Nepafenac 0.1% as prophylaxis can prevent cystoid macular edema in post operative patients

1. TO DETERMINE THE EFFECT OF NEPAFENAC
0.1% IN MACULAR THICKNESS IN PATIENTS
WHO HAD UNDERGONE CATARACT
SURGERY AS DETERMINED BY OCT
By Dr. RAMA VADAPALLI
Department of Ophthalmology, Regional Eye Hospital,
Kurnool, Andhra Pradesh, India

2. INTRODUCTION
CYSTOID MACULAR EDEMA
• One of the most common preventable
causes of vision loss after cataract surgery.
• Pathogenesis- surgical manipulations
appears to be a major cause.
PATHOGENESIS
Surgical Trauma – Triggers Arachidonic Acid Cascade,
which in turn generates prostaglandins by activation of
cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-
2).
Prostaglandins - The most important lipid derived
mediators of inflammation[18] and implicated in causing
macular capillary hyperpermeability.
As a result, transudate accumulates in the retina’s
outer plexiform and inner nuclear layers, and CME
develops.[93]
93.Yonekawa Y, Kim IK. Pseudophakic cystoid macular edema. Curr Opin Ophthalmol. 2012;23(1):26-32

3. INCIDENCE OF CME POST CATARACT SURGERY:
• Between 4% and 20% of healthy eyes develop CME after cataract
surgery,[94,95,96]
• Majority of cases – between 4 weeks and 12 weeks after Cataract
Surgery. [27][28].
• Most instances of CME (approximately 75%) resolve spontaneously
within 6 months.
• Clinically best – Slit Lamp and Contact Lens.
• Fluorescein angiography and OCT – much better than Clinical
Examination to show CME.
• However, fluorescein angiography yields only qualitative information.
• Quantitative data on retinal thickness can be derived with techniques
such as optical coherence tomography.[26]
27.Yanoff M., Fine B.S.: Ocular pathology: a text and atlas. 3rd ed. Philadelphia, JB Lippincott, 1989. xxi, 737s
28.Gass J.D., Norton E.W.: Cystoid macular edema and papilledema following cataract extraction. A fluorescein fundoscopic and angiographic
study. Arch Ophthalmol 1966; 76:646-661.94.

4. STEPWISE APPROACH TO THE MANAGEMENT OF CME
MEDICAL MANAGEMENT
1.Non steroidal Anti Inflammatory Drugs.
2.CORTICOSTEROIDS – inhibits prostaglandins.
3.CARBONIC ANHYDRASE INHIBITORS (CAIs) – alter the polarity of the ionic
transport systems in the RPE moving fluid away from the intracellular spaces [141].
4.LASER PHOTOCOAGULATION – One hypothesis-reform tight junctional retinal
barrier [142]. alternative hypothesis-a reduction of oxygen consumption in the
outer retina allowing diffusion of oxygen to the inner retina relieving hypoxia
causing constriction of retinal vasculature and a decrease in fluid
accumulation [143].
5.ANTI-VEGF AGENTS – act by decreasing vascular permeability from disrupted
endothelial cells.
SURGICAL MANAGEMENT
1.PARS PLANA VITRECTOMY.
141.Cox SN, Hay E, Bird AC. Treatment of chronic macular edema with acetazolamide. Arch Ophthalmol. 1988;106:1190-1195.
142.Androudi S, Letko E, Meniconi M, et al. Safety and efficacy of intravitreal triamcinolone acetonide for uveitic macular edema. Ocul Immunol Inflamm.
2005;13:205–212.
143.Molnar I, Poitry S, Tsacopoulos M, et al. Effect of laser photocoagulation on oxygenation of the retina in miniature pigs. Invest Ophthalmol Vis
Sci.1985;26:1410–1414

5. Non steroidal Anti Inflammatory Drugs which are
available commercially for topical ophthalmic use are
organic acids, with the exception of nepafenac, which
is a benzoylbenzeneacetamide, prodrug metabolized
in vivo to its corresponding acid.
NSAIDS
CHEMICAL STRUCTURE OF NEPAFENAC

6. MECHANISM OF ACTION OF NEPAFENAC
INHIBITION OF THE CYCLOOXYGENASE ENZYME IN
THE ARACHIDONIC ACID PATHWAY, LIMITING
PROSTAGLANDIN FORMATION. [17]
17.McColgin AZ, Heier JS. Control of intraocular inflammation associated with cataract surgery.
Curr Opin Ophthalmol. 2000;11:3-6.

