REVIEW

CURRENT
OPINION Endophthalmitis after cataract surgery:
epidemiology, risk factors, and evidence
on protection
Prashant Garg a, Aravind Roy b, and Savitri Sharma c

Purpose of review
After publication of the results of the European Society of Cataract and Refractive Surgery (ESCRS) study,
there is a lot of enthusiasm for using intracameral antibiotics for the prevention of postcataract
endophthalmitis. However, despite level 1 evidence, the practice has not been adopted universally. The
aim of this review is to present a summary of the articles published in the last 18 months on this topic.
Recent findings
The published literature highlights that the incidence rate of endophthalmitis declined after 2007.
Simultaneously, there is a rising trend for using intracameral injection of antibiotics at the conclusion of
cataract surgery. Although various drugs have been used for this purpose, nearly all provide comparable
protection. Industry has started manufacturing formulations for commercial availability of intracameral
injection. Innovations are also ongoing to use intraocular lens for drug delivery and developing other
intraocular drug delivery devices.
Summary
Endophthalmitis prevention is at an interesting crossroad.Although there is hesitation the intracameral
injection of antibiotics is increasingly being adopted by physicians, which is likely to grow further with
commercial availability of formulations. However, it will be important to be cautious and report all adverse
reactions associated with this practice.
Keywords
antibiotics, cataract surgery, endophthalmitis, intracameral injection, povidone iodine

INTRODUCTION endophthalmitis rates using intracameral injection

Cataract surgery technique has undergone a series
of transformations from intracapsular cataract
extraction to the now most recent femtosecond
laser-assisted surgery. The objectives of these trans-
formations have been two-fold: improving visual
outcomes and reducing risk of complications.
Endophthalmitis is one such complication that
every surgeon strives to avoid. Although proper
patient selection, meticulous surgery, and strict
adherence to asepsis each help to prevent this com-
plication, physicians additionally use a variety of
antiseptic and antibiotic protocols to prevent or
counteract intraocular contamination. Although
there is widespread agreement on some of the prac-
tices, especially the preoperative use of povidone
iodine (PVI) in the conjunctival cul-de-sac, there
is no unanimity as to the type and route of
antibiotic usage. Furthermore, despite the demon-
stration of a five-fold reduction in postoperative
of cefuroxime in a multicenter prospective random-
ized clinical trial [1], the recommendation of intra-
ocular injection after an uncomplicated surgery has
not been universally accepted.
In the wake of these conflicts and changing
practices, it will be prudent to review the epidemi-
ology, risk factors, and prevention/elimination of
endophthalmitis after cataract surgery – a dream
a
Tej Kohli Cornea Institute, KAR Campus, L. V. Prasad Eye Institute,
Hyderabad, bTej Kohli Cornea Institute, KVC Campus, L. V. Prasad Eye
Institute, Vijayawada and cJhaveri Microbiology Centre, KAR Campus, L.
V. Prasad Eye Institute, Hyderabad, India
Correspondence to Dr Prashant Garg, MBBS, MS, L. V. Prasad Eye
Institute, L. V. Prasad Marg, Banjara Hills, Hyderabad 500034, India.
Tel: +91 40 30612345; fax: +91 40 23548271;
e-mail: prashant@lvpei.org
Curr Opin Ophthalmol 2017, 28:67–72
DOI:10.1097/ICU.0000000000000326

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Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Ophthalmology
KEY POINTS
 Experience of many investigators indicates that with the
adoption of the practice of intracameral antibiotic
injection, the rate of endophthalmitis
reduces significantly.
 There are increasing trends of routine use of
intracameral antibiotic injections for the prevention of
endophthalmitis after cataract surgery.
 Using all direct costs, the budget impact model
demonstrates that the use of commercially available
preparation is going to be more cost effective
compared to the prefilled syringes prepared through
compounding pharmacy.
 In addition to the classical risk factors of postcataract
endophthalmitis, other risk factors identified in recent
literature include nontreatment with intracameral
antibiotics and past history of intravitreal injections.
