EDITORIAL Povidone-Iodine for Endophthalmitis Prophylaxis YASIR AHMED, INGRID U. SCOTT, AVINASH PATHENGAY, ABHISHEK BAWDEKAR, AND HARRY W. FLYNN, JR
E
NDOPHTHALMITIS IS AN UNCOMMON POSTPROCE-
dure complication with a reported incidence of 0.028% after cataract surgery, 0.011% after pars plana vitrectomy, and 0.108% after penetrating keratoplasty.1 The reported rate of endophthalmitis after intravitreal injection of anti–vascular endothelial growth factor (anti-VEGF) agents is 0.02%.2 Although endophthalmitis is an infrequent complication, it often portends a very poor visual prognosis.2 The most common sources of ocular pathogen contamination include the conjunctiva and eyelids.3 The goal of preprocedure antisepsis is to reduce the ocular surface pathogen load but not alter the bacterial flora in a manner leading to antimicrobial resistance or the presence of more virulent organisms. In the current issue of American Journal of Ophthalmology, Hsu and associates report a study of conjunctiva floral cultures and their antimicrobial resistance patterns in patients treated with anti-VEGF intravitreal injections for age-related macular degeneration. In this study, the intravitreal injection procedure included preprocedure application of povidone-iodine but no use of topical antibiotics.4 The authors conclude that the antibiotic susceptibility and growth patterns remain unaltered when using povidone-iodine prophylaxis alone (without topical antibiotics) for repeated monthly intravitreal injections. However, the study is limited by a small sample size, relatively short follow-up, and lack of a control group.4 Povidone-iodine, an iodophor containing a loose combination of iodine with a nonionic surfactant in which some of the iodine may be available in its molecular form, is a potent antiseptic with a wide spectrum of activity against both gram-positive and gram-negative bacteria, fungi, and viruses.5 Preoperative antisepsis with povidoneiodine has been reported to reduce bacterial colony counts on the ocular surface.6 Allergies to seafood as well as See accompanying article on page 514. Accepted for publication Dec 3, 2013. From Penn State Hershey Eye Center (Y.A., I.U.S.) and Department of Public Health Sciences (I.U.S.), Penn State College of Medicine, Hershey, Pennsylvania; L.V. Prasad Eye Institute, Varalakshmi Campus, Visakhapatnam, Andhra Pradesh, India (A.P., A.B.); and Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida (H.W.F.). Inquiries to Ingrid U. Scott, Penn State Hershey Eye Center, 500 University Dr, HU19, Hershey, PA 17036; e-mail: [email protected]. edu 0002-9394/$36.00 http://dx.doi.org/10.1016/j.ajo.2013.12.001
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2014 BY
iodinated contrast media are not contraindications to povidone-iodine.7 There is general consensus to use povidone-iodine as prophylaxis for endophthalmitis, but variations exist in practice patterns and recommendations regarding usage of povidone-iodine in preventing postprocedure endophthalmitis. Preoperative preparation of the skin and periocular area is typically performed using 10% povidone-iodine. This preparation minimizes transfer of bacteria from the periocular skin and eyelids into the eye.6,8 A study comparing different concentrations of povidone-iodine for skin preparation found that use of 5% povidone-iodine was associated with an 11-fold greater odds of acute post–cataract surgery endophthalmitis compared with 10% povidone-iodine, when both were combined with conjunctival 5% povidone-iodine instillation.6 Dilute povidone-iodine has a smaller iodine reservoir compared to more concentrated povidone-iodine; therefore, dilute povidone-iodine may become saturated and depleted upon tissue contact. Conversely, 10% povidone-iodine has a greater iodine reservoir and more efficacious antiseptic effect when used for preoperative skin preparation.6 The American Academy of Ophthalmology ‘‘Cataract in the Adult Eye’’ Preferred Practice Patterns Guidelines recommend that topical 5% povidone-iodine drops be instilled into the conjunctival cul de sac preoperatively, whereas the Royal College of Ophthalmology Cataract Surgery Guidelines recommend a flush irrigation of 5% povidone-iodine into the conjunctival sac.8,9 De Kaspar and associates compared the effect of instillation of two 5% povidone-iodine drops vs 10 mL conjunctival irrigation of 5% povidone-iodine, and found that conjunctival irrigation was associated with fewer positive conjunctival cultures.10 It has been hypothesized that irrigation can reach the conjunctival crypts, especially those located in the fornices, which is not possible with topical drops alone.10 Conjunctival exposure to 5% povidone-iodine for a period of 30 seconds achieves a significant reduction in the bacterial colony-forming units and appears to be an adequate contact time before intravitreal injection.11 Topical antibiotic use for prophylaxis of endophthalmitis following intravitreal injection is not the current standard of care owing to emerging antimicrobial resistance and failure to reduce endophthalmitis rates.12,13 Experimental studies have shown that microbial
ELSEVIER INC. ALL
RIGHTS RESERVED.
