Corneal Collagen Crosslinking + Intacs for Keratoconus

(CXL Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Cornea and Laser Eye Institute

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

160 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will determine the efficacy of corneal collagen crosslinking (CXL) combined with Intacs for the treatment of keratoconus and corneal ectasia. The goal of CXL is to decrease the progression of keratoconus, while Intacs has been shown to decrease corneal steepness in keratoconus. This study will attempt to determine the relative efficacy of the two procedures either performed at the same session versus CXL performed 3 months after Intacs.

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 coordinators or your doctor.

What data supports the effectiveness of the treatment Corneal Collagen Crosslinking + Intacs for Keratoconus?

Research shows that corneal collagen cross-linking (CXL) with riboflavin can stabilize or improve the corneal properties in keratoconus patients, and combining it with Intacs may enhance the treatment effect. ^{1 2 3 4 5}

Is corneal collagen crosslinking with riboflavin safe for humans?

Corneal collagen crosslinking (CXL) with riboflavin is commonly used for treating keratoconus, but its long-term safety is not fully known. Some studies have reported severe complications after additional eye surgeries in CXL-treated patients. ^{1 4 5 6 7}

How is the treatment of Corneal Collagen Crosslinking with Riboflavin and Intacs unique for keratoconus?

This treatment is unique because it combines corneal collagen crosslinking (CXL) with riboflavin, which strengthens the cornea using ultraviolet A (UVA) light, with Intacs, which are small implants that help reshape the cornea. This combination aims to stabilize and improve the corneal structure more effectively than using either method alone. ^{1 2 3 4 6}

Research Team

Peter Hersh, MD

Principal Investigator

Cornea and Laser Eye Institute

Eligibility Criteria

This trial is for adults over 21 with keratoconus or corneal ectasia, not perfect vision (worse than 20/20), and specific topography changes. It's not for those with other eye conditions that could complicate treatment, thin corneas at certain measurements, pregnant or lactating individuals, known drug sensitivities, or healing issues.

Inclusion Criteria

I am 21 years old or older.

I have been diagnosed with keratoconus or corneal ectasia after having eye surgery like LASIK.

BSCVA worse than 20/20 (<55 letters on ETDRS chart)

Exclusion Criteria

Corneal pachymetry ≤ 400 microns at the thinnest point measured by Pentacam in the eye(s) to be treated when the isotonic riboflavin solution is used or ≤ 300 microns when the hypotonic riboflavin is used, provided that the corneal thickness after treatment with the hypotonic riboflavin solution is > 400 microns

Corneal pachymetry ≤ 450 microns at the proposed insertion site for the Intacs

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Intacs placement followed by corneal collagen crosslinking with UV light and riboflavin

3 months

Multiple visits for Intacs placement and CXL procedure

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Regular follow-up visits to assess corneal stability and visual acuity

Treatment Details

Interventions

• Corneal Collagen Crosslinking (CXL)
• Intacs
• Riboflavin

Trial Overview The study tests the effectiveness of combining two treatments—corneal collagen crosslinking (CXL) and Intacs inserts—for keratoconus and corneal ectasia. One group receives both treatments in one session; another has CXL three months after Intacs to compare results.

Participant Groups

Group I: Intacs combined with CXL Active Control 1 Intervention

Intacs placement followed by collagen crosslinking with UV light and riboflavin

Group II: Intacs followed by CXL Active Control 1 Intervention

Intacs placement, to be followed by corneal collagen crosslinking with UV light and riboflavin 3 months later

Who Is Running the Clinical Trial?

Cornea and Laser Eye Institute

Lead Sponsor

Trials

10

Recruited

1,100+

Findings from Research

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]

In a study involving 25 eyes from 21 patients, combining corneal collagen cross-linking with riboflavin (C3-R) with inferior-segment Intacs significantly improved keratoconus outcomes compared to Intacs alone, showing greater reductions in cylinder measurements and keratometry values.

The results indicate that the addition of C3-R enhances the effectiveness of Intacs in treating keratoconus, leading to better overall corneal shape and stability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of inferior-segment Intacs with and without C3-R on keratoconus. Chan, CC., Sharma, M., Wachler, BS.[2022]

In a study of 38 eyes from 25 patients over 36 months, riboflavin UVA collagen crosslinking (CXL) treatment for keratoconus did not show significant changes in corneal topography indices or uncorrected visual acuity, indicating stability in corneal properties post-treatment.

While best-corrected visual acuity showed a slight improvement, it was not statistically significant, and importantly, no corneal thinning occurred, suggesting that CXL is a safe option for stabilizing keratoconus without adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of corneal topography indices after collagen crosslinking for keratoconus. Hassan, Z., Szalai, E., Módis, L., et al.[2022]

Both the Sina Darou and Uznach formulations of Riboflavin were found to be equally effective in improving visual acuity and corneal topography in 60 keratoconus patients after 6 months of corneal collagen cross-linking (CXL).

The Sina Darou formulation resulted in a greater decrease in corneal hysteresis compared to the Uznach formulation, suggesting potential differences in their effects on corneal biomechanical properties, which will be further evaluated in long-term studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of clinical results of two pharmaceutical products of riboflavin in corneal collagen cross-linking for keratoconus. Hashemi, H., Seyedian, MA., Miraftab, M., et al.[2021]

A study involving 100 eyes from 61 patients with progressive keratoconus found that both 0.1% riboflavin solutions used in corneal collagen crosslinking (CXL) were equally safe and effective, with no significant differences in visual and corneal measurements after 12 months.

No serious complications occurred in either group during or after the procedure, indicating that both riboflavin solutions can be safely used for treating keratoconus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective, Comparative, Clinical Study to Evaluate the Safety and Efficacy of Two Different 0.1% Riboflavin Solutions Used in Collagen Crosslinking Treatment for Patients with Keratoconus. Brar, S., Ganesh, S., Reddy, SS., et al.[2022]

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]

References

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

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

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

Corneal infiltrates after corneal collagen cross-linking. [2022]

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

Effect of inferior-segment Intacs with and without C3-R on keratoconus. [2022]

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

Assessment of corneal topography indices after collagen crosslinking for keratoconus. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of clinical results of two pharmaceutical products of riboflavin in corneal collagen cross-linking for keratoconus. [2021]

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

A Prospective, Comparative, Clinical Study to Evaluate the Safety and Efficacy of Two Different 0.1% Riboflavin Solutions Used in Collagen Crosslinking Treatment for Patients with Keratoconus. [2022]

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

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