- Email: [email protected]
ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery
J CATARACT REFRACT SURG - VOL 32, MARCH 2006
ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery Preliminary report of principal results from a European multicenter study Peter Barry, FRCS, David V. Seal, MD, George Gettinby, DPhil, Fiona Lees, MSc, Magnus Peterson, MSc, Crawford W. Revie, MSc, for the ESCRS Endophthalmitis Study Group
PURPOSE: To report results in the European Society of Cataract & Refractive Surgeons (ESCRS) multicenter study of the prophylaxis of endophthalmitis after cataract surgery. SETTING: Twenty-four ophthalmology units and eye clinics in Austria, Belgium, Germany, Italy, Poland, Portugal, Spain, Turkey, and the United Kingdom, with an administrative office in Ireland, coordinating center in England, and data management and statistical unit in Scotland. METHODS: This partially masked randomized placebo-controlled multinational clinical study to evaluate prospectively the prophylactic effect of intracameral cefuroxime injection and/or perioperative levofloxacin eyedrops on the incidence of endophthalmitis after phacoemulsification cataract surgery began in September 2003 and was terminated early in January 2006. The study used random allocation of patients in a 2 2 factorial design. RESULTS: By the end of 2005, complete follow-up records had been received for 13 698 study patients. Such a clear beneficial effect from the use of intracameral cefuroxime had been observed that it was agreed it would be unethical to continue the study and to wait for the completion of all follow-up procedures before reporting this important result. If total reported cases of endophthalmitis are considered, the incidence rate observed in those treatment groups not receiving cefuroxime prophylaxis (23 cases in 6862 patients) was almost 5 times as high (odds ratio [OR], 4.59; 95% confidence interval [CI], 1.74-12.08; P Z .002) as that in the groups receiving this treatment (5 cases in 6836 patients). If only cases proved to be due to infection are considered, the rate was more than 5 times as high (OR, 5.32; 95% CI, 1.55-18.26; P Z .008) in the treatment groups not receiving cefuroxime. Although the use of perioperative levofloxacin eyedrops as prophylaxis was also associated with a reduction in the observed incidence rate of postoperative endophthalmitis, this effect was smaller and was not statistically significant, whether total reported cases or only cases proven to be due to infection are used in calculating the rates. As not all follow-up procedures are complete, it is possible that further cases of endophthalmitis may be reported; however, it is not expected that this will alter the main conclusion. Nevertheless, it is anticipated that successful completion of follow-up procedures in all patients will increase the total number in the study to approximately 16 000. CONCLUSION: Intracameral cefuroxime administered at the time of surgery significantly reduced the risk for developing endophthalmitis after cataract surgery. J Cataract Refract Surg 2006; 32:407–410 Q 2006 ASCRS and ESCRS
The rationale and methodology of a large multinational prospective randomized investigation of 2 possible methods of prophylaxis against endophthalmitis after cataract surgery are fully reported in this issue of the journal.1 Thus, a brief description is given in this short Q 2006 ASCRS and ESCRS Published by Elsevier Inc.
communication, which is intended to outline the principal results that have emerged and led to cessation of patient recruitment in January 2006. A full account will be prepared for later publication when the follow-up procedures are complete and extensive analysis of the data has been done. 0886-3350/06/$-see front matter doi:10.1016/j.jcrs.2006.02.021
407
ESCRS STUDY ON POSTOPERATIVE ENDOPHTHALMITIS
Group A
Group B
No intracameral cefuroxime and no perioperative levofloxacin
Intracameral cefuroxime only
Followed-up number
3438
Total reported endophthalmitis
13
Proven infective endophthalmitis
9
Followed-up number
3408
Total reported endophthalmitis
3
Proven infective endophthalmitis
2
Group C
Group D
Perioperative levofloxacin only
Intracameral cefuroxime and perioperative levofloxacin
Followed-up number
3424
Total reported endophthalmitis Proven infective endophthalmitis
10 7
Followed-up number
Figure 1. Numbers of patients followed up in each treatment group and associated numbers of total reported and proven infective endophthalmitis cases as of January 6, 2006.
3428
Total reported endophthalmitis
2
Proven infective endophthalmitis
1
*All groups received povidone–iodine preoperatively and topical levofloxacin postoperatively for 6 days.
