithelium off (CXL epi off) versus trans-epithelial (CXL epi on) cross ...