Standard vs. Accelerated Corneal Crosslinking for Keratoconus

Overseen By Francis Price, Jr., MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Price Vision Group

Disqualifiers: Insufficient corneal thickness, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

510 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two methods to strengthen the cornea for individuals with keratoconus or corneal ectasia, conditions where the cornea becomes thin and weak. Both treatments use riboflavin eye drops and UV light, but one method is faster. The trial aims to determine if the quicker method is as safe and effective as the standard one. Individuals diagnosed with keratoconus or ectasia after eye surgery might be suitable candidates for this trial. As a Phase 2, Phase 3 trial, it focuses on measuring the treatment's effectiveness in a smaller group and represents the final step before FDA approval, offering participants a chance to contribute to advancing eye care.

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 has shown that both standard and accelerated corneal crosslinking with riboflavin 0.1% are generally safe for treating keratoconus. In studies, patients who received these treatments did not report significant side effects. Safety data from 193 treated eyes indicated that the procedures were well-tolerated.

For the accelerated treatment, published studies found no side effects. Riboflavin, the main ingredient, is safe for the body. The difference between the accelerated and standard treatments lies in the duration and intensity of UV light use. The accelerated method uses stronger UV light for a shorter time, while the standard method uses gentler light for a longer time. Despite this difference, both methods have demonstrated similar safety levels.

Overall, these treatments appear well-tolerated with no major safety concerns reported. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments in this trial because they offer promising new approaches to managing keratoconus. Unlike traditional corneal crosslinking, which typically involves a longer exposure to low-intensity UVA light, the accelerated treatment uses a higher intensity UVA light for a shorter duration. This could mean significantly reduced treatment times, making the procedure more convenient for patients. Additionally, both treatments utilize riboflavin combined with UVA light to strengthen the cornea, but the accelerated method aims to achieve similar results more efficiently, potentially broadening access to care and improving patient experience.

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

Research has shown that corneal crosslinking with riboflavin (a type of vitamin B2) and UVA light effectively treats progressive keratoconus. This trial will compare two methods: the accelerated treatment, which uses stronger UVA light for a shorter period, and the standard treatment, which involves longer exposure to weaker UVA light. Studies have found that both methods can help stabilize the condition. Specifically, one study showed that the accelerated treatment can greatly improve vision and stop keratoconus from worsening. Another study found that the standard treatment is also effective and safe for managing keratoconus. Both treatments strengthen the cornea, the eye’s outer layer, to prevent further bulging and vision problems. ^{3 6 7 8 9}

Who Is on the Research Team?

Francis Price, Jr., MD

Principal Investigator

Price Vision Group

Are You a Good Fit for This Trial?

This trial is for people with progressive keratoconus or corneal ectasia after refractive surgery. It's not suitable for those with conditions affecting eye healing, a history of chemical injury or slow healing, known sensitivity to the medications used in the study, pregnant individuals, those with thin corneas, or other ocular conditions that could complicate treatment.

Inclusion Criteria

I have been diagnosed with keratoconus or had corneal thinning after eye surgery.

Exclusion Criteria

You are known to be sensitive to the medications used in the study.

I have an eye condition that could lead to complications.

You are currently pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either accelerated or standard corneal crosslinking treatment

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Riboflavin 0.1%

Trial Overview The trial aims to compare two methods of corneal crosslinking: accelerated and standard. Both use riboflavin (vitamin B2) drops but differ in how quickly UV light is applied to strengthen the cornea and halt progression of keratoconus or ectasia.

How Is the Trial Designed?

Group I: Accelerated Active Control 1 Intervention

Treatment with 0.1% riboflavin eye drops and 9 mW/cm2 UVA light for 10 minutes

Group II: Standard Active Control 1 Intervention

Treatment with 0.1% riboflavin eye drops and 3 mW/cm2 UVA light for 30 minutes

Riboflavin 0.1% is already approved in United States, European Union for the following indications:

Approved in United States as Photrexa for:

• Progressive keratoconus
• Corneal ectasia following refractive surgery

Approved in European Union as Riboflavin ophthalmic for:

• Progressive keratoconus
• Corneal ectasia

Who Is Running the Clinical Trial?

