56

ARTICLE

Safety and efficacy of intravitreal injection

of steroid and antibiotics in the setting
of cataract surgery and trabecular
microbypass stent
Trevor Kindle, MD, Tanner Ferguson, BS, Mitch Ibach, OD, Michael Greenwood, MD, Justin Schweitzer, OD,
Russell Swan, MD, Ramu G. Sudhagoni, PhD, John P. Berdahl, MD

Purpose: To evaluate the safety and efficacy of intravitreal admin-
istration of a steroid and antibiotics during cataract surgery
compared with the typical postoperative topical regimen in prevent-
ing postoperative inflammation, pain, cystoid macular edema
(CME), and endophthalmitis.
Setting: Private practice, Sioux Falls, South Dakota, USA.
Design: Retrospective case series.
Methods: The study group included eyes that had an intravitreal
injection of triamcinolone–moxifloxacin–vancomycin at the time of
cataract surgery with concomitant trabecular microbypass stent
insertion. The control eyes had the same procedure but were pre-
scribed topical antibiotics, steroids, and nonsteroidal antiinflamma-
tory drugs postoperatively. Data were recorded preoperatively and
1 day, 1 week, 1 month, and 3 months postoperatively. Primary
outcomes included the number of glaucoma medications,
intraocular pressure (IOP), and IOP spikes of at least 15 mm Hg
from baseline.
Results: There were 234 eyes in the study group and 249 eyes in
the control group. The mean reduction in glaucoma medications
was 0.24 drops in the study group and 0.80 drops in the control
group 3 months postoperatively, whereas the mean IOP reduction
was 2.59 mm Hg in the study group and 3.63 mm Hg in the control
group. Pressure spikes were detected at 54 (5.7%) of 936 postop-
erative visits in the study group and at 37 (3.7%) of 996 visits in the
control group. There were no cases of severe inflammation, CME,
infection, or retinal detachments.
Conclusions: Both groups had similar postoperative pressure
reductions and incidence of IOP spikes. The results indicate that in-
travitreal injections of a steroid and antibiotics might be a safe
option for glaucomatous eyes having cataract surgery with trabec-
ular microbypass stent insertion.
J Cataract Refract Surg 2018; 44:56–62 Q 2018 ASCRS and ESCRS

surgery.4 Combinations of steroids and nonsteroidal antiin-

C
ataract surgery is 1 of the most commonly
performed surgeries worldwide.1 With the aging
population, this number will only continue to
rise.2 As a consequence, new tools and techniques are
frequently being introduced in efforts to obtain better out-
comes and improve the safety and efficacy of the proce-
dure. Although complications are not particularly
common, the complications that can result are serious
and have sight-threatening potential.3
Ophthalmologists use chemoprophylaxis to prevent po-
tential complications. Cystoid macular edema (CME) is
the most common cause of decreased vision after cataract
flammatory drugs (NSAIDs) have been shown to be appro-
priate prophylactic and definitive treatment regimens for
CME.5 Inflammation and pain are also potential complica-
tions, and these can be prevented or treated similarly using
steroids and NSAIDs.6,7 Endophthalmitis is likely the most
feared complication of cataract surgery because of its sight-
threatening potential. Although the overall incidence is less
than 0.1%, clinicians remain motivated to minimize its
occurrence.8 Povidone–iodine surgical preparations and
antibiotics (perioperative and postoperative) are typically
used as preventative measures against infection.

Submitted: April 28, 2017 | Final revision submitted: September 9, 2017 | Accepted: October 14, 2017
From the University of South Dakota Sanford School of Medicine (Kindle, Ferguson), the University of South Dakota School of Health Sciences (Sudhagoni), and Vance
Thompson Vision (Ibach, Schweitzer, Berdahl), Sioux Falls, South Dakota, and Vance Thompson Vision (Greenwood), Fargo, North Dakota, and Vance Thompson
Vision (Swan), Bozeman, Montana, USA.
Presented as a poster at the ASCRS Symposium on Cataract, IOL and Refractive Surgery, New Orleans, Louisiana, USA, May 2016
Corresponding author: Trevor Kindle, MD, Vance Thompson Vision, 3101 West 57th Street, Sioux Falls, South Dakota 57108, USA. E-mail: trevor.kindle@usd.edu.

