Treatment of Macular Edema

8/9/2019 Treatment of Macular Edema

1/48

TREATMENT OF MACULAR EDEMA

A JOURNAL REVIEW ON


2/48


3/48


4/48


5/48

Why is MACULA so prone for

edema?

The structure of the thick fibre layer of Henlewhich canabsorblarge quantities of fluid;

theavascularity of the centralarea for the

absence of capillaries whichlimit absorption;

thehigher susceptibility of themacula to both

hypoxic and oxidative stress due to thinness of

fovea.


6/48

What is macular edema?

A common cause ofvisualdiminision inawidevariety of ocular conditions.

It is anon specific pathologic response to the

disruption to thenormalpermeabilitybarrierthat protects the retina.

Macular edemais definedas retinal thickeningfromaccumulation of fluidwithin 1 Discdiameter of themacula.

It maybe focal,diffuse or cystic andischaracterizedbyextracellular accumulation offluid, specificallyin Henles layer and theinnernuclear layer of retina.


7/48

CAUSES OF MACULAR EDEMA

Retinalvascular disease:diabetic retinopathy, retinalvein occlusion,hypertensive retinopathy

Inflammatorydisorders:intraocular surgery, uveitic syndromes,laserprocedures

Choroidal vascular disease: choroidal neovascularization

Tractional maculopathies:epiretinal membrane,vitreomacular tractionsyndromes

Drug reactions:epinephrine,prostaglandinanalogs,nicotinic acid,timolol, tamoxifen, glitazones

Inherited retinaldystrophies: retinitis pigmentosa

Retinaldetachment:exudative, rhegmatogenous

Intraocular tumors: choroidal melanoma

Optic nerveheadabnormalities:diabetic/ hypertensivepapillopathy,neuroretinitis, optic nervepits/colobomas

Trauma (blunt/penetrating injuries)

Idiopathic


8/48

Molecular and cellular alterations leading to

macular edema

Thebreakdown of theblood-retinalbarrier seems to bethemost important mechanisminexplaining theextravasation of fluidalthough similar changes to the

retinalblood flowmayplaya role. In general,anincreaseinpassivepermeability through

theendothelium can occur via three generalmechanisms:

1. dysfunction of theintercellularjunctions2. increased transcellular transport

3. increasedendothelial celldestruction


9/48

DIAGNOSIS

Direct Ophthalmoscopy

Indirect Ophthalmoscopy

Biomicroscopic slit-lampexamination


10/48

Fluorescein angiography

Hiedelberg Retina Angiograph 2


11/48

Vitreous fluorometry

Optical coherence tomography (OCT) &

Retinal thickness analysis (RTA)

Echography

OCT showing sponge like

diabetic macular edema

OCT showing cystoiddiabetic macular edema


12/48

Folia Med (Plovdiv). 2010 Jan-Mar;52(1):40-8.

Optical coherence tomography for the detection of early

macular edema in diabetic patients with retinopathy.

Koleva-Georgieva DN, Sivkova NP.

AIM:To compare the retinal thickness measurements with spectral-domain optical coherencetomography (OCT) inhealthy subjects with those of type 2 diabetes patients with or withoutdiabetic retinopathy (DR) andwithno clinicalevidence ofdiabetic macular edema (DME).

PATIENTS AND METHODS:Thepresent prospective studyincluded 29 diabetic patients (57 eyes)withno DR (group 1), 32 diabetic patients (63 eyes) with DR (group 2) and 25 healthyvolunteers(39 eyes, control group). Eyes showing macular edema on slit-lampbiomicroscopy or leakage onfluorescein angiographywerenot includedin the study. Themean retinal thickness at the centralfixationpoint (CFP) and the 9 ETDRSmacular regions were comparedin subgroups ofhealthy

volunteers byage, sex and right or left eye. Thesemean retinal thickness values werealsocomparedin the control group, group 1 and group 2.Early DME was diagnosedwith OCTifitexceeded themean thickness +2.SD (standarddeviation) inhealthy subjects.

RESULTS: Mean retinal thickness at the CFP and foveainhealthyeyes was 176 +/- 16.8 micromand 198.3 +/- 21.4 microm, respectively. It was significantly greater inmen thaninwomen (p or =250 microm). At the 16-week visit and continuing every 8weeks,eyes wereassessed for retreatment andadditionallaser treatment was deferredif thevisualacuityletter scoreimproved > or =5 letters or optical coherence tomography CSTdecreased> or =10% comparedwith thevisit 16 weeks prior.

