REVIEW/UPDATE

Endophthalmitis prophylaxis in cataract surgery:

Overview of current practice patterns
in 9 European countries
Anders Behndig, MD, PhD, Beatrice Cochener, MD, PhD, Jos
e Luis G uell, MD, PhD,
Laurent Kodjikian, MD, PhD, FEBO, Rita Mencucci, MD, PhD,
Rudy M.M.A. Nuijts, MD, PhD, Uwe Pleyer, MD, PhD, Paul Rosen, FRCS, FRCOphth,
Jacek P. Szaflik, MD, PhD, Marie-Jos
e Tassignon, MD, PhD

Data on practice patterns for prophylaxis against infectious postoperative endophthalmitis (IPOE)
during cataract surgery in 9 European countries were searched in national registers and reviews of
published surveys. Summary reports assessed each nations IPOE rates, nonantibiotic prophylac-
tic routines, topical and intracameral antibiotic use, and coherence to the European Society of
Cataract & Refractive Surgeons (ESCRS) 2007 guidelines. Although the reliability and complete-
ness of available data vary between countries, the results show that IPOE rates differ significantly.
Asepsis routines with povidoneiodine and postoperative topical antibiotics are generally adopted.
Use of preoperative and perioperative topical antibiotics as well as intracameral cefuroxime varies
widely between and within countries. Five years after publication of the ESCRS guidelines, there is
no consensus on intracameral cefuroxime use. Major obstacles include legal barriers or persisting
controversy about the scientific rationale for systematic intracameral cefuroxime use in some
countries and, until recently, lack of a commercially available preparation.
Financial Disclosure: Dr. Pleyer has received research funding from Bundesministerium fur
Bildung und Forschung and Deutsche Forschungsgemeinschaft and has served as a consultant
for Abbott Medical Optics, Inc., Alcon Laboratories, Inc., Allergan, Inc., Bausch & Lomb, Novartis
Corp., Santen, Inc., Laboratoires Th
ea, and Ursapharm Arzneimittel GmbH. Dr. Tassignon has a pro-
prietary interest in the bag-in-the-lens technique and intraocular lenses licensed to Morcher GmbH.
No other author has a financial or proprietary interest in any material or method mentioned.
J Cataract Refract Surg 2013; 39:14211431 Q 2013 ASCRS and ESCRS

Cataract surgery is the most commonly performed
surgical procedure in many developed countries,13
and the frequency continues to increase, probably
because of changes in population structure,4 technical
advances with better outcomes, and an increasing pro-
portion of outpatient and second-eye procedures.5
Infectious postoperative endophthalmitis (IPOE) is
the most dreaded complication of cataract surgery.
Infectious postoperative endophthalmitis has a devas-
tating prognosis, with a visual outcome of 20/200 or
worse in 15% to 30% of cases.68 The severity and
clinical course of IPOE depend on the virulence and
the number of inoculated pathogens, as well as the
patient's immune state and the time of diagnosis and
treatment.9,10 The most common pathogens remain
gram-positive Staphylococcus epidermidis (or
coagulase-negative staphylococci [CNS]) and S aureus
(Table 1).6,1016
Increasing resistance of Staphylococcus sp to a broad
spectrum of antibiotics, including the latest fourth-
generation fluoroquinolones, eg, methicillin-resistant
S aureus (MRSA) and methicillin-resistant S epidermidis
(MRSE), is currently a major concern.17,18 Fortunately,
IPOE is a rare complication. Reported IPOE frequency
varies widely, but a systematic review has shown an
overall estimate of 0.128% between 1963 and 2003.2
Despite the low incidence rate, IPOE generates a sub-
stantial healthcare burden because of the high number
of procedures performed and the severe consequences
of overt infections.
Various operative and nonoperative measures have
been advocated to prevent this serious complica-
tion.19,20 Preoperative antisepsis of the periocular
area with topical povidoneiodine is widely adopted
and is considered the basic standard of IPOE preven-
tion,21 although chlorhexidine is preferred in some

Q 2013 ASCRS and ESCRS 0886-3350/$ - see front matter 1421

Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jcrs.2013.06.014
1422 REVIEW/UPDATE: EUROPEAN IPOE PROPHYLAXIS PRACTICE PATTERNS
countries. Antibiotic prophylaxis is another commonly
used preventive measure. However, proposed antibi-
otic prophylaxis protocols are very diverse in agents
used (eg, aminoglycosides, cephalosporins, fluoroqui-
nolones, chloramphenicol), administration routes
(topical, intraocular, subconjunctival, oral, intrave-
nous), and timing (preoperative, intraoperative, peri-
operative, postoperative).2225
The European Society of Cataract & Refractive Sur-
geons (ESCRS) prospective randomized controlled
trial of IPOE prophylaxis26 served as the basis for the
2007 ESCRS practice guidelines, which recommended
systematic use of intracameral cefuroxime.10 The re-
sults were coherent, with data from over 400 000 pa-
tients in the Swedish National Cataract Registry27,28
showing an IPOE rate of 0.048%.29,30 In the Swedish
National Cataract Registry, the 1.0% of cataract sur-
geries that did not receive intracameral cefuroxime
had a significantly higher risk for IPOE (odds ratio
[OR], 7.24; 95% confidence interval [CI], 3.71-14.11).29
In addition, a series of retrospective studies from
France, Spain, and the United Kingdom consistently
confirmed a significant decrease in IPOE rates with sys-
tematic intracameral cefuroxime injections.15,20,24,31,32
Given these data, we decided to assess the IPOE
prophylaxis practice patterns and intracameral cefur-
oxime use in Europe in 2012, ie, 5 years after publica-
tion of the ESCRS study and guidelines.