Q 2018 ASCRS and ESCRS 0886-3350/$ - see frontmatter

Published by Elsevier Inc. https://doi.org/10.1016/j.jcrs.2017.10.040
 SAFETY OF INTRAVITREAL INJECTION OF STEROID AND ANTIBIOTICS
Although the actual drug classes used to prevent CME,
inflammation, pain, and endophthalmitis after cataract sur-
gery are generally agreed upon, the practice patterns for
administration of these medications vary widely. In the
United States, topical administration remains the most
common practice. Topical NSAIDs lower the risk for
CME and help treat postoperative pain and/or inflamma-
tion.7 Similarly, topical steroids are effective at reducing
postoperative pain and inflammation.9 In the U.S., the peri-
operative use of topical antibiotics remains the most com-
mon method of endophthalmitis prevention.10
For various reasons, the use of topical medications, in
particular antibiotics, has been debated in recent years. Sur-
geons have questioned the efficacy of topical antibiotics as a
means of endophthalmitis prophylaxis, whereas others have
suggested that simply using perioperative povidone–iodine
alone is equally effective at preventing endophthalmitis.11,12
Furthermore, eyedrops can irritate the cornea and regimens
are often complicated and burdensome to patients, which
contributes to poor compliance.13–15 In addition, the drops
are typically expensive, and 1 study that evaluated patient
compliance in cataract surgery14 found that patients only
used one half of the prescribed number of drops as part of
their regimen. Ultimately, these challenges and data suggest
that compliance is a legitimate concern and can contribute
to poor outcomes and complications for patients.
Thus, surgeons have been evaluating and pursuing drug-
delivery alternatives to topical medications. In European
countries such as Sweden, intracameral antibiotics are
used almost exclusively and have been shown to be effica-
cious.16,17 Similarly, the use of intracameral triamcinolone
to reduce postoperative inflammation has been studied.15
Although it is encouraging that surgeons have been able to
safely and effectively use medications inside the eye, barriers
remain that might slow adoption. In the U.S., intracameral
antibiotics are not available in a compounded form.18 Other
concerns include reports of delayed adverse sequelae and
lack of an approved antibiotic in some markets.
Recently, there has been an increased interest in the use of
intraocular medications after cataract surgery. Much of this
interest was stimulated by the results of the European Soci-
ety of Cataract and Refractive Surgeons clinical trial, which
showed the use of intracameral cefuroxime significantly
reduced the risk for endophthalmitis.19 Another group
studied the use of a regulated and compounded combina-
tion of triamcinolone, moxifloxacin, and vancomycin, and
found this transzonular intravitreal injection was effective
at preventing infection and inflammation.20 Similarly, a
study performed at a private practice group evaluating in-
travitreal triamcinolone–moxifloxacin had comparable re-
sults.A Although steroid response resulting in increased
intraocular pressure (IOP) is a concern, in particular in
glaucoma patients, studies have shown intravitreal triam-
cinolone to be generally well tolerated.21,22
There are numerous approaches for administering prophy-
lactic medications, including intracameral, pars plana, and
transzonular. The transzonular technique has been consid-
ered more challenging and disruption of the anterior hyaloid
57
membrane is a concern. Because ophthalmologists around
the world use the pars plana approach every day in clinics
to treat various retinal conditions, we feel it is a more suitable
approach. In this study, we evaluated the safety and efficacy of
an intravitreal injection of a steroid (triamcinolone) and anti-
biotics (moxifloxacin, vancomycin) at the time of cataract sur-
gery using a pars plana approach of administration.
PATIENTS AND METHODS
In addition to complying with the U.S. Health Insurance Porta-
bility and Accountability Act of 1996, this project was granted
approval from the University of South Dakota Institutional Re-
view Board.
This was a single-center retrospective chart review of eyes from
January 2015 to December 2015 that had concurrent cataract sur-
gery and implantation of a trabecular microbypass stent in a pri-
vate practice setting. All patients had been previously diagnosed
with primary open-angle glaucoma.
The patients had a preoperative assessment to establish a baseline.
Demographic information (age, sex), corrected distance visual acuity
(CDVA), glaucoma medications, and IOP were recorded. To assess
outcomes, data were collected at postoperative visits from 1 day,
1 week, 1 month, and 3 months. At each visit, the data collected
included IOP, number and type of medications, and CDVA.
The primary outcome measures in the study included IOP by
Goldmann applanation tonometry and the number of glaucoma
medications. To evaluate safety, the incidence of IOP spikes was
also recorded, which was defined as an increase of at least
15 mm Hg from baseline IOP.
The patients were divided into 2 groups. The study group included
patients who had a pars plana intravitreal injection of triamcinolone,
moxifloxacin, and vancomycin at the time of surgery and a topical
NSAID drop daily for 4 weeks after the procedure. The study group
is also referred to as the dropless or injection group throughout this
paper. The intravitreal injection, which is available in a compounded
form, was a 0.2 mL injection of the combination of 15 mg/1 mg/
10 mg/mL concentration of triamcinolone, moxifloxacin, and vanco-
mycin, respectively. Therefore, the eye received 3 mg of triamcinolone,
0.2 mg of moxifloxacin, and 2 mg of vancomycin with each injec-
tion. Of note, in January of 2016, the center transitioned to a
triamcinolone–moxifloxacin only injection because of concerns
regarding the potential association between vancomycin and
hemorrhagic occlusive retinal vasculitis that has been
described previously. 23 However, only eyes treated with triam-
cinolone–moxifloxacin–vancomycin were included in the
study population. The control group comprised eyes that
received a standard topical regimen postoperatively. In this
cohort, patients used a postoperative topical medication regimen
consisting of an antibiotic (moxifloxacin 0.05% 4 times a day for
1 week), an NSAID (bromfenac 0.07% or nepafenac 0.3% once
daily for 4 weeks), and a steroid (difluprednate 0.05% or pre-
dnisolone acetate 1.0% tapered over 4 weeks).
For statistical analysis, a 2 independent-sample t test procedure
was used to compare the mean IOP change between groups. A
Wilcoxon Mann-Whitney test was used to compare the number
of medications used between the 2 groups. A chi-square test was
used to test sex dependency between the groups. The Fisher exact
test was applied to test the difference between 2 population pro-
portions. The significance level was set at 5%. All data analyses
were performed using R software.B
RESULTS
Of the 483 eyes in the study, 234 eyes were in the study
group, which received the intravitreal injection of a steroid
and antibiotics at the time of surgery, and the remaining
249 eyes were in the control group, which used all topical
Volume 44 Issue 1 January 2018
58 SAFETY OF INTRAVITREAL INJECTION OF STEROID AND ANTIBIOTICS