RESULTS: Of the 115 eyes that completed the 16-week visit, 54 (47%) hadadecreasein CSTby >or =10% comparedwithbaseline. Of these, 26 (48%) hada CST > or =250 microm at 16 weeks andwereevaluableat 32 weeks. Eleven (42%; 95% confidenceinterval, 23-63%) of the 26 eyes hada

further decreasein CST > or =10% from 16 weeks to 32 weeks without further treatment.

CONCLUSION:Sixteenweeks after focal/gridlaser for diabeticmacular edemaineyes withadefinite reduction,but notresolution, of centraledema, 23% to 63% likelywill continue to

improvewithout additional treatment.


20/48

Am J Ophthalmol. 2010 Jan;149(1):133-9. Epub 2009 Oct 28.

Subthreshold micropulse diode laser photocoagulation for diabetic macular

edema in Japanese patients.

Ohkoshi K,YamaguchiT.

PURPOSE:To assess theefficacyand safety of subthreshold micropulse diodelaserphotocoagulation for diabetic macular edema (ME).

DESIGN: Prospective,nonrandomizedinterventional case series.

METHODS:SETTING: Institutional. PATIENTS:Thirty-six consecutivediabetic patients (43 eyes)with clinically significant ME anda centralmacular thickness (CMT)


21/48

3. Vitrectomy

Indications ofvitrectomy in DME includes

1. Diffusemacular edemawith taut posterior hyaloid

membrane (TPHM)

2. Recalcitrant diffusemacular edemawithout TPHM

A 60-year-olddiabetic with 20/400 visionwith PRP and gridlaser scars in theleft eye(A),OCT shows

taut posterior hyaloid withincreased retinal thickness (B). Patient underwent Pars plana Vitrectomy

(PPV) withTPHM removal. Four weeks after surgery OCT shows normal foveal contour (C).


22/48

Ophthalmology. 2010 Mar 16. [Epub ahead of print]

Vitrectomy Outcomes in Eyes with Diabetic Macular Edema and Vitreomacular

Traction.

Diabetic Retinopathy Clinical Research Network() Writing Committee onbehalf of the DRCR.net.

PURPOSE:To evaluatevitrectomy for diabetic macular edema (DME) ineyes withat least moderatevisionloss andvitreomacular traction.

DESIGN: Prospective cohort study. PARTICIPANTS:Theprimary cohort included 87 eyes with DME andvitreomacular tractionbased oninvestigator's evaluation,visualacuity 20/63-20/400, optical coherencetomography (OCT) central subfield >300 microns andno concomitant cataract extractionat the time ofvitrectomy. METHODS:Surgerywas performedaccording to theinvestigator's usual routine. Follow-upvisits wereperformedafter 3 months, 6 months (primaryendpoint),and 1 year.

MAIN OUTCOME MEASURES: Visualacuity, OCT retinal thickening,and operative complications.

RESULTS: At baseline,medianvisualacuityin the 87 eyes was 20/100 andmedian OCT thickness was491 microns. During vitrectomy,additionalprocedures includedepiretinal membranepeeling in 61%,internallimiting membranepeeling in 54%,panretinal photocoagulationin 40%,andinjection ofcorticosteroids at the close of theprocedurein 64%. At 6 months,median OCT central subfieldthickness decreasedby 160 microns,with 43% having central subfield thickness /=10 letters in 38% (95%confidenceinterval, 28%-49%) anddeterioratedby >/=10 letters in 22% (95% confidenceinterval, 13%-31%). Postoperative complications through 6 months includedvitreous hemorrhage (5 eyes),elevatedintraocular pressure requiring treatment (7 eyes), retinaldetachment (3 eyes),andendophthalmitis (1eye). Few changes in results werenotedbetween 6 months and 1 year.

CONCLUSIONS:After vitrectomy performed for DME andvitreomacular traction, retinalthickening was reducedinmost eyes. Between 28% and 49% ofeyes withcharacteristics similar to thoseincludedin this studyarelikely to haveimprovement ofvisualacuity,whereas between 13% and 31% arelikely to haveworsening. Theoperative complication rateis lowand similar to what has been reported for thisprocedure. Thesedataprovideestimates of surgical outcomes and serveas a referencefor future studies that might consider vitrectomy for DME ineyes withat least

moderatevisionloss andvitreomacular traction.


