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Prospective Randomized Comparison of 2 Different Methods of 5% Povidone-Iodine Applications for Anterior Segment Intraocular Surgery
Herminia Miño de Kaspar, PhD;
Robert T. Chang, MD;
Kuldev Singh, MD;
Peter R. Egbert, MD;
Mark S. Blumenkranz, MD;
Christopher N. Ta, MD
Arch Ophthalmol. 2005;123:161-165.
ABSTRACT
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Objective To determine the efficacy of reducing conjunctival bacteria flora with 2 different regimens of 5% povidone-iodine application: 2 drops on the conjunctiva cul-de-sac vs a 10-mL conjunctival irrigation of the fornices.
Methods In this prospective controlled trial, 200 eyes undergoing anterior segment intraocular surgery were randomized to control and study groups. All patients from both groups received topical ofloxacin and a povidone-iodine scrub of the periorbital area before the surgical procedure. The eyes in the control group received 2 drops of povidone-iodine on the conjunctiva preoperatively, whereas eyes in the study group had irrigation of the fornices with 10 mL of povidone-iodine. Conjunctival cultures were obtained at 4 separate time points before and after surgery.
Results Twenty (26%) of 78 eyes in the study group had positive conjunctival cultures immediately prior to surgery compared with 40 (43%) of 94 eyes in the control group (P = .02). At the conclusion of the surgery, 14 (18%) of 78 eyes and 30 (32%) of 94 eyes had positive cultures in the study and control groups, respectively (P = .05).
Conclusion Irrigation of the fornices with 5% povidone-iodine was associated with significantly fewer positive conjunctival cultures at the time of surgery compared with the application of 2 drops on the conjunctiva.
INTRODUCTION
Postoperative endophthalmitis is a rare but potentially devastating complication of intraocular surgery. The incidence of endophthalmitis after intraocular surgery was found to be 0.093% in one study.1 The goal of an antiseptic is to eliminate or greatly reduce the number of microorganisms in the surgical field at the time of the surgery. It is believed that the most common microorganisms responsible for the development of endophthalmitis reside in the eyelids and conjunctiva.2-3 Further, it has been theorized that reducing the bacterial load on the ocular surface at the time of surgery may reduce the risk of endophthalmitis.
Previous studies have shown that 5% povidone-iodine is a safe and effective agent in reducing the number of bacteria on the ocular surface at the time of surgery.3-12 The use of 1 to 2 drops of 5% povidone-iodine on the eye has been shown to reduce the number of bacteria by 91% in 1 study.4 Furthermore, 2 published studies have shown that preoperative application of povidone-iodine reduces the risk of postoperative endophthalmitis.13-14 To our knowledge, the various methods of applying povidone-iodine preoperatively have not been previously studied prospectively. Several investigators have supported placing 1 or 2 drops of 5% povidone-iodine in the conjunctival sac,4, 10, 14-15 while others have advocated irrigating the conjunctival sac with 1% or 5% povidone-iodine.5-6,16-17 The purpose of our study was to compare the efficacy of 2 drops of 5% povidone-iodine applied to the conjunctival cul-de-sac vs a 10-mL conjunctival irrigation of the fornices.
METHODS
Two hundred patients, consecutively scheduled to undergo anterior segment intraocular surgery, were asked to participate in this prospective, randomized, clinical trial. After obtaining approval from the institutional review board at Stanford University, Stanford, Calif, appropriate consent was obtained from each patient. No patient had a known, active ocular infection at the time of the surgery, or allergies to iodine or fluoroquinolones. All patients received 3 applications of topical 0.3% ofloxacin, 5 minutes apart, 1 hour before surgery. In each case, a topical anesthetic was given and the periorbital area, eyelids, and eyelashes were scrubbed with 5% povidone-iodine (5% Betadine Sterile Ophthalmic Prep Solution; Alcon Laboratories, Inc, Fort Worth, Tex) for 1 minute.
The Microsoft Excel software program (Redmond, Wash) was used to randomize patients to the control and study groups. Of the 200 patients enrolled in the study, there were 108 in the control group and 92 in the study group. The control group received 2 drops of 5% povidone-iodine in the lower conjunctival sac. In the study group, the superior and inferior fornices were each irrigated with 5 mL of 5% povidone-iodine. This was performed by attaching a small sterile flexible plastic tubing to a 10-mL syringe filled with 5% povidone-iodine and vigorously irrigating the base of the eyelids and conjunctival fornices. Specifically, the eyelids were pulled back with a sterile gloved hand, and the conjunctiva and upper and lower eyelid margins and fornices were irrigated forcefully with 10 mL of 5% povidone-iodine. Sterile gauze was applied at the side of the face to catch the povidone-iodine as it spilled out of the fornices laterally. In addition, the excess povidone-iodine was blotted with sterile gauze with the eyelids closed with the remaining povidone-iodine left to dry. The ocular surface was not rinsed with isotonic sodium chloride or a balanced salt solution in either group. The surgical site was covered with an adhesive sterile drape. The eyelashes were tucked under the drape and speculum. Surgery was begun approximately 5 minutes after the application of povidone-iodine.
