Corneal Collagen Cross-Linking for Keratoconus

Overseen by David Huang, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Oregon Health and Science University

Disqualifiers: Retinal diseases, Glaucoma, Cataracts, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial uses a special laser treatment with precise scanning and medication to improve vision in patients with keratoconus by strengthening and smoothing their corneas.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Corneal Collagen Cross-Linking for Keratoconus?

Research shows that corneal collagen cross-linking (CXL) is effective in stopping the progression of keratoconus, a condition where the cornea (the clear front part of the eye) becomes thin and cone-shaped. Studies have found that CXL can improve the shape of the cornea and stabilize vision in people with this condition. ^{1 2 3 4 5}

Is corneal collagen cross-linking safe for humans?

Corneal collagen cross-linking (CXL) is generally considered a safe procedure with a low complication rate, although rare severe complications like keratitis (inflammation of the cornea) and corneal scarring have been reported. ^{2 6 7 8 9}

How is the treatment for keratoconus unique?

Corneal collagen cross-linking (CXL) is unique because it is the only treatment available that can stop the progression of keratoconus by strengthening the cornea. It uses a combination of riboflavin (vitamin B2) and ultraviolet-A light to create new bonds between collagen fibers in the cornea, making it more stable. ^{2 5 10 11 12}

Research Team

David Huang, MD, PhD

Principal Investigator

Oregon Health and Science University

Eligibility Criteria

This trial is for individuals with keratoconus, a condition that affects the cornea of the eye. Participants must have a minimum corneal thickness of 410 microns and be able to commit to study visits and give informed consent. Those with mature cataracts, difficulty maintaining fixation for imaging, or other eye conditions like glaucoma are excluded.

Inclusion Criteria

Minimum corneal thickness of 410 microns

I have been diagnosed with keratoconus.

Exclusion Criteria

You have difficulty keeping your eyes still during OCT imaging.

My cataracts limit my vision to worse than 20/40.

Inability to commit to required study visits

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo OCT-guided custom laser corneal collagen cross-linking (CXL) procedure

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the CXL procedure

6 months

Multiple visits (in-person) at various time points

Treatment Details

Interventions

• Laser Custom Corneal Collagen Cross-Linking (Procedure)

Trial Overview The trial is testing Laser Custom Corneal Collagen Cross-Linking (CXL), which aims to reduce corneal aberrations and improve vision in keratoconus patients. The procedure's effectiveness will be assessed using OCT-guided lasers for precision in corneal smoothing.

Participant Groups

Group I: Surgery Experimental Treatment 1 Intervention

OCT-guided custom laser CXL

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

John Hunter

Oregon Health and Science University

Chief Medical Officer since 2024

MD, specific details unavailable

Ann Madden Rice

Oregon Health and Science University

Chief Executive Officer

FACHE certification, extensive leadership experience in academic health centers

National Eye Institute (NEI)

Collaborator

Trials

572

Recruited

1,320,000+

Dr. Michael F. Chiang

National Eye Institute (NEI)

Chief Executive Officer since 2020

MD from Harvard Medical School

Dr. Richard Lee

National Eye Institute (NEI)

Chief Medical Officer since 2021

MD, PhD from Harvard Medical School

Findings from Research

In a study of 239 eyes from 171 patients with progressive keratoconus, the CXL-plus-PTK procedure showed superior effectiveness compared to the standard Accelerated CXL, particularly in reducing maximum keratometry (Kmax).

The Iontophoresis CXL procedure also demonstrated better outcomes in terms of minimum corneal thickness (C value) compared to the Accelerated CXL group, indicating that different CXL modalities can have varying impacts on corneal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Independent-effect comparison of five crosslinking procedures for Progressive Keratoconus based on Keratometry and the ABCD Grading System using Generalized Estimating Equations (GEE). Liu, Y., Shen, D., Wang, HY., et al.[2023]

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 cross-linking (CXL) is an effective treatment for keratoconus, showing improvements in visual acuity of 1 to 2 Snellen lines at least 3 months post-procedure, particularly in uncorrected visual acuity.