23/48

4. STEROIDS IVTA (Triamcinolone acetonide )


24/48

Ophthalmology. 2009 May;116(5):902-11; quiz 912-3.

Intravitreal triamcinolone acetonide injection for treatment of

refractory diabetic macular edema: a systematic review.

YilmazT,Weaver CD,Gallagher MJ,Cordero-Coma M,Cervantes-Castaneda RA,Lavaque AJ,Larson RJ.

OBJECTIVE:To compareintravitreal triamcinolone acetonide (IVTA) injectionversus notreatment or sub-Tenon triamcinolone acetonide (STTA) injectioninimproving visualacuity (VA)ofpatients with refractorydiabetic macular edema (DME; unresponsive to focallaser therapy).

CLINICAL RELEVANCE: Diabetic macular edemais theleading cause ofvisualloss indiabeticretinopathy. Laser therapyhas been the standard of care for patients withpersistent orprogressivedisease. More recently,it has been suggested that IVTA injectionmayimprove VA.

METHODS AND LITERATURE REVIEWED:The following databases were searched: Medline

(1950-September Week 2 2008),The Cochrane Library (Issue 3, 2008),and theTRIP Database (upto September 1, 2008), using no language or other limits. Randomized controlled trials wereincluded that consisted ofpatients with refractory DME, those comparing IVTA injectionwithnotreatment or STTA injection, those reporting VA outcomes,and thosehaving aminimum follow-up of 3 months.

RESULTS: In the 4 randomized clinical trials comparing IVTA injectionwithplacebo or notreatment, IVTA injectiondemonstrated greater improvement in VA at 3 months,but thebenefitwas no longer significant at 6 months. Thosewho received IVTA injectionhad significantlyhigher

IOP at 3 months andat 6 months. In the 2 randomized clinical trials comparing IVTA injectionwithSTTA injection, IVTA injectiondemonstrated greater improvement in VA at 3 months,but not at 6months. Intravitreal triamcinolone acetonide injectiondemonstratedno differencein IOP at 3months or at 6 months.

CONCLUSIONS:Intravitreal triamcinolone acetonide injectionis effectiveinimproving VA inpatients with refractory DME in the short-term,but thebenefits do not seem to persist in thelong-term.


25/48

Ophthalmologica. 2010 Feb 17;224(4):258-264. [Epub ahead of print]

Comparison of Intravitreal Bevacizumab versus Triamcinolone for the

Treatment of Diffuse Diabetic Macular Edema.

Kreutzer TC, AlSaeidi R, Kook D, Wolf A, Ulbig MW, Neubauer AS, Haritoglou C.

Background: Our purposewas to compare theeffect of triamcinolone andbevacizumab (Avastin) on theretinal thickness and functional outcomeinpatients withdiabetic macular edema.

Methods and Materials: A collective of 32 patients,who hadbeen treatedbya single 4.0-mg intravitrealtriamcinolone injection (group 1),was matched to 32 patients ('matchedpairs'),who had received 3injections of 1.25 mg ofbevacizumab within 3 months in 4-week intervals (group 2). The outcomevariables were changes inbest correctedvisualacuity (VA) and central retinal thickness 3 months aftertherapy.

Results:Both groups didnot differ regarding preoperative VA and central retinal thickness measuredbyoptical coherence tomography. Thebaselinemean VA was 0.72 +/- 0.39 logMAR in group 1 and 0.73 +/-0.39 logMAR in group 2 (p= 0.709).Themean central retinal thickness measuredby optical coherencetomographywas 548 +/- 185 mumin group 1 and 507 +/- 192 mumin group 2. While thepatients ingroup 1 experienceda slight increasein VA of onaverage 0.7 lines following a single triamcinoloneinjection to amean of 0.64 +/- 0.40 logMAR (p= 0.066) after 3 months, thepatients in group 2 showedalmost no effect on VA withanaverageincrease of 0.2 lines to amean VA of 0.72 +/- 0.30 logMAR (p=

0.948) following 3 intravitreal injections ofbevacizumab. Comparing theeffect on VA betweenbothgroups no statistically significant difference (p= 0.115) was noted. Concerning decreasein central retinalthickness both therapies werehighlyeffective (p < 0.001 each),again,without statistically significantdifferencebetween the groups (p < 0.128).