Patients were recruited into the study by clinical partners operating at 24 centers in Europe starting in September 2003. By the end of 2005, approximately 16 000 patients had been recruited to the study, 13 698 of whom had completed follow-up. Exact recruitment figures were not available at the end of 2005 as clinical partners had yet to return details of their December recruitment to the study’s data center. When the quarterly analysis of the figures to date was performed, it became clear that 1 of the regular tests for an early reason to reject the hypothesis of no treatment effect, along with associated analyses, was giving a clear signal of a probable beneficial treatment effect. To allow this analysis to be fully considered, the study chairman called a meeting of the Study Management Team and the Data Monitoring Committee (DMC). During the
Accepted for publication January 20, 2006. From the European Society of Cataract & Refractive Surgeons (Barry, Seal), Dublin, Ireland; and the Department of Statistics and Modelling Science (Gettinby, Lees, Peterson, Revie), University of Strathclyde, Glasgow, United Kingdom. The members of the ESCRS Endophthalmitis Study Group are given in the Appendix. Funded by the European Society of Cataract & Refractive Surgeons, Dublin, Ireland, with support from Santen GmbH, Germering, Germany. No author has a financial or proprietary interest in any material or method mentioned. Reprint requests to Peter Barry, ESCRS, Temple House, Temple Road, Blackrock, County Dublin, Ireland. E-mail: escrs@ agenda-comm.ie.
408
course of this meeting, the DMC recommended that the study be unmasked. When masking was removed, the result was so clear that the DMC advised the study chairman that not only should recruitment be stopped, but it was the duty of those managing the study to publish as soon as practicable the principal result that had emerged as it was likely to be of fundamental importance to all cataract surgeons. This short communication meets that recommendation.
RESULTS
The study was conducted using a 2 2 factorial design. By the time of the meeting held on January 6, 2006, the results obtained in the 4 treatment groups were as summarized in Figure 1. Because follow-up procedures are not yet complete, the statistical analyses that follow must remain subject to adjustment in the unlikely event that further cases of endophthalmitis are reported. All patients were expected to have a complete follow-up record by the end of March 2006. Two statistical analyses were carried out, the first using the total number of reported endophthalmitis cases as the response variable and the other using the proven infective cases that produced a positive Gram stain, microbiology culture, or polymerase chain reaction result from the intraocular sample. The 13 698 patients whose follow-up had been reported up to January 6, 2006, appropriately distributed across the treatment groups, were used as the interim study population. The results of these analyses are summarized in Tables 1A and 1B.
J CATARACT REFRACT SURG - VOL 32, MARCH 2006
ESCRS STUDY ON POSTOPERATIVE ENDOPHTHALMITIS
Table 1A. Results of analysis of total endophthalmitis cases based on patients followed up to January 6, 2006.
Incidence per 10 000 Treatment Group Cefuroxime Levofloxacin
Odds Ratio
Withheld
Administered
Point Estimate
95% CI
P Value
33.52 23.37
7.31 17.51
4.59 1.33
1.74-12.08 0.63-2.82
.002 .454
CI Z confidence interval
Table 1B. Results of analysis of proven infective endophthalmitis cases based on patients followed up to January 6, 2006.
Incidence Per 10 000 Treatment Group Cefuroxime Levofloxacin
Odds Ratio
Withheld
Administered
Point Estimate
95% CI
P Value
23.32 16.07
4.39 11.68
5.32 1.37
1.55-18.26 0.55-3.42
.008 .496
CI Z confidence interval
Under these analyses, it became clear that prophylaxis with cefuroxime was having a significant beneficial effect in reducing the incidence of endophthalmitis, to approximately one fifth the value observed without that prophylaxis. Although there appeared to be some benefit from the use of perioperative levofloxacin, the effect was smaller and not significant under any analysis performed. There was no evidence of a significant interaction between the 2 treatments. Because most patients are expected to provide a complete follow-up record and further cases of endophthalmitis may occur, the number of cases in each group may change; however, in the final analyses, to be reported later, there should be approximately 4000 patients in each treatment group. DISCUSSION
The study found that the risk for contracting endophthalmitis following phacoemulsification cataract surgery was significantly reduced by an intracameral injection of cefuroxime at the end of surgery. The best estimate of the size of this effect is that the use of intracameral cefuroxime reduces the risk to approximately one-fifth the value observed without this prophylaxis when best practice for surgical hygiene is followed. However, it should be noted that this estimate has a wide confidence interval; therefore, it cannot be regarded as precise. Nevertheless, we are confident that intracameral cefuroxime provides positive protection against postoperative endophthalmitis. At the outset of the study, it was anticipated that approximately 32 000 patients would have to be recruited to demonstrate conclusively an effect for either treatment.