Table 1. Preoperative demographics and baseline measurements.

Parameter Intravitreal Injection* Traditional Drops† P Value
Mean age (y) 69.8 G 8.7 74.0 G 8.0 !.001z
Female Sex, n (%) 149 (64) 152 (61) .62
Mean preop IOP (mm Hg) 17.78 G 5.29 19.00 G 6.04 .018z
Mean preop glaucoma meds (n) 0.84 G 0.91 1.19 G 1.00 .024z
Mean preop CDVA (logMAR) 0.28 G 0.20 0.28 G 0.22 .52

CDVA Z corrected distance visual acuity; IOP Z intraocular pressure; logMAR Z logarithm of the minimum angle of resolution
Means G SD
*Study group
†
Control group
z
Statistically significant

medications. Table 1 shows the patient demographics and
baseline information. Of note, there was a statistically sig-
nificant difference in mean age, preoperative IOP, and pre-
operative glaucoma medications between the 2 groups. The
study (dropless) group was younger, had lower preopera-
tive IOP readings, and used fewer glaucoma medications
at baseline than the control group.
Figure 1 shows the mean IOP at each timepoint in both
groups. The mean IOP increased in both groups 1 day
postoperatively.
Table 2 and Figure 2 show the incidence of IOP spikes in
the 2 groups. The total or cumulative spikes at any postop-
erative visit were statistically similar between the 2 groups.
In the dropless or injection group, 48 (20.5%) of 234 eyes
experienced at least 1 IOP spike during the follow-up,
whereas 33 (13.25%) of 249 eyes in the topical or control
group experienced at least 1 IOP spike during the follow-
up (P Z .038). Four of 234 eyes in the injection group
and 3 of 249 eyes in the topical group had repeat pressure
spikes (P Z .72).
In the study group, there was a pressure spike of 15 mm
Hg or higher at 54 (5.7%) of 936 postoperative visits. In the
control group, there was a pressure spike of 15 mm Hg or
higher at 37 (3.7%) of 996 postoperative visits. There was
no statistically significant difference in the rate of IOP
spikes between the 2 groups (P Z .051).
Table 3 shows the 3-month postoperative data. There was
no statistically significant difference in IOP change from
baseline between the 2 groups. However, the control group
had a more robust reduction in medication use, which was
statistically significant.
Figure 3 shows the mean number of glaucoma medica-
tions at each visit. The difference in the mean reduction
in medication use between each group was statistically sig-
nificant (P ! .001).
The CDVA assessments were similar between each group
at all timepoints.
DISCUSSION
Numerous studies in the peer-reviewed literature have es-
tablished the usefulness of intravitreal injections as chemo-
prophylaxis to reduce the likelihood of infection,
inflammation, and postoperative discomfort after cataract
surgery. This might be because of the poor compliance
associated with topical medication regimens. There are
multiple factors that contribute to poor compliance with

Figure 1. Mean IOP measure-

ments (G1 SD) in the 2 groups af-
ter cataract surgery with trabecular
microbypass stent placement
(IOP Z intraocular pressure).

Volume 44 Issue 1 January 2018

 SAFETY OF INTRAVITREAL INJECTION OF STEROID AND ANTIBIOTICS 59

Table 2. Incidence of IOP spikes by specific criteria.

IOP Spike (%)

Parameter Injection/Dropless* Topical/Drops† P Value

1 day postop 13.25 10.44 .40
1 week postop 4.70 3.21 .49
1 month postop 3.42 0.80 .056
3 month postop 1.28 0.40 .36
Cumulative spikes for all visits 5.66 3.71 .051
Eyes with at least 1 spike 20.51 13.25 .038
Cumulative visit spikes minus 1 day 3.13 1.47 .036
Visits with repeat pressure spikes 0.71 (5/[234*3])z 0.54 (4/[249*3])x .75
Eyes with multiple spikes 1.71 1.20 .72

IOP Z intraocular pressure

*Study group
†
Control group
z
Five postop visits at which an eye that previously had a pressure spike experienced a repeat pressure spike; 234*3 refers to the total number of postop visits
after the 1 d visit (234 eyes  3 for 1 wk, 1 mo, 3 mo visits)
x
Four postop visits at which an eye that previously had a pressure spike experienced a repeat pressure spike; 249*3 refers to the total number of postop visits
after the 1 d visit (249 eyes  3 for 1 wk, 1 mo, 3 mo visits)