MATERIALS AND METHODS
This overview was based on a comprehensive review of
available literature completed by summary reports by the
Submitted: October 30, 2012.
Final revision submitted: January 24, 2013.
Accepted: January 26, 2013.
From the Department of Clinical Sciences/Ophthalmology
(Behndig), Umea University Hospital, Umea, Sweden; Service
dOphtalmologie (Cochener), CHU Morvan, Brest, France; Autono-
ma University of Barcelona (Guell), Barcelona, Spain; Hopital de la
Croix-Rousse (Kodjikian), Lyon, France; Istituto de Clinica Oculisti-
ca (Mencucci), Cattedra di Ottica Fisiopathologica, Florence, Italy;
Department of Ophthalmology (Nuijts), Academic Hospital Maas-
tricht, Maastricht, The Netherlands; University-Eye Clinic (Pleyer),
Charit
e, CVK, Berlin, Germany; Oxford Eye Hospital (Rosen), Oxford,
United Kingdom; Department of Ophthalmology (Szaflik), Medical
University of Warsaw, Warsaw, Poland; Faculty of Medicine and
Health Science (Tassignon), University of Antwerp, Wilrijk, Belgium.
Author group meetings were supported by an unrestricted grant
from Laboratoires Th
ea, Clermont-Ferrand, France.
Corresponding author: Anders Behndig, MD, PhD, Department of
Clinical Sciences/Ophthalmology, Umea University Hospital, SE-
901 85 Umea, Sweden. E-mail: anders.behndig@ophthal.umu.se.
J CATARACT REFRACT SURG - VOL 39, SEPTEMBER 2013
Table 1. Pathogens found in proven cases of post-cataract-
surgery infectious endophthalmitis.
Percentage
Organism of Cases
Coagulase-negative staphylococci 3080
Staphylococcus aureus 1020
Streptococci (-haemolytic streptococci, 1035
S pneumoniae, a-haemolytic streptococci
including S mitis and S salivarius)
Enterococci !5
Gram-negative bacteria, including Pseudomonas 520
aeruginosa (occurs rarely)
Fungi (Candida sp, Aspergillus sp, Fusarium sp) Up to 8
Polymicrobial culture !5
Negative or equivocal culture 3040
Rounded figures; adapted from the ESCRS 2007 review10 and additional
sources6,1116
authors, who represented 9 European countries: Belgium,
France, Germany, Italy, the Netherlands, Poland, Spain,
Sweden, and United Kingdom. Identification of relevant
sources and findings were discussed during meetings of
the authors. Questions of interest were pooled within 5 do-
mains: (1) Current cataract surgery procedures and known
IPOE incidence rates from a National Registry or other sour-
ces; (2) nonantibiotic prophylactic measures used: hygiene
rules, patient selection, antisepsis; (3) topical antibiotic use:
type(s) and rationale, dose regimens; (4) intracameral anti-
biotic use: frequency of use, preferred type, legal incentives,
or barriers; (5) guidelines: existence or absence of national
practice guidelines for IPOE prevention, guideline source
(health authorities, learned societies), coherence to the
ESCRS 2007 guidelines. A summary of the findings in these
countries is presented in Table 2.
Sweden
Sweden has a long experience with intracameral
cefuroxime-based antibiotic prophylaxis, which has already
been highlighted. The National Cataract Register was imple-
mented in 1992 and now covers 100% of clinics and 98.5% of
procedures. Updated data covering more than 1 000 000
cataract surgeries were recently published.33 In 2010, 91 421
cataract surgery procedures were performed by 60 cataract
centers (43 public, 17 private). The IPOE rate is currently
less than 0.02,A whereas it was 0.1% in 1998 and 0.0595%
during the 1999 to 2001 period.
Ordinary routines are followed in patient selection, hy-
giene rules in the operating room, and eyedrop instillation.
Antiseptic showers before surgery are not used. Ocular
antisepsis is based on chlorhexidine. Use of intracameral
cefuroxime (1.0 mg/0.1 mL at the end of the procedure)
started in 1999 and currently applies to about 90% of cataract
surgery procedures, but intracameral antibiotics are used
almost unanimously, with moxifloxacin as the preferred
option in a few centers. Cefuroxime is prepared in various
settings (local pharmacy, national pharmacy, or operating
room). A combined antibiotic prophylaxis with cefuroxime
and ampicillin is sometimes used in bilateral surgery or in
patients with risk factors. Likewise, routine use of topical
 REVIEW/UPDATE: EUROPEAN IPOE PROPHYLAXIS PRACTICE PATTERNS 1423

Table 2. Summary findings on current antibiotic prophylaxis for cataract surgery in 9 European countries.

