Cornea Crosslinking for Keratoconus

(CXL Trial)

Overseen By GREGORY R Cohen, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Cohen Laser and Vision Center

Disqualifiers: Active infections, Collagen vascular disease, Pregnancy, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 day

300 Participants Needed

Trial Summary

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, contact lens wearers must stop wearing their lenses for a certain period before the screening.

What data supports the effectiveness of the treatment PXL Platinum 330 system for keratoconus?

Research shows that combining corneal cross-linking (CXL) with other procedures, like in the Athens Protocol, can be safe and effective for stabilizing keratoconus in children over several years. This suggests that CXL, a key part of the PXL Platinum 330 system, can help strengthen the cornea and slow the progression of keratoconus. ^{1 2 3 4 5}

Is cornea crosslinking for keratoconus safe for humans?

The research articles provided do not contain specific safety data for cornea crosslinking for keratoconus or the PXL Platinum 330 system. They focus on different medical devices and conditions, such as spinal implants, and do not address the safety of cornea crosslinking. ^{6 7 8 9 10}

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

The PXL Platinum 330 system is unique because it uses a specific type of light to strengthen the cornea, which is different from other treatments like surgery or contact lenses that don't change the cornea's structure. This system is part of a newer approach called corneal cross-linking, which aims to stop the progression of keratoconus by making the cornea more stable. ^{1 2 3 11 12}

What is the purpose of this trial?

This study study is to determine the effectiveness of cornea cross linking in patients with Keratoconus or other cornea thinning conditions.

Research Team

Kelly Fitzgerald

Principal Investigator

WCG IRB

Eligibility Criteria

This trial is for adults over 18 with Keratoconus or similar conditions causing cornea thinning. Participants must show signs like Fleischer ring, Vogt's striae, and have a specific shape to their cornea. Those with other medical or eye issues are not eligible.

Inclusion Criteria

I have streaks in the eye's clear layer.

Decentered corneal apex

My eye shows a bulging sign when looking downward.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive cornea collagen crosslinking using the PXL Platinum 330 system with riboflavin and UVA light

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with evaluations at multiple time points

12 months

1 day, 1 week, 1, 3, 6, and 12 months (in-person)

Treatment Details

Interventions

• PXL Platinum 330 system

Trial Overview The study tests the PXL-Platinum 330 system's ability to strengthen the cornea in patients with Keratoconus by using a technique called crosslinking.

Participant Groups

Group I: PXL 330 Experimental Treatment 1 Intervention

Participants will receive riboflavin 0.25% solution (Peschke TE), one drop every minute for 25 minutes to the eye, followed by UVA light 9mW/cm2 continuous mode for 10 minutes

PXL Platinum 330 system is already approved in United States for the following indications:

Approved in United States as PXL Platinum 330 system for:

• Keratoconus
• Post-refractive corneal ectasia
• Pellucid marginal degeneration
• Refractory corneal ulcers

Who Is Running the Clinical Trial?

Cohen Laser and Vision Center

Lead Sponsor

Trials

1

Recruited

300+

Findings from Research

The Athens Protocol, which combines topography-guided partial PRK with corneal cross-linking, showed significant improvements in visual acuity and corneal shape in 39 pediatric patients with keratoconus over a 4-year follow-up period.

While the procedure was generally safe and effective, two cases of late-onset deep corneal haze were noted, highlighting a potential complication in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Stability With the Athens Protocol (Topography-Guided Partial PRK Combined With Cross-Linking) in Pediatric Patients With Keratoconus. Kanellopoulos, AJ., Vingopoulos, F., Sideri, AM.[2019]

A 14-year-old boy with advanced bilateral keratoconus showed significant improvement after treatment with the combined MARK + CXL intervention, with long-term follow-up results indicating stabilization of the condition and enhanced visual acuity.

