Corneal Crosslinking for Corneal Neovascularization

Overseen By Marianne Price, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Price Vision Group

Disqualifiers: Pregnancy, Lactation, Sensitivity to medications, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

62 Participants Needed

Trial Summary

What is the purpose of this trial?

The study objective is to assess safety and efficacy of photo-activation of riboflavin for treatment of corneal neovascularization with or without concomitant inflammation and/or infection.

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 this treatment for corneal neovascularization?

Research shows that corneal cross-linking (CXL) with riboflavin and ultraviolet-A (UVA) light is effective in treating infectious keratitis, a condition where the cornea becomes inflamed due to infection. This treatment strengthens the cornea and has a microbicidal effect, which may suggest potential benefits for other corneal conditions like neovascularization. ^{1 2 3 4 5}

Is corneal crosslinking generally safe for humans?

Corneal crosslinking (CXL) with riboflavin and ultraviolet-A (UVA) light is generally considered safe, but there are rare reports of complications like secondary keratitis (inflammation of the cornea). Further evaluation of its safety is necessary, especially for different conditions. ^{1 2 3 4 6}

How is the corneal crosslinking treatment for corneal neovascularization different from other treatments?

Corneal crosslinking (CXL) with riboflavin and UV-A light is unique because it strengthens the cornea by creating new bonds between collagen fibers, which can help prevent further damage and has a microbicidal effect. This treatment is different from traditional methods as it not only addresses structural issues but also has potential antimicrobial properties, making it a novel approach for conditions like corneal neovascularization. ^{1 2 3 4 7}

Research Team

Francis Price, Jr., MD

Principal Investigator

Price Vision Group

Eligibility Criteria

This trial is for adults over 18 with corneal neovascularization, which can cause vision problems due to abnormal blood vessels in the eye. It's open to those who haven't responded well to steroid treatments or are at risk of cornea transplant rejection. Pregnant individuals, those planning pregnancy, lactating, or with known sensitivity to treatment drugs cannot participate.

Inclusion Criteria

My eye has severe inflammation or infection affecting the cornea.

I am 18 years old or older.

Signed written informed consent.

Exclusion Criteria

You have had an allergic reaction to the medication being used in the study.

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

Current condition that in the investigator's opinion could compromise safety or data integrity.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo photoactivation of riboflavin using UV light for either 10 or 30 minutes

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Regular visits as per study protocol

Treatment Details

Interventions

• 10 minute photoactivation of riboflavin 0.1%
• 30 minute photoactivation of riboflavin 0.1%

Trial Overview The study tests two durations of photoactivation (light exposure) of riboflavin (vitamin B2) on the eye: one lasting 30 minutes and another lasting 10 minutes. The goal is to see how safe and effective this treatment is for reducing unwanted blood vessel growth in the cornea.

Participant Groups

Group I: 30 minute photoactivation Active Control 1 Intervention

photoactivation of riboflavin 0.1% using 365-nm UV light, 3mW/cm2 for 30 minutes

Group II: 10 minute photoactivation Active Control 1 Intervention

photoactivation of riboflavin 0.1% using 365-nm UV light, 9mW/cm2 for 10 minutes

10 minute photoactivation of riboflavin 0.1% is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Corneal Crosslinking for:

• Keratoconus
• Corneal Ectasia
• Infectious Keratitis
• Corneal Neovascularization

Approved in United States as Corneal Crosslinking for:

• Keratoconus
• Corneal Ectasia
• Infectious Keratitis

Approved in Canada as Corneal Crosslinking for:

• Keratoconus
• Corneal Ectasia

Who Is Running the Clinical Trial?

Price Vision Group

Lead Sponsor

Trials

12

Recruited

1,700+

Cornea Research Foundation of America

Collaborator

Trials

8

Recruited

3,000+

Findings from Research

In an ex vivo study using 117 porcine corneas, both riboflavin/UV-A light and rose bengal/green light PACK-CXL significantly reduced bacterial loads of Staphylococcus aureus and Pseudomonas aeruginosa, with rose bengal/green light showing superior efficacy.

The rose bengal/green light approach achieved bacterial killing ratios of 76.7% for S. aureus and 81.0% for P. aeruginosa, compared to 52.8% and 45.8% respectively for riboflavin/UV-A light, suggesting it may be a more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Fluence Accelerated PACK-CXL for Bacterial Keratitis Using Riboflavin/UV-A or Rose Bengal/Green in the Ex Vivo Porcine Cornea. Lu, NJ., Koliwer-Brandl, H., Hillen, M., et al.[2023]

In a study of 40 patients with advanced infectious keratitis, corneal collagen cross-linking (PACK-CXL) combined with antimicrobial therapy did not significantly reduce healing time compared to antimicrobial therapy alone, with healing times averaging 39.76 days for PACK-CXL and 46.05 days for the control group.