503
strains that acquired resistance against one antiseptic agent also showed cross-resistance to other antiseptics, such as chlorhexidine gluconate and alkyldiaminoethylglycine hydrochloride, but not to povidone-iodine.14 Furthermore, a study was conducted in the 1970s to determine whether bacterial resistance to povidoneiodine could be induced in vitro using strains of pathogenic bacteria. The study found that even after repeated exposure to povidone-iodine and with 20 serial passages, no significant change was observed in the minimal inhibitory concentration, minimal bactericidal concentration, and killing times between parent strains and
20th subcultures under standardized conditions.15 Considering that iodine-containing antiseptic agents have been in use for more than a century, it is likely that the mechanism of action of povidone-iodine is not associated with the development of antimicrobial resistance. In conclusion, compared to topical antibiotics, prophylaxis with povidone-iodine is the most effective and least expensive method to prevent postprocedure endophthalmitis, and it has not been associated with the development of antimicrobial resistance or the presence of more virulent species of bacteria.
ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST. None of the authors has a financial interest in the subject matter of this manuscript. Dr Scott has served as a consultant for Alcon, Genentech, Sanofi Fovea, Santen, and Thrombogenics and has received lecture fees from Genentech; Dr Flynn has served as a consultant for Santen. The authors indicate no funding support. Contributions of authors: conception and design (Y.A., I.S., A.P., A.B., H.F.), preparation of manuscript (Y.A., I.S., A.P., A.B., H.F.), approval of manuscript (Y.A., I.S., A.P., A.B., H.F.).
REFERENCES 1. Wykoff CC, Parrott MB, Flynn HW Jr, Shi W, Miller D, Alfonso EC. Nosocomial acute-onset postoperative endophthalmitis at a university teaching hospital (2002-2009). Am J Ophthalmol 2010;150(3):392–398. 2. Moshfeghi AA, Rosenfeld PJ, Flynn HW Jr, et al. Endophthalmitis after intravitreal vascular [corrected] endothelial growth factor antagonists: a six-year experience at a university referral center. Retina 2011;31(4):662–668. 3. Speaker MG, Milch FA, Shah MK, Eisner W, Kreiswirth BN. Role of external bacterial flora in the pathogenesis of acute postoperative endophthalmitis. Ophthalmology 1991;98(5): 639–649. 4. Hsu J, Gerstenblith AT, Garg SJ, Vander JF. Conjunctival flora antibiotic resistance patterns after serial intravitreal injections without postinjection topical antibiotics. Am J Ophthalmol 2014;157(3):514–518. 5. Lachapelle JM, Castel O, Casado AF, et al. Antiseptics in the era of bacterial resistance: a focus on povidone iodine. Clin Pract 2013;10(5):579–592. 6. Wu PC, Li M, Chang SJ, et al. Risk of endophthalmitis after cataract surgery using different protocols for povidone- iodine preoperative disinfection. J Ocul Pharmacol Ther 2006;22(1): 54–61. 7. Wykoff CC, Flynn HW Jr, Han DP. Allergy to povidoneiodine and cephalosporins: the clinical dilemma in ophthalmic use. Am J Ophthalmol 2011;151(1):4–6. 8. American Academy of Ophthalmology Cataract and Anterior Segment Panel. Preferred Practice Pattern Guidelines. Cataract in the adult eye. San Francisco, CA: American Academy of Ophthalmology; 2011.
