Riboflavin for Keratoconus

Recruiting at 1 trial location

Overseen By Lindsey M McDaniel, MD

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: University of Missouri-Columbia

Must not be taking: Sunlight sensitivity drugs

Disqualifiers: Riboflavin sensitivity, Sunlight sensitivity, 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: Unknown

Duration: 3-6 months

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for keratoconus and corneal ectasia, where the cornea becomes thin and bulges, causing blurry vision. Researchers aim to determine if taking riboflavin (vitamin B2) and spending 15 minutes in natural sunlight daily can strengthen the cornea, similar to an existing treatment using riboflavin and UV light. This approach could potentially reduce costs and simplify treatment for those with these eye conditions. The trial seeks participants with keratoconus or post-surgery corneal ectasia with significant astigmatism, a common vision issue causing blurred vision. As an unphased trial, it offers a unique opportunity to contribute to innovative research that could simplify and lower the cost of treatment for 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 prior data suggests that this treatment is safe for corneal cross-linking?

Research has shown that using riboflavin (vitamin B2) for corneal cross-linking is generally safe. In a small study with seven patients, taking riboflavin and spending 15 minutes in sunlight each day yielded promising results. No side effects were reported, and all patients experienced stabilization or flattening of the cornea.

Riboflavin doses up to 400 mg per day have also been found safe for children with migraines, indicating that the vitamin is well-tolerated in humans. Additionally, combining riboflavin with UVA (ultraviolet A) light is considered a safe and effective treatment for keratoconus, a condition that causes the cornea to bulge and distort vision.

Overall, riboflavin appears to be a safe option for stabilizing the cornea, with no known negative effects from dietary intake in this context. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard of care for keratoconus, which often involves rigid contact lenses or corneal cross-linking procedures, this new approach uses dietary riboflavin (Vitamin B-2) combined with natural UV light exposure. Researchers are excited because riboflavin is a simple vitamin supplement, potentially making it an easy and accessible treatment. Additionally, the use of natural UV light for cornea cross-linking offers a non-invasive method to stabilize the condition, which could be a gentler alternative to current procedural interventions.

What evidence suggests that dietary riboflavin might be an effective treatment for keratoconus?

Research has shown that taking riboflavin (Vitamin B2) with natural sunlight can stabilize the cornea in people with keratoconus. In a small study with 7 patients, all experienced corneal stabilization or flattening without negative effects. Other studies have also found that high doses of riboflavin can improve keratoconus by strengthening the cornea, helping it maintain its shape. This trial will evaluate the effects of daily 400 mg dietary riboflavin and natural UV light exposure on cornea cross-linking and stabilization of ectatic disease. Riboflavin reacts with UV light to create new bonds in the cornea's tissue, strengthening it. These promising results suggest that this method could be as effective as current FDA-approved treatments. ^{1 2 4 6 7}

Who Is on the Research Team?

John S Jarstad, MD

Principal Investigator

University of South Florida - Department of Ophthalmology

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Dietary Riboflavin (Vitamin B-2)

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.

How Is the Trial Designed?

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.

Dietary Riboflavin (Vitamin B-2) is already approved in United States, European Union for the following indications:

Approved in United States as Riboflavin for:

• Corneal ectasia
• Keratoconus

Approved in European Union as Riboflavin for:

• Corneal ectasia
• Keratoconus

Who Is Running the Clinical Trial?

University of Missouri-Columbia

Lead Sponsor

Trials

387

Recruited

629,000+

University of South Florida

Collaborator

Trials

433

Recruited

198,000+

Published Research Related to This Trial

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]

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 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]

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]

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03095235?term=AREA%5BBasicSearch%5D(RIBOFLAVIN)&rank=4

Dietary Riboflavin (Vitamin B-2) and Cornea Cross-Linking These patients reported no adverse effects and preliminary results showed corneal stabilization and/or corneal flattening in all 7 patients It is hypothesized ...

2. scientificarchives.com scientificarchives.com/article/mega-dose-dietary-riboflavin-in-treatment-in-keratoconus-post-refractive-cornea-ectasia-and-migraine-has-its-time-arrived

Mega-Dose Dietary Riboflavin in Treatment in Keratoconus ... Several studies and investigators have shown the beneficial effects of high dose dietary riboflavin (vitamin B2) in the treatment of keratoconus, post- ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12010184/

Long-term Effects and Prognostic Factors of Accelerated ... Survival analysis showed successful halting rates of 71% and 89% in A-CXL with 5- and 10- minute–applied riboflavin, respectively. Best-corrected visual acuity ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2855667/

Riboflavin-Ultraviolet A Corneal Cross-linking for Keratoconus Our results show statistically significant reduction in keratometric readings; revealing that riboflavin-UVA corneal cross-linking could partially reverse ...

5. rbojournal.org rbojournal.org/wp-content/plugins/xml-to-html/include/lens/index.php?xml=0034-7280-rbof-84-e0036.xml&lang=en

Corneal collagen cross-linking by sun exposure and high ... Oral riboflavin treatment combined with sun exposure appears to be effective in stabilizing the progression of keratoconus.

6. mayoclinic.org mayoclinic.org/drugs-supplements/riboflavin-5-phosphate-ophthalmic-route/description/drg-20235484

Riboflavin 5-phosphate (ophthalmic route) - Side effects & ... Safety and efficacy have not been established. Geriatric. No information is available on the relationship of age to the effects of Photrexa® or ...

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

Crosslinking with UV-A and riboflavin in progressive ... Riboflavin is a vitamin (vitamin B2) that is also used for food coloring ... data supporting the efficacy and safety of CXL in patients with keratoconus.