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Review Article

Endophthalmitis Prophylaxis for Cataract Surgery

Haripriya, Aravind MD*; Baam, Zervin R. MS*; Chang, David F. MD

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The Asia-Pacific Journal of Ophthalmology: July 2017 - Volume 6 - Issue 4 - p 324-329
doi: 10.22608/APO.2017200
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Endophthalmitis, although very rare, is one of the most serious postoperative complications of ocular surgery. Infectious postoperative endophthalmitis is caused by entry of microorganisms into the eye during or after the surgical procedure. Although it can occur with any intraocular surgery, most cases are associated with cataract surgery, as it is the most common eye operation performed.1

The reported rate of endophthalmitis after cataract surgery ranges from 0.03% to 0.70%.2,3 There has been wide variation in the postoperative endophthalmitis rate over time, with the rate reported to be 0.087% in 1990 and 0.265% in 2000.2 It has been hypothesized that the increased rate observed during the 1990s was related to the use of sutureless, clear corneal incisions (CCIs) during phacoemulsification.2,4,5 There are also some studies that seem to discredit this hypothesis and instead suggest that CCIs may be associated with less endophthalmitis.6,7 Advanced age (>85 years old), rural residence, male sex, and immunosuppressive states such as diabetes mellitus may be patient-associated risk factors.8-10 The European Society of Cataract and Refractive Surgeons (ESCRS) multicenter prospective study11 identified 3 factors that significantly increased the risk of postoperative infectious endophthalmitis: a CCI, silicone intraocular lenses (IOLs), and the occurrence of surgical complications.

According to the Endophthalmitis Vitrectomy Study (EVS),12 most affected individuals lose visual acuity permanently, and visual outcomes are often are poor. One third of individuals do not gain vision better than counting fingers, and 50% do not recover vision better than 20/40.13 A more recent study reported that 34% of affected patients achieved a final visual acuity of 20/200 or worse.14 With the significant increase in cataract surgery due to population aging worldwide, effective endophthalmitis prophylaxis is a rising global imperative.


We reviewed the recent literature using the PubMed database to identify original articles using the key words “endophthalmitis prophylaxis,” “povidone iodine cataract surgery,” and “intracameral antibiotic prophylaxis.” Additional advanced search criteria included the time period from January 1, 2008, to December 30, 2016, humans, and English language. Special consideration was focused on all articles published on this topic in the past 18 months.


In recent years, trends in endophthalmitis prophylaxis have evolved considerably. Both surgical and nonsurgical preventive strategies have been advocated.15 We highlight a number of options and global practices below.

Povidone-Iodine Prophylaxis

The single most effective method of preoperative antisepsis is the application of povidone-iodine (PVI) solution (5-10%) to the cornea, the conjunctival sac, and the periocular skin surface for a minimum of 3 minutes before the commencement of surgery.16 This results in a significant decrease in the ocular surface microbial flora and has been convincingly shown to reduce endophthalmitis rates.11,17-22 The systematic implementation of PVI prophylaxis was the single most important factor for endophthalmitis reduction at an institution during a 20-year period of analysis.23 Shimada et al24 recently reported that the rate of anterior chamber bacterial contamination was significantly lessened when the operative field was irrigated every 20 seconds with balanced salt solution (BSS) containing 0.025% or 0.0025% PVI (0% rate) compared with irrigation with BSS alone (5% rate).24 There was no difference in endothelial cell density or postoperative inflammation among the 3 groups. When PVI is contraindicated (true allergy is rare and hyperthyroidism is a relative contraindication),25 aqueous chlorhexidine 0.05% may be used.11 Preoperative antisepsis of the periocular area with topical PVI is widely adopted and is considered the standard of care for endophthalmitis prevention.26,27