504
9.
10.
11.
12.
13.
14.
15.
Available at: http://one.aao.org/preferred-practice-pattern/ cataract-in-adult-eye-ppp-october-2011. Accessed November 29, 2013. The Royal College of Ophthalmologists Scientific Department. Cataract Surgery Guidelines. London, UK: The Royal College of Ophthalmologists; 2010. Available at: http://www.rcophth.ac.uk/core/core_picker/download. asp?id¼544. Accessed November 29, 2013. De Kaspar MH, Chang RT, Singh K, Egbert PR, Blumenkranz MS, Ta CN. Prospective randomized comparison of 2 different methods of 5% povidone-iodine applications for anterior segment intraocular surgery. Arch Ophthalmol 2005;123(2):161–165. Friedman DA, Mason JO, Emond T, Mcgwin G. Povidoneiodine contact time and lid speculum use during intravitreal injection. Retina 2013;33(5):975–981. Chen RW, Rachitskaya A, Scott IU, Flynn HW Jr. Is the use of topical antibiotics for intravitreal injections the standard of care or are we better off without antibiotics? JAMA Ophthalmol 2013;131(7):840–842. Bhavsar AR, Stockdale CR, Ferris FL III, Brucker AJ, Bressler NM, Glassman AR, for theDiabetic Retinopathy Clinical Research. Update on risk of endophthalmitis after intravitreal drug injections and potential impact of elimination of topical antibiotics. Arch Ophthalmol 2012;130(6): 809–810. Kunisada T, Yamada K, Oda S, Hara O. Investigation on the efficacy of povidone-iodine against antiseptic-resistant species. Dermatology 1997;195(Suppl 2):14–18. Houang ET, Gilmore OJ, Reid C, Shaw EJ. Absence of bacterial resistance to povidone-iodine. J Clin Pathol 1976; 29(8):752–755.
AMERICAN JOURNAL OF OPHTHALMOLOGY
MARCH 2014
E
NDOPHTHALMITIS IS AN UNCOMMON POSTPROCE-
dure complication with a reported incidence of 0.028% after cataract surgery, 0.011% after pars plana vitrectomy, and 0.108% after penetrating keratoplasty.1 The reported rate of endophthalmitis after intravitreal injection of anti–vascular endothelial growth factor (anti-VEGF) agents is 0.02%.2 Although endophthalmitis is an infrequent complication, it often portends a very poor visual prognosis.2 The most common sources of ocular pathogen contamination include the conjunctiva and eyelids.3 The goal of preprocedure antisepsis is to reduce the ocular surface pathogen load but not alter the bacterial flora in a manner leading to antimicrobial resistance or the presence of more virulent organisms. In the current issue of American Journal of Ophthalmology, Hsu and associates report a study of conjunctiva floral cultures and their antimicrobial resistance patterns in patients treated with anti-VEGF intravitreal injections for age-related macular degeneration. In this study, the intravitreal injection procedure included preprocedure application of povidone-iodine but no use of topical antibiotics.4 The authors conclude that the antibiotic susceptibility and growth patterns remain unaltered when using povidone-iodine prophylaxis alone (without topical antibiotics) for repeated monthly intravitreal injections. However, the study is limited by a small sample size, relatively short follow-up, and lack of a control group.4 Povidone-iodine, an iodophor containing a loose combination of iodine with a nonionic surfactant in which some of the iodine may be available in its molecular form, is a potent antiseptic with a wide spectrum of activity against both gram-positive and gram-negative bacteria, fungi, and viruses.5 Preoperative antisepsis with povidoneiodine has been reported to reduce bacterial colony counts on the ocular surface.6 Allergies to seafood as well as See accompanying article on page 514. Accepted for publication Dec 3, 2013. From Penn State Hershey Eye Center (Y.A., I.U.S.) and Department of Public Health Sciences (I.U.S.), Penn State College of Medicine, Hershey, Pennsylvania; L.V. Prasad Eye Institute, Varalakshmi Campus, Visakhapatnam, Andhra Pradesh, India (A.P., A.B.); and Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida (H.W.F.). Inquiries to Ingrid U. Scott, Penn State Hershey Eye Center, 500 University Dr, HU19, Hershey, PA 17036; e-mail: [email protected]. edu 0002-9394/$36.00 http://dx.doi.org/10.1016/j.ajo.2013.12.001
Ó
2014 BY