To obtain such a clear result after recruiting only half this number of patients was unexpected. Two factors aided the study in this satisfactory outcome. The first was the rate of postoperative endophthalmitis observed in the group receiving neither intracameral cefuroxime nor perioperative levofloxacin (0.38%). This rate is almost twice as high as the estimated background rate of 0.20%, which was used for sample size estimation and was based on an extensive literature search of reported endophthalmitis cases following cataract surgery.2–4 However, with hindsight, this result is not as surprising because many of these were retrospective studies, which are notorious for their tendency to under-report incidence rates. In addition, many used some form of prophylaxis that, while not proven to be effective, may have reduced the incidence of the condition to a greater or lesser extent. The second factor in the study’s favor was the large size of the effect produced by the use of intracameral cefuroxime. The 5-fold reduction in the incidence of endophthalmitis observed is in line with that reported by Montan et al.5,6 in Sweden in their long-running retrospective and prospective, but uncontrolled, study. Similarly, a recent 3-year retrospective uncontrolled study7 involving 9157 cataract surgery patients in Barcelona reports that the incidence of postoperative endophthalmitis decreased from 0.42% to 0.03% with the use of an intracameral injection of cefazolin (2.5 mg in 0.01 mL of Ringer’s lactate solution). The confirmation that the Swedish technique has now received in a large multinational prospective randomized placebo-controlled study should convince surgeons of its value and encourage them to consider its adoption as a standard part of the procedure of modern phacoemulsification cataract surgery.
J CATARACT REFRACT SURG - VOL 32, MARCH 2006
409
ESCRS STUDY ON POSTOPERATIVE ENDOPHTHALMITIS
APPENDIX
Ophthalmology Nurse Managers and Administrative Assistants
The ESCRS Endophthalmitis Study Group
Belgium: Eveline Callens, Gent; Danny Mathysen, Antwerp; Franc¸oise Molemans, Ge´rald de Rassenfosse, and Christel Schenkeveld, Melveren.
Study Management Team Peter Barry (study chairman), Royal Victoria Eye & Ear Hospital and St. Vincent’s University Hospital, Dublin, Ireland; David Seal (study coordinator), Applied Vision Research Centre, City University, London, United Kingdom; George Gettinby, Magnus Peterson, Crawford Revie, and Fiona Lees, Department of Computer and Information Sciences/Department of Statistics and Modelling Science, University of Strathclyde, Glasgow, United Kingdom; Mary Dardis and Betsan Bradley ESCRS, Dublin, Ireland.
Pharmaceutical Associates Klaus Geldsetzer, Santen GmbH, Germering, Germany; David Lloyd, Renaissance Health Care, Surrey, United Kingdom.
Germany: Andrea Eckelmann and Andreas Haselhoff, Ahaus. Poland: Renata Franczuk, Warsaw. Portugal: Liliana Carvalho and Ana Catarina, Coimbra. Spain: Laurent Bataille and Elena Jime´nez, Alicante; Ana Martı´n de Nicola´s, Madrid. Turkey: Hakan Kuheylan, Izmir. United Kingdom: Sue Bovill and Ian Tate, Sunderland; Suzanne Cabral and Tim Withers, London; Deborah Cox and Trudi Yeates, Exeter and Axminster; Jean Dash, Linda Lindsell, and Rebecca Turner, Oxford.
Molecular and Microbiologists Clinical Partner Ophthalmologists Austria: Guenther Grabner, Stefan F. Egger, and Josef Ruckhofer, University Eye Clinic, Paracelsus Private Medical University, Salzburg. Belgium: Johan Blanckaert, Jan Yperman Ziekenhuis, Campus Zwarte Zuster, Ieper; Camille Budo, Oogheelkunde, Melveren; Albert Galand, Jessica Crommen, Jean Rakic, Gae¨l Xhauflaire, Centre Hospitalier Universitaire, Liege; Marie-Jose´ Tassignon, UZA Ophthalmology, Edegem; Hugo Verbraeken and Rita de Donker, Universitair Ziekenhuis, Gent. Germany: Stefanie Schmickler, Augenklinik Ahaus, Ahaus. Italy: Roberto Bellucci, Simonetta Morselli, and Sandro Soldati, Ospedale Borgo Trento, Verona; Fausto Vigasio, Marco Bertelli, Andrea Bottoli, Marta Cassamali, Fabrizio Danieli, Samer Khuri, and Luigina Rosa, Azienda Ospedaliera di Desenzano del Garda, Desenzano del Garda.
