Intracameral antibiotic prophylaxis: Where do we stand?

Welcome to another edition of CEDARS/ASPENS Debates. CEDARS/ASPENS is a society of cornea, cataract and refractive surgery specialists, here to discuss some of the latest hot topics in ophthalmology.

This month we are going to discuss the use of intracameral antibiotics in the course of cataract surgery as a prophylaxis against endophthalmitis. Since the early 2000s, several large studies have shown the efficacy of this method, reporting a threefold to fivefold reduction in the risk of developing endophthalmitis. However, concerns remain, particularly in the U.S., where no FDA-approved commercial formulation of antibiotics for intracameral use is currently available. The jury is still out: Audrey R. Talley Rostov, MD, and Deepinder K. Dhaliwal, MD, LAc, stand on opposite sides.

Kenneth A. Beckman, MD, FACS
OSN CEDARS/ASPENS Debates Editor

Increased efficacy has been largely proven

Cataract surgery is the most commonly performed surgical procedure in medicine, and we want it to be the safest, with the best outcomes, for all our patients.

Endophthalmitis is the complication we fear the most because, as rare as it might be, it is one of the most sight-threatening infections in our field, potentially leading to blindness. Even with prompt diagnosis and treatment, outcomes are usually poor, and prevention remains key. So far, no global consensus has been reached regarding the optimal prophylactic strategy for endophthalmitis, and trends, preferences and practice patterns vary around the world.

In 2007, the European Society of Cataract and Refractive Surgeons published its seminal results, showing a fivefold decrease in endophthalmitis rate with the use of intracameral cefuroxime. The study included 13,698 patients from 24 ophthalmology units and eye clinics in nine European countries, within a time span of 3 years. In 2013, Shorstein and co-authors also reported a significant decline in the rate of postoperative endophthalmitis with intracameral antibiotic prophylaxis (cefuroxime, moxifloxacin or vancomycin) at a Kaiser Permanente eye department in Northen California. The study included 16,264 cataract surgeries within 3 years. Another large study was performed in India, at the Madurai Aravind Eye Hospital, and included 116,714 cataract surgeries (manual small-incision cataract surgery, or MSICS, and phaco) over 14 months. A fourfold reduction in postoperative endophthalmitis in patients undergoing MSICS was reported with the use of intracameral moxifloxacin. A number of other smaller studies have reported similar outcomes. When I was part of the Clinical Cataract Committee, the American Society of Cataract and Refractive Surgery published a review article giving an overview of endophthalmitis prophylaxis, and again, looking at all the studies, we showed a significant decrease in endophthalmitis rate with the use of intracameral antibiotics.

When administering intracameral antibiotics, ideally you want to do this as a single-unit dose at the end of the procedure. Moxifloxacin should be used in a preservative-free formulation because some issues have been reported with preserved intracameral moxifloxacin. In the U.S., single-use doses for cataract surgery can be ordered from some pharmacies, one of which is ImprimisRx. Many of us prepare intracameral Vigamox (moxifloxacin, Harrow) by diluting topical Vigamox 5:1 with balanced salt solution. Obviously, there are always concerns about potential errors with preparation, dilution and use of these compounds, but this is true for all other intracameral medications, such as epinephrine or lidocaine. You want to make sure that those are preservative free as well because preservatives are potentially toxic to the corneal endothelium.

Overall, no procedure is 100% safe, but the small risk involved in intracameral antibiotic prophylaxis vs. the larger risk of a potentially devastating, blinding complication is more than acceptable.

We use intracameral moxifloxacin in our practice unless there is a documented allergy to fluoroquinolones. In those cases, we prescribe the use of topical antibiotics every 2 hours for the first 24 hours and then four times a day for the first week.

The 2021 survey of the ASCRS showed that the use of intracameral prophylaxis has increased globally and was reported as the first choice by 66% of respondents. Because there is no FDA-approved antibiotic for intracameral injection, and not all hospitals allow us to use antibiotics off label, the uptake in the U.S. is slower compared with other parts of the world. However, it is growing and would definitely take off if a commercially approved agent became available.

• References:
• Barry P. J Cataract Refract Surg. 2013;doi:10.1016/j.jcrs.2012.11.003.
• Barry P. J Cataract Refract Surg. 2014;doi:10.1016/j.jcrs.2013.11.002.
• Barry P, et al. J Cataract Refract Surg. 2006;doi:10.1016/j.jcrs.2006.02.021.
• Braga-Mele R, et al. J Cataract Refract Surg. 2014;doi:10.1016/j.jcrs.2014.10.010.
• Chang DF, et al. J Cataract Refract Surg. 2022;doi:10.1097/j.jcrs.0000000000000757.
• Friling E, et al. J Cataract Refract Surg. 2024;doi:10.1097/j.jcrs.0000000000001464.
• Haripriya A, et al. Ophthalmology. 2016;doi:10.1016/j.ophtha.2015.09.037.
• Lieu AC, et al. Curr Opin Ophthalmol. 2024;doi:10.1097/ICU.0000000000001010.
• Montan PG, et al. J Cataract Refract Surg. 2002;doi:10.1016/s0886-3350(01)01269-x.
• Myers WG, et al. J Cataract Refract Surg. 2023;doi:10.1097/j.jcrs.0000000000001237.
• Shorstein NH, et al. Perm J. 2021;doi:10.7812/TPP/20.274.
• Shorstein NH, et al. Am J Ophthalmol. 2021;doi:10.1016/j.ajo.2021.02.007.
• Shorstein NH, et al. J Cataract Refract Surg. 2013;doi:10.1016/j.jcrs.2012.07.031.