Conclusion:Our data suggest that a single triamcinolone injectionmaybeas effective

as a 3 times repeatedintravitreal administration ofbevacizumab for the treatment of

diabetic macular edema.F

urther prospective trials shouldbeperformed.


26/48

5.Anti-VEGF Therapies

Threedrugs are currentlyin use.

Bevacizumab (Avastin) was approvedby theFDA for intravenoususein cancer patients. This drug has been used off-labelas anintravitreal injection, first for AMD,and subsequently for avariety

of other ocular diseases including macular edema.Dose:1.25 mg, 2.5 mg / 0.05 ml

Ranibizumab (Lucentis) is FDA-approved for intravitreal injectioninpatients with AMD,andhas been used off-label for other oculardiseases including diabetic macular edema.

Dose: 0.3 mg, 0.5 mg Pegaptanib (Macugen) was FDA-approved for intravitreal injection

inpatients with AMD before theadvent of ranibizumab andbevacizumab.

Dose:0.3 mg, 1 mg,and 3mg


27/48

Ophthalmology. 2009 Aug;116(8):1488-97, 1497.e1. Epub 2009 Jul 9.

Primary intravitreal bevacizumab for diffuse diabetic macular edema: the

Pan-American Collaborative Retina Study Group at 24 months.

Arevalo JF, Sanchez JG, Wu L, Maia M, Alezzandrini AA, Brito M, Bonafonte S, LujanS, Diaz-LlopisM, Restrepo N, Rodrguez FJ, Udaondo-Mirete P; Pan-American Collaborative RetinaStudyGroup.

PURPOSE:To report the 24-monthanatomic and EarlyTreatment Diabetic RetinopathyStudy (ETDRS)best-correctedvisualacuity (BCVA) responseafter primaryintravitreal bevacizumab (Avastin;Genentech, Inc.,SanFrancisco, CA; 1.25 or 2.5 mg) inpatients withdiffusediabetic macular edema(DDME). Inaddition,a comparison of the 2 different doses ofintravitreal bevacizumab (IVB) usedispresented.

DESIGN: Retrospective,multicenter,interventional, comparative case series.

PARTICIPANTS:The clinical records of 115 consecutivepatients (139 eyes) with DDME at 11 centers from8 countries were reviewed. METHODS: Patients were treatedwithat least 1 intravitreal injection of 1.25

or 2.5 mg ofbevacizumab. Allpatients were followed up for 24 months. Patients underwent ETDRSBCVA testing, ophthalmoscopic examination, optical coherence tomography (OCT),and fluoresceinangiography (FA) at thebaseline, 1-, 3-, 6-, 12-,and 24-monthvisits.

MAIN OUTCOME MEASURES: Changes inBCVA and OCT results.

RESULTS:Themeanage of thepatients was 59.4+/-11.1 years. Themeannumber of IVBinjections pereyewas 5.8 (range, 1-15 injections). In the 1.25-mg groupat 1 month,BCVA improved from 20/150 (0.88logarithm of theminimumangle of resolution [logMAR] units) to 20/107, 0.76 logMAR units (P


28/48

6.Sustained-release

corticosteroid delivery devices Retisert (fluocinolone acetonide) is an

intraocular implant that delivers 0. 59 mg of

fluocinolone acetonide to theposterior segmentup to 3 years.

Posurdex (dexamethasone) is another sustained

deliveryintraocular implant that has been foundto improvevisualacuityineyes withpersistent

macular edemaat adose of 700 mcg comparedwith observation through 6 months.


29/48

Ophthalmology. 2010 Mar 2. [Epub ahead of print]

Sustained Ocular Delivery of Fluocinolone Acetonide by an

Intravitreal Insert.

Campochiaro PA, HafizG, ShahSM, BloomS, Brown DM, Busquets M, CiullaT, Feiner L, Sabates

N, Billman K, Kapik B, GreenK, KaneF; Famous StudyGroup(). PURPOSE:To compare Iluvien intravitreal inserts that release 0.2 or 0.5 mug/day of fluocinolone

acetonide (FA) inpatients withdiabetic macular edema (DME).

