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Endophthalmitis: incidence and prevention

Eduardo S. Soriano and Mauro Nishi
Purpose of review To present current peer-reviewed articles related to the incidence and prevention of postoperative endophthalmitis. Recent findings Recent literature indicates that the incidence of postoperative endophthalmitis may be on the rise. Although the preoperative use of antibiotics as prophylaxis is still controversial, it is becoming more common. Summary The reports of endophthalmitis analyzed from peerreviewed ophthalmic journals suggest that the incidence of endophthalmitis has increased, ranging from 0.1 to 0.18% in different countries. This may be related to factors associated with the incision. Although some resistance has been detected, fourth-generation fluoroquinolones seem to be a proper antibiotic for endophthalmitis prophylaxis because of their spectrum, mode of action, and penetration. Keywords cataract, endophthalmitis, incidence, prevention
Curr Opin Ophthalmol 16:6570. 2005 Lippincott Williams & Wilkins. Cataract Institute, Federal University of Sa o Paulo, Brazil Correspondence to Eduardo S. Soriano, R. Tome de Souza, 35. Embu, SP - 06844-010, Brazil E-mail: higdon@amcham.com.br Current Opinion in Ophthalmology 2005, 16:6570 Abbreviation IOL intraocular lens

Introduction
Recently, endophthalmitis has returned to the center of the ophthalmologic debate on the basis of two facts: the apparent increase in its incidence and the introduction of new antibiotics that might improve its prevention [1]. Although rare, this surgical complication is associated with a poor prognosis, causing frustration to both patients and physicians, which frequently leads to legal implications. Preventive measures have both medical and economic importance, considering the high number of cataract surgeries performed annually in the world. Establishing practice patterns based on scientific evidence is essential; however, it is difficult to conduct conclusive studies of endophthalmitis because of its low prevalence. Prospective studies to evaluate preventive methods would need large reference samples to establish reliable epidemiologic results. Multicenter studies have problems in standardizing all the potential risk factors such as the presence of blepharitis or other ocular surface disorders, sterilization conditions, operative environment, length of surgery, size and location of incision, presence of suture, type of intraocular lens (IOL), and postoperative care. Most of the articles related to endophthalmitis are retrospective or laboratory studies, allowing only indirect conclusions. The objective of this article is to review the most recent peer-reviewed publications related to the incidence and prevention of postcataract surgery endophthalmitis, with a focus on practical information.

Incidence and risk factors

2005 Lippincott Williams & Wilkins. 1040-8738

Phacoemulsification with topical anesthesia and a clear corneal nonsutured temporal incision enabled a decrease in cost and length of surgery, more operating room efficiency, faster recovery, reduced need for patching the eye, and less astigmatism. With a small incision and a closed maintained anterior chamber associated with the wide use of antibiotics, less bacterial contamination is now expected in comparison with the extracapsular extraction era. In the past two decades, several studies have suggested that the incidence of endophthalmitis was approximately 1 case in 1000 procedures, but several recent largescale international studies have reported significantly higher rates of endophthalmitis: as many as 3 cases in 1000 procedures [1]. Several possible causes may contribute to the development of endophthalmitis, including incision type, surgical technique, IOL type, reuse of disposable material, and emerging bacterial resistance to existing antibiotic agents.
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The definition of endophthalmitis represents an important factor in the comparison of incidence studies. The inclusion of presumed or culture-proven cases, as well as the specification of the time between the cataract procedure and the diagnosis, will affect estimations of incidence. The incidence of presumed endophthalmitis in a 10-year retrospective survey in a single United Kingdom eye unit was 0.16%, with higher frequency in extracapsular extraction (0.31%) than in phacoemulsification (0.07%). The rate for folded lenses (1.21%) was higher than for injectable lenses (0.028%), suggesting that the use of injectors reduces the incidence of infection [2]. In a prospective study, with active surveillance of patients with clinical diagnoses of endophthalmitis in the United Kingdom for 12 months (between 1999 and 2000), Kamalarajah et al. [3] estimated the incidence of endophthalmitis at 0.14% after adjustment for underreporting data. The number of cataract extractions for the study period was approximately 230,000, and gram-positive organisms were identified in 93% of the isolates and gram-negative organisms in only 7%. In an Australian retrospective survey of 117,083 cataract procedures, the incidence of confirmed postoperative endophthalmitis was 0.18%, remaining relatively constant despite a threefold increase in cataract surgery over the 21 years studied. Besides the decrease of endophthalmitis after extracapsular extraction over the whole period (and not after phacoemulsification over the past 12 years), the incidence was similar for extracapsular extraction and phacoemulsification. However, a significantly higher risk was found in patients older than 80 years, those having surgery in private hospitals, those receiving same-day surgery, and those undergoing the procedure in winter. A prolonged stay, at least 2 days, could optimize perioperative prophylactic protocols, mainly in private hospitals. Cataract surgery with lacrimal or eyelid procedures increased the risk of endophthalmitis. No association was found between gender, comorbidity, or volume of cataract surgery performed at each hospital [4,5]. A 3-year survey between 1996 and 1998, conducted by use of a national registry in Norway, showed that the incidence of suspected postoperative endophthalmitis was 0.16% for a total of 71,190 cases over the 3-year period, when phacoemulsification was estimated to be used in more than 90% of the cases. Microbial growth occurred in 75% of the cases and was an important predictor of the visual outcome [6]. In a prospective study, the Swedish National Cataract Register identified a 0.1% rate of presumed endophthalmitis in 54,666 cataract operations. In this study, acrylic IOLs were seen to decrease the risk of endophthalmitis in comparison with hydrogel and polymethylmethacrylate lenses, although surgical complications could have occurred with a bias in the IOL selection [7].