iodinated contrast media are not contraindications to povidone-iodine.7 There is general consensus to use povidone-iodine as prophylaxis for endophthalmitis, but variations exist in practice patterns and recommendations regarding usage of povidone-iodine in preventing postprocedure endophthalmitis. Preoperative preparation of the skin and periocular area is typically performed using 10% povidone-iodine. This preparation minimizes transfer of bacteria from the periocular skin and eyelids into the eye.6,8 A study comparing different concentrations of povidone-iodine for skin preparation found that use of 5% povidone-iodine was associated with an 11-fold greater odds of acute post–cataract surgery endophthalmitis compared with 10% povidone-iodine, when both were combined with conjunctival 5% povidone-iodine instillation.6 Dilute povidone-iodine has a smaller iodine reservoir compared to more concentrated povidone-iodine; therefore, dilute povidone-iodine may become saturated and depleted upon tissue contact. Conversely, 10% povidone-iodine has a greater iodine reservoir and more efficacious antiseptic effect when used for preoperative skin preparation.6 The American Academy of Ophthalmology ‘‘Cataract in the Adult Eye’’ Preferred Practice Patterns Guidelines recommend that topical 5% povidone-iodine drops be instilled into the conjunctival cul de sac preoperatively, whereas the Royal College of Ophthalmology Cataract Surgery Guidelines recommend a flush irrigation of 5% povidone-iodine into the conjunctival sac.8,9 De Kaspar and associates compared the effect of instillation of two 5% povidone-iodine drops vs 10 mL conjunctival irrigation of 5% povidone-iodine, and found that conjunctival irrigation was associated with fewer positive conjunctival cultures.10 It has been hypothesized that irrigation can reach the conjunctival crypts, especially those located in the fornices, which is not possible with topical drops alone.10 Conjunctival exposure to 5% povidone-iodine for a period of 30 seconds achieves a significant reduction in the bacterial colony-forming units and appears to be an adequate contact time before intravitreal injection.11 Topical antibiotic use for prophylaxis of endophthalmitis following intravitreal injection is not the current standard of care owing to emerging antimicrobial resistance and failure to reduce endophthalmitis rates.12,13 Experimental studies have shown that microbial
ELSEVIER INC. ALL
RIGHTS RESERVED.
503
strains that acquired resistance against one antiseptic agent also showed cross-resistance to other antiseptics, such as chlorhexidine gluconate and alkyldiaminoethylglycine hydrochloride, but not to povidone-iodine.14 Furthermore, a study was conducted in the 1970s to determine whether bacterial resistance to povidoneiodine could be induced in vitro using strains of pathogenic bacteria. The study found that even after repeated exposure to povidone-iodine and with 20 serial passages, no significant change was observed in the minimal inhibitory concentration, minimal bactericidal concentration, and killing times between parent strains and
20th subcultures under standardized conditions.15 Considering that iodine-containing antiseptic agents have been in use for more than a century, it is likely that the mechanism of action of povidone-iodine is not associated with the development of antimicrobial resistance. In conclusion, compared to topical antibiotics, prophylaxis with povidone-iodine is the most effective and least expensive method to prevent postprocedure endophthalmitis, and it has not been associated with the development of antimicrobial resistance or the presence of more virulent species of bacteria.
ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST. None of the authors has a financial interest in the subject matter of this manuscript. Dr Scott has served as a consultant for Alcon, Genentech, Sanofi Fovea, Santen, and Thrombogenics and has received lecture fees from Genentech; Dr Flynn has served as a consultant for Santen. The authors indicate no funding support. Contributions of authors: conception and design (Y.A., I.S., A.P., A.B., H.F.), preparation of manuscript (Y.A., I.S., A.P., A.B., H.F.), approval of manuscript (Y.A., I.S., A.P., A.B., H.F.).
