Corneal Collagen Crosslinking for Keratoconus

Overseen By Stacey Lazar

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Cornea and Laser Eye Institute

Disqualifiers: Corneal disease, Pregnancy, Nystagmus, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

170 Participants Needed

Trial Summary

What is the purpose of this trial?

Corneal collagen crosslinking has been demonstrated as an effective method of reducing progression of both keratoconus and post-refractive corneal ectasia, as well as decreasing the steepness of the cornea in these pathologies. Performing an accelerated CXL procedure with pulsed UVA light may increase the oxygenation of the cornea, which may improve the crosslinking efficacy.

Do I need to stop 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 trial team or your doctor.

What data supports the effectiveness of the treatment Riboflavin Ophthalmic Solution for keratoconus?

Research shows that corneal collagen crosslinking with riboflavin and UV light can stabilize or improve the cornea in keratoconus patients, with 80% of cases showing a decrease in corneal curvature and improved vision. ^{1 2 3 4 5}

Is corneal collagen crosslinking with riboflavin safe for humans?

Research shows that corneal collagen crosslinking with riboflavin is generally safe when performed correctly, with most studies reporting no serious side effects. However, there have been cases of persistent eye surface defects and cloudiness when the wrong type of additive was used, highlighting the importance of using the correct formulation. ^{1 2 3 6 7}

How is the treatment for keratoconus using riboflavin ophthalmic solution unique?

The treatment for keratoconus using riboflavin ophthalmic solution is unique because it involves a process called corneal collagen cross-linking, where riboflavin (vitamin B2) is applied to the eye and activated by ultraviolet A (UVA) light to strengthen the cornea and slow the progression of the disease. This method is different from other treatments as it directly targets the corneal structure to improve its stability and prevent further deterioration. ^{3 6 8 9 10}

Research Team

Peter S Hersh, MD

Principal Investigator

Cornea and Laser Eye Institute, Hersh Vision Group

Eligibility Criteria

Adults diagnosed with keratoconus or corneal ectasia following refractive surgery can join. They must have specific corneal steepening, be willing to follow the visit schedule, and not wear contact lenses for a week before screening. Pregnant women, those planning pregnancy, lactating individuals, or people with certain eye conditions or sensitivities are excluded.

Inclusion Criteria

I am 18 or older with a diagnosis of keratoconus or corneal ectasia.

Presence of central or inferior corneal steepening on the Pentacam map

My eye condition is related to keratoconus or corneal ectasia after surgery.

Exclusion Criteria

I have noticeable scarring in the treated eye area.

Pregnancy (including plan to become pregnant) or lactation during the course of the study

I do not have any conditions like nystagmus that would prevent me from keeping my gaze steady during treatments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive corneal collagen crosslinking treatment with either continuous or pulsed UVA light

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in maximum keratometry (Kmax) and mean keratometry (meanK) post-treatment

6 months

Multiple visits (in-person)

Treatment Details

Interventions

• Riboflavin Ophthalmic Solution

Trial Overview The trial is testing an accelerated method of strengthening the cornea using riboflavin ophthalmic solution and UV-A light (either pulsed or continuous). The goal is to see if this speeds up oxygenation and improves treatment outcomes for patients with keratoconus or ectasia.

Participant Groups

Group I: Continuous UVA Active Control 1 Intervention

Riboflavin administration one drop every two minutes with administration of 12mW/cm2 of continuous UVA light for 7.5 minute exposure time

Group II: Pulsed UVA Active Control 1 Intervention

Riboflavin administration one drop every two minutes with administration of 12mW/cm2 of pulsed UVA light for 15 minute exposure time

Riboflavin Ophthalmic Solution is already approved in United States, European Union for the following indications:

Approved in United States as Riboflavin Ophthalmic Solution for:

• Progressive keratoconus
• Corneal ectasia following refractive surgery

Approved in European Union as Riboflavin Ophthalmic Solution for:

• Progressive keratoconus
• Corneal ectasia following refractive surgery

Who Is Running the Clinical Trial?

Cornea and Laser Eye Institute

Lead Sponsor

Trials

10

Recruited

1,100+

Findings from Research

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]

Corneal cross-linking using riboflavin and UV light is a safe procedure, as none of the patients experienced a loss in best spectacle corrected visual acuity (BSCVA) after treatment.

The treatment effectively halted the progression of keratoconus in all patients, with a notable reduction in corneal curvature and improvements in unaided visual acuity over six months, although some changes were not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Corneal Cross-linking for the treatment of keratoconus: preliminary results]. Jankov, MR., Hafezi, F., Beko, M., et al.[2019]

Photooxidative crosslinking of corneal collagen using 0.1% riboflavin and UVA light at 370 nm is a safe and effective treatment for keratoconus, preventing disease progression.