 Although intracameral therapy has a very good safety
record, reports of intraocular toxicity published in
recent literature suggest the need for close monitoring
and prompt reporting for better risk benefit analysis.
most cataract surgeons strive to achieve. In this
manuscript, we are presenting key findings of the
studies addressing the issue of postcataract endoph-
thalmitis published from January 2015 to June 2016.
EPIDEMIOLOGY
Many nations, societies, and institutions monitor
the incidence of cataract surgery-associated endoph-
thalmitis. On the basis of the reports published in
ophthalmic literature, the current incidence varies
from 0.03 to 0.2% across the world [2]. These rates
are much lower than the incidence rate of 0.128%
reported between 1963 and 2003. Beginning 2003, a
slight increase in the incidence was registered,
which was attributed to the practice of clear corneal
incision (0.29 compared to 0.05% with sclerocor-
neal incision) [3,4].
After publication of the ESCRS report [1], several
investigators evaluated the rates of postcataract
surgery endophthalmitis and its relationship with
antibiotic and antiseptic prophylaxis practices
adopted by physicians.
Nentwich et al. [5 ] published the incidence of
&&
postoperative endophthalmitis from 1990 to 2009 at
a single center in Germany. For data analysis, the
authors divided the study period into three groups:
Period 1 (1990–1992), no standardized prophylaxis
regimen; period 2 (1993–1998), preoperative topical
antibiotic, PVI 10.0% periorbitally, and 1 drop of
PVI 1.0% in the conjunctiva sac; and period 3
68 www.co-ophthalmology.com
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
(1999–2009), similar to period 2 except with irriga-
tion of the conjunctival sac with 10 ml of PVI 1.0%.
The incidence of endophthalmitis decreased from
0.338% in period 1 to 0.224% in period 2 to 0.041%
in period 3 (P < 0.001). The authors attributed this
reduction to implementation of a preoperative pro-
phylaxis protocol using copious PVI. It is important
to note that none of these cases received intracam-
eral antibiotics. Asencio et al. [6], in a study of 13
years duration, reported a significant reduction in
postoperative endophthalmitis rates (from 0.34 to
0.03%) after change in the type of antibiotic pro-
phylaxis from subconjunctival gentamicin to the
addition of both vancomycin and gentamicin to
the irrigating solution. In a population-based study
from France, Daien et al. [7] reported a decreasing
trend (from 0.11 to 0.05%) of postoperative endoph-
thalmitis from 2010 to 2014. This reduction in the
incidence was attributed to increase in the usage of
intracameral cefuroxime (11.1% in 2010 to 79.1% in
2014). The lower incidence was noted even in
patients who received intracameral cefuroxime fol-
lowing posterior capsular rupture. In yet another
study from France [8 ] wherein the authors col-
&&
lected information from national database using
billing codes, it was observed that during the period
from 2005 to 2014 the incidence of endophthalmitis
reduced from 0.145 to 0.053% whereas the usage of
intracameral injection increased from 0.60 in 2005
to 80.03% in 2014.
Haripriya et al. [9], in a retrospective registry-
based study, reported a 0.02% rate of endophthal-
mitis following the introduction of routine use of
intracameral moxifloxacin, which was a four-fold
reduction from the rates before the adoption of the
practice of intracameral antibiotics. In a retrospec-
tive longitudinal cohort study from Australia, Au
et al. [10 ] reported a nine-fold reduction (0.43–
&
0.049%, P < 0.0001) in postcataract surgery endoph-
thalmitis after the introduction of the routine use of
intracameral vancomycin.
Reports of reduction in rates of endophthalmitis
have been published from other parts of the world as
well and nearly all attributed it to the use of intra-
cameral antibiotics [6,11 ,12–14].
&
The microbiology of endophthalmitis has
remained same from the time of publication of
the endophthalmitis vitrectomy study (EVS), with
Gram-positive bacteria being most common
(94.2%) and Gram-negative bacteria accounting
for only as small fraction of culture positive cases
(5.9%). Though dominated by Gram-positive cocci,
the spectrum of organisms includes higher percent-
age of Gram-negative bacteria and fungi in post-
operative endophthalmitis reported from Asian
countries. With the advent of automated methods
Volume 28  Number 1  January 2017

of bacterial and yeast identification using API or
Vitek systems (bioMerieux, France) as well as
increasing use of molecular methods, much wider
spectrum of organisms are lately being identified
expanding the spectrum of causative organisms
associated with postoperative endophthalmitis.
