The Role of Topical Antibiotic Prophylaxis to

Prevent Endophthalmitis after Intravitreal

Injection
Philip Storey, MD, MPH,1 Michael Dollin, MD,1 John Pitcher, MD,1 Sahitya Reddy, BA,2 Joseph Vojtko, BA,2
James Vander, MD,1 Jason Hsu, MD,1 Sunir J. Garg, MD,1for the Post-Injection Endophthalmitis Study Team*
Objective: To compare the incidence of endophthalmitis after intravitreal injection with and without topical
postinjection antibiotic prophylaxis.
Design: Retrospective case-control study.
Participants: All patients treated with intravitreal injection of ranibizumab, bevacizumab, or aibercept for
a variety of retinal vascular diseases at a single, large retina practice between January 1, 2009, and October 1,
2012, were included.
Methods: The total numbers of patients and injections were determined from a review of billing code and
practice management records. Endophthalmitis cases were determined from billing records and from an infection
log. All cases of endophthalmitis were conrmed with chart review. A 28-month period when topical antibiotics
were prescribed after intravitreal injection was compared with a 9-month period when topical antibiotics were not
prescribed. Patients treated during an 8-month transition period were excluded to allow for the conversion of
antibiotic prescription practices.
Main Outcome Measures: Incidence of endophthalmitis, visual acuity outcomes, and microbial spectrum.
Results: During the study period, a total of 117 171 intravitreal injections were performed (57 654 injections
during the topical antibiotic period, 24 617 during the transition period, and 34 900 during the no-antibiotic
period), with a total of 44 cases of suspected endophthalmitis (0.038%; 1 in 2663 injections), 17 of which
showed culture-positive results (0.015%; 1 in 6892 injections). During the 28-month topical antibiotic period,
there were 28 cases of suspected endophthalmitis (0.049%; 1 in 2059 injections), 10 of which showed culturepositive results (0.017%; 1 in 5765 injections). During the 9-month no-antibiotic period, there were 11 cases of
suspected endophthalmitis (0.032%; 1 in 3173 injections), 4 of which showed culture-positive results (0.011%; 1
in 8725 injections). Topical antibiotic use was associated with a trend toward increased risk of suspected
endophthalmitis (odds ratio [OR], 1.54; 95% condence interval [CI], 0.77e3.10) and culture-positive endophthalmitis (OR, 1.51; 95% CI, 0.47e4.83).
Conclusions: The incidence of endophthalmitis after intravitreal injection is low. Using postinjection topical
antibiotic drops does not reduce the risk of endophthalmitis developing and is associated with a trend toward
higher incidence of endophthalmitis. Ophthalmology 2014;121:283-289 2014 by the American Academy of
Ophthalmology.
*Group members listed online in Appendix 1 (available at http://aaojournal.org).

The use of intravitreal injections for eye disease has increased

dramatically because of the efcacy of several medications,
including steroids and antievascular endothelial growth
factor (VEGF) agents. Although uncommon, postinjection
endophthalmitis can cause signicant ocular morbidity.1
Prophylactic measures, including the use of various topical
antibiotics, have been used to reduce the incidence of
endophthalmitis. Topical antibiotics long have been
the standard of care after ocular surgery, and this
practice was carried over to ocular injections. Although
topical antibiotics reduce conjunctival bacterial growth2
and may have a possible synergistic effect when combined
with povidoneeiodine,3 no randomized trials have
 2014 by the American Academy of Ophthalmology
Published by Elsevier Inc.

demonstrated a reduction in postprocedure or postinjection

endophthalmitis through use of prophylactic antibiotic
drops.4e6 Recent evidence suggests that topical antibiotics
may even be harmful by increasing antibiotic-resistant
bacterial strains7,8 and may increase the risk of endophthalmitis.9 The previous studies were relatively small and may
not have been powered adequately to detect a difference in
endophthalmitis incidence. Many physicians continue to
prescribe antibiotics after intravitreal injection.10 This study
evaluates the role of topical antibiotic prophylaxis after
intravitreal injection of anti-VEGF agents as well as the
microbial spectrum after injection in the largest series of
intravitreal injections to date.
ISSN 0161-6420/14/$ - see front matter
http://dx.doi.org/10.1016/j.ophtha.2013.08.037

283

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Volume 121, Number 1, January 2014