DESIGN: Prospective, randomized,interventional,multicenter clinical trial.

PARTICIPANTS:Weincluded 37 patients with DME.

METHODS:Subjects withpersistent DME despite >/=1 focal/gridlaser therapywere randomized 1:1 toreceiveanintravitreal insertion ofa 0.2- or a 0.5-mug/dayinsert.

MAIN OUTCOME MEASURES:Theprimaryendpoint was aqueous levels ofFA throughout the studywithanimportant secondary outcome of the change frombaselineinbest-correctedvisualacuity(BCVA) at month 12.

RESULTS:Themeanaqueous level ofFA peakedat 3.8 ng/mlat 1 week and 1 monthafter administrationofa 0.5-mug/dayinsert andwas 3.4 and 2.7 ng/ml 1 week and 1 monthafter administration ofa 0.2-mug/dayinsert. For bothinserts,FA levels decreased slowly thereafter andwereapproximately 1.5ng/ml for eachat month 12. Themean change frombaselineinBCVA was 7.5, 6.9,and 5.7 letters at

months 3, 6,and 12, respectively,after administration ofa 0.5 mug/day-insert andwas 5.1, 2.7,and 1.3letters at months 3, 6,and 12, respectively,after administration ofa 0.2-mug/dayinsert. Therewas amildincreaseinmeanintraocular pressureafter administration of 0.5-mug/dayinserts,but not afteradministration of 0.2-mug/dayinserts.

CONCLUSIONS:TheFA intravitreal inserts provideexcellent sustainedintraocularrelease ofFA for >/=1 year. Although thenumber ofpatients in this trialwas small, thedata suggest that theinserts provide reduction ofedemaandimprovement inBCVA in

patients with DME withmildeffects onintraocular pressure over the span of 1 year.


30/48

7.OTHER GROWTH FACTOR MODULATORS

Activatedprotein kinase C has beenassociatedwithincreasedlevels of VEGFandis also implicatedinincreased retinalvascular permeability.

PK

C412 is an oral kinase inhibitor that was found toreduce foveal thickening by 66. 7 mcm at doses of100-150 mg/d comparedwithplacebo witha smallbut significant improvement invisualacuityat 3months.

Ruboxistaurin,a selective oralprotein kinase C betainhibitor administeredat doses of 4, 16, or 32 mg/dover 18 months,was also found to reduce retinalvascular leakage comparedwithplacebo inpatientswith severediabetic macular edema.


31/48

8. Miscellaneous therapies

Other potential targets in the treatment ofmacular edemaincludepigment epithelium-derived factor andinterferonalpha-2a.

Pigment epithelium-derived factor mayinterferewith VEGF-inducedvascular permeabilityandhas been found to occur inlower concentrationsin thevitreous ofeyes with DME.

Supplemental oxygenhas also been found toreduceexcess foveolar thickness by 42% andimprovevisualacuitybyat least 2 lines ina smallstudy ofpatients with chronic ME.


32/48

Macular edema in Vascular occlusions

Macular gridlaser treatment has been themainstay of treatment of CME due to

BRVO since thepublication of theBranch Vein OcclusionStudy (BVOS) in 1984. TheBVOSdemonstrateda clear benefit of gridlaser treatment for eyes with

vision of 20/40 or less secondary to macular edema fromperfused BRVO.

Unfortunately, the Central Vein OcclusionStudy (CVOS) showedno benefit ofmacular gridlaser treatment on CME due to CRVO.

Additionally,not allBRVO eyes are good candidates for laser becauseit cannotbeappliedineyes withdenseintraretinal hemorrhage,andeyes with severe

macular ischemiamayactuallydo better without treatment.

Accordingly,investigators havelookedat other approaches to treat CME due toBRVO and CRVO,including

laser-induced chorioretinal anastamosis,

radial optic neurotomy,

arteriovenous sheathotomy,and

therapywithintravitreal steroids or

anti-vascular endothelial growth factor (VEGF) agents

Vitrectomy.

Theimagepart with relationship ID rId2wasnotfound in thefile.


33/48

Graefes Arch Clin Exp Ophthalmol. 2008 Dec;246(12):1671-6. Epub 2008 Aug 16.

Combined intravitreal triamcinolone injection and laser

photocoagulation in eyes with persistent macular edema after

branch retinal vein occlusion.

