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ARTICLE

Nepafenac 0.1% plus dexamethasone


0.1% versus dexamethasone alone: Effect
on macular swelling after cataract surgery
Anna Zaczek, MD, PhD, Ditte Artzen, MD, Carl-Gustaf Laurell, MD, PhD, Ulf Stenevi, MD, PhD,
Per Montan, MD, PhD

PURPOSE: To evaluate the efficacy of adding nepafenac 0.1% ophthalmic suspension to dexameth-
asone 0.1% eyedrops in controlling macular swelling and other manifestations of inflammation after
uneventful cataract surgery.
SETTING: Ophthalmology Department, M€olndal Hospital, Gothenburg, and St. Erik Eye Hospital,
Stockholm, Sweden.
DESIGN: Randomized double-masked clinical trial.
METHODS: Patients at low risk for postoperative inflammation were recruited and randomized to
the nepafenac group or to the control group. Postoperative swelling of the macula was assessed
with ocular coherence tomography. Laser flare intensity, corrected distance visual acuity, ocular
discomfort, and visual complaints were also recorded.
RESULTS: The analysis of intent-to-treat population comprised 75 patients in the nepafenac group
and 77 patients in the control group. Compared with the control regimen, add-on nepafenac resulted
in statistically significant reductions in the following parameters: change in macular volume at 3
weeks and 6 weeks (P<.001), proportion of patients with more than 10 mm of swelling in the
central macula at 3 weeks (P<.0001) and 6 weeks (PZ.02), mean laser flare intensity at 1 day
(PZ.029), pain during the first 24 hours postoperatively (P<.0001), and ocular discomfort and
photophobia during the first 3 postoperative weeks (PZ.0058 and PZ.0052, respectively).
CONCLUSION: The combination of topical nepafenac and steroid treatment reduced subclinical
macular swelling and inflammation as well as subjective complaints, indicating it is an efficient anti-
inflammatory regimen after cataract surgery.
Financial Disclosure: No author has a financial or proprietary interest in any material or method
mentioned.
J Cataract Refract Surg 2014; 40:1498–1505 Q 2014 ASCRS and ESCRS

Cystoid macular edema (CME) is not an uncommon CME.4,5 Notwithstanding, optical coherence tomogra-
complication after cataract surgery.1 It may cause phy (OCT) has shown that a benign and mild increase
significant temporary visual impairment that in the in macular thickness without an impact on visual acuity
worst scenario may not resolve despite attempted occurs early on, even after uneventful surgery in low-
treatment. The reaction is explained by an accumula- risk patients, and this swelling may last for months.6,7
tion of extracellular intraretinal fluid in the outer plex- Until now, a gold-standard antiinflammatory treat-
iform and in the inner nuclear layers of the retina ment for patients having cataract surgery has not been
resulting from a breakdown of the blood–retinal established. Although both topical steroids and
barrier in response to a postoperative inflammation NSAIDs are indicated for postoperative inflammation,
in the anterior chamber.2,3 there is no licensed product for the prevention of CME
Advances in cataract surgery techniques and the use after cataract surgery except nepafenac, which has
of a new generation of nonsteroidal antiinflammatory this labeling for patients with diabetic retinopathy.8
drugs (NSAIDs) may have diminished the rate of Nepafenac ophthalmic suspension 0.1% is a topical

1498 Q 2014 ASCRS and ESCRS 0886-3350/$ - see front matter


Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jcrs.2013.12.023
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NEPAFENAC AS ADD-ON TO STEROIDS AFTER UNEVENTFUL PHACOEMULSIFICATION 1499