Number of IC Cefuroxime
Cataract IPOE Incidence Main Guidelines Prophylaxis Adoption
Surgeries Rate (Period)/ for Antibiotic Rates/Specific Factors Topical Antibiotic
Country per Year Origin of Source Data Prophylaxis Favoring or Limiting Use Prophylaxis

SwedenA 91 000 !0.04% (19922009) National Cataract 90% (2012) Not recommended
!0.02% (2012) Registry; and no routine use
Swedish Ophthalmological except RLE or high-
Society risk patients
National registry33 Omission of IC
(covering O98% antibiotics considered
of procedures)* unethical
FranceB,C 630 000 0,21%0.32% (19922002) National Agency for !5% (2006) Preoperative: 28%
0.03%0.06% (20072011) Health Products 40% (2011) (2007)36, currently
Safety (AFSSAPS)18 not recommended
National registry14 Recommended by Per-/post-operative:
(non-mandatory reporting); regulatory national 95%(2007)36, currently
limited surveys)12,34,32 guidelines since 201118 recommended
United O330 000 0.03%0.20% (19972006) Scottish Intercollegiate 10% (2005)23 Preoperative:
KingdomD Guidelines Network49; 45%-61% 6%-9% (2005)23
Royal College of (2009-2010)19,45,48
Ophthalmologists50
Multiple, often large Historically, the Per-/post-operative:
surveys7,13,19,20,23,37-45 subconjunctival route 90% (2005)23
was the preferred choice23
SpainE 200 000 0.48%/0.50% ESCRS guidelines10 Not known Preoperative:
0.056%/0.11% (1999-2008) variable15,31

Single-centre surveys15,24,31 Per-/post-operative:

100%15,24,31
GermanyF 700 000 0.15% (1999) ESCRS guidelines10 Not known, Pre- and per-/
0.060.07% (20062011) probably !20% post-operative: 100%
Multicenter or single- Opposed by legal issues
center surveys25,51,52
BelgiumG 120 000 0.036% ESCRS guidelines10 Not known Not known
(20092011)
Extrapolated from the Implementation of
EUREQUO registry5 ESCRS guidelines
started in 2009
ItalyH 350 000 0.05%0.35% ESCRS guidelines10 20% (2010)53 Preoperative: 76%,
Peroperative: 40%
Postoperative: 100% 53
Extrapolated from the Implementation of
ESCRS trial4 ESCRS guidelines started
in 2008
NetherlandsI,J 140 000 0.03% (2012) Dutch Ophthalmological 27% (2010) Pre- and per-/
Society post-operative:
100%
National registry Recommended in
(mandatory high-risk patients only
outcome reporting)
PolandK O160 000 0.29%* (2004)55 Polish Society of Not known, probably Not known
Current rate not known Ophthalmologists not used in most cases
Off-label use, complex
preparation

ESCRS Z European Society of Cataract & Refractive Surgeons; IC Z intracameral; IPOE Z infectious postoperative endophthalmitis; RLE Z refractive lens exchange
Italics: yet unpublished, extrapolated or estimated figures
AK
Additional information from personal communications (2012) or from conference proceedings (see list in Other Cited Material).
*This figure may have included cases of toxic anterior segment syndrome.

J CATARACT REFRACT SURG - VOL 39, SEPTEMBER 2013

1424 REVIEW/UPDATE: EUROPEAN IPOE PROPHYLAXIS PRACTICE PATTERNS
antibiotics is uncommon, but fluoroquinolones may be used
in refractive lens exchange and in high-risk patients. The rate
of IPOE was lower from 1999 to 2009 than in 1998, and ana-
lyses clearly showed that this was attributable to generalized
intracameral cefuroxime use.
There are no formal national guidelines, but there are
informal recommendations from the National Cataract
Registry and the Swedish Ophthalmological Society.
France
In France, national guidelines on intracameral cefuroxime
were recently released by the Health Ministry-governed
regulatory Agence Francaise de S
ecurit
e Sanitaire des
Produits de Sant
e,18 a unique feature among the 9 reviewed
countries. About 630 000 cataract procedures are performed
each year by 706 cataract centers (237 public hospitals, 469
private clinics).B Endophthalmitis reporting to the national
register (Observatoire National Des Endophtalmies)14 is
not mandatory. Historical epidemiological studies have re-
ported various incidence rates over timed0.32% in 1992,12
0.21% during the 2000 to 2002 period34d but the true current
rate is not known.
Patients' infection risk assessments and antiseptic showers
and shampoos (povidoneiodine the day before and the
morning before surgery) are routinely performed. Recom-
mended antiseptic preparation of the operative site is based
on povidoneiodine applied 3 times (10% on skin during
dilation, 5% on skin and eye in the anesthesia room, 5%
into conjunctival sac on the operating table). Moreover, anti-
sepsis duration should be timed with a stopwatch (2 minutes
at each step). These measures must be associated with a
patient-selection process to identify infected and high-risk
patients, as well as hygiene measures in the operating room
applicable to staff, equipment, and the environment.18
Topical antibiotics are not recommended before cataract
surgery. The national guidelines emphasize that because of
their high selective power, topical fluoroquinolones should
be reserved for curative treatment of severe eye infection.18
However, postoperative topical antibiotic prophylaxis is
recommended during 1 week and should target common
IPOE-causative bacteria, ie, gram-positive cocci.18,35 Cefur-
oxime (1.0 mg/0.1 mL) intracameral injection at the end of
the procedure is a strongly recommended antibiotic prophy-
laxis in the absence of any contraindication to cephalospo-
rins.18 The drug is usually prepared by the center's local
pharmacy. Subconjunctival injections and antibiotic prophy-
laxis added to the irrigation fluid are not recommended.
