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 prophylactic routines, topical and intracameral antibiotic use, and coherence to the European Society of
Cataract & Refractive Surgeons (ESCRS) 2007 guidelines. Although the reliability and completeness 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 proprietary 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 proportion of outpatient and second-eye procedures.5
Infectious postoperative endophthalmitis (IPOE) is
the most dreaded complication of cataract surgery.
Infectious postoperative endophthalmitis has a devastating 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
Q 2013 ASCRS and ESCRS
Published by Elsevier Inc.

Increasing resistance of Staphylococcus sp to a broad

spectrum of antibiotics, including the latest fourthgeneration 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 substantial 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 complication.19,20 Preoperative antisepsis of the periocular
area with topical povidoneiodine is widely adopted
and is considered the basic standard of IPOE prevention,21 although chlorhexidine is preferred in some
0886-3350/$ - see front matter
http://dx.doi.org/10.1016/j.jcrs.2013.06.014

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REVIEW/UPDATE: EUROPEAN IPOE PROPHYLAXIS PRACTICE PATTERNS

countries. Antibiotic prophylaxis is another commonly

used preventive measure. However, proposed antibiotic prophylaxis protocols are very diverse in agents
used (eg, aminoglycosides, cephalosporins, fluoroquinolones, chloramphenicol), administration routes
(topical, intraocular, subconjunctival, oral, intravenous), and timing (preoperative, intraoperative, perioperative, postoperative).2225
The European Society of Cataract & Refractive Surgeons (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 results were coherent, with data from over 400 000 patients 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 surgeries 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 systematic intracameral cefuroxime injections.15,20,24,31,32
Given these data, we decided to assess the IPOE
prophylaxis practice patterns and intracameral cefuroxime use in Europe in 2012, ie, 5 years after publication 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

Table 1. Pathogens found in proven cases of post-cataractsurgery infectious endophthalmitis.

Organism
Coagulase-negative staphylococci
Staphylococcus aureus
Streptococci (-haemolytic streptococci,
S pneumoniae, a-haemolytic streptococci
including S mitis and S salivarius)
Enterococci
Gram-negative bacteria, including Pseudomonas
aeruginosa (occurs rarely)
Fungi (Candida sp, Aspergillus sp, Fusarium sp)
Polymicrobial culture
Negative or equivocal culture

Percentage
of Cases
3080
1020
1035

!5
520
Up to 8
!5
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 domains: (1) Current cataract surgery procedures and known
IPOE incidence rates from a National Registry or other sources; (2) nonantibiotic prophylactic measures used: hygiene
rules, patient selection, antisepsis; (3) topical antibiotic use:
type(s) and rationale, dose regimens; (4) intracameral antibiotic 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

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; Autonoma University of Barcelona (Guell), Barcelona, Spain; Hopital de la
Croix-Rousse (Kodjikian), Lyon, France; Istituto de Clinica Oculistica (Mencucci), Cattedra di Ottica Fisiopathologica, Florence, Italy;
Department of Ophthalmology (Nuijts), Academic Hospital Maastricht, 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, SE901 85 Umea, Sweden. E-mail: anders.behndig@ophthal.umu.se.

Sweden has a long experience with intracameral

cefuroxime-based antibiotic prophylaxis, which has already
been highlighted. The National Cataract Register was implemented 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, hygiene 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

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REVIEW/UPDATE: EUROPEAN IPOE PROPHYLAXIS PRACTICE PATTERNS

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

Country

Number of
Cataract
Surgeries
per Year

SwedenA

91 000

FranceB,C

United
KingdomD

630 000

IPOE Incidence
Rate (Period)/
Origin of Source Data

Main Guidelines
for Antibiotic
Prophylaxis

!0.04% (19922009)
!0.02% (2012)

National Cataract
Registry;
Swedish Ophthalmological
Society

National registry33
(covering O98%
of procedures)*
0,21%0.32% (19922002)
0.03%0.06% (20072011)

National registry14
(non-mandatory reporting);
limited surveys)12,34,32
O330 000
0.03%0.20% (19972006)

National Agency for

Health Products
Safety (AFSSAPS)18

Scottish Intercollegiate
Guidelines Network49;
Royal College of
Ophthalmologists50

Multiple, often large

surveys7,13,19,20,23,37-45
SpainE

200 000

0.48%/0.50%
0.056%/0.11% (1999-2008)

