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A trial of topical prednisolone acetate before
intravitreal triamcinolone acetonide decreases
intraocular pressure spikes
Hussein Hollands,* MD,MSc (Epid),BSc; Gamal Seif,
{
MD,MSc,BSc; Simon Hollands,* MSc;
Jeffrey Gale,* MD,FRCSC,BSc
ABSTRACT NRE
´SUME
´
Objective: To compare adverse intraocular pressure (IOP) spikes in patients receiving intravitreal triamcinolone
acetonide (IVTA) in 2 cohorts: (i) patients who underwent a topical prednisolone acetate trial (PAT) without
incurring a short-term IOP rise, and (ii) control patients who did not undergo a PAT.
Design: Retrospective cohort study.
Participants: Charts of all patients who underwent any intravitreal injection during the study period were reviewed
(n51150).
Methods: Patients in the PAT group received a 6-week course of prednisolone acetate 1% 4 times per day and had an
IOP that did not rise above 25 mm Hg or above 8 mm Hg over the IOP in the contralateral eye. Patients undergoing a
PAT and having a short-term IOP rise were not studied. Control patients did not receive a PAT. All patients received
12–20 mg of IVTA. Patients were followed for a minimum of 6 weeks and follow-up lasted for 1 year or until
intraocular surgery or another IVTA injection was performed.
Results: There were 97 patients in the PAT cohort and 75 control patients. Patients in the PAT cohort had a lower
proportional rise between maximum IOP and baseline (43%) compared with controls (64%) (p50.035). Patients in the
PAT group also had a lower risk of incurring a 40% (p50.05), 60% (p50.018), and 100% (p50.045) increase in maximum
IOP (vs baseline) compared with controls and were less likely to require glaucoma filtration surgery (p50.035).
Conclusions: Patients undergoing a PAT who did not have a subsequent short-term IOP rise had a lower risk of severe
IOP spikes after IVTA compared with those patients receiving IVTA but not having undergone a PAT.
Objet : Comparaison des pointes de pression intraoculaire (PIO) de´favorables chez des patients recevant une injection
intravitre´enne d’ace´tonide de triamcinolone (IVAT) chez 2 cohortes : (i) des patients qui ont subi un essai d’ace´tate
de prednisolone (EAP) topique sans hausse de PIO a` court terme, et (ii) des patients te´ moins qui n’ont pas subi d’EAP.
Nature : E
´tude re´trospective de cohorte.
Participants : Les dossiers de tous les patients qui ont subi une injection intravitre´enne pendant la pe´riode e´tudie´e ont
e´te´ examine´s (n51150).
Me´ thodes : Les patients du groupe EAP ont rec¸ u pendant 6 semaines de l’ace´tate de prednisolone 1 % 4 fois par jour et
n’ont pas vu leur PIO augmenter au dela` de 25 mm Hg ou de 8 mm Hg au-dessus de la PIO de l’autre œil. Les patients
qui ont subi l’EAP et eu une hausse de la PIO a` court terme n’ont pas e´te´e´tudie´ s. Les patients te´moins n’ont pas subi
d’EAP. Tous les patients ont rec¸u 12–20 mg d’IVAT. Les patients ont e´te´ suivis pendant un minimum de 6 semaines, et
le suivi a dure´ 1 an ou jusqu’a` la chirurgie intraoculaire ou a` l’administration d’une autre injection d’IVAT.
Re´ sultats : La cohorte d’EAP a compte´ 97 patients et le groupe te´moin, 75. Les patients de la cohorte d’EAP ont eu
proportionnellement une hausse plus faible, entre le maximum de PIO et la base (43 %), comparativement au groupe
te´ moin (64 %) (p50,035). Les patients du groupe EAP ont aussi un risque plus faible de hausse de PIO maximale de
40 % (p50,05), 60 % (p50,018) et 100 % (p50,045) (versus la pression de base), comparativement aux te´moins, et
ils ont moins tendance a` avoir besoin d’une chirurgie de filtration pour le glaucome (p50,035).
Conclusions : Les patients qui subissent un EAP et qui n’ont pas de hausse subse´quente de PIO a` court terme risquent
moins d’avoir des pointes graves de PIO apre` s l’injection d’IVTA comparativement a` ceux qui rec¸oivent une IVTA
mais sans EAP.
