Rose Bengal Electromagnetic Activation with Green Light for Infection Reduction Study: A Randomized Controlled Trial.

PURPOSE: To determine the effect of adjunctive rose bengal (RB) photodynamic therapy (PDT) in the treatment of fungal, Acanthamoeba, and smear- or culture-negative infectious keratitis. DESIGN: International, randomized, double-masked, sham-controlled clinical trial. PARTICIPANTS: Patients with corneal ulcers randomized in a 1:1 fashion to 1 of 2 treatment arms: (1) topical antimicrobial therapy plus sham RB PDT or (2) topical antimicrobial therapy plus RB PDT. MAIN OUTCOME MEASURES: The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 6 months. Secondary outcomes included BSCVA at 3 weeks and 3 months; infiltrate, scar size, or both at 3 weeks, 3 months, and 6 months; and corneal perforation (CP), the rate of therapeutic penetrating keratoplasty (TPK), or both; and microbiological cure rate. RESULTS: Three hundred thirty patients were enrolled. Isolated organisms included filamentous fungus (n = 301 [91%]), Acanthamoeba (n = 10 [3%]), and negative culture or smear findings (n = 19 [6%]). No evidence was found of a benefit of RB PDT versus sham for BSCVA at 6 months (-0.0004; 95% confidence interval [CI], -0.13 to 0.13; P = 0.62). Evidence was found of a statistically significant interaction between treatment arm and fungal organism with regard to BSCVA (P = 0.02). Rose bengal PDT improved BSCVA among eyes with Fusarium infections (difference, -0.17 logarithm of the minimum angle of resolution [logMAR]; 95% CI, -0.37 to 0.03 logMAR), but worsened BSCVA among eyes with Aspergillus infections (difference, 0.39 logMAR; 95% CI, -0.03 to 0.80 logMAR). Scar size was 0.45 mm smaller in the RB PDT group at 3 weeks (95% CI, -0.76 to -0.15 mm; P = 0.004), but this finding was no longer statistically significant at 3 and 6 months. No difference between groups was found in rates of CP, TPK, or microbiological cure. CONCLUSIONS: We were unable to find a benefit of adjuvant RB PDT overall. Future directions may include trying alternative photosensitizers or other treatment algorithms. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.