Methods

Transition Period

Overview

Before May 2011, all patients were prescribed postinjection topical

antibiotics to use 4 times daily for 4 days. As early as June 2011,
some physicians stopped using antibiotic prophylaxis, and on
September 1, 2011, retinal physicians practicing at Wills Eye
Institute adopted a practice-wide policy stopping use of postinjection topical antibiotics. We considered May 1, 2011, through
December 31, 2011, to be a transition period during which
physicians and patients changed prophylaxis strategies. A review
of all endophthalmitis cases conrmed that all patients from
January 1, 2009, through April 30, 2011, received postinjection
antibiotics, whereas all patients from January 1, 2012, through
October 1, 2012, did not receive postinjection antibiotics. We did
not include injections or endophthalmitis cases during the transition period in our analysis of endophthalmitis incidence. We did,
however, include transition period cases in our analysis of visual
outcomes and bacterial spectrum.

This single-center retrospective, comparative, case-control study

was approved by the Wills Eye Institute Institutional Review
Board. As part of an ongoing infection surveillance program, the
authors prospectively recorded endophthalmitis cases occurring
after intravitreal injection secondary to intravitreal injection of
bevacizumab (Genentech, South San Francisco, CA), ranibizumab
(Genentech), triamcinolone, or aibercept (Regeneron, Tarrytown,
NY). The endophthalmitis log and billing records were used to
identify retrospectively all cases of endophthalmitis treated with
vitreous tap and injection between January 1, 2009, and October 1,
2012, at a single retina practice. The total number of intravitreal
injections performed during the period was determined from billing
data. Charts of all patients who were treated for endophthalmitis
were reviewed. Recorded data included date of causative injection;
date of tap and injection; visual acuity before causative injection, at
time of tap and injection, at 3 months after the procedure, and at 6
months after the procedure; type of injection; lot number; underlying diagnosis; culture results; and antibiotic resistance.

Inclusion and Exclusion Criteria

All eyes with presumed infectious endophthalmitis following
intravitreal injection of an anti-VEGF medication were included.
Endophthalmitis was dened as any case in which clinical suspicion was high enough to warrant tap and inject (typically decreased
visual acuity, pain,
2 anterior chamber cell, and vitreitis). Eyes
with presumed inammatory endophthalmitis treated primarily
with topical steroids without tap-and-inject treatment were
excluded from analysis.

Injection Technique
All injections were performed in ofce-based settings. Eyes were
prepped in a standardized method with a topical nonviscous
anesthetic, one topical antibiotic drop during the initial 28 months
of the study period, topical 5% povidoneeiodine (Betadine 5%;
Alcon Labs, Fort Worth, TX), followed by another drop of topical
anesthetic and another drop of 5% povidoneeiodine before injection. Rarely, a subconjunctival 2% lidocaine injection was
administered before the second administration of topical anesthetic
and 5% povidoneeiodine. A sterile drape and eyelash preparation
were not used. Injection with a 30- or 31-gauge needle was performed 3.5 to 4.0 mm from the limbus. Physicians individually
determined use of a bladed lid speculum, conjunctival displacement before injection, and superior versus inferior injection site.

Endophthalmitis Treatment Protocol

All eyes with presumed infectious endophthalmitis immediately
underwent a pars plana vitreous tap using a 25- or 27-gauge needle
with attempted aspiration and subsequent injection of intravitreal
antibiotics. If the physician was unable to obtain vitreous uid, an
aqueous tap was performed. Patients received intravitreal vancomycin (1 mg/0.1 ml) and ceftazidime (2 mg/0.1 ml). Intravitreal
amikacin (400 mg/0.1 ml) was substituted for ceftazidime for
patients with penicillin allergy. Subsequent intravitreal antibiotics
were modied based on culture sensitivities. Patients variably were
prescribed atropine sulfate 1% drops twice daily as well as fortied
vancomycin (25 mg/ml), fortied tobramycin (15 mg/ml), and
prednisolone acetate 1% drops every hour. Patients were followed
up daily until evidence of clinical improvement was apparent. At
that point, the drops were tapered slowly and the follow-up interval
was extended.