When cephalosporin administration is contraindicated or
in patients at risk, the national guidelines recommend oral
levofloxacin (500 mg the day before and 500 mg on the day
of surgery). In general, at-risk patients are those with
diabetes mellitus, previous implantation of an intraocular
device other than for cataract surgery, and previous postop-
erative endophthalmitis in the fellow eye; for cataract
surgery only, cited risk factors are intracapsular extraction
and secondary implantation. In cases of capsule rupture
in patients who did not receive a preoperative systemic
antibiotic, perioperative intravenous levofloxacin is
recommended.18
According to a prospective longitudinal multicenter
observational study that enrolled 781 patients from
September 2007 to February 2008 before the ESCRS study,
28.5% of patients received preoperative topical antibiotic
prophylaxis and 94.7% received postoperative topical
J CATARACT REFRACT SURG - VOL 39, SEPTEMBER 2013
combined antibiotic plus steroid drops.36 A recent report
from 2 large centers covering 3316 patients during a 2-year
period (January 2007 to December 2008) showed a 0.06%
IPOE rate after the implementation of systematic intracam-
eral cefuroxime injections.32 A recent survey showed that
the use of intracameral antibiotics (cefuroxime in 60% to
73% of cases) dramatically increased from 2006 to 2011
(from 7% to 61%, respectively).C This trend is expected to
increase in future years because of the publication of the
national guidelines in 2011.
United Kingdom
Data on IPOE epidemiology and practice patterns in the
U.K. are fairly well known from the large series of reports
published over the past decade.7,13,19,20,23,3744 According
to a recent survey by the Royal National Institute of Blind
People, the number of cataract operations reached 350 602
in 2010 but fell to 338 565 in 2011 because of cost-cutting
measures.D The baseline IPOE rate reported in the British
Ophthalmological Surveillance Unit study was 1/700 cata-
ract surgeries (0.14%); it was also estimated that only 62%
of IPOE cases were reported.7 A 2009 review by Carrim
et al.13 found that published IPOE rates during the 1997 to
2006 period (observed at single-unit, regional, or national
level) varied from 0.03% to 0.2%.7,13,3740
According to 4 surveys of ophthalmologists' practices,
subconjunctival antibiotics, predominantly cefuroxime,
were administered at the end of surgery in 68% to 82% of
cases compared with intracameral antibiotics in only 10%
to 16% of cases.7,23,42,43 Some clinicians have argued that
there is no evidence that a change from subconjunctival to
intracameral cefuroxime would be more effective.45,46 Later
surveys have shown a strong shift toward the use of
intracameral cefuroxime, with 44.7% to 61.0% of surgeons
preferring the intracameral administration route.19,44,47 A
single-center retrospective analysis of 36 743 phacoemulsifi-
cation procedures reported that intracameral cefuroxime
was a safe alternative to subconjunctival cefuroxime with a
significantly lower rate of IPOE (subconjunctival versus in-
tracameral route: OR, 3.01; 95% CI, 1.37-6.63).20
Regarding practice guidelines, intracameral antibiotic
prophylaxis is recommended for cataract surgery by the
Scottish Intercollegiate Guidelines Network48 whereas the
Royal College of Ophthalmologists49 leaves the details of
antibiotic use to the surgeon's discretion.
Spain
There is no national register for cataract surgery or IPOE
in Spain, but some centers have developed their own local
observational databases, allowing estimates of IPOE rates
based on single-center samples: for instance, no cases of
IPOE were observed among the 1151 cataract surgery proce-
dures performed in 2011 at Barcelona's Instituto de Micro-
ciruga Ocular, with cefuroxime intracameral injections in
all cases.E About 200 000 cataract procedures are performed
each year.E
The following protocol, based on the ESCRS 2007 guide-
lines, is used very commonly in private and public Spanish
institutions: preoperative prophylaxis combining lid hy-
giene (scrubs with baby shampoo), topical antibiotics, and
povidoneiodine 10% solution applied on the skin before
the patient enters the operating room, then again before
starting surgery (5-minute wait), combined with a povi-
doneiodine 5% solution into the conjunctival sac. In case
 REVIEW/UPDATE: EUROPEAN IPOE PROPHYLAXIS PRACTICE PATTERNS
of allergy, povidoneiodine is replaced by a chlorhexidine
0.05% solution. Topical antibiotics (ofloxacin 0.3%) are
used both before surgery (1 drop 3 times a day for 3 days)
and after surgery (1 drop 4 times a day for 1 week).E
A retrospective survey from the University Hospital
Fundaci
on Alcorc
on (Madrid) covering a 10-year period
(1999 to 2008) showed a mean IPOE rate of 0.30% (95% CI,
0.26%-0.35%),24 with a significant difference in mean rates
before and after the implementation of cefuroxime (1999 to
2005: 8099 patients, 0.48% IPOE rate; 2005 to 2008: 7074 pa-
tients, 0.056% rate; relative risk 0.12 [0.04-0.33], ie, a nearly
9-fold risk reduction).15 In case of a beta-lactam antibiotic
allergy, intracameral vancomycin (0.1 mg/0.1 mL) was
used. In another retrospective study covering 4281 cataract
surgeries,31 the IPOE rate dropped from 0.5% to 0.11% after
the implementation of cefuroxime.
Germany
According to the results of an annual survey by the
Deutschsprachige Gesellschaft f ur Intraokularlinsen-
Implantation, Interventionelle und Refraktive Chirurgie
and Deutsche Ophthalmologische Gesellschaft (DGII/
DOG) involving all major centers and encompassing half
of all cataract surgery procedures, about 700 000 cataract sur-
geries are performed each year in Germany, 75% of which
are done in private office settings.F There is no national
register, but data are available from the DGII/DOG joint
committee questionnaire.