In a retrospective case-control study of Asian patients performed in Singapore, silicone IOLs (compared with polymethylmethacrylate or acrylic IOL) and rupture of the posterior capsule were independently associated with acute endophthalmitis, although the authors pointed out that information and selection (nonrandom allocation of patients) biases could have accentuated some associations and attenuated others [8]. Table 1 summarizes the incidence of endophthalmitis in different countries.

Cataract surgery and incision type: do sutureless corneal incisions increase the risk for endophthalmitis?
Wound abnormality has been identified as a risk factor for endophthalmitis, but attention has recently been brought to the role of the incision location in the genesis of endophthalmitis. A case-control study by Cooper et al. [9] suggests a possible relation between clear corneal wounds and an increased risk of endophthalmitis. In this retrospective review, surgical technique was compared between 38 culture-proven cases of endophthalmitis and 371 randomly selected uncomplicated cataract surgery cases. The authors observed that clear cornea wounds were associated with a threefold greater risk of endophthalmitis than was scleral tunnel incision. Of all the patients in whom the integrity of the cataract wound was checked, about half received diagnoses of wound abnormality. In addition, the presence or absence of a suture was not significant in increasing the risk of endophthalmitis. However, case patients and control patients were not matched, and statistical analysis determined that if the proportion of clear corneal incisions in the control group was increased to 40% (instead of 20% in the control group in this study), the association of type of incision and endophthalmitis might not have been significant. In Japan, a multicenter study evaluated 11,595 eyes prospectively to assess the association between incision type in phacoemulsification and endophthalmitis. Fifteen eyes (0.13%) had clinically diagnosed endophthalmitis. The relative risk of endophthalmitis in eyes where an acrylic IOL (MA60BM, Alcon) or a silicone IOL (SI-40NB, Allergan) was implanted via a superior sclerocorneal
Table 1. Incidence of endophthalmitis in different countries during the phacoemulsification era Study Mayer et al. [2 ] Kamalarajah et al. [3] Semmens et al. [4] Sandvig and Dannevig [6] Montan et al. [7] Nagaki et al. [10]