Intravitreal triamcinolone acetonide (IVTA) (Kenalog;
Bristol-Myers Squibb Co, Montreal, Que.) is used in
ophthalmology to treat diabetic macular edema,
1–4
retinal vein
occlusion,
2,5,6
exudative age-related macular degeneration,
2,7,8
and other retinal disease processes.
2
The insoluble nature
of IVTA increases its half-life within the vitreous cavity
and allows it to be used therapeutically for up to
6–9monthsafter1injection.
9
Intravitreal steroid allows
From *the Department of Ophthalmology, Queen’s University, Kingston,
Ont.; and
{
the Department of Ophthalmology, McMaster University,
Hamilton, Ont.
Presented as a poster at the annual meeting of the American Academy of
Ophthalmology in San Francisco, Calif., October 2009
Originally received Nov. 27, 2009. Final revision Mar. 23, 2010
Accepted Mar. 24, 2010
Published online Sep. 20, 2010
Correspondence to Hussein Hollands, MD, Department of Ophthalmology,
Hotel Dieu Hospital, Johnson 6, 166 Brock St., Kingston ON K7L 5S9;
hussein.hollands@yahoo.com
This article has been peer-reviewed. Cet article a e
´te
´e
´value
´par les pairs.
Can J Ophthalmol 2010;45:484–8
doi:10.3129/i10-050
484 CAN J OPHTHALMOL—VOL. 45, NO. 5, 2010
for therapeutic concentrations of the drug to be reached
without widespread systemic side effects.
2
However, com-
plications with local injection of IVTA are well documented
and include raised intraocular pressure (IOP), cataract
formation, infection, and sterile endophthalmitis.
2,9
The most common complication of IVTA is raised
IOP.
2,9
Jonas et al.
10
found that 44%, 15%, and 2.5% of
patients had a maximum IOP §21 mm Hg, 30 mm Hg,
and 40 mm Hg, respectively, within 9 months of receiving
20 mg IVTA. A well-designed randomized clinical trial by
Gillies et al.,
1
investigating 4 mg IVTA for the treatment of
diabetic macular edema (n564), showed that 68% of
patients had an IOP §5 mm Hg over baseline (vs 10%
for control), 44% required new glaucoma medication to
control IOP (vs 3% for control), and 6% required glau-
coma filtration surgery to control IOP (vs 0% for control).
Some ophthalmologists use a short course of the topical
steroid prednisolone acetate (Predforte; Allergan, Irvine,
Calif.) before IVTA to determine who is at risk of an IOP
spike after the injection. This will be referred to in this report
as a prednisolone acetate trial (PAT). Those patients who have
an IOP rise over the short-term PAT are deemed to be steroid
responders and are at higher risk of a serious IOP spike after
IVTA; thus, those patients would generally not be given
IVTA. Those patients who do not have an IOP rise after
the short-term PAT are considered at a lower risk of devel-
opinganIOPspikeafterIVTAandaretreatedwithIVTA.
To our knowledge, the efficacy of using a PAT to predict
IOP spikes after IVTA has not been reported. However, a
recent study tested the diagnostic accuracy of dexametha-
sone 0.1% (DXM) drops (a stronger steroid than predni-
solone acetate) in predicting a steroid response of 6 mm Hg
or greater after IVTA injection in 35 patients.
11
The
researchers found that DXM had a sensitivity of 25% and
a specificity of 100% in predicting an IOP spike after IVTA
injection. The purpose of this study was to compare adverse
IOP spikes among patients undergoing a PAT without a
short-term IOP rise followed by IVTA, with those patients
not undergoing a PAT before receiving IVTA.
METHODS
Ethics committee approval was obtained from the
Queen’s University Research Ethics Board. This paper
describes a retrospective cohort study based on a chart review
of all patients undergoing IVTA injection by 1 retinal sur-
geon (JG) at our centre between 2005 and 2008.
Two cohorts were defined for this study. The first group
underwent a PAT of topical prednisolone acetate 1%
4 times per day for 6 weeks and did not incur an IOP rise.
Rises in IOP were defined as IOP above 25 mm Hg or
IOPs that were 8 mm Hg above the IOP in the contra-
lateral eye. The control group did not undergo a PAT and
were treated with IVTA. The decision to use a PAT was
based on clinical situation, urgency of required treatment,
applicability of other therapeutic options, and presence of
previous glaucoma or family history of glaucoma. If a
patient had an IOP rise (as defined above) after a PAT,
then they were considered a steroid responder and did not
receive IVTA; this group of patients was not identified or
analyzed in our study. Patients who had received previous
steroid drops or injections for another reason but did not
receive a formal PAT represented an intermediate group
and these patients were excluded.
