Preoperative topical indomethacin to prevent pseudophakic cystoid macular edem

Güliz Fatma Yavas

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Preoperative topical indomethacin to prevent
pseudophakic cystoid macular edema
Gu ¨liz Fatma Yavas, MD, Faruk O ¨ ztu ¨rk, MD, Tuncay Ku ¨sbeci, MD
PURPOSE: To evaluate the effectiveness of a nonsteroidal antiinflammatory drug (NSAID) on pseu-
dophakic cystoid macular edema (CME) and determine the efficacy when used preoperatively and
after uneventful phacoemulsification surgery.
SETTING: Department of Ophthalmology, Kocatepe University, School of Medicine, Afyonkarahisar,
Turkey.
METHODS: One hundred seventy-nine eyes of 189 patients having uneventful phacoemulsification
surgery were enrolled in the study. After surgery, all patients used topical steroids and antibiotics 4
times daily. Sixty-one eyes, chosen randomly, received a topical NSAID (indomethacin) 4 times
daily for 3 days preoperatively and 1 month postoperatively. Sixty eyes received topical indometh-
acin 4 times daily for 1 month postoperatively. Fifty-eight eyes served as a control group and re-
ceived only topical steroids and antibiotics. At the third postoperative month, visual acuity,
fluorescein angiograms, and macular thresholds were evaluated. Statistical analysis was by chi-
square and 1-way analysis of variance tests.
RESULTS:Cystoidmacularedema was notseen inthegroupreceiving indomethacin preoperatively
and postoperatively. The incidence of angiographic CME was 15.0% in the group receiving postop-
erative indomethacin and 32.8% in the control group (P<.001). Mean sensitivity in the macular
threshold test did not show a significant change between groups (P Z .83). Postoperative visual
acuity was significantly higher in the group receiving preoperative indomethacin (P<.001).
CONCLUSION: Nonsteroidal antiinflammatory drugs decreased the incidence of CME, and their ef-
ficacy increased when begun preoperatively.
J Cataract Refract Surg 2007; 33:804–807 Q 2007 ASCRS and ESCRS
The most common cause of vision loss after cataract
surgery is the development of cystoid macular edema
(CME). Cystoid macular edema is related to the dis-
ruption of the blood–retinal barrier and blood–aque-
ous barrier (BAB) and the inflammation induced by
prostaglandins or other inflammatory mediators.
1
Cystoidmacularedemacanbeseenclinicallyorangio-
graphically. The incidence of clinical CME has been re-
ported to be 0% to 6% and of angiographic CME, 9.1%
to 54.7%.
1–3 In clinical CME, Snellen visual acuity is
worse than 20/40. In fluorescein angiographic CME,
there is dye leakage on angiography and visual acuity
does not change. The use of postoperative nonsteroi-
dalantiinflammatorydrugs(NSAIDs)hasbeenshown
to decrease aqueous prostaglandin levels and thus the
development of CME.
4
In this study, we evaluated the effect of NSAID use
on the development of CME after uneventful phaco-
emulsification surgery with the macular threshold vi-
sual field test and fluorescein angiography.
PATIENTS AND METHODS
The prospective study comprised the right eyes of 189 pa-
tients. The institution’s ethics committee approved the
study, and all patients provided written informed consent.
Patients with a history of intraocular surgery; any complica-
tion during cataract surgery; glaucoma; uveitis; vitreoretinal
pathology; history of diabetes mellitus, hypertension, or car-
diac disease; or topical or systemic drug use were excluded
from the study.
Accepted for publication January 29, 2007.
From the Afyon Kocatepe University, Faculty of Medicine, Depart-
ment of Ophthalmology, Afyonkarahisar, Turkey.
No author has a financial or proprietary interest in any material or
method mentioned.
Corresponding author: Gu ¨liz Yavas, P.K. 25, 06502 Bahcelievler,
Ankara, Turkey. E-mail: gkumbar@ttnet.net.tr.
