Rose Bengal Electromagnetic Activation With Green Light for Infection Reduction

Importance: Infectious keratitis results in poor outcomes despite maximal medical therapy. While rose bengal photodynamic therapy (RB-PDT) has not been shown to be beneficial at improving best spectacle-corrected visual acuity (BSCVA) or cure rate, decreasing scar size, or complication rate at a shorter period of 6 months, long-term results are essential to evaluate clinically relevant scarring and visual recovery. Objective: To evaluate 12-month outcomes from the clinical trial (REAGIR) comparing adjunctive rose bengal photodynamic therapy (RB-PDT) vs sham in treatment of fungal, acanthamoeba, and smear/culture-negative infectious keratitis. Design, Setting, and Participants: This international multicenter, randomized, double-masked, sham-controlled clinical trial took place at Aravind Eye Hospitals in India (Madurai, Coimbatore, and Pondicherry) and the Federal University of São Paulo in Brazil. The study included a total of 330 participants with corneal ulcers who were randomized to the above groups. These data were analyzed from June 1, 2025, to July 15, 2025. Intervention: Participants were randomized to receive (1) a standardized loading dose of topical 0.1% rose bengal, followed by 15 minutes of green light irradiation (RB-PDT) or (2) identical procedure without activating the green light source (sham). All participants received standard antimicrobial therapy. Main Outcomes and Measures: Prespecified primary outcome was BSCVA (logarithm of the minimum angle of resolution) at 6 months. Prespecified secondary outcomes included BSCVA, infiltrate and/or scar size at 12 months, corneal perforation (CP) and/or the rate of therapeutic penetrating keratoplasty (TPK), and microbiological cure rate at 12 months. Results: Of 330 enrolled patients (mean [SD] age, 50 [13] years; 213 male [65%] and 117 female [35%]), 282 (85%) had BSCVA measurements and 250 (75%) had 12-month infiltrate/scar measurements. There was no evidence of benefit of RB-PDT vs sham for BSCVA at 12 months (mean difference, 0.01; 95% CI -0.13 to 0.14; P = .91). Scar size was not different at 12 months (mean difference, 0.006 mm; 95% CI, -0.32 to 0.33; P = .97). CP/TPK rates were 31 vs 34 events at 12 months (hazard ratio, 1.21; 95% CI, 0.74-1.98; P = .44), indicating no difference. There was no difference in outcomes by organism subgroup. Conclusions and Relevance: In this study, at 12 months, RB-PDT did not confer a benefit over sham therapy for BSCVA, infiltrate/scar size, or rates of CP/TPK. These findings support 6-month REAGIR results, supporting the likelihood that there is no benefit to adjunctive RB-PDT for infectious keratitis at 1 year. These findings do not rule out the possibility that alternative photosensitizers or treatment algorithms might be beneficial. Trial Registration: ClinicalTrials.gov Identifier: NCT05110001.