armd-cme

8/7/2019 ARMD-cme

1/64

AGE RELATED MACULARDEGENERATION

8/7/2019 ARMD-cme

2/64

AGE RELATED MACULARDEGENERATION

Age related maculardegeneration (ARMD)is

theleadingcauseofseverevisuallossinthe western worldin peopleover 50 years

ofage.

Ref: Surveysofophthalmology 32 (6) 1988:375-

413

8/7/2019 ARMD-cme

3/64

AGERELATEDMACULARDEGENERATION

TheUNestimatesthenumberofpeople withage

related maculardegenerationat 20-25 million worldwide

WHOsestimateis 8 million people withseverevisualimpairment

AMD wasfoundto besecondtocataractasthecause

ofseverevisualloss

Ref:BMJ2003; 326:485-8

8/7/2019 ARMD-cme

4/64

Macula

The maculaisthe posterioraspectofthe retina

Hashighestconcentrationofphotoreceptors

whichfacilitatecentralvisionand permithigh

resolutionvisualacuity

The maculaisanareaup to 5.5 mm indiameter

withthefoveaatitscentre

NEJM; 342(7):2000; 483-492

8/7/2019 ARMD-cme

5/64

Macula

8/7/2019 ARMD-cme

6/64

Thefovea depressionat

centreofmacula with

diameter 1.5mm.Give rise

toovallight reflex (

thicknessofretinaand

internallimiting membraneatits border)

8/7/2019 ARMD-cme

7/64

Thefoveola centralfloorof

fovea wf diameter 0.35mm.

Thinnest part-only consistsofconesandthenuclei.

Theumbo tiny depression

atvery centreoffoveola

light reflex

8/7/2019 ARMD-cme

8/64

MACULA:CROSS SECTION

Ref:http://www.eyesight.org

8/7/2019 ARMD-cme

9/64

The retinal pigmentepithelium (RPE)isasinglelayerofhexagonally shapedcells. They reachouttothe photoreceptorlayerofthe retina

FunctionsofRPEincludes maintainanceofthe photoreceptors,absorptionofstray light,formationoftheouter blood retinalbarrier, phagocytosisand regenerationofvisual pigment

Bruchs membraneseparatestheRPEfrom vascularchoroid,

FunctionofBruchs membraneisto providesupporttothe retina

Choroidcapillariesarealayeroffine bloodvesselsthatnourishesthe retinaand providesO2

Ref:http://www.ahaf.org

http://www.eyesight.org

8/7/2019 ARMD