Aqueous Chlorhexidine Compared to Povidone Iodine as Ocular Antisepsis Prior to Intravitreal Injection: A Randomized Clinical Trial

Written by: Daniel Su, MD

December 2020

Ali FS, Jenkins TL, Boparai RS, Obeid A, Ryan ME, Wibblesman TD, Chiang A, Garg SJ; Post-Injection Endophthalmitis (PIE) Study Group. Aqueous Chlorhexidine Compared to Povidone Iodine as Ocular Antisepsis Prior to Intravitreal Injection: A Randomized Clinical Trial. Ophthalmol Retina. 2020 Nov 19:S2468-6530(20)30458-9

Topical providone iodine (PI) is widely used as an ocular surface antiseptic prior to intravitreal injections to minimize the risk of injection associated endophthalmitis. It is highly effective and generally well tolerated. However, it can be associated with significant ocular irritation, corneal epitheliopathy, as well as post-injection pain. In addition, certain patients may have self-reported allergies to PI or have cross-reactivity concerns due to previous allergic reactions to iodinated intravenous contrast or seafood. Topical aqueous chlorhexidine (AC) has broad-spectrum antimicrobial coverage and is widely used for the treatment of acanthamoeba keratitis. Prior reports have studied the use of AC prior to intravitreal injections, including a large Australian series with more than forty thousand injections and a reported endophthalmitis rate of 0.0074%.

In this prospective, double-masked study, Ali et al. included patients who underwent bilateral same-day anti-VEGF injections and randomized one eye to receive either PI or AC while the fellow eye received the other agent based on pre-specified randomization. Topical anesthetic eye drops were used for analgesia in all injections. Conjunctival culture swabs were obtained from the superior and inferior fornices of each eye prior to application of antiseptics as well as ten minutes after completion of intravitreal injections. The ocular surface was assessed using a standardized Ocular Surface Score based on fluorescein staining patterns after completion of the intravitreal injection. Patients were asked to rate their pain in each eye using a standardized pain scale one minute after instillation of antiseptics and one day after the injection. The patients and the treating physicians were masked to the antiseptic used in each eye.

One hundred eyes of fifty patients were included in this study. The authors reported a significantly greater pain score immediately following injection in eyes prepped with PI compared to AC (1.44 vs 0.44, p<0.001) but not one day after the procedure (1.04 vs 0.48, p=0.06), although there is a trend towards significance. In addition, eyes that received PI had significantly worse corneal epitheliopathy with a mean Ocular Surface Score of 4.22 compared to 3.10 in eyes that received AC (p<0.001). Both antiseptics were effective in reducing the conjunctival microbial load and no significant difference was found between the two groups.

In summary, AC may be a better tolerated ocular antiseptic and a suitable alternative to PI especially in sensitive patients with previously documented ocular irritation related to PI. In addition, it can be offered to patients who are concerned about history of allergic reaction to iodinated intravenous contrast. As injection volumes continue to increase, decreasing antiseptic associated ocular discomfort may result in a decrease in return visits and improve patient experience.