Corneal Collagen Cross-Linking for Keratoconus

Overseen By Denzil Romfh, OD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Oregon Health and Science University

Disqualifiers: Retinal diseases, Glaucoma, Cataracts, 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: 1 day

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Laser Custom Corneal Collagen Cross-Linking for individuals with keratoconus, a condition where the cornea thins and bulges. The treatment aims to improve vision by using a laser, guided by Optical Coherence Tomography (a special imaging tool), to smooth the cornea. Individuals diagnosed with keratoconus and a corneal thickness of at least 410 microns may qualify for this trial. As an unphased trial, it provides a unique opportunity to contribute to innovative research that could enhance treatment options for keratoconus.

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 prior data suggests that this OCT-guided laser custom corneal collagen cross-linking is safe?

Research has shown that corneal collagen cross-linking (CXL) is a safe treatment for keratoconus, a condition that alters the shape of the eye's cornea. Studies have found that CXL effectively halts the progression of this condition. Most patients maintain a stable corneal shape and vision for many years following the treatment. Complications from CXL are rare, and patients generally tolerate the procedure well. Long-term evidence supports the high safety of this treatment, making it a reliable choice for those with keratoconus. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional treatments for keratoconus, like rigid contact lenses or standard corneal cross-linking, the Laser Custom Corneal Collagen Cross-Linking is unique because it uses OCT-guided technology for precision. This customized approach targets the cornea more accurately, potentially leading to better outcomes and quicker recovery. Researchers are excited about this technique because it promises to enhance vision correction and stabilize the cornea more effectively than current methods.

What evidence suggests that Laser Custom Corneal Collagen Cross-Linking is effective for keratoconus?

Research has shown that Laser Custom Corneal Collagen Cross-Linking (CXL) effectively treats keratoconus, a condition where the cornea thins and bulges. Studies have found that CXL can significantly reduce imperfections in the cornea's shape and improve vision. Long-term evidence supports its safety and effectiveness in halting or slowing the progression of keratoconus. In some cases, it has successfully stabilized the condition for several years. This procedure offers promise for those seeking to maintain and improve their vision with keratoconus. ^{1 6 7 8 9}

Who Is on the Research Team?

David Huang, MD, PhD

Principal Investigator

Oregon Health and Science University

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Laser Custom Corneal Collagen Cross-Linking

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.

How Is the Trial Designed?

Group I: Surgery Experimental Treatment 1 Intervention

OCT-guided custom laser CXL

Laser Custom Corneal Collagen Cross-Linking is already approved in United States, European Union for the following indications:

Approved in United States as Corneal Cross-Linking for:

• Keratoconus

Approved in European Union as Corneal Cross-Linking for:

• Keratoconus

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

National Eye Institute (NEI)

Collaborator

Trials

572

Recruited

1,320,000+

Published Research Related to This Trial

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]

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]

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) 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 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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10302271/

Safety and Efficacy of Corneal Cross-Linking in Patients ... CXL is a safe and effective treatment for avoiding keratoconus progression. Long-term data are encouraging, supporting a high safety profile for this procedure.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03760432

NCT03760432 | Collagen Cross-linking in Keratoconus Laser Custom Corneal Collagen Cross-linking (CXL) significantly decreases corneal aberrations and improves vision. This study will use OCT-guided setting for ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2162098923006485

Corneal Collagen Cross-linking: A Review of Clinical ... Corneal collagen cross-linking (CXL) has been shown to slow down or stop the progression of keratoconus. In addition, CXL has been applied in cases of ...

4. nature.com nature.com/articles/s41433-023-02641-6

5-year outcomes from the Save Sight Keratoconus Registry Both standard and accelerated CXL were safe and effective procedures for stabilising keratoconus in the long term.

5. blueshieldca.com blueshieldca.com/content/dam/bsca/en/provider/docs/2023/May/PRV_Corneal_ClgnCross.pdf

9.03.28 Corneal Collagen Cross-Linking 10,. Of 59 eyes for which investigators had longer-term follow-up data (4 to 6.7 years), 30.9% showed worsening corrected distance visual acuity ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10361434/

and long-term safety and efficacy of corneal collagen cross ... The purpose of the study is to evaluate the safety and outcomes of corneal collagen cross-linking (CXL) and different CXL protocols in progressive keratoconus ...

7. aaojournal.org aaojournal.org/article/S0161-6420(24)00282-3/fulltext

Safety and Efficacy of Epithelium-Off Corneal Collagen ... A decrease in corneal thickness was observed in both groups but was greater in the CXL group. Complications were rare. Conclusions. Epithelium- ...

8. vision-institute.com vision-institute.com/understanding-the-risks-and-side-effects-of-corneal-cross-linking-cxl/

Corneal Crosslinking (CXL) For Keratoconus | Risks & Side ... Long-term data from our center shows promising outcomes: over 80% of keratoconus patients maintain stable corneal structure and stable vision even 10 years post ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2162098923001639

Review Article Corneal Cross-Linking for Keratoconus Corneal collagen cross-linking (CXL) with riboflavin is an accepted universal standard of care for our keratoconus patients with progressive disease.