The charts of all patients in the practice who received an
intravitreal injection were identified using billing codes,
and those receiving IVTA were included. Patients receiving
IVTA with intraocular surgery were excluded. Patients
were followed for 1 year after the injection or until they
had intraocular surgery or another IVTA injection. A
6-week follow-up period was required for inclusion.
The centralized electronic medical records used at our cen-
tre allowed accurate determination of patients requiring med-
ical therapy, laser surgery, or filtration surgery to manage IOP.
All patients received an injection of 12–20 mg IVTA in a
standardized fashion. A vial of triamcinolone acetonide
(40 mg/mL) was allowed to stand for 1 week, the clear
supernatant was withdrawn and discarded, and the remain-
ing crystalline solution was drawn up. Next, 0.05 mL of the
crystalline solution was injected 3.5 mm posterior to the
limbus in the inferotemporal quadrant using a 27-guage
needle on a tuberculin syringe. A sterile Q-tip was then
placed on the injection site to prevent medication reflux.
Data were analyzed using SPSS, v. 12.0 for Windows
(SPSS Inc, Chicago, Ill.). Outcome measurements were
based on the maximum IOP measured after IVTA injec-
tion during the follow-up period (defined as IOP max) and
the baseline IOP. Univariate analysis used Student’s ttests
for continuous data and x
2
tests or Fisher’s exact tests as
appropriate for categorical data. The main IOP outcomes
used were proportion of patients with IOP max above
35 mm Hg, 40 mm Hg, and 45 mm Hg, and proportion
of patients with a 40%, 60%, and 100% increase in IOP
max above baseline. In addition, the proportions ofpatients
requiring medical and surgical intervention for glaucoma
were compared. Finally, multivariate logistic regression ana-
lyses with backward selection (exclusion of p§0.15) and
multivariate linear regression were used to simultaneously
investigate factors associated with raised IOP after IVTA.
RESULTS
The charts of all patients who underwent any intravitreal
injection during the study period were reviewed
(n51150). The majority of patients (864) were excluded
because they received bevacizumab or another intravitreal
medication and not IVTA, 55 patients were excluded
because the IVTA was administered with an intraocular
surgery, 38 were excluded because they had received ster-
oid drops or IVTA in the past, and 21 were excluded
because of follow-up less than 6 weeks. This analysis therefore
Topical prednisolone acetate before intravitreal TA—Hollands et al.
CAN J OPHTHALMOL—VOL. 45, NO. 5, 2010 485
includes 172 patients who received IVTA; 97 (56%)
underwent a PAT and 75 (44%) were controls.
Baseline demographic and clinical information is shown
in Tables 1 and 2. There was no significant difference in
mean age, follow-up time, or baseline IOP between the 2
cohorts. Approximately 5% of all patients were taking
glaucoma medication at baseline and those patients
who underwent a PAT were more likely to be taking it
(p50.042). Patients in the PAT cohort had a lower pro-
portional rise in IOP between IOP max and baseline com-
pared with controls (p50.035) (Table 3). There was also a
statistical trend towards patients in the PAT cohort having a
lower IOP max compared with controls (p50.074).
Patients in the PAT cohort were less likely to incur an
IOP max §40 mm Hg and 45 mm Hg (p50.022,
p50.081, respectively) compared with controls (Table 4)
but there was no difference in the proportion of patients
attaining an IOP max §35 mm Hg. Patients in the PAT
group also had a lower risk of incurring a 40%, 60%, and
100% increase in IOP (vs baseline) compared with con-
trols (p50.05, p50.018, and p50.045, respectively).
Patients in the PAT cohort were less likely to require glau-
coma filtration surgery (p50.035).