Consuelo Ferrer, Instituto Oftalmologico VISSUM, Alicante Spain; Roland Koerner, Sunderland Royal Hospital, Sunderland, United Kingdom; Udo Reischl and Anke Behr, Institute of Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.
Data Monitoring Committee Steven Barrett (chairman), Chelsea & Westminster Hospital, London, United Kingdom; Susanne Gardner, St. Joseph’s Hospital/Research, Atlanta, Georgia, USA; Susan Kennedy, National Ophthalmic Pathology Laboratory, Royal Victoria Eye and Ear Hospital, Dublin, Ireland; John Ludgate, London, United Kingdom; Per Montan, St. Erik’s Hospital, Stockholm, Sweden; Kirk Wilhelmus, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA.
Poland: Jerzy Szaflik and Justyna Izdebska, Kierownik Katedry i Kliniki, Samodzielny Publiczny Kliniczny Szpital Okulistyczny, Warsaw. Portugal: Concieca˜o Lobo, Jose Cunha Vaz, and Joaquin Mira, Department of Ophthalmology, Coimbra.
REFERENCES
Spain: Augusto Abreu, Jose Aguilar, Victor Arteaga, Luis Cordoves, Valentin T. Dı´az-Aleman, Manuel Gonzalez de la Rosa, and Cristina Mantolan, Servicio de Oftalmologia, Hospital Universitario de Canarias, Tenerife; Pedro Abreu, Jorge Alvarez-Marin, and Maria Antonia Gil, La Candelaria University Hospital, Tenerife; Jorge Alio´, Instituto Oftalmologico VISSUM, Alicante; Miguel Teus, M.T. Alvarez, and J.M. Roma´n, Hospital Oftalmologico Internacional, Madrid.
1. Seal DV, Barry P, Gettinby G, et al. ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery: case for European multicenter study. J Cataract Refract Surgery 2006; 32:396–406 2. Ciulla TA, Starr MB, Masket S. Bacterial endophthalmitis prophylaxis for cataract surgery; an evidence-based update. Ophthalmology 2002; 109:13–24 3. West ES, Behrens A, McDonnell PJ, et al. The incidence of endophthalmitis after cataract surgery among the U.S. Medicare population increased between 1994 and 2001. Ophthalmology 2005; 112:1388–1394 4. Taban M, Behrens A, Newcomb RL, et al. Acute endophthalmitis following cataract surgery; a systematic review of the literature. Arch Ophthalmol 2005; 123:613–620 5. Montan PG, Wejde G, Koranyl G, Rylander M. Prophylactic intracameral cefuroxime: efficacy in preventing endophthalmitis after cataract surgery. J Cataract Refract Surg 2002; 28:977–981 6. Montan PG, Wejde G, Setterquist H, et al. Prophylactic intracameral cefuroxime; evaluation of safety and kinetics in cataract surgery. J Cataract Refract Surg 2002; 28:982–987 7. Garat M, Moser CL, Alonso-Tarre´s C, et al. Intracameral cefazolin to prevent endophthalmitis in cataract surgery; 3-year retrospective study [correspondence]. J Cataract Refract Surg 2005; 31:2230–2234
Turkey: Suleyman Kaynak, Retina Ophthalmic Research Centre, Izmir. United Kingdom: David Allen, Peter Phelan, David Steel, and Chris Wood, Sunderland Eye Infirmary, Sunderland; Carol Cunningham, Michael Miller, Ramesh Moorthy, Andleeb Zafar, Moorfields Eye Outreach Unit, Northwick Park Hospital, Harrow; Alex Ionidis, Damian Lake, and Graham Thompson, Moorfields Eye Outreach Unit, St. George’s Hospital, London; John Jacob, Daniel Byles, Casper Gibbon, Andrew Kleinschmidt, Roland Ling, Anthony Quinn, Peter Simcock, and George Sturrock, West of England Eye Unit, Royal Devon & Exeter Hospital (Wonford), Exeter, and Axminster Hospital, Axminster; William Kiel, Ipswich Hospital, Ipswich; Denise Mabey, David Spalton, and Anupma Kumar, Department of Ophthalmology, St. Thomas’ Hospital, London; Paul Rosen, C.K. Patel, and John Salmon, Oxford Eye Hospital, Oxford.