nonsteroidal antiinflammatory prodrug that has been Products Agency, Uppsala, Sweden. The trial was registered
approved for the inhibition of pain and inflammation at the European Clinical Trials Database according to the
standards set by the World Health Organization.A All pa-
precipitated by cataract surgery.9–11
tients signed a document with written informed consent.
Nepafenac has a unique prodrug structure Patients with small pupils (!5.0 mm after pharmacologic
compared with other topical NSAID eyedrops, allow- dilation), dark brown irides, exfoliation syndrome, history of
ing a rapid penetration through the cornea to ulti- uveitis, glaucoma, macular degeneration, or any vision-
mately reach the posterior segment of the eye and, impairing eye disorder except cataract were not eligible.
Diabetic patients, pregnant women, and patients using any
particularly, the macula.12–14 Nepafenac converts in
topical or systemic antiinflammatory treatment or with hy-
the aqueous humor to amfenac, a potent NSAID.12 In persensitivity to any of the given study treatments were
line with what has been found for other topical also excluded. The cataract had to be translucent enough to
NSAIDs, nepafenac appears to have an effect on allow good-quality OCT scans of the macular area at base-
diabetic and pseudophakic macular edema, as shown line. Eyes with intraoperative difficulties such as loose zonu-
lar fibers, extended operating time, or residual cortical
in observational and mostly uncontrolled studies.15–18
material or with complications such as posterior capsule
It can be anticipated that if given prophylactically, ne- rupture and vitreous loss were excluded from the study after
pafenac would reduce the incidence of CME after un- randomization. In addition to the cataract surgery, the study
eventful cataract surgery. involved 5 visits; 1 recruitment visit, 1 preoperative exami-
The objective of this study was to evaluate whether nation within 1 week of surgery, and postoperative examina-
tions at 1 day, 3 weeks, and 6 weeks.
adding nepafenac 0.1% ophthalmic suspension to a The patients were randomized in a 1:1 fashion to 1 of 2
standard topical steroid treatment of dexamethasone treatment groups. The study group received a combination
0.1% would confer a benefit in controlling subclinical therapy of nepafenac ophthalmic suspension 0.1% and dexa-
macular swelling and other inflammatory manifesta- methasone 0.1%. The control group received dexamethasone
tions after uneventful cataract surgery in a low-risk 0.1% (Isopto-Maxidex) and a placebo (Tears Naturale II
Polyquad). All products used in this clinical trial were
cohort of patients. produced, labeled, packaged, and released by S.A. Alcon-
Couvreur N.V. Puurs, Belgium. Nepafenac and placebo
PATIENTS AND METHODS suspensions were supplied in identical bottles labeled with
a protocol and a patient number so neither the investigators
This prospective randomized double-masked controlled nor the patients were able to identify their contents.
2-center study recruited 160 patients between 45 and 85 The eyedrops were given 3 times a day for 3 weeks after
years of age who were scheduled for cataract surgery under surgery except the nepafenac and the placebo, which were
local anesthesia at the Ophthalmology Department, M€olndal started 2 days before surgery and were given 30 minutes
Hospital, Gothenburg, and at St Erik Eye Hospital, Stock- right before surgery 3 times 5 minutes apart. If CME ap-
holm. This study was approved by the Ethical Committee, peared at any time during the treatment period or beyond
Sahlgrenska University, Gothenburg, and the Medical the 3-week visit, topical treatment was given at the discretion
of the surgeon.
Primary outcome measures were the change in total mac-
ular volume 6 weeks after cataract surgery compared with
Submitted: September 28, 2013. baseline and the proportion of patients with macular
Final revision submitted: December 14, 2013. swelling of at least 10 mm 6 weeks after surgery compared
Accepted: December 19, 2013. with baseline.
Secondary outcome measures were the change in total
From Sahlgrenska University Hospital (Zaczek, Stenevi), M€
olndal, macular volume 3 weeks postoperatively compared with
and St. Erik Eye Hospital (Artzen, Laurell, Montan), Stockholm, baseline; the proportion of patients with macular swelling
Sweden. of at least 10 mm 3 weeks postoperatively compared with
baseline; visual acuity at 3 weeks and 6 weeks; anterior
Supported by Alcon Research Ltd, Fort Worth, Texas, USA, and S.A. segment inflammation measured with a laser flare meter at
Alcon-Couvreur N.V., Puurs, Belgium, which produced and provided 1 day, 3 weeks, and 6 weeks; ocular pain sensation during
the masked eyedrop bottles. Partially supported by Alcon, Inc., Swe- surgery and 24 hours and 3 weeks postoperatively; ocular
den. Financial support was also provided through the regional agree- discomfort and photophobia 1 day postoperatively and
ment on Medical training and Clinical research (ALF) between during the 3-week treatment course; and intraoperative
Stockholm County Council and Karolinska Institutet (20120623). pupil dilation measured with a caliper.
Adverse events were intraocular pressure (IOP) changes
The statistical analyses were supported by G. Andersson versus baseline measured at 1 day, 3 weeks, and 6 weeks
Foundation. and ocular or systemic symptoms and signs with a relation-
ship to the study regimens during the 3 weeks after surgery.
Presented in part at the XXXI Congress of the European Society of One hour before surgery, pupils were dilated 3 times by
Cataract and Refractive Surgeons, Amsterdam, the Netherlands, topical instillation of a mixture of cyclopentolate hydrochlo-
October 2013. ride 0.75% with phenylephrine hydrochloride 2.5% (APL).
Tetracaine 1.0% drops (Meda Sverige AB) were used for local
Corresponding author: Anna Zaczek, MD, PhD, Scanloc Healthcare anesthesia. After a paracentesis was created, 0.15 mL of a
AB, Lilla Bommen 6, 411 04 Gothenburg, Sweden. E-mail: anna. mixture of phenylephrine 1.5%, cyclopentolate 0.1%, and
zaczek@scanloc.se. lidocaine hydrochloride 1.0% was injected into the anterior

