Aqueous Chlorhexidine Compared with Povidone-Iodine as Ocular Antisepsis before Intravitreal Injection: A Randomized Clinical Trial

Post-Injection Endophthalmitis Study Group

Research output: Contribution to journalArticlepeer-review


Purpose: Topical povidone-iodine (PI) is widely used as an ocular surface antiseptic for intravitreal injections (IVIs). Although PI is generally well tolerated, it can be associated with significant ocular irritation. Aqueous chlorhexidine (AqCHX) has been described as a possibly better tolerated antimicrobial for ophthalmic procedures. We compared patient pain scores, ocular surface characteristics, and antimicrobial efficacy between PI 5% and AqCHX 0.1% during IVIs. Design: Prospective single-center, randomized clinical trial. Participants: Patients receiving same-day bilateral intravitreal anti–vascular endothelial growth factor (VEGF) injections. Methods: Each patient had 1 eye randomized to PI or AqCHX, and the second eye received the other agent. Both eyes received topical proparacaine 0.5%. Main Outcome Measures: After IVIs, participants rated their pain (Wong-Baker, scale 0–10) for each eye 1 minute after PI or AqCHX instillation and 1 day after the procedure. Each eye was assessed using a standardized quantitative grading system of corneal epitheliopathy (ocular staining score). Microbial swab cultures of the conjunctiva both before instillation of topical antisepsis and 10 minutes after IVIs were given. Results: A total of 100 eyes of 50 patients were included. The mean patient age was 68 years (range, 39–92), and 30 of 50 (60%) were male. Compared with AqCHX, eyes receiving PI had a greater mean pain score immediately after injection (1.44 vs. 0.44, P < 0.001) but not on postprocedure day 1 (1.04 vs. 0.48, P = 0.06). Eyes that received PI had a higher ocular staining score indicating worse corneal epitheliopathy (4.22 vs. 3.10, P < 0.001). There was no difference in rates of positive microbial cultures between groups. There was no difference in rates of adverse events between groups (P = 0.99), and no cases of endophthalmitis occurred. Conclusions: Povidone-iodine demonstrated greater ocular surface discomfort and corneal epitheliopathy compared with AqCHX during same-day bilateral IVIs. The 2 agents otherwise demonstrated no difference in positive microbial cultures or adverse events. Aqueous chlorhexidine may be a better tolerated alternative to PI for antimicrobial prophylaxis during IVIs for some patients.

Original languageEnglish (US)
Pages (from-to)788-796
Number of pages9
JournalOphthalmology Retina
Issue number8
StatePublished - Aug 2021


  • aqueous chlorhexidine
  • intravitreal injection
  • pain score
  • povidone iodine

ASJC Scopus subject areas

  • Ophthalmology


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