Q 2007 ASCRS and ESCRS 0886-3350/07/$dsee front matter
Published by Elsevier Inc. doi:10.1016/j.jcrs.2007.01.033
804
ARTICLEAlloperationswereperformedbythesamesurgeon (F.O ¨ ).
After topical anesthesia of proparacaine 0.5% was adminis-
tered, a 3.2 mm clear corneal tunnel incision was created.
A capsulorhexis was made, and phacoemulsification and bi-
manual cortical aspiration were performed. A hydrophilic
monofocal foldable acrylic intraocular lens (AR40e, AMO)
was implanted in the capsular bag.
Patients were randomized into 3 groups. All groups re-
ceived 1 drop of topical steroid (prednisolone acetate 1%) 4
times daily for 1 month and 1 drop of topical antibiotic
(ofloxacin 0.3%) 4 times daily for 1 week. Group 1 received
1 drop of a topical NSAID (indomethacin 0.1%) 4 times daily
for 3 days preoperatively and continued indomethacin 4
times daily for 1 month postoperatively. Group 2 received
1 drop of topical indomethacin 0.1% 4 times daily for
1 month postoperatively as well as the topical steroid and
antibiotic. Group 3 served as a control group and did not
receive additional medication other than the topical steroid
and antibiotic.
Best corrected visual acuity (BCVA) was measured with
the Snellen chart at the preoperative examination and
3 months postoperatively. The BCVA values were converted
to logarithm of the minimum angle of resolution (logMAR).
Three months postoperatively, macular threshold perimetry
was performed with the Humphrey Visual Field Analyzer II
(Humphrey/Zeiss) and the mean macular sensitivity was
calculated in terms of decibels. White background illumina-
tion was used, and the stimulus was Goldmann size III.
Fluorescein angiography was performed in all patients,
and fluorescein leakage to diagnose angiographic CME was
evaluated by a masked observer. Five milliliters of sodium
fluorescein 10% was administered through an antecubital
vein, and photographs of the macular area were taken, with
late views 5 minutes after injection. Slight fluorescein leakage
into the cystic space without enclosing the entire central
fovea or complete fluorescein accumulation in the cystic
space was diagnosed as angiographic CME.
Statistical analysis was performed using SPSS software
(version 10.0, SPSS, Inc). Sex distribution of the patients
and the development of angiographic CME were evaluated
by the chi-square test. The differences in visual acuities and
mean macular sensitivities between groups were evaluated
by a 1-way analysis of variance (ANOVA). When a statisti-
cally significant difference was detected, the independent
sample t test was used to compare 2 groups. A P value less
than 0.05 was considered significant.
RESULTS
Two patients in Group 1, 3 patients in Group 2, and 5
patients in the control group refused fluorescein angi-
ography and were excluded from the study. Group 1
consisted of 61 patients; Group 2, 60 patients; and
the control group, 58 patients. Surgery was uneventful
in all cases.
Table 1 shows the patients’ demographic data. The
sex distribution between groups was not statistically
significant (P Z .55).
The mean BCVA before surgery was 0.74 logMAR
G 0.54 (SD) in Group 1, 0.86 G 0.69 logMAR in Group
2, and 1.06 G 0.83 logMAR in the control group
(P Z .11). Table 1 shows the BCVA 3 months after sur-
gery. The postoperative BCVA was significantly diff-
erent between the groups (P!.001). The difference
between Group 1 and the other 2 groups was signifi-
cant (P Z .005 versus Group 2; P!.001 versus control
group). The difference between Group 2 and the
control group was not significant (P Z .49).
