Corneal Collagen Cross-Linking for Keratoconus

Overseen By BALAMURALI AMBATI, MD, PhD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Pacific Clear Vision Institute

Disqualifiers: Pregnancy, Corneal disease, Nystagmus, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: 10 minutes

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called the PXL-330 system, a device for corneal collagen cross-linking, to determine its safety and effectiveness for people with keratoconus. This condition thins and reshapes the cornea into a cone. The treatment will be tested in two ways: one with continuous light and another with pulsed light. Candidates for this trial include those diagnosed with keratoconus who have experienced worsening vision over the past three months. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this innovative 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. However, if you wear contact lenses, you will need to stop wearing them for a certain period before the screening.

What prior data suggests that the Peschke PXL-330 system is safe for treating corneal thinning conditions?

Research shows that the Peschke PXL-330 system, combined with a vitamin B2 solution, is undergoing safety testing for conditions where the cornea thins. This device uses a special light to strengthen the cornea.

Specific safety data from human studies is not yet available, as this trial is in its early stages. The primary goal is to assess safety and identify possible side effects. Early-phase trials like this receive close monitoring to ensure participant safety.

If this treatment has approval for other conditions, it generally indicates reasonable safety, though details may vary. Participants in this study will receive close medical supervision to monitor for any side effects during the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about the PXL-330 Platinum device for corneal collagen cross-linking in keratoconus because it offers a potentially faster and more efficient treatment approach compared to current options. Unlike conventional methods that use a steady 9 mW light for 10 minutes, the pulsed, accelerated method employs an 18 mW light with a unique on-off pattern, which might enhance the cross-linking process while reducing treatment time. This innovative technique could lead to better patient outcomes and more convenient procedures, making it a promising advance in the management of keratoconus.

What evidence suggests that the PXL-330 Platinum device is effective for corneal thinning conditions?

Research has shown that the PXL-330 Platinum device, when combined with a vitamin B2 solution, may help treat conditions where the cornea becomes thin, such as keratoconus. In this trial, participants will be assigned to one of two treatment arms: the Conventional arm, which involves 9 mW continuous illumination for 10 minutes, or the Pulsed, accelerated arm, which involves 18 mW with 5 seconds on and 5 seconds off for 10 minutes. Studies have found that over 85% of eyes treated with the PXL-330 Platinum device experienced much clearer vision. Six months after treatment, many patients also showed reduced astigmatism, a common vision issue caused by an unevenly shaped cornea. This suggests that the treatment strengthens the cornea and improves vision. These early results are promising for those considering this treatment. ^{1 2 3 4 5}

Who Is on the Research Team?

BALAMURALI AMBATI, MD, PhD

Principal Investigator

PCVI

Are You a Good Fit for This Trial?

This trial is for people aged 12 or older with certain corneal thinning conditions like keratoconus, who haven't improved after two weeks of standard treatment for bacterial/fungal keratitis. Candidates must have specific signs of corneal disease and be willing to follow the study schedule. Pregnant individuals, those planning pregnancy, lactating, or with a history of certain eye diseases are excluded.

Inclusion Criteria

Contact Lens Type Minimum Discontinuation Time Soft 1 Week Soft Extended Wear 2 Weeks Soft Toric 3 Weeks Rigid gas permeable Scleral Lenses 2 Weeks per decade of wear Investigator Discretion

Posterior corneal elevation >16 microns

Apical Corneal scarring consistent with Bowman's breaks

Exclusion Criteria

You have a known sensitivity or allergy to the medications used in the study.

Eyes classified as either normal or atypical normal on the severity grading scheme.

I have a history of or currently have a corneal disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo epithelial-on corneal crosslinking with the Peschke PXL-330 system using pulsed, accelerated energy delivery

10 minutes

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including serial measurements of corneal topography, visual acuity, intraocular pressure, and visual function questionnaire

12 months

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• PXL-330 Platinum device for crosslinking with Peschke riboflavin solution

Trial Overview The trial tests the safety and effectiveness of the PXL-330 Platinum device paired with Peschke riboflavin solution in treating corneal thinning disorders. It aims to see if this combination can strengthen the cornea by cross-linking its collagen fibers.