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1500 NEPAFENAC AS ADD-ON TO STEROIDS AFTER UNEVENTFUL PHACOEMULSIFICATION

chamber for a mydriatic and a local anesthetic effect.19 study regimen would achieve a similar benefit. It was calcu-
Adrenaline 0.3 mL (1 mg/mL) was added to 500 mL of a lated that at least 60 patients would be needed in each group
buffered salt irrigation solution (BSS, Alcon). Four surgeons to detect a statistically significant difference with an 80% po-
performed the operations using a standard phaco stop-and- wer. Presuming a dropout rate of approximately 15%, it
chop or divide-and-conquer nuclear fracturing technique. was decided to recruit 80 patients into each arm. Primary
The Infiniti phacoemulsification machine with a torsional ul- statistical analyses were performed in the intent-to-treat
trasound delivery system (Alcon) was used in all cases. The population. This population was defined as all screened, ran-
energy of the phacoemulsification and the duration of the domized, operated, and treated patients who completed at
entire surgical procedure were recorded. A foldable intraoc- least the 3-week visit. Protocol deviations later in the course
ular lens (Acrysof SN60AT, Alcon Laboratories, Inc.) was im- of the study were treated with the last observation carried
planted in the capsular bag. At the end of the operation, all forward principle. Continuous variables were analyzed
patients received an injection of off-label moxifloxacin with independent as well as paired nonparametric tests, cat-
0.2 mg (Vigamox) in the anterior chamber to prevent postop- egorical variables were analyzed with the Fisher exact test,
erative endophthalmitis. and correlations were determined with the Spearman test
The surgeons performed the slitlamp examinations at the by an independent biostatistician using the SAS software
recruitment visit and 3 weeks postoperatively. In addition, (version 9.2, SAS Institute, Inc.). A P value less than 0.05
they performed an intraoperative evaluation of the hardness was considered significant.
of the cataract and estimated the pupil diameter horizontally
with a caliper before entering the anterior chamber and at the
end of the surgical procedure. These measurements were RESULTS
made to the nearest half millimeter and were performed
with the anterior chamber filled with a balanced salt Of the 160 patients recruited, 152 (75 patients on nepafe-
solution. nac and 77 on placebo) were included in the intent-to-
All other measurements in this study were performed by treat subset. Reasons for study withdrawal in the
the research nurse at baseline, 1 day, 3 weeks, and 6 weeks.
Examinations were scheduled in the morning from 8 AM to
actively treated group were as follows: cortical remnants
12 AM. Uncorrected distance visual acuity and corrected dis- in the anterior chamber on the postoperative day (n Z 1),
tance visual acuity (CDVA) were assessed with the Early loose zonular fibers intraoperatively requiring a place-
Treatment Diabetic Retinopathy Study eye meter chart un- ment of a capsule tension ring (n Z 1), improper dosing
der standardized conditions. Values were converted to log- of study medication (n Z 1), use of non-allowed concom-
MAR notation. The IOP was measured with a Goldmann
applanation tonometer.
itant medicine (n Z 1), and appearance of general health
Macular thickness was assessed with the Stratus OCT sys- problems judged to be unrelated to the study treatments