7. • Unique prodrug structure.
• Making it a neutral molecule .
• Upon ocular dosing that rapidly
penetrates the cornea and is
deaminated to form the active
metabolite amfenac by
intraocular hydrolases in the
ocular tissues, including the
ciliary body epithelium, retina,
and choroid. [10].
• The prodrug mechanism of action
maximises bioactivation to
amfenac in the iris, ciliary body,
retina, choroid and cornea to a
lesser extent, making nepafenac
a target-specific NSAID.
NEPAFENAC 0.1% IS THE FIRST AND ONLY ONE TOPICAL
NONSTEROIDAL ANTI-INFLAMMATORY WITH
10. Gamache DA, Graff G, Brady MT, et al. Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced
ocular inflammation: I. Assessment of anti-inflammatory efficacy. Inflammation 2000;Aug 24(4):357-370.

8. ADVERSE EFFECTS
• Impaired corneal sensation.
• Persistent epithelial defects.
• Superficial punctate keratitis.
• Stromal infiltrates.
• Subepithelial infiltrates.
• Corneal complications, including corneal melts
have been reported to occur with nepafenac
[66,67]
66.Wolf EJ, Kleiman LZ. Schrier A. Nepafenac-Associated Corneal Melt. J Cataract Refract Surg
2007;33:1974-1975
67.Di Pascuale MA, Whitson JT, Mootha VV. Corneal Melting After Use of Nepafenac in a Patient
With Chronic Cystoid Macular Edema After Cataract Surgery. Eye Contact Lens 2008;34:129-30.

9. • Cataract surgeons have therefore been
interested in decreasing dependence on
steroid use alone, seeking alternative or
complementary treatments for
postoperative inflammation that are equally
effective but have fewer complications than
steroid therapy (O’Brien 2005).
Topical steroid therapy effectively treats
inflammation, but can increase intraocular
pressure, inhibit wound healing, increase
the likelihood of infection, or worsen an
existing one (Heier et al 2000; Simone and
Whitacre et al 2001).
Deciding which Nonsteroidal anti-inflammatory agent to use as
standard in patients undergoing cataract surgery is important to
ensure a favourable outcome.

10. TAKEN TOGETHER
THIS PRECLINICAL EVIDENCE
SUGGESTS THAT NEPAFENAC
WOULD COMPARE FAVORABLY TO
CONVENTIONAL NSAIDS IN THE
PREVENTION AND TREATMENT OF
OCULAR INFLAMMATION
ASSOCIATED WITH CATARACT
SURGERY.

11. AIM OF STUDY
TO STUDY - ROLE OF NEPAFENAC 0.1% USAGE IN ALTERING
THE STATUS OF CME AS DETERMINED BY OCT WHO
UNDERWENT CATARACT SURGERY.
PLACE OF STUDY :
SANTHIRAM
GENERAL HOSPITAL
NANDYAL
PERIOD OF STUDY
2012-2015

12. INCLUSION CRITERIA
PATIENTS WHO UNDERWENT CATARACT SURGERY WITHOUT ANY
SYSTEMIC DISEASE.
EXCLUSION CRITERIA :
1. Conditions that could increase risk of post cataract CME like
Hypertension.
Diabetes
IHD
History of uveitis.
Use of topical prostaglandin analogues for glaucoma.
2. Cases with other macular diseases accounting for macular
thickness such as:
a. Retinal vascular diseases
b. Macular degenerations.
3.Opacities of media affecting vision – Corneal, lenticular, vitreous
opacities (as the OCT images will be lesser quality.