• For more information:
• Audrey R. Talley Rostov, MD, of Bellevue Precision Vision, can be reached at audreyrostov@gmail.com.

Equally effective and safer options

From the vitreous specimens of endophthalmitis cases, we know that the organisms that cause the infection are genetically identical to the organisms found on the patient’s ocular surface, eyelids and lashes.

Consequently, to tackle the problem at the source, the most critical part of endophthalmitis prophylaxis is antisepsis before we make our cataract incision.

There is no standardized method to do presurgical antisepsis. Most studies agree upon the use of 5% povidone-iodine (PI) but suggest a variable number of eye drops or irrigation, a single vs. a double application. The most recent literature has shown that irrigating the fornix with a significant volume of PI is more effective in decreasing the bacterial load on the ocular surface, and the double PI wash method has been validated as the best protocol at procurement to decrease the rate of infection in corneal transplant procedures. In our center, we performed a retrospective analysis of 17 years of cataract surgery and found a significantly lower endophthalmitis rate among patients who had been prepared with double PI prep. Our paper has recently been submitted for publication.

We routinely use PI double prep in a regimented way, and we perform careful draping of the lids and lashes. We then administer fourth-generation fluoroquinolone drops every 15 minutes, starting the hour before surgery, and postoperatively we have the patient use the drops every 2 hours while awake. Achieving a watertight wound closure at the end of surgery is another important step to prevent postoperative bacterial contamination. We meticulously check incisions and will hydrate the incisions a little more or even apply a suture if needed.

We examine every patient the day after surgery, check the incisions, anterior chamber, lens and posterior segment, and if everything is in good order, decrease the antibiotic to four times a day. Fourth-generation fluoroquinolones are concentration-dependent killers, and with our postoperative protocol, we achieve a stable, prolonged concentration in the anterior chamber that is more effective at eradicating infectious organisms than just a single dose injected in the chamber that is reduced to half the concentration after a little more than 1 hour. Our endophthalmitis rate is very low, similar to or even lower than the rates reported in the literature with the use of intracameral antibiotics.

Our method is also safer. I have personally performed endothelial keratoplasty in patients who developed toxic anterior segment syndrome after intracameral moxifloxacin injection, and some of these cases have been reported in the literature. In the U.S., we do not have a commercially available agent, so the risk of contamination or dilutional error is never zero. In Europe, Aprokam (Théa), a single-use cefuroxime preparation for intracameral use, is commercially available, but cases of patients who developed anaphylaxis have been reported. With the high number of cataract surgeries that are performed globally, we have to be aware that some patients may have at-risk allergy profiles and hypersensitivity issues. For us, safety is the No. 1 concern, and the potential allergic reactions to drops will never be as severe and dangerous as those related to an intracameral injection, which is a systemic load with potentially systemic adverse effects.

In summary, we feel that a double PI prep prior to cataract surgery in conjunction with topical antibiotics, careful draping and meticulous technique is the safest way to prevent endophthalmitis after cataract surgery.

• References:
• Liu DT, et al. J Cataract Refract Surg. 2006;doi:10.1016/j.jcrs.2005.12.050.
• Mahiat C, et al. J Investig Allergol Clin Immunol. 2022;doi:10.18176/jiaci.0741.
• Moisseiev E, et al. J Cataract Refract Surg. 2013;doi:10.1016/j.jcrs.2013.06.008.
• Peyman A, et al. Adv Biomed Res. 2020;doi:10.4103/abr.abr_155_19.
• Salisbury CD, et al. Cornea. 2019;doi:10.1097/ICO.0000000000002006.
• Sawant OB, et al. Cornea. 2022;doi:10.1097/ICO.0000000000003057.
• Soleimani M, et al. Surv Ophthalmol. 2024;doi:10.1016/j.survophthal.2023.11.002.
• Trinavarat A, et al. Dermatology. 2006;doi:10.1159/000089197.
• Villada JR, et al. J Cataract Refract Surg. 2005;doi:10.1016/j.jcrs.2004.06.086.
• Wu PC, et al. J Ocul Pharmacol Ther. 2006;doi:10.1089/jop.2006.22.54.

• For more information:
• Deepinder K. Dhaliwal, MD, LAc, of UPMC Vision Institute in Pittsburgh, can be reached at dhaliwaldk@upmc.edu.

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Disclosures:
Dhaliwal and Talley Rostov report no relevant financial disclosures.

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