284

Outcomes
The primary outcome was occurrence of endophthalmitis after
intravitreal injection. Secondary outcomes were microbial spectrum and clinical outcomes including return to baseline visual
acuity (plus or minus 2 lines of Snellen acuity), nal visual acuity
of counting ngers or worse, and the presence of pain, vitreitis, or
hypopyon on initial presentation. Endophthalmitis results were
considered culture positive if there were positive gram stain or
positive growth results on culture plates. Clinical variables were
analyzed using Excel (Microsoft, Redmond, WA), and statistical
analysis was performed using GraphPad Software (GraphPad, La
Jolla, CA).

Results
Effect of Antibiotics
Between January 1, 2009, and October 1, 2012, a total of 117 171
intravitreal injections (71 791 ranibizumab, 44 007 bevacizumab,
and 1373 aibercept) were performed, and a total of 44 patients
with suspected endophthalmitis after intravitreal injection underwent vitreous tap with antibiotic injection (0.038%; 1 in 2663
injections). Seventeen cases showed culture-positive results
(0.015%; 1 in 6892 injections). Overall rates of suspected
endophthalmitis were 24 in 71 791 injections for ranibizumab
(0.033%; 1 in 2991 injections); 20 in 44 007 injections for bevacizumab (0.045%; 1 in 2200 injections); and 0 in 1373 injections
for aibercept. Overall rates of culture-positive endophthalmitis
were 12 in 71 791 for ranibizumab (0.017%; 1 in 5983 injections),
5 in 44 007 for bevacizumab (0.011%; 1 in 8801 injections), and
0 in 1373 for aibercept. There was no statistically signicant
difference in suspected or culture-positive endophthalmitis among
the various agents.
During the 28-month period when postinjection topical antibiotics were prescribed, 57 654 injections (36 781 ranibizumab,
20 873 bevacizumab, and 0 aibercept) were administered and 28
cases of suspected endophthalmitis occurred (0.049%; 1 in 2059
injections), 10 of which showed culture-positive results (0.017%; 1
in 5765 injections; Table 1). Twenty-four eyes received anti-VEGF
injection for neovascular age-related macular degeneration (AMD)
and 4 received injection for macular edema secondary to retina
vein occlusion. Causative organisms included 4 cases of Streptococcus viridans, 2 cases of Enterococcus, 2 cases of coagulasenegative Staphylococcus, and 1 case each of Staphylococcus
aureus and Lactobacillus.

Storey et al

Antibiotics to Prevent Endophthalmitis

Table 1. Suspected Endophthalmitis Cases and Antibiotic Prophylaxis Strategies

Prophylactic Topical Antibiotics
Intravitreal Medication
Ranibizumab
Bevacizumab
Aibercept
Total

No Prophylactic Antibiotics

Injections

Cases (Incidence)

Injections

Cases (Incidence)

Odds Ratio (95% Condence Interval)

36 781
20 873
0
57 654

16 (0.044%)
12 (0.057%)
0
28 (0.049%)

20 832
12 697
1371
34 900

7 (0.034%)
4 (0.032%)
0
11 (0.032%)

1.29 (0.53e3.15)
1.83 (0.59e5.66)
d
1.54 (0.77e3.10)

During the 8-month transition period, 24 617 injections (14 178

ranibizumab, 10 437 bevacizumab, and 2 aibercept) were performed. Five cases of suspected endophthalmitis occurred
(0.020%; 1 in 4923), and 3 showed culture-positive results
(0.012%; 1 in 8206 injections). The 3 cases in which topical
antibiotics were used all grew coagulase-negative Staphylococcus.
No growth was found in the 2 cases in which no topical antibiotics
were prescribed. Three patients were being treated for neovascular
AMD, whereas 2 patients received treatment for diabetic macular
edema.
During the 9-month period in which postinjection antibiotics
were not prescribed, 34 900 injections (20 832 ranibizumab, 12 697
bevacizumab, and 1371 aibercept) were administered and 11
cases of suspected endophthalmitis occurred (0.032%; 1 in 3173
injections), 4 of which showed culture-positive results (0.011%; 1
in 8725 injections; Table 1). All 11 cases of suspected
endophthalmitis received anti-VEGF injection for neovascular
AMD. Causative organisms included 2 cases of S. viridans, 1 case
of S. aureus, and 1 case of nonspeciated gram-positive cocci on
gram stain.
Compared with the period in which no antibiotics were used,
the use of postinjection topical antibiotics was associated with
a trend toward increased incidence of both suspected endophthalmitis (odds ratio, 1.54; 95% condence interval, 0.77e3.10;
Table 1) and culture-positive endophthalmitis (odds ratio, 1.51;
95% condence interval, 0.47e4.83; Table 2).