Perioperative Topical Antibiotics

Antibiotic prophylaxis is another common preventive measure. However, there is wide variation in the antibiotic agents used (eg, fluoroquinolones, aminoglycosides, cephalosporins, chloramphenicol), the administration routes (topical, intraocular, subconjunctival, oral), and the timing (preoperative, intraoperative, perioperative, postoperative).26,28,32 The most common causative bacteria are Gram-positive species, such as coagulase-negative Staphylococcus (CoNS), Streptococcus viridans, or Staphylococcus aureus.33,34 Gram-negative organisms, such as Pseudomonas or Haemophilus, are less common; fungi and Nocardia are rare.3,15,35,36

There is wide variability in the use of topical antibiotic prophylaxis. In contrast to PVI prep, the evidence supporting topical antibiotic prophylaxis is not as compelling, leading some surgeons to forgo it entirely.37 The theoretical goal of topical antibiotic prophylaxis is to reduce the conjunctival bacterial load, thereby lowering the risk of intraocular contamination either intraoperatively or postoperatively. Strong evidence to support its efficacy is lacking, and there is the theoretical risk that prolonged and repeated administration may induce bacterial antibiotic resistance.11 The vast majority of respondents in the 2014 American Society of Cataract and Refractive Surgery (ASCRS) survey (90%) used topical perioperative antibiotics and virtually all surgeons used them postoperatively (97%). The American Academy of Ophthalmology Cataract Preferred Practice Pattern cites that starting topical antibiotics on the day of surgery seems to be preferable to waiting until the next day to initiate them.38 Topical antibiotics are frequently used for up to 1-2 weeks postoperatively until the incision fully heals and should not be tapered, as this would encourage emergence of resistant organisms.

Intracameral Antibiotics

Corneal incisions may permit influx of fluid during surgery and even after hydration of the main incision and side port. 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%.39 Similar rates of anterior chamber contamination have been reported with both phacoemulsification and manual small-incision cataract surgery (M-SICS).40 Injecting antibiotics intracamerally (IC) at the end of surgery is intended to kill bacterial microbes that have been introduced during the procedure. This practice is becoming more popular worldwide. The 2014 ASCRS endophthalmitis prophylaxis survey found that 50% of the 1147 global respondents injected an IC antibiotic at the conclusion of surgery.41 This is significantly more than in the comparable 2007 ASCRS endophthalmitis prophylaxis survey, where 30% of respondents were using intraocular antibiotic prophylaxis.42 Antibiotics for intracameral use should have broad antimicrobial coverage and have the least potential for toxicity. The most commonly used antibiotics for intraocular prophylaxis are cephalosporins (cefuroxime and cefazolin), vancomycin, and moxifloxacin.


Cefuroxime, a second-generation cephalosporin, was initially studied for intracameral prophylaxis by Montan et al43,44 in the early 1990s. In 2006, the prospective, multicenter ESCRS endophthalmitis prophylaxis study reported a significant reduction in endophthalmitis rates with IC cefuroxime injection.9,45 This landmark randomized controlled trial enrolled 16,603 total patients and provides the strongest support for the efficacy of intracameral antibiotic prophylaxis. The rates of culture-proven endophthalmitis in the 2 groups receiving intracameral cefuroxime prophylaxis were 0.050% and 0.025% compared with 0.226% and 0.176% in the 2 groups without intracameral antibiotic. Overall, direct intracameral cefuroxime injections resulted in a 5.86-fold decrease in the rate of culture-positive endophthalmitis. A large number of international retrospective studies5,44,46-53 have also found a significant decrease in the postoperative endophthalmitis rate after initiation of intracameral cefuroxime prophylaxis. One such long-term study from France54 reported on 6,371,242 eyes over the 10-year period from 2005 to 2014. During this period, a significant decrease in endophthalmitis coincided with the commercial availability of cefuroxime for intracameral injection. Two large studies from Spain reported an approximately 10-fold reduction in endophthalmitis rates with IC cefazolin injections.55,56

The approval in multiple European countries of a commercial cefuroxime preparation for intracameral injection (Aprokam, Thea) has led to a significant increase in intracameral antibiotic prophylaxis in these countries.47 The 2013 ESCRS endophthalmitis prophylaxis guidelines support using a commercially approved cefuroxime formulation based on the published evidence.11 A 2014 ESCRS survey showed that 74% of the respondents regularly employed intracameral antibiotic prophylaxis. However, Aprokam is largely unavailable outside of the European region. This may explain why the 2014 ASCRS survey found that, in addition to cefuroxime, vancomycin and moxifloxacin are also commonly used by those respondents injecting antibiotics intracamerally.

