Rose Bengal Electromagnetic Activation With Green Light for Infection Reduction (REAGIR)

August 13, 2026 updated by: University of California, San Francisco

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

330

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • São Paulo, Brazil
        • Federal University of São Paulo
  • India
    • Tamil Nadu
      • Madurai, Tamil Nadu, India
        • Aravind Eye Care System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Standard Therapy
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
Topical moxifloxacin 0.5% is a fluoroquinolone antibiotic that is used to treat bacterial infections. This is a standard therapy for bacterial keratitis.
Drug: Chlorhexidine Gluconate
Topical chlorhexidine gluconate 0.02% is an antiseptic agent, with both antibacterial and antifungal properties. This is a standard therapy for Acanthamoeba keratitis.
Drug: Natamycin
Natamycin 5% is an antifungal agent used to treat fungi that cause keratitis. This is a standard therapy for fungal keratitis.
Other: Placebo
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.
Experimental: Cross-Linking with rose Bengal (RB-PDT)
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
Topical moxifloxacin 0.5% is a fluoroquinolone antibiotic that is used to treat bacterial infections. This is a standard therapy for bacterial keratitis.
Drug: Chlorhexidine Gluconate
Topical chlorhexidine gluconate 0.02% is an antiseptic agent, with both antibacterial and antifungal properties. This is a standard therapy for Acanthamoeba keratitis.
Drug: Natamycin
Natamycin 5% is an antifungal agent used to treat fungi that cause keratitis. This is a standard therapy for fungal keratitis.
Drug: Rose Bengal
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.
Other Names:
  • Corneal Cross Linking with rose Bengal

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best Spectacle-Corrected Visual Acuity
Time Frame: 6 Months
Best Spectacle-Corrected Visual Acuity
6 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best Spectacle-Corrected Visual Acuity
Time Frame: 3 Weeks, 3 Months, 12 Months
Best Spectacle-Corrected Visual Acuity
3 Weeks, 3 Months, 12 Months
Scar Size
Time Frame: 3 Weeks, 3 Months, 6 Months 12 Months
Geometric Mean
3 Weeks, 3 Months, 6 Months 12 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

National Eye Institute (NEI)
Stanford University
Federal University of São Paulo
Aravind Eye Care System

Investigators

  • Principal Investigator: Jennifer Rose-Nussbaumer, MD, Stanford University
  • Study Director: Nicole Varnado, MPH, Stanford University
  • Principal Investigator: Tom Lietman, MD, University of California, San Frnasco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 3, 2022

Primary Completion (Actual)

December 14, 2024

Study Completion (Actual)

June 30, 2025

Study Registration Dates

First Submitted

October 26, 2021

First Submitted That Met QC Criteria

November 4, 2021

First Posted (Actual)

November 5, 2021

Study Record Updates

Last Update Posted (Actual)

September 3, 2026

Last Update Submitted That Met QC Criteria

August 13, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18-26045-R
  • UG1EY028518 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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