Clinical Outcomes
Overall, patients with presumed endophthalmitis reported pain,
redness, or decreased vision an average of 3.7 days after injection
(range, 1e11 days). Patients prescribed topical antibiotics sought
treatment an average of 3.7 days after injection versus an average
of 3.5 days for patients not prescribed antibiotics (P 0.82).
Regardless of antibiotic prophylaxis strategy, culture-positive cases
sought treatment an average of 3.6 days after injection, compared
with 3.7 days for culture-negative cases (P 0.84). One culturenegative case was excluded from analysis because the patients
nursing home delayed seeking care until 17 days after injection.
Postinjection antibiotic use did not alter the clinical presentation
of patients with suspected or culture-positive endophthalmitis. For
suspected endophthalmitis cases, all patients had decreased vision
and most reported pain (29/31 postintravitreal injection antibiotic

eyes vs. 13/13 no postintravitreal injection antibiotic eyes;

P 1.0), vitreitis (23/31 postintravitreal injection antibiotic eyes
vs. 7/13 no postintravitreal injection antibiotic eyes; P 0.29), and
hypopyon (24/31 postintravitreal injection antibiotic eyes vs. 7/13
no postintravitreal injection antibiotic eyes; P 0.16). Clinical
presentation of patients with culture-positive endophthalmitis did
not differ with the use of topical antibiotics: all patients had
decreased vision and most reported pain (11/13 postintravitreal
injection antibiotic eyes vs. 4/4 no postintravitreal injection antibiotic eyes; P 1.0), vitreitis (12/13 postintravitreal injection
antibiotic eyes vs. 3/4 no postintravitreal injection antibiotic eyes;
P 0.43), and hypopyon (11/13 postintravitreal injection antibiotic eyes vs. 3/4 no postintravitreal injection antibiotic eyes;
P 1.0). We found no statistically signicant differences in
clinical presentation between culture-positive versus culturenegative cases.

Visual Outcomes
Mean follow-up for all suspected endophthalmitis cases was 20.7
months. Two of 44 patients (1 culture positive, 1 culture negative)
had follow-up of less than 1 month and were excluded from visual
outcome analysis. Most eyes (54.8%; 23/42) returned to baseline
visual acuity (2 lines of visual acuity) by 3 months after injection.
Four additional cases returned to baseline visual acuity by 6
months. We found that use of postinjection topical antibiotics did
not affect return to baseline visual acuity at 6 months (16/29
postintravitreal injection antibiotic eyes vs. 8/13 no postintravitreal
injection antibiotic eyes; P 0.75). There was also no difference
between the 2 groups in the proportion of patients with visual
acuity of counting ngers or worse at 6 months (11/29 postintravitreal injection antibiotic eyes vs. 6/13 no postintravitreal
injection antibiotic eyes up; P 0.74).
Visual acuity outcomes were signicantly worse for culturepositive cases compared with culture-negative cases, regardless
of topical antibiotic use. At 6 months, only 18.8% of culturepositive cases (3/16) returned to baseline visual acuity compared
with 80.8% (21/26) of culture-negative cases (P < 0.001). At 6
months, 62.5% of culture-positive cases (10/16) had vision of
counting ngers or worse compared with 26.9% (7/26) of culturenegative cases (P 0.029). Visual outcomes of culture-positive
and culture-negative cases are displayed in Tables 3 and 4,
respectively.

Table 2. Culture-Positive Endophthalmitis Cases and Antibiotic Prophylaxis Strategies

Prophylactic Topical Antibiotics
Intravitreal Medication
Ranibizumab
Bevacizumab
Aibercept
Total

No Prophylactic Antibiotics

Injections

Cases (Incidence)

Injections

Cases (Incidence)

Odds Ratio (95% Condence Interval)

36 781
20 873
0
57 654

8 (0.022%)
2 (0.010%)
0
10 (0.017%)

20 832
12 697
1371
34 900

3 (0.014%)
1 (0.0079%)
0
4 (0.011%)

1.51 (0.40e5.69)
1.22 (0.11e13.4)
d
1.51 (0.47e4.83)

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Ophthalmology

Volume 121, Number 1, January 2014

Table 3. Visual Acuity Outcomes for Culture-Positive Cases

Patient No.