How Is the Trial Designed?

Group I: Pulsed, accelerated Experimental Treatment 1 Intervention

18 mW, 5 sec, 5 sec off, 10 minutes of illumination

Group II: Conventional Active Control 1 Intervention

9 mW, continuous 10 minutes of illumination

PXL-330 Platinum device for crosslinking with Peschke riboflavin solution is already approved in United States, European Union for the following indications:

Approved in United States as PXL Platinum 330 for:

• Progressive keratoconus
• Pellucid marginal degeneration
• Post-refractive corneal ectasia

Approved in European Union as PXL Platinum 330 for:

• Keratoconus
• Corneal ectasia
• Pellucid marginal degeneration

Who Is Running the Clinical Trial?

Pacific Clear Vision Institute

Lead Sponsor

Trials

1

Recruited

300+

Published Research Related to This Trial

Corneal collagen crosslinking (CXL) may negatively affect the healing process after corneal surgery, as demonstrated in a case where a patient developed severe complications following a deep anterior lamellar keratoplasty after CXL treatment for keratoconus.

Histopathological analysis revealed that the patient developed conjunctival intraepithelial neoplasia, a precursor to invasive squamous cell carcinoma, suggesting a potential link between CXL and neoplastic changes in corneal tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of neoplasia after deep anterior lamellar keratoplasty in a CXL-treated cornea. Krumeich, JH., Brand-Saberi, B., Chankiewitz, V., et al.[2022]

Corneal collagen cross-linking (CXL) significantly improves best-corrected visual acuity (BCVA) in keratoconus patients, with notable improvements observed at 6 and 12 months post-treatment.

CXL also leads to a significant decrease in corneal volume and an increase in anterior chamber volume and angle, indicating enhanced corneal stability and anterior chamber parameters after the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of changes in corneal volume, volume and angle of anterior chamber in keratoconus patients using Pentacam after CXL. Ostadian, F., Nickkhah, S., Farrahi, F., et al.[2022]

Peripheral corneal cross-linking (P-CXL) is a novel treatment for patients with severe keratoconus and very thin corneas (as thin as 215 µm), which is typically considered too risky for standard corneal cross-linking.

After four months of P-CXL, patients showed significant improvements: corneal thickness increased by 42 µm, maximum keratometry (Kmax) decreased by 1.4 D, and astigmatism reduced by 3.2 D, indicating the treatment's efficacy in stabilizing corneal shape.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Peripheral corneal cross-linking (P-CXL) for ultrathin corneas with severe keratoconus: a new technique]. Abbondanza, M., Felice, V., Abbondanza, G.[2018]

A combined treatment of topography-guided photorefractive keratectomy (PRK) with mitomycin-C and corneal collagen cross-linking (CXL) significantly improved best corrected visual acuity in patients with mild to moderate keratoconus over a 2-year follow-up, with a notable improvement from 0.15 to 0.08 logMAR.

The procedure also effectively reduced keratometry measurements, indicating a flattening of the cornea, which is crucial for managing keratoconus, with significant reductions in both steepest and flattest meridian keratometry values.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined photorefractive keratectomy and corneal collagen cross-linking for treatment of keratoconus: a 2-year follow-up study. De Rosa, G., Rossi, S., Santamaria, C., 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]

Corneal collagen cross-linking (CXL) significantly improves visual acuity in patients with progressive keratoconus, with notable enhancements observed in both uncorrected and best-corrected visual acuity after 6 months.

The procedure also leads to a significant reduction in higher-order aberrations (HOAs), particularly total HOAs and coma, which are correlated with improved visual function, indicating that CXL effectively stabilizes the cornea and enhances vision quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the effect of corneal collagen cross-linking for keratoconus on the ocular higher-order aberrations. El-Massry, AA., Dowidar, AM., Massoud, TH., et al.[2020]

Corneal ultraviolet A/riboflavin collagen cross-linking (CXL) is a safe and effective treatment for stabilizing mild-to-moderate keratoconus, showing significant improvement in uncorrected distance visual acuity (UDVA) over 24 months in a study of 39 eyes from 30 patients.