Riese J,Loukopoulos V,Meier C,Timmermann M,Gerding H.

BACKGROUND:To determine theefficacy of combinedintravitreal triamcinolone (TA) injectionandlaser

photocoagulationinpersistent macular edemaafter branch retinalvein occlusion (BRVO).

METHODS:Follow-upanalysis ofa case series of 24 patients withmacular edemaafter BRVO (15 of 24 non-

ischaemic, 9 of 24 ischaemic). Patients receivedanintravitreal injection of 4 mg TA followedbylaser

photocoagulationwithin thepreviouslyedematous area,appliedin one or two sessions. Standardized clinical

examinations includedbest correctedvisualacuity testing,anterior andposterior segment biomicroscopy,

intraocular pressure,and optical coherence tomography (OCT). Fluorescein angiographywas performedbefore

treatment and 3 and 6 months later.

RESULTS: Medianvisualacuityimproved significantly from 0.58 logMAR (95%-confidenceinterval (KI): 0.54-

0.75,decimal 0.27) at baseline to 0.41 logMAR (KI: 0.37-0.64,decimal 0.39) at 1 month (p= 0.001), 0.33 logMAR

(KI: 0.32-0.62,decimal 0.47) at 3 months (p= 0.002),and 0.41 logMAR (KI: 0.33-0.67,decimal 0.39) at 6 months

(p= 0.016). A gain of one or morelogarithmic lines was evaluatedin 16/24 eyes (67 %) anda gain of 3 lines or

morein 8/24 eyes (33 %) at 6 months. Threeeyes hadlost more than 1 lineduring the follow-upperiod. Median

change ofvisualacuityat 6 months was +2.0 lines (KI: 0.2-2.4). Median central foveal thickness (OCT-CFT) was

423 microm (KI: 378-456,n= 24) at baselineanddecreased to 270 microm (KI: 249-311,n= 24) at 1 month (p or = 2 lines was observedin 10 eyes (45%). Themeanpreoperative fovea thickness measuredby OCTwas 595.22 +/- 76.83microm (510-737 microm) andpostoperative fovea thickness was 217.60 +/-47.33 microm (164-285 microm).

CONCLUSIONS:Vitrectomywith AV sheathotomy canbeone treatment option for thepatients with recurrent

macular edemainBRVO.


39/48

Cystoid Macular Edema


40/48

Non-steroidal Anti-

inflammatory Drugs (NSAIDs)

CME develops,inpart,because ofaprostaglandin-inducedbreach of theblood-retinalbarrier and,subsequently, secondary retinaledema.

Topical NSAIDs inhibit theproduction ofprostaglandinsbyaffecting the cyclooxygenase enzyme.

NSAIDs also target other inflammatorymediators thatare responsible for edema formationandhavebeeninvestigatedin theprophylaxis and therapy of

postsurgical cystoid macular edema. Numerous studies havedetermined that NSAIDs are

effectivein the treatment ofpseudophakicCME,including Ketorolac tromethamine 0.5%, Diclofenacsodium 0.1%, Nepafenac 0.1% andBromfenac 0.09%.

i b ( )


41/48

Retina. 2010 Feb;30(2):260-6.

NSAIDs in combination therapy for the treatment of chronic pseudophakic

cystoid macular edema.

WarrenKA, Bahrani H, Fox JE.

PURPOSE:Thepurpose of this studywas to evaluate theaddition of topicalnonsteroidalantiinflammatory drugs (NSAIDs) to intravitreal corticosteroidandantivascular endothelialgrowth factor injections for the treatment of chronic cystoid macular edema.

METHODS:Thirty-ninepatients with chronic pseudophakic cystoid macular edemacompleteda single-center, randomized,investigator-masked study. Allpatients weretreatedwithanintravitreal triamcinolone andbevacizumab injectionat studyentry; thebevacizumab injectionwas repeatedat 1 month. To evaluate theeffect ofadding an NSAID,patients were randomized to treatment with 1 of 4 topical NSAIDs (diclofenac 0.1%,

ketorolac 0.4%,nepafenac 0.1%,andbromfenac 0.09%) or placebo for 16 weeks. RESULTS: At Weeks 12 and 16,both thenepafenac andbromfenac groups showeda

