Aqueous chlorhexidine is an effective alternative to povidone–iodine for intravitreal injection prophylaxis

Editor, W e would like to thank Grzybowski & Brona (2016) for their interest in our work regarding the use of chlorhexidine gluconate as an alternative to povidone–iodine for asepsis in intravitreal injections (IVI). Highlighting possible resistance to our antiseptic preparations is an important consideration for such prevalent procedures as intravitreal injections. While multiple outbreaks in other settings have been linked to contaminated chlorhexidine, typically these have been traced to use of contaminated water to prepare diluted preparations, failure to adequately disinfect bottles being reused to dispense chlorhexidine or inappropriate disinfection applications (rather than antisepsis applications) (Weber et al. 2007). For the outbreak referenced (vigeant), nonsterile water was used for dilution to 2% concentration anddistribution occurred in reusable non-sterile containers. We agree that more research is required to quantify theantimicrobial effectofaqueous chlorhexidine gluconate 0.1%, including demonstrated reduction in flora counts using chlorhexidine gluconate solutions,particularly inresistant bacterial strains. In our cohort, though, the rate of endophthalmitis was comparable with published rates suggesting efficacy in the clinical setting (Oakley & Vote 2016). However, multiple outbreaks have also been reported duetocontaminatediodophorsandhave typically represented intrinsic (manufacturing) contamination (Weber et al. 2007). Our understanding of iodophor chemistry improved from analysis of these outbreaks, highlighting that ‘free’ iodine (I2) contributes to thebactericidal activity with more dilute solutions demonstrating more rapid bactericidal action, possibly byweakening the iodine linkage to the carrier polymer povidone, with an accompanying increase in free iodine in solution (Berkelman et al. 1982;Weber et al. 2007). We agree with the authors’ points raised regarding the proven efficacy of povidone–iodine solutions and that reduced concentrations of povidone iodine, such as 2.5% used by Shimada et al. (2013), may be another method for reducing pain related to IVI while retaining efficacious antisepsis; however, patient comfort and pain studies are lacking in this area (Berkelman et al. 1982). We agree that future studies are warranted to find the optimal povidone–iodine concentration, balancing patient comfort with effective antisepsis. With the prevalence of intravitreal injections, these are studies that should be proceeding as the significance to patients of post-injection pain is not representative in our literature. Finally,we thank the authors for their valuable comments and highlight that our study was not intended to suggest chlorhexidine gluconate as a replacement antiseptic agent of choice. Rather, it was intended to highlight that postinjection pain from povidone–iodine sensitivity is significant for many patients. In our experience, this can be reduced for thosepatientswith the useof aqueous chlorhexidine gluconate 0.1%, with our study also providing clinical evidence for its utilization as antisepsis in the intravitreal injection setting.