Place UK UK Australia Norway Sweden Japan

Period 19912001 19992000 19801998 19961998 1998 19982001

Incidence (%) 0.16 0.14 0.18 0.16 0.10 0.13

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incision was 4.8-fold lower than in eyes with an acrylic IOL (MA60BM, Alcon) implanted through a temporal corneal incision. The wounds remained sutureless, and only the sclerocorneal incisions were covered with the conjunctival flap. There was no significant difference in the incidence of endophthalmitis between patients with or without diabetes mellitus, nasolacrimal duct obstruction, or eyelid disorders [10]. In a laboratory investigation, McDonnell et al. [11] evaluated the stability of the sutureless clear corneal cataract incision, demonstrating that transient reduction of intraocular pressure might result in poor wound apposition. The incision edges tended to gape starting at the internal aspect of the wound, with a potential for fluid flow across the cornea and into the anterior chamber. Histologic examination showed dye particles applied to the ocular surface penetrate in all incisions for up to three fourths of the length of the wound. Using the same method (OCT) in another study, the authors compared different incision angles (angle of knife relative to ocular surface) in clear corneal, limbal, and scleral incisions. Larger (more perpendicular) wound angles were associated with greater wound edge gaping as intraocular pressure was increased. By contrast, smaller wound angles were associated with tighter apposition of incision edges at high intraocular pressures. In general, for smaller (standard) angles, limbal incisions resulted in better wound apposition/sealing relative to clear corneal incisions [12]. Clear corneal sutureless temporal incisions may be more prone to endophthalmitis because the wound is not protected by the eyelid or conjunctiva and is more exposed to bacteria in tear film and eyelid margins. It is possible that there is a learning curve to the construction of a watertight clear corneal incision, or a stable, self-sealing incision may be technically more difficult in the cornea than in the sclera. At least, a red flag has been raised regarding clear corneal sutureless temporal incisions, and further studies are necessary to clarify whether they really increase the risk of endophthalmitis. So far, it is advised that more attention be paid to the architecture of the incisions, and any questionable incision should be sutured.

Several studies have suggested that the patients external tissues represent the major sources of infection, and evidence has been presented that surface flora routinely gain entry to the anterior chamber during cataract surgery [13,14]. Considering the hypothesis that the most common sources of postoperative endophthalmitis are the patients external flora, sterilization has become a priority in preventive measures. Until now, the only significant measure to prevent eye infection has been the use of topical povidone-iodine in the conjunctiva before the surgery. A 5% concentration of povidone-iodine is more effective than 1% povidone-iodine in decreasing the conjunctival bacterial flora, according to the study conducted by Ferguson et al. [15] that compared conjunctival cultures taken before and after irrigation with different concentrations of povidone-iodine. The 5% povidone-iodine group showed a decrease in median colony-forming units of 96.7% compared with 40% in the 1% povidone-iodine group. Other prophylactic measures have also been studied, like preoperative topical antibiotics, lash trimming, saline irrigation; intracameral antibiotics or heparin, and postoperative subconjunctival antibiotics. However, according to an extensive review published in 2002 by Ciulla et al. [16], none of these methods demonstrated strong evidence of reducing the risk of endophthalmitis.
Antibiotics

The use of antibiotics to prevent endophthalmitis has been promoted, but consistent antibiotic use is still not routine practice. To the best of our knowledge, there are no prospective randomized controlled studies to support this assumption. The topical administration of antibiotic agents preoperatively is thought to be beneficial because of the potential effect in diminishing superficial flora. Considering that ocular flora play a major role in the etiology of endophthalmitis, using anti-infective agents like povidone-iodine to lower surface bacterial contamination before surgery would prevent infection. Also, some drugs, such as quinolones, are capable of penetrating the cornea to achieve significant intraocular concentrations sufficient to suppress the growth of infective pathogens that might contaminate the eye during or after a surgical procedure. A broad-spectrum, highly permeable, inexpensive antibiotic with low toxicity is ideal.
Quinolones

Prevention
Strategies for preventing postoperative endophthalmitis begin with the adoption of universal prophylactic measures like preparation of the operative site with povidoneiodine, preoperative hand scrubbing by the surgical team, maintenance of a sterile operative field and material, and strict hospital polices regarding infection deterrence. The underlying principle behind prophylaxis is to decrease the chance that any pathogen will enter the eye and eradicate the pathogens that gained access to the eye during or after surgery.