Agent

Postinjection
Topical
Antibiotics Used

Visual Acuity
At Injection

At Presentation

At 3 Months after
Endophthalmitis

At 6 Months after
Endophthalmitis

1
2

Ranibizumab
Bevacizumab

Yes
Yes

20/300
20/200

HM
HM

NLP
20/200

NLP
CF

3
4
5
6
7
8
9
10

Ranibizumab
Ranibizumab
Ranibizumab
Ranibizumab
Ranibizumab
Ranibizumab
Bevacizumab
Ranibizumab

Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes

20/100
20/200
20/200
20/40
20/40
20/200
20/100
20/30

NLP
LP
HM
20/400
CF
HM
HM
HM

NLP
20/400
CF
CF
CF
LP
Lost to follow-up
20/80

NLP
20/400
20/400
CF
HM
HM
Lost to follow-up
20/60

11

Ranibizumab

20/30

HM

HM

20/50

12

Bevacizumab

20/20

HM

20/70

20/40

13

Bevacizumab

20/40

HM

20/50

HM

14
15
16

Bevacizumab
Ranibizumab
Ranibizumab

Yes (transition
period)
Yes (transition
period)
Yes (transition
period)
No
No
No

20/80
CF
20/20

HM
LP
HM

NLP
LP
20/70

NLP
LP
20/50

17

Ranibizumab

No

20/40

HM

CF

CF

Culture Results
Streptococcus viridans
Coagulase- negative
staphylococcus
Enterococcus faecalis
Enterococcus faecalis
Staphylococcus aureus
Streptococcus mitis
Streptococcus veridans
Streptococcus mitis
Lactobacillus
Coagulase- negative
staphylococcus
Coagulase- negative
staphylococcus
Coagulase- negative
staphylococcus
Coagulase- negative
staphylococcus
Streptococcus salivarius
Streptococcus sanguis
Nondifferentiated
gram-positive cocci
Staphylococcus aureus

CF counting ngers; HM hand movements; LP light perception; NLP no light perception.

Discussion
In this single-center, retrospective, case-control study, we
compared endophthalmitis incidence during a 28-month
period when topical antibiotics were prescribed with
that during a 9-month period when no antibiotics were
prescribed, separated by an 8-month transition period as
providers and patients altered prophylaxis practices. We
found that postinjection topical antibiotics did not decrease
endophthalmitis incidence and that the clinical presentation
and visual outcomes of patients with suspected endophthalmitis were similar regardless of whether postinjection
topical antibiotics were used initially.
Previous studies comparing topical antibiotics prescribed
for several days after injection with no topical antibiotics
have not found statistically signicant differences in
endophthalmitis rates, although all had relatively small
sample sizes. Bhatt et al4 concluded that there was
no difference in rates of suspected endophthalmitis with
or without topical antibiotics (5/2287 or 0.22%
with antibiotics vs. 5/2480 or 0.20% no antibiotics; P
0.90). Cheung et al9 concluded that the overall rate of
intravitreal injection-related endophthalmitis is greater with
the use of topical antibiotics compared with no antibiotics
(5/8259 or 0.061% with 5 days of antibiotics vs. 2/5266 or
0.038% with no antibiotics; P 0.57). Cheung et al also
concluded that if only culture-positive endophthalmitis
cases were considered, the use of topical antibiotics showed
lower endophthalmitis rates compared with patients
receiving no antibiotics (1/8259 or 0.012% with 5 days of

286

antibiotics vs. 2/5266 or 0.038% no antibiotics; P 0.32).