Recently, there have been several reports of endophthalmitis caused by cefuroxime-resistant organisms. Data from the Swedish National Cataract Surgery Database suggests that the overall postoperative endophthalmitis rates with intracameral cefuroxime and moxifloxacin were similar.57 However, postoperative endophthalmitis after cefuroxime prophylaxis was associated with worse visual outcomes, largely due to a higher proportion of cases infected with resistant Enterobacter species. This raised a concern over increasing rates of cefuroxime-resistant Gram-negative isolates in Sweden. At least 2 cases of anaphylaxis associated with intracameral cefuroxime injection have been reported in the literature.58,59


Vancomycin is a broad-spectrum antibiotic that covers nearly all staphylococcal and streptococcal species, the most frequent causes of postoperative endophthalmitis after cataract surgery. It has been a common choice for intraocular endophthalmitis prophylaxis, but there is no preparation that is commercially approved for intracameral use. Most commonly, 1 mg/0.1 mL of the drug is injected intracamerally at the end of surgery. In the 2014 ASCRS survey this was the most commonly used antibiotic among those respondents employing intracameral prophylaxis: 37% overall and 52% of American respondents. However in 2015, Witkin et al60 reported on 6 patients that had an extremely rare but devastating complication associated with intracameral vancomycin: hemorrhagic occlusive retinal vasculitis (HORV). Findings of a joint ASCRS-American Society of Retina Specialists (ASRS) task force on HORV were subsequently published and included 36 eyes from 23 patients (13 bilateral cases).61 Every single case occurred after uncomplicated cataract surgery in which intraocular vancomycin was administered. Hemorrhagic occlusive retinal vasculitis seems to be a type III hypersensitivity reaction because the onset is delayed (mean onset after 1 week) and exposure of the second eye results in an earlier and more severe vasculitis. Outcomes are frequently poor because of rapid onset of neovascular glaucoma. Although likely very rare, the true incidence of this devastating complication is unknown, and many surgeons have abandoned vancomycin for routine endophthalmitis prophylaxis.


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 after topical administration and reduced susceptibility to the emergence of bacterial resistance, which is dose-dependent as opposed to absolute.62-64 There is a trend of increasing resistance of CoNS to third and fourth generation fluoroquinolones.65 However, intracameral moxifloxacin achieves bactericidal levels at least 10 times the minimum inhibitory concentration of the most resistant bacteria for a limited time period but, because of its potent dose-dependent activity even at low injection concentrations, it remains bactericidal for a much longer duration than cefuroxime.65 In many countries, such as the United States, moxifloxacin can be compounded for intracameral prophylaxis by outsourcing to compounding pharmacies. Intracameral injection of Vigamox brand topical moxifloxacin, which is unpreserved, is a more popular option.30 Several studies have reported on the method and the safety of using the topical brand Vigamox for intracameral prophylaxis.66,67 Generic topical moxifloxacin contains preservatives and other adjuvants that are not safe for intraocular use.