The treatment led to notable decreases in corneal steepness (Kmax) and increases in corneal thickness, demonstrating that conservative approaches can effectively manage severe keratoconus in young patients without the need for corneal transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mini Asymmetric Radial Keratotomy and Corneal Cross-linking for the Treatment of a Bilateral Stage IV Keratoconus in a 14-year-old Child. Abbondanza, M., Abbondanza, G., De Felice, V.[2022]

The study analyzed tomographic features of pellucid-like keratoconus (PLK) and identified that the claw pattern on the anterior sagital map (ASM) is not exclusive to pellucid marginal degeneration (PMD), as it can also appear in PLK cases.

A new diagnostic sign, the 'bell' sign on the pachymetry map, was found to be present in all PMD cases, making it a useful tool for differentiating PMD from PLK, where this sign was absent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pellucid-like keratoconus. Sinjab, MM., Youssef, LN.[2021]

Aphakic/pseudophakic corneal edema was identified as the leading reason for penetrating keratoplasty (PKP) in Greece, accounting for 29.1% of cases, followed closely by keratoconus at 26%.

The study revealed a significant increase in the prevalence of regrafts as an indication for PKP over the 25-year period, indicating a trend that may reflect changes in patient management or surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changing indications for penetrating keratoplasty in Greece, 1982-2006: a multicenter study. Siganos, CS., Tsiklis, NS., Miltsakakis, DG., et al.[2022]

In a study of 17 pediatric patients with severe kyphosis (greater than 60°), the use of posterior spinal fusion with sublaminar bands resulted in a low rate of proximal junctional kyphosis (PJK) at 5.8%, which is lower than rates reported in previous studies.

The technique demonstrated effective correction of kyphosis, reducing preoperative angles from an average of 62°-111° to 12°-55° postoperatively, indicating both safety and efficacy in managing spinal deformities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of Proximal Junctional Kyphosis & Failure Using Sublaminar Bands in a Hybrid Construct in Pediatric Kyphosis Deformity. Battista, C., Wild, C., Kreul, S., et al.[2022]

A 62-year-old male with a known severe allergy to epoxy resin experienced significant pain and erythema after receiving a PEEK-containing medical device, suggesting a potential allergic reaction to PEEK.

This case highlights the importance of considering cross-reactivity between materials like PEEK and epoxy resin, especially since PEEK is widely used in medical devices and the sensitization route remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allergic Reaction to Polyether Ether Ketone Following Cross-Reactivity to Epoxy Resin. Kofler, L., Wambacher, M., Schweinzer, K., et al.[2021]

In a study of 172 patients who underwent surgery for degenerative lumbar spinal diseases, significant improvements in low back pain and leg pain were observed postoperatively, with VAS and ODI scores showing high statistical significance (p < 0.0001).

While dynamic stabilization using PEEK rods did not lead to significant radiological correction of lumbar lordosis, the mid-term clinical outcomes were satisfactory, with a low reoperation rate of 5.8% and a low incidence of adjacent segment disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polyetheretherketone Rods in Lumbar Spine Degenerative Disease: Mid-term Results in a Patient Series Involving Radiological and Clinical Assessment. Ogrenci, A., Koban, O., Yaman, O., et al.[2021]

In a study of 321 patients with spinal metastases or primary bone tumors, the use of carbon-fiber-reinforced (CFR) PEEK pedicle screw systems demonstrated a low complication rate, with only 9.3% experiencing intraoperative complications and 17.1% requiring revision surgery for postoperative issues.

CFR-PEEK implants showed rare implant-related complications, such as a 3.4% rate of intraoperative screw breakage and 2.2% screw loosening, making them a safe and effective alternative to traditional titanium implants for spinal stabilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CFR-PEEK Pedicle Screw Instrumentation for Spinal Neoplasms: A Single Center Experience on Safety and Efficacy. Joerger, AK., Seitz, S., Lange, N., et al.[2022]

A novel cross-link configuration that passes through the base of the spinous processes significantly increased the mechanical resistance of spinal constructs in pullout and flexion-compression tests compared to a conventional cross-link system, indicating improved stability.

