Rose Bengal Electromagnetic Activation With Green Light for Infection Reduction

NCT05110001 | Completed Phase 3 Results DMC

• 2 other identifiers: 18-26045-RUG1EY028518
• Study Type: interventional
• Target: 330
• Locations: 2 countries
• Sites: 2

Brief Summary

Rose Bengal Electromagnetic Activation with Green light for Infection Reduction (REAGIR ) is an international, randomized, doubled masked, clinical trial. The purpose of this study is to determine differences in 6-month visual acuity between medical antimicrobial treatments alone versus antimicrobial treatment plus cross-linking with rose Bengal (RB-PDT). Patients presenting to one of the Aravind Eye Hospitals in India or to the Federal University of São Paulo ophthalmology clinic in Brazil with either smear or culture positive fungal or acanthamoeba keratitis or smear and culture negative corneal ulcers and moderate to severe vision loss, defined as Snellen visual acuity of 20/40 or worse, will be eligible for inclusion. Those who agree to participate will be randomized to one of two treatment groups: Group 4, Sham RB-PDT: topical chlorhexidine gluconate 0.02% (acanthamoeba), moxifloxacin 0.5% (smear/culture negative) or natamycin 5% (fungal keratitis) plus sham RB-PDT Group 5, RB-PDT: topical chlorhexidine gluconate 0.02% (acanthamoeba), moxifloxacin 0.5% (smear/culture negative) or natamycin 5% (fungal keratitis) plus RB-PDT.

Conditions

Acanthamoeba Keratitis; Fungal Keratitis

Outcome Measures

Primary Outcomes (1)

• Best Spectacle-Corrected Visual Acuity

  Best Spectacle-Corrected Visual Acuity

  6 Months

Secondary Outcomes (2)

• Best Spectacle-Corrected Visual Acuity

  3 Weeks, 3 Months, 12 Months

• Scar Size

  3 Weeks, 3 Months, 6 Months 12 Months

Study Arms (2)

Standard Therapy

PLACEBO COMPARATOR

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

Drug: Moxifloxacin Ophthalmic; Drug: Chlorhexidine Gluconate; Drug: Natamycin; Other: Placebo

Cross-Linking with rose Bengal (RB-PDT)

EXPERIMENTAL

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

Drug: Moxifloxacin Ophthalmic; Drug: Chlorhexidine Gluconate; Drug: Natamycin; Drug: Rose Bengal

Interventions

Natamycin DRUG

Natamycin 5% is an antifungal agent used to treat fungi that cause keratitis. This is a standard therapy for fungal keratitis.

Cross-Linking with rose Bengal (RB-PDT); Standard Therapy

Rose Bengal DRUG

Study participants receive RB-PDT within 48 hours of randomization. All participants will receive a 30-minute loading dose of topical Rose Bengal (0.1% RB in 0.9% sodium chloride) which will be applied in 5-minute intervals to the de-epithelialized cornea. This will be followed by irradiation with a 6mW/cm2 custom-made green LED source for 15 minutes (5.4J/cm2). Repeat cornea culture will be collected within 24 hours after the procedure.

Also known as: Corneal Cross Linking with rose Bengal

Cross-Linking with rose Bengal (RB-PDT)

Placebo OTHER

Study participants receive sham RB-PDT within 48 hours of randomization. Participants will receive a 30-minute loading dose of topical balanced salt solution which will be applied in 5-minute intervals to the de-epithelialized cornea. A pen light covered with a green filter will be used for 15 minutes. Repeat cornea culture will be collected 30 minutes after the sham procedure.

Standard Therapy

Moxifloxacin Ophthalmic DRUG

Topical moxifloxacin 0.5% is a fluoroquinolone antibiotic that is used to treat bacterial infections. This is a standard therapy for bacterial keratitis.

Cross-Linking with rose Bengal (RB-PDT); Standard Therapy

Chlorhexidine Gluconate DRUG

Topical chlorhexidine gluconate 0.02% is an antiseptic agent, with both antibacterial and antifungal properties. This is a standard therapy for Acanthamoeba keratitis.

