Intracameral Antibiotics During Cataract Surgery

Evidence and Barriers

Aravind Haripriya; David F. Chang

Disclosures

Curr Opin Ophthalmol. 2018;29(1):33-39. 

In This Article

Intracameral Antibiotic Prophylaxis During Cataract Surgery: Supporting Rationale and Evidence

There are two well accepted mechanisms for intraocular bacterial contamination associated with cataract surgery. Entry of multiple instruments may carry periocular bacteria from the lids, lashes, or ocular surface into the eye. In addition, unsutured clear corneal incisions may permit retrograde influx of external surface fluid during and after surgery until a watertight hermitic seal develops postoperatively. Despite using preoperative antibiotics and povidone iodine and following careful sterilization and aseptic protocols, the rate of intraocular bacterial contamination has been shown to be as high as 31%.[4] Similar rates of anterior chamber contamination have been reported with both phacoemulsification and manual small incision cataract surgery (M-SICS).[5]

Injecting antibiotics intracamerally at the end of surgery is intended to kill any intraocular bacteria that may have gained entry during the procedure. Although some intraocular antibiotic level can be obtained with topical administration, a direct intraocular injection achieves extremely high concentrations that may persist for many hours.[6] This practice is becoming more popular worldwide. The 2014 American Society of Cataract and Refractive Surgery (ASCRS) endophthalmitis prophylaxis survey found that 50% of the 1147 global respondents were employing intraocular antibiotic prophylaxis compared to 30% of respondents in the comparable 2007 ASCRS survey.[7,8] A recent review suggests that intracameral antibiotic use is lower in the United States compared to many other countries because of the lack of a commercially available antibiotic formulation for intracameral injection.[9] Indeed, nearly 84% of respondents to the 2014 ASCRS survey would use intracameral antibiotic prophylaxis if a commercially approved formulation were available.[7]

The most commonly used antibiotics for intraocular prophylaxis are cephalosporins (cefuroxime and cefazolin), vancomycin and moxifloxacin. Additional evidence regarding intracameral prophylaxis with each of these agents has been published in the past 2 years. Cefuroxime, a second-generation cephalosporin, was initially studied for intracameral prophylaxis by Montan et al.[10,11] in the early 1990s. In 2006, the prospective, multicenter, European Society of Cataract & Refractive Surgeons (ESCRS) endophthalmitis prophylaxis study reported a significant reduction in endophthalmitis rates with intracameral cefuroxime injection.[12,13] This landmark study enrolled 16 603 total patients, and remains the only large randomized controlled trial (RCT) to analyze the efficacy of intracameral antibiotic prophylaxis. The rates of culture-proven endophthalmitis in the two groups receiving intracameral cefuroxime prophylaxis were 0.050 and 0.025% compared with 0.226 and 0.176% in the two groups without intracameral antibiotic. Overall, direct intracameral cefuroxime injections resulted in a 5.86-fold decrease in the rate of culture positive endophthalmitis. A specific concern with the ESCRS study was the high rate of endophthalmitis in patients without intracameral cefuroxime, which may have potentially exaggerated the treatment benefit.

Because of the difficulty in performing large RCTs, the preponderance of evidence supporting intracameral antibiotic prophylaxis efficacy has been in the form of large retrospective trials, most of which involved intracameral cefuroxime. Adding to this evidence are three new retrospective studies of intracameral cefuroxime efficacy published within the past 2 years.[14,15,16] A long-term study from France[14] reported on 6 371 242 cataract surgeries performed between 2005 and 2014. During this 10-year period, a significant decrease in endophthalmitis rate coincided with commercial availability of cefuroxime for intracameral injection. Analysis of a subsect of these patients by Daien et al.[15] in a separate paper concluded that the incidence of postoperative endophthalmitis following posterior capsular rupture (PCR) was lower for patients who received an intracameral injection of cefuroxime than for those who did not. This study also found no difference in the risk for cystoid macular edema between the groups that did or did not receive intracameral cefuroxime.

Availability of a commercially approved antibiotic formulation clearly affects the prevalence of intracameral prophylaxis. Commercial approval of an intraocular cefuroxime preparation (Aprokam, Thea) in multiple European countries was followed by a significant increase in intracameral antibiotic prophylaxis.[17] The 2013 ESCRS endophthalmitis prophylaxis guidelines recommend using a commercially approved cefuroxime formulation based on the cumulative published evidence.[18] A subsequent 2014 ESCRS survey showed that 74% of the respondents regularly employed intracameral antibiotic prophylaxis, and 90% would if such an antibiotic formulation were commercially available to them.[17] Kessel et al's[19] analysis of practice patterns following introduction of formal guidelines found that all respondents were using intracameral cefuroxime even before the ESCRS guidelines were released.

Aprokam is largely unavailable outside of the European region. This may explain why vancomycin (37%) and moxifloxacin (35%) were more frequently chosen than cefuroxime (26%) by 2014 ASCRS survey respondents employing intraocular antibiotic prophylaxis.[6] Among American respondents, the preferences for these same three antibiotics were 52, 31, and 14%, respectively. Including the most recent studies, international antibiotic prophylaxis preferences and practice patterns continue to vary widely.[20,21,22,23–27]

Vancomycin is a broad-spectrum antibiotic that covers nearly all staphylococcal and streptococcal species, the most frequent causes of postoperative endophthalmitis after cataract surgery. As noted in the 2014 ASCRS survey, it has been a common choice for intraocular prophylaxis, particularly in the United States, despite the lack of a commercially approved formulation for intraocular use. Most commonly, 1 mg/0.1 ml of the drug is injected intracamerally at the end of surgery. Au et al.[28] analyzed data from 2000 to 2014 and concluded that routine intracameral vancomycin prophylaxis dramatically reduced the incidence of postoperative endophthalmitis at their hospital in Sydney. Their analysis also showed that intracameral vancomycin prophylaxis was very cost effective.