Much about German practices was learned from the re-
sults of a cross-sectional anonymous survey published in
1999 by Schmitz et al.25 that analyzed 311 surgical centers
(67% answer rate) and reported data on 340 633 cataract sur-
geries performed in 1996. The survey found a mean IPOE
rate of 0.148% and provided a comprehensive picture of pro-
phylactic treatments used at that time. The use of intraocular
antibiotics (60% of the respondents) was associated with a
significantly lower incidence of IPOE in both univariate
and multivariate analyses (OR, 0.65; 95% CI, 0.43-0.98).
However, in more than 90% of cases, the intraocular antibi-
otics were added to the irrigating solution; intracameral in-
jection was used in only 5% of cases. Aminoglycoside
antibiotics were used in 85% of cases, vancomycin in 7%,
and a combination of vancomycin and aminoglycoside in
5%. The application of povidoneiodine (68% of respon-
dents) to the conjunctiva was also associated with a signi-
ficantly decreased risk for IPOE (OR, 0.59; 95% CI,
0.36-0.99). However, the use of preoperative topical antibi-
otics was associated with a significantly increased risk (OR,
2.38; 95% CI, 1.21-4.68), and a comparable trend was found
with topical antibiotic use after surgery (OR, 1.3; 95% CI,
0.87-1.92).25 A later and comparable survey involving 538
centers and more than 400 000 cataract procedures found a
0.072% IPOE overall rate.50
Currently, povidoneiodine 5% is usually applied on the
ocular surface during 5 C 5 minutes. Various topical antibi-
otics (quinolones, aminoglycosides) are applied before, dur-
ing, and after the procedure for 1 to 4 weeks.F A recently
published single-center retrospective survey including
more than 26 500 procedures found a 0.06% IPOE rate
when prophylaxis was based on topical povidoneiodine
and gentamicin-containing irrigation fluid administered
preoperatively.51
Use of intracameral cefuroxime commenced after the pub-
lication of the ESCRS 2007 guidelines. Intracameral
J CATARACT REFRACT SURG - VOL 39, SEPTEMBER 2013
1425
cefuroxime is currently used in an unknown proportion of
procedures, probably fewer than 20%, because specific legal
issues oppose this practice. There are no national IPOE pre-
vention guidelines, but German ophthalmologists tend to
follow the ESCRS 2007 recommendations.
Belgium
The estimated annual number of cataract surgery proce-
dures is 120 000.G The number of active centers is unknown.
Belgium does not have a mandatory registry of postopera-
tive complications after cataract surgery, thus current figures
are not known. However, IPOE incidence at the Antwerp
University Hospital is 0.0% since the voluntary registry of
the cataract surgeries performed at this center in the
European Registry for Quality Outcomes of Cataract and
Refractive SurgeryG (partner countries: Austria, Belgium,
Denmark, Finland, Greece, Germany, Hungary, Ireland,
Italy, the Netherlands, Norway, Slovakia, Spain, Sweden,
Turkey, and U.K.).5
Only limited information about current national practice
trends is available, but implementation of the ESCRS
endophthalmitis guidelines started in 2009. No endophthal-
mitis occurred during the past 2 years at the Antwerp
University Hospital where this protocol is routinely used.G
Regarding other routine prophylactic measures, patients
are checked before surgery for infection and povidone
iodine (5% on ocular surface, 10% on skin over 3 minutes)
is used as an antiseptic without prior shower and no pre-
operative topical antibiotics. Hygiene rules at the operation
are focused on a standardized protocol for sterile draping.
Topical antibiotics, mainly quinolones, are used during
and after surgery, according to licensed doses. Cefuroxime
(1.0 mg/0.1 mL intracameral route or during incision hydra-
tion) is used in 100% of cataract surgery procedures, accord-
ing to the ESCRS 2007 guidelines.
Italy
A large but unknown number of Italian cataract centers
perform an estimated 300 000 to 400 000 cataract surgery pro-
cedures per year.H Although there is no national register, the
incidence of IPOE has been estimated to be 0.05% to 0.35%,
ie, similar to other European figures.4
Prophylactic measures usually start with the screening of
high-risk patients for local risks (blepharitis, dacryocystitis,
severe dry eye), systemic comorbidities (diabetes mellitus,
immunosuppression, pulmonary infections, sustained anti-
biotic/steroid therapy), and very high age (O85 years old).
The reported data are the result of a survey conducted in
2010 by the Italian Association of Cataract and Refractive
Surgeons. An eyelid cleaning is advised during the week
before surgery. Antiseptics are used in 100% of the proce-
dures, mainly povidoneiodine (10% on periocular skin,
5% on ocular surface [conjunctival fornix] applied for at least
3 minutes) or chlorhexidine 0.05% in case of povidone
iodine allergy. Routine hygiene and draping rules and
single-dose eyedrops are used. A wide-spectrum topical
antibiotic (aminoglycosides, fluoroquinolones) is used
during the preoperative phase in 76% of cases,52 during the
procedure in 41%, and postoperatively in all patients.
Intracameral antibiotics have been used since 2008,
following the ESCRS 2007 guidelines and legal aspects.
Currently, either cefuroxime (1.0 mg/0.1 mL; 52%) or vanco-
mycin (48%) is used in 41% of procedures.52 Syringes are
prepared by local pharmacies. Since there are no specific
1426 REVIEW/UPDATE: EUROPEAN IPOE PROPHYLAXIS PRACTICE PATTERNS
national guidelines, Italian surgeons tend to follow the
ESCRS 2007 recommendations, but the reference source is
mainly surgeon-dependent.