ESCRS guidelines10

IC Cefuroxime
Prophylaxis Adoption
Rates/Specific Factors
Favoring or Limiting Use
90% (2012)

Omission of IC
antibiotics considered
unethical
!5% (2006)
40% (2011)
Recommended by
regulatory national
guidelines since 201118
10% (2005)23
45%-61%
(2009-2010)19,45,48
Historically, the
subconjunctival route
was the preferred choice23
Not known

Single-centre surveys15,24,31
GermanyF

700 000

BelgiumG

120 000

ItalyH

350 000

0.15% (1999)
0.060.07% (20062011)
Multicenter or singlecenter surveys25,51,52
0.036%
(20092011)
Extrapolated from the
EUREQUO registry5

ESCRS guidelines10

Not known,
probably !20%
Opposed by legal issues

ESCRS guidelines10

Not known

0.05%0.35%

ESCRS guidelines10

Implementation of
ESCRS guidelines
started in 2009
20% (2010)53

Extrapolated from the

ESCRS trial4
NetherlandsI,J

PolandK

140 000

O160 000

0.03% (2012)

National registry
(mandatory
outcome reporting)
0.29%* (2004)55
Current rate not known

Dutch Ophthalmological
Society

Implementation of
ESCRS guidelines started
in 2008
27% (2010)

Topical Antibiotic
Prophylaxis
Not recommended
and no routine use
except RLE or highrisk patients

Preoperative: 28%
(2007)36, currently
not recommended
Per-/post-operative:
95%(2007)36, currently
recommended
Preoperative:
6%-9% (2005)23

Per-/post-operative:
90% (2005)23
Preoperative:
variable15,31
Per-/post-operative:
100%15,24,31
Pre- and per-/
post-operative: 100%

Not known

Preoperative: 76%,
Peroperative: 40%
Postoperative: 100% 53

Pre- and per-/

post-operative:
100%

Recommended in
high-risk patients only
Polish Society of
Ophthalmologists

Not known, probably

not used in most cases
Off-label use, complex
preparation

Not known

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.

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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 analyses 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.

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 intracameral 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.

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 reported 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. Recommended 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, antisepsis 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 Cefuroxime (1.0 mg/0.1 mL) intracameral injection at the end of
the procedure is a strongly recommended antibiotic prophylaxis in the absence of any contraindication to cephalosporins.18 The drug is usually prepared by the center's local
pharmacy. Subconjunctival injections and antibiotic prophylaxis 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 postoperative 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

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 cataract 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 phacoemulsification procedures reported that intracameral cefuroxime
was a safe alternative to subconjunctival cefuroxime with a
significantly lower rate of IPOE (subconjunctival versus intracameral 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 procedures performed in 2011 at Barcelona's Instituto de Microciruga 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 guidelines, is used very commonly in private and public Spanish
institutions: preoperative prophylaxis combining lid hygiene (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 povidoneiodine 5% solution into the conjunctival sac. In case

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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 patients, 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 IntraokularlinsenImplantation, 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 surgeries 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 results 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 surgeries performed in 1996. The survey found a mean IPOE
rate of 0.148% and provided a comprehensive picture of prophylactic 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 antibiotics were added to the irrigating solution; intracameral injection 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 respondents) to the conjunctiva was also associated with a significantly decreased risk for IPOE (OR, 0.59; 95% CI,
0.36-0.99). However, the use of preoperative topical antibiotics 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 antibiotics (quinolones, aminoglycosides) are applied before, during, 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 publication of the ESCRS 2007 guidelines. Intracameral

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 prevention guidelines, but German ophthalmologists tend to
follow the ESCRS 2007 recommendations.

Belgium
The estimated annual number of cataract surgery procedures is 120 000.G The number of active centers is unknown.
Belgium does not have a mandatory registry of postoperative 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 endophthalmitis 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 preoperative 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 hydration) is used in 100% of cataract surgery procedures, according 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 procedures 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 antibiotic/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 procedures, 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 vancomycin (48%) is used in 41% of procedures.52 Syringes are
prepared by local pharmacies. Since there are no specific

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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 academic hospitals, and 8% within an increasing number of
ambulatory surgery centers with multiple facilities.I
Outcome registration is mandatory for all surgeons, as requested 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 available 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; administrations and dosages vary. Use of intracameral antibiotics
started in 2007 after the publication of the ESCRS 2007 guidelines 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 Ophthalmological 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 pathogens, and 2.4% polymicrobial cultures.

