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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called corneal collagen crosslinking (CXL) to determine if it can slow or stop the progression of eye conditions like keratoconus and corneal ectasia, which cause blurry vision. The researchers aim to discover whether maintaining corneal thickness during the procedure enhances the treatment's predictability and effectiveness. Participants will receive either riboflavin/dextran or hypotonic riboflavin, both used in the CXL procedure, during the trial. Individuals diagnosed with worsening keratoconus or corneal ectasia after surgery, whose vision does not improve beyond 20/20 with glasses or contacts, may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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.

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

Studies have shown that corneal collagen crosslinking (CXL) is generally safe for treating eye conditions like keratoconus. Research using a specific method with riboflavin and dextran has confirmed its safety over six months. However, more information is needed to understand its safety and effectiveness over several years.

Similarly, using hypotonic riboflavin has been found to be safe and effective in stabilizing keratoconus. One study showed it is just as safe as other treatments for this condition.

Both treatments aim to stop or slow the progression of eye problems, helping to maintain stable vision. While research supports short-term safety, the long-term effects are still under investigation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about corneal collagen crosslinking for keratoconus because it strengthens the corneal tissue by encouraging new collagen bonds, potentially halting the progression of the disease. Unlike standard treatments like glasses or contact lenses, which only correct vision, this method targets the root cause by reinforcing the cornea itself. The use of riboflavin (vitamin B2) combined with UV light makes the cornea more rigid, providing a novel approach compared to traditional options. Additionally, the study explores two formulations: riboflavin/dextran and hypotonic riboflavin, both of which are administered during UV exposure, offering potential improvements in efficacy and safety.

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

Research has shown that corneal collagen crosslinking (CXL) can effectively slow keratoconus, a condition where the cornea thins and bulges. In this trial, participants will receive either riboflavin/dextran or hypotonic riboflavin as part of the treatment. Studies have found that riboflavin/dextran can significantly improve vision and stabilize the condition. Another study discovered that both riboflavin/dextran and hypotonic riboflavin solutions lead to similar positive outcomes, such as improved vision and corneal shape. Hypotonic riboflavin may help maintain corneal thickness by preserving hydration, potentially making the treatment more predictable. Both treatments have demonstrated similar long-term effectiveness and safety in enhancing corneal health and vision. ^{2 4 6 7 8}

Who Is on the Research Team?

Peter Hersh, MD

Principal Investigator

Cornea and Laser Eye Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/32032432/

Long-term Outcomes of Accelerated Corneal Cross-linking ...

Conclusions: The efficacy of accelerated CXL with hypotonic riboflavin solution was comparable to that with the standard riboflavin solution in ...

2.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0002939425005173

Effectiveness and safety of cross-linking in keratoconus ...

Key outcomes included maximum and mean corneal curvature (Kmax and Kmean) corrected and uncorrected distance visual acuity, refractive error, ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01152541

NCT01152541 | Corneal Collagen Crosslinking for ...

... hypotonicity may tend to keep the cornea better hydrated and thicker. The primary goal of the study is to see if the use of hypotonic riboflavin (rather ...

4.

healio.com

healio.com/ophthalmology/journals/jrs/2020-2-36-2/%7B919fe78e-7ff9-431e-81f4-1384a781c659%7D/long-term-outcomes-of-accelerated-corneal-cross-linking-in-the-treatment-of-keratoconus-comparison-of-hypotonic-riboflavin-solution-with-standard-riboflavin-solution?logout=0

Long-term Outcomes of Accelerated Corneal Cross-linking ...

To the best of our knowledge, this is the first study reporting the long-term clinical outcomes of accelerated CXL using hypotonic riboflavin.

5.

iovs.arvojournals.org

iovs.arvojournals.org/article.aspx?articleid=2794640

The comparative efficacy and safety of hypotonic vs isotonic ...

Conclusions : This real-world study found that CXL was associated with improved visual and keratometry outcomes irrespective of the riboflavin type in 'thick' ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/25050368/

a contralateral study with 0.5% hypotonic riboflavin solution

Corneal collagen cross-linking with and without epithelial ... hypotonic 0.5% riboflavin were equally safe and effective in stabilization of keratoconus.

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6507378/

The Outcome of Corneal Collagen Cross-Linking in Patients ...

The present study showed that CXL prevented the further progression of advanced progressive keratoconus in 29 of 30 eyes at the 2-year follow-up.

8.

health.ny.gov

health.ny.gov/health_care/medicaid/ebbrac/docs/2024-07-25_keratoconus.pdf

Collagen Cross-Linking in Individuals With Keratoconus ...

Reported outcomes should include visual acuity, corneal topography, and quality of life. Data on long-term outcomes for all types of CXL using riboflavin and ...