Aqueous chlorhexidine (0.1%) is an effective alternative to povidone–iodine for intravitreal injection prophylaxis

Effective antisepsis along with strict aseptic technique (of drug and delivery) are recognized as the most important factors in the prevention of endophthalmitis associated with intravitreal injections (IVI). United States medicare data confirms an overall rate of about 0.1% for IVI-associated endophthalmitis (Schwartz & Flynn 2014), although many studies report lower rates (Dossarps et al. 2015). Povidone–iodine (5% aqueous) preparations have historically been considered the most effective antimicrobial prophylaxis for ophthalmic procedures and have been adopted as routine for IVI, although effective antisepsis has been demonstrated at lower concentrations, with 0.25% povidone–iodine a commonly used preparation in some countries (Berkelman et al. 1982; Shimada et al. 2013). Povidone–iodine has also previously been shown to be non-toxic to ocular tissues at concentrations up to 4%, with higher concentrations more likely to cause ocular surface side-effects (Trost et al. 2007). Postprocedure pain is a commonly recognized adverse event of IVI and has typically been attributed to chemical sensitivity (not allergy) to povidone–iodine on the ocular surface (especially concentrations of 5–10%). Aqueous chlorhexidine gluconate (0.1%) (see Fig. 1) has been described as an alternative antisepsis agent for IVI but has not been previously reported in published literature, and the label does caution against use ‘in irrigating eyes'. We report our own experience and rationale in using aqueous chlorhexidine gluconate (0.1% Pfizer, New York) after incorporating it into exclusive use as antisepsis for IVI in two sites. All IVI were performed by a single surgeon in a dedicated procedure room with vinyl surfaces and HEPA-filtered air-conditioning system in keeping with RCOphth (UK) guidelines (Amaoku et al. 2009). After instilling a drop of topical anaesthesia (tetracaine), an initial drop of 0.1% chlorhexidine gluconate was instilled prior to lignocaine gel anaesthesia and the eye taped closed (10 mins). Following adequate anaesthesia time, the eye was irrigated with 0.1% chlorhexidine gluconate and a surgical drape applied. A further drop of chlorhexidine was instilled over the area marked for injection immediately prior to the injection. Aseptic technique (drug and needle) was observed at all times by both the ophthalmologist and assistant. There were a total of 4322 IVI performed between May 2013 and July 2015 using 0.1% chlorhexidine gluconate exclusively as antisepsis. There was one case of endophthalmitis, equating to a rate of 0.023%. This is comparable with the published rates of endophthalmitis with povidone–iodine preparations (Schwartz & Flynn 2014; Dossarps et al. 2015). The rationale for making a switch to aqueous 0.1% chlorhexidine gluconate came from our own patient surveillance of postprocedure pain scores on 121 patients undergoing intravitreal injection with povidone–iodine 5% preparation. Patients were asked to rank the pain they experienced on a scale of 0 to 10 with 0 representing no pain and 10 representing the worst possible pain. Of the 121 patients surveyed, 65% reported pain following the procedure and for 17% of patients this pain was reported as severe (eight of 10 or more). In an initial cohort (n = 20) of patients reporting high levels of pain, the antisepsis agent was switched to a 0.1% chlorhexidine gluconate preparation. The pain survey was continued, and we found a decrease in the average pain score from eight of 10 to three of 10. According to guidelines from the Center for Disease Control and Prevention, both chlorhexidine gluconate and povidone–iodine have a broad spectrum of activity; however, in regard to preoperative hand scrubs, chlorhexidine gluconate was superior in reducing skin microflora. Povidone–iodine is considered to provide intermediate level disinfection, while chlorhexidine gluconate is considered a low-level disinfectant (recommendations reflecting that limited studies exist for chlorhexidine in both efficacy and toxicity) (CDC 1999). There have previously been concerns about the safety of chlorhexidine for use in ophthalmic procedures, given the reported effect it can have on the corneal epithelium and corneal endothelium. However, aqueous chlorhexidine (gluconate) has been proven to be safe for ophthalmic use at concentrations of less than or equal to 1% (Hamill et al. 1984). Although literature on efficacy of chlorhexidine as an ophthalmic antiseptic preparation is limited, in vitro studies have been conducted looking at inhibition of bacterial growth on disc assays, as well as isolates of Staphylococcus epidermidis following irrigation of conjunctiva with various concentrations of chlorhexidine. This study found chlorhexidine has broad-spectrum action and effectively reduces bacterial counts when used as conjunctival irrigation, but requires longer contact time to achieve antisepsis (~2 min) (Hamill et al. 1984). There are some safety issues to consider in relation to the use of chlorhexidine as antisepsis for IVI. The use of chlorhexidine for irrigation of cutaneous wounds has previously been studied in a porcine model, and it was shown to delay re-epithelialization at a concentration of 0.2%; however, chlorhexidine was the only treatment to eradicate all bacteria at 48 h (Archer et al. 1990). In a rabbit model of corneal abrasions, concentrations of 2% or more delayed re-epithelialization, but concentrations of 1% did not (Hamill et al. 1984; Archer et al. 1990). Hypersensitivity reactions to chlorhexidine are varied, including contract dermatitis, urticarial, dyspnoea and anaphylactic shock; however, the rate of allergic reactions to chlorhexidine has not been well established. Patch testing using chlorhexidine in one study revealed a positive rate of 2%, (Abdallah 2015) while in another study 0.47% of patients with contact allergy were sensitive to chlorhexidine (Nagendran et al. 2009). We did not have any episodes of allergic reaction to 0.1% chlorhexidine gluconate in our cohort. We have found chlorhexidine gluconate (0.1%) is safe and efficacious antisepsis prophylaxis for IVI, particularly for those patients with betadine sensitivity in whom the significance of postprocedure pain should not be underestimated. We have also successfully used chlorhexidine gluconate 0.1% for cataract surgery antisepsis.