Christopher J. Rudnisky, MD, MPH, Darwin Wan, MD, Ezekiel Weis, MD, MPH Objective: To determine the 8-year incidence of endophthalmitis after cataract surgery and to determine which surgical practices were associated with higher rates of endophthalmitis. Design: Case-control study. Participants: A total of 75 318 eyes undergoing cataract extractions, performed by 26 different surgeons at 4 public hospitals and 5 nonhospital surgical facilities. Methods: Cases of endophthalmitis were acquired using a detailed, prospectively designed demographic database. Controls were tabulated using volume data available from the provincial health care system. Main Outcome Measures: The primary outcome was the development of endophthalmitis. Results: A total of 23 cases (13 with culture-positive results) of postoperative endophthalmitis occurred, yielding an overall 8-year incidence of 0.03%. The incidence of endophthalmitis varied between surgeons from 0% to 0.20%. Two surgeons had higher rates than the rest of the group: 1 high-volume surgeon (1059.4231.9 mean cases per year) with an incidence of 0.08% (n 7; P 0.004) and 1 low-volume surgeon (123.544.8 mean cases per year) with an incidence of 0.20% (n 2; P 0.002). On univariate analysis, the rate of endophthalmitis was not inuenced by the use of intracameral (0.898) or subconjunctival antibiotics (0.331), whereas the use of moxioxacin was associated with a lower rate of endophthalmitis (P 0.029). Surgery at 1 private facility (P 0.046) and the use of timolol at the end of the procedure (P 0.007) were associated with a higher rate of endophthalmitis. Multivariate analysis demonstrated that the odds of endophthalmitis was lower if a second-generation (P 0.02) or fourth-generation (P 0.008) uoroquinolone antibiotic was used after surgery. In contrast, the odds of endophthalmitis occurring was higher if timolol (P 0.0002) was used at the end of the procedure or if the surgery was performed at one of the private facilities (P 0.009). Conclusions: The rate of endophthalmitis was lower if a uoroquinolone was used after surgery. In contrast, endophthalmitis was more likely to occur if timolol was used at the end of the procedure or if surgery was performed at one of the private facilities. Ophthalmology 2014;121:835-841 2014 by the American Academy of Ophthalmology. Supplemental material is available at www.aaojournal.org Endophthalmitis is a visually devastating complication of cataract surgery. Its incidence ranges from0.028%to 0.345% 1,2 and has varied over time because of changes in surgical tech- nique, 3 such as the widespread adoption of clear corneal incisions. However, apart from povidoneeiodine antisepsis, 4 there is no clear consensus regarding prophylaxis. A large, prospective, randomized, multicenter study initiated by the European Society of Cataract & Refractive Surgeons 1 found that intracameral cefuroxime reduces the rate of endophthalmitis; although this was the rst prophylactic regimen shown to be effective, it has not changed practice 5 because the study had a signicantly higher rate of endophthalmitis (0.074%) than expected. Fourth-generation uoroquinolones, which are effective in a laboratory environ- ment, 6 have not yet been proven to have a clinical prophylactic benet. The large volume of cataract surgery performed and uniform data acquisition in our health region allow for well- powered comparisons of different prophylactic routines in patients undergoing phacoemulsication cataract extraction. The purpose of the present study was to determine the incidence of postoperative endophthalmitis after cataract surgery over an 8-year period and to determine which sur- gical practices, if any, were associated with a higher rate of endophthalmitis. Methods Before initiation of this population-based case-control study, approval was obtained from the Health Research Ethics Board at the University of Alberta. A single tertiary retina service practice provides care for the entire region from a single hospital. This hospital has used a detailed, prospectively designed de- mographic database since 2002. This regional retinal service pro- vides a unique opportunity to capture all endophthalmitis cases occurring after cataract surgery for many surgeons from multiple sites. Controls were tabulated using volume data available from the provincial health care system. 