topical regimens, including complicated schedules, expen-
sive costs, difficulty with administration, and irritation
from the agents.4,14,15 Recently, companies have started to
combine multiple therapies into a single drop. For example,
1 available combination eyedrop is a topical formulation
consisting of prednisolone acetate, moxifloxacin hydro-
chloride, and ketorolac tromethamine (Pred–Moxi–Ketor).
Although combination drops simplify regimens, patients
are still required to administer drops into their eye
numerous times a day.
Overall, the results of this retrospective chart review of
483 eyes are encouraging. The results showed there was
IOP reduction in both groups. At 3 months, the mean
pressure reduction was 2.59 mm Hg in the study group
and 3.63 mm Hg in the control group. The difference in
IOP reduction between both groups was similar and was
not statistically significant (P Z .062). The pressure
reduction observed in both groups in this study is consis-
tent with data in previous studies that evaluated the safety
and efficacy of the combined procedure.24–27 Further-
more, no eyes required further surgical intervention
within the first 3 months to decrease an elevated IOP after
surgery. Regarding medication, both groups achieved a
mean reduction in medication use 3 months after surgery;
however, the control group had a more robust decrease in
medication use with 0.8 fewer medications than baseline
(P ! .001).
The more significant decrease in medication use
observed in the control group might be a result of the in-
jected triamcinolone in the vitreous space remaining in
the eye much longer than the types of topical steroids
administered over 1 month. Previous studies found that

Figure 2. Percentage of eyes in the

2 groups with an IOP spike of at
least 15 mm Hg from baseline
(IOP Z intraocular pressure).

