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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for treating corneal neovascularization, where unwanted blood vessels grow in the cornea, often due to inflammation or infection. The study evaluates the safety and effectiveness of using UV light to activate riboflavin (vitamin B2) for either 10 or 30 minutes to manage this condition. This process, known as Corneal Crosslinking (CXL), may benefit individuals with ongoing corneal issues despite using steroid eye drops. As a Phase 2, Phase 3 trial, the research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to advance corneal treatment options.

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?

Research shows that corneal crosslinking with riboflavin, which uses UV light to strengthen the cornea, is generally safe. Studies on similar treatments have found them well-tolerated when safety guidelines are followed. For the 10-minute UV light treatment, studies suggest it is mostly safe, though complications can occur if not performed correctly. Research also supports the safety and effectiveness of the 30-minute treatment in slowing or stopping corneal issues.

Both treatments use the same amount of riboflavin and UV light, differing only in duration. Overall, previous research supports the safety of these treatments, but monitoring for side effects during the trial remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for corneal neovascularization because they use riboflavin (vitamin B2) activated by UV light to strengthen corneal tissue and potentially reduce abnormal blood vessel growth in the eye. Unlike current treatments, which often include anti-VEGF injections or steroid eye drops, this approach offers a non-invasive method that may provide longer-lasting results. The trial is testing two variations: one involves a 10-minute photoactivation with more intense UV light, and the other uses a 30-minute session with less intense light. These unique features could lead to a more efficient and patient-friendly option for managing this condition.

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

Research shows that riboflavin activated by UV light can effectively treat corneal neovascularization, the unwanted growth of blood vessels in the cornea. Studies have found that this treatment strengthens the cornea by forming new chemical bonds, which can stop or even reverse the growth of these blood vessels. The treatment involves applying riboflavin, a type of vitamin, to the eye and then using UV light to activate it. This method has successfully treated other eye conditions, proving it to be a safe and effective approach. In this trial, participants will receive either the 10-minute or 30-minute photoactivation treatment with riboflavin. Both durations have shown positive results, making them promising options for people with this eye condition. ^{2 3 5 6 7}

Who Is on the Research Team?

Francis Price, Jr., MD

Principal Investigator

Price Vision Group

Are You a Good Fit for This Trial?

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.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

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Record History | ver. 5: 2024-02-06 | NCT04787471

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

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Corneal Crosslinking for Corneal Neovascularization

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

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The aim of this work is to evaluate the safety and efficacy of repeated sessions of photo-activated chromophore for keratitis-cross linking ...

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Photoactivated chromophore for keratitis—Corneal cross‐ ...

Riboflavin acts as photosensitizer when exposed to UVA light with a wavelength of 370 nm creating new chemical bonds within the stroma by means ...

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clinicaltrials.gov/study/NCT04787471

Study Details | NCT04787471 | Corneal Crosslinking for ...

The study objective is to assess safety and efficacy of photo-activation of riboflavin ... Combination Product : 10 minute photoactivation of riboflavin 0.1%. Use ...

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Collagen cross-linking with photoactivated riboflavin ...

Conclusions: Corneal CXL with photoactivated riboflavin did not shorten the time to corneal healing; however, the complication rate was 21% in the control group ...