835 2014 by the American Academy of Ophthalmology ISSN 0161-6420/14/$ - see front matter Published by Elsevier Inc. http://dx.doi.org/10.1016/j.ophtha.2013.08.046 Similar to the Endophthalmitis Vitrectomy Study, 7 the diagnosis of endophthalmitis was made clinically, and all cases, including culture-negative endophthalmitis, were considered posi- tive. Patients were included if they: (1) underwent cataract surgery between April 1, 2002, and March 31, 2009, in an Edmonton zone public or private facility, and (2) demonstrated clinical signs and symptoms of endophthalmitis within 42 days of cataract extraction. Exclusion criteria included: (1) patients in whom endophthalmitis developed after intraocular surgery other than cataract extraction, (2) patients who underwent combined cataract extraction and vit- rectomy, or (3) patients with chronic endophthalmitis (developing more than 42 days after cataract extraction). Surgeon parameters and operative preferences by year were obtained retrospectively from hospital records and were veried with each surgeon. This information was then used to populate covariates for cases and controls. Parameters and preferences collected included the type of preoperative antibiotics used before the surgical date, topical antibiotics administered at the facility before surgery (on the same day), incision type and location, blade size, type of intraoperative antibiotics and route of delivery (sub- conjunctival, intracameral, topical), administration of intra- operative steroid (topical, injected), topical glaucoma agent, and type of postoperative antibiotics used. According to institution policies, all patients were prepped using a sterilizing agent, the most common of which was povidoneeiodine solution; patients with an iodine allergy were prepped using chlorhexidine. Because a detailed database of specic preparations was not available for controls, this covariate was not included in the analysis. SAS statistical software version 9.2 (SAS Inc., Cary, NC) was used for all analyses. The association between each covariate and the development of endophthalmitis was analyzed using the chi- square test. Logistic regression was used for continuous data. For the purposes of analysis, uoroquinolones were grouped together by generation: second-generation uoroquinolones, ooxacin and ciprooxacin; fourth-generation uoroquinolones, gatioxacin and moxioxacin. Tests for trend were carried out using the Mantel-Haenszel chi-square test. Antibiotics were also analyzed as a binary variable (used versus not used). Surgeon mean annual volume was categorized according to previously described groupings: 50 to 250 procedures per year, 251 to 500 procedures per year, 501 to 1000 procedures per year, and more than 1000 procedures per year. 8 A multivariate logistic regression model was constructed to determine which variables were most predictive of endoph- thalmitis. Only covariates with a statistically signicant relation- ship on univariate analysis (P<0.1) were included. Post hoc exploratory simple regression analysis was performed to assist in the interpretation of the analysis of postoperative antibiotic choice. Power calculations, using an a error of 0.05, were performed for analyses that had nonsignicant results to determine if the study was powered to detect a clinically signicant difference in endophthalmitis rates. For these calculations, a reference rate indicating a clinically signicant increase in endophthalmitis rates was set at 0.1%. Results During the study period, 75 692 cataract extractions were per- formed by 29 different surgeons. Covariate information regarding surgical preferences and technique could not be obtained from 3 surgeons. Their cases, accounting for 0.49% of the data, were excluded. No cases of endophthalmitis occurred after cataract ex- tractions by these 3 surgeons. A total of 75 318 cataract extractions, performed by 26 different surgeons, were included in the analysis. If patients were equally split between comparative groups, this study had 88.7% power to detect a difference in endophthalmitis rates of 0.04%. Surgery was performed at 4 public hospitals and 5 nonhospital surgical facilities, where publicly funded care is delivered in a private setting. Twenty-six cases of postoperative endophthalmitis occurred, 