410
J CATARACT REFRACT SURG - VOL 32, MARCH 2006
ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery Preliminary report of principal results from a European multicenter study Peter Barry, FRCS, David V. Seal, MD, George Gettinby, DPhil, Fiona Lees, MSc, Magnus Peterson, MSc, Crawford W. Revie, MSc, for the ESCRS Endophthalmitis Study Group
PURPOSE: To report results in the European Society of Cataract & Refractive Surgeons (ESCRS) multicenter study of the prophylaxis of endophthalmitis after cataract surgery. SETTING: Twenty-four ophthalmology units and eye clinics in Austria, Belgium, Germany, Italy, Poland, Portugal, Spain, Turkey, and the United Kingdom, with an administrative office in Ireland, coordinating center in England, and data management and statistical unit in Scotland. METHODS: This partially masked randomized placebo-controlled multinational clinical study to evaluate prospectively the prophylactic effect of intracameral cefuroxime injection and/or perioperative levofloxacin eyedrops on the incidence of endophthalmitis after phacoemulsification cataract surgery began in September 2003 and was terminated early in January 2006. The study used random allocation of patients in a 2 2 factorial design. RESULTS: By the end of 2005, complete follow-up records had been received for 13 698 study patients. Such a clear beneficial effect from the use of intracameral cefuroxime had been observed that it was agreed it would be unethical to continue the study and to wait for the completion of all follow-up procedures before reporting this important result. If total reported cases of endophthalmitis are considered, the incidence rate observed in those treatment groups not receiving cefuroxime prophylaxis (23 cases in 6862 patients) was almost 5 times as high (odds ratio [OR], 4.59; 95% confidence interval [CI], 1.74-12.08; P Z .002) as that in the groups receiving this treatment (5 cases in 6836 patients). If only cases proved to be due to infection are considered, the rate was more than 5 times as high (OR, 5.32; 95% CI, 1.55-18.26; P Z .008) in the treatment groups not receiving cefuroxime. Although the use of perioperative levofloxacin eyedrops as prophylaxis was also associated with a reduction in the observed incidence rate of postoperative endophthalmitis, this effect was smaller and was not statistically significant, whether total reported cases or only cases proven to be due to infection are used in calculating the rates. As not all follow-up procedures are complete, it is possible that further cases of endophthalmitis may be reported; however, it is not expected that this will alter the main conclusion. Nevertheless, it is anticipated that successful completion of follow-up procedures in all patients will increase the total number in the study to approximately 16 000. CONCLUSION: Intracameral cefuroxime administered at the time of surgery significantly reduced the risk for developing endophthalmitis after cataract surgery. J Cataract Refract Surg 2006; 32:407–410 Q 2006 ASCRS and ESCRS
The rationale and methodology of a large multinational prospective randomized investigation of 2 possible methods of prophylaxis against endophthalmitis after cataract surgery are fully reported in this issue of the journal.1 Thus, a brief description is given in this short Q 2006 ASCRS and ESCRS Published by Elsevier Inc.
communication, which is intended to outline the principal results that have emerged and led to cessation of patient recruitment in January 2006. A full account will be prepared for later publication when the follow-up procedures are complete and extensive analysis of the data has been done. 0886-3350/06/$-see front matter doi:10.1016/j.jcrs.2006.02.021
407
ESCRS STUDY ON POSTOPERATIVE ENDOPHTHALMITIS
Group A
Group B
No intracameral cefuroxime and no perioperative levofloxacin
Intracameral cefuroxime only
Followed-up number
3438
Total reported endophthalmitis
13
Proven infective endophthalmitis
9
Followed-up number
3408
Total reported endophthalmitis
3
Proven infective endophthalmitis
2
Group C
Group D
Perioperative levofloxacin only
Intracameral cefuroxime and perioperative levofloxacin
Followed-up number
3424
Total reported endophthalmitis Proven infective endophthalmitis
10 7
Followed-up number
Figure 1. Numbers of patients followed up in each treatment group and associated numbers of total reported and proven infective endophthalmitis cases as of January 6, 2006.
3428
Total reported endophthalmitis
2
Proven infective endophthalmitis
1
*All groups received povidone–iodine preoperatively and topical levofloxacin postoperatively for 6 days.
