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Safety first
FROM THE EDITOR
Safety first Be wary then; best safety lies in fear. William Shakespeare, Hamlet Sight-threatening complications of lens surgery are the surgeon’s and patient’s worst fear. In terms of informed consent, it is appropriate that patients are made aware of serious risks, however unlikely. Quantification of the risk has to be evidence based. The literature reveals a statistical risk for postoperative endophthalmitis (POE) ranging from 0.03% to 0.06%; ie, 1 in 3333 eyes to 1 in 1666 eyes.1 In the recent European Society of Cataract & Refractive Surgeons’ (ESCRS) study of POE after cataract and intraocular lens (IOL) surgery,2 the rate varied from a best figure of 1 in 1400 eyes after instillation of an intracameral antibiotic agent (cefuroxime) to 1 in 300 eyes with no intracameral preoperative prophylaxis,3 a seemingly compelling case for intracameral prophylaxis. The Swedish experience4 reports POE rates between 0.06% and 0.26%; ie, 1 in 1666 eyes and 1 in 384 eyes. The recent survey of members of ESCRS and of the American Society of Cataract and Refractive Surgery (pages 1801–1805) indicates that about 30% of Europeans use an intracameral antibiotic agent and a further 30% add an antibiotic agent to the irrigating solution. In contrast, only 12% of U.S. surgeons use an intracameral antibiotic agent, but similar to the Europeans, 30% include an antibiotic agent in the irrigating solution. There is a protocol for preventing infection in IOLrelated surgery that varies according to local patterns of application and is sometimes governed by economic issues. The following are the elements in prophylaxis during preoperative, perioperative, and postoperative IOL surgery. Preoperative Regimens Povidone–iodine antisepsis Dousing the eyelashes and conjunctival fornices for 5 minutes before surgery will destroy harmful pathogens that may linger to compromise the surgical procedure. The most common pathogen, Staphylococcus epidermidis, frequently resides in eyelashes. Povidone–iodine 10% rather than 5% appears to be more effective than chlorhexidine for skin and conjunctival sterilization. Rongrungruang et al.5 studied bacteria from the eyelids and conjunctival sacs of patients having cataract surgery before and after the application of chlorhexidine 4% and then after the application of povidone–iodine 10% and at the end of surgery. Cultures for bacteria and Candida were positive in 90.2% and 82.4% of specimens before and after cleaning the face with chlorhexidine 4%. Topical application of povidone–iodine 10% Q 2007 ASCRS and ESCRS Published by Elsevier Inc.
did not achieve total eradication of potential pathogens, but positive cultures were reduced to 19.6%. Isolates included skin flora and Candida species. This indicates the need for additional prophylaxis. Wu et al.6 also demonstrated that skin preparation with povidone–iodine 5% was associated with an increased risk for postoperative infection compared with the risk when povidone–iodine 10% was used. Surgical hygiene Sequestering eyelashes and eyelid margins is a vital step in removing the potential source of operating zone contamination by harmful pathogens. Too often, as seen in live surgery sessions, eyelids and eyelashes are poorly enclosed by the surgical drape, yielding an insight into some surgical techniques. This reminds us that this aspect of surgical hygiene requires meticulous application. For example, Propionibacterium acnes, a commonly found organism on the skin and at the openings of sebaceous glands and on eyelashes, is a causative agent of POE. It is gram-positive, immotile, and non-spore-forming and thrives anaerobically or where the oxygen concentration is low. Typically, POE occurs when Propionibacterium species are enclosed in the capsular bag.7 Prophylactic topical antibiotic agents Many surgeons use topical antibiotic agents, specifically fluoroquinolones, prophylactically for 3 days before surgery, 4 times each day. Levofloxacin is the S-isomer of ofloxacin and a fluoroquinolone antibiotic that inhibits bacterial DNA synthesis. It has a half life of 8 hours, is lipophilic, and penetrates the eye accordingly.8 Levofloxacin is the most soluble of the currently used fluoroquinolones, which accounts for its widespread use (both preoperatively and postoperatively). Oral administration of 400 mgm per day achieves aqueous and vitreous penetration that is high enough to be effective against most ocular pathogens. Topical applications achieve satisfactory aqueous concentrations, while combined topical and oral medication have an additive effect on intraocular potent concentrations.9 This suggests that maximum prophylactic effect is dictated by a combination of oral and topical applications. However, in a prospective randomized parallel double-masked clinical trial, Kim et al.10 demonstrated that after topically administered perioperative antibiotic agents in cataract surgery, moxifloxacin 0.5% ophthalmic solution achieved a statistically significantly higher concentration in the aqueous humor (P Z .00003) than gatifloxacin (both fourth-generation fluoroquinolones) and was biologically more active against S epidermidis than gatifloxacin 0.3% in aqueous humor after topical application. O’Brien et al. (pages 1790–1800) go further 0886-3350/07/$dsee front matter doi:10.1016/j.jcrs.2007.08.014
1669
1670
FROM THE EDITOR
and advocate moxifloxacin as a preferential intracameral solution.
