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Effectiveness of diclofenac eyedrops

in reducing inflammation and the


incidence of cystoid macular edema
after cataract surgery
Luca Rossetti, MD, Eugenia Bujtar, MD, Daniela Castoldi, MD,
Carlo Torrazza, MD, Nicola Orzalesi, MD

ABSTRACT
Purpose: To evaluate the effectiveness of diclofenac eyedrops in reducing inflamma-
tion and the incidence of angiographic cystoid macular edema (CME) after cataract
surgery and intraocular lens (IOL) implantation.
Setting: Eye Clinic, Institute of Biomedical Sciences, San Paolo Hospital, Milan, Italy.

Methods: Eighty-eight patients having cataract extraction were enrolled in a random-


ized clinical trial: 42 were given diclofenac eyedrops and 46, placebo. Postopera-
tive inflammation in both groups was graded for 6 months using a dedicated
system.
Results: Eight patients (9%) had evidence of angiographic CME approximately
1 month after surgery; seven of these were in the placebo group (P = .039). This
difference was not significant 3 and 6 months postoperatively. The signs of ocular
inflammation were greater in the eyes receiving placebo; the difference was par-
ticularly evident up to 1 week after surgery. There was no significant difference in
visual acuity between the two groups at any follow-up point, but the contrast
sensitivity of the eyes that received diclofenac improved significantly at 10.5 cycles
per degree 1 month postoperatively.
Conclusion: Diclofenac eyedrops effectively reduced ocular inflammation and the
occurrence of angiographic CME after cataract surgery. J Cataract Refract Surg
1996; 22:794-799

N onsteroidal anti-inflammatory drugs (NSAIDs),


recently available as ophthalmic eyedrops, are ef-
fective in managing postoperative ocular inflammation
vious investigators have documented the anti-inflamma-
tory effect of different topical NSAID treatments after
cataract surgery by slitlamp observation and fluoropho-
and useful in other aspects of ophthalmic surgery. 1 Pre- tometry.2-6 Some of these drugs are as effective as ste-
roidal anti-inflammatory agents but do not have the
associated risks?-9
Presented in part at the annual meeting ofthe Association for Research in Nonsteroidal anti-inflammatory drugs have also
Vision and Ophthalmolugy, Fort Lauderdale, Florida, May 1995.
been tested to prevent pseudophakic cystoid macular
None of the authors has a proprietary interest in the instruments or
materials mentioned
edema (CME) , an often self-limiting condition but a
frequent complication after otherwise uneventful cata-
Reprint requests to Prof Nicola Orzalesi, Clinica Oculistica Universitti
di Milano, Istituto di Scienze Biomediche, Ospedale San Paolo, Via di ract surgery. 1 Several controlled studies have demon-
Rudini 8,20142 Milano, Italy. strated that NSAIDs may be successfully used to prevent

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EFFECTIVENESS OF DICLOFENAC EYEDROPS

