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Ophthalmology Management

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Prevent postoperative endophthalmitis

Intracameral antibiotics play a key role in reducing the rate of this cataract surgery complication.

By: ELIZABETH T. VIRIYA, MD, Francis S. Mah, MD
Ophthalmology Management May 1, 2021 Vol 25, Issue May 2021 Page(s): 42-44, 53

Cataract surgery is performed worldwide more than 10 million times annually. However, the many benefits of cataract surgery can be negated by postoperative endophthalmitis (POE) amongst other less severe complications. POE is an ophthalmic emergency that can cause low vision in approximately 1/3 of affected eyes.1

The incidence of POE varies worldwide from 0.02-1.16%1 with the AAO’s Intelligent Research in Sight Registry (IRIS) reporting 0.04% in the United States from 2013-2017. Identifying risk factors and methods of reducing the rate of POE is critical to implementing prophylactic measures and increasing success of cataract surgery.

A patient with post-cataract surgery endophthalmitis. Image courtesy: Francis S. Mah, MD
A patient with post-cataract surgery endophthalmitis. Image courtesy: Francis S. Mah, MD

PREOPERATIVE CONSIDERATIONS

Manage the ocular surface

Preexisting ocular surface conditions that are associated with a higher microbial burden or that impair re-epithelialization of surgical incisions should be managed preoperatively. Examples include blepharitis, dry eye, exposure conjunctivitis, hordeola and canaliculitis.

Surgical preparation

In addition, surgical preparation of the ocular surface reduces the risk of POE. Microbial clearance of the periocular surgical area is achieved with the application of 5% povidone-iodine solution to the conjunctiva and the cul-de-sac for 2-5 minutes, and 5-10% povidone-iodine detergent to the periocular skin. This method has been shown to be effective in reducing the incidence of acute POE.2-4 Another effective method to prevent normal flora from entering the eye and therefore causing POE is isolation of the lids and lashes by meticulous draping.

Perioperative topical antibiotic use — pre- or postoperatively — has yet to be proven statistically significantly effective at reducing the risk of POE in prospective clinical trials.

INTRAOPERATIVE MEASURES

Antibiotic prophylaxis

There is currently no consensus on the preferred drug, dosing, timing and modality of application antibiotic prophylaxis for POE. Topical eyedrops, subconjunctival injections and use in the irrigating fluid intraoperatively have all been reported, and each has gained some proponents. However, none of these modalities has demonstrated efficacy in a randomized, placebo-controlled, prospective clinical trial like intracameral antibiotic use.

Cefuroxime

The European Society of Cataract and Refractive Surgery (ESCRS) Endophthalmitis Study group compared intracameral antibiotic use to perioperative topical antibiotic use. The control group, which encompassed those patients who received topical antibiotics or no antibiotics preoperatively, had a POE rate consistent with the higher end of the worldwide incidence at 0.345%. In comparison, the incidence of POE with the use of intracameral cefuroxime was 0.062% overall, which is associated with a statistically and clinically significant 4.92-fold reduction in the POE incidence.5 In this landmark study, the addition of perioperative topical drops suggests a possible adjunctive benefit, but the difference was not statistically significant. Since then, numerous retrospective studies have shown a reduction in POE rates with the adoption of intracameral cefuroxime.6-14

The risks of intracameral cefuroxime also warrant some attention. Dilutional errors have been associated with toxic anterior segment syndrome, and, if severe, vision loss from corneal decompensation, glaucoma and/or severe macular edema can occur.15,16 Anaphylaxis to the cephalosporin drug is a catastrophic systemic complication that has been reported.17,18 Therefore, a careful allergy history is advised prior to considering the use of this prophylactic agent.

Some reports have cautioned about the limited spectrum of coverage for cefuroxime, which might make it a less favorable antibiotic choice. Even though intracameral doses can exceed the minimal inhibitory concentrations of many of the common intraocular inoculum, findings from the LV Prasad Institute and Swedish National Cataract Surgery Database demonstrated less efficacy against gram-negative isolates and methicillin resistant S. aureus.18,19 This lack in coverage is particularly important because visual loss from gram-negative endophthalmitis is devastating, and MRSA POE reports have been increasing.

Vancomycin

Vancomycin is another agent that has been reported for intracameral use to prevent POE. However, it lost favor because of its association with hemorrhagic occlusive retinal vasculitis (HORV), a type III hypersensitivity reaction that is more destructive than POE. About two-thirds of affected patients suffer with a final visual acuity of 20/200 or worse, and about one-fifth of the patients have no light perception.20 Furthermore, more than half of the patients who are affected by HORV rapidly progress to neovascular glaucoma. Therefore, vancomycin should not be used as an intraocular prophylactic agent.