Cross-Linking with rose Bengal (RB-PDT); Standard Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Presence of smear or culture positive fungal or acanthamoeba ulcer; smear or culture negative ulcer; or any atypical bacteria (such as Nocardia)
• Moderate to severe vision loss, defined as Snellen visual acuity of 20/40 (6/12) or worse
• Corneal thickness ≥350 µm, as measured on AS-OCT
• Age over 18 years
• Basic understanding of the study as determined by the physician
• Commitment to return for follow up visits

You may not qualify if:

• Evidence of concomitant infection on exam, gram stain, or confocal microscopy (i.e. herpes, both bacteria and acanthamoeba on gram stain)
• Impending or frank perforation at recruitment
• Involvement of sclera at presentation
• Non-infectious or autoimmune keratitis
• History of corneal transplantation
• History of intraocular surgery within last three months
• Pinhole visual acuity worse than 20/200 in the unaffected eye
• Participants who are decisionally and/or cognitively impaired
• Presence of demestocele at recruitment

Sponsors & Collaborators

• National Eye Institute (NEI): collaborator
• Stanford University: collaborator
• Federal University of São Paulo: collaborator
• Aravind Eye Care System: collaborator
• University of California, San Francisco: lead

Study Sites (2)

Federal University of São Paulo

São Paulo, Brazil

Location

Aravind Eye Care System

Madurai, Tamil Nadu, India

Location

Related Publications (3)

• Christy SJ, Mandlik K, Kumar V, Kanchugantla SSSM, Abdelrahman S, Rose-Nussbaumer J. Adjunctive tacrolimus in the treatment of fungal keratitis requiring therapeutic penetrating keratoplasty. Am J Ophthalmol Case Rep. 2025 Dec 29;41:102506. doi: 10.1016/j.ajoc.2025.102506. eCollection 2026 Mar.

  PMID: 41561665 DERIVED

• Prajna NV, Lalitha P, Sharma S, de Freitas D, Hofling-Lima A, Varnado N, Abdelrahman S, Cavallino V, Arnold BF, Lietman TM, Rose-Nussbaumer J. A double-masked, sham-controlled trial of rose bengal photodynamic therapy for the treatment of fungal and acanthamoeba keratitis: Rose Bengal Electromagnetic Activation with Green Light for Infection Reduction (REAGIR) study. Trials. 2024 Aug 28;25(1):566. doi: 10.1186/s13063-024-08376-3.

  PMID: 39192339 DERIVED

• Prajna V, Prajna L, Sharma S, de Freitas D, Hofling-Lima AL, Varnado N, Abdelrahman S, Cavallino V, Arnold B, Lietman T, Rose-Nussbaumer J. A double-masked, sham-controlled trial of rose bengal photodynamic therapy for the treatment of fungal and acanthameoba keratitis: Rose Bengal Electromagnetic Activation with Green Light for Infection Reduction (REAGIR) Study. Res Sq [Preprint]. 2024 Jul 2:rs.3.rs-4165312. doi: 10.21203/rs.3.rs-4165312/v1.

  PMID: 39011096 DERIVED

MeSH Terms

Conditions

Acanthamoeba Keratitis

Interventions

chlorhexidine gluconate; Natamycin; Rose Bengal; Corneal Cross-Linking

Condition Hierarchy (Ancestors)

Eye Infections, Parasitic; Parasitic Diseases; Infections; Amebiasis; Protozoan Infections; Keratitis; Corneal Diseases; Eye Diseases; Eye Infections

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Fluoresceins; Spiro Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Xanthenes; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Polycyclic Compounds; Photochemotherapy; Combined Modality Therapy; Therapeutics; Drug Therapy; Phototherapy

Results Point of Contact

• Title: Sarah Abdelrahman
• Organization: F.I. Proctor Foundation

Sarah.abdelrahman@ucsf.edu

7143064525

Study Officials

• Tom Lietman, MD

  University of California, San Frnasco

  PRINCIPAL INVESTIGATOR

• Jennifer Rose-Nussbaumer, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Nicole Varnado, MPH

  Stanford University

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2021
• First Posted: November 5, 2021
• Study Start: August 3, 2022
• Primary Completion: December 14, 2024
• Study Completion: June 30, 2025
• Last Updated: January 30, 2026
• Results First Posted: January 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1); BR (1)