Rose Bengal + Light Therapy for Corneal Inflammation

(REAGIR Trial)

Recruiting at 3 trial locations

Overseen By Jennifer Rose-Nussbaumer, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of California, San Francisco

Disqualifiers: Concomitant infection, Corneal perforation, Scleral involvement, others

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: 6 months

330 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment using a special dye and green light to help patients with severe eye infections and vision loss. The dye and light work together to kill infections and improve vision.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions specific treatments for the trial, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment Rose Bengal + Light Therapy for Corneal Inflammation?

Research shows that Rose Bengal Photodynamic Antimicrobial Therapy (RB-PDAT) can effectively treat infectious keratitis by using light to activate Rose Bengal, which then kills harmful microorganisms. Studies indicate that this treatment is safe for the corneal endothelium and does not harm important cells in the eye, suggesting it could be a promising option for corneal inflammation. ^{1 2 3 4 5}

Is Rose Bengal + Light Therapy for Corneal Inflammation safe for humans?

The safety data for similar treatments like Chlorhexidine Gluconate (found in products like Hibiclens and ChloraPrep) shows that they can cause severe eye damage if they come into contact with the eyes. This suggests caution should be taken with any similar treatments for the eyes. ^{6 7 8 9 10}

What makes the Rose Bengal + Light Therapy treatment unique for corneal inflammation?

This treatment is unique because it uses Rose Bengal, a dye that becomes active when exposed to light, to produce oxygen radicals that kill microorganisms causing corneal inflammation. Unlike traditional treatments, this method combines a photosensitizer with light exposure to target infections, offering a novel approach to treating progressive infectious keratitis. ^{1 2 11 12 13}

Research Team

Tom Lietman, MD

Principal Investigator

University of California, San Frnasco

Jennifer Rose-Nussbaumer, MD

Principal Investigator

Stanford University

Nicole Varnado, MPH

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for adults over 18 with corneal infections like fungal or acanthamoeba keratitis, or negative smear/culture ulcers causing moderate to severe vision loss. Participants must understand the study and commit to follow-up visits. Those with other eye infections, recent eye surgery, very poor vision in the unaffected eye, or cognitive impairments cannot join.

Inclusion Criteria

Basic understanding of the study as determined by the physician

Commitment to return for follow up visits

I am over 18 years old.

Exclusion Criteria

I am at risk of or currently have a ruptured organ.

I have not had eye surgery in the last three months.

Pinhole visual acuity worse than 20/200 in the unaffected eye

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either standard antimicrobial treatment plus sham RB-PDT or antimicrobial treatment plus RB-PDT

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Chlorhexidine Gluconate
• Moxifloxacin Ophthalmic
• Natamycin
• Rose Bengal Electromagnetic Activation

Trial Overview The REAGIR trial tests if adding Rose Bengal Photodynamic Therapy (RB-PDT) to standard antimicrobial treatments improves visual acuity in patients with certain corneal infections. It's a randomized study where participants either receive RB-PDT or a sham treatment alongside their regular medication.

Participant Groups

Group I: Cross-Linking with rose Bengal (RB-PDT) Experimental Treatment 4 Interventions

Patients in this arm will receive topical chlorhexidine gluconate 0.02% (acanthamoeba), moxifloxacin 0.5% (smear/culture negative) or natamycin 5% (fungal keratitis) plus RB-PDT

Group II: Standard Therapy Placebo Group 4 Interventions

Patients in this arm will receive topical chlorhexidine gluconate 0.02% (acanthamoeba), moxifloxacin 0.5% (smear/culture negative) or natamycin 5% (fungal keratitis) plus sham RB-PDT

Chlorhexidine Gluconate is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Chlorhexidine Gluconate for:

• Skin disinfection before surgery
• Wound cleaning
• Preventing dental plaque
• Treating yeast infections of the mouth
• Keeping urinary catheters from blocking

Approved in Canada as Chlorhexidine Gluconate for:

• Skin disinfection before surgery
• Wound cleaning
• Preventing dental plaque
• Treating yeast infections of the mouth

Approved in European Union as Chlorhexidine Gluconate for:

• Skin disinfection before surgery
• Wound cleaning
• Preventing dental plaque
• Treating yeast infections of the mouth
• Keeping urinary catheters from blocking

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Thomas M. Lietman

Lead Sponsor

Trials

4

Recruited

1,400+

Federal University of São Paulo

Collaborator

Trials

477

Recruited

109,000+

Aravind Eye Care System

Collaborator

Trials

13

Recruited

102,000+

National Eye Institute (NEI)

Collaborator

Trials

572

Recruited

1,320,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Findings from Research

Chlorhexidine Gluconate (CHG) and its derivatives can cause severe eye and ear damage, even with minimal exposure during surgical preparations, leading to serious conditions like corneal injury and potential blindness.

In contrast, 10% Povidone-Iodine (PI) solutions show minimal toxicity to the eyes and ears while providing similar effectiveness in preventing surgical site infections, making them a safer alternative for preoperative skin preparation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review: Perspective on ocular toxicity of presurgical skin preparations utilizing Chlorhexidine Gluconate/Hibiclens/Chloraprep. Epstein, NE.[2022]

The review analyzed six randomized controlled trials to compare the antimicrobial efficacy and safety of various antiseptics for preoperative skin preparation, including combinations of chlorhexidine gluconate and isopropyl alcohol, and other antiseptics like povidone-iodine.

Results indicated that 2% chlorhexidine gluconate combined with 70% isopropyl alcohol (ChloraPrep) showed superior immediate and persistent antimicrobial efficacy compared to other antiseptics, suggesting it may be the best option for preventing nosocomial infections during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analyses comparing the antimicrobial activity and safety of current antiseptic agents: a review. Hibbard, JS.[2019]

Accidental exposure to Hibiclens (chlorhexidine 4% and detergent) can lead to severe and permanent corneal opacification, as seen in two patients.

Experimental studies on rabbit eyes showed that exposure to Hibiclens for just 5 to 15 minutes caused severe, irreversible corneal damage in all cases, highlighting its high toxicity to corneal tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hibiclens keratitis. Hamed, LM., Ellis, FD., Boudreault, G., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Cellular and molecular assessment of rose bengal photodynamic antimicrobial therapy on keratocytes, corneal endothelium and limbal stem cell niche. [2020]

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

Rose Bengal Photodynamic Antimicrobial Therapy for Patients With Progressive Infectious Keratitis: A Pilot Clinical Study. [2020]

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

Topical prophylaxis with moxifloxacin prevents endophthalmitis in a rabbit model. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Clinical Outcomes of Rose Bengal Mediated Photodynamic Antimicrobial Therapy on Fungal Keratitis with Their Microbiological and Pathological Correlation. [2022]

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

Photoactivated Chromophore for Moderate to Severe Infectious Keratitis as an Adjunct Therapy: A Randomized Controlled Trial. [2022]

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

Review: Perspective on ocular toxicity of presurgical skin preparations utilizing Chlorhexidine Gluconate/Hibiclens/Chloraprep. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Multiple cases of sensitization to an antiseptic containing chlorhexidine digluconate/benzalkonium chloride/benzyl alcohol with different profiles of sensitization in adults and children. [2022]

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

Analyses comparing the antimicrobial activity and safety of current antiseptic agents: a review. [2019]

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

Hibiclens keratitis. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Preservative cytotoxicity to cultured corneal epithelial cells. [2015]

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

Photoinactivation of herpes simplex virus by rose bengal and fluorescein. In vitro and in vivo studies. [2019]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Antibacterial Activity of Pharmaceutical-Grade Rose Bengal: An Application of a Synthetic Dye in Antibacterial Therapies. [2022]

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

Potassium Iodide Potentiates Antimicrobial Photodynamic Inactivation Mediated by Rose Bengal in In Vitro and In Vivo Studies. [2020]