Table1showsthemeanmacularsensitivity3months
postoperatively by group. The mean macular sensitiv-
ity was 408.94 G 89.10 dB in eyes with angiographic
CME (n Z 28) and 444.75 G 36.90 dB in eyes without
angiographicCME(nZ151).Thedifferencewasstatis-
tically significant (P Z .004). Group 1 had no cases of
CME. In Group 2, the mean macular sensitivity was
419.60 G 43.67 dB in eyes with CME and 443.18 G
35.86 dB in eyes without CME (P Z .18). In the control
group, the mean macular sensitivity was 440.36 G
60.28 dB in eyes with CME and 448.14 G 45.62 dB in
eyes without CME (P Z .66).
Table 2 shows the angiographic results 3 months
postoperatively. No patient in Group 1 developed an-
giographicCME.InGroup2,15.0%ofcaseshadangio-
graphic CME and in the control group, 32.8% of cases.
The difference between groups was statistically signif-
icant (P!.001). The incidence of angiographic CME
Table 1. Characteristics by group.
Characteristic Group 1 (n Z 61) Group 2 (n Z 60)
Control Group
(n Z 58) P Value
Mean age (y) G SD 65.28 G 9.90 62.25 G 11.57 64.78 G 9.18 .33*
Sex, n (%) .55
†
Male 33 (54.1) 36 (60.0) 37 (63.8)
Female 28 (45.9) 24 (40.0) 21 (36.2)
Mean macular
sensitivity (dB) G SD 3 mo postop
443.92 G 28.13 441.00 G 36.83 446.00 G 49.38 .83*
Mean visual
acuity (logMAR) G SD 3 mo
postop
0.02 G 0.04 0.09 G 0.16 0.11 G 0.12 !.001*
*One-way ANOVA
†Chi-square
805 PREOPERATIVE INDOMETHACIN TO PREVENT PSEUDOPHAKIC CME
J CATARACT REFRACT SURG - VOL 33, MAY 2007was significantly higher in the control group than in
Group 1 and Group 2 (P Z .020 and P!.001, respec-
tively). The difference between Group 1 and Group 2
was also significant (P Z .001).
DISCUSSION
Topical NSAIDs are widely used to prevent intraoper-
ative miosis, ocular inflammation, and CME.
1,3,5
Miyake
6hypothesizedthatprostaglandinsplayalead-
ing role in the development of aphakic CME. Cystoid
macular edema after cataract surgery is thought to be
related to the disruption of the BAB and an increase in
prostaglandins in the aqueous.
4 The incidence of CME
is highest between the sixth to eighth postoperative
weeks but can be seen years after surgery, although
at a lower incidence.
Ursell et al.
2 report that 60 days postoperatively,
19% of patients who had uneventful phacoemulsifica-
tion and who did not use an NSAID preoperatively or
postoperatively had angiographic CME. Miyake et al.
1
compared NSAIDs and fluorometholone and found
angiographic CME in 5.7% of patients receiving an
NSAID and in 54.7% of patients receiving fluorome-
tholone.Inourstudy,32.8%ofpatientswhodidnotre-
ceive a preoperative or postoperative NSAID (control
group) developed CME. This incidence agrees with
that reported in the literature.
There is no standard treatment modality for the pre-
vention or treatment of CME, and some NSAIDs are
being tried. Mentes et al.
3 report that after administra-
tion of postoperative topical prednisolone and tobra-
mycin for 1 month, the incidence of clinical CME
after uneventful phacoemulsification surgery was 0%
and of angiographic CME, 9.1%. Rossetti et al.
7 report
that the use of NSAIDs decreased the incidence of
CME. Wolfensberger and Herbort
8 report that postop-
erative use of NSAID helped in the prevention and
treatment of inflammatory CME as 90% of their cases
with CME recovered with NSAID use.Rho
9compared
diclofenac sodium 0.1% and ketorolac tromethamine
0.5% and found that both topical agents significantly
decreasedthe developmentof CME.Reis et al.
10 report
that valdecoxib, a new systemic cyclooxygenase 2 in-
hibitor, was useful in the treatment of CME. Singal
and Hopkins
11 found that topical ketorolac trometh-
amine 0.5% was effective in preventing CME. In
our study, 15.0% of patients using a postoperative
NSAID (Group 2) developed CME. This incidence
was significantly lower than that in the control group
(P!.001).