The first case of Rothia mucilaginosa, a Gram-positive
bacteria of Micrococcaceae family, was reported
recently from a case of postcataract endophthalmitis
[15]. Similarly, among the coagulase negative staph-
ylococci, Staphylococcus hemolyticus is being increas-
ingly reported. [16] A mini review identified
Fusarium and Aspergillus species to be the common-
est mould and Candida species to be the commonest
yeast involved in fungal endophthalmitis associated
with cataract surgery [17 ].
&
RISK FACTORS
The knowledge of risk factors of endophthalmitis is
crucial in its prevention. This helps not only patient
selection and appropriate counseling but also intra-
operative interventions and postoperative vigilance.
Few of the well-known risk factors are advanced age
(80 years or more), immunocompromised state sec-
ondary to systemic diseases, presence of septic focus
in and around the eye, posterior capsular break, and
wound leak.
Lundström et al. [18] analyzed data of Swedish
national cataract register and found nontreatment
with intracameral antibiotic, communication with
vitreous, and age over 85 years as three most com-
mon risk factors. In another large epidemiological
study by Jabbarvand et al. [11 ], diabetes mellitus,
&
older age (above 80 years), conventional large
incision extracapsular cataract extraction, and peri-
operative communication with the vitreous were
associated with a significantly higher risk of
endophthalmitis. The authors also reported that
compared with no prophylaxis, use of preoperative
antibiotics and subconjunctival injection at the
conclusion of surgery were associated with a 40–
50% reduced odds of endophthalmitis (P ¼ 0.2) and
no cases of endophthalmitis occurred in the group
that received intracameral cefuroxime. The authors
concluded that intracameral injection of antibiotic
may be far more effective than traditional topical
or subconjunctival approaches for prevention of
endophthalmitis.
Same risk factors were identified in a nested case
control study of a retrospective cohort by our group
[19].
Weston et al. [20 ] found that the rate of post-
&
operative endophthalmitis was significantly lower
in patients where IOLs were inserted using injec-
tors compared with the forceps-inserted foldable
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Endophthalmitis after cataract surgery Garg et al.
IOL group (0.008 vs. 0.081%, P ¼ 0.008). This
difference remained significant when controlling
for posterior capsular rupture and lens material.
The study supports the use of injectable IOLs and
the availability of preloaded IOLs will ensure
greater safety.
In addition to these conventional risk factors,
emerging one is cataract surgery in patients who had
previously undergone intravitreal injections. Hahn
et al. [21 ] published surgical and postoperative
&&
complications associated with cataracts surgery in
a population that received intravitreal injection and
found that prior injections were associated with
increased risk of both acute [HR, 2.29; 95% confi-
dence interval (CI), 1.001–5.22] and delayed-onset
endophthalmitis (HR, 3.65; 95% CI, 1.65–8.05). The
results of the study suggest the need for additional
intraoperative caution and postoperative vigilance
in these patients.
PREFERRED PRACTICES TOWARD
PREVENTION OF ENDOPHTHALMITIS
Physicians follow a variety of perioperative proto-
cols for prevention of endophthalmitis. These
include: preoperative topical and/or oral antibiotic;
use of PVI including irrigation of conjunctival cul-
de-sac with PVI solution; antibiotics in irrigating
solutions; subconjunctival injection; postoperative
topical antibiotics; and more recently, intracameral
injection of antibiotic at the conclusion of surgery.
The question of preferred practice for prevention of
endophthalmitis has been studied time and again by
several investigators including national and inter-
national societies [22–25]. Nearly all of these studies
found that there is general acceptance on use of PVI
and postoperative topical antibiotics. The use of
preoperative and perioperative antibiotics, however,
varies widely between and within countries. The
first iteration of the European Observatory of Cata-
ract Surgery initiated to track changes in surgical
antiseptic and antibiotic practices in cataract
surgery subsequent to the publication of ESCRS
guidelines in nine European countries confirmed
these findings with universal adoption of intracam-
eral cefuroxime in some whereas in others it was less
than half [26].