Conjunctival cultures were obtained from the eye undergoing surgery using a cotton swab moistened with blood culture broth medium (BBL SeptiCheck System, Fisher Scientific, Los Angeles, Calif). The cultures were obtained at the following time points: immediately on arrival at the surgery center on the day of surgery, before receiving any topical medications (T1), after application of topical 0.3% ofloxacin (given 1 hour before surgery) and before 5% povidone-iodine scrub (T2), immediately before surgery (approximately 5 minutes after povidone-iodine scrub) (T3), and at the conclusion of the surgical procedure (T4). The culture samples were immediately inoculated on 5% sheep blood and chocolate agar plates as well as pediatric (20-mL) blood culture broth media. All of the culture media were purchased through Fisher Scientific, Los Angeles, Calif. The blood culture media plates were incubated with 5% carbon dioxide to encourage microaerophilic and aerobic bacterial growth. The chocolate agar plates were incubated in an anaerobic bag for isolation of anaerobic bacteria. All culture media were incubated at 37°C for 10 days. All bacterial isolates were identified and quantified. The number of colony-forming units (CFUs) was determined for the blood and chocolate agar cultures, and the number of days prior to bacterial growth in blood culture liquid media was recorded. The microbiologist (H.M.K.) and the physician (R.T.C.) obtaining the cultures at time points T1 and T2 were not masked for the time point of culture acquisition or from which group of patients the samples were obtained. The surgeons obtaining the culture samples at time points T3 and T4, however, were masked with regard to study vs control group. The microbiologist was masked with regard to the patients’ groups during the interpretation and recording of the microbiological results.
Anterior chamber aqueous fluid was obtained both at the beginning and conclusion of surgery using either a 27-gauge blunt cannula or a 30-gauge needle attached to a tuberculin syringe. Approximately 100 µL of aqueous fluid was obtained, after which the original cannula was removed. Aqueous fluid in the syringe was then injected into a pediatric (20-mL) blood culture liquid media bottle. Statistical analysis was performed using 2-tailed Fisher exact tests with the Analyze-It software program (Analyze-It Software, Leeds, England).
RESULTS
Among the 200 cases that were randomized, 108 were in the control group and 92 were in the study group. There were 13 cancelled cases in each group, resulting in 95 cases in the control group and 79 cases in the study group. In the control group, there were 44 (46%) male and 51 (54%) female patients. In the study group, there were 33 (42%) male and 46 (58%) female patients. The mean age was 70 years for both groups. In 10 patients, surgery was performed on both eyes, 21 to 189 days apart, with a mean separation of 45 days. In 8 of these 10 patients, one eye was randomized to the control group and the other eye to the study group. In the remaining 2 patients, both eyes of one patient were randomized to the control group while both eyes in the other patient were in the study group. Only data from the first eye that had surgery in these 2 patients were included in the analysis. Among the available 172 cases, there were 134 cases of cataract surgery by phacoemulsification technique, 17 cases of trabeculectomy, 5 cases of penetrating keratoplasty, and 16 miscellaneous anterior segment intraocular surgical procedures, such as combined cataract and trabeculectomy surgery, bleb revision, secondary intraocular lens implantation, and pupilloplasty.
The baseline conjunctival cultures (T1) revealed that 75 (80%) of 94 eyes in the control group had bacterial growth, yielding 92 different species of bacteria, of which 69 (75%) were coagulase-negative staphylococci. The baseline cultures in the study group were positive for bacteria in 79% of the cases (62 of 78 eyes). Of the 75 bacterial species isolated from the 62 positive cultures in the study group, 54 (72%) were coagulase-negative staphylococci. The other bacterial isolates in both the control and study groups included 10 Staphylococcus aureus, 10 Streptococcus species, 8 Corynebacterium species, 5 Propionibacterium acnes, 2 Pseudomonas species, 1 Bacillus species, 1 Micrococcus species, and 7 gram-negative bacteria, each of which was not Pseudomonas species.