In 80% of cases, this treatment resulted in a decrease in corneal curvature by about 2 diopters, leading to stabilization of the cornea and improved visual acuity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Collagen crosslinking with riboflavin and UVA-light in keratoconus]. Kohlhaas, M.[2021]

In a study of 38 eyes from 25 patients over 36 months, riboflavin UVA collagen crosslinking (CXL) treatment for keratoconus did not show significant changes in corneal topography indices or uncorrected visual acuity, indicating stability in corneal properties post-treatment.

While best-corrected visual acuity showed a slight improvement, it was not statistically significant, and importantly, no corneal thinning occurred, suggesting that CXL is a safe option for stabilizing keratoconus without adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of corneal topography indices after collagen crosslinking for keratoconus. Hassan, Z., Szalai, E., Módis, L., et al.[2022]

In a study of 49 eyes from 47 patients with progressive keratoconus and thin corneas, both corneal collagen crosslinking (CXL) with hypoosmolar riboflavin and standard CXL showed significant improvements in uncorrected and best-corrected visual acuity after 3 years, with no significant differences between the two methods.

Both treatment groups demonstrated safety, as there was no significant endothelial cell loss or sight-threatening complications, and no progression of keratoconus was observed in any patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term visual, refractive, tomographic and aberrometric outcomes of corneal collagen crosslinking (CXL) with or without hypoosmolar riboflavin solution in the treatment of progressive keratoconus patients with thin corneas. Celik Buyuktepe, T., Ucakhan, OO.[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]

A study involving 100 eyes from 61 patients with progressive keratoconus found that both 0.1% riboflavin solutions used in corneal collagen crosslinking (CXL) were equally safe and effective, with no significant differences in visual and corneal measurements after 12 months.

No serious complications occurred in either group during or after the procedure, indicating that both riboflavin solutions can be safely used for treating keratoconus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective, Comparative, Clinical Study to Evaluate the Safety and Efficacy of Two Different 0.1% Riboflavin Solutions Used in Collagen Crosslinking Treatment for Patients with Keratoconus. Brar, S., Ganesh, S., Reddy, SS., et al.[2022]

An 18-year-old boy developed bilateral viral keratitis after undergoing corneal collagen crosslinking for keratoconus, highlighting a rare complication associated with this procedure.

The condition was successfully treated with antiviral medication, leading to a good visual outcome, suggesting that prophylactic antiviral treatment may be beneficial for patients with a history of viral keratitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral viral keratitis following corneal collagen crosslinking for progressive keratoconus. Sitaula, S., Singh, SK., Gurung, A.[2020]

Corneal collagen cross-linking (CXL) with riboflavin significantly improved corneal topography and refractive outcomes in 66 patients with keratoconus over a one-year follow-up period, indicating its efficacy as a treatment.

Postoperative measurements showed a significant reduction in the mean spherical equivalent and improvements in corneal shape, demonstrating that CXL can effectively stabilize and enhance corneal structure in patients with progressive keratoconus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topographic corneal changes after collagen cross-linking in patients with corneal keratoconus. Razmjoo, H., Nasrollahi, AP., Salam, H., et al.[2022]

In a long-term study of 44 keratoconic eyes treated with riboflavin ultraviolet A collagen cross-linking, the procedure demonstrated significant stability of keratoconus over an average follow-up of 52.4 months, with no major side effects reported.

Patients experienced notable improvements in visual acuity, with an average increase of 1.9 Snellen lines for best spectacle-corrected vision and 2.7 lines for uncorrected vision, alongside reductions in corneal irregularities and aberrations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term results of riboflavin ultraviolet a corneal collagen cross-linking for keratoconus in Italy: the Siena eye cross study. Caporossi, A., Mazzotta, C., Baiocchi, S., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

2. Brazil pubmed.ncbi.nlm.nih.gov

[Corneal Cross-linking for the treatment of keratoconus: preliminary results]. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

[Collagen crosslinking with riboflavin and UVA-light in keratoconus]. [2021]

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

Assessment of corneal topography indices after collagen crosslinking for keratoconus. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Long-term visual, refractive, tomographic and aberrometric outcomes of corneal collagen crosslinking (CXL) with or without hypoosmolar riboflavin solution in the treatment of progressive keratoconus patients with thin corneas. [2022]

6. 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]

7. New Zealand pubmed.ncbi.nlm.nih.gov

A Prospective, Comparative, Clinical Study to Evaluate the Safety and Efficacy of Two Different 0.1% Riboflavin Solutions Used in Collagen Crosslinking Treatment for Patients with Keratoconus. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Bilateral viral keratitis following corneal collagen crosslinking for progressive keratoconus. [2020]

9. India pubmed.ncbi.nlm.nih.gov

Topographic corneal changes after collagen cross-linking in patients with corneal keratoconus. [2022]

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

Long-term results of riboflavin ultraviolet a corneal collagen cross-linking for keratoconus in Italy: the Siena eye cross study. [2022]