REFERENCES 1. Wykoff CC, Parrott MB, Flynn HW Jr, Shi W, Miller D, Alfonso EC. Nosocomial acute-onset postoperative endophthalmitis at a university teaching hospital (2002-2009). Am J Ophthalmol 2010;150(3):392–398. 2. Moshfeghi AA, Rosenfeld PJ, Flynn HW Jr, et al. Endophthalmitis after intravitreal vascular [corrected] endothelial growth factor antagonists: a six-year experience at a university referral center. Retina 2011;31(4):662–668. 3. Speaker MG, Milch FA, Shah MK, Eisner W, Kreiswirth BN. Role of external bacterial flora in the pathogenesis of acute postoperative endophthalmitis. Ophthalmology 1991;98(5): 639–649. 4. Hsu J, Gerstenblith AT, Garg SJ, Vander JF. Conjunctival flora antibiotic resistance patterns after serial intravitreal injections without postinjection topical antibiotics. Am J Ophthalmol 2014;157(3):514–518. 5. Lachapelle JM, Castel O, Casado AF, et al. Antiseptics in the era of bacterial resistance: a focus on povidone iodine. Clin Pract 2013;10(5):579–592. 6. Wu PC, Li M, Chang SJ, et al. Risk of endophthalmitis after cataract surgery using different protocols for povidone- iodine preoperative disinfection. J Ocul Pharmacol Ther 2006;22(1): 54–61. 7. Wykoff CC, Flynn HW Jr, Han DP. Allergy to povidoneiodine and cephalosporins: the clinical dilemma in ophthalmic use. Am J Ophthalmol 2011;151(1):4–6. 8. American Academy of Ophthalmology Cataract and Anterior Segment Panel. Preferred Practice Pattern Guidelines. Cataract in the adult eye. San Francisco, CA: American Academy of Ophthalmology; 2011.
504
9.
10.
11.
12.
13.
14.
15.
Available at: http://one.aao.org/preferred-practice-pattern/ cataract-in-adult-eye-ppp-october-2011. Accessed November 29, 2013. The Royal College of Ophthalmologists Scientific Department. Cataract Surgery Guidelines. London, UK: The Royal College of Ophthalmologists; 2010. Available at: http://www.rcophth.ac.uk/core/core_picker/download. asp?id¼544. Accessed November 29, 2013. De Kaspar MH, Chang RT, Singh K, Egbert PR, Blumenkranz MS, Ta CN. Prospective randomized comparison of 2 different methods of 5% povidone-iodine applications for anterior segment intraocular surgery. Arch Ophthalmol 2005;123(2):161–165. Friedman DA, Mason JO, Emond T, Mcgwin G. Povidoneiodine contact time and lid speculum use during intravitreal injection. Retina 2013;33(5):975–981. Chen RW, Rachitskaya A, Scott IU, Flynn HW Jr. Is the use of topical antibiotics for intravitreal injections the standard of care or are we better off without antibiotics? JAMA Ophthalmol 2013;131(7):840–842. Bhavsar AR, Stockdale CR, Ferris FL III, Brucker AJ, Bressler NM, Glassman AR, for theDiabetic Retinopathy Clinical Research. Update on risk of endophthalmitis after intravitreal drug injections and potential impact of elimination of topical antibiotics. Arch Ophthalmol 2012;130(6): 809–810. Kunisada T, Yamada K, Oda S, Hara O. Investigation on the efficacy of povidone-iodine against antiseptic-resistant species. Dermatology 1997;195(Suppl 2):14–18. Houang ET, Gilmore OJ, Reid C, Shaw EJ. Absence of bacterial resistance to povidone-iodine. J Clin Pathol 1976; 29(8):752–755.
AMERICAN JOURNAL OF OPHTHALMOLOGY
MARCH 2014
