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

Trial Summary

What is the purpose of this trial?

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

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 data supports the effectiveness of the treatment PXL-330 Platinum device for crosslinking with Peschke riboflavin solution in treating keratoconus?

Research shows that corneal collagen cross-linking (CXL) using riboflavin and ultraviolet-A light is effective in stopping the progression of keratoconus, a condition where the cornea becomes thin and cone-shaped. Studies have demonstrated improvements in corneal thickness and shape, which are important for better vision. ^{1 2 3 4 5}

Is corneal collagen cross-linking generally safe for humans?

Corneal collagen cross-linking (CXL) is widely used for treating keratoconus, but its long-term safety is not fully known. Some studies report severe complications after additional eye procedures in CXL-treated patients, while others focus on its effectiveness and short-term safety. ^{3 4 6 7 8}

How is the PXL-330 Platinum device treatment for keratoconus different from other treatments?

The PXL-330 Platinum device treatment for keratoconus is unique because it uses a specific device and riboflavin solution to strengthen the cornea by activating collagen fibers with ultraviolet A light, which is currently the only method to stop the progression of keratoconus. ^{1 5 9 10 11}

Research Team

BALAMURALI AMBATI, MD, PhD

Principal Investigator

PCVI

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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 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 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]

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]

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]

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]

References

1. India pubmed.ncbi.nlm.nih.gov

Collagen cross-linking effect on progressive keratoconus in patients younger than 18 years of age: A clinical trial. [2020]

2. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Peripheral corneal cross-linking (P-CXL) for ultrathin corneas with severe keratoconus: a new technique]. [2018]

3. 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]

4. India pubmed.ncbi.nlm.nih.gov

Evaluation of changes in corneal volume, volume and angle of anterior chamber in keratoconus patients using Pentacam after CXL. [2022]

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

Evaluation of the effect of corneal collagen cross-linking for keratoconus on the ocular higher-order aberrations. [2020]

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

Induction of neoplasia after deep anterior lamellar keratoplasty in a CXL-treated cornea. [2022]

7. England 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. [2016]

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

Corneal collagen cross-linking: a review of 1-year outcomes. [2022]

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

Collagenase-mediated tissue modeling of corneal ectasia and collagen cross-linking treatments. [2013]

10. India pubmed.ncbi.nlm.nih.gov

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

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

Combined photorefractive keratectomy and corneal collagen cross-linking for treatment of keratoconus: a 2-year follow-up study. [2022]