Moxifloxacin

Compared to cefuroxime and vancomycin, moxifloxacin, a fourth-generation fluoroquinolone, has multiple proposed advantages. It has a broader spectrum of activity than both of the agents previously mentioned, which includes Pseudomonas and community-acquired MRSA. Moxifloxacin is a concentration-dependent, rapidly bactericidal agent that is easily formulated as an injectable intracameral agent and is associated with low toxicity to intraocular structures compared to cefuroxime and vancomycin. An in vitro study by Libre et al demonstrated that the most common gram positive and gram negative strains that cause POE were eradicated by high dose moxifloxacin compared with vancomycin or cefuroxime.21

Efficacy of intracameral moxifloxacin prophylaxis for POE was demonstrated in a prospective, placebo-controlled, randomized controlled trial that concluded a seven-fold reduction compared to no intracameral moxifloxacin from 0.38% to 0.05%.22 Follow up retrospective studies have demonstrated a three- to six-fold reduction in POE rates after switching from topical to intracameral moxifloxacin.23-28 The concentration of safely instilled intracameral moxifloxacin reported in the peer-reviewed literature ranges from 50-500ug/uL without any incidence of TASS.

The highest dose of intracameral moxifloxacin safely tolerated might want to be considered since the bactericidal effect is dose- or concentration-dependent. Delivering a dose that exceeds the minimal inhibitory concentration for resistant organisms improves microbial coverage.29

Studies by Aravind used 500mg/0.1 mL of moxifloxacin in 2 million cases. The advantage of their method is ease of use, because it is taken directly from a commercially available preparation. However, loss from reflux or leakage from corneal incisions upon application can reduce the final amount of drug and, theoretically, bactericidal effect.

To improve reproducibility of the intraocular drug concentration, a dilution of 150mg/0.1mL moxifloxacin was proposed, where 0.4-0.6mL is used to entirely replace the fluid within the anterior chamber and hydrate the paracentesis.30-32

These drug concentrations have been studied in vitro and theoretically optimized after an evaluation of POE cases despite intracameral moxifloxacin use. However, there has been no proven reduction in POE between these two different methods of intracameral moxifloxacin delivery.

Biocompatibility, intraocular safety and lack of toxicity have been demonstrated with the wide range of moxifloxacin drug concentrations. The prospective, placebo-controlled study by Melega et al demonstrated no difference in acuity, endothelial cell count, central corneal thickness and IOP with the use of intracameral moxifloxacin. When observations were extended to 3 years post-exposure to intracameral moxifloxacin, Matsuura et al confirmed the lack of adverse events reported by Melega and added that no difference in foveal thickness occurred.33

Moxeza (Alcon), the formulation of moxifloxacin with additives such as xanthum gum, sorbitol or tyloxapol, has been reported to incite TASS. Although the branded topical formulation has been discontinued, reports of generic moxifloxacin containing these excipients have been reported to have caused TASS. Therefore, caution should be used if using a generic, and all generics should probably be avoided to be certain not to cause TASS.

How I approach intracameral antibiotics during eye surgery

By Steven R. Sarkisian, Jr., MD

All surgeons are trained to be hyper-vigilant with their sterile technique to minimize the risk of endophthalmitis. As a cataract and glaucoma surgeon, I have also been keenly concerned with postoperative inflammation. For more than a decade, I have been injecting intracameral dexamethasone at the end of every incisional eye surgery. I had been reticent to inject intracameral moxifloxacin into the anterior chamber, because there was no form of the antibiotic commercially available besides drawing it up from a bottle of medicine meant for use as an external eyedrop.

My solution is using compounded intracameral moxifloxacin. It is available from several trusted sources, but I use OMNI (dexamethasone phosphate 0.1%/moxifloxacin HCI 0.5%, OSRX), because it allows me to keep doing an intracameral steroid while adding the protective effect of this proven intracameral antibiotic to lower the rates of endophthalmitis. I use 0.15 cc of this combination after every case. It is clear in color, so doesn’t affect the “wow” factor with refractive cataract surgery, and it helps lower the risk of infection in all patients, including those with glaucoma. It has been a major change in my practice that I now consider my standard of care for all eye surgery. 

In conjunction with postop drops

Intracameral antibiotics have not been used without povidone-iodine in any landmark studies on POE prophylaxis. Even when using intracameral antibiotics in the United States, many are still reporting use with perioperative topical antibiotics. The 2014 ASCRS survey reported 97% of participants use postoperative antibiotic eyedrops.34 Topical antibiotics are usually dosed four times a day for 5-7 days postoperatively.