The blood culture broth medium was defined as yielding a positive culture if it was cloudy after 4 days of incubation. Table 1 and the Figure summarize the results of the liquid media. At T3 (immediately before surgery), 20 (26%) of 78 samples in the study group had positive cultures compared with 40 (43%) of 94 samples in the control group (P = .02). Similarly, at T4 (at the conclusion of surgery), 14 (18%) of 78 samples in the study group had positive conjunctival cultures compared with 30 (32%) of 94 in the control group (P = .05).
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Table 1. Results of the Blood Culture Broth Media*
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Figure. Conjunctival culture results of blood culture broth medium (BLL-SeptiCheck System; Fisher Scientific, Los Angeles, Calif), indicating the percentage of eyes with positive cultures at different time points. The cultures were obtained at the following time points: immediately on arrival at the surgery center on the day of surgery, before receiving any topical medications (T1), after application of topical 0.3% ofloxacin (given 1 hour before surgery) and before 5% povidone-iodine scrub (T2), immediately before surgery (approximately 5 minutes after povidone-iodine scrub) (T3), and at the conclusion of the surgical procedure (T4). Asterisk Indicates P<.05.
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Blood and chocolate agar plates were used to quantify the number of bacteria found on the ocular surface. For the purpose of analyzing the blood and chocolate agar culture results, these data were categorized based on the number of CFUs isolated (Table 2). The categories were CFUs of at least 1, 5, or 10. Using the Fisher exact tests, there was no statistical difference between the control and study groups for any time points in each of these categories.
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Table 2. Summary of Combined Blood and Chocolate Agar Results*
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In many cases, no anterior chamber aqueous fluid was obtained for various reasons, including technical difficulty and the emphasis on maximizing operation safety. The anterior chamber fluid was obtained from 31 cases at the initiation of surgery and 30 cases at the conclusion of the surgery in the control group. In the study group, aqueous fluid samples were obtained from 43 and 45 cases at the beginning and conclusion of surgery, respectively. None of the aqueous fluid samples were found to have bacterial growth.
There were no povidone-iodine–related complications in either group. In particular, no eyes developed intraoperative or postoperative epithelial defects, persistent postoperative corneal edema, or toxic conjunctivitis.
COMMENT
It is believed that the most common sources of bacteria causing endophthalmitis are the eyelids and conjunctiva.3 We theorize that by eliminating the presence of bacteria on the conjunctiva at the time of surgery, the risk of developing endophthalmitis is decreased. However, to our knowledge, no published studies have shown a correlation between the number of bacteria present on the ocular surface and the risk of developing endophthalmitis. Nevertheless, povidone-iodine given before and at the conclusion of surgery has been shown to be effective in reducing the conjunctival bacterial count.4-5,11-12 Furthermore, in a prospective, nonrandomized study, Speaker and Menikoff14 reported a significant decrease in the incidence of endophthalmitis in patients treated with povidone-iodine preoperatively. The application of povidone-iodine in these studies was accomplished by placing 1 to 2 drops in the conjunctival cul-de-sac,4, 11, 14 or by irrigating the fornices.5-6 Our study results suggest that irrigation of the conjunctiva preoperatively with 5% povidone-iodine is more effective in eliminating bacteria from the ocular surface than topical application of 2 drops of the same solution. The results of the blood culture broth medium showed that eyes in the study group that were irrigated with 10 mL of 5% povidone-iodine had significantly fewer positive cultures at the time of surgery compared with eyes in the control group that received 2 drops of the same solution. The conjunctiva in the fornices has many deep crypts. A reasonable assumption is that povidone-iodine reaches the fornices and the inner surface of these crypts much more effectively after mechanical irrigation than 2-drop povidone-iodine application on the bulbar conjunctiva.
We were unable to show any difference in the number of bacteria isolated from either blood or chocolate agar plates between the groups. In the combined blood and chocolate agar groups, at least 84% had no bacterial growth from samples obtained immediately before and after surgery for both groups. For those with a positive culture, very few bacteria were isolated using blood or chocolate agar plates. Only 1 eye (1%) from each group was found to have more than 5 CFUs at the beginning of surgery. Only 2 eyes (2%) from the control group and none in the study group had greater than 5 CFUs at the conclusion of surgery. The few positive blood and chocolate agar cultures and the low number of CFUs among these positive cultures may explain why we did not find a statistically significant difference between the control and study groups. It may be that the sensitivity of the blood and chocolate agar plates was inadequate to detect a difference between the groups. When only a few bacteria are present, blood culture broth media are more sensitive than solid agar media in cultivating bacterial growth. We postulate that the difference in positive cultures found in the liquid blood culture, but not in solid media, is likely because of the fact that bacteria are more likely to grow in the liquid blood culture media than on solid media. For example, the percentage of positive liquid media cultures was 43% and 26% for the control and study groups, respectively, immediately before surgery. In contrast, only 16% and 14% of the control and study group cases tested positive in solid agar media. The overwhelming effectiveness of povidone-iodine as an antiseptic, whether given as 2 drops or by irrigation of the fornices, combined with the poor sensitivity of solid culture media, may explain why we found no statistical difference between the control and study groups. Our results are consistent with those of Grimes et al,15 who reported no difference in the number of CFUs and percentage of positive cultures when comparing the applications of 1 to 2 drops of 5% povidone-iodine with 0.02% povidone-iodine irrigation. However, this study was limited to 22 patients, only blood and chocolate agar culture media were used, and irrigation was performed with 0.02% povidone-iodine, compared with 5% povidone-iodine solution in our study.