Quinolones, because of their broad-spectrum activity and favorable pharmacokinetic and safety profiles, have become a popular topical agent. Unfortunately, resistance to this class of antibacterials, particularly among grampositive organisms, is emerging. Resistance has been attributed in part to inappropriate sublethal dosing and slow tapering, which have induced mutagenesis in once susceptible pathogens. Because of increasing resistance, newer agents must be considered. The fourth-generation quinolones, such as gatifloxacin and moxifloxacin, confer a

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dual-binding mechanism of action in gram-positive organisms, inhibiting both DNA gyrase and topoisomerase intravenously. This is believed to expand their spectrum of activity to inhibit bacterial strains that are otherwise resistant to older fluoroquinolones, and they therefore hold great promise for treating and preventing endophthalmitis [17]. Knowledge of the most common organisms associated with endophthalmitis and their resistance profile is important in the decision to use antibiotic prophylaxis. In a retrospective study, the records of all patients with culture-positive endophthalmitis caused by Streptococcus pneumoniae treated at the Bascom Palmer Eye Institute between 1989 and 2003 were reviewed. In a total of 27 cases, only 5 were secondary to a cataract procedure, and the rest were related to other causes. Some resistance to fluoroquinolones was detected: 8% to ofloxacin, 14% to levofloxacin, and 7% to gatifloxacin. All isolates were sensitive to ciprofloxacin and moxifloxacin, in addition to vancomycin, clindamycin, and cefazolin. Only 8% were sensitive to gentamicin [18]. In another study from the same center, in which all cases of endophthalmitis (cataract surgery, posttraumatic, endogenous, and miscellaneous) between 1996 and 2001 were reviewed, the sensitivities were as follows: for gram-positive organisms, vancomycin 100%, gentamicin 78.4%, ciprofloxacin, 68.3%, ceftazidime 63.6%, and cefazolin 66.8%. For gram-negative organisms, the sensitivities were as follows: ciprofloxacin 94.2%, amikacin 80.9%, ceftazidime 80.0%, and gentamicin 75.0% [19]. A recent report compared the in vitro susceptibilities and potencies of ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, and gatifloxacin in retrospective bacteria isolated from cases of endophthalmitis. In general, fourth-generation fluoroquinolones covered bacterial resistance to the secondand third-generation fluoroquinolones, and moxifloxacin was the most potent fluoroquinolone for gram-positive bacteria, whereas all the antibiotics studied demonstrated equivalent potencies to gram-negative bacteria [20].
Antibiotic regimen

Two prospective randomized studies compared the administration of topical ofloxacin 1 hour before surgery with administration four times daily for 3 days before surgery; the results suggested that the longer regimen was better for decreasing surface contamination. In the first study, 42% of eyes in the 1-hour group had positive conjunctival culture immediately before surgery, compared with 19% of eyes in the 3-day group. Immediately after surgery, 34% and 14% of eyes had positive cultures in the 1-hour and 3-day groups, respectively. Quantitatively, fewer bacteria were isolated from eyes in the 3-day group compared with those in the 1-hour group [22]. The second study evaluated the rate of contamination of microsurgical knives during cataract surgery, comparing the 3-day with the 1-hour preoperative application of topical ofloxacin. The results showed that 26% of knives in the 1-hour group were positive for bacterial growth compared with only 5% in the 3-day group [23].
Intraoperative use of antibiotics

In addition to susceptibility, other issues still need to be discussed regarding the use of antibiotics in prophylaxis, like best timing, frequency, and routes, including oral, subconjunctival, and intracameral. An experimental in vivo study investigated three different topical regimens of moxifloxacin to prevent bacterial endophthalmitis when Staphylococcus aureus was injected into rabbit eyes. Saline was used as a control. The use of moxifloxacin before and after bacterial injection showed lower clinical scores than when the antibiotic was used either before or after the injection. Cultures from the anterior and posterior chambers were negative for S. aureus in all three moxifloxacin treatment regimens, suggesting that it reached sufficient intraocular levels to prevent endophthalmitis in an animal model [21].

In addition to preoperative use, antibiotics are also used intraoperatively (intracamerally or subconjunctivally) and after surgery. The effect of antibiotics in the irrigation solution may be ephemeral because the half-life of any antibiotic is achieved approximately 2 hours after surgery. Libre et al. [24] designed an experiment that simulated the halflife of vancomycin in the anterior chamber. Incubation with vancomycin for 2 hours caused a slight decline in the growth of methicillin-resistant S. aureus but did not eliminate it. Methicillin-resistant S. aureus growth in the control group was higher, suggesting that the intracameral injection of antibiotic agents could be used in prophylaxis. A randomized controlled prospective clinical trial showed that the intraoperative infusion of vancomycin and gentamicin decreased aqueous humor contamination during phacoemulsification. Aqueous samples taken at the end of surgery were contaminated in 21.1% of eyes in the group with balanced salt solution only and in 6.8% eyes in the group with balanced salt solution plus antibiotics. Capsular rupture was associated with a higher rate of contamination in both groups. Endophthalmitis developed in 2 eyes in the group with balanced salt solution only, and these patients had posterior capsular rupture during the surgery and had cultures that were positive for Staphylococcus epidermidis [25]. Resistance is always a concern when antibiotics are used in prophylaxis, mainly with vancomycin, which is the first choice for the treatment of endophthalmitis. Seppala et al. [26] evaluated the minimal inhibitory concentrations of different antimicrobials for Streptococci viridans isolated from throat, nasopharyngeal, and conjunctival swabs of 23 patients, on four sampling occasions: before cataract surgery and 1 day, 1 month, and 3 months after surgery. For all patients, vancomycin was used in the irrigating solution and topical chloramphenicol as prophylaxis. Resistance to vancomycin or chloramphenicol was not observed. The routine use of prophylactic vancomycin in cataract

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patients should be cautiously evaluated. Although resistance has not been shown, limited evidence supports the prevention of endophthalmitis, with a risk of toxicity. Subconjunctival antibiotic injection is probably the oldest prophylactic regimen to use antibiotics. Many reports showed a beneficial trend, but the strength of the data supporting this clinical practice have not been convincing, and the administration of subconjunctival antibiotics at the close of surgery has been associated with risk [27]. Because topical phacoemulsification surgery permits fast recovery, eyedrops have replaced antibiotic injections. Generally, the topical antibiotics are used for 1 week when the wound epithelializes. The preferred practice pattern guideline sponsored by the American Academy of Ophthalmology has stated that it is up to the ophthalmologist to decide whether to use topical, intracameral, or subconjunctival antibiotics perioperatively because of inconclusive evidence about the risks and benefits of antibiotics [28]. By contrast, the potentially severe consequences of endophthalmitis support the use of precautions to minimize the risk of infection, especially when known risk factors for endophthalmitis are present, including rupture of the capsule, long duration of surgery, diabetes, significant periocular skin disease, occlusion of the lacrimal system, immunodeficiency, or anterior vitrectomy [29].

In this retrospective study of cataract surgeries in a single UK eye department between 1991 and 2001, the authors investigated the potential link between method of IOL implantation and risk of endophthalmitis. Kamalarajah S, Silvestri G, Sharma N, et al. Surveillance of endophthalmitis following cataract surgery in the UK. Eye 2004; 18:580587. This prospective study provides data on the incidence, presentation, management, microbiology, and outcome of presumed endophthalmitis in the UK. The cases were identified through the British Ophthalmological Surveillance Unit reporting card system. 3

Semmens JB, Li J, Morlet N, Ng J: Team EPSWA. Trends in cataract surgery and postoperative endophthalmitis in Western Australia (1980-1998): the Endophthalmitis Population Study of Western Australia. Clin Experiment Ophthalmol 2003; 31:213219. This article provides an estimation of the incidence rates of postoperative endophthalmitis based on record linkage of health data supplemented by case validation in Western Australia for the period 1980 to 1998. 4

Li J, Morlet N, Ng JQ, et al. Team EPSWA. Significant nonsurgical risk factors for endophthalmitis after cataract surgery: EPSWA fourth report. Invest Ophthalmol Vis Sci 2004; 45:13211328. The study identifies the sociodemographic, environmental, and clinical risk factors for endophthalmitis, using population-based administrative data from Western Australia. 5

Sandvig KU, Dannevig L: Postoperative endophthalmitis: establishment and results of a national registry. J Cataract Refract Surg 2003; 29:12731280. This retrospective/prospective study describes the results of a national registry in Norway from 1996 to 1998. Data on presentation, diagnosis, treatment, and outcomes are presented. 6

Montan P, Lundstrom M, Stenevi U, et al. Endophthalmitis following cataract surgery in Sweden: The 2002 national prospective survey. Acta Ophthalmol Scand 2002; 80:258261.

Wong TY, Chee SP: Risk factors of acute endophthalmitis after cataract extraction: a case-control study in Asian eyes. Br J Ophthalmol 2004; 88: 2931. This retrospective case-control study describes the risk factors for acute endophthalmitis after cataract extraction at an ophthalmic hospital in Singapore. 8

Cooper BA, Holekamp NM, Bohigian G, et al. Case-control study of endophthalmitis after cataract surgery comparing scleral tunnel and clear corneal wounds. Am J Ophthalmol 2003; 136:300305. This retrospective, comparative, case-controlled study analyzes the association between clear corneal incision with or without placement of a suture and postoperative endophthalmitis. 9

Conclusion
The reports of endophthalmitis analyzed from peerreviewed ophthalmic journals suggest that the incidence of endophthalmitis has increased, ranging from 0.1 to 0.18% in different countries. This may be related to factors associated with the incision. Although some resistance has been detected, fourth-generation fluoroquinolones seem to be an appropriate antibiotic for endophthalmitis prophylaxis to complement the use of povidone-iodine because of their spectrum, mode of action, and penetration. Nonetheless, despite growing scientific data, there remain many questions about the incidence, risk factors, and prevention of endophthalmitis.

10 Nagaki Y, Hayasaka S, Kadoi C, et al. Bacterial endophthalmitis after small incision cataract surgery: effect of incision placement and intraocular lens type. J Cataract Refract Surg 2003; 29:2026. This study used a case-control design to evaluate the potential risk for clear corneal wounds and the development of endophthalmitis. 11 McDonnell PJ, Taban M, Sarayb M, et al. Dynamic morphology of clear corneal cataract incisions. Ophthalmology 2003; 110:23422348. This paper was based on a laboratory study to determine whether clear corneal cataract wounds might permit the flow of surface fluid into the wound and across the cornea, using optical coherence tomography and India ink applied to the corneal surface.

12 Taban M, Rao B, Reznik J, et al. Dynamic morphology of sutureless cataract wounds: effect of incision angle and location. Surv Ophthalmol 2004; 49(Suppl 2):S62S72. This laboratory study evaluated the effect of intraocular pressure, location, and angle of cataract incisions on wound apposition and sealing in postmortem globes. 13 Speaker MG, Milch FA, Shah MK, et al. Role of external bacterial flora in the pathogenesis of acute postoperative endophthalmitis. Ophthalmology 1991; 98:639649. 14 Dickey JB, Thompson KD, Jay WM: Anterior chamber aspirate cultures after uncomplicated cataract surgery. Am J Ophthalmol 1991; 112:278282.

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 Olson RJ: Reducing the risk of postoperative endophthalmitis. Surv Ophthal mol 2004; 49 (Suppl 2):S55S61. This article reviews the studies of incidence, preventive measures, and causes of postoperative endophthalmitis, based on Medline searches from 1966 to 2003. 1 2

15 Ferguson AW, Scott JA, McGavigan J, et al. Comparison of 5% povidoneiodine solution against 1% povidone-iodine solution in preoperative cataract surgery antisepsis: a prospective randomized double-blind study. Br J Ophthalmol 2003; 87:163167. This prospective randomized double blind comparative study compared the effect of 5% povidone-iodine against 1% povidone-iodine on the bacterial flora of the human conjunctiva in vitro. 16 Ciulla TA, Starr MB, Masket S: Bacterial endophthalmitis prophylaxis for cataract surgery: an evidence-based update. Ophthalmology 2002; 109:1324.

Mayer E, Cadman D, Ewings P, et al. A 10-year retrospective survey of cataract surgery and endophthalmitis in a single eye unit: injectable lenses lower the incidence of endophthalmitis. Br J Ophthalmol 2003; 87:867869.

17 Hwang DG: Fluoroquinolone resistance in ophthalmology and the potential role for newer ophthalmic fluoroquinolones. Surv Ophthalmol 2004; 49(Suppl 2):S79S83. This review article provides an understanding of the potential role of these newer fluoroquinolones in addressing the problem of increasing fluoroquinolone resistance among bacterial ocular isolates.

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18 Miller JJ, Scott IU, Flynn HW Jr, et al. Endophthalmitis caused by streptococcus pneumoniae. Am J Ophthalmol 2004; 138:231236. This retrospective, observational case series investigated clinical settings, management strategies, antibiotic sensitivities, and visual acuity outcomes in all patients with endophthalmitis caused by Streptococcus pneumoniae treated at the Bascom Palmer Eye Institute between 1989 and 2003. 19 Benz MS, Scott IU, Flynn HW Jr, et al. Endophthalmitis isolates and antibiotic sensitivities: a 6-year review of culture-proven cases. Am J Ophthalmol 2004; 137:3842. The authors report the bacterial pathogens isolated from all patients with endophthalmitis at Bascom Palmer Eye Institute between 1996 and 2001. 20 Mather R, Karenchak LM, Romanowski EG, et al. Fourth generation fluoroquinolones: new weapons in the arsenal of ophthalmic antibiotics. Am J Ophthalmol 2002; 133:463466.

This prospective randomized trial was conducted to determine the rate of contamination of microsurgical knives during cataract surgery, comparing a 3-day with a 1-hour preoperative application of topical ofloxacin. 24 Libre PE, Della-Latta P, Chin N: Intracameral antibiotic agents for endophthalmitis prophylaxis: a pharmacokinetic model. J Cataract Refract Surg 2003; 29:17911794. This research laboratory study assessed in vitro whether intracameral antibiotic agents are plausibly effective prophylaxis against S. aureus endophthalmitis.

25 Sobaci G, Tuncer K, Tas A, et al. The effect of intraoperative antibiotics in irrigating solutions on aqueous humor contamination and endophthalmitis after phacoemulsification surgery. Eur J Ophthalmol 2003; 13:773778. This randomized prospective clinical trial evaluated the efficacy of intraoperative antibiotics in irrigating solutions on aqueous humor contamination during phacoemulsification surgery.

21 Kowalski RP, Romanowski EG, Mah FS, et al. Topical prophylaxis with moxifloxacin prevents endophthalmitis in a rabbit model. Am J Ophthalmol 2004; 138:3337. This in vivo laboratory investigation evaluated the prophylaxis potential of topical moxifloxacin to prevent endophthalmitis after the injection of S. aureus into the anterior chamber in a rabbit model. 22 Ta CN, Egbert PR, Singh K: Prospective randomized comparison of 3-day versus 1-hour preoperative ofloxacin prophylaxis for cataract surgery. Ophthalmology 2002; 109:20362041.

26 Seppala H, Al-Juhaish M, Jarvinen H, et al. Effect of prophylactic antibiotics on antimicrobial resistance of viridans streptococci in the normal flora of cataract surgery patients. J Cataract Refract Surg 2004; 30:307315. This study evaluated the in vitro activity of 15 antibiotics for viridans-group streptococci isolated in the normal flora (throat, nasopharynx, and conjunctiva) of patients undergoing cataract surgery, prophylactically treated with vancomycin in the irrigating solution and topical chloramphenicol.

27 Schmitz S, Dick HB, Krummenauer F, et al. Endophthalmitis in cataract surgery: results of a German survey. Ophthalmology 1999; 106:18691877. 28 American Academy of Ophthalmology Anterior Segment Panel. Preferred Practice Pattern Cataract in the adult eye. 2001. 29 Liesegang TJ: Use of antimicrobials to prevent postoperative infection in patients with cataracts. Curr Opin Ophthalmol 2001; 12:6874.

23 De Kaspar HM, Chang RT, Shriver EM, et al. Three-day application of topical ofloxacin reduces the contamination rate of microsurgical knives in cataract surgery: a prospective randomized study. Ophthalmology 2004; 111:1352 1355.