However, PACK-CXL showed a better safety profile, with no serious complications such as corneal perforation or infection recurrence, while the control group had a 21% complication rate, indicating that PACK-CXL may be a beneficial adjunct treatment for severe cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Collagen cross-linking with photoactivated riboflavin (PACK-CXL) for the treatment of advanced infectious keratitis with corneal melting. Said, DG., Elalfy, MS., Gatzioufas, Z., et al.[2022]

PACK-CXL treatment significantly reduces inflammation and prevents corneal melting in infections caused by Pseudomonas aeruginosa and Staph aureus, as shown in a study involving 20 rabbit eyes, where none of the cross-linked eyes experienced melting compared to 6 in the control group.

Histopathological analysis revealed that PACK-CXL confines inflammation to the superficial stroma, enhancing corneal rigidity and resistance to infection, suggesting its potential as an effective early intervention in treating corneal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corneal cross-linking guards against infectious keratitis: an experimental model. Marrie, A., Abdullatif, AM., Gamal El Dine, S., et al.[2023]

Corneal crosslinking (CXL) using riboflavin and ultraviolet-A (UVA) is an effective new treatment for infectious keratitis, showing promising results in clinical practice.

Despite its efficacy, there are rare complications associated with CXL, such as secondary keratitis, indicating the need for further evaluation of both its benefits and potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic and inducing effect of corneal crosslinking on infectious keratitis. Jiang, LZ., Qiu, SY., Li, ZW., et al.[2020]

Accelerated riboflavin-ultraviolet A-induced corneal collagen cross-linking (CXL) effectively halts the progression of keratoconus, with significant improvements in corneal topography metrics like Kmax after a mean follow-up of 21.7 months involving 28 eyes of 20 patients.

No complications were reported during the postoperative follow-up, indicating that this treatment is safe for patients, although further prospective studies are needed to confirm these results and explore different CXL settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated (18 mW/cm²) Corneal Collagen Cross-Linking for Progressive Keratoconus. Alnawaiseh, M., Rosentreter, A., Böhm, MR., et al.[2022]

A 62-year-old woman with multiresistant fungal keratitis after penetrating keratoplasty (PKP) was successfully treated using a novel technique called photoactivated chromophore for infectious keratitis-corneal cross-linking (PACK-CXL) during a repeat PKP, showing promising results.

The combination of PACK-CXL with PKP was safe, with no intra- or postoperative complications, and the graft remained clear without signs of infection during a 9-month follow-up, indicating its efficacy in managing resistant fungal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative Photoactivated Chromophore for Infectious Keratitis-Corneal Cross-Linking (PACK-CXL) During Penetrating Keratoplasty for the Management of Fungal Keratitis in an Immunocompromised Patient. Mikropoulos, DG., Kymionis, GD., Voulgari, N., et al.[2020]

Corneal cross-linking with riboflavin is an effective method for stabilizing or reducing corneal ectasia in conditions like keratoconus and post-LASIK ectasia.

There is a growing interest in accelerated corneal cross-linking techniques to shorten treatment times, which is important for improving patient flow and overall treatment efficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of accelerated corneal cross-linking. Mrochen, M.[2022]

References

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

High-Fluence Accelerated PACK-CXL for Bacterial Keratitis Using Riboflavin/UV-A or Rose Bengal/Green in the Ex Vivo Porcine Cornea. [2023]

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

Collagen cross-linking with photoactivated riboflavin (PACK-CXL) for the treatment of advanced infectious keratitis with corneal melting. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Corneal cross-linking guards against infectious keratitis: an experimental model. [2023]

4. China pubmed.ncbi.nlm.nih.gov

Therapeutic and inducing effect of corneal crosslinking on infectious keratitis. [2020]

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

Accelerated (18 mW/cm²) Corneal Collagen Cross-Linking for Progressive Keratoconus. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Intraoperative Photoactivated Chromophore for Infectious Keratitis-Corneal Cross-Linking (PACK-CXL) During Penetrating Keratoplasty for the Management of Fungal Keratitis in an Immunocompromised Patient. [2020]

7. India pubmed.ncbi.nlm.nih.gov

Current status of accelerated corneal cross-linking. [2022]