Riboflavin for Keratoconus

Recruiting at1 trial location

Overseen by John S Jarstad, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of Missouri-Columbia

Must not be taking: Sunlight sensitivity drugs

Disqualifiers: Riboflavin sensitivity, Sunlight sensitivity, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests if taking vitamin B2 pills and spending time in the sun can help strengthen the cornea in patients with certain eye conditions. The goal is to provide a less painful and cheaper alternative to current treatments. A method using vitamin B2 and sunlight has been developed since the late 1990s to strengthen the cornea in these conditions.

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

The trial protocol does not specify if you need to stop your current medications. However, if you are on medications that make you more sensitive to sunlight, you should talk to your doctor before joining the trial.

What data supports the effectiveness of the treatment Dietary Riboflavin (Vitamin B-2) for Keratoconus?

Research shows that riboflavin, when used with ultraviolet-A light in a process called corneal collagen cross-linking, can help stabilize keratoconus, a condition where the cornea becomes thin and cone-shaped. This treatment has shown long-term benefits in halting the progression of the disease. ^{1 2 3 4 5}

Is riboflavin safe for use in treating keratoconus?

Riboflavin, when used in combination with ultraviolet-A light for corneal collagen cross-linking, is generally considered safe for treating keratoconus, as it has been used in various studies without major safety concerns. It also acts as a protective shield for deeper eye structures during the procedure. ^{3 5 6 7 8}

How is the riboflavin treatment for keratoconus different from other treatments?

The riboflavin treatment for keratoconus is unique because it involves a non-invasive method called 'epi-on' that uses riboflavin (Vitamin B2) and ultraviolet-A light to strengthen the cornea, unlike the traditional 'epi-off' method that requires removing the corneal surface and can cause more side effects. ^{3 5 7 8 9}

Research Team

John S Jarstad, MD

Principal Investigator

University of South Florida - Department of Ophthalmology

Eligibility Criteria

This trial is for individuals with keratoconus or post-refractive cornea ectasia and significant astigmatism. It's not suitable for those sensitive to sunlight or riboflavin, or on medications that increase sunlight sensitivity unless cleared by their doctor.

Inclusion Criteria

Patients identified as having keratoconus or post refractive cornea ectasia with astigmatism of 1.5 Diopters or greater

Exclusion Criteria

You are allergic or sensitive to riboflavin.

Patients on medications with side effects of increased sunlight sensitivity should discuss participation with their prescribing provider prior to participation

You have a known sensitivity to sunlight.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants take 400 mg dietary riboflavin per day and are exposed to natural sunlight for 15 minutes daily to evaluate the effects on cornea cross-linking and stabilization

3-6 months

Regular check-ins as needed

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Dietary Riboflavin (Vitamin B-2) (Vitamin)

Trial Overview The study tests if dietary riboflavin (Vitamin B-2) combined with natural sunlight exposure can strengthen the cornea similarly to FDA-approved Avedro therapy, potentially offering a less expensive treatment option.

Participant Groups

Group I: Treatment with riboflavin Experimental Treatment 1 Intervention

Patients will take 400 mg dietary riboflavin per day and go outside without sunglasses for 15 minutes per day to evaluate the effects of riboflavin B2 and natural UV light from sun exposure on cornea cross linking and stabilization of ectatic disease.

Who Is Running the Clinical Trial?

University of Missouri-Columbia

Lead Sponsor

Trials

387

Recruited

629,000+

Mun Y. Choi

University of Missouri-Columbia

Chief Executive Officer since 2017

PhD in Mechanical and Aerospace Engineering from Princeton University

Richard Barohn

University of Missouri-Columbia

Chief Medical Officer since 2020

MD from the University of Missouri-Columbia School of Medicine

University of South Florida

Collaborator

Trials

433

Recruited

198,000+

Dr. Barbara White

University of South Florida

Chief Medical Officer since 2021

MD, University of Pennsylvania School of Medicine

Dr. Sylvia W. Thomas

University of South Florida

Chief Executive Officer since 2023

Ph.D. in Electrical Engineering, University of South Florida

Findings from Research

In a study of 100 keratoconus patients and 200 healthy individuals, riboflavin levels were significantly lower in the keratoconus group, suggesting a potential link between low riboflavin and the development of keratoconus.

