Standard vs. Accelerated Corneal Crosslinking for Keratoconus

Overseen by Francis Price, Jr., MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Price Vision Group

Disqualifiers: Insufficient corneal thickness, Pregnancy, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial compares two methods of corneal crosslinking, a procedure that strengthens the cornea using special eye drops and light. It targets people with progressive keratoconus or corneal ectasia, conditions where the cornea weakens and bulges out. The treatment aims to make the cornea more stable and prevent further vision problems. Corneal crosslinking (CXL) has become the standard treatment for rapidly progressing 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. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment for keratoconus?

Research shows that corneal cross-linking with riboflavin and UV light is effective in stopping the progression of keratoconus, a condition where the cornea (the clear front part of the eye) becomes thin and cone-shaped. Studies indicate that this treatment helps stabilize the cornea and improve its strength, with rare complications. ^{1 2 3 4 5}

Is corneal cross-linking safe for humans?

Corneal cross-linking with riboflavin and UV light is generally considered safe, but there are rare cases of complications, such as infections, that may require further treatment. ^{1 2 6 7 8}

How is the treatment for keratoconus using Riboflavin 0.1% unique?

This treatment, known as corneal crosslinking, uses riboflavin (a type of vitamin B2) combined with UV light to strengthen the cornea, which is different from other treatments that may not address the underlying structural weakness of the cornea. The accelerated version of this treatment is faster and may be more convenient for patients compared to the standard method. ^{1 5 9 10 11}

Research Team

Francis Price, Jr., MD

Principal Investigator

Price Vision Group

Eligibility Criteria

This trial is for people with progressive keratoconus or corneal ectasia after refractive surgery. It's not suitable for those with conditions affecting eye healing, a history of chemical injury or slow healing, known sensitivity to the medications used in the study, pregnant individuals, those with thin corneas, or other ocular conditions that could complicate treatment.

Inclusion Criteria

I have been diagnosed with keratoconus or had corneal thinning after eye surgery.

Exclusion Criteria

You are known to be sensitive to the medications used in the study.

I have an eye condition that could lead to complications.

You are currently pregnant.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either accelerated or standard corneal crosslinking treatment

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Multiple visits (in-person)

Treatment Details

Interventions

• Riboflavin 0.1% (Crosslinking Agent)

Trial Overview The trial aims to compare two methods of corneal crosslinking: accelerated and standard. Both use riboflavin (vitamin B2) drops but differ in how quickly UV light is applied to strengthen the cornea and halt progression of keratoconus or ectasia.

Participant Groups

Group I: Accelerated Active Control 1 Intervention

Treatment with 0.1% riboflavin eye drops and 9 mW/cm2 UVA light for 10 minutes

Group II: Standard Active Control 1 Intervention

Treatment with 0.1% riboflavin eye drops and 3 mW/cm2 UVA light for 30 minutes

Who Is Running the Clinical Trial?

Price Vision Group

Lead Sponsor

Trials

12

Recruited

1,700+

Findings from Research

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]

In a study of 57 eyes from 55 patients with progressive keratoconus, corneal crosslinking (CXL) with riboflavin led to significant improvements in best corrected visual acuity and reductions in key corneal measurements over a 24-month follow-up period.

CXL was effective in stabilizing keratoconus, as evidenced by a decrease in keratometry readings and corneal volume, while maintaining its efficacy even as the cornea began to recover its original volume after the initial treatment phase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term results of corneal collagen crosslinking for progressive keratoconus. De Bernardo, M., Capasso, L., Lanza, M., et al.[2022]

Corneal crosslinking using UVA-riboflavin is an effective treatment for conditions like keratoconus and infectious keratitis that haven't responded to other therapies, enhancing the stability of corneal tissue.

The procedure generally halts the progression of these eye conditions, with rare complications reported for surrounding structures like the corneal endothelial cells and retina.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The progress of corneal crosslink in corneal disease]. Yu, JF., Huang, YF.[2013]

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]

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]

In a study of 280 eyes from 237 patients, both short (15 minutes) and standard (30 minutes) riboflavin induction times in corneal cross-linking for keratoconus showed similar improvements in visual acuity and keratometry after one year.

However, the short induction time resulted in greater flattening of maximum keratometry (Kmax) and a higher incidence of corneal haze, indicating a trade-off between efficacy and potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Standard Corneal Cross-Linking Procedures Performed With Short Versus Standard Riboflavin Induction: A Save Sight Keratoconus Registry Study. Benito-Pascual, B., Kandel, H., Abbondanza, M., et al.[2023]

Riboflavin/UV cross-linking is a generally safe surgical method for stabilizing keratoconus, with rare complications reported.

However, there is a risk of severe infections, as demonstrated in a case where a 40-year-old patient developed a methicillin-resistant Staphylococcus aureus (MRSA) infection post-procedure, leading to the need for a corneal transplant despite intensive treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Corneal ulcer caused by MRSA after UV/riboflavin cross-linking in a patient with bilateral keratoconus]. Bödemann, M., Kohnen, T.[2021]

Riboflavin-induced ultraviolet light cross-linking is an approved treatment in Europe for keratoconus and is being explored for other corneal disorders, highlighting its growing acceptance in ophthalmology.

The review focuses on key studies that demonstrate the safety and efficacy of this treatment, particularly for patients in the early stages of keratoconus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corneal cross linking for keratoconus. Keating, A., Pineda, R., Colby, K.[2013]

In a study of 40 eyes from 30 young adult patients with early progressive keratoconus, transepithelial enhanced fluence pulsed light M accelerated crosslinking effectively halted disease progression over a 3-year follow-up, with significant improvements in visual acuity and corneal curvature.

No adverse events were reported during the treatment, indicating that this method is safe, and it achieved a mean demarcation line depth of 282.6 μm, suggesting effective treatment penetration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transepithelial Enhanced Fluence Pulsed Light M Accelerated Crosslinking for Early Progressive Keratoconus with Chemically Enhanced Riboflavin Solutions and Air Room Oxygen. Mazzotta, C., Balamoun, AA., Chabib, A., et al.[2022]

Accelerated corneal collagen crosslinking (CXL) effectively stabilizes corneal topography in patients with mild to moderate keratoconus, with no complications reported during a 12-month follow-up of 16 eyes from 14 patients.

There was a significant improvement in uncorrected distance visual acuity (UDVA) after 12 months, indicating that while overall visual acuity measures remained stable, patients experienced some functional improvement post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated (9-mW/cm2) corneal collagen crosslinking for keratoconus-A 1-year follow-up. Elbaz, U., Shen, C., Lichtinger, A., 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]

References

1. Brazil pubmed.ncbi.nlm.nih.gov

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

2. Spain pubmed.ncbi.nlm.nih.gov

Long-term results of corneal collagen crosslinking for progressive keratoconus. [2022]

3. China pubmed.ncbi.nlm.nih.gov

[The progress of corneal crosslink in corneal disease]. [2013]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

5. 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]

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

Efficacy and Safety of Standard Corneal Cross-Linking Procedures Performed With Short Versus Standard Riboflavin Induction: A Save Sight Keratoconus Registry Study. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

[Corneal ulcer caused by MRSA after UV/riboflavin cross-linking in a patient with bilateral keratoconus]. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Corneal cross linking for keratoconus. [2013]

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

Transepithelial Enhanced Fluence Pulsed Light M Accelerated Crosslinking for Early Progressive Keratoconus with Chemically Enhanced Riboflavin Solutions and Air Room Oxygen. [2022]

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

Accelerated (9-mW/cm2) corneal collagen crosslinking for keratoconus-A 1-year follow-up. [2022]

11. 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]