Assuming that the risk of endophthalmitis is related to the presence of bacteria on the ocular surface at the time of surgery, and the subsequent introduction of bacteria into the eye, it is reassuring that very few or no bacteria were isolated in either group. For example, 21% of the eyes in the control group and 16% in the study group had 10 CFUs or more at baseline. After the treatment of antibiotics and povidone-iodine, regardless of methods of application, only 1% of the eyes in each group had 10 CFUs or more.
A study by Isenberg et al18 showed that irrigating the conjunctiva with an isotonic sodium chloride solution resulted in a significant increase in conjunctival bacterial count. Our study showed a significant reduction in positive conjunctival culture by irrigating with povidone-iodine. We postulate that by vigorously irrigating the eyelids and conjunctiva with povidone-iodine, we may be mechanically removing bacteria from these areas, particularly among the crypts of the conjunctiva in the fornices. The povidone-iodine then may kill the remaining bacteria. We further speculate that when an isotonic sodium chloride solution is used for irrigation, the effect is limited to dislodging the bacteria since this agent is unlikely to kill bacterial organisms.
We noted no adverse effects with povidone-iodine application in either group. Postoperatively, there were no cases of increased conjunctival hyperemia, epithelial defects, persistent punctate epithelial erosions, or corneal edema. This is consistent with the report by Hale,6 who found no adverse effect of irrigation with 30 mL of 0.5% active povidone-iodine in more than 2000 ophthalmic surgical cases.
One potential weakness of our study is the unequal randomization of patients between the groups that was due to chance alone. However, the demographic data of the 2 groups were similar. Another weakness is that the microbiologist (H.M.K.) and the physician (R.T.C.) obtaining the cultures at time points T1 and T2 were not masked. However, there was no difference in the culture results between the groups at time points T1 and T2. Furthermore, the surgeons obtaining the cultures at T3 and T4 were masked with regard to the study groups. These were the most important time points since they represent the time points closest to surgery. The microbiologist was also masked during the interpretation of the culture results.
CONCLUSIONS
Irrigating the fornices with 5% povidone-iodine resulted in significantly fewer positive bacterial conjunctival cultures in the perioperative period compared with an application of 2 drops of the same solution. Given the powerful antiseptic effect of povidone-iodine with minimal or no toxic effect to the ocular surface, and its low cost, we recommend irrigating the conjunctiva and fornices with 5% povidone-iodine before ophthalmic surgery. Furthermore, a combination of topical antibiotic and povidone-iodine, regardless of the methods of application, resulted in very few bacteria present on the ocular surface, presumably reducing the risk of postoperative endophthalmitis.
AUTHOR INFORMATION
Correspondence: Christopher N. Ta, MD, Department of Ophthalmology, Stanford University, 900 Blake Wilbur Dr, Room W-3036, Palo Alto, CA 94304-5353 (cta{at}stanford.edu).
Submitted for Publication: January 26, 2004; final revision received October 7, 2004; accepted October 7, 2004.
Funding/Support: This study was supported in part by the Edward E. Hills Foundation, San Francisco, Calif; Allergan, Inc, Irvine, Calif; and Hannelore-Georg Zimmermann Foundation, Munich, Germany.
Previous Presentation: Preliminary results of this study were presented as a scientific poster at the American Academy of Ophthalmology; October 22, 2002; Orlando, Fla.
Financial Disclosure: None.
Author Affiliations: Departments of Ophthalmology, Ludwig–Maximilians University, Munich, Germany (Dr Miño de Kaspar), and Stanford University, Stanford, Calif (Drs Chang, Singh, Egbert, Blumenkranz, and Ta).
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SECTION EDITOR: ROY W. BECK, MD, PhD
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