Despite this variability, a review of the pub-
lished literature shows increasing trends for using
intracameral injection of antibiotics. Survey of the
members of the ASCRS conducted in 2014 [27 ]
&
showed that 47% respondents already started using
or planning to adopt intracameral injection of
antibiotics. In France, the use of intracameral
cefuroxime increased from 11.1% in 2010 to
79.1% in 2014.
www.co-ophthalmology.com 69
Ophthalmology
Reasons for variability in adoption of
intracameral injections
Nearly all surveys point out that a majority of surgeons
not using intracameral prophylaxis expressed concern
about the risks of using formulations that are neither
approved nor available commercially for ophthalmic
usage. Kessel et al. [28 ] in their meta-analysis ident-
&&
ified the lack of availability of a commercial prep-
aration, fear of dilution errors, and the lack of
support from major ophthalmology associations as
major barriers to universal usage of intracameral anti-
biotics. Further, after the launch of commercially
available preparation specifically registered for intra-
cameral use in Europe, there was a significant increase
in number of surgeons using intracameral antibiotics
and most surgeons in countries wherein intracameral
injection practices were widely adopted started using
this formulation [27 ,28 ].
& &&
EVIDENCE FOR AND AGAINST DIFFERENT
PROTOCOLS FOR PREVENTION OF
ENDOPHTHALMITIS
Ever since the publication of the ESCRS study, many
investigators have evaluated the change in rate of
endophthalmitis and its relationship with antibiotic
and antiseptic prophylaxis practices. Some of these
studies have been highlighted in the epidemiology
section of this manuscript.
Evidence for use of povidone iodine
By and large, the use of PVI has the highest level of
evidence and is universally accepted as the single most
effective intervention for reducing risk of endophthal-
mitis [29]. In a recent review of preoperative prophy-
laxis measures, Grzybowski et al. [30] attributed 57–
60.8% reduction of the conjunctival flora by irrigation
of conjunctival cul-de-sac with 5% PVI before surgery.
Nentwich et al. [5 ] reported a 0.041% incidence of
&&
endophthalmitis over a 20-year period that is similar
to the rates in the group, which received intracameral
cefuroxime in the ESCRS study (0.062%) [31]. They
attributed such a low rate to meticulous preoperative
protocol involving copious irrigation of the conjunc-
tival sac with 10 ml of 1% PVI.
Evidence in favor of intracameral antibiotic
injection
Kessel et al. [28 ] conducted a systematic review of
&&
published literature on intracameral antibiotics use.
In aggregated data of all studies, they noted endoph-
thalmitis rate of 0.035% in cataract surgeries
wherein intracameral antibiotics were used as
opposed to 0.2% where intracameral antibiotics
70 www.co-ophthalmology.com
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
were not used. None of the reports included in this
analysis reported adverse events attributable to
intracameral antibiotic usage. The authors esti-
mated that two of four cases of endophthalmitis
could be prevented if intracameral cefuroxime was
used and strongly recommended its usage.
Contrary to reports that documented significant
protection with intracameral injections, Sharma
et al. [32 ] found no significant reduction in the
&
rates of endophthalmitis with the use of intracam-
eral cefuroxime. The intracameral group, however,
was associated with lower rate of culture positive
endophthalmitis. The debate of intracameral versus
topical antibiotics is very well captured in recent
editorials by Olson [33] and Javitt [34].
Which antibiotics are more effective in
prevention of endophthalmitis?
Several antibiotics are used as intracameral injections
and include cefuroxime, cefazolin, vancomycin, ami-
noglycosides, and fluoroquinolones. In the meta-
analysis, Kessel et al. [28 ] noted a significantly lower
&&
rate of endophthalmitis in patients treated with intra-
cameral cefuroxime, cefazolin, and moxifloxacin. Sig-
nificance was, however, not achieved for intracameral
vancomycin. In an observational cohort study of
315 246 phacoemulsification procedures, Herrinton
et al. [35 ] did not find any difference in risk of
&
endophthalmitis among intracameral cefuroxime
and moxifloxacin groups. In the subgroup of eyes that
did not receive intracameral antibiotics, there was no
difference in risk among eyes that received topical
fluoroquinolone alone. The risk was, however, elev-
ated in the group that received aminoglycosides and
was comparable to the group that did not receive any
topical antibiotics. The authors, however, did not find
a benefit of intracameral over topical antibiotics in
eyes that developed posterior capsular rent.