Multivariate logistic regression showed that patients
undergoing a PAT were less likely to have an IOP max
§40 mm Hg (p50.05 vs baseline) and were less likely
to have a rise in IOP max §40%, 60%, and 100% (vs
baseline) compared with controls (p50.018, p50.017,
and p50.048, respectively) (Table 5). Previous glaucoma
mediations were not associated with IOP spikes in our
models. Patients with higher baseline IOP tended to have
a lower chance of proportional IOP spikes of IOP max
§40%, 60%, and 100% (vs baseline) compared with con-
trols (p50.002, p50.004, and p50.011, respectively)
(Table 5). Older age (p50.057), higher baseline IOP
(p50,0.005), and a PAT (p50.008) were all associated
Table 1—Baseline data (continuous)
Continuous variable
Control,
mean (SD)
PAT,
mean (SD) Difference*pvalue
Age, y 71.6 (11) 70.7 (12) 0.884 0.61
Follow-up time, d 267 (109) 239 (123) 27.6 0.11
Baseline IOP,mm Hg 15.6 (5) 15.2 (4) 0.36 0.58
*Difference defined as mean value in No PAT minus mean value in PAT.
Note: PAT, prednisolone acetate trial; IOP, intraocular pressure.
Table 2—Baseline data (categorical)
Categorical variable No (%) No (%) Odds ratio pvalue
Previous glaucoma medication 1 (1.3) 8 (8.3) 6.65 0.042
Reason for IVTA
Diabetic macular edema 26 (34.6) 44 (46.8) 1.625 0.084
CNVM 31 (41.3) 13 (13.8) 0.25 0.0005
CME 6 (8.0) 6 (6.3) 0.59 0.39
Macular edema
(due to venous occlusion)
10 (13.3) 29 (30.8) 1.71 0.22
Other*2 (2.6) 2 (2.1) 0.59 0.60
*Macular edema secondary to juxtafoveal telangiectasia.
Note: IVTA, intravitreal triamcinolone acetonide; CNVM, choroidal neovascular membrane;
CME, cystoid macular edema.
Table 3—IOP outcome data (continuous)
Continuous variable
Control,
mean (SD)
PAT,
mean (SD) Difference*pvalue
Time until IOP max, d 89.7 (90)
(range 0–364)
99.3 (88)
(range 0–365)
210.16 0.47
IOP max, mm Hg 23.7 (9) 21.5 (8) 2.19 0.074
Difference (IOP max2
baseline), mm Hg
8.16 (8.9) 6.32 (7.2) 1.83 0.122
Percentage change in IOP
(IOP max vs baseline)
64 (83) 43% (52%) 21% 0.035
*Difference defined as mean value in No PAT minus mean value in PAT.
Note: IOP, intraocular pressure; PAT, prednisolone acetate trial.
Table 4—Outcome data (categorical)
Categorical variable
Control
No. (%)
PAT
No. (%)
Odds
ratio pvalue
IOP max §35 mm Hg 8 (11) 6 (6) 0.55 0.28
IOP max §40 mm Hg 6 (8) 1 (1) 0.11 0.022
IOP max §45 mm Hg 3 (4) 0 NA 0.081
IOP max §40% over baseline 43 (57) 41 (42) 0.54 0.05
IOP max §60% over baseline 33 (44) 26 (27) 0.46 0.018
IOP max §100% over baseline 21 (28) 15 (15) 0.47 0.045
Additional topical glaucoma
medication
8 (11) 14 (14) 1.41 0.46
Selective laser trabeculoplasty 3 (4) 5 (4) 1.30 0.72
Glaucoma filtration surgery 4 (5) 0 NA 0.035
Note: PAT, prednisolone acetate trial; IOP, intraocular pressure; NA, not available.
Table 5—Multivariate logistic regression analyses
Regression models Odds ratio pvalue
Model 1 (IOP max §40 mm Hg)
PAT 0.12 0.05
Constant 0.087 ,0.0005
Model 2 (IOP max §40% over baseline)
Previous glaucoma drops 3.2 0.12
Baseline IOP 0.85 0.002
Age 0.965 0.018
PAT 0.45 0.018
Constant 193.5 ,0.0005
Model 3 (IOP max §60% over baseline)
Baseline IOP 0.87 0.004
Age 0.98 0.142
PAT 0.45 0.017
Constant 32.0 ,0.0005
Model 4 (IOP max §100% over baseline)
Baseline IOP 0.86 0.011
Age 0.96 0.02
PAT 0.45 0.048
Constant 68 0.006
Note: IOP, intraocular pressure; PAT, prednisolone acetate trial.
Table 6—Multiple linear regression predicting changes i n IOP (IOP
max vs baseline) from age, baseline IOP, and cohort allocation
Predictor Coefficient Standard error pvalue
Age 20.0078 0.04 0.057
Baseline IOP 20.052 0.01 ,0.005
PAT 20.25 0.094 0.008
Intercept 1.99 0.388 —
Note: IOP, intraocular pressure; PAT, prednisolone acetate trial.