While best corrected distance visual acuity (BDVA) did not show significant overall improvement, patients with lower preoperative BDVA values experienced better outcomes, and no complications were reported during the follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corneal collagen cross-linking using riboflavin and ultraviolet A for the treatment of mild to moderate keratoconus: 2-year follow-up. Legare, ME., Iovieno, A., Yeung, SN., et al.[2016]

In a study of 37 patients under 18 years old with progressive keratoconus, collagen cross-linking (CXL) significantly improved refractive values, including a notable decrease in cylinder value and enhancements in uncorrected and best corrected visual acuity after 12 months.

CXL also positively affected corneal topographic measurements, with significant improvements in maximum keratometry and other indices, indicating its efficacy in managing keratoconus in younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Collagen cross-linking effect on progressive keratoconus in patients younger than 18 years of age: A clinical trial. Peyman, A., Kamali, A., Khushabi, M., et al.[2020]

The study successfully created a model of corneal ectasia using collagenase on human corneoscleral specimens, showing a significant increase in maximum axial curvature (K(max)) compared to control specimens, indicating the model effectively mimics the condition.

Corneal collagen cross-linking (CXL) was found to significantly reduce K(max) after treatment, suggesting that CXL can effectively reverse the steepening of the cornea associated with ectatic diseases, while also increasing anterior corneal aberrations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Collagenase-mediated tissue modeling of corneal ectasia and collagen cross-linking treatments. Hong, CW., Sinha-Roy, A., Schoenfield, L., et al.[2013]

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]

Corneal collagen cross-linking (CXL) is effective in slowing the progression of keratoconus (KC) and improving visual acuity, with an average flattening of 1.7 diopters in maximum keratometry (KMax) and a slight improvement in best-corrected visual acuity (BCVA) over 12 months in a study of 104 eyes.

Patients with a preoperative KMax of 55 diopters or steeper and those with a BCVA of 20/40 or worse were significantly more likely to experience greater improvements in KMax flattening and visual acuity after CXL, indicating these factors can help predict positive treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corneal collagen cross-linking: a review of 1-year outcomes. Chang, CY., Hersh, PS.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04213885

Safety and Effectiveness of the PXL Platinum 330 System ... Study Overview. Brief Summary. To determine whether the Peschke PXL-330 is safe and effective in the treatment of corneal thinning conditions.

2. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT03918408?term=TETRAHYDROZOLINE&draw=2&rank=8

Safety and Effectiveness of the PXL-Platinum 330 System ... To determine whether the Peschke PXL-330 system is safe and effective in the treatment of corneal thinning conditions. Detailed Description. Patients with ...

3. ophtec.com ophtec.com/hubfs/Producten/PDP%20downloads/A901000636-1%20PXL%20Platinum%20330%20Folder%20e-mail.pdf

PXL Platinum 330 More than 85 % of eyes treated with CXL showed a significant increase in BCVA. Six months after the procedure cylinder was reduced in the majority of patients.

4. trialx.com trialx.com/clinical-trials/listings/275969/safety-and-effectiveness-of-the-pxl-platinum-330-system-for-corneal-collagen-cross-linking-in-eyes-with-corneal-thinning-conditions/?&geo_lat=44.0462362&geo_lng=-123.0220289&radius=10&place=Springfield&user_country=United%20States

Safety and Effectiveness of the PXL-Platinum 330 System ... Overview. To determine whether the Peschke PXL-330 system is safe and effective in the treatment of corneal thinning conditions.

5. trial.medpath.com trial.medpath.com/clinical-trial/1d679d4228029ea2/nct04667572-safety-effectiveness-pxl-platinum-330-system-corneal-thinning

Safety & Effectiveness of the PXL-Platinum 330 System for CXL ... Safety and Effectiveness of the PXL-Platinum 330 System for Corneal Collagen Cross-linking in Eyes With Corneal Thinning Conditions.