significant reductionin retinal thickness comparedwith that inplacebo (nepafenac, P =0.0048,bromfenac, P = 0.0113). A difference,however,between these 2 NSAID groups wasobservedin that only thenepafenac groupwas able to maintain thedemonstrated retinalthickness decreaseat Weeks 12 and 16. Thenepafenac groupalso experienceda significantimprovement invisualacuityat Weeks 12 (P = 0.0084) and 16 (P = 0.0233).Theaddition ofNSAIDs didnot produceanincreaseinmeanintraocular pressure over the course of

therapy. CONCLUSION:Although NSAID therapy seems to potentiate theimprovements

producedby corticosteroids andantivascular endothelial growth factortherapy for chronic pseudophakic cystoid macular edema, onlynepafenac-andbromfenac-treatedeyes showed reduced retinal thickness at 12 weeksand 16 weeks. Furthermore,nepafenac produceda sustainedimprovement invisualacuity.


42/48

CARBONIC ANHYDRASE INHIBITORS

The rationale of carbonic anhydrase inhibitors as a therapeutic

agent in the treatment ofmacular edemais to improve theability of retinalpigment epithelial cells to pump fluid out of

the retina.

Carbonic anhydrase inhibitors mayalter thepolarity of theionic transport systems in the retinalpigment epithelium

through theinhibition of carbonic anhydrase and -glutamyltransferase. As a result thereis increased fluid transport across

the retinalpigment epithelium from the sub-retinal space tothe choroidwith reduction of theedema.

Acetazolamide (Diamox) has been found to beparticularlybeneficialinpatients in the treatment of uveitic CME,pseudophakicCME andinmacular edemadue to retinitis

pigmentosa.

Doseis 500 mg/day,which shouldbe continued for at least 1

month to seeaneffect.

E J O hth l l 2008 N D 18(6) 1011 3


43/48

Eur J Ophthalmol. 2008 Nov-Dec;18(6):1011-3.

Pseudophakic macular edema and oral acetazolamide: an optical coherence

tomography measurable, dose-related response.

Ismail RA, Sallam A, Zambarakji HJ.

PURPOSE: Although uncommonafter phacoemulsification surgery, cystoid macular edema(CME) is animportant cause ofpostoperative reduction ofvisionafter cataract surgery. To

demonstratean optical coherence tomography (OCT) measurable,dose-related response

to orallyadministeredacetazolamide inapatient presenting withpseudophakic CME.

METHODS: A 76-year-oldwomanwith reducedvisionin right eyedue to cataract haduneventfulphacoemulsification. Surgerywas complicatedbyearly onset endophthalmitis

that was treatedwithintravitreal antibiotics with goodvisual recovery. At 6 months follow-up, shepresentedwith further reduction ofvision (0.5 LogMAR) due to CME anda central

foveal thickness (CFT) of 587 microm.

RESULTS: Acetazolamide treatment was startedin combinationwith topical ketorolac. At adailydose of 500 mg, CFTandvisualacuitywere 262 microm and 0.34 LogMAR,

respectively. Dose reduction ofacetazolamide to 250 mg/daywas associatedwith

worsening of the CFT to 335 microm. CFTwas subsequentlymeasuredat 230 microm onincreasing theacetazolamide dose to 500 mg/dayandmeasured 353 microm when

acetazolamide dosewas halved. CFTwas 478 microm whenacetazolamide was ceased.

CONCLUSIONS. In this report, theauthors have shownadose-related response of

pseudophakic CME to oralacetazolamide. This would suggest that the clinical responseto oralacetazolamide maybe titrated to theextent of CME andmonitoredby OCT.

J O l Ph l Th 2010 A 26(2) 199 206


44/48

J Ocul Pharmacol Ther. 2010 Apr;26(2):199-206.

Intravitreal bevacizumab versus triamcinolone acetonide for refractory

uveitic cystoid macular edema: a randomized pilot study.

Soheilian M, Rabbanikhah Z, Ramezani A, Kiavash V,Yaseri M, PeymanGA.

PURPOSE:To compareintravitreal bevacizumab (IVB) versus intravitrealtriamcinolone acetonide (IVT) for treatment of refractory uveitic cystoid macularedema (CME).

METHODS: In this randomized clinical trial, 31 eyes with uveitic CME wereallocatedinto the IVB group-eyes that received 1-3 injections of 1.25 mg bevacizumab (15 eyes)and the IVT group-eyes that received 1-3 injections of 2 mg triamcinolone (16 eyes).