that suggests the biomaterial does not pose an extra risk.13 Postoperative Regimens
Perioperative Regimens Swift, uncomplicated closed-eye surgery Surgical trauma, which is by definition the nature of a surgical procedure, is minimized by swift and uncomplicated closed-eye surgery. The corollary of a prolonged procedure and additional trauma such as capsule rupture increases the prospect of postoperative inflammation, the precursor companion of an intraocular infection.3 Surgical incisions Do clear corneal incisions increase the risk for postoperative endophthalmitis? Not only the main incision, in a coaxial approach, but also the companion paracenteses and/or the twin incisions of a bimanual approach? If these are ports of access for potential pathogens, it emphasizes the importance of sterilizing the ocular surface at the outset and maintaining that sterility by early instillation of topical antibiotics. Wound architecture may be important in resisting the postoperative influx of material from the ocular surface.11 In the presence of complicated surgery, such as a ruptured posterior capsule, clear corneal incisions may put extra strain on their security so a temporary safety suture may be prudent. This is emphasized in the ESCRS study outcome, which suggests a 7.43-fold increase in proven POE with clear corneal incisions compared with scleral tunnel incisions. Intracameral antibiotics? The ESCRS endophthalmitis study demonstrated overwhelmingly that intracameral cefuroxime (a second-generation cephalosporin, inhibitor of bacterial cell wall synthesis) dramatically reduced the rate of infection. Alternative antibiotic agents that are used routinely in some centers include vancomycin (inhibitor of bacterial cell wall synthesis) and moxifloxacin (inhibitor of nucleic acid function or synthesis). O’Brien et al. (pages 1790–1800) offer evidence that moxifloxacin is as effective as cefuroxime as an intracameral agent because of its potent and rapid bactericidal activity and its ability to combat the cefuroxime-resistant gram-positive bacteria. It is also available in a state ready for intraocular use, whereas cefuroxime requires local preparation. Detractors of intracameral antibiotic prophylaxis express concern about the toxic effects of intraocular antibiotic solutions on macular function in the presence of a complicated lens extraction.12 Intraocular lens biomaterials The ESCRS study outcome suggests a 3.13-fold increase in proven POE with the use of silicone IOLs compared with the use of acrylic IOLs, but this is offset by other experience
Postoperative antiinflammatory agents Topical dexamethasone is used almost routinely by all lens surgeons to combat the postsurgical inflammation induced by a surgical intervention. Inflammation may encourage bacterial growth and therefore increase POE risks. Subconjunctival postoperative antibiotic injection Buzard et al. reported14 a prospective institutional study of cataract surgery with IOL implantation performed between 1998 and 2002 by 1 surgeon. The surgeon used a blue-line incision at the superior location, povidone– iodine prophylaxis, and postoperative injection of subconjunctival antibiotic agents. The authors reported 5131 cases that were followed for a mean of 2 years (range 3 months to 4 years). No case of endophthalmitis occurred. The absence of POE was attributed to 4 factors: povidone–iodine prophylaxis, meticulous draping of the eyes, operative technique (blue-line incision), and postoperative injection of subconjunctival antibiotic agents. Subconjunctival cefuroxime in conjunction with a depot steroid is in common use in Europe, but only 13% of U.S. surgeons seem to add this element of prophylaxis (pages 1801–1805). Postoperative antibiotic agents Fourth-generation fluoroquinolones applied topically for several days postoperatively to treat residual microbes inadvertently inoculated during the procedure and also to maintain a clean conjunctival sac and guard against wound ingress is common practice. Emanuel S. Rosen, FRCSE REFERENCES 1. Taban M, Behrens A, Newcombe RL, et al. Acute endophthalmitis following cataract surgery; a systematic review of the literature. Arch Ophthalmol 2005; 123:613–620 2. Seal DV, Barry P, Gettinby G, et al. ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery; case for a European multicenter study; the ESCRS Endophthalmitis Study Group. J Cataract Refract Surg 2006; 32: 390–406 3. Barry P, Seal DV, Gettinby G, et al. ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery; preliminary report of principal results from a European multicenter study; the ESCRS Endophthalmitis Study Group. J Cataract Refract Surg 2006; 32:407–410 4. Wejde G, Montan P, Lundstro¨m M, et al. Endophthalmitis following cataract surgery in Sweden: national prospective survey 1999-2001. Acta Ophthalmol Scand 2005; 83:7–10 5. Rongrungruang Y, Tantaterdthum J, Tuntiwattanapibul Y, et al. Bacterial flora - a potential source of endophthalmitis after cataract surgery. J Med Assoc Thai 2005; 88(suppl 10):S49–S53; Available at: http://www.medassocthai.org/journal/files/Vol88_ No10_49.pdf; Accessed August 7, 2007
J CATARACT REFRACT SURG - VOL 33, OCTOBER 2007
FROM THE EDITOR
6. Wu P-C, Li M, Chang S-J, et al. Risk of endophthalmitis after cataract surgery using different protocols for povidone–iodine preoperative disinfection. J Ocul Pharmacol Ther 2006; 22:54–61 7. Binder CA, Min˜o de Kaspar H, Engelbert M, et al. Bakterielle Keimbesiedelung der Konjunktiva mit Propionibacterium acnes vor und nach Polyvidon-Jod-Applikation vor intraokula¨ren Eingriffen. [Colonization of the conjunctiva with Propionibacterium acnes before and after application of povidone iodine before intraocular surgery.]. Ophthalmologe 1998; 95:438–441 8. Ernst ME, Ernst EJ, Klepser ME. Levofloxacin and trovafloxacin: the next generation of fluoroquinolones? Am J Health Syst Pharm 1997; 54:2569–2584 9. Sakamoto H, Sakamoto M, Hata Y, et al. Aqueous and vitreous penetration of levofloxacin after topical and/or oral administration. Eur J Ophthalmol 2007; 17:372–376
1671
10. Kim DH, Stark WJ, O’Brien TP, Dick JD. Aqueous penetration and biological activity of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution in cataract surgery patients. Ophthalmology 2005; 112:1992–1996 11. Fine IH, Hoffman RS, Packer M. Profile of clear corneal cataract incisions demonstrated by ocular coherence tomography. J Cataract Refract Surg 2007; 33:94–97 12. Gupta MS, McKee HDR, Saldan˜a M, Stewart OG. Macular thickness after cataract surgery with intracameral cefuroxime. J Cataract Refract Surg 2005; 31:1163–1166 13. 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; 29:20–26 14. Buzard K, Liapis S. Prevention of endophthalmitis. J Cataract Refract Surg 2004; 30:1953–1959
J CATARACT REFRACT SURG - VOL 33, OCTOBER 2007
Safety first Be wary then; best safety lies in fear. William Shakespeare, Hamlet Sight-threatening complications of lens surgery are the surgeon’s and patient’s worst fear. In terms of informed consent, it is appropriate that patients are made aware of serious risks, however unlikely. Quantification of the risk has to be evidence based. The literature reveals a statistical risk for postoperative endophthalmitis (POE) ranging from 0.03% to 0.06%; ie, 1 in 3333 eyes to 1 in 1666 eyes.1 In the recent European Society of Cataract & Refractive Surgeons’ (ESCRS) study of POE after cataract and intraocular lens (IOL) surgery,2 the rate varied from a best figure of 1 in 1400 eyes after instillation of an intracameral antibiotic agent (cefuroxime) to 1 in 300 eyes with no intracameral preoperative prophylaxis,3 a seemingly compelling case for intracameral prophylaxis. The Swedish experience4 reports POE rates between 0.06% and 0.26%; ie, 1 in 1666 eyes and 1 in 384 eyes. The recent survey of members of ESCRS and of the American Society of Cataract and Refractive Surgery (pages 1801–1805) indicates that about 30% of Europeans use an intracameral antibiotic agent and a further 30% add an antibiotic agent to the irrigating solution. In contrast, only 12% of U.S. surgeons use an intracameral antibiotic agent, but similar to the