CXL is safe, with no significant changes in intraocular pressure, although it does lead to a temporary decrease in endothelial cell density and a slight reduction in corneal thickness, which stabilizes after 24 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Corneal Collagen Cross-Linking for the Treatment of Keratoconus: A Systematic Review and Meta-Analysis. Meiri, Z., Keren, S., Rosenblatt, A., et al.[2022]

In a study of 16 patients with keratoconus, transepithelial corneal collagen cross-linking (CXL) significantly improved corrected distance visual acuity (CDVA) and reduced corneal irregularities after 12 months, indicating its efficacy in treating this condition.

The procedure had a quick corneal reepithelization time of about 1 day, suggesting it is a safe and efficient treatment option for keratoconus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical results of transepithelial corneal collagen cross-linking in the treatment of keratoconus]. Chen, SH., Zhang, J., Li, YN., et al.[2018]

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]

The new high-intensity corneal collagen crosslinking (CXL) treatment protocol for keratoconus, using 9 mW/cm² irradiance for 10 minutes, showed no significant complications during or after the procedure in a study of 9 patients (10 eyes).

Three months post-treatment, there was a significant reduction in the steep keratometry readings, indicating improved corneal shape, while endothelial cell density remained stable and no patients experienced a loss in visual acuity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of high-intensity corneal collagen crosslinking. Kymionis, GD., Grentzelos, MA., Kankariya, VP., et al.[2022]

In a case series of four keratoconus patients treated with corneal collagen cross-linking (CXL), severe complications occurred within the first month, including bacterial infections and an autoimmune response, leading to permanent corneal scarring in some cases.

While severe complications after CXL are rare, they often arise from indirect factors during the healing process, such as patient behavior and the use of bandage contact lenses, highlighting the need for improved techniques and careful postoperative management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe Complications after Corneal Collagen Cross-Linking (CXL). Blaser, F., Zweifel, S., Wiest, MRJ., et al.[2023]

In a study of 117 eyes treated with corneal collagen cross-linking (CXL) for keratoconus, four cases of severe keratitis were reported, highlighting a potential risk associated with this treatment.

The keratitis led to significant inflammation and corneal scarring, resulting in a persistent decrease in visual acuity in some patients, indicating the need for careful monitoring and management post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Keratitis and corneal scarring after UVA/riboflavin cross-linking for keratoconus. Koppen, C., Vryghem, JC., Gobin, L., et al.[2022]

Corneal collagen cross-linking (CXL) is an effective and FDA-approved treatment for halting the progression of keratoconus, a condition that affects the cornea's shape.

The procedure is considered relatively safe with a low complication rate, but it is important for practitioners to be aware of potential complications and their management as CXL becomes more widely used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications of corneal collagen cross-linking. Agarwal, R., Jain, P., Arora, R.[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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Independent-effect comparison of five crosslinking procedures for Progressive Keratoconus based on Keratometry and the ABCD Grading System using Generalized Estimating Equations (GEE). [2023]

2. 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]

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

Efficacy of Corneal Collagen Cross-Linking for the Treatment of Keratoconus: A Systematic Review and Meta-Analysis. [2022]

4. China pubmed.ncbi.nlm.nih.gov

[Clinical results of transepithelial corneal collagen cross-linking in the treatment of keratoconus]. [2018]

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

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

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

Safety of high-intensity corneal collagen crosslinking. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Severe Complications after Corneal Collagen Cross-Linking (CXL). [2023]

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

Keratitis and corneal scarring after UVA/riboflavin cross-linking for keratoconus. [2022]

9. India pubmed.ncbi.nlm.nih.gov

Complications of corneal collagen cross-linking. [2022]

10. 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]

11. India pubmed.ncbi.nlm.nih.gov

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

12. 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]