tem (software version 2.0, Carl Zeiss Meditec AG). Three se- (n Z 1). Three patients in the control group were
ries of 6 OCT scans were captured at baseline and 3 weeks excluded from the study for the following reasons: pa-
and 6 weeks postoperatively. The best-quality map from tient decision (n Z 2) and lost to follow-up (n Z 1).
each visit was selected for further analysis. Data for retinal
thickness, including total macular volume, the central
The mean age in the nepafenac group was higher
macula, and 4 inner and 4 outer quadrants of the retina, than that in the control group, although the difference
were obtained for statistical analysis. fell short of being statistically significant (PZ.0558).
The anterior chamber inflammatory response was evalu- For this reason, the impact of age was tested in a logis-
ated by aqueous protein detection with a laser flare–cell me- tic regression model analyzing 1 of the 2 main outcome
ter (FC-500, Kowa Co. Ltd.). Ten to 15 minutes before each
measurement, the pupils were dilated with topical applica-
measures. The age effect, however, was found to be
tion of a combination of cyclopentolate hydrochloride negligible (data not shown). Table 1 shows the patient
0.75% and phenylephrine hydrochloride 2.5%. Nine consec- characteristics. Table 2 shows surgical parameters and
utive measurements, expressed in photons/ms, were taken; the classification of cataract; there were no statistically
then, the mean of the 5 central values was calculated. significant differences in these parameters between the
Patients were asked to use a 5-point scale (0 Z none, 1 Z
barely noticeable, 2 Z mild, 3 Z moderate, and 4 Z severe)
2 groups.
to report the level of ocular pain during surgery, during the The nepafenac group had less macular swelling than
first 24 hours, and during the following 3 weeks after sur- the control group, and the differences were statistically
gery. Patients were also asked to record, in the same fashion, significant for primary and secondary outcome mea-
ocular discomfort and photophobia in the postoperative sures (Tables 3 and 4). No CME developed in the nepa-
period. Subjective symptom scores were categorized for sta-
tistical evaluation as absent (score Z 0) or present (score Z 1
fenac group; 2 cases were found in the placebo group
to 4) of the respective sensation. (PZ.5099). One of these patients developed clinically
Ocular adverse events were evaluated on a 3-point scale significant CME, and the other patient developed
(0 Z none, 1 Z mild-moderate, and 2 Z severe). General typical cystoid changes without vision symptoms on
adverse events with a potential relationship to the study the OCT examination 3 weeks after surgery. They
treatments were reported as present or absent.
With reference to prospective studies that showed that
were given a round of combined nepafenac and dexa-
combined topical steroids and ketorolac versus steroids methasone 3 times a day at the surgeon's discretion
alone had a dampening effect on macular swelling after after the study treatment phase and recovered
cataract surgery, 19,20 it was theorized that the present completely by the 6-week follow-up. Another patient

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NEPAFENAC AS ADD-ON TO STEROIDS AFTER UNEVENTFUL PHACOEMULSIFICATION 1501

Table 1. Patient characteristics. Table 2. Surgical parameters and classification of cataract.

Nepafenac Placebo Nepafenac Placebo


C Steroid C Steroid C Steroid C Steroid
Parameter (n Z 75) (n Z 77) P Value Parameter (n Z 75) (n Z 77) P Value