Europeans, 30% include an antibiotic agent in the irrigating solution. There is a protocol for preventing infection in IOLrelated surgery that varies according to local patterns of application and is sometimes governed by economic issues. The following are the elements in prophylaxis during preoperative, perioperative, and postoperative IOL surgery. Preoperative Regimens Povidone–iodine antisepsis Dousing the eyelashes and conjunctival fornices for 5 minutes before surgery will destroy harmful pathogens that may linger to compromise the surgical procedure. The most common pathogen, Staphylococcus epidermidis, frequently resides in eyelashes. Povidone–iodine 10% rather than 5% appears to be more effective than chlorhexidine for skin and conjunctival sterilization. Rongrungruang et al.5 studied bacteria from the eyelids and conjunctival sacs of patients having cataract surgery before and after the application of chlorhexidine 4% and then after the application of povidone–iodine 10% and at the end of surgery. Cultures for bacteria and Candida were positive in 90.2% and 82.4% of specimens before and after cleaning the face with chlorhexidine 4%. Topical application of povidone–iodine 10% Q 2007 ASCRS and ESCRS Published by Elsevier Inc.
did not achieve total eradication of potential pathogens, but positive cultures were reduced to 19.6%. Isolates included skin flora and Candida species. This indicates the need for additional prophylaxis. Wu et al.6 also demonstrated that skin preparation with povidone–iodine 5% was associated with an increased risk for postoperative infection compared with the risk when povidone–iodine 10% was used. Surgical hygiene Sequestering eyelashes and eyelid margins is a vital step in removing the potential source of operating zone contamination by harmful pathogens. Too often, as seen in live surgery sessions, eyelids and eyelashes are poorly enclosed by the surgical drape, yielding an insight into some surgical techniques. This reminds us that this aspect of surgical hygiene requires meticulous application. For example, Propionibacterium acnes, a commonly found organism on the skin and at the openings of sebaceous glands and on eyelashes, is a causative agent of POE. It is gram-positive, immotile, and non-spore-forming and thrives anaerobically or where the oxygen concentration is low. Typically, POE occurs when Propionibacterium species are enclosed in the capsular bag.7 Prophylactic topical antibiotic agents Many surgeons use topical antibiotic agents, specifically fluoroquinolones, prophylactically for 3 days before surgery, 4 times each day. Levofloxacin is the S-isomer of ofloxacin and a fluoroquinolone antibiotic that inhibits bacterial DNA synthesis. It has a half life of 8 hours, is lipophilic, and penetrates the eye accordingly.8 Levofloxacin is the most soluble of the currently used fluoroquinolones, which accounts for its widespread use (both preoperatively and postoperatively). Oral administration of 400 mgm per day achieves aqueous and vitreous penetration that is high enough to be effective against most ocular pathogens. Topical applications achieve satisfactory aqueous concentrations, while combined topical and oral medication have an additive effect on intraocular potent concentrations.9 This suggests that maximum prophylactic effect is dictated by a combination of oral and topical applications. However, in a prospective randomized parallel double-masked clinical trial, Kim et al.10 demonstrated that after topically administered perioperative antibiotic agents in cataract surgery, moxifloxacin 0.5% ophthalmic solution achieved a statistically significantly higher concentration in the aqueous humor (P Z .00003) than gatifloxacin (both fourth-generation fluoroquinolones) and was biologically more active against S epidermidis than gatifloxacin 0.3% in aqueous humor after topical application. O’Brien et al. (pages 1790–1800) go further 0886-3350/07/$dsee front matter doi:10.1016/j.jcrs.2007.08.014
1669
1670
FROM THE EDITOR
and advocate moxifloxacin as a preferential intracameral solution.