In our study, no patient receiving a preoperative
NSAID (Group 1) had angiographic CME. The inci-
dence of CME was significantly lower than in the con-
trol group and the group receiving only postoperative
indomethacin. Similarly, BCVA 3 months postopera-
tively was significantly higher in the group receiving
indomethacin preoperatively and postoperatively.
The use of NSAIDs preoperatively may limit the re-
lease of prostaglandins. By the time postoperative
NSAIDsaregiven, theintraoperativereleaseofprosta-
glandins has already occurred. In our opinion, this
explains why preoperative use of topical NSAIDs is
more effective in preventing postoperative CME.
Miyake and Ibaraki
4 report that the synthesis of
prostaglandins caused by surgical trauma could be
suppressed by pretreatment with NSAIDs, perhaps
decreasing the incidence of CME. The treatment mo-
dality in which topical indomethacin 1% is used pre-
operatively and postoperatively to reduce aphakic
CME was developed in Japan.
6 Donnenfeld et al.
12
evaluated the clinical benefit of ketorolac trometh-
amine 0.4% in phacoemulsification surgery. They ran-
domized the patients into 4 groups before surgery.
Patients in Group 1 instilled ketorolac tromethamine
0.4% 4 times daily for 3 days preoperatively and every
15 minutes during the hour before surgery. Group 2
patients instilled ketorolac tromethamine 0.4% 4 times
daily for 1 day preoperatively and every 15 minutes
during the hour before surgery. Group 3 patients in-
stilled ketorolac tromethamine 0.4% every 15 minutes
during the hour before surgery. The control group in-
stilled a placebo every 15 minutes during the hour be-
fore surgery. Postoperatively, the study groups
received ketorolac tromethamine 0.4% 4 times daily
and the control group received a placebo for 3 weeks.
At the end of 2 weeks, no patient in Group 1 or Group
2 had clinically significant CME; 4% in Group 3 and
12% in the control group had clinically significant
CME, although the difference between groups was
not significant (P Z .24). We could not find another
study in the literature of the effect of preoperative
NSAID instillation on CME development. Our results
should be evaluated in studies that use different kinds
of NSAIDs and in patients with ocular disease such as
diabetic retinopathy, age-related macular degenera-
tion, and uveitis.
The mean macular sensitivity was less in cases with
angiographic CME. The comparison of mean macular
sensitivitiesingroupsaccordingtothedevelopmentof
Table 2. Angiographic results 3 months postoperatively.
Number (%)
CME Group 1 Group 2 Control Group Total
Yes 0 9 (15.0) 19 (32.8) 28 (15.6)
No 61 (100) 51 (85.0) 39 (67.2) 151 (84.4)
CME Z cystoid macular edema
806 PREOPERATIVE INDOMETHACIN TO PREVENT PSEUDOPHAKIC CME
J CATARACT REFRACT SURG - VOL 33, MAY 2007angiographic CME revealed no statistically significant
difference (P Z .18 in Group 2; P Z .66 in control
group).Wecould not find astudy evaluating the effect
of cataract surgery on macular sensitivity. Lobo et al.
13
evaluated the macula with optical coherence tomogra-
phy and the retinal thicknessanalyzer afteruneventful
phacoemulsification; patients did not receive a topical
NSAID, and macular thickness increased in 41% of
patients.
In our study, we found the use of a topical preopera-
tive NSAID to be effective in preventing pseudophakic
CME after uneventful phacoemulsification surgery.
We believe that it would be of value to add a topical
preoperative NSAID to routine treatment protocols.
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First author:
Gu ¨liz Fatma Yavas, MD
807 PREOPERATIVE INDOMETHACIN TO PREVENT PSEUDOPHAKIC CME
J CATARACT REFRACT SURG - VOL 33, MAY 2007

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