The Netherlands
In the Netherlands, 140 000 cataract surgery procedures
are performed each year, 80% in general hospitals, 12% in ac-
ademic hospitals, and 8% within an increasing number of
ambulatory surgery centers with multiple facilities.I
Outcome registration is mandatory for all surgeons, as re-
quested by the Dutch Ophthalmological Society and the
Netherlands IntraOcular Implant Club. According to these
databases, the IPOE rate is 0.03%.J
Povidoneiodine eyedrops in a concentration varying
from 0.3% to 5.0% are instilled preoperatively (0.3% is avail-
able as a commercial preparation for topical use), and then
povidoneiodine 5% to 10% is applied on the skin and
diluted solution (dilution according to surgeon's preference)
on the ocular surface for 0.5 to 3.0 min. Class 1 hygiene rules
are applied to the operating room.53 Topical antibiotics are
often used before, during, and after the procedure; adminis-
trations and dosages vary. Use of intracameral antibiotics
started in 2007 after the publication of the ESCRS 2007 guide-
lines and was used in approximately 27% of procedures in
2010.J Syringes are prepared at the hospital's pharmacy.
In the absence of specific guidelines from national health
authorities and on the basis of the low endophthalmitis
rate of 0.03% in the Netherlands, the Dutch Ophthalmolog-
ical Society recommends cefuroxime in high-risk cases only
(capsule breaks, clear cornea incisions). Systematic use is
considered debatable.
A retrospective review of all consecutive patients treated
for acute IPOE after cataract surgery (N Z 250) in a single
center from 1996 to 2006 was recently published.16 Bacterial
cultures (250 cases) showed bacterial growth in 66.4% of
cases. Of these, 53.6% revealed gram-positive CNS, 38.0%
other gram-positive bacteria, 6.0% gram-negative patho-
gens, and 2.4% polymicrobial cultures.
Poland
According to the national health insurance refunding sys-
tem, 152 000 cataract surgery procedures were performed in
Poland in 2011. About 15 000 to 20 000 additional cataract
surgeries are performed in private practices, although their
exact number is not known.K No reliable data on current
IPOE incidence rates are available. A survey published in
2004 assessed data from 53 ophthalmology centers in
Poland, involving 28 674 cases of routine cataract surgery,
6518 cases of complicated cataract surgery, 1387 cases of
combined cataract and glaucoma surgery, and 2978 cases
of glaucoma surgery. The prevalence of IPOE in this group
of patients ranged from 0.29% after cataract surgery to
0.93% after complex surgery (cataract and glaucoma).54
These high incidence rates were interpreted as possible selec-
tion bias due to the small size of the study sample. In addi-
tion, IPOE was not proven by culture or polymerase chain
reaction so some cases of toxic anterior segment syndrome
might have been included.
In the absence of an accurate national observational data-
base, the following information applies to the protocol used
in a single center in Warsaw onlyK: Prophylactic measures
include patient selection, antiseptic showers before surgery,
and systematic povidoneiodine 5% antisepsis on the ocular
surface for 1 to 3 min. Routine sterile environment is
J CATARACT REFRACT SURG - VOL 39, SEPTEMBER 2013
respected in the operating room. Topical antibiotics are
applied before, during, and after surgery. The drug of choice
is levofloxacin, and the administration schedule is 1 drop
twice daily the day before surgery, 1 drop before surgery,
1 drop during and the night after surgery, 1 drop 4 times a
day for 2 weeks after surgery. In high-risk patients (blephar-
itis, complicated cases), the postoperative dosage is
increased to 1 drop every 2 hours on the day of surgery.
Although no hard data are available, intracameral antibi-
otics are probably not injected in most procedures because of
off-label use and complex preparation.K However, cefurox-
ime (1.0 mg/0.1 mL) has been used in 100% of the proce-
dures in the Warsaw center since 2005; until 2012, the
preparation was outsourced to a commercial pharmacy,
but currently syringes are prepared in the operating room.
Specific national guidelines have been prepared and are
now in the process of being approved. The Polish Society
of Ophthalmologists' recommendations are similar to the
ESCRS 2007 guidelines.
DISCUSSION
We found that the current practice patterns for IPOE
prophylaxis between European countries differ signi-
ficantly and often diverge from the antibiotic prophy-
laxis practices recommended by the ESCRS guidelines.
The data reported in the present overview come from
heterogeneous sources: Swedish data are based on a
national register with a high coverage; Dutch IPOE
rates are based on a mandatory outcome reporting
and practice trends; IPOE rates in the U.K. were
described by a series of dedicated surveys; in some
other countries, data about the volume of cataract sur-
geries, IPOE prophylaxis practice patterns, and IPOE
incidence rates are more or less unknown because an
adequate national epidemiological system does not
exist. Between these extremes, a variable amount of
reliable data documents exists in the remaining
countries.
While acknowledging that the variability of source
data limits our study's value, we believe that this lim-
itation is not specific to this review but rather reflects
the lack of adequate epidemiologic tools and system-
atic reporting in most countries. In addition, this over-
view can by no means determine whether differences
in practice patterns and hygiene routines are reflected
in the varying IPOE rates. One also has to consider a
possible bias since centers participating in surveys or
reporting systems may be more attentive to all steps
in the processes of patient preparation and surgical
procedures. Thus, the present overview does not pre-
tend to report actual practice patterns and epidemio-
logical facts in the reviewed countries or to provide
answers to why the IPOE rates differ, but it probably
offers a fair picture of the current status in this field.
It also helps to explain why the ESCRS guidelines
are not yet consistently adopted in these countries.
