Endophthalmitis following cataract surgery is a serious though rare complication. Despite aggressive treatment, only about half of patients with endophthalmitis achieve 20/40 or better vision and many are left without light perception [1,2]. The organisms responsible are skin and conjunctival flora, usually bacterial and rarely fungal, which gain access to the anterior chamber or vitreous cavity of the eye at the time of surgery or during the postoperative period . The Endophthalmitis Vitrectomy Study showed that 70% of infections are caused by coagulase-negative Staphylococcus, followed by 9.9% Staphylococcus aureus, 2.2% Enterococcus, and another 5.9% Gram-negative bacteria [1,4]. Fungi are estimated to cause 3% of cases .
Overall, the incidence of postoperative endophthalmitis is very low. A recent systematic review found a rate of 0.265% from 2000 to 2003, compared with 0.087% in the previous decade . This low incidence has made it difficult for prospective studies to be adequately powered to detect significant changes in outcome in terms of number of cases of endophthalmitis. To date, only two agents have been demonstrated to be effective in reducing the rate of postoperative endophthalmitis in prospective studies: preoperative topical povidone–iodine and intraoperative intracameral cefuroxime [3,7▪▪].
Although the exact regimens of prophylactic antiseptic and antibiotics vary, both are always administered in the perioperative period. Several extensive reviews have been written regarding this topic [8–11]. Here, we seek to review the most up-to-date evidence and provide our opinion with regard to methods of endophthalmitis prophylaxis for cataract surgery.
Risk factors for the development of postoperative endophthalmitis logically include conditions which increase the number of ocular bacteria. Retrospective studies suggest that blepharitis and ectropion are associated with an increased risk of developing endophthalmitis [8–11]. Other studies have shown that patients with chemosis, hyperemia, and discharge have an increased number of antibiotic-resistant bacteria [12,13]. Intraoperative complications, specifically break in the posterior capsule or vitreous loss, also greatly increase the risk of endophthalmitis . A recent, retrospective, chart review from Spain of 1325 known diabetics showed a higher quantity of conjunctival bacteria, including staphylococcus, streptococcus, enterococcus, and klebsiella than in patients without diabetes . This is consistent with the earlier studies showing increased risk of endophthalmitis in diabetics [16,17]. Though scrubbing at home by the patient in the days prior to surgery has been suggested, there have been no studies regarding its effectiveness. A study of 617 suspected cases of endophthalmitis in Canada found a 10-fold increase in incidence in those with intraoperative complication of capsular rupture [18▪]. It has also been reported that topical anesthesia has been retrospectively associated with increased risk of endophthalmitis (odds ratio 11.8, 95% confidence interval 2.4–58.7, n = 27) . Prospective data with a larger sample size is needed, however, before suggestions can be made with regard to method of anesthesia.
METHOD OF WOUND INCISION
Some investigators have attributed an apparent increase in the incidence of postcataract endophthalmitis over the past decade to more widespread use of the clear corneal incision . Retrospective data appear to agree with such an assertion . However, other studies have found no significant difference [21–23,24▪▪]. More recently, a case series of 815 patients who underwent cataract surgery in a 5-year period by a single surgeon showed a rate of postoperative endophthalmitis to be 1.3% in sutureless surgeries vs. 0% in sutured wounds . The relationship between the clear corneal incision and postcataract endophthalmitis remains controversial. Although data have been collected on the use of ocular bandages as well as more novel techniques such as laser welding and bubble injection, they have not been evaluated with regard to their effects on endophthalmitis risk or bacteria concentration in the anterior chamber [26–29]. There is inadequate evidence at this time to advise specific types of wound closure. A study has suggested that surface tears can influx into the wound following cataract surgery, especially in the presence of postoperative hypotony or eye rubbing . Therefore, it is essential to construct a watertight wound and to place a suture if there is any uncertainty.
Povidone–iodine is the only topical prophylactic agent to have shown to reduce endophthalmitis in a prospective manner . Numerous other studies have demonstrated the reduction of conjunctival bacterial concentration with various regimens of povidone–iodine [31–34]. Although povidone–iodine is universally used in every case of ocular surgery unless the patient has an allergy, there is no consensus with regard to the povidone–iodine concentration, duration, or timing of application. The most common concentration of 5% is generally recommended [33–37]. We conducted a randomized prospective study in 39 patients, showing no difference in conjunctival cultures obtained at the beginning and conclusion of surgery when using 10% povidone–iodine vs. 5%, arguing against the need for higher concentrations . Although there is demonstration of the toxicity of povidone–iodine in animal models and in vitro, the clinical significance has not been clearly evaluated [39–43]. A recent study examining the addition of 0.25% povidone–iodine to irrigation solution during cataract surgery found no change in surface bacteria but a significant decrease in positive bacterial cultures of anterior chamber aspirates (5 vs. 0%, n = 404) . However, the potential for intraocular povidone–iodine toxicity must weigh against any possible benefit. Overall, the published evidence strongly supports the application of povidone–iodine to the periorbital area and ocular surface at the time of cataract surgery.