Poland
According to the national health insurance refunding system, 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 selection bias due to the small size of the study sample. In addition, 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 database, 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

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 (blepharitis, 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 antibiotics are probably not injected in most procedures because of
off-label use and complex preparation.K However, cefuroxime (1.0 mg/0.1 mL) has been used in 100% of the procedures 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 significantly and often diverge from the antibiotic prophylaxis 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 surgeries, 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 limitation is not specific to this review but rather reflects
the lack of adequate epidemiologic tools and systematic reporting in most countries. In addition, this overview 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 pretend to report actual practice patterns and epidemiological 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.

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Practice patterns for general hygiene rules in the

operating room and systematic preoperative antisepsis with povidoneiodine or chlorhexidine tend to
converge. The use of preoperative antisepsis with povidoneiodine (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 povidoneiodine is contraindicated, chlorhexidine 0.05%
is an alternative.10,18,59 The use of chlorhexidine as a
primary antisepsis agent in Sweden has proven efficient and safe over a long period.33,60
Regarding antibiotic prophylaxis regimens, data of
landmark importance came out of the ESCRS randomized 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 perioperative 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 levofloxacin 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 cefuroxime, 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 antibiotic prophylaxis is also commonly used in all countries (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, levofloxacin was administered to all groups postoperatively. According to the authors, the relatively high
incidence rates of IPOE in subgroups without intracameral cefuroxime suggested that postoperative levofloxacin alone conferred little benefit. An alternative
explanation is that had this type of antibiotic prophylaxis not been used, the rates across all groups would
have been higher.4
Much wider variation in preoperative and perioperative 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 previous systematic review concluded that its efficacy was
not yet scientifically proven.21 Thus, the ESCRS 2007
guidelines cite preoperative topical antibiotic prophylaxis as an option to consider,10 while the French 2011

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 prevention 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 Intercollegiate Guidelines Network,48 and by Canadian guidelines,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 recommendations 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 subconjunctival 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 barriers, and the lack of a commercially available preparation 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 cefuroxime 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 cataract 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 results4 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 disturbance.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 prophylaxis, and the equally low rate reported in the

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REVIEW/UPDATE: EUROPEAN IPOE PROPHYLAXIS PRACTICE PATTERNS

Netherlands (0.03%),J where topical antibiotics are the

basis of IPOE prophylaxis while intracameral cefuroxime 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 consistently 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 questions such as the relative efficacy of intracameral cefuroxime 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 gatifloxacin 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 Refractive Surgery survey respondents in 2007,64 and their
efficacy and safety are further supported by a retrospective 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 established 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 cefuroxime is a rare issue. Anaphylactic hypersensitivity reactions, 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 allergy to cephalosporins, cefuroxime is not recommended.10,18 Suggested alternatives are intracameral
injection of vancomycin with intensive topical quinolones (eg, levofloxacin, which may be a useful adjunct
for coverage of gram-negative bacteria)10 or preoperative oral levofloxacin.18
Antibiotic prophylaxis should be regarded as one
component of a global effective strategy for the control

of healthcare-associated infections.48 The first line of

prevention must always be general hygiene and asepsis measures, which encompass patient selection, hygiene 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 effectiveness, minimizing the effects on the patient's normal
bacterial flora and causing minimal change to the
patient's host defenses.48 To prevent resistance development, guidelines have recommended limiting the
prescription of oral fluoroquinolones to high-risk patients (eg, severe atopic dermatitis).10,76
Pathogens found in proven IPOE cases mostly originate from the eye-surrounding flora,56 and the microbial spectrum is dominated by gram-positive
staphylococci and streptococci. Intraocular contamination 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 complications, silicone versus acrylic intraocular lenses
(IOLs), less experienced surgeon versus more experienced surgeon, and no use of intracameral cefuroxime.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 contradictory. Although some risk factors (such as capsule
rupture and vitreous loss) are undisputable, the occurrence of an IPOE is very difficult to predict, which emphasizes 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 antibiotics (despite the findings of the ESCRS study), with
few exceptions. On the contrary, the use of preoperative 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 intracameral cefuroxime use in some countries, legal

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barriers, and the lack of a commercially available preparation appeared to be the major obstacles to systematic application of this routine.
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