Other vitamins such as B12, folic acid, and homocysteine levels did not show significant differences between the two groups, indicating that riboflavin deficiency may be a specific risk factor for keratoconus rather than a general deficiency in these nutrients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of blood levels of vitamin B12, folic acid, riboflavin, and homocysteine in keratoconus and healthy subjects. Sozer, O., Ozalp, O., Atalay, E., et al.[2023]

In a long-term study of 480 eyes from 272 patients with progressive keratoconus, collagen crosslinking using riboflavin and ultraviolet-A demonstrated significant stabilization of corneal steepening over a follow-up period of up to 6 years.

The procedure also led to improved best corrected visual acuity (BCVA) in over half of the patients within the first year, indicating that collagen crosslinking is an effective treatment option for managing progressive keratoconus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: long-term results. Raiskup-Wolf, F., Hoyer, A., Spoerl, E., et al.[2022]

Riboflavin and ultraviolet-A induced collagen cross-linking (CXL) effectively stabilizes keratoconus over a long-term period, with significant improvements in corneal curvature and best corrected visual acuity (BCVA) observed 10 years post-treatment in a study of 30 eyes from 20 patients.

The procedure is minimally invasive and safe, showing no damage to the corneal endothelium or deeper structures, with only two patients experiencing continued progression of keratoconus requiring re-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Corneal collagen cross-linking with riboflavin and ultraviolet-A light in progressive keratoconus. Results after 10-year follow-up]. Theuring, A., Spoerl, E., Pillunat, LE., 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]

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 long-term study of 111 patients with progressive keratoconus, riboflavin and UVA-induced collagen cross-linking significantly reduced keratectasia (corneal steepening) over three years, with an average decrease of 4.34 D by the third year.

The treatment also improved or stabilized visual acuity in a substantial number of patients, with no severe side effects reported, indicating that collagen cross-linking is a safe and effective long-term option for managing progressive keratoconus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Collagen cross-linking with riboflavin and UVA light in keratoconus. Results from Dresden]. Hoyer, A., Raiskup-Wolf, F., Spörl, E., et al.[2021]

In a study involving 78 eyes with progressive keratoconus, riboflavin-assisted corneal collagen cross-linking (C3R) demonstrated significant improvements in various corneal parameters, including keratometry and visual acuity, at 3 and 6 months post-treatment.

The treatment was found to be effective in the Northeast Indian population, but further long-term studies are needed to assess the durability of these improvements and the safety of potential repeat therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of riboflavin-assisted collagen cross-linking of cornea in progressive keratoconus patients: A prospective study in North East India. Bhattacharyya, A., Sarma, P., Das, K., et al.[2021]

The study developed a non-invasive treatment for keratoconus using riboflavin-5-phosphate sodium loaded in nanostructured lipid carriers (NLCs), which showed promising results in enhancing drug permeability through the cornea without significant accumulation.

The most effective formulation included Transcutol P as a permeation enhancer, demonstrating high functional performance in corneal crosslinking, suggesting it could be a safer alternative to the invasive 'epi-off' technique currently used in clinics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of ocular drug delivery platforms and in vitro - in vivo evaluation of riboflavin to the cornea by non-interventional (epi-on) technique for keratoconus treatment. Aytekin, E., Öztürk, N., Vural, İ., et al.[2022]

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]

References

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

Comparison of blood levels of vitamin B12, folic acid, riboflavin, and homocysteine in keratoconus and healthy subjects. [2023]

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

Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: long-term results. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

[Corneal collagen cross-linking with riboflavin and ultraviolet-A light in progressive keratoconus. Results after 10-year follow-up]. [2022]

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

Effect of inferior-segment Intacs with and without C3-R on 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. Germany pubmed.ncbi.nlm.nih.gov

[Collagen cross-linking with riboflavin and UVA light in keratoconus. Results from Dresden]. [2021]

7. India pubmed.ncbi.nlm.nih.gov

Safety and efficacy of riboflavin-assisted collagen cross-linking of cornea in progressive keratoconus patients: A prospective study in North East India. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Design of ocular drug delivery platforms and in vitro - in vivo evaluation of riboflavin to the cornea by non-interventional (epi-on) technique for keratoconus treatment. [2022]

9. Brazil pubmed.ncbi.nlm.nih.gov

[Corneal Cross-linking for the treatment of keratoconus: preliminary results]. [2019]