In India and several other countries outside Europe and the United States, specific intracameral preparations of moxifloxacin have been available since 2013, including Auromox 0.5% (Aurolab, Madurai, India) single-use 1 mL vials and 4-Quin PFS 0.5% (Entod Pharmaceutical, India) single-use prefilled syringes. Injection of 0.1 mL containing 500 μg of these ready-to-use commercial preparations achieves anterior chamber concentrations exceeding 1 mg/mL. Our early experience using intracameral moxifloxacin (Auromox, Aurolab, India) for endophthalmitis prophylaxis on charity patients of the Aravind Eye Hospital in Madurai showed a significant 4-fold reduction in the endophthalmitis rate in eyes that underwent M-SICS.68 Based on this positive experience, routine intracameral moxifloxacin prophylaxis became standard at all 10 surgical facilities of the Aravind Eye Care System. When the endophthalmitis rate was analyzed in more than 600,000 consecutive cataract surgeries performed over a 2.5-year period, we saw a significant overall endophthalmitis reduction from 0.07% to 0.02%. This was separately true for both phacoemulsification (7-fold) and M-SICS (3.5-fold) and at each of the large regional centers individually.33Table 1 summarizes recent large retrospective studies that support the efficacy of intracameral antibiotics for endophthalmitis prophylaxis.

Most Recent Retrospective Studies Comparing Endophthalmitis Rates With and Without Intracameral Antibiotic (Published Since 2012)

Although the debate regarding the safety and efficacy of using intracameral antibiotic prophylaxis continues, a recent Cochrane review69 analyzed studies that had been published through December 2016 and concluded that the 2007 ESCRS study demonstrated the efficacy of using intracameral antibiotics for reducing endophthalmitis. However, the antibiotic of choice may differ based on the clinical setting. Although there may be concerns regarding toxicity and contamination with cefuroxime, increasing resistance to endophthalmitis-causing organisms may be the concern with moxifloxacin. This review also cited the fact that clinical trials with rare outcomes require very large sample sizes and are very costly to conduct. This explains why most published evidence regarding postoperative endophthalmitis comes from retrospective trials and that practitioners must consider different types of studies to make informed decisions regarding endophthalmitis prophylaxis.


Javitt's75 oft-cited editorial elegantly summarizes the multiple reasons that a prospective randomized placebo controlled trial is so difficult, expensive, impractical, and potentially unethical to now perform.

Although there is strong evidence supporting the efficacy of intracameral antibiotic prophylaxis, the most important deterrent seems to be the lack of a commercially approved preparation in most countries, and this explains the wide global variation in this practice.76 Mixing antibiotics in the operating room raises the theoretical risk of dosing errors. Using pharmacies to compound antibiotics raises the theoretical risk of introducing contaminants or adjuvants that can cause toxic anterior segment syndrome.

Others have raised concerns that routine intraocular antibiotic prophylaxis can lead to increasing bacterial drug resistance. The recent editorial by Naseri et al77 effectively quiets this concern because a 1-time, highly concentrated dose of antibiotic injected into a physiologically isolated space is extremely unlikely to promote bacterial resistance. In fact, the concern over promoting antibiotic resistance should be directed more toward the common use of topical antibiotic prophylaxis.78 Posterior capsular rupture is one of the greatest risk factors for infectious endophthalmitis. There is strong evidence that intracameral antibiotics reduce the risk of endophthalmitis in eyes with this complication, and this is true of both cefuroxime72 and moxifloxacin.33

In summary, there is much stronger evidence supporting the efficacy of intracameral antibiotic injection than for topical administration for endophthalmitis prophylaxis. Despite weaker evidence for efficacy, topical antibiotic prophylaxis is ubiquitous and the most common method in use. This is because it is considered safe and readily available. In countries where an approved antibiotic formulation for intraocular use is commercially available, adoption is increasingly widespread. Where no such commercial source is available, the rare incidence of bacterial endophthalmitis must be weighed against the theoretical risks of using compounded formulations or those mixed by the operating room staff. In addition to theoretical compounding risks, vancomycin poses the additional risk of HORV. Although rare, it can result in bilateral blindness when used for close sequential surgery. If a commercial formulation is not available, surgeons must individually weigh the potential benefits and risks of using or not using an intracameral injection.


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    endophthalmitis prophylaxis; povidone-iodine; perioperative antibiotics; intracameral antibiotic prophylaxis

    © 2017 by Asia Pacific Academy of Ophthalmology