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 VADAPALLIDepartment of Ophthalmology, Regional Eye Hospital,

Kurnool, Andhra Pradesh, India

INTRODUCTIONCYSTOID MACULAR EDEMA

• One of the most common preventable causes of vision loss after cataract surgery.

• Pathogenesis- surgical manipulations appears to be a major cause.

PATHOGENESISSurgical 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

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, 737s28.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.

STEPWISE APPROACH TO THE MANAGEMENT OF CMEMEDICAL 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 MANAGEMENT1.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

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

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.

• 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.

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;33:1974-197567.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.

• 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.

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.

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 : SANTHIR

AM GENERAL HOSPITALNANDYAL

PERIOD OF

STUDY2012-2015

INCLUSION CRITERIAPATIENTS WHO UNDERWENT CATARACT SURGERY WITHOUT ANY

SYSTEMIC DISEASE.

EXCLUSION CRITERIA : 1. Conditions that could increase risk of post cataract CME like

Hypertension.DiabetesIHDHistory of uveitis.Use of topical prostaglandin analogues for glaucoma.

2. Cases with other macular diseases accounting for macular thickness such as:

a. Retinal vascular diseasesb. Macular degenerations.

3.Opacities of media affecting vision – Corneal, lenticular, vitreous opacities (as the OCT images will be lesser quality.

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

OCT REPORTS OF CONTROL/TREATMENT GROUP

ANALYSIS

WITH NEPAFENAC WITHOUT NEPAFENAC0

50

100

150

200

250

DAY 1 POST OP4 WEEKS POST OP

COMPARISON OF IMPACT OF 0.1% NEPAFENAC ON MACULAR THICKNESS AFTER CATARACT SURGERY

MCU

LAR

THIC

KNES

S IN

MIC

RON

S

• 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.

RELATED STUDIESMiyake 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.

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.

TAKE HOME MESSAGE

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

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