Patients were recruited into the study by clinical partners operating at 24 centers in Europe starting in September 2003. By the end of 2005, approximately 16 000 patients had been recruited to the study, 13 698 of whom had completed follow-up. Exact recruitment figures were not available at the end of 2005 as clinical partners had yet to return details of their December recruitment to the study’s data center. When the quarterly analysis of the figures to date was performed, it became clear that 1 of the regular tests for an early reason to reject the hypothesis of no treatment effect, along with associated analyses, was giving a clear signal of a probable beneficial treatment effect. To allow this analysis to be fully considered, the study chairman called a meeting of the Study Management Team and the Data Monitoring Committee (DMC). During the
Accepted for publication January 20, 2006. From the European Society of Cataract & Refractive Surgeons (Barry, Seal), Dublin, Ireland; and the Department of Statistics and Modelling Science (Gettinby, Lees, Peterson, Revie), University of Strathclyde, Glasgow, United Kingdom. The members of the ESCRS Endophthalmitis Study Group are given in the Appendix. Funded by the European Society of Cataract & Refractive Surgeons, Dublin, Ireland, with support from Santen GmbH, Germering, Germany. No author has a financial or proprietary interest in any material or method mentioned. Reprint requests to Peter Barry, ESCRS, Temple House, Temple Road, Blackrock, County Dublin, Ireland. E-mail: escrs@ agenda-comm.ie.
408
course of this meeting, the DMC recommended that the study be unmasked. When masking was removed, the result was so clear that the DMC advised the study chairman that not only should recruitment be stopped, but it was the duty of those managing the study to publish as soon as practicable the principal result that had emerged as it was likely to be of fundamental importance to all cataract surgeons. This short communication meets that recommendation.
RESULTS
The study was conducted using a 2 2 factorial design. By the time of the meeting held on January 6, 2006, the results obtained in the 4 treatment groups were as summarized in Figure 1. Because follow-up procedures are not yet complete, the statistical analyses that follow must remain subject to adjustment in the unlikely event that further cases of endophthalmitis are reported. All patients were expected to have a complete follow-up record by the end of March 2006. Two statistical analyses were carried out, the first using the total number of reported endophthalmitis cases as the response variable and the other using the proven infective cases that produced a positive Gram stain, microbiology culture, or polymerase chain reaction result from the intraocular sample. The 13 698 patients whose follow-up had been reported up to January 6, 2006, appropriately distributed across the treatment groups, were used as the interim study population. The results of these analyses are summarized in Tables 1A and 1B.
J CATARACT REFRACT SURG - VOL 32, MARCH 2006
ESCRS STUDY ON POSTOPERATIVE ENDOPHTHALMITIS
Table 1A. Results of analysis of total endophthalmitis cases based on patients followed up to January 6, 2006.
Incidence per 10 000 Treatment Group Cefuroxime Levofloxacin
Odds Ratio
Withheld
Administered
Point Estimate
95% CI
P Value
33.52 23.37
7.31 17.51
4.59 1.33
1.74-12.08 0.63-2.82
.002 .454
CI Z confidence interval
Table 1B. Results of analysis of proven infective endophthalmitis cases based on patients followed up to January 6, 2006.
Incidence Per 10 000 Treatment Group Cefuroxime Levofloxacin
Odds Ratio
Withheld
Administered
Point Estimate
95% CI
P Value
23.32 16.07
4.39 11.68
5.32 1.37
1.55-18.26 0.55-3.42
.008 .496
CI Z confidence interval
Under these analyses, it became clear that prophylaxis with cefuroxime was having a significant beneficial effect in reducing the incidence of endophthalmitis, to approximately one fifth the value observed without that prophylaxis. Although there appeared to be some benefit from the use of perioperative levofloxacin, the effect was smaller and not significant under any analysis performed. There was no evidence of a significant interaction between the 2 treatments. Because most patients are expected to provide a complete follow-up record and further cases of endophthalmitis may occur, the number of cases in each group may change; however, in the final analyses, to be reported later, there should be approximately 4000 patients in each treatment group. DISCUSSION
The study found that the risk for contracting endophthalmitis following phacoemulsification cataract surgery was significantly reduced by an intracameral injection of cefuroxime at the end of surgery. The best estimate of the size of this effect is that the use of intracameral cefuroxime reduces the risk to approximately one-fifth the value observed without this prophylaxis when best practice for surgical hygiene is followed. However, it should be noted that this estimate has a wide confidence interval; therefore, it cannot be regarded as precise. Nevertheless, we are confident that intracameral cefuroxime provides positive protection against postoperative endophthalmitis. At the outset of the study, it was anticipated that approximately 32 000 patients would have to be recruited to demonstrate conclusively an effect for either treatment.