Moxifloxacin is a fourth-generation fluoroquinolone that was approved for systemic use in the United States in 1999 and for topical ophthalmic use in 2003. It has excellent ocular penetration following topical administration and reduced susceptibility to the emergence of bacterial resistance, which is dose-dependent as opposed to absolute.[29–31] There is a trend among bacterial endophthalmitis isolates of increasing coagulase negative staphylococcus resistance to third-generation and fourth-generation fluoroquinolones.[32] However, at clinically administered doses, intracameral moxifloxacin achieves bactericidal levels at least 10 times the MIC of the most resistant bacteria for several hours. Because of its potent dose-dependent activity even at low injection concentrations, moxifloxacin remains bactericidal for a much longer duration than cefuroxime.[33] Libre et al. through their in-vitro study showed that only moxifloxacin was effective against all isolates because vancomycin and cefuroxime were inactive against Pseudomonas aeruginosa. Elimination of staphylococci and pseudomonads requires maximum doses, so a 0.5 mg moxifloxacin dosage is required in order to be effective against these organisms.[34] Lira et al.[35] reported similar endothelial cell loss and central corneal thickness at 2 years postoperative with intracameral moxifloxacin compared with controls who did not receive intracameral moxifloxacin.

In many countries, such as the United States, moxifloxacin can be compounded for intracameral prophylaxis by outsourcing compounding pharmacies. Intracameral injection of Vigamox brand topical moxifloxacin, which is unpreserved, is also a popular option.[33,36] Several studies have reported on the method and the safety of using topical branded Vigamox for intracameral prophylaxis.[33,36] Because it is unpreserved, the branded Vigamox formulation must be used. Generic topical moxifloxacin contains preservatives and other adjuvants that are not well tolerated for intraocular use. In India and several other countries, moxifloxacin formulations specifically for intracameral injection have been commercially available since 2013. Intracameral injection of 0.1 cc containing 500 μg of moxifloxacin achieves anterior chamber concentrations exceeding 1 mg/ml.

Our experience injecting 0.1 ml of a 5 mg/ml intracameral moxifloxacin solution (Auromox, Aurolab, India) for endophthalmitis prophylaxis at the Aravind Eye Care System (AECS) in Tamil Nadu, India, has been reported in several recent publications.[37,38,39] Approximately 60% of AECS cataract surgery is performed at little or no cost on charity patients using sutureless, manual small incision cataract surgery (MSICS). This technique involves a larger incision to manually remove an undivided nucleus, followed by implantation of a rigid PMMA IOL. Because of a historically higher rate of postoperative endophthalmitis with MSICS, routine intracameral moxifloxacin prophylaxis was started for all charity patients at one of AECS's 10 regional hospitals (Madurai, Tamil Nadu, India) in August 2014. During a 14-month study period, in which 38 160 consecutive cases done immediately prior to this change were compared with the first 37 777 consecutive eyes that received intracameral moxifloxacin, the endophthalmitis rate fell four-fold from 0.079% (30/37 777) to 0.016% (6/38 160)[37]

Based on this convincing efficacy data, AECS initiated routine intracameral moxifloxacin prophylaxis in all cataract patients at all 10 of its hospitals. We analyzed 617 453 consecutive cataract surgeries performed during the 29-month period from January 2014 to May 2016.[36] There was a 3.5-fold reduction in the endophthalmitis rate in the 314 638 consecutive eyes receiving intracameral moxifloxacin (0.02%) compared with the 302 815 consecutive eyes that did not (0.07%). The reduction was three-fold among MSICS eyes and six-fold among phaco eyes. This study also compared the endophthalmitis rates in all eyes that experienced PCR during the study period. Without intracameral moxifloxacin, PCR increased the rate to 0.48% (20/4186), whereas intracameral moxifloxacin lowered the rate to 0.21% (9/4293) (P = 0.034) in PCR eyes. New 51-month Aravind data on 1 087 907 consecutive cataract surgeries was reported in October 2017[39*] (Figure 1). Similarly, the pre-intracameral moxifloxacin endophthalmitis rate was 0.07% (376/532 357) and the post-intracameral moxifloxacin rate continued to be 3.5-fold lower at 0.02% (107/555 550). The reduction in endophthalmitis with intracameral moxifloxacin in eyes with PCR was highly significant (P < 0.001) – 0.46% (32/7671) without antibiotic compared to 0.18% (13/7174) with intracameral moxifloxacin.

Figure 1.

Quarterly rates of postoperative endophthalmitis at Aravind hospital network (January 2013 to March 2017).

Rabbit studies, which have combined intracameral moxifloxacin injection with implantation of moxifloxacin-presoaked hydrophilic acrylic IOLs, proved that high intraocular concentrations of moxifloxacin were achieved. Another trial confirmed that rabbit eyes implanted with intraocular lenses presoaked with moxifloxacin had significant reduction in endophthalmitis, which reduced further on combining it with intracameral antibiotics.[40,41]

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