However, the studys sample size was small, leading some
investigators to state that the conclusions may be the result
of a random sampling error.11
Given the increasing number of studies suggesting that
topical antibiotics after intravitreal injection do not prevent
endophthalmitis, some investigators believe that there is no
need for topical antibiotic use after intravitreal injection.11,12
In 2012, the American Academy of Ophthalmology joined
the Choosing Wisely campaign initiated by the American
Board of Internal Medicine Foundation to create a list of
Five Things Physicians and Patients Should Question.13 The
American Academy of Ophthalmology listed [not]
routinely providing antibiotics before or after intravitreal
injections as a possible intervention to eliminate
unnecessary costs.14 However, there are variable data on
the usefulness of postinjection antibiotics to prevent
endophthalmitis, and therefore no current guidelines
recommending for or against their use.
Our study aimed to evaluate the effect of prophylactic
antibiotics in the largest series to date. Our study conrmed
the nding of Cheung et al9 of greater incidence of
endophthalmitis
with
the
use
of
topical
antibioticsdalthough neither study found the increased
risk to be statistically signicant. Although our infection
rates were lower, we found a similarly sized increased risk
of endophthalmitis with the use of topical antibiotics
(odds ratio, 1.54 in the current study vs. 1.59 in the study
by Cheung et al). In contrast to Cheung et al, we found
that topical antibiotics also were associated with a trend

Storey et al

Antibiotics to Prevent Endophthalmitis

Table 4. Visual Acuity Outcomes for Culture-Negative Cases

Patient No.
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44

Visual Acuity

Agent

Postinjection
Topical
Antibiotics Used

At Injection

Bevacizumab
Bevacizumab
Ranibizumab
Bevacizumab
Bevacizumab
Bevacizumab
Bevacizumab
Bevacizumab
Ranibizumab
Bevacizumab
Bevacizumab
Ranibizumab
Ranibizumab
Ranibizumab
Ranibizumab
Bevacizumab
Ranibizumab
Ranibizumab
Bevacizumab
Bevacizumab
Bevacizumab
Ranibizumab
Ranibizumab
Bevacizumab
Bevacizumab
Ranibizumab
Ranibizumab

Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No (transition period)
No (transition period)
No
No
No
No
No
No
No

20/100
20/70
20/50
20/70
20/200
20/200
20/200
20/30
20/30
20/30
CF
20/200
20/400
20/40
20/60
20/30
20/60
20/125
CF
CF
20/100
20/40
20/400
20/40
20/40
20/50
CF

At Presentation

At 3 Months
after Endophthalmitis

At 6 Months after
Endophthalmitis

CF
HM
HM
HM
HM
HM
HM
20/250
20/400
HM
CF
HM
CF
LP
HM
CF
20/200
HM
CF
CF
20/200
CF
CF
CF
CF
20/80
HM

20/80
CF
20/100
20/100
CF
20/400
20/300
20/30
20/50
20/30
CF
Lost to follow-up
20/400
CF
20/100
20/30
20/60
LP
20/60
20/400
20/50
20/70
CF
20/40
CF
20/50
CF

20/200
20/70
20/100
20/50
CF
20/200
20/200
20/30
20/60
20/30
CF
Lost to follow-up
20/400
CF
20/100
20/40
20/30
NLP
20/60
20/400
20/60
20/70
CF
CF
20/60
20/30
CF

CF counting ngers; HM hand movements; LP light perception; NLP no light perception.

toward increased risk of culture-positive endophthalmitis.

We found no difference in rates of suspected or culturepositive endophthalmitis between anti-VEGF agents.
Several possibilities may explain the trend toward
increased endophthalmitis rates with topical antibiotic use.
Several studies have shown that topical antibiotics lead to an
increase in resistant organisms. Milder et al8 showed that
repeated use of topical uoroquinolone drops after
intravitreal injection resulted in a signicantly increased
rate of bacterial resistance (63.6%) compared with control
eyes (32.1%). Kim et al15 demonstrated substantial
levels of resistance to third- and fourth-generation uoroquinolones as well as multidrug resistance in patients
treated with topical antibiotics after multiple intravitreal
injections. Cultures from eyes with endophthalmitis have
shown a higher incidence of antibiotic resistance among
bacterial isolates,16,17 and resistant bacterial strains have
been found to cause more severe ocular inammation than
sensitive strains.18
Several recent studies have found that organisms typically associated with oral ora are more prevalent with
endophthalmitis occurring after intravitreal injection than
after other vitreoretinal procedures.1,7,19 Our study also
found that oropharyngeal organisms were more common
after intravitreal injection than in reports of other eye
procedures.20 For the 17 culture-positive cases of endophthalmitis, 6 cases grew Streptococcus species (35.3%).