that suggests the biomaterial does not pose an extra risk.13 Postoperative Regimens
Perioperative Regimens Swift, uncomplicated closed-eye surgery Surgical trauma, which is by definition the nature of a surgical procedure, is minimized by swift and uncomplicated closed-eye surgery. The corollary of a prolonged procedure and additional trauma such as capsule rupture increases the prospect of postoperative inflammation, the precursor companion of an intraocular infection.3 Surgical incisions Do clear corneal incisions increase the risk for postoperative endophthalmitis? Not only the main incision, in a coaxial approach, but also the companion paracenteses and/or the twin incisions of a bimanual approach? If these are ports of access for potential pathogens, it emphasizes the importance of sterilizing the ocular surface at the outset and maintaining that sterility by early instillation of topical antibiotics. Wound architecture may be important in resisting the postoperative influx of material from the ocular surface.11 In the presence of complicated surgery, such as a ruptured posterior capsule, clear corneal incisions may put extra strain on their security so a temporary safety suture may be prudent. This is emphasized in the ESCRS study outcome, which suggests a 7.43-fold increase in proven POE with clear corneal incisions compared with scleral tunnel incisions. Intracameral antibiotics? The ESCRS endophthalmitis study demonstrated overwhelmingly that intracameral cefuroxime (a second-generation cephalosporin, inhibitor of bacterial cell wall synthesis) dramatically reduced the rate of infection. Alternative antibiotic agents that are used routinely in some centers include vancomycin (inhibitor of bacterial cell wall synthesis) and moxifloxacin (inhibitor of nucleic acid function or synthesis). O’Brien et al. (pages 1790–1800) offer evidence that moxifloxacin is as effective as cefuroxime as an intracameral agent because of its potent and rapid bactericidal activity and its ability to combat the cefuroxime-resistant gram-positive bacteria. It is also available in a state ready for intraocular use, whereas cefuroxime requires local preparation. Detractors of intracameral antibiotic prophylaxis express concern about the toxic effects of intraocular antibiotic solutions on macular function in the presence of a complicated lens extraction.12 Intraocular lens biomaterials The ESCRS study outcome suggests a 3.13-fold increase in proven POE with the use of silicone IOLs compared with the use of acrylic IOLs, but this is offset by other experience
Postoperative antiinflammatory agents Topical dexamethasone is used almost routinely by all lens surgeons to combat the postsurgical inflammation induced by a surgical intervention. Inflammation may encourage bacterial growth and therefore increase POE risks. Subconjunctival postoperative antibiotic injection Buzard et al. reported14 a prospective institutional study of cataract surgery with IOL implantation performed between 1998 and 2002 by 1 surgeon. The surgeon used a blue-line incision at the superior location, povidone– iodine prophylaxis, and postoperative injection of subconjunctival antibiotic agents. The authors reported 5131 cases that were followed for a mean of 2 years (range 3 months to 4 years). No case of endophthalmitis occurred. The absence of POE was attributed to 4 factors: povidone–iodine prophylaxis, meticulous