Corneal Collagen Crosslinking for Keratoconus

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Cornea and Laser Eye Institute

Disqualifiers: Pregnancy, Nystagmus, Corneal scarring, 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: 2

Duration: Intraoperative

160 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a treatment that uses UV light and vitamin B2 to strengthen weak or misshapen corneas in patients with keratoconus or post-surgery ectasia. The treatment works by creating new bonds in the cornea, making it more stable. This method has been widely adopted and refined to treat progressive keratoconus by increasing the strength of the cornea.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the treatment Corneal Collagen Crosslinking for Keratoconus?

Research shows that corneal collagen cross-linking (CXL) with riboflavin and ultraviolet-A light is effective in stopping the progression of keratoconus, a condition where the cornea becomes thin and cone-shaped, over a long period, with studies indicating positive results even 10 years after treatment. ^{1 2 3 4 5}

Is corneal collagen cross-linking safe for humans?

Corneal collagen cross-linking is generally considered safe, but there can be complications like persistent epithelial defects (problems with the outer layer of the eye) and corneal opacity (cloudiness of the cornea) if the wrong type of dextran is used in the riboflavin solution. ^{1 3 5 6 7}

How is the treatment Corneal Collagen Crosslinking for Keratoconus unique?

This treatment is unique because it uses a combination of riboflavin (a type of vitamin B2) and dextran to strengthen the cornea by creating new bonds between collagen fibers, which helps stop the progression of keratoconus (a condition where the cornea becomes thin and cone-shaped). The use of hypotonic riboflavin can be particularly beneficial for patients with thinner corneas, although it may not be effective in extremely thin cases. ^{1 2 3 5 6}

Research Team

Peter Hersh, MD

Principal Investigator

Cornea and Laser Eye Institute

Eligibility Criteria

This trial is for adults over 18 with progressive keratoconus or corneal ectasia, whose vision isn't fully corrected to 20/20 with lenses. Their cornea must be thicker than 300 microns. It's not for those sensitive to the study drugs, have certain eye conditions, are pregnant/lactating, can't keep a steady gaze during treatment, or have other risks as assessed by the investigator.

Inclusion Criteria

Vision with contact lenses or glasses is worse than 20/20

Corneal thickness greater than 300 microns at the thinnest point

My eye condition has worsened in the last 2 years or occurred after eye surgery.

Exclusion Criteria

I have noticeable scarring on my cornea where I received CXL treatment.

I have had an eye condition that could cause future problems.

I do not have conditions like nystagmus that make it hard to keep my gaze steady.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo corneal collagen crosslinking (CXL) with either riboflavin/dextran or hypotonic riboflavin during UV exposure

Intraoperative

1 visit (in-person)

Follow-up

Participants are monitored for changes in corneal thickness, keratometry, refraction, visual acuity, and endothelial cell density

12 months

Multiple visits at 1, 3, 6, and 12 months

Treatment Details

Interventions

• Corneal Collagen Crosslinking
• Hypotonic Riboflavin
• Riboflavin/Dextran

Trial Overview The trial tests two types of corneal collagen crosslinking (CXL) treatments using Hypotonic Riboflavin and Riboflavin/Dextran in patients with keratoconus or ectasia. The goal is to see if maintaining corneal thickness improves the consistency and predictability of CXL outcomes.

Participant Groups

Group I: Riboflavin/dextran Active Control 1 Intervention

Administration of Riboflavin/dextran every 2 minutes for the duration of UV exposure.

Group II: Hypotonic Riboflavin Active Control 1 Intervention

Administration of hypotonic riboflavin every 2 minutes for the duration of UV exposure.

Who Is Running the Clinical Trial?

Cornea and Laser Eye Institute

Lead Sponsor

Trials

10

Recruited

1,100+

Findings from Research

Accelerated corneal cross-linking (CXL) using hypotonic riboflavin solution is as effective as using standard riboflavin solution in treating keratoconus over a 2-year period, with similar outcomes in corneal thickness, keratometry, and visual acuity.