.
anglOgrap h'lC CME WIt . h IO - 12 or Wit
• h out 13 t h e concur- measurement by applanation tonometry, and ophthal-
rent use of steroids. moscopic evaluation.
Diclofenac sodium (Voltaren®) is a potent, rapidly The number of anterior chamber cells and flare were
acting NSAID, recently approved by the U.S. Food and determined by two well-trained, masked evaluators us-
Drug Administration (FDA) for the treatment of post- ing the following clinical grades. For anterior chamber
cataract extraction inflammation. Although steroids are cells, 0 = none, 1 = 1 to 5 cells, 2 = 6 to 15 cells,
not specifically approved by FDA for the treatment of 3 = 16 to 30 cells, 4 = more than 30 cells; for flare,
postoperative ocular inflammation, they are widely ad- o = none, 1 = trace of flare, 2 = mild flare, 3 = mod-
ministered as standard therapy after cataract extraction. erate flare, 4 = strong flare. All the evaluations were
This randomized clinical trial was designed to evaluate made under standard conditions: dim room illumina-
whether diclofenac sodium ophthalmic solution should tion, the highest lamp voltage, the smallest aperture
be added to the standard therapy to reduce postoperative (0.3 mm), a 30 degree angle, and a magnification of
inflammation and the incidence of angiographic CME 16X.
after cataract surgery. Contrast sensitivity was assessed 1, 3, and 6 months
after surgery using a computer-based system (Conel Sys-
tem) that presents sinusoidal bars on a screen and mea-
Subjects and Methods sures contrast sensitivity at five levels of spatial
Patients scheduled for extracapsular cataract extrac- frequency. Contrast sensitivity was evaluated with best
tion (ECCE) with implantation of an intraocular lens corrected refraction.
(IOL) were eligible for inclusion in the trial. We ex- All patients were scheduled for fluorescein angiog-
cluded patients with diabetes, glaucoma, and a diagnosis raphyat 1, 3, and 6 months postoperatively. The angio-
of maculopathy, and those being systemically treated grams were read and graded according to the Miyake
with steroids, acetazolamide, or NSAIDs. After giving classification 11 by one masked retinal specialist: 0 = no
informed consent, the patients were randomized to re- leakage, 1 = less than perifovealleakage, 2 = clinically/
ceive 0.1 % diclofenac sodium ophthalmic solution or a ophthalmoscopically evident 360 degree perifovealleak-
placebo. Randomization was obtained using a table of age, and 3 = severe (>one disc diameter).
random numbers. The trial was double-masked. The A two-sample t-test was used to test for significance
eyedrops were administered by the nursing staff four of differences in group means. The chi-square test, Fish-
times daily starting 3 days before surgery until patient er's exact test, and trend analysis were used for statistical
discharge. Patients were then instructed to instill one analysis of proportions.
drop four times daily for 3 months after surgery.
The majority of the surgeries were performed by one
surgeon (N.O.) using both conventional ECCE and
phacoemulsification. Approximately half the ECCEs
Results
were performed by residents in training. Eighty-eight patients were included in the study:
All patients received a 2 ml sub-Tenon' s injection of 42 received diclofenac eyedrops and 46, placebo. In the
betamethasone (1 m!) and amikacin (1 m!) at the end of diclofenac group, 14 eyes (33.3%) had phacoemulsifica-
surgery and 1 day postoperatively. Drops containing to- tion and 28 (66.7%), ECCE. In the placebo group, 11
bramycin and dexamethasone were administered four (23.9%) had phacoemulsification and 35 (76.1%),
times daily for 3 weeks after surgery. In addition, a myd- ECCE. All patients completed the study, and treatment
riatic (tropicamide 1%) was instilled twice daily during regimens were well tolerated with no evidence of rele-
the first postoperative week. vant side effects.
Complete ocular examinations were performed and Patient characteristics are shown in Table 1. There
recorded 2 days before surgery, at 1, 5, and 28 days were no significant differences between the two groups
postoperatively, and at 3 and 6 months. Examinations in age, sex, and preoperative visual acuity. Complica-
included visual acuity assessment (Snellen chart), slit- tions and additional surgical procedures are shown in
lamp biomicroscopy, intraocular pressure (lOP) Table 2. The posterior capsule ruptured in eight pa-

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EFFECTIVENESS OF DICLOFENAC EYEDROPS

Table 1. Patient characteristics. Table 3. Anterior chamber cell scores.

Oiclofenac Group Placebo Group Oiclofenac Group Placebo Group

Number (%) Number (%) Number (%) Number (%)

Total 42 (100) 46 (100) Postop day 1


Male 12 (28.6) 20 (43.5) 0 3 (7.1) (2.2)
Female 30 (71.4) 26 (56.5) +1++ 26 (61.9) 23 (50)
Age (SO) 74.2 (8.8) 72.9 (9.4) +++1++++ 13 (31) 22 (47.8)
Preop VA (SO) 0.32 (0.26) 0.34 (0.24) Total 42 (100) 46 (100)
Postop day 5*
SO = standard deviation
0 14 (33.3) 5 (10.9)
VA = visual acuity
+ 23 (54.8) 25 (54.3)
++1+++ 5 (11.9) 16 (34.8)
Table 2. Types of cataract surgery and complications. Total 42 (100) 46 (100)

*Chi-square for trend = 9.95 (P = .007)


Diclofenac Placebo
Group Group

Number (%) Number (%) Table 4. Anterior chamber flare scores.