Primary outcomemeasurewas changeinbest-correctedvisualacuity (VA) at 36weeks.

RESULTS:Visualacuityimprovement comparedwithbaselinevalues was meaningfulin the IVB groupat 12, 24,and 36 weeks (-0.35 + or - 0.45 logMAR [P = 0.016]) andinthe IVT groupat 24 and 36 weeks (-0.32 + or - 0.32 logMAR [P = 0.001]). A significantcentralmacular thickness (CMT) reductionwas observed onlyin the IVT groupatweek 36 (74.6 + or - 108.0 microm [P = 0.049]). Between-groupanalysis disclosedno

significant differenceinany outcomemeasure. By statistically removing the factor ofcataract, the IVT grouphadmoreimprovement in VA (P = 0.007).

CONCLUSIONS:IVBwas as effectiveas IVTin refractory uveiticCME regarding VA improvement up to 36 weeks. Irrespective oftriamcinolone-induced cataract,amorebeneficialeffect of IVT

maybeattainable.

A i J O hth l l V l 148 I 2 P 303 309 2 (A t 2009)


45/48

Asian J Ophthalmol,Volume 148, Issue 2, Pages 303-309.e2 (August 2009)

Ranibizumab for Refractory Uveitis-related Macular Edema

Nisha R.Acharyaab,Kevin C. Honga,Salena M. Leea

Purpose To evaluate theeffect ofintravitreal ranibizumab injections (Lucentis;

Genentech Inc,SouthSanFrancisco, California, USA) on refractory cystoid macularedema (CME) inpatients with controlled uveitis who have failed oraland regionalcorticosteroid treatment, themainstays of current medical therapy.

Design Prospective,noncomparative,interventional case series.

Methods Seven consecutivepatients with controlled uveitis and refractory CMEwho had failed corticosteroid treatment were studied. Oneeligiblepatient chosenot to participateandanother didnot complete follow-up for nonmedical reasons.

Intravitreal ranibizumab injections (0.5 mg) were givenmonthly for 3 months,followedby reinjectionas needed. Theprimary outcomewas themean changeinbest spectacle-correctedvisualacuity (VA) frombaseline to 3 months,and thesecondary objectivewas themean changein central retinal thickness (CRT) onocular coherence tomography. Six-month outcomes werealso assessed.

Results At 3 months, themeanincreaseinacuity for the 6 patients who completedfollow-upwas 13 letters (2.5 lines),and themeandecreasein CRTwas 357 m.

Both VA and CRTimproved significantlybetweenbaselineand 3 months (P = .03for each). Althoughmost patients required reinjection, this benefit was maintainedat 6 months. Therewereno significant ocular or systemic adverseeffects.

Conclusions Intravitreal ranibizumab led to anincreasein VAand regression of uveitis-associated CME inpatients refractoryto or intolerant of standard corticosteroid therapy. Further

studies of this promising treatment arewarranted.


46/48

Stepwise Approach for Treating

CME (IRVINE GASS SYNDROME) Step 1 Wait andwatch

Topical NSAIDs

Step 2 Topical Corticosteroids Step 3 Sub-tenon steroidinjection

Step 4 Oral Acetazolamide (Diamox)

Oral Corticosteroid Step 5 Laser Nd-YAGvitreolysis

Vitrectomy


47/48

Conclusion

Macular edemais a condition ofenormous medicalandsocioeconomic importancebecause ofits highprevalenceand occurrenceinalargenumber ofpathologic conditions.

It is theendpoint ofavariety ofpathophysiologicprocesses that canbeeffectivelymanagedby recognizing

andaddressing thepathogenic factors that are operativeina given clinical setting.

So far, thereareno clear guidelines for the treatment ofsubclinical cystoid macular edemaandeverypractitionerhas their own strategy using avariety ofpharmacologic

agents,as wellas vitreous surgerywhenneeded. Although treatment options continue to expandwith the

development ofnewdrugs and surgicalprocedures,long-termefficacyand safety ofmost newapproaches haveyetto beestablishedin controlled clinical trials.


48/48

THANK YOU

THANK YOU!

Treatment of Macular Edema

Documents

Transcript of Treatment of Macular Edema