Age (y) Incision, n (%) .4719


Mean G SD 70.4 G 7.4 68.3 G 7.5 .0558 2.20 mm 60 (80.0) 66 (85.7)
Range 51.0, 84.0 51.0, 83.0 2.75 mm 15 (20.0) 11 (14.3)
Sex, n (%) 1.000 Hardness of cataract, .7336
Female 48 (64.0) 50 (64.9) n (%)
Male 27 (36.0) 27 (35.1) Light 8 (10.8) 13 (17.1)
Study eye Moderate 63 (85.1) 57 (75.0)
Right 50 (66.7) 49 (63.6) .8248 Severe 3 (4.1) 6 (7.9)
Left 25 (33.3) 28 (36.4) Surgical time (min)
Mean G SD 9.87 G 2.13 10.00 G 2.60 .9852
Range 6.0, 16.0 5.4, 21.1
CDE
in the control group received prolonged dexametha- Mean G SD 12.8 G 8.1 12.3 G 5.5 .9251
sone treatment because of pronounced irritation in Range 2.5, 57.3 4.9, 29.9
the eye at the 3-week examination.
CDE Z cumulative dissipated energy
The CDVA improved significantly in both groups,
from 0.23 to 0.012 logMAR (at 3 weeks) and to
0.06 logMAR (at 6 weeks) in the nepafenac group
and from 0.24 to 0.03 logMAR (at 3 weeks) and to fluorescein staining (20 [26.7%] versus 8 [10.4%])
0.05 logMAR (at 6 weeks) in the control group. Dif- (PZ.0119). Headache was reported by 3 patients
ferences between the 2 groups were not statistically (4.0%) in the nepafenac group and 2 patients (2.6%)
significant preoperatively (PZ.8869) or postopera- in the control group (PZ.9750). No other systemic or
tively (PZ.1464 and PZ.7314 at 3 weeks and 6 weeks, local untoward effects were recorded during 3 weeks
respectively). of treatment in either study group.
Aqueous flare increased significantly less in the ne-
pafenac group 1 day postoperatively (PZ.0285); there
was no statistically significant between-group differ- Table 3. Total macular volume measurements and changes in
ence at any other timepoint (Figure 1). No correlation volume 3 weeks and 6 weeks postoperatively compared with
baseline values.
was found between 1-day laser flare measurements
and total macular volume values 3 weeks and 6 weeks Nepafenac Placebo
after surgery (PZ.1168 and PZ.3337, respectively). C Steroid C Steroid
The median pupil size preoperatively was 7.00 mm Parameter (n Z 75) (n Z 77) P Value
(range 5.50 to 9.00 mm) in the nepafenac group and
TMV (mm3)
7.00 mm (range 5.50 to 11.0 mm) in the placebo group Preop
(PZ.2260). The median pupil size at the end of surgery Mean G SD 6.81 G 0.49 6.81 G 0.43 .8422
was 7.50 mm (range 6.00 to 9.00 mm) and 8.00 mm Range 5.18, 8.12 5.83, 8.02
(range 5.00 to 11.0 mm), respectively (PZ.2571). 3 wk postop
Statistically significantly more patients in the nepa- Mean G SD 6.92 G 0.44 7.16 G 0.51 .0032*
fenac group than in the control group reported being Range 5.51, 7.92 5.99, 8.41
pain free during the day after surgery (P!.0001); there 6 wk postop
was no significant difference between groups during Mean G SD 6.98 G 0.49 7.14 G 0.48 .0900
surgery (PZ.1931) (Figure 2). Range 5.51, 8.18 5.98, 8.41
Change in TMV (mm3)
A higher percentage of patients in the nepafenac
3 wk preop
group than in the control group reported having no
Mean G SD 0.122 G 0.205 0.349 G 0.267 .0001*
ocular discomfort or photophobia 1 day and 3 weeks Range 0.500, 0.620 0.200, 1.110
postoperatively (P!.0001 and PZ.0058, respectively) 6 wk preop
(Figures 3 and 4). Mean G SD 0.179 G 0.222 0.329 G 0.276 .0002*
Mild to moderate punctuate epithelial defects of the Range 0.430, 1.080 0.480, 1.080
cornea were found in both groups 3 weeks after treat-
TMV Z total macular volume
ment. Statistically significantly more patients in the ne- *Statistically significant difference (P!.05, Mann-Whitney U test)
pafenac group than in the control group had corneal

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1502 NEPAFENAC AS ADD-ON TO STEROIDS AFTER UNEVENTFUL PHACOEMULSIFICATION

Table 4. Numbers and percentage of patients with macular swelling of more than 10 mm 3 weeks and 6 weeks postoperatively.