To obtain such a clear result after recruiting only half this number of patients was unexpected. Two factors aided the study in this satisfactory outcome. The first was the rate of postoperative endophthalmitis observed in the group receiving neither intracameral cefuroxime nor perioperative levofloxacin (0.38%). This rate is almost twice as high as the estimated background rate of 0.20%, which was used for sample size estimation and was based on an extensive literature search of reported endophthalmitis cases following cataract surgery.2–4 However, with hindsight, this result is not as surprising because many of these were retrospective studies, which are notorious for their tendency to under-report incidence rates. In addition, many used some form of prophylaxis that, while not proven to be effective, may have reduced the incidence of the condition to a greater or lesser extent. The second factor in the study’s favor was the large size of the effect produced by the use of intracameral cefuroxime. The 5-fold reduction in the incidence of endophthalmitis observed is in line with that reported by Montan et al.5,6 in Sweden in their long-running retrospective and prospective, but uncontrolled, study. Similarly, a recent 3-year retrospective uncontrolled study7 involving 9157 cataract surgery patients in Barcelona reports that the incidence of postoperative endophthalmitis decreased from 0.42% to 0.03% with the use of an intracameral injection of cefazolin (2.5 mg in 0.01 mL of Ringer’s lactate solution). The confirmation that the Swedish technique has now received in a large multinational prospective randomized placebo-controlled study should convince surgeons of its value and encourage them to consider its adoption as a standard part of the procedure of modern phacoemulsification cataract surgery.
J CATARACT REFRACT SURG - VOL 32, MARCH 2006
409
ESCRS STUDY ON POSTOPERATIVE ENDOPHTHALMITIS
APPENDIX
Ophthalmology Nurse Managers and Administrative Assistants
The ESCRS Endophthalmitis Study Group
Belgium: Eveline Callens, Gent; Danny Mathysen, Antwerp; Franc¸oise Molemans, Ge´rald de Rassenfosse, and Christel Schenkeveld, Melveren.
Study Management Team Peter Barry (study chairman), Royal Victoria Eye & Ear Hospital and St. Vincent’s University Hospital, Dublin, Ireland; David Seal (study coordinator), Applied Vision Research Centre, City University, London, United Kingdom; George Gettinby, Magnus Peterson, Crawford Revie, and Fiona Lees, Department of Computer and Information Sciences/Department of Statistics and Modelling Science, University of Strathclyde, Glasgow, United Kingdom; Mary Dardis and Betsan Bradley ESCRS, Dublin, Ireland.
Pharmaceutical Associates Klaus Geldsetzer, Santen GmbH, Germering, Germany; David Lloyd, Renaissance Health Care, Surrey, United Kingdom.
Germany: Andrea Eckelmann and Andreas Haselhoff, Ahaus. Poland: Renata Franczuk, Warsaw. Portugal: Liliana Carvalho and Ana Catarina, Coimbra. Spain: Laurent Bataille and Elena Jime´nez, Alicante; Ana Martı´n de Nicola´s, Madrid. Turkey: Hakan Kuheylan, Izmir. United Kingdom: Sue Bovill and Ian Tate, Sunderland; Suzanne Cabral and Tim Withers, London; Deborah Cox and Trudi Yeates, Exeter and Axminster; Jean Dash, Linda Lindsell, and Rebecca Turner, Oxford.
Molecular and Microbiologists Clinical Partner Ophthalmologists Austria: Guenther Grabner, Stefan F. Egger, and Josef Ruckhofer, University Eye Clinic, Paracelsus Private Medical University, Salzburg. Belgium: Johan Blanckaert, Jan Yperman Ziekenhuis, Campus Zwarte Zuster, Ieper; Camille Budo, Oogheelkunde, Melveren; Albert Galand, Jessica Crommen, Jean Rakic, Gae¨l Xhauflaire, Centre Hospitalier Universitaire, Liege; Marie-Jose´ Tassignon, UZA Ophthalmology, Edegem; Hugo Verbraeken and Rita de Donker, Universitair Ziekenhuis, Gent. Germany: Stefanie Schmickler, Augenklinik Ahaus, Ahaus. Italy: Roberto Bellucci, Simonetta Morselli, and Sandro Soldati, Ospedale Borgo Trento, Verona; Fausto Vigasio, Marco Bertelli, Andrea Bottoli, Marta Cassamali, Fabrizio Danieli, Samer Khuri, and Luigina Rosa, Azienda Ospedaliera di Desenzano del Garda, Desenzano del Garda.