There has been much speculation concerning the potential

increased association of intravitreal injections with oral
ora. Oropharyngeal droplet transmission may be the cause
of this increased risk of Streptococcus infection after
injection. One difference between intravitreal injections and
other ocular procedures is that injections often are performed in the ofce, often with no masking of the physician, patient, or technician. In contrast, all persons in the
operating room are masked and the patient is draped. A
recent study found that rates of postintravitreal injection
endophthalmitis were lower when the procedure was performed in the operating room as compared with in
the ofce.21 One suggested strategy to reduce droplet
transmission is talking cessation. However, this has the
inherent limitation of prohibiting communication between
the physician and patient during the procedure and could
increase the potential for incorrect site procedures. Our
study was not designed to evaluate the role of other
strategies such as wearing protective masks during
intravitreal procedures.
Strengths of this study include the large number of
intravitreal injections performed by a single retina group
over a fairly short period. A potential limitation of this
study is its retrospective, case-control nature. However,
identication of endophthalmitis cases did not depend on
physician recall. All cases were identied using a combination of a prospective endophthalmitis log, as well as

287

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Volume 121, Number 1, January 2014

from billing records and chart review of all patients treated

for endophthalmitis resulting from any cause during
the study period. Adherence to antibiotic drop use after
injection was not assessed during the period when antibiotics were prescribed. If antibiotics do increase rates of
endophthalmitis, nonadherence to topical antibiotics would
tend to underestimate the incidence of endophthalmitis in
the antibiotic use group. Conversely, some patients could
have continued to use antibiotic drops even after being
instructed not to do so. An 8-month transition period was
included in the study design to limit this potential source of
bias. Additionally, a patient could have developed
endophthalmitis and sought treatment elsewhere, but given
the tertiary care nature of our practice, this is less likely,
and we know of no instances in which this occurred.
Finally, retina specialists involved in the study knew that
topical antibiotic prophylaxis was discontinued at a specic
time. It is possible that physicians increased precautions
(e.g., extra povidoneeiodine, refraining from talking,
change in speculum use) after topical antibiotic use was
discontinued. However, no retina specialists reported
increasing their customary precautions after stopping
prophylactic antibiotic use. Furthermore, physicians were
unaware that a study would evaluate the effect of
prophylactic antibiotics, making an unmasking bias less
likely.
Although the probability of developing endophthalmitis
after intravitreal injection is low, treatment of AMD, retinal
vein occlusions, and diabetic macular edema can require
years of repeated injections. Consequently, ophthalmologists have attempted to prevent infection through a number
of measures, including prophylactic topical antibiotics. Our
study adds to the current body of literature indicating that
postinjection topical antibiotics do not decrease rates of
endophthalmitis. Given evidence suggesting potential harm
of topical antibiotics and a potential increase in endophthalmitis rates with their use, we recommend against the
routine use of topical antibiotics after intravitreal injection.

6.

7.

8.

9.
10.
11.

12.

13.
14.
15.

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Storey et al

Antibiotics to Prevent Endophthalmitis

Footnotes and Financial Disclosures

Manuscript no. 2013-861.

Presented at: Wills Eye Hospital Annual Conference, 2013; Retina Society
Annual Meeting, 2013; and as a poster at: Association for Research in
Vision and Ophthalmology Annual Meeting, 2013; and American Academy
of Ophthalmology Annual Meeting, November 2013, New Orleans, LA.

The Retina Service of Wills Eye Hospital, Mid Atlantic Retina, The
Retina Service of Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.

Financial Disclosure(s):
The author(s) have no proprietary or commercial interest in any materials
discussed in this article.

Originally received: May 29, 2013.

Final revision: August 24, 2013.
Accepted: August 27, 2013.
Available online: October 21, 2013.
1

Department of Ophthalmology, Thomas Jefferson University, Philadelphia, Pennsylvania.

*A full listing of The Post-Injection Endophthalmitis (PIE) Study Team is

available online in appendix 1 (http://aaojournal.org). All members of the
PIE Study Team are from The Retina Service of Wills Eye Hospital,
MidAtlantic Retina, Thomas Jefferson University, Philadelphia, PA.

Correspondence:
Sunir J. Garg, MD, Mid Atlantic Retina, The Retina Service of Wills Eye
Hospital, Thomas Jefferson University, 840 Walnut Street, Suite 1020,
Philadelphia, PA 19107. E-mail: sunirgarg@yahoo.com.

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