3 Weeks Postoperative 6 Weeks Postoperative

Number (%) Number (%)

Area Nepafenac C Steroid Placebo C Steroid P Value Nepafenac C Steroid Placebo C Steroid P Value

A1 15 (20.0) 41 (53.2) !.0001* 30 (40.0) 46 (59.7) .0228*


A2 25 (33.3) 48 (62.3) .0006* 30 (40.0) 49 (63.6) .0057*
A3 19 (25.3) 47 (61.0) !.0001* 24 (32.0) 43 (55.8) .0050*
A4 27 (36.0) 49 (63.6) .0011* 26 (34.7) 45 (58.4) .0053*
A5 22 (29.3) 55 (71.4) !.0001* 30 (40.0) 48 (62.3) .0093*
A6 18 (24.0) 37 (48.1) .0033* 15 (20.0) 31 (40.3) .0010*
A7 12 (16.0) 34 (44.2) .0003* 15 (20.0) 33 (42.9) .0040*
A8 15 (20.0) 41 (53.2) !.0001* 22 (29.3) 41 (53.2) .0045*
A9 24 (32.0) 45 (58.4) .0018* 26 (34.7) 44 (57.1) .0086*

A1 Z central macula; A2 Z inner superior; A3 Z inner temporal; A4 Z inner inferior; A5 Z inner nasal; A6 Z outer superior; A7 Z outer temporal; A8 Z outer
inferior; A9 Z outer nasal
*Statistically significant difference (P!.05, Fisher exact test)

Both groups had a statistically significant reduction determine the most efficient regimen for the preven-
in IOP from baseline to the 6-week postoperative visit tion of clinically manifest CME. With the advent of
(both P!.0001). The mean IOP decreased from posterior segment OCT, a subclinical increase in foveal
15.5 mm Hg G 3.0 (SD) to 13.8 G 2.6 mm Hg in the thickness can be easily detected. Such an increase can
nepafenac group and from 14.6 G 2.6 mm Hg to be regarded as a precursor to, and thus a surrogate
12.8 G 2.9 mm Hg in the control group. variable for, frank CME.
In the present study, 3 weeks of treatment with a
combination of topical nepafenac and dexamethasone
DISCUSSION was found to be better than dexamethasone alone in
Cystoid macular edema has an expected incidence of controlling macular swelling up to 6 weeks after un-
1% to 2% or less after present-day uneventful cataract eventful cataract surgery in low-risk patients. The
surgery when standard antiinflammatory regimens swelling was discrete and did not translate into a
are used.5,20 Thus, several hundreds of participants difference in CDVA between the groups at the
would have to be recruited to each treatment arm to 6-week examination. Nevertheless, 2 occurrences of

Figure 1. Anterior chamber flare values measured with a laser flare


meter preoperatively and 1 day and 3 and 6 weeks postoperatively.
At 1 day, there were 5 extreme values in the control group; that is,
1056 photons/ms, 160 photons/ms, 104 photons/ms, 96 photons/ Figure 2. Percentage of pain-free patients during the surgical proce-
ms, and 82 photons/ms (* Z P!.05, statistically significant differ- dure and 1 day after surgery (* Z P!.05, statistically significant dif-
ence, Mann-Whitney U test; IR Z interquartile range; Q Z quartile). ference, Fisher exact test).

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NEPAFENAC AS ADD-ON TO STEROIDS AFTER UNEVENTFUL PHACOEMULSIFICATION 1503

Figure 3. Percentage of ocular discomfort–free patients 1 day and 3 Figure 4. Percentage of photophobia-free patients 1 day and 3 weeks
weeks after surgery (* Z P!.05, statistically significant difference, after surgery (* Z P!.05, statistically significant difference, Fisher
Fisher exact test). exact test).