Total 42 (100) 46 (100) Oiclofenac Group Placebo Group


Phacoemulsification 14 (33.3) 11 (23.9)
Number (%) Number (%)
ECCE 28 (66.7) 35 (76.1)
Posterior capsule rupture 3 (7.1) 5 (10.9) Postop day 1
Hyphema (2.4) (2.2) 0 4 (9.5) (2.2)
Anterior chamber implantation 2 (4.8) 4 (8.7) +1++ 29 (69) 28 (60.9)
Anterior vitrectomy 2 (4.8) 3 (6.5) +++1++++ 9 (21.5) 17 (36.9)
Iridectomy (2.4) (2.2) Total 42 (100) 46 (100)
Postop day 5*
There was no significant difference between complication rates in
0 27 (64.3) 17 (36.9)
the two groups (P = .47)
+ 13 (30.9) 27 (58.7)
++1+++ 2 (4.8) 2 (4.4)
tients; an anterior vitrectomy was required in five eyes Total 42 (100) 46 (100)
and an anterior chamber IOL was placed in six. *Chi-square for trend = 9.79 (P = .007)
At 1 day postoperatively, the mean anterior cham-
ber cell scores were 2.12 and 2.65 in the diclofenac and
Table 5. Postoperative visual acuities.
placebo groups, respectively, and the mean flare scores
were 1.90 and 2.25, respectively. Diclofenac treatment Oiclofenac Group Placebo Group

was associated with less postoperative inflammation Postoperative Mean (SO) Mean (SO)
Month >20/40 (%) >20/40 (%)
than placebo. The difference between the two groups
was statistically significant at 5 days (Tables 3 and 4). 0.76 (0.26) 83 0.72 (0.26) 80
3 0.84 (0.22) 88 0.83 (0.27) 89
Intraocular pressure was similar in the two groups at
6 0.90 (0.25) 93 0.90 (0.24) 91
all follow-up visits (P = .38).
Visual acuity at 1, 3, and 6 months postoperatively There was no significant difference in mean visual acuity between
the groups
is shown in Table 5. There were no significant differ-
ences between the two groups. Mean contrast sensitivity
was higher in the diclofenac patients (Figure 1), al- (Table 6). Of the eight cases, one (in the placebo group)
though the difference between the two groups was sta- had clinical signs of CME and was given 250 mg of
tistically significant only at 1 month and for higher acetazolamide orally twice daily. The other seven cases
spatial frequencies (10.5 cycles per degree). had only angiographic evidence, with normal postoper-
At 1 month postoperatively, eight patients (9.0%) ative visual acuities. However, five had significantly
had angiographic evidence of CME: seven in the placebo lower contrast sensitivities. Five of the eight cases were
group and one in the diclofenac group (P = .039). At self-limiting by 6 months postoperatively and were as-
3 and 6 months, this difference was no longer significant sociated with an intraoperative complication or an ad-

796 J CATARACT REFRACT SURG-VOL 22, SUPPLEMENT 1996


EFFECTIVENESS OF DICLOFENAC EYEDROPS

120,---------------------------------------------------~

Figure 1. (Rossetti) Mean contrast sensi-


tivity 1 month postoperatively.

Spatial Frequency (cpd)