Topical antibiotics are used in conjunction with povidone–iodine to achieve superior antisepsis and theoretically reduce the incidence of endophthalmitis [45,46]. A majority of surgeons use antibiotics preoperatively, and nearly all prescribe them postoperatively, typically for approximately 1 – 2 weeks . No prospective trial has yet demonstrated the efficacy of topical antibiotic in reducing the risk of postoperative endophthalmitis. As with povidone–iodine studies, the quantity of bacterial cultured from the conjunctiva and anterior chamber serves as a measure of efficacy, although there is no direct evidence proving that reducing conjunctival bacterial flora decreases the risk of endophthalmitis. Fluoroquinolones are most commonly prescribed by ophthalmologists because of their broad-spectrum of activity against both Gram-positive and Gram-negative bacteria. The particular antibiotics used have changed with time. Prior to the introduction of levofloxacin, ciprofloxacin and ofloxacin were commonly prescribed. Our previous work has shown that topical ofloxacin administered 3 days prior to surgery was more effective in reducing conjunctival bacteria than applied 1 h before surgery [47,48].
In the last decade, due in part to the reports of resistance of bacteria to ciprofloxacin and ofloxacin, there has been increased use of the broad-spectrum fluoroquinolones with improved efficacy against Gram-positive bacteria. These include levofloxacin, moxifloxacin, and gatifloxacin. More than 80% of surveyed American Society of Cataract and Refractive Surgery (ASCRS) members used either moxifloxacin or gatifloxacin as their choice of antibiotic in 2007 . One retrospective study suggested a significantly lower rate of endophthalmitis following a change to the newer broad-spectrum fluoroquinolones . This study also found a significantly higher rate of endophthalmitis in patients who received moxifloxacin prophylaxis compared with patients who were prescribed gatifloxacin (0.1 vs. 0.015%, P = 0.04), though this remains controversial because of the methods of data analysis . A recent publication of cultures from cases of endophthalmitis in Brazil showed the susceptibility of coagulase-negative Staphylococcus of 79.5 and 89.5% to gatifloxacin and moxifloxacin, respectively . Moxifloxacin has also shown to have better penetration to the aqueous humor than gatifloxacin in several studies [51–54]. Gatifloxacin was shown to have no additional benefit when used together with povidone–iodine in patients undergoing intravitreal injection when applied just prior to the procedure. However, a similar finding was also observed with moxifloxacin [55▪,56▪]. The optimal dose regimen of topical antibiotic is unknown. A study of 148 patients did not find a difference in bacterial conjunctival cultures with moxifloxacin when given 1 day prior to surgery compared to the day of surgery . Our own study showed no difference between using moxifloxacin 1 day prior to surgery compared with 3 days prior to surgery . However, a 1-day application of gatifloxacin was shown to be more effective in reducing conjunctival bacterial flora than if the antibiotic was administered just 1 h before surgery . Although there is no evidence proving a correlation between the presence of conjunctival bacterial flora at the time of surgery and the risk of endophthalmitis, it is prudent to prescribe an antibiotic 1–3 days prior to surgery. This should be weighed against the cost, side-effects, and risk of overuse of antibiotics.
Besifloxacin is the newest fluoroquinolone developed for ophthalmic use. It is approved for the treatment of conjunctivitis and has been shown to have good ocular penetration and to be the most potent fluoroquinolone against a variety of Gram-positive and Gram-negative organisms [60,61]. Its efficacy and side-effect profile has been compared with moxifloxacin in treating conjunctivitis and was found to be similar in both aspects . Other studies, however, have suggested it has poor ocular penetration [63,64]. It is unclear, however, the clinical significance of ocular penetration with regard to the prevention of endophthalmitis. Besifloxacin was found to be effective in treating endophthalmitis in a rabbit model . One possible advantage of besifloxacin is that the proprietary vehicle, DuraSite, theoretically allows the drug to adhere to the ocular surface for a longer period of time. Also, as besifloxacin is not available as a systemic medication, it has the potential to have a lower resistance profile. Although a few studies have found poor ocular penetration, besifloxacin has been shown to be effective in a rabbit model and is a promising new antibiotic.