This new design showed greater resistance to construct failure, particularly under flexion-compression forces, suggesting it may enhance the safety and efficacy of spinal instrumentation in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomechanical Analysis of a Pedicle Screw-Rod System with a Novel Cross-Link Configuration. Nakajima, Y., Hara, M., Umebayashi, D., et al.[2020]

The study found that cross-linkage in posterior spinal constructs does not significantly improve stability under axial loading but has a more pronounced effect under torsion loading, indicating its importance in certain stress conditions.

Fatigue tests showed that spinal implants without cross-linkage could endure 1 million cycles at loads of 500-750 N, but their endurance dropped significantly at 1,000 N, suggesting that cross-linkage could help improve the endurance limits of spinal implants, especially for patients with higher physiological loads.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of cross-linkage on fatigue life and failure modes of stainless steel posterior spinal constructs. Stambough, JL., Sabri, EH., Huston, RL., et al.[2006]

In a study involving 233 patients with hyperopia, 12-month results showed that 91% achieved uncorrected visual acuity of 20/40 or better, indicating high efficacy of conductive keratoplasty (CK) for treating hyperopia.

The procedure demonstrated good safety and stability, with 58% of patients achieving a manifest refractive spherical equivalent within +/- 0.50 D, and minimal changes in residual refraction after 6 months, suggesting that CK provides a stable correction for hyperopia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conductive keratoplasty for the correction of hyperopia. Asbell, PA., Maloney, RK., Davidorf, J., et al.[2022]

In a study involving 126 patients (79 LASIK and 47 PRK), both simultaneous LASIK and PRK with cornea inlay implantation were found to be effective treatments for presbyopia, meeting FDA efficacy criteria with high rates of achieving good near visual acuity (95% for LASIK and 83% for PRK at 20/40 vision).

Both procedures demonstrated similar safety profiles, with 92% of the LASIK group and 95% of the PRK group achieving 20/40 or better distance vision at 6 months, indicating that they are viable options for improving vision in presbyopic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Comparison of Visual Outcomes After KAMRA Corneal Inlay Implantation With Simultaneous PRK or LASIK. Moshirfar, M., Bean, AE., Albarracin, JC., et al.[2018]

References

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

Long-Term Stability With the Athens Protocol (Topography-Guided Partial PRK Combined With Cross-Linking) in Pediatric Patients With Keratoconus. [2019]

2. Bosnia and Herzegovina pubmed.ncbi.nlm.nih.gov

Mini Asymmetric Radial Keratotomy and Corneal Cross-linking for the Treatment of a Bilateral Stage IV Keratoconus in a 14-year-old Child. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Pellucid-like keratoconus. [2021]

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

Changing indications for penetrating keratoplasty in Greece, 1982-2006: a multicenter study. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Prevention of Proximal Junctional Kyphosis & Failure Using Sublaminar Bands in a Hybrid Construct in Pediatric Kyphosis Deformity. [2022]

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

Allergic Reaction to Polyether Ether Ketone Following Cross-Reactivity to Epoxy Resin. [2021]

7. Turkey pubmed.ncbi.nlm.nih.gov

Polyetheretherketone Rods in Lumbar Spine Degenerative Disease: Mid-term Results in a Patient Series Involving Radiological and Clinical Assessment. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

CFR-PEEK Pedicle Screw Instrumentation for Spinal Neoplasms: A Single Center Experience on Safety and Efficacy. [2022]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Biomechanical Analysis of a Pedicle Screw-Rod System with a Novel Cross-Link Configuration. [2020]

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

Effects of cross-linkage on fatigue life and failure modes of stainless steel posterior spinal constructs. [2006]

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

Conductive keratoplasty for the correction of hyperopia. [2022]

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

Retrospective Comparison of Visual Outcomes After KAMRA Corneal Inlay Implantation With Simultaneous PRK or LASIK. [2018]