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60 SAFETY OF INTRAVITREAL INJECTION OF STEROID AND ANTIBIOTICS
Table 3. Three-month postoperative data.
Mean ± SD
Parameter Injection/Dropless*
Reduction in IOP (mm Hg) 2.59 G 5.89
Reduction in medications (n) 0.24 G 0.94
CDVA (logMAR) 0.13 G 0.23
CDVA Z corrected distance visual acuity; IOP Z intraocular pressure; logMAR Z logarithm of the minimum angle of resolution
*Study group
†
Control group
z
Statistically significant
clinically significant amounts of triamcinolone can remain
for approximately 3 months after intravitreal injections,
and furthermore, trace amounts of triamcinolone have
been detected in animal models up to 8 months after in-
travitreal injection.28,29 In the case of the rabbit-eye
model, the concentration of the triamcinolone does drop
substantially in the first few months.29 This lingering con-
centration of steroid in the eye might contribute to
increased IOP in patients who respond to steroids. How-
ever, in this study, both groups had similar reductions in
IOP and both achieved reductions in glaucoma medica-
tions from baseline.
The incidence of pressure spikes of 15 mm Hg or higher
above baseline was a primary outcome of interest in this
study. A statistically significant difference was not found
between the 2 groups in the cumulative number of pressure
spikes (P Z .051). Most of the pressure spikes occurred in
the first 24 hours after surgery in both groups. These data
suggest that despite the lingering steroid in the vitreous
(discussed previously), the steroid effect on IOP does not
lead to significant pressure increases above baseline days
to months after surgery. This finding is consistent with a
previous study that evaluated the use of a intracanalicular
Volume 44 Issue 1 January 2018
Topical/Drops† P Value
3.63 G 6.38 .062
0.80 G 0.91 !.001z
0.12 G 0.25 .65
depot of dexamethasone for slow release of a steroid that
did not result in greater incidence of IOP spikes than those
experienced by a group that had a standard topical
regimen.30
The safety profiles of both groups were favorable. In the
study group, there were no reported cases of inflammation,
CME, or infection. No retinal detachments (RD) occurred
during the 3-month postoperative period. These findings
are consistent with previous literature evaluating the pars
plana approach of intravitreal injections that found infec-
tion rates and RD rates were less than 1.0%.31 Furthermore,
the use of topical povidone–iodine, which is already part of
the cataract surgery preparation, has been shown to
decrease postintravitreal injection endophthalmitis rates
even more.32
In addition, the usefulness of intraocular antibiotics in
preventing endophthalmitis has been shown previously.
One study showed that intracameral cefuroxime had a
100% success rate in preventing postsurgical endophthalmi-
tis.33 Another study34 found that intracameral moxifloxacin
resulted in a statistically significant reduction in endoph-
thalmitis rates compared with patients who received topical
chemoprophylaxis. Last, another study could not find an
Figure 3. Mean number of glau-
coma medications (G1 SD) used
by patients in both groups after
cataract surgery with trabecular
microbypass stent placement.
 SAFETY OF INTRAVITREAL INJECTION OF STEROID AND ANTIBIOTICS
appreciable difference in the effectiveness of preventing
postoperative endophthalmitis between intraocular moxi-
floxacin and cefuroxime, and both of these intracameral
options were better than topical antibiotics in preventing
infection.35 One can see the benefits associated with using
intraocular antibiotics for chemoprophylaxis.
Our study was not without limitations. It was an open-
label nonrandomized study. The use of the stent in both
groups could have mitigated the effect of the steroid on
pressure. At baseline, the 2 groups were statistically