Topical prednisolone acetate before intravitreal TA—Hollands et al.
486 CAN J OPHTHALMOL—VOL. 45, NO. 5, 2010
with a lower rise in proportional IOP max versus baseline,
using linear regression analysis (Table 6).
DISCUSSION
A simple method for determining which patients are at
greatest risk of an IOP spike after IVTA injection would be
beneficial. The results of this large retrospective cohort study
of patients being treated with IVTA shows that those under-
going a PAT (without a short-term IOP rise) have a lower
risk of severe IOP spikes compared with those not under-
going a PAT. Presumably, this is because those patients who
underwent a PAT and had a short-term IOP rise were at
higher risk of an IOP spike after IVTA, and were filtered
from the study, leaving the patients in our PAT cohort a
lower-risk group when compared with control patients.
To our knowledge, only 1 other study has looked at
topical steroids as a diagnostic predictor of IOP spike after
IVTA. Breusegem et al.
11
found that topical DXM had a
sensitivity of 25% and a specificity of 100% in predicting
an IOP spike over 6 mm Hg after IVTA. They found that in
DXM responders, theIOP increased by 17(SD 7.8) mm Hg,
whereas in DXM nonresponders, it increased by 5.0
(SD 4.4) mm Hg, and they concluded that a trial of
DXM may be useful in predicting which patients will have
IOP spikes after IVTA. Because in our study we did not
administer IVTA to patients found to have had an IOP spike
after a trial of topical steroid, we cannot compare our results
quantitatively with the study by Breusegem and others.
A 100% rise in IOP max above baseline was seen in
15.5% of patients who underwent a PAT and in 28.0%
of controls. In other words, 1 IOP spike of 100% IOP max
versus baseline could have been prevented by having 7.8
patients undergo PAT (without having a short-term IOP
rise) before IVTA. A PAT also resulted in a lower rate of
glaucoma filtration surgery (5.3% vs 0%); this translates
into a number needed to treat of 19 patients.
The overall prevalence of raised IOP in our study was
similar to that found in previous reports in the literature.
Jonas et al.
10
found that 15% of patients had a maximum
IOP §30 mm Hg and 2.5% had a maximum IOP of
40 mm Hg after IVTA, and our study found 17% and
4% of patients reached these cut-offs, respectively. In addi-
tion, Gillies et al.
1
found that 6% of patients receiving 4 mg
IVTA required glaucoma filtration surgery, and our study
found that 2.3% of patients required this surgery.
Given the retrospective nature of this study, there are some
inherent biases. Patients were given a PAT at the discretion of
the surgeon; therefore, patients with previous glaucoma or a
family history of glaucoma were much more likely to be given
a PAT. Because patients with glaucoma or a family history of
glaucoma may be more likely to have an IOP spike after IVTA,
the group of patients receiving a PAT in our study was biased
towards having a higher risk of an IOP spike after injection.
Consequently, we believe that our results are conservative and
that if the groups had been allocated randomly, we would have
seen even stronger results favoring the PAT cohort.
This study has a number of weaknesses. First, the study
was based on a chart review; therefore, strict inclusion and
exclusion criteria could not be defined a priori. Second, we
were not able to follow those patients who had had an IOP
rise after a short-term PAT. One consequence of this is that
we cannot accurately determine the true number-needed-
to-treat estimate for this intervention. Finally, the decision
as to whether patients received a PAT or not was based on
their presumed likelihood of an IOP spike after IVTA.
This represents selection bias but, as noted above, we feel
that this resulted in our findings being conservative.
In conclusion, a PAT for patients about to undergo IVTA
may be useful in determining which patients are at increased
risk of a severe IOP spike after IVTA. This study showed
that those patients undergoing a PAT who did not have a
subsequent short-term IOP rise have a lower risk of severe
IOP spikes after IVTA, compared withthose patients receiv-
ing IVTA but not having undergone a PAT. Our study
represents preliminary data that need to be confirmed with
a prospective randomized clinical study; this multicentred
investigation is currently underway at our institution.
The authors have no proprietary or commercial interest in any materials
discussed in this article.
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Keywords: intraocular pressure spikes, IOP, prednisolone acetate,
intravitreal triamcinolone acetonide
Topical prednisolone acetate before intravitreal TA—Hollands et al.
488 CAN J OPHTHALMOL—VOL. 45, NO. 5, 2010