13. MATERIALS
AND
METHODS
SUBJECTS RANDOMISED IN TO
50 control group
(standard of care
only).
50 treatment group
(Standard of care plus
nepafenac).
Immediate post operatively, OCT scans carried out
on 1st post operative day and at 4 weeks, using the
macular thickness protocol with the stratus OCT
version 5.0.1

14. OCT REPORTS OF CONTROL/TREATMENT GROUP

15. ANALYSIS
0
50
100
150
200
250
WITH NEPAFENAC WITHOUT NEPAFENAC
DAY 1 POST OP
4 WEEKS POST OP
COMPARISON OF IMPACT OF 0.1% NEPAFENAC ON
MACULAR THICKNESS AFTER CATARACT SURGERY
MCULARTHICKNESSINMICRONS

16. • The mean macular thickness:
• On 1st post operative day is 196 µm and at 4weeks it is 183 µm
in the treatment group with nepafenac.
• Whereas it was 184 µm on 1st post operative day and 198 µm
at 4 weeks in the control group.
• That means there is increased macular thickness at 4weeks in
the control group which was statistically significant.
• Enumerating the number of patients who evidenced with
cystoid macular edema, at 4 weeks, it was nill in case of
treatment group.(standard care plus nepafenac)
• In our study, results demonstrated that topical 0.1% therapy
has promising results for prevention of pseudophakic cystoid
macular edema.

17. RELATED STUDIES
Miyake et al study Compared the postoperative use of
nepafenac 0.1% with fluorometholone
0.1% for 5 weeks
The study group that received nepafenac had
thinner foveal thickness at the end of the trial,
Hariprasad SM et al, [32]
Multicenter retrospective.
Review of 22 CME cases (20 patients)
treated with nepafenac 0.1% (six with
concomitant prednisolone acetate 1%)
conducted from December 2005 to April
2008
Following treatment for six weeks to six months, six
eyes with uveitic CME showed a mean retinal
thickness improvement of 227 +/- 168.1 µm; mean
best-corrected visual acuity (BCVA) improvement
was 0.36 +/- 0.20 logMAR. All three cases of acute
pseudophakic CME improved after four to 10
weeks of nepafenac, with a mean improvement in
retinal thickness of 134 +/- 111.0 µm. BCVA
improved in two patients (0.16 and 0.22 logMAR)
but not in the third due to underlying retinal
pigment epithelium changes. Thirteen eyes with
chronic/recalcitrant pseudophakic CME
demonstrated a mean improvement in retinal
thickness of 178 +/- 128.7µm after nepafenac and
mean BCVA improvement of 0.33 +/- 0.19 logMAR.
They concluded that the positive outcomes of
these 22 eyes strongly suggest that nepafenac
0.1% is a promising drug
Dr.Rama V An interventional follow up study to
determine the effect of nepafenac 0.1% in
macular thickness in patients who had
undergone cataract
Surgery as determined by oct. 50 control
and 50 treatment group.
Nepafenac is effective in preventing post operative
cystoid macular oedema.

18. CONCLUSION
 In present study, the results demonstrated that with usage of postoperative topical
nepafenac 0.1% there were differences between the treatment group and control group
regarding the OCT measured macular thickness.
 Macular thickness, as assessed by OCT in patients without Pseudophakic CME, peaks at
approximately 4 to 6 weeks postoperatively. Thus, it is not likely that many cases of
Pseudophakic CME were missed in our studies.
 Our study has relied on OCT for estimating changes in macular thickness.
 Currently, in the literature OCT was found to be in good agreement with the clinical gold
standard (slit lamp examination through a dilated pupil with a Non contact lens) for
detecting the presence or absence of macular edema and was found to be potentially
more sensitive in cases of mild foveal thickening.
 After analysing the data and applying appropriate statistical analysis it can be concluded
that 0.1% Nepafenac can be used as a treatment option for primary CME in post
cataract patients.
 Topical therapy of 0.1% Nepafenac related side effects like Keratitis, corneal melt &
corneal perforation were not encountered in any patient in our study.
 The drawbacks of the study were not considering BCVA, short follow up periods.
 Macular thickness, as assessed by OCT in patients without Pseudophakic CME, peaks at
approximately 4 to 6 weeks postoperatively.
 Thus, it is not likely that many cases of Pseudophakic CME were missed in our studies.

19. TAKE HOME MESSAGE
IN OUR STUDY, RESULTS
DEMONSTRATED THAT
TOPICAL NEPAFENAC
0.1% THERAPY HAS
PROMISING RESULTS FOR
PREVENTION OF
PSEUDOPHAKIC CYSTOID
MACULAR EDEMA.