SUBCONJUNCTIVAL AND INTRACAMERAL ANTIBIOTICS
Only 13 and 15% of surgeons who responded to the 2007 ASCRS survey use subconjunctival and intracameral antibiotic, respectively . In Europe, however, the British Ophthalmologic Surveillance Unit recommended the use of subconjunctival cefuroxime given its ease of delivery and few potential side-effects .
The only prospective randomized clinical trial ever conducted evaluating the role of antibiotics in reducing the risk of postoperative endophthalmitis was the European Society of Cataract and Refractive Surgeon (ESCRS) Study. This study group conducted a trial with 16 603 patients and demonstrated an endophthalmitis incidence of 0.247% in those treated with topical levofloxacin alone compared with a rate of 0.049% in those treated with both topical levofloxacin and intracameral cefuroxime. Lack of intracameral cefuroxime was associated with a significant increase in the incidence of endophthalmitis (0.062 vs. 0.296%, P < 0.0005), whereas lack of topical levofloxacin was not (0.148 vs. 0.210%, P = 0.353) [7▪▪] (Fig. 1). All patients also received povidone–iodine. As a result of this study, the ESCRS recommended the administration of intracameral cefuroxime at the conclusion of surgery . Intracameral cefuroxime is now a common practice in Europe, with 61% of surveyed ophthalmologic units in the United Kingdom National Health Services using intracameral cefuroxime in 2010 . Further studies have shown that intracameral cefuroxime is also cost-effective [69,70]. Despite the evidence for the administration of intracameral cefuroxime, its use has not become widespread in the USA. It has been speculated that the main reasons for not adopting this regimen is because of a lack of commercially available ophthalmic formulation. As the medication has to be compounded by the pharmacy, there is a concern for potential errors which could cause toxicity. Given the different practice patterns in Europe and the USA, we should expect to see a lower incidence of postcataract endophthalmitis in Europe if intracameral cefuroxime is superior to the current United States regimen. In contrast, the incidence of postoperative endophthalmitis is as of yet quite similar between the two continents [24▪▪,49]. As long as the incidence of postoperative endophthalmitis in the USA remains low and comparable to Europe, and there continues to be a lack of commercially available single-dose intraocular antibiotic in the USA, we can expect that the adoption of intracameral antibiotics to be slow in the USA.
Studies have examined the penetration of fluoroquinolones into the anterior chamber and found encouraging results [71–73]. There are, however, no studies evaluating the effect of these oral antibiotics on the quantity of bacteria in human eyes. There is insufficient evidence to recommend the routine use of systemic antibiotics given the potential for resistance and systemic side-effects. However, there may be a role for systemic antibiotics in complicated cases of cataract surgery, but it is unlikely that a study could be designed to support such a recommendation .
As with any widespread use of antibiotics, microbial resistance is an increasing concern for ophthalmologists. A study examined coagulase-negative staphylococcal isolates from cases of endophthalmitis and found that sensitivity to gatifloxacin and moxifloxacin had declined from 96.6 to 65.4% over the past decade . Recently, investigators examining 32 cases of S. aureus endophthalmitis found that 41% were caused by methicillin-resistant S. aureus (MRSA) and less than half of these were sensitive to broad-spectrum fluoroquinolones . Yet another study examining 97 cases of postcataract endophthalmitis found 38% of bacterial isolates to be resistant to fluoroquinolones, although they did not distinguish between specific fluoroquinolones . In cases of ocular infections in general, a nationwide registry found that only 15.2% of MRSA isolates were susceptible to each of fluoroquinolones [77▪▪] (Table 1). Resistance will become an increasing concern and in the longer term may force a change in our antibiotic choices. It may be that eventually all fluoroquinolones will fall out of favor as we search for new ocular antibiotics that are effective against MRSA. Lastly, it is also of concern whether preoperative antibiotics select for antibiotic resistant bacteria. A study showed that a 3-day course of moxifloxacin was less likely to select for resistant bacteria than a 1-day course .
It is our recommendation that patients undergoing cataract surgery be evaluated and be treated for potential risk factors that can increase the chance of developing postoperative endophthalmitis. At the time of surgery, the area surrounding the eye as well as the ocular surface should be cleaned thoroughly with at least 5% povidone–iodine. Patient should be meticulously draped in a sterile manner. The wound construction should form a water-tight incision at the conclusion of the surgery and to ensure this a suture or sutures should be placed if necessary. The application of topical antibiotics is reasonable, although there is a paucity of data supporting their use. Intracameral cefuroxime has been shown to reduce the risk of endophthalmitis, but its adoption in the USA has been slow because of the lack of a commercially available unit dose for intraocular injection.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
- ▪ of special interest
- ▪▪ of outstanding interest
Additional references related to this topic can also be found in the Current World Literature section in this issue (pp. 74–75).
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