Price Vision Group

Lead Sponsor

Trials

12

Recruited

1,700+

Published Research Related to This Trial

In a study of 280 eyes from 237 patients, both short (15 minutes) and standard (30 minutes) riboflavin induction times in corneal cross-linking for keratoconus showed similar improvements in visual acuity and keratometry after one year.

However, the short induction time resulted in greater flattening of maximum keratometry (Kmax) and a higher incidence of corneal haze, indicating a trade-off between efficacy and potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Standard Corneal Cross-Linking Procedures Performed With Short Versus Standard Riboflavin Induction: A Save Sight Keratoconus Registry Study. Benito-Pascual, B., Kandel, H., Abbondanza, M., et al.[2023]

Riboflavin/UV cross-linking is a generally safe surgical method for stabilizing keratoconus, with rare complications reported.

However, there is a risk of severe infections, as demonstrated in a case where a 40-year-old patient developed a methicillin-resistant Staphylococcus aureus (MRSA) infection post-procedure, leading to the need for a corneal transplant despite intensive treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Corneal ulcer caused by MRSA after UV/riboflavin cross-linking in a patient with bilateral keratoconus]. Bödemann, M., Kohnen, T.[2021]

In a study of 40 eyes from 30 young adult patients with early progressive keratoconus, transepithelial enhanced fluence pulsed light M accelerated crosslinking effectively halted disease progression over a 3-year follow-up, with significant improvements in visual acuity and corneal curvature.

No adverse events were reported during the treatment, indicating that this method is safe, and it achieved a mean demarcation line depth of 282.6 μm, suggesting effective treatment penetration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transepithelial Enhanced Fluence Pulsed Light M Accelerated Crosslinking for Early Progressive Keratoconus with Chemically Enhanced Riboflavin Solutions and Air Room Oxygen. Mazzotta, C., Balamoun, AA., Chabib, A., 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]

Accelerated corneal cross-linking (CXL) using hypotonic riboflavin solution is as effective as using standard riboflavin solution in treating keratoconus over a 2-year period, with similar outcomes in corneal thickness, keratometry, and visual acuity.

Both treatment groups showed comparable decreases in corneal thickness after 6 months, indicating that hypotonic riboflavin can effectively preserve corneal structure while preventing keratoconus progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Outcomes of Accelerated Corneal Cross-linking in the Treatment of Keratoconus: Comparison of Hypotonic Riboflavin Solution With Standard Riboflavin Solution. Akkaya, S., Ulusoy, DM., Duru, Z., et al.[2020]

Accelerated corneal collagen crosslinking (CXL) effectively stabilizes corneal topography in patients with mild to moderate keratoconus, with no complications reported during a 12-month follow-up of 16 eyes from 14 patients.

There was a significant improvement in uncorrected distance visual acuity (UDVA) after 12 months, indicating that while overall visual acuity measures remained stable, patients experienced some functional improvement post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated (9-mW/cm2) corneal collagen crosslinking for keratoconus-A 1-year follow-up. Elbaz, U., Shen, C., Lichtinger, A., et al.[2022]

Corneal crosslinking using UVA-riboflavin is an effective treatment for conditions like keratoconus and infectious keratitis that haven't responded to other therapies, enhancing the stability of corneal tissue.

The procedure generally halts the progression of these eye conditions, with rare complications reported for surrounding structures like the corneal endothelial cells and retina.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The progress of corneal crosslink in corneal disease]. Yu, JF., Huang, YF.[2013]

In a study of 49 eyes from 47 patients with progressive keratoconus and thin corneas, both corneal collagen crosslinking (CXL) with hypoosmolar riboflavin and standard CXL showed significant improvements in uncorrected and best-corrected visual acuity after 3 years, with no significant differences between the two methods.