 REVIEW/UPDATE: EUROPEAN IPOE PROPHYLAXIS PRACTICE PATTERNS
Practice patterns for general hygiene rules in the
operating room and systematic preoperative antisep-
sis with povidoneiodine or chlorhexidine tend to
converge. The use of preoperative antisepsis with po-
vidoneiodine (5% solution on the conjunctiva and
cornea and 5% to 10% solution on the periorbital
area for R3 min) is based on a microbiological and
clinical rationale since it has been shown to diminish
the bacterial load and prevent IPOE.21,25,5558 Its use
is recommended by current guidelines.10,17,18 If povi-
doneiodine is contraindicated, chlorhexidine 0.05%
is an alternative.10,18,59 The use of chlorhexidine as a
primary antisepsis agent in Sweden has proven effi-
cient and safe over a long period.33,60
Regarding antibiotic prophylaxis regimens, data of
landmark importance came out of the ESCRS random-
ized trial, which comprised 16 603 patients and
compared (1) intracameral cefuroxime (1.0 mg/0.1 mL)
bolus injections at the end of cataract surgery with
no intracameral cefuroxime and (2) topical periopera-
tive levofloxacin 0.5% eyedrops with no perioperative
topical levofloxacin. Topical levofloxacin was given in
all groups postoperatively. The results showed a
nearly 5-fold decrease in the risk for presumed and
proven IPOE when intracameral cefuroxime was
included.4 The effect of topical perioperative levoflox-
acin was not significant. The incidence rates were
0.345% for total IPOE and 0.247% for proven IPOE in
the group with placebo drops and no intracameral ce-
furoxime, which may be regarded as the true current
background rates of IPOE after phacoemulsification
in Europe in the absence of antibiotic prophylaxis.4
Our overview shows that postoperative topical anti-
biotic prophylaxis is also commonly used in all coun-
tries (except Sweden), particularly in clear corneal
incision surgery, for up to 2 weeks.10,18 Its efficacy,
however, is not proven or only weakly proven by
retrospective studies.61,62 In the ESCRS study, levo-
floxacin was administered to all groups postopera-
tively. According to the authors, the relatively high
incidence rates of IPOE in subgroups without intra-
cameral cefuroxime suggested that postoperative lev-
ofloxacin alone conferred little benefit. An alternative
explanation is that had this type of antibiotic prophy-
laxis not been used, the rates across all groups would
have been higher.4
Much wider variation in preoperative and perioper-
ative topical antibiotic prophylaxis regimens, as well
as intracameral cefuroxime, is observed in this
overview. The ESCRS study has not assessed the role
of preoperative topical antibiotic prophylaxis. A previ-
ous systematic review concluded that its efficacy was
not yet scientifically proven.21 Thus, the ESCRS 2007
guidelines cite preoperative topical antibiotic prophy-
laxis as an option to consider,10 while the French 2011
J CATARACT REFRACT SURG - VOL 39, SEPTEMBER 2013
1427
guidelines do not recommend it.18 Subconjunctival
antibiotic prophylaxis has also been used over the
past 30 years, particularly in the U.K. However, on
the basis of available data, the ESCRS guidelines stated
that it probably has little prophylactic effect on the pre-
vention of IPOE9,10,21 and the French 2011 guidelines
do not recommend its use.18
Intracameral cefuroxime is recommended by ESCRS
and French guidelines,11,13 by the Scottish Intercolle-
giate Guidelines Network,48 and by Canadian guide-
lines,63 while details of antibiotic use are left to the
individual surgeon's discretion by the Royal College
of Ophthalmologists49 and the American Academy
of Ophthalmology.17
Ophthalmologists tend to follow the ESCRS recom-
mendations for intracameral cefuroxime in many
European countries lacking national guidelines, but
legal barriers may oppose its use. Controversy about
the scientific rationale for systematic intracameral
cefuroxime persists in the U.K., where the subconjunc-
tival route has been historically dominant and in the
Netherlands where its use is limited to high-risk
patients. Generally, persisting controversies about
the scientific rationale for systematic use, legal bar-
riers, and the lack of a commercially available prepara-
tion appear to have conferred major practical barriers
to intracameral cefuroxime's widespread use,18,44,64
although a commercially available product is
currently being introduced.
Cefuroxime is a second-generation cephalosporin
that is effective against most bacteria that cause
IPOE,26 in particular staphylococci and streptococci
(except MRSA, MRSE, and Enterococcus faecalis). It is
also effective against gram-negative bacteria (except
Pseudomonas aeruginosa) and P acnes. Bactericidal ce-
furoxime concentrations of 2742 mg/L are achieved
within 30 seconds of intracameral injection and drops
to 756 mg/L 1 hour later.27 This was the rationale for
establishing the administration regimen still in use
(1.0 mg/0.1 mL at the end of phacoemulsification cata-
ract surgery before the wound is closed), which started
in Sweden 13 years ago.2730,33 The regimen has been
further supported by the ESCRS randomized trial re-
sults4 and additional retrospective studies in France,
Spain, and the U.K.20,24,31,32 Intracameral cefuroxime
has been shown to have a good safety profile, with
no evidence of increased endothelial cell loss or any
proof of increased bloodaqueous barrier distur-
bance.28 The main disadvantage with cefuroxime
may instead be the gaps in its antimicrobial spectrum.
Notably, there is a striking convergence between the
very low IPOE rate in Sweden (!0.040%; 1992
2009),33 where intracameral cefuroxime is used in
90% of cases, mostly without topical antibiotic pro-
phylaxis, and the equally low rate reported in the
1428 REVIEW/UPDATE: EUROPEAN IPOE PROPHYLAXIS PRACTICE PATTERNS
Netherlands (0.03%),J where topical antibiotics are the
basis of IPOE prophylaxis while intracameral cefurox-
ime is used in only 27% of cases.