different in terms of age, IOP, and baseline glaucoma
medications. This difference at baseline might contribute
to challenges in comparing medication reduction be-
tween the 2 groups. However, it should be emphasized
that the study group represented the final 234 eyes that
had the triamcinolone–moxifloxacin–vancomycin intra-
vitreal injection immediately before the site transitioned
to an injection containing only triamcinolone and moxi-
floxacin. No additional inclusion or exclusion criteria
were used in the study group to prevent selection bias
and to mimic the clinical use of the intravitreal injection
approach.
From this study, there are numerous avenues for further
evaluation. Future studies could focus on the safety and ef-
ficacy of the currently used injection of triamcinolone and
moxifloxacin without vancomycin. Additional research
could explore the rate of pressure spikes in nonglaucoma-
tous eyes versus glaucomatous eyes using the intravitreal
approach. Previously, subconjunctival, intracameral, and
transzonule intravitreal triamcinolone injections have
been shown to be generally well tolerated without signifi-
cant pressures spikes when administered in conjunction
with phacoemulsification only.20,36,37 There have also been re-
ports of significant pressure elevations after intravitreal steroid
injection; however, these occurred when treating macular
edema and retinal neovascularization in nonglaucomatous
eyes.38
Although the most critical aspect of intravitreal adminis-
tration is reducing the risk for infection, pain, and other
adverse events, patient experience is also an important
consideration. For some patients, the highest out-of-
pocket expense in the entire process are the drops after sur-
gery. This present study did not use surveys and/or reviews
to assess patient satisfaction with either regimen. However,
a previous study39 found that patients prefer the intravitreal
injection over the topical regimen. In addition, triamcino-
lone injections often cause visual disturbances (eg, floaters),
and using a clear steroid solution such as dexamethasone
might alleviate this problem. Future studies focusing on
the patient experience between the 2 approaches would be
beneficial.
With no exclusion criteria, this study mimics the clinical
use of the intravitreal approach for delivering medications
after cataract surgery. The early results from this study sug-
gest that the intravitreal approach of administering medica-
tions might be a safe and effective option for glaucomatous
eyes having cataract surgery with concomitant trabecular
microbypass stent insertion. Although further studies are
61
required to solidify its role for both glaucomatous and non-
glaucomatous eyes, our study suggests clinicians might
consider the pars plana intravitreal injection of steroid
and antibiotic as an alternative to topical regimens after
cataract surgery.
WHAT WAS KNOWN
 Patient compliance with eyedrop medications is not
outstanding.
 Intracameral and intravitreal antibiotics have been shown to
be better than topical antibiotics in preventing postoperative
endophthalmitis.
WHAT THIS PAPER ADDS
 Pars plana intravitreal injection of a steroid and antibiotics
with a topical NSAID seemed to be a safe and effective
option for reducing postoperative pain, inflammation, CME,
and endophthalmitis.
 The intravitreal injection of triamcinolone–moxifloxacin–van-
comycin did not contribute to significant pressure increases
after cataract surgery in glaucomatous eyes.
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Disclosures: Drs. Ibach, Schweitzer, and Berdahl are consultants
to and speakers for Glaukos Corp. None of the other authors has a
financial or proprietary interest in any material or method mentioned.
First author:
Trevor Kindle, MD
University of South Dakota Sanford School
of Medicine, Sioux Falls, South Dakota,
USA