Endophthalmitis after Anti-VEGF Intravitreal Injections with Aqueous Chlorhexidine versus Povidone-Iodine as Ocular Antiseptics

March 2024 

Samir N. Patel, MD
Retina Vitreous Consultants, Pittsburgh PA


Ton NS, Goncharov V, Zapata I, Adam MK. Endophthalmitis after Anti-VEGF Intravitreal Injections with Aqueous Chlorhexidine versus Povidone-Iodine as Ocular Antiseptics. Ophthalmol Retina. 2023 Dec 18:S2468-6530(23)00648-6. PMID: 38122867.

Infectious endophthalmitis is a rare but potentially severe complication of intravitreal injections.

Multiple strategies have been employed to reduce the risk of post-injection endophthalmitis including avoidance of post-injection antibiotics, enforcing a “no-talking” policy before and during the treatment, and the use of prefilled syringes.

For infection prophylaxis, povidone-iodine (5% PI) has been the standard prophylactic antiseptic regimen used for intravitreal injections. Although 5% PI is an effective antiseptic agent, it may be associated with significant post injection ocular discomfort. In some patients, the self-reported adverse reactions to povidone iodine are one of the biggest barriers to treatment adherence. Aqueous chlorhexidine (CHX) is a broad-spectrum antimicrobial that has traditionally been used for the treatment of acanthamoeba keratitis. More recently, aqueous chlorhexidine has been proposed as a potential alternative antiseptic agent for patients undergoing intravitreal injections who have a sensitivity or intolerance to povidone-iodine.

In this retrospective, single-center, comparative cohort study over 2 years published in Ophthalmology Retina by Ton et al., the authors evaluated rates of post-injection endophthalmitis in eyes receiving antisepsis with 5% povidone-iodone compared to aqueous chlorhexidine.

All intravitreal injections were administered by 13 retina specialists over the two-year study period. The injection protocols amongst the doctors were similar, and the availability of povidone-iodine and CHX were equally accessible at all office locations.

In total, 67,695 intravitreal injections were performed over the study period, and the presumed endophthalmitis rate was 13 of 32,802 injections (1 in 2,523) in the PI group compared to 9 of 34893 injections (1 in 3,877) in the CHX group (p = 0.395). For cases of culture-positive endophthalmitis, the rate was 2 of 32,802 injections (1 in 16,401) in the PI group compared to 2 of 34,893 injections (1 in 17,447) in the CHX group (p > 0.99). For the cases that did develop post-injection endophthalmitis, visual outcomes were similar at the causative injection, endophthalmitis presentation, and 3-month follow up in both eyes.

The authors also performed a subgroup analysis evaluating the usage of prefilled syringes by the PI and CHX groups and found that there was a significantly higher proportion of prefilled syringe use in the CHX group (81% prefilled) compared to the PI group (50% prefilled). When accounting for the potential effect of prefilled syringe use on endophthalmitis risk, subgroup analysis showed no difference in endophthalmitis risk using either PI or CHX in the prefilled syringe subgroup or the non-prefilled syringe subgroup.

Overall, this study found that there was no difference in endophthalmitis risk in eyes treated with aqueous chlorhexidine compared to 5% povidone iodine for antisepsis before intravitreal injections. For patients with a self-reported adverse reaction to povidone iodine, CHX may be a reasonable alternative with a good safety and efficacy profile for ocular antisepsis.