Corneal Collagen Crosslinking + Intacs for Keratoconus

(CXL Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Cornea and Laser Eye Institute

Disqualifiers: Normal eyes, Corneal disease, Pregnancy, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the combined effectiveness of corneal collagen crosslinking (CXL) and Intacs (intrastromal corneal ring segments) for individuals with keratoconus or corneal ectasia, where the cornea becomes thin and misshapen. CXL can slow the progression of keratoconus, while Intacs may help flatten the cornea. The study will compare the outcomes of performing both procedures simultaneously versus conducting CXL three months after Intacs. Individuals diagnosed with keratoconus or corneal ectasia following eye surgery, who experience vision problems not corrected by glasses, may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment validation.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that corneal collagen crosslinking (CXL) is a safe treatment for keratoconus, an eye condition. Long-term studies indicate that CXL effectively halts the progression of this condition and is generally safe. Most patients notice their vision stabilizes over time.

Intacs, small devices placed in the cornea, are also well-tolerated. Studies on Intacs report that many patients experience improved vision. The procedure is considered safe, with many patients seeing better without major problems.

Both CXL and Intacs have undergone thorough testing, and research supports their safety for treating keratoconus. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Corneal Collagen Crosslinking (CXL) combined with Intacs for keratoconus because it offers a potentially more effective way to strengthen the cornea and halt disease progression. Unlike traditional treatments like rigid contact lenses or corneal transplants, which focus on managing symptoms or replacing damaged tissue, this approach aims to reinforce the corneal structure itself. The combination of Intacs, small implants that reshape the cornea, with CXL, which uses UV light and riboflavin to stiffen the corneal collagen fibers, could provide a synergistic effect, improving the corneal shape and stability more effectively than either treatment alone. This dual-action method could significantly enhance vision and quality of life for patients with keratoconus.

What evidence suggests that this trial's treatments could be effective for keratoconus?

Research has shown that combining corneal collagen crosslinking (CXL) with Intacs effectively treats keratoconus. In this trial, participants will join one of two treatment arms: one where Intacs placement is immediately followed by CXL, and another where Intacs placement is followed by CXL three months later. Studies have found that this combination improves both vision without glasses and vision with glasses, reducing the need for corrective lenses. Intacs are small devices placed in the cornea to help flatten and reshape it. Meanwhile, CXL strengthens the cornea, helping to stop keratoconus from worsening. Long-term evidence also supports the benefits of these treatments in maintaining the eye's shape stability and improving vision quality over time. ^{6 7 8 9 10}

Who Is on the Research Team?

Peter Hersh, MD

Principal Investigator

Cornea and Laser Eye Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11523831/

Effects and safety of combined corneal collagen crosslinking ... Both combined and separate CXL and ICRS treatments resulted in significant improvement in UCVA and BCVA and reduced manifest refraction.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12446827/

Intrastromal corneal ring segments for keratoconus CAIRS, combined with corneal crosslinking, showed promising outcomes with enhanced biocompatibility and minimal complications, particularly for ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0886335019300446

Corneal crosslinking and intracorneal ring segments for ... Outcomes included changes in maximum keratometry (K) and topographic inferior–superior (I–S) difference, maximum flattening of topographic K, and changes in ...

4. nature.com nature.com/articles/s41598-018-36668-7

Long-term outcome of intrastromal corneal ring segments ... ICRS has advantages in improving CDVA with topographic stabilization and decreasing coma in keratoconus for five years.

5. journals.lww.com journals.lww.com/egos/fulltext/2021/14030/corneal_collagen_cross_linking__cxl__versus.4.aspx

Corneal collagen cross-linking (CXL) versus combined CXL... The corneal cross-linking procedure has been proven to be an effective method to treat and stabilize keratoconus progression, but early vision ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37367742/

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.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37369766/

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. The standard CXL resulted in greater ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0002939425005173

Effectiveness and safety of cross-linking in keratoconus ... In this systematic review and meta-analysis, we found that CXL was generally safe and effective for treating progressive keratoconus in patients ...

9. link.springer.com link.springer.com/article/10.1007/s00417-025-06803-y

Outcomes of localized corneal collagen crosslinking with a ... CXL is safe and effective in treating progressive keratoconus. Previous studies have shown that customized cone centered CXL is effective in ...

10. ajo.com ajo.com/article/S0002-9394(23)00022-3/abstract

Long-term Safety and Efficacy of Corneal Collagen ... SCXL reduced KC progression in children up to 7 years of follow-up and revealed improvement and stability of UDVA and CDVA in 82% of eyes. For visual acuity and ...