Both treatment groups demonstrated safety, as there was no significant endothelial cell loss or sight-threatening complications, and no progression of keratoconus was observed in any patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term visual, refractive, tomographic and aberrometric outcomes of corneal collagen crosslinking (CXL) with or without hypoosmolar riboflavin solution in the treatment of progressive keratoconus patients with thin corneas. Celik Buyuktepe, T., Ucakhan, OO.[2022]

Riboflavin-induced ultraviolet light cross-linking is an approved treatment in Europe for keratoconus and is being explored for other corneal disorders, highlighting its growing acceptance in ophthalmology.

The review focuses on key studies that demonstrate the safety and efficacy of this treatment, particularly for patients in the early stages of keratoconus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corneal cross linking for keratoconus. Keating, A., Pineda, R., Colby, K.[2013]

Corneal cross-linking using riboflavin and UV light is a safe procedure, as none of the patients experienced a loss in best spectacle corrected visual acuity (BSCVA) after treatment.

The treatment effectively halted the progression of keratoconus in all patients, with a notable reduction in corneal curvature and improvements in unaided visual acuity over six months, although some changes were not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Corneal Cross-linking for the treatment of keratoconus: preliminary results]. Jankov, MR., Hafezi, F., Beko, M., et al.[2019]

In a study of 57 eyes from 55 patients with progressive keratoconus, corneal crosslinking (CXL) with riboflavin led to significant improvements in best corrected visual acuity and reductions in key corneal measurements over a 24-month follow-up period.

CXL was effective in stabilizing keratoconus, as evidenced by a decrease in keratometry readings and corneal volume, while maintaining its efficacy even as the cornea began to recover its original volume after the initial treatment phase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term results of corneal collagen crosslinking for progressive keratoconus. De Bernardo, M., Capasso, L., Lanza, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12358722/

Six-Month Outcomes of Accelerated Corneal Cross-Linking ... A-CXL using a total energy dose of 7.2 J/cm2 with 0.1% dextran-free riboflavin effectively stabilizes keratoconus progression, significantly improves visual ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6436846/

An Investigation of the Effects of Riboflavin Concentration on ... Our results demonstrate a dose-response curve with increasing riboflavin solution concentrations up to 0.3% achieving greater CXL efficacy.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1350946224000417

Crosslinking with UV-A and riboflavin in progressive ... Corneal crosslinking (CXL) with riboflavin and ultraviolet light (type A, UVA) is a new treatment option for progressive corneal ectatic diseases. It creates ...

4. eandv.biomedcentral.com eandv.biomedcentral.com/articles/10.1186/s40662-024-00375-4

An in vitro investigation into the impact of corneal rinsing ... Application of riboflavin/HPMC to the de-epithelialised cornea resulted in a significant increase in CCT of 73 ± 14 µm (P < 0.01) after 16 min, ...

5. tandfonline.com tandfonline.com/doi/full/10.2147/OPTH.S313647

A Prospective, Comparative, Clinical Study to Evaluate the ... Both riboflavin solutions were equally safe and effective in the management of progressive keratoconus, and resulted in similar changes in terms of mean ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2025/203324s010lbl.pdf

HIGHLIGHTS OF PRESCRIBING INFORMATION These ... Each CXL treated eye received a single course of CXL treatment only. Safety data were obtained from: 193 randomized CXL study eyes (102 keratoconus, 91 corneal.

7. glaukos.com glaukos.com/prescribing-information/photrexa-viscous-and-photrexa/

Photrexa® Viscous & Photrexa® | Prescribing Information Each CXL treated eye received a single course of CXL treatment only. Safety data were obtained from: 193 randomized CXL study eyes (102 keratoconus, 91 corneal ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4670830/

Standard versus accelerated riboflavin–ultraviolet corneal ... At present, published clinical studies of patients treated with accelerated CXL protocols are few; however, they report no adverse effects associated with ...

9. eyewiki.org eyewiki.org/Corneal_Cross-Linking

Corneal Cross-Linking In CXL, the photosensitizer is riboflavin, with an absorption peak of 370 nm. Riboflavin is a systemically safe molecule that can be adequately ...