Considering the significant differences in IPOE rates
seen in scientific reports (including the ESCRS
randomized trial), it may appear a bit surprising that
intracameral cefuroxime is still far from being consis-
tently adopted by European ophthalmologists either
systematically or in targeted cases (ie, high-risk
patients). However, it should be noticed that the
comparative evidence base is incomplete; for instance,
the ESCRS trial did not answer many relevant ques-
tions such as the relative efficacy of intracameral cefur-
oxime compared with a full course of preoperative,
perioperative, and postoperative topical antibiotics;
subconjunctival injections; or antibiotics in irrigation
fluid. Although a systematic comparison of all
possible options in large randomized trials is not
feasible, it may explain why these ophthalmologists
remain unconvinced that they should have changed
their practices.
It has been suggested that topical fourth-generation
fluoroquinolones such as moxifloxacin and gatifloxa-
cin would be preferable to intracameral cefuroxime,
among other things because of their broader spectrum
of activity.61,6567 Fourth-generation fluoroquinolones
were the most frequent topical antibiotic prophylaxis
used by the American Society of Cataract and Refrac-
tive Surgery survey respondents in 2007,64 and their
efficacy and safety are further supported by a retro-
spective study involving 29 276 cataract surgeries.68
Other studies have also reported that intracameral
moxifloxacin is safe for IPOE prophylaxis.69,70 The
ESCRS guidelines, on the other hand, state that the
use of topical fourth-generation fluoroquinolones,
similar to that of intracameral vancomycin, raises
ethical questions about the use of reserve antibiotics
for prophylaxis, as opposed to treatment of estab-
lished IPOE,10 and the French guidelines state that
topical fluoroquinolones are reserved for curative
treatment of severe eye infections.18
Managing patients with contraindications for cefur-
oxime is a rare issue. Anaphylactic hypersensitivity re-
actions, occurring a few minutes after intracameral
cefuroxime injection, have been reported27,7173 but
are extremely rare, the risk being estimated at
0.0001% to 0.1%.19,74,75 In patients with a known al-
lergy to cephalosporins, cefuroxime is not recommen-
ded.10,18 Suggested alternatives are intracameral
injection of vancomycin with intensive topical quino-
lones (eg, levofloxacin, which may be a useful adjunct
for coverage of gram-negative bacteria)10 or preopera-
tive oral levofloxacin.18
Antibiotic prophylaxis should be regarded as one
component of a global effective strategy for the control
J CATARACT REFRACT SURG - VOL 39, SEPTEMBER 2013
of healthcare-associated infections.48 The first line of
prevention must always be general hygiene and asep-
sis measures, which encompass patient selection, hy-
giene rules in the operating room, and surgical site
antisepsis. As stated by the Scottish Intercollegiate
Guidelines Network, antibiotics may then be used in
a manner that is supported by evidence of effective-
ness, minimizing the effects on the patient's normal
bacterial flora and causing minimal change to the
patient's host defenses.48 To prevent resistance devel-
opment, guidelines have recommended limiting the
prescription of oral fluoroquinolones to high-risk pa-
tients (eg, severe atopic dermatitis).10,76
Pathogens found in proven IPOE cases mostly orig-
inate from the eye-surrounding flora,56 and the micro-
bial spectrum is dominated by gram-positive
staphylococci and streptococci. Intraocular contami-
nation by the facultative pathogenic surrounding flora
has been shown to occur in a high proportion of the
procedures.10,7784 Still, the development of a true
IPOE is rare. In the ESCRS study, 5 significant risk
factors for IPOE development were identified: clear
corneal incisions versus scleral tunnel, surgical com-
plications, silicone versus acrylic intraocular lenses
(IOLs), less experienced surgeon versus more experi-
enced surgeon, and no use of intracameral cefurox-
ime.4 Notably, factors such as the use of an IOL
injector, immunosuppression, diabetes mellitus, and
the use of perioperative topical levofloxacin did not
affect the IPOE rate significantly in the ESCRS study.4
It should be emphasized, however, that the literature
regarding many of these IPOE risk factors is contradic-
tory. Although some risk factors (such as capsule
rupture and vitreous loss) are undisputable, the occur-
rence of an IPOE is very difficult to predict, which em-
phasizes the importance of an effective prophylactic
strategy in routine practice.
In conclusion, intracameral cefuroxime reduces the
risk for IPOE after cataract surgery, as shown by the
ESCRS study and multiple retrospective European
studies, and is recommended by the ESCRS and the
national guidelines in France.
Five years have passed since the publication of the
ESCRS study, but the IPOE prophylaxis routines,
including the use of intracameral cefuroxime, still
vary widely between European countries. There is a
convergence in antisepsis routines with povidone
iodine and in the use of postoperative topical antibi-
otics (despite the findings of the ESCRS study), with
few exceptions. On the contrary, the use of preopera-
tive and intraoperative topical antibiotics and the use
of intracameral or subconjunctival antibiotics differ
significantly between, and also within, countries.
Controversies about the scientific rationale for intra-
cameral cefuroxime use in some countries, legal
 REVIEW/UPDATE: EUROPEAN IPOE PROPHYLAXIS PRACTICE PATTERNS
barriers, and the lack of a commercially available prep-
aration appeared to be the major obstacles to system-
atic application of this routine.
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