COMPOUNDED COMBINATION INTRACAMERAL MEDICATIONS

A different approach

With strong evidence in favor of intracameral antibiotic delivery at the conclusion of cataract surgery, the next step to consider is transzonular and pars plana injection of antibiotic. The anterior chamber is able to clear some microorganisms, but when they move posteriorly they tend to grow in the vitreous, which may be a protective matrix; a more posterior delivery of antibiotic might address this.

One concern of the transzonular approach is the possible disruption of the anterior hyaloid face with resultant retinal tears and/or detachments. From the patient perspective, intracameral delivery of corticosteroid suspension such a triamcinolone can cause a few days to weeks of blurring and floaters from the deposits, but advances in formulation are addressing this. With the pars plana approach, there is a long track record of safety and efficacy for the treatment of macular degeneration, idiopathic photosensitive occipital lobe epilepsy and other diseases. Both approaches to deliver prophylaxis are now available through compounding companies, including Imprimis Pharmaceuticals and OSRX, and warrant further clinical study.

The data

Intracameral delivery of corticosteroids in cataract surgery is also not new. It has been frequently discussed in the literature for more than a decade but lacks support by large, well-designed studies and fruition to market, possibly overthrown by the popularity of intravitreal injections and depots of corticosteroid for nonsurgical indications. In 2005, Gills and Gills analyzed 608 eyes and reported using up to 3 mg of intracameral triamcinolone with safety and good success in the reduction of postoperative inflammation that obviated the need for postoperative corticosteroid drops in those patients receiving a dose of 2.8 mg or more. At 1.8 mg or higher, no CME occurred. His group delivered the triamcinolone through the anterior chamber, but facilitated flow through the zonules by aiming the cannula posteriorly.35

In 2009, Chang et al in Pittsburgh reported safety and efficacy of 0.4 mg intracameral dexamethasone given at the conclusion of surgery in conjunction with standard postoperative corticosteroid drops; this retrospective study included 91 patients undergoing phacoemulsification with and without glaucoma.36 They did not find a significant increase in postoperative IOP in dexamethasone-treated glaucoma patients. When injected into the anterior chamber, dexamethasone, unlike triamcinolone acetonide, has not been associated with ocular hypertension.36,37 This is likely due to the rapid aqueous volume turnover and short half-life of intraocular dexamethasone vs the sustained duration of action when triamcinolone acetonide is placed sub-Tenon’s capsule and or intravitreally.36,38,39 Studies in pediatric cataract surgery have also not found an increased risk for glaucoma with the use of intracameral dexamethasone.39-41

Available agents

These studies led to various steroid with antibiotic combination agents to be used intraocularly at the conclusion of surgery. One of the agents, triamcinolone-moxifloxacin-vancomycin, should not be recommended due to the discussion of vancomycin and HORV that was outlined previously. Triamcinolone-moxifloxacin is an agent only to be used transzonularly. It has gained modest interest from U.S. surgeons, however, due to some concerns about the blurry immediate postoperative vision, occasional increased IOP with or without migration of the steroid suspension into the anterior chamber and possible movement of the effective IOL position. Another compounded intracameral combination agent, dexamethasone-moxifloxacin, can be injected into the anterior chamber due to the fact the steroid is in solution, not suspension. As previously mentioned, there is less concern about postoperative IOP rise.

CONCLUSION

POE is one of the most devastating complications of any ocular procedure. Throughout the history and evolution of anterior segment surgery, many measures have been attempted to reduce the risk of this devastating sight-threatening infection. Many of the strategies to reduce the multifactorial POE focus on antibiotics.

In the past two decades, the optimal drug, timing, placement and concentration have started to become elucidated. Eye surgeons are on the cusp of further reducing POE rates by optimizing antibiotics. Current recommendations to reduce POE include the use of the antiseptic, povidone-iodine 5% in the conjunctiva; meticulous draping of the lids, lashes and lacrimal system; and, incisions which are water-tight.

The use of intracameral antibiotics is becoming more commonplace and should be considered at the conclusion of surgery. OM

For images, see the online version of this article.

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About the Authors

Elizabeth T. Viriya, MD, is a clinical assistant professor at the Department of Ophthalmology at the NYU Grossman School of Medicine and specializes in cornea, external disease, and refractive surgery.

Elizabeth T. Viriya, MD, is a clinical assistant professor at the Department of Ophthalmology at the NYU Grossman School of Medicine and specializes in cornea, external disease, and refractive surgery.

Francis S. Mah, MD, is director of Cornea Service at Scripps Clinic in La Jolla, Calif.

Francis S. Mah, MD, is director of Cornea Service at Scripps Clinic in La Jolla, Calif.

Disclosures: Dr. Mah is a consultant for Alcon, Allergan, Bausch + Lomb and Novartis.

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