Both treatment groups showed comparable decreases in corneal thickness after 6 months, indicating that hypotonic riboflavin can effectively preserve corneal structure while preventing keratoconus progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Outcomes of Accelerated Corneal Cross-linking in the Treatment of Keratoconus: Comparison of Hypotonic Riboflavin Solution With Standard Riboflavin Solution. Akkaya, S., Ulusoy, DM., Duru, Z., et al.[2020]

Both the Sina Darou and Uznach formulations of Riboflavin were found to be equally effective in improving visual acuity and corneal topography in 60 keratoconus patients after 6 months of corneal collagen cross-linking (CXL).

The Sina Darou formulation resulted in a greater decrease in corneal hysteresis compared to the Uznach formulation, suggesting potential differences in their effects on corneal biomechanical properties, which will be further evaluated in long-term studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of clinical results of two pharmaceutical products of riboflavin in corneal collagen cross-linking for keratoconus. Hashemi, H., Seyedian, MA., Miraftab, M., et al.[2021]

Riboflavin and ultraviolet-A induced collagen cross-linking (CXL) effectively stabilizes keratoconus over a long-term period, with significant improvements in corneal curvature and best corrected visual acuity (BCVA) observed 10 years post-treatment in a study of 30 eyes from 20 patients.

The procedure is minimally invasive and safe, showing no damage to the corneal endothelium or deeper structures, with only two patients experiencing continued progression of keratoconus requiring re-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Corneal collagen cross-linking with riboflavin and ultraviolet-A light in progressive keratoconus. Results after 10-year follow-up]. Theuring, A., Spoerl, E., Pillunat, LE., et al.[2022]

Using dextran sulfate instead of the standard dextran (T-500) in riboflavin solutions during collagen cross-linking (CXL) for keratoconus led to severe complications, including persistent corneal epithelial defects and stromal haze, resulting in poor visual outcomes for all patients involved.

The study of 6 eyes from 4 male patients showed that these complications not only caused loss of vision but also complicated subsequent corneal transplants, highlighting the critical importance of using the correct dextran formulation in CXL procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistent Epithelial Defects and Corneal Opacity After Collagen Cross-Linking With Substitution of Dextran (T-500) With Dextran Sulfate in Compounded Topical Riboflavin. Höllhumer, R., Watson, S., Beckingsale, P.[2022]

Corneal collagen cross-linking (CXL) using dextran-free isotonic riboflavin solution is a safe treatment for keratoconus, with no reported intraoperative or postoperative complications in a study of 26 patients.

At a 6-month follow-up, patients showed significant improvements in best corrected visual acuity and reductions in maximum keratometry and corneal thickness, indicating effective short-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Six-month outcomes of corneal crosslinking with dextran-free isotonic riboflavin solution. Oltulu, R., Satirtav, G., Donbaloglu, M., et al.[2017]

References

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

Long-term Outcomes of Accelerated Corneal Cross-linking in the Treatment of Keratoconus: Comparison of Hypotonic Riboflavin Solution With Standard Riboflavin Solution. [2020]

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

Limitation of collagen cross-linking with hypoosmolar riboflavin solution: failure in an extremely thin cornea. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of clinical results of two pharmaceutical products of riboflavin in corneal collagen cross-linking for keratoconus. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

[Corneal collagen cross-linking with riboflavin and ultraviolet-A light in progressive keratoconus. Results after 10-year follow-up]. [2022]

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

Persistent Epithelial Defects and Corneal Opacity After Collagen Cross-Linking With Substitution of Dextran (T-500) With Dextran Sulfate in Compounded Topical Riboflavin. [2022]

6. Brazil pubmed.ncbi.nlm.nih.gov

Six-month outcomes of corneal crosslinking with dextran-free isotonic riboflavin solution. [2017]

7. England pubmed.ncbi.nlm.nih.gov

Superior outcome of corneal collagen cross-linking using riboflavin with methylcellulose than riboflavin with dextran as the main supplement. [2019]