OCT-confirmed CME were documented in the control than with the control treatment in our study. Results
group. Our results are at odds with those in an un- in 2 controlled studies10,24 confirm these properties
masked prospective study of a low-risk cataract popu- of nepafenac; however, the studies evaluated nepafe-
lation21 in which OCT data of the macula did not differ nac as a single treatment versus a placebo.
between those receiving prednisolone alone and those Another quality of NSAID eyedrops is that they
treated with prednisolone and added nepafenac for 4 may reduce the miotic effect induced by surgery
weeks after surgery. However, our results do concur when they are administered with mydriatics before
with those in 2 other studies4,17 performed under the operation.16,17,22,23 However, in our study, pupil
different protocols, although both evaluated mainly size was not different between the nepafenac group
patients at low risk. In a retrospective open-label and the control group. We believe that the intracam-
study,4 4 weeks of nepafenac in combination with eral injection of dilating and anesthetic agents given
prednisolone eyedrops provided better protection right after the paracentesis is created, along with the
against clinically manifest pseudophakic CME than 4 adrenaline added in the rinsing solution, may have
weeks of prednisolone alone. In addition, a single- masked the dilating effect of nepafenac.8
masked prospective trial with a standard regimen of Punctuate corneal erosions were the only adverse
dexamethasone for 10 days and an add-on arm with events deemed to be treatment related in the present
nepafenac for 6 weeks found less swelling of the mac- study. They occurred in both groups, but significantly
ula with the latter regimen 2 and 6 weeks after un- more often with nepafenac use (27% versus 10%). All
eventful cataract surgery.17 erosions were mild to moderate in nature and did not
A recently published prospective double-masked translate into clinical symptoms because photophobia
study showing the superiority of nepafenac combined was significantly more pronounced in the control
with steroids over steroids alone in preventing group. Of previous studies of nepafenac, only 1 reported
macular edema in diabetic patients with nonprolifera- occasional punctuate keratitis8; it was a randomized
tive retinopathy having phacoemulsification8 lends clinical study that recruited patients with diabetic reti-
further support to our findings. Other prospective nopathy. There is also 1 case report of corneal melting
controlled studies19–23 with a design different than associated with nepafenac treatment.25 That case, how-
ours showed that NSAID eyedrops other than ever, had multiple risk factors that impaired the defense
nepafenac given in addition to topical steroids cur- mechanisms of the cornea. Still, the propensity of long-
tailed increases in fovea thickness or mitigated CME term topical NSAIDs to induce corneal erosions and
after phacoemulsification. even corneal melts calls for caution, and one should be
Anterior chamber flare 1 day after surgery and the mindful when prescribing nepafenac to patients who
subjective parameters of pain, ocular discomfort, and are at risk for developing corneal problems.26,27
photophobia during the first 3 postoperative weeks In summary, this study shows the beneficial effect of
were better controlled with the combined regimen adding nepafenac to a standard regimen of topical

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1504 NEPAFENAC AS ADD-ON TO STEROIDS AFTER UNEVENTFUL PHACOEMULSIFICATION

dexamethasone to inhibit inflammation, with special 8. Singh R, Alpern L, Jaffe GJ, Lehmann RP, Lim J, Reiser HJ,
reference to subclinical macular swelling, after cataract Sall K, Walters T, Sager D. Evaluation of nepafenac in
prevention of macular edema following cataract surgery in pa-
surgery in low-risk patients. Further studies should tients with diabetic retinopathy. Clin Ophthalmol 2012; 6:1259–
explore the potential for this regimen in high-risk situ- 1269. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/
ations, such as in patients with pseudoexfoliation, uve- PMC3422154/pdf/opth-6-1259.pdf. Accessed May 4, 2014
itis, or perioperative capsule and iris complications. As 9. Maxwell WA, Reiser HJ, Stewart RH, Cavanagh HD,
for low-risk situations, the present findings could be Walters TR, Sager DP, Meuse PA. the Nepafenac Study Group.
Nepafenac dosing frequency for ocular pain and inflammation
used in studies in which the protocol is reversed. associated with cataract surgery. J Ocul Pharmacol Ther
Given the evidence that nepafenac as a single treat- 2008; 24:593–599
ment protects against angiographically proven CME 10. Lane SS, Modi SS, Lehmann RP, Holland EJ. Nepafenac
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