Rose Bengal Electromagnetic Activation With Green Light For Infection Reduction (Reagir): Randomized, Double-Masked, Sham-Controlled Clinical Trial Outcomes After Twelve Months
Published 2026 - 44th Congress of the ESCRS
Reference: FP10.01 | Type: Free paper | DOI: 10.82333/gd8g-vg10
Authors: Dr Alec Bernard* 1 , A/Prof. N Venkatesh Prajna 2 , Lalitha Prajna 2 , Revathi Rajaraman 2 , Sankalp Sharma 2 , Christy Josephine 2 , Naveen Radhakrishnan 2 , Kunal Mandlik 2 , Denise Freitas 3 , Ana Lima 3 , Nicole Varnado 4 , Sarah Abdelrahman 5 , Benjamin Arnold 6 , Thomas Lietman 5 , Jennifer Rose-Nussbaumer 1
1Ophthalmology,Byers Eye Institute,Palo Alto,United States, 2Aravind Eye Hospital,Madurai, Pondicherry, Coimbator,India, 3Federal University of São Paulo,Sao Paulo,Brazil, 4Byers Eye Institute,Palo Alto,United States, 5Francis I. Proctor Foundation, University of California San Francisco,San Francisco,United States, 6Department of Epidemiology and Biostatistics,Francis I. Proctor Foundation, University of California San Francisco,San Francisco,United States
Purpose
The objective of this study is to evaluate 12-month outcomes of the Rose Bengal Electromagnetic Activation with Green Light for Infection Reduction (REAGIR) clinical trial. Rose bengal photodynamic therapy (RB-PDT) has direct antimicrobial effect and has been used as adjunctive treatment in severe non-responsive keratitis. Infectious keratitis secondary to fungal or acathamoebic causes has poor visual outcomes and short term outcomes from RB-PDT have been previously shown to have benefit at 3 weeks, but longer followup is needed. We report 12 month outcomes from the REAGIR trial, which compated RB-PDT against sham therapy for patients with acanthamoeba, fungal, and smear/culture-negative infectious keratitis.
Setting
Enrollment occurred across four specific sites: the Federal University of São Paulo in Brazil (IRB# 482/21, CONEP# 5.900.981) and three Aravind Eye Hospital locations in India—Madurai, Coimbatore, and Pondicherry (IRB# 2020009CLI, ICMR# 011-26589492). The University of California, San Francisco (IRB# 18-26045) also granted institutional review board approval.
Methods
In this international, multi-center, double-masked, sham-controlled, randomized clinical trial, we randomized 330 participants with corneal ulcers to intervention or control groups. Every participant received standard antimicrobial therapy and were randomized to either an intervention or control arm. The intervention protocol consisted of a standardized loading dose of topical 0.1% rose bengal followed by 15 minutes of green light irradiation (RB-PDT). The control group underwent an identical procedure, but without activation of the green light source. Patients, providers, and outcome assessors remained masked. Twelve-month oucomes were pre-specified and included visual acuity, scar/infiltrate size and corneal perforation rates.
Results
Follow-up measurements were available for 85% (n=282) of patients for BSCVA and 75% (n=250) for infiltrate/scar size. Comparisons between RB-PDT and control therapy showed no evidence of benefit for 12-month BSCVA (0.01; 95% CI -0.13 to 0.14; P=0.91) or scar size (0.006 mm; 95% CI, –0.32 to 0.33; P=0.97). CP/TPK event rates were 31 and 34 for the respective groups, showing no significant difference (HR=1.21; 95% CI, 0.74 to 1.98; P=0.44). Outcomes were unaffected by fungal organism subgroup.
Conclusions
Twelve-month follow-up data indicates adjunctive RB-PDT demonstrates there is likely no clear benefit over sham therapy for CP/TPK rates, BSCVA, or infiltrate/scar size. Despite prior findings of a short-term scar and/or infiltrate size benefit at 3 weeks, these long-term results indicate there may be no significant value of the addition of RB-PDT to standard antimicrobial therapy. Future directions may include adjusting phtodynamic therapy parameters (higher fluence/frequency) or identifying high-risk subgroups or susceptible organisms to identify populations where RB-PDT may be an effective adjuctive therapy.