draping of the eyes, operative technique (blue-line incision), and postoperative injection of subconjunctival antibiotic agents. Subconjunctival cefuroxime in conjunction with a depot steroid is in common use in Europe, but only 13% of U.S. surgeons seem to add this element of prophylaxis (pages 1801–1805). Postoperative antibiotic agents Fourth-generation fluoroquinolones applied topically for several days postoperatively to treat residual microbes inadvertently inoculated during the procedure and also to maintain a clean conjunctival sac and guard against wound ingress is common practice. Emanuel S. Rosen, FRCSE REFERENCES 1. Taban M, Behrens A, Newcombe RL, et al. Acute endophthalmitis following cataract surgery; a systematic review of the literature. Arch Ophthalmol 2005; 123:613–620 2. Seal DV, Barry P, Gettinby G, et al. ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery; case for a European multicenter study; the ESCRS Endophthalmitis Study Group. J Cataract Refract Surg 2006; 32: 390–406 3. Barry P, Seal DV, Gettinby G, et al. ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery; preliminary report of principal results from a European multicenter study; the ESCRS Endophthalmitis Study Group. J Cataract Refract Surg 2006; 32:407–410 4. Wejde G, Montan P, Lundstro¨m M, et al. Endophthalmitis following cataract surgery in Sweden: national prospective survey 1999-2001. Acta Ophthalmol Scand 2005; 83:7–10 5. Rongrungruang Y, Tantaterdthum J, Tuntiwattanapibul Y, et al. Bacterial flora - a potential source of endophthalmitis after cataract surgery. J Med Assoc Thai 2005; 88(suppl 10):S49–S53; Available at: http://www.medassocthai.org/journal/files/Vol88_ No10_49.pdf; Accessed August 7, 2007
J CATARACT REFRACT SURG - VOL 33, OCTOBER 2007
FROM THE EDITOR
6. Wu P-C, Li M, Chang S-J, et al. Risk of endophthalmitis after cataract surgery using different protocols for povidone–iodine preoperative disinfection. J Ocul Pharmacol Ther 2006; 22:54–61 7. Binder CA, Min˜o de Kaspar H, Engelbert M, et al. Bakterielle Keimbesiedelung der Konjunktiva mit Propionibacterium acnes vor und nach Polyvidon-Jod-Applikation vor intraokula¨ren Eingriffen. [Colonization of the conjunctiva with Propionibacterium acnes before and after application of povidone iodine before intraocular surgery.]. Ophthalmologe 1998; 95:438–441 8. Ernst ME, Ernst EJ, Klepser ME. Levofloxacin and trovafloxacin: the next generation of fluoroquinolones? Am J Health Syst Pharm 1997; 54:2569–2584 9. Sakamoto H, Sakamoto M, Hata Y, et al. Aqueous and vitreous penetration of levofloxacin after topical and/or oral administration. Eur J Ophthalmol 2007; 17:372–376
1671
10. Kim DH, Stark WJ, O’Brien TP, Dick JD. Aqueous penetration and biological activity of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution in cataract surgery patients. Ophthalmology 2005; 112:1992–1996 11. Fine IH, Hoffman RS, Packer M. Profile of clear corneal cataract incisions demonstrated by ocular coherence tomography. J Cataract Refract Surg 2007; 33:94–97 12. Gupta MS, McKee HDR, Saldan˜a M, Stewart OG. Macular thickness after cataract surgery with intracameral cefuroxime. J Cataract Refract Surg 2005; 31:1163–1166 13. 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; 29:20–26 14. Buzard K, Liapis S. Prevention of endophthalmitis. J Cataract Refract Surg 2004; 30:1953–1959
J CATARACT REFRACT SURG - VOL 33, OCTOBER 2007