\ ...... SUmdard treatment -+- Diclofenac

Table 6. Cases of angiographic CME. day, the anti-inflammatory effect was greater and the
Diclofenac Placebo diclofenac-treated eyes had significantly less flare and
Group Group fewer anterior chamber cells than the placebo-treated
Postoperative Month Number (%) Number (%) eyes.
l' (2.4) 7 (15.2) Diclofenac treatment was not associated with in-
3 (2.4) 4 (8.7) creased postoperative lOP. Some previous studies have
6 (2.4) 2 (4.3)
concluded that NSAID treatment can influence postop-
With complicated surgery 1/3 (33.3) 4/5 (80.0)
erative lOP, particularly when NSAIDs are combined
'Chi-square = 4.38 (P = .04) . h sterol'ds. 16-18 In th e current study, t he group
wIt
treated with the combination of diclofenac and steroids
ditional surgical procedure. No CME occurred later had lOP values very similar to those observed in the
than 1 month postoperatively. group receiving the combination of placebo and ste-
roids, suggesting that diclofenac did not affect lOP.
Although visual acuities in the two groups were sim-
Discussion ilar, the diclofenac-treated patients had better contrast
sensitiviry; the difference between them and the place-
In this study, the diclofenac-treated eyes had less
postoperative inflammation and a lower incidence of bo-treated patients was particularly evident for higher
angiographic CME than the placebo-treated eyes. Pre- spatial frequencies. This finding confirms Ginsburg and
vious reports have shown that diclofenac sodium effec- coauthors'19 findings for other NSAIDs. Flurbiprofen
tively decreases ocular inflammation after cataract treatment improved contrast sensitivity in patients with
surgery and 10L implantation. 5,6,9,14,15 The results of and without CME significantly at 12 cycles per degree
this study suggest that diclofenac can enhance the effect on postoperative day 40. In our study, the higher con-
of steroids in reducing postoperative inflammation. trast sensitivities observed in the diclofenac-treated pa-
This enhancement is probably because the anti-inflam- tients did not seem to be due to the reduced
matory effect of the two drugs is obtained by two sepa- postoperative inflammation in the anterior chamber
rate mechanisms. Diclofenac seemed to become since 1 month after surgery, there was no inflammation
effective 24 hours after surgery, probably due to the in either group. Perhaps other mechanisms are involved
preoperative administration. On the fifth postoperative in the positive effect of NSAIDs on contrast sensitivity.

J CATARACT REFRACT SURG-VOL 22, SUPPLEMENT 1996 797


EFFECTIVENESS OF DICLOFENAC EYEDROPS

Diclofenac treatment was effective in reducing the with diclofenac; a fluorophotometric study. Arch Oph-
incidence of angiographic CME, which supports the thalmol1990; 108:380-383
6. Araie M, Sawa M, Takase M. Topical flurbiprofen and
conclusions of several investigators about the effective-
didofenac suppress blood-aqueous barrier breakdown in
ness of a variety of NSAIDs in preventing angiographic
cataract surgery: a fluorophotometric study. Jpn J Oph-
CME. 10 - 13 One month after surgety the incidence of thalmol1983; 27:535-542.
angiographic CME was approximately 9.0%, which is 7. Flach AJ, Jaffe NS, Akers WA. The effect of ketorolac
consistent with other published data. 10-13 In our study, tromethamine in reducing postoperative inflammation:
as in a previous one,20 the majorityofCME cases were in double-mask, parallel comparison with dexamethasone.
Ann Ophthalmol1989; 21:407-411
eyes in which surgical complications had occurred. Al-
8. Flach AJ, Kraff MC, Sanders DR, Tanenbaum L. The
though "clinical" CME is today an infrequent compli-
quantitative effect of 0.5% ketorolac tromethamine solu-
cation21 following cataract surgery (perhaps less than tion and 0.1 % dexamethasone sodium phosphate solu-
1.0% with advanced surgical procedures), preventing tion on postsurgical blood-aqueous barrier. Arch
the condition is important because of the number of Ophthalmol 1988; 106:480 - 483
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published literature on preventing CME indicated that
Ophthalmology 1989; 96(suppl): 109
NSAID treatment can decrease the incidence of clini- 10. KraffMC, Sanders DR, Jampol LM, et al. Prophylaxis of
cally relevant CME and improve vision. 22 pseudophakic cystoid macular edema with topical indo-
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NSAIDs could completely replace the use of steroids in laxis of aphakic cystoid macular edema without cortico-
steroids; a paired-comparison, placebo-controlled
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1258
14. Ronen S, Rozenman Y, Zylbermann R, Berson D. Treat-
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