CONCERNS: WHAT HAS BEEN THE
SAFETY RECORD?
Safety of intraocular antibiotics has always been a
concern for physicians and is one of the major
reasons for not adopting the practice for routine
use. This apprehension is despite very good safety
records in several large series including the ESCRS
study. The primary reason is the need for com-
pounding pharmacy with associated risk of dilution
errors with resultant toxicity. These possibilities are
not entirely theoretical. Witkin et al. [36 ] described
&&
a syndrome of hemorrhagic occlusive retinal vascu-
litis (HORV) after uncomplicated cataract surgery
possibly associated with the intracameral use of van-
comycin. Faure et al. [37 ] published a case of sudden
&&
Volume 28  Number 1  January 2017

loss of vision from retinal toxicity related to the
intracameral cefuroxime. Promelle et al. [38 ] carried
&
out a prospective study to evaluate tolerability of
intracameral cefuroxime in patients with known
penicillin allergy. They found that one out of 43 cases
showed positive skin test with cefuroxime and two
out of 36 patients with negative skin test developed
allergic conjunctivitis postoperatively.
All these publications bring forth a question ‘Is it
justified to expose our patients to the risk of intra-
ocular toxicity although extremely low in an attempt
to prevent equally rare complication?’ Well, there is
no definitive answer to this question but these reports
clearly highlight the need for being vigilant.
FUTURE TRENDS IN PROPHYLAXIS OF
INFECTIOUS ENDOPHTHALMITIS
With increasing enthusiasm in intracameral anti-
biotics and support for its uses by regulatory
agencies and national and international ophthal-
mology societies [27 ], a favorable environment for
&
innovations has been created that is helping avail-
ability of commercial preparations as well as newer
ways of drug delivery [33].
Commercial preparation of cefuroxime (Apro-
kam) is now available in European union. A budget
impact assessment model comparing commercially
available unit dose of cefuroxime (Aprokam) to
hospital-prepared or commercially procured pre-
filled syringes recommended former and attributed
it to direct lower costs, decreased risk of dilution
errors, and liability coverage [39].
Other novel approaches for prophylaxis include
drug delivery nanoparticles. Double crosslinking has
been used to conjugate chitosan gelatin with cefur-
oxime and has been found to result in controlled in-
vivo drug release with optimal ocular bio-distribution
[40 ]. Attempts have been made to coat IOL surfaces
&&
as well as presoak IOLs with antibiotics. In addition,
attempts have been made to load haptics of IOL with
drugs, which acts as a slow release system without
interfering with the optical quality of the lens [41].
Rabbit eyes implanted with intraocular lenses
presoaked with moxifloxacin had significant
reduction in endophthalmitis, which reduced further
on combining it with intracameral antibiotics [42].
CONCLUSION
With population-based epidemiological studies pro-
viding evidence of reduction in incidence rate of
endophthalmitis attributable to intracameral injec-
tion of antibiotics, the practice is becoming more
popular. This change is promoting development of
commercial preparations of antibiotics specifically
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Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
Endophthalmitis after cataract surgery Garg et al.
meant for intracameral use that in turn will help
alleviate apprehensions associated with compound-
ing pharmacy and greater acceptance of the practice.
Though few, reports of adverse events clearly point
toward the need for monitoring side-effects. It is an
exciting time in prevention of this serious side effect.
Acknowledgements
None.
Financial support and sponsorship
The authors have no financial disclosures to make
regarding the work published in this manuscript.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
& of special interest
&& of outstanding interest
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&& endophthalmitis: a systematic review and meta-analysis. Acta Ophthalmol
2015; 93:303–317.
The authors in this systematic review aimed at evaluating the effect of intracameral
and topical antibiotics on the prevention of endophthalmitis after cataract surgery.
The pooled data showed that the incidence rate of endophthalmitis was 0.035%
when intracameral antibiotics were used compared to 0.2% when intracameral
antibiotics were not used. There was no evidence of the value of topical antibiotic
therapy in reducing endophthalmitis.