Consuelo Ferrer, Instituto Oftalmologico VISSUM, Alicante Spain; Roland Koerner, Sunderland Royal Hospital, Sunderland, United Kingdom; Udo Reischl and Anke Behr, Institute of Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.
Data Monitoring Committee Steven Barrett (chairman), Chelsea & Westminster Hospital, London, United Kingdom; Susanne Gardner, St. Joseph’s Hospital/Research, Atlanta, Georgia, USA; Susan Kennedy, National Ophthalmic Pathology Laboratory, Royal Victoria Eye and Ear Hospital, Dublin, Ireland; John Ludgate, London, United Kingdom; Per Montan, St. Erik’s Hospital, Stockholm, Sweden; Kirk Wilhelmus, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA.
Poland: Jerzy Szaflik and Justyna Izdebska, Kierownik Katedry i Kliniki, Samodzielny Publiczny Kliniczny Szpital Okulistyczny, Warsaw. Portugal: Concieca˜o Lobo, Jose Cunha Vaz, and Joaquin Mira, Department of Ophthalmology, Coimbra.
REFERENCES
Spain: Augusto Abreu, Jose Aguilar, Victor Arteaga, Luis Cordoves, Valentin T. Dı´az-Aleman, Manuel Gonzalez de la Rosa, and Cristina Mantolan, Servicio de Oftalmologia, Hospital Universitario de Canarias, Tenerife; Pedro Abreu, Jorge Alvarez-Marin, and Maria Antonia Gil, La Candelaria University Hospital, Tenerife; Jorge Alio´, Instituto Oftalmologico VISSUM, Alicante; Miguel Teus, M.T. Alvarez, and J.M. Roma´n, Hospital Oftalmologico Internacional, Madrid.
1. Seal DV, Barry P, Gettinby G, et al. ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery: case for European multicenter study. J Cataract Refract Surgery 2006; 32:396–406 2. Ciulla TA, Starr MB, Masket S. Bacterial endophthalmitis prophylaxis for cataract surgery; an evidence-based update. Ophthalmology 2002; 109:13–24 3. West ES, Behrens A, McDonnell PJ, et al. The incidence of endophthalmitis after cataract surgery among the U.S. Medicare population increased between 1994 and 2001. Ophthalmology 2005; 112:1388–1394 4. Taban M, Behrens A, Newcomb RL, et al. Acute endophthalmitis following cataract surgery; a systematic review of the literature. Arch Ophthalmol 2005; 123:613–620 5. Montan PG, Wejde G, Koranyl G, Rylander M. Prophylactic intracameral cefuroxime: efficacy in preventing endophthalmitis after cataract surgery. J Cataract Refract Surg 2002; 28:977–981 6. Montan PG, Wejde G, Setterquist H, et al. Prophylactic intracameral cefuroxime; evaluation of safety and kinetics in cataract surgery. J Cataract Refract Surg 2002; 28:982–987 7. Garat M, Moser CL, Alonso-Tarre´s C, et al. Intracameral cefazolin to prevent endophthalmitis in cataract surgery; 3-year retrospective study [correspondence]. J Cataract Refract Surg 2005; 31:2230–2234
Turkey: Suleyman Kaynak, Retina Ophthalmic Research Centre, Izmir. United Kingdom: David Allen, Peter Phelan, David Steel, and Chris Wood, Sunderland Eye Infirmary, Sunderland; Carol Cunningham, Michael Miller, Ramesh Moorthy, Andleeb Zafar, Moorfields Eye Outreach Unit, Northwick Park Hospital, Harrow; Alex Ionidis, Damian Lake, and Graham Thompson, Moorfields Eye Outreach Unit, St. George’s Hospital, London; John Jacob, Daniel Byles, Casper Gibbon, Andrew Kleinschmidt, Roland Ling, Anthony Quinn, Peter Simcock, and George Sturrock, West of England Eye Unit, Royal Devon & Exeter Hospital (Wonford), Exeter, and Axminster Hospital, Axminster; William Kiel, Ipswich Hospital, Ipswich; Denise Mabey, David Spalton, and Anupma Kumar, Department of Ophthalmology, St. Thomas’ Hospital, London; Paul Rosen, C.K. Patel, and John Salmon, Oxford Eye Hospital, Oxford.
410
J CATARACT REFRACT SURG - VOL 32, MARCH 2006