Rose Bengal Electromagnetic Activation With Green Light for Infection Reduction

Study Overview
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Brief Summary
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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.

Official Title
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Rose Bengal Electromagnetic Activation With Green Light for Infection Reduction

Conditions
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Acanthamoeba Keratitis, Fungal Keratitis

Intervention / Treatment
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* Drug: Moxifloxacin Ophthalmic
* Drug: Chlorhexidine Gluconate
* Drug: Natamycin
* Drug: Rose Bengal
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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