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29. Ciulla TA, Starr MB, Masket S. Bacterial endophthalmitis prophylaxis for
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30. Grzybowski A, Kuklo P, Pieczynski J, et al. A review of preoperative man-
oeuvres for prophylaxis of endophthalmitis in intraocular surgery: topical
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2016; 27:9–23.
31. Endophthalmitis Study Group. European Society of Cataract & Refractive
Surgeons. Prophylaxis of postoperative endophthalmitis following cataract
surgery: results of the ESCRS multicenter study and identification of risk
factors. J Cataract Refract Surg 2007; 33:978–988.
32. Sharma S, Sahu SK, Dhillon V, et al. Reevaluating intracameral cefuroxime as
& a prophylaxis against endophthalmitis after cataract surgery in India. J Catar-
act Refract Surg 2015; 41:393–399.
This prospective randomized study did not find a significant benefit from the use of
intracameral cefuroxime in prevention of endophthalmitis.
33. Olson RJ. Has the time come for all to routinely use intracameral antibiotic
prophylaxis at the time of cataract surgery? Am J Ophthalmol 2016; 166:xii–
xiv.
34. Javitt JC. Intracameral antibiotics reduce the risk of endophthalmitis after
cataract surgery: does the preponderance of the evidence mandate a global
change in practice? Ophthalmology 2016; 123:226–231.
35. Herrinton LJ, Shorstein NH, Paschal JF, et al. Comparative effectiveness of
& antibiotic prophylaxis in cataract surgery. Ophthalmology 2016; 123:287–
294.
This study published from United States upheld the value of intracameral antibiotic
in preventing postcataract endophthalmitis. Most significant finding of the study
was that administration of topical antibiotics does not add to the effectiveness of
intracameral regimen.
36. Witkin AJ, Shah AR, Engstrom RE, et al. Postoperative hemorrhagic occlusive
&& retinal vasculitis: expanding the clinical spectrum and possible association
with vancomycin. Ophthalmology 2015; 122:1438–1451.
In this case series, the authors described 11 eyes of six patients from six
institutions who developed painless vision loss from occlusive vasculitis that
was attributed to the intracameral injection of vancomycin.
37. Faure C, Perreira D, Audo I. Retinal toxicity after intracameral use of a standard
&& dose of cefuroxime during cataract surgery. Doc Ophthalmol 2015; 130:57–
63.
The authors described a patient who developed diffuse retinal pallor with small
intraretinal cysts 2 days after cataract surgery attributed to intracameral cefurox-
ime.
38. Promelle V, Jany B, Drimbea A, et al. Tolerability of intracameral cefuroxime
& during cataract surgery in case of penicillin allergy. J Fr Ophtalmol 2015;
38:283–287.
As cross-reaction of cefuroxime is known in patients allergic to penicillin, this study
assessed the tolerability of intracameral cefuroxime in patients with a penicillin
allergy. Positive skin reaction was seen in one of 43 patients and two of 36 patients
with negative skin test showing allergic conjunctival reaction.
39. Purslow C, Davey K, Johnson M, et al. Budget impact assessment of
Aprokam1 compared with unlicensed cefuroxime for prophylaxis of post-
cataract surgery endophthalmitis. BMC Ophthalmol 2015; 15:72.
40. Andrei G, Peptu CA, Popa M, et al. Formulation and evaluation of cefuroxime
&& loaded submicron particles for ophthalmic delivery. Int J Pharm 2015;
493:16–29.
Authors of this study developed a budget impact model using direct cost items and
estimated the potential financial implications of using Aprokam (commercially
available product) over cefuroxime prepared through compounding pharmacy
for intracameral administration. The authors found that the direct cost of commer-
cially available licensed product is much lower.
41. Eibl-Lindner KH, Wertheimer C, Kampik A. [Intraocular lens as a drug delivery
device: state of the art and future perspective]. Klin Monbl Augenheilkd 2016;
233:172–178.
42. Yovel OS, Ben Eliahu S, Kleinmann G. Prevention of Staphylococcus epi-
dermidis endophthalmitis by different moxifloxacin prophylaxis routes. Curr
Drug Deliv 2016; 13:90–94.
Volume 28  Number 1  January 2017