3 of which were diagnosed more than 42 days after cataract surgery. These cases of chronic endophthalmitis were excluded, leaving a total of 23 cases of acute endophthalmitis occurring after cataract extraction (Table 1, available at www.aaojournal.org) and yielding an overall 8-year incidence of 0.03%. The incidence ranged from as low as 0.01% in 2004 and 2008 to as high as 0.07% in 2006 (Fig 1). Thirteen cases showed positive culture results; the overall 8-year incidence of culture- positive postoperative endophthalmitis was 0.03%. The incidence of endophthalmitis varied between surgeons from 0% to 0.20%. Surgeon volume by year varied signicantly from a low of 4 cases to a high of 1586 cases (Fig 2), but there was no difference in the rate of endophthalmitis by surgeon mean annual volume (P 0.507). Two surgeons were found to have higher rates than the rest of the group: 1 high-volume surgeon (1059.4231.9 mean cases per year) with an incidence of 0.08% (n 7; P 0.004) and 1 low-volume surgeon (123.544.8 mean cases per year) with an incidence of 0.20% (n 2; P 0.002). Most surgical procedures (n 50 471 [67.0%]) were performed at a single hospital (Fig 3). There was no difference in the rate of endophthalmitis when comparing each hospital and nonhospital surgical facilities grouped together (P 0.769). However, among the 5 (private) nonhospital surgical facilities, one center had a statistically signicantly higher rate of endophthalmitis than the other facilities (0.21%; P 0.046). Preoperative Antibiotics A slim majority of surgeons (n 14 [53.8%]) used preoperative antibiotics on the days leading up to surgery (Fig 4). Of the surgeons prescribing preoperative antibiotics, 84.6% (n 11) used a uoroquinolone. In the univariate analysis, neither the choice to use any preoperative antibiotics (Table 2; P 0.132) nor any specic antibiotic (P 0.135) affected the rate of endophthalmitis. Using the reference rate, there was 99.6% power to detect a 0.1% difference in endophthalmitis rates between use and nonuse of preoperative antibiotics. Same-Day Antibiotics Most surgeons (n 21 [80.8%]) applied antibiotic drops during the preparation phase on the day of surgery, and all but one (n 20 [95.2%]) used a uoroquinolone (Fig 5). In the univariate analysis, there was no difference in the rate of endophthalmitis among different antibiotic choices (P 0.890) or between use and nonuse (Table 2; P 0.817). Using the reference rate, this analysis had 88.9% power to detect a difference between use and nonuse. Figure 1. Graph showing the incidence rate of endophthalmitis by year. Ophthalmology Volume 121, Number 4, April 2014 836 Intracameral Antibiotics Only 6 surgeons (23.1%) used intracameral antibiotics; 5 used vancomycin and 1 used moxioxacin. Overall, 20.7% of study eyes (n 15 561) were treated with intracameral antibiotics, for which an endophthalmitis rate of 0.03% was observed. This was the same as in eyes not treated with intracameral antibioticsdthere was no sta- tistically signicant difference between these rates (P 0.898) on univariate analysis (Table 2). Using the reference rate, this analysis had 83.9% power to detect a difference between use and nonuse. Subconjunctival Antibiotics Subconjunctival antibiotics were used much more commonly, with 11 surgeons (42.3%) using either cefazolin (n 6), gentamicin (n 4), or cefuroxime (n 1). More than one third of eyes (35.8%; n 26 971) received an injection of subconjunctival an- tibiotics at the end of their surgery, but again, there was no sta- tistically signicant difference in the endophthalmitis rate (P 0.331) in the univariate analysis (Table 2). Even if intracameral and subconjunctival antibiotics were grouped together and analyzed as a single variable, there was still no difference in the rate of endophthalmitis (P 0.209) compared with those that received neither. Using the reference rate, this analysis had 99.2% power to detect a difference between use and nonuse. Intraoperative Steroids Most surgeons used intraoperative steroids (topical, injected, or both) as part of the procedure (n 21 [80.8%]). Accordingly, 74.1% of procedures used intraoperative steroids, with 76.2% of these applying a topical antibiotic and steroid combination drop at the end of the procedure, 13.7% using subconjunctival dexa- methasone or betamethasone, and 10.1% using both. In the uni- variate analysis (Table 2), there was no statistical difference in endophthalmitis rates between eyes that received subconjunctival (P 0.259) or topical (P 0.575) steroids. Using the reference rate, this analysis had 90.6% power to detect a difference between use and nonuse. Topical Glaucoma Medications Twelve surgeons (46.2%) used topical glaucoma medications at the end of the procedure (n 40 193) to try to prevent a postoperative intraocular pressure spike. Endophthalmitis developed twice as frequently in these eyes (0.04%) in comparison with cases in which Figure 2. Bar graph showing the surgical volume (y-axis) by surgeon (x-axis) and year (z-axis). Figure 3. Graph showing the number of procedures performed by facility. NHSF nonhospital surgical facilities; RAH Royal Alexandra Hospital. Figure 4. Graph showing the number of eyes treated with preoperative antibiotics. Rudnisky et al
Prevention of Endophthalmitis after Cataract Surgery 837 topical glaucoma therapy was not used (0.02%; P 0.048). Six different medications were used: 8.0% received pilocarpine, 39.7% received brimonidine, 6.2% received Iopidine, 2.6% received timolol, 16.4% received levobunolol, and 27.2% received betaxolol. The rate of endophthalmitis varied between 0% (pilocarpine) and 0.20% (timolol), with most being between 0.02% and 0.08%; in the univariate analysis, the rate of endophthalmitis in timolol-treated eyes was statistically signicantly higher than in eyes treated with the other medications (P 0.007). Using the reference rate, there was 85.9% power to detect a difference between use and nonuse. Postoperative Antibiotics All eyes received postoperative antibiotics (Fig 6): 37.5% received polymyxin B and trimethoprim, 35.1% received moxioxacin, 9.5% received ooxacin, 8.2% received ciprooxacin, 4.3% received gatioxacin, 4.0% received both moxioxacin and tobramycin, 1.0% received polymyxin B, and 0.5% received both moxioxacin and neomycin and polymyxin B (Maxitrol). Because of these antibiotic combinations and the absence of an obvious control group (everyone received some form of post- operative antibiotic), individual indicator variables were created for each antibiotic. Using all other antibiotics grouped together as a control in each analysis (Table 2), the rate of endophthalmitis ranged between 0% (ooxacin) and 0.09% (Polysporin). Only moxioxacin demonstrated a statistically signicant lower rate of endophthalmitis (0.01%) in comparison with all others grouped together (0.04%; P 0.029). Interestingly, if antibiotics were grouped by class, there was a trend (P 0.04) for the rate of endophthalmitis to decline as a stronger antibiotic class was used (Table 3), with the lowest rate of endophthalmitis (0.02%) observed if a fourth-generation uoroquinolone was used. If a power calculation were performed to evaluate the strength of the comparison between the use of a fourth-generation uoroquinolone versus any other antibiotic, the analysis had 99.5% power to detect a difference. Wound Construction Almost all cases of endophthalmitis (n 22) developed in eyes in which a temporal incision was used. However, the difference in endophthalmitis rates between temporal (0.04%) and superior (0.01%) incisions was not statistically signicant (P 0.06) in the univariate analysis (Table 2). Regarding wound types, 61.8% of procedures were clear corneal, 33.4% were limbal, and 4.7% were a scleral tunnel; there was no statistically signicant difference in the rate of endophthalmitis between wound types (P 0.564). The average wound size for endophthalmitis cases was 2.810.13 mm in comparison with 2.780.14 mm, but this difference was not statistically signicant (P 0.337). Antibiotic Combinations An exploratory analysis was performed to determine if certain combinations of antibiotic choices improved prophylaxis. To assess this, surgeon prophylactic regimens were awarded 1 point for each: if a fourth-generation uoroquinolone was used before surgery, if either a subconjunctival or intracameral injection was performed during surgery, and if a fourth-generation uo- roquinolone was used after surgery. As such, points ranged bet- ween 0 and 3. Eyes were divided fairly evenly between point categories: 26.1% had 0 points, 30.4% had 1 point, 17.1% had 2 points, and 26.4% had 3 points. There was a statistically Table 2. Univariate Analyses of Endophthalmitis Covariates Variable Endophthalmitis Rate (%) P Value* Yes No Public surgical facility 0.03 0.03 0.769 Preoperative antibiotics 0.02 0.04 0.132 Antibiotic choices Same day 0.03 0.03 0.817 Intracameral 0.03 0.03 0.898 Subconjunctival 0.02 0.04 0.331 Intraoperative steroids Subconjunctival dexamethasone 0.02 0.03 0.259 Topical 0.03 0.03 0.575 Topical glaucoma medications 0.04 0.02 0.048 Temporal wound location 0.04 0.01 0.060 Postoperative antibiotic choice Polymyxin B 0.09 0.03 0.260 Tobramycin 0.04 0.02 0.300 Ooxacin 0 0.03 0.121 Ciprooxacin 0.07 0.03 0.106 Moxioxacin 0.01 0.04 0.029 Gatioxacin 0.06 0.03 0.290 *Chi-square test. Figure 5. Graph showing the number of eyes treated with same-day an- tibiotics during the preoperative preparatory phase conducted at the fa- cility. Note that for tobramycin, n 35. Figure 6. Graph showing the number of eyes treated with each post- operative antibiotic choice (dark bars; left y-axis). Light grey diamonds indicate the rate of endophthalmitis (right y-axis) that was observed for each antibiotic choice. Ophthalmology Volume 121, Number 4, April 2014 838 signicant trend for the rate of endophthalmitis to decline as the point value increased (P 0.04). Multivariate Exploratory Analysis Because a single private surgical center, use of timolol, and tem- poral wound placement were associated with the development of endophthalmitis on univariate analysis and because moxioxacin alone a higher antibiotic class, and point score seemed protective, these variables were included in an exploratory multivariate model. Timolol was analyzed as a categorical variable with the following categories: 0 no glaucoma medication used, 1 timolol used, 2 betaxolol or levobunolol used, and 3 any other topical glaucoma agent. Antibiotic class also was analyzed categorically: 1 polymyxin B, 2 tobramycin, 3 ooxacin or ciprooxacin, and 4 moxioxacin or gatioxacin. The variables with the weakest association with endoph- thalmitis rates were moxioxacin (P 0.916) and antibiotic point score (P 0.487); these variables were removed from the model as part of backward, stepwise logistic regression. The nal model (Table 4) demonstrated that the use of timolol (P 0.0002) or surgery at one of the private surgical suites (P 0.009) were associated independently with a higher rate of endophthalmitis, whereas the use of a second-generation uoroquinolone (P 0.019) or fourth-generation uoroquinolone (P 0.008) was independently associated with a lower rate of endophthalmitis. Discussion From a total of 75 318 cataract surgeries performed by 26 surgeons at 9 Edmonton-area hospitals or ambulatory surgical centers, 23 cases of endophthalmitis developed, yielding an overall incidence of 0.03%. This is on the lower end of incidences reported in the literature. 1,2,9e11 In a systematic review of 3 140 650 cataract surgeries, Taban et al 3 found an aggregate incidence of endophthalmitis occurring after cataract surgery of 0.128%. Our study demonstrates that a low endophthalmitis rate can be achieved in a group of surgeons using heterogeneous prophylactic regimens. Multivariate analysis found that the use of timolol was associated with a higher rate of endophthalmitis. There is controversy over whether intraocular pressure-lowering agents can prevent an intraocular pressure spike effec- tively after surgery. 12e18 Before conducting this study, the authors would not have hypothesized that there would be any disadvantage to using topical glaucoma agents at the end of cataract surgery. Possible explanations for the asso- ciation between timolol and endophthalmitis could be bottle tip contamination 19 or transient, postoperative hypotony with resultant ingress of uid through the wound. However, only one surgeon used timolol, and it was the surgeon with the highest rate of endophthalmitis (0.20%). It is therefore unclear if this signicant association is because of differences in technique, the use of timolol, a patient population with a higher baseline risk of endophthalmitis, or other unmeasured surgeon or patient confounders. This nding is important because it suggests that further research into the use of topical b-blockers in this setting is warranted. This study also found that surgery at one of the private surgical centers was associated with a higher rate of endophthalmitis. However, there was a low volume of surgery (n 944) performed at this center, which suggests that chance alone may explain this nding; one fewer case and there would be no statistically signicant relationship. However, it is also possible that this center has a higher rate because it is a low-volume site. The surgeons who operate there also operate at other sites; their overall rate was not different in comparison with that of their peers. As such, it suggests the difference observed could be related to location-based factors, whether they be surgical assistants, management procedures, air quality issues, differences in patient preparatory technique, or unmeasured patient- specic variables. Although the exact reason is impor- tant, it cannot be determined with any accuracy from these data; it is noteworthy that one case occurred in 2005 and the other in 2007, indicating there was not a so-called mini- epidemic. This study suggests that uoroquinolones are a superior antibiotic prophylactic choice for the prevention of endoph- thalmitis; multivariate analysis demonstrated that both second- and fourth-generation uoroquinolones decrease the odds of endophthalmitis when used after surgery. In vitro and in vivo animal models 20 have shown that fourth-generation uo- roquinolones have superior efcacy compared with second- Table 3. Endophthalmitis Rates by Antibiotic Class Antibiotic No. of Endophthalmitis Cases No. of Control Participants Rate (%) P Value Polymyxin B or polymyxin B trimethoprim 1 738 0.14 0.04* Tobramycin 12 28 234 0.04 Ooxacin or ciprooxacin 4 13 284 0.03 Moxioxacin or gatioxacin 6 33 039 0.02 *Mantel-Haenszel chi-square test for trend. Table 4. Final Multivariate Exploratory Logistic Regression Model Variable Odds Ratio 95% Wald Condence Limits P Value Private surgical facility 10.57 1.81e61.79 0.009 Glaucoma agent* Timolol 33.61 5.25e215.28 0.0002 Levobunolol or betaxolol 3.27 0.91e11.70 0.069 Other topical agent 2.74 0.89e8.47 0.079 Postoperative antibiotic class y Tobramycin 0.18 0.02e1.52 0.115 Ooxacin or ciprooxacin 0.05 0.004e0.61 0.019 Moxioxacin or gatioxacin 0.04 0.004e0.44 0.008 *Categorical variable; reference category was no glaucoma agent used. y Categorical variable; reference category was polymyxin B. Rudnisky et al
Prevention of Endophthalmitis after Cataract Surgery 839 and third-generation uoroquinolones in terms of potency and the development of bacterial resistance. 6 Similarly, there were statistically stronger and slightly lower odds of developing endophthalmitis when a fourth-generation uoroquinolone was used (Table 4). Although these ndings are statistically signicant and were detected within a large overall sample, this study still reects only 23 cases of endophthalmitis. As such, these results contribute to, rather than resolve, the debate over which postoperative antibiotic choice is the best. Unfortunately, the optimal overall strategy remains contro- versial. The European Society of Cataract & Refractive Sur- geons initiated a prospective, randomized, partially masked, multicenter study in 2003 1 demonstrating that intracameral cefuroxime is effective in reducing the rate of postoperative endophthalmitis. Although the injection of intracameral antibiotics has been supported by other authors, 21 this study did not nd a protective effect. Indeed, adoption of the European Society of Cataract & Refractive Surgeons recommendations has been slow; a subsequent survey revealed that only 6% of respondents reported injecting intracameral cefuroxime, and 77% did not plan to start, 5 perhaps in part because there are large studies in which intracameral antibiotics were not used 11 that have reported lower endophthalmitis rates (0.04%) than those observed in the European Society of Cataract & Refractive Surgeons intracameral antibiotic group (0.07%). Similarly, previous reports have suggested that subconjunctival antibiotics are associated with decreased endophthalmitis rates, 22,23 but this also was not observed in our study, despite a power of 99%. Surgeon volume was recently reported to be associated with endophthalmitis. Keay et al 24 found that surgeons with annual volumes of 50 cases or fewer had a relative risk of 3.8 (95% condence interval, 3.13e4.61) in comparison with surgeons who perform more than 1000 cases annually. A recent letter about this study, and the author response, 25 suggested that the explanation for this gradient may be a choice by high-volume surgeons for more inten- sive prophylactic strategies, such as intracameral antibiotics. In our study, one of the highest rates of endophthalmitis was experienced by a surgeon who had the third highest volume of 26 surgeons (mean, 1059 cases/year). The discrepancy between our ndings and those of Keay et al, whose study was very large, may be because the variables in endophthalmitis studies could be surrogates for something else more specic. Intuitively, patient ora, postoperative behavior, and activities, which are unmeasurable, or other unmeasured surgeon preferences, such as wound construc- tion technique, could inuence infection risk. Similarly, strategies such as patching after surgery or other unmea- sured intraoperative details also could affect the rate of endophthalmitis. Clearly, if an answer is to be found, the net must be cast wider than the usual focus on costly prophy- lactic antibiotics and their differences. There are a number of limitations of this study. Endoph- thalmitis studies are often criticized for missing cases, and although it is possible that a case could have been missed if a patient sought care at another hospital in Alberta, it is un- likely given that the retina service for the region (Edmonton Health Zone) operates out of only 1 hospital and provides service to patients in a 2 000 000-km 2 catchment area. Similarly, the overwhelming majority of patients undergoing cataract surgery reside in the same catchment area. Another limitation is the retrospective method by which covariates for cases and controls were constructed. Recall bias by the cataract surgeons may have affected the assembly of surgeon preferences that were used to populate covariate data for controls. For example, patients who are allergic to penicillin would not have received subconjunctival cefazolin injections, and that discrepancy is not captured in this dataset. However, this weakness has little impact given that there would be induced bias in favor of the use of antibiotic strategies, and yet no associations were found and the study was powered adequately. Another deciency is that most study eyes would represent the right and left eyes of a single patient. Given the correlation between eyes, the analyses performed do not ac- count for intereye correlation, and it is possible that even the signicant results are actually underpowered. Unfortunately, the extent to which this issue affects the study cannot be quantied because of the indirect and retrospective method used to obtain control data. However, nonsimultaneous sequential surgery, which almost every eye would have un- dergone, is performed to mitigate infection risk. As a result, there may be less correlation between eyes for an outcome like endophthalmitis than one might normally observe. In this large, population-based, case-control study, the rate of endophthalmitis was lower if a uoroquinolone was used after surgery. In contrast, endophthalmitis was more likely to occur if timolol was used at the end of the procedure or if surgery was performed at one of the private facilities. References 1. ESCRS Endophthalmitis Study Group. Prophylaxis of post- operative endophthalmitis following cataract surgery: results of the ESCRS multicenter study and identication of risk factors. J Cataract Refract Surg 2007;33:97888. 2. Wykoff CC, Parrott MB, Flynn HWJr, et al. Nosocomial acute- onset postoperative endophthalmitis at a university teaching hospital (2002e2009). Am J Ophthalmol 2010;150:3928. 3. Taban M, Behrens A, Newcomb RL, et al. Acute endoph- thalmitis following cataract surgery: a systematic review of the literature. Arch Ophthalmol 2005;123:61320. 4. Ciulla TA, Starr MB, Masket S. Bacterial endophthalmitis prophylaxis for cataract surgery: an evidence-based update. Ophthalmology 2002;109:1324. 5. Chang DF, Braga-Mele R, Mamalis N, et al; ASCRS Cataract Clinical Committee. Prophylaxis of postoperative endoph- thalmitis after cataract surgery: results of the 2007 ASCRS member survey. J Cataract Refract Surg 2007;33:18015. 6. Mather R, Karenchak LM, Romanowski EG, Kowalski RP. Fourth generation uoroquinolones: new weapons in the arsenal of ophthalmic antibiotics. Am J Ophthalmol 2002;133: 4636. 7. Endophthalmitis Vitrectomy Study Group. Results of the Endophthalmitis Vitrectomy Study: a randomized trial of im- mediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Arch Ophthalmol 1995;113:147996. 8. Bell CM, Hatch WV, Cernat G, Urbach DR. Surgeon volumes and selected patient outcomes in cataract surgery: a population- based analysis. Ophthalmology 2007;114:40510. Ophthalmology Volume 121, Number 4, April 2014 840 9. Aaberg TM Jr, Flynn HW Jr, Schiffman J, Newton J. Noso- comial acute-onset postoperative endophthalmitis survey. A 10-year review of incidence and outcomes. Ophthalmology 1998;105:100410. 10. Freeman EE, Roy-Gagnon MH, Fortin E, et al. Rate of endophthalmitis after cataract surgery in Quebec, Canada, 1996e2005. Arch Ophthalmol 2010;128:2304. 11. Lloyd JC, Braga-Mele R. Incidence of postoperative endoph- thalmitis in a high-volume cataract surgicentre in Canada. Can J Ophthalmol 2009;44:28892. 12. Erdogan H, Ozec AV, Caner C, et al. Effect of latanoprost/ timolol and dorzolamide/timolol on intraocular pressure after phacoemulsication surgery. Int J Ophthalmol 2011;4:1904. 13. Kir E, Cakmak H, Dayanir V. Medical control of intraocular pressure with brinzolamide 1% after phacoemulsication. Can J Ophthalmol 2008;43:55962. 14. Pharmakakis N, Giannopoulos K, Stasinos S, et al. Effect of a xed brimonidine-timolol combination on intraocular pressure after phacoemulsication. J Cataract Refract Surg 2011;37: 27983. 15. Borazan M, Karalezli A, Akman A, Akova YA. Effect of antiglaucoma agents on postoperative intraocular pressure after cataract surgery with Viscoat. J Cataract Refract Surg 2007;33: 19415. 16. Cetinkaya A, Akman A, Akova YA. Effect of topical brinzo- lamide 1% and brimonidine 0.2% on intraocular pressure after phacoemulsication. J Cataract Refract Surg 2004;30:173641. 17. Kasetti SR, Desai SP, Sivakumar S, Sunderraj P. Preventing intraocular pressure increase after phacoemulsication and the role of perioperative apraclonidine. J Cataract Refract Surg 2002;28:217780. 18. Katsimpris JM, Siganos D, Konstas AG, et al. Efcacy of brimonidine 0.2% in controlling acute postoperative intra- ocular pressure elevation after phacoemulsication. J Cataract Refract Surg 2003;29:228894. 19. Geyer O, Bottone EJ, Podos SM, et al. Microbial contamina- tion of medications used to treat glaucoma. Br J Ophthalmol 1995;79:3769. 20. Scoper SV. Review of third-and fourth-generation uo- roquinolones in ophthalmology: in-vitro and in-vivo efcacy. Adv Ther 2008;25:97994. 21. Wejde G, Montan P, Lundstrom M, et al. Endophthalmitis following cataract surgery in Sweden: national prospective survey 1999e2001. Acta Ophthalmol Scand 2005;83:710. 22. Colleaux KM, Hamilton WK. Effect of prophylactic anti- biotics and incision type on the incidence of endophthalmitis after cataract surgery. Can J Ophthalmol 2000;35:3738. 23. Ng JQ, Morlet N, Bulsara MK, Semmens JB. Reducing the risk for endophthalmitis after cataract surgery: population- based nested case-control study: Endophthalmitis Population Study of Western Australia sixth report. J Cataract Refract Surg 2007;33:26980. 24. Keay L, Gower EW, Cassard SD, et al. Postcataract surgery endophthalmitis in the United States: analysis of the complete 2003 to 2004 Medicare database of cataract surgeries. Ophthalmology 2012;119:91422. 25. Naseri A. Surgeon cataract volume and endophthalmitis [let- ter]. Ophthalmology 2012;119:2415; author reply 2416. Footnotes and Financial Disclosures Originally received: May 17, 2013. Final revision: August 18, 2013. Accepted: August 22, 2013. Available online: December 9, 2013. Manuscript no. 2013-792. Department of Ophthalmology, University of Alberta, Edmonton, Canada. Presented at: Eye Physicians and Surgeons of Alberta Annual Meeting, February 2013, Banff, Canada. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Supported by the University of Alberta Endowment Award for Student Research, Edmonton, Canada. The funding organization had no role in the design or conduct of this research. Correspondence: Christopher J. Rudnisky, MD, MPH, Department of Ophthalmology, Royal Alexandra Hospital, 10240 Kingsway Avenue, Room 2316, Edmonton, Alberta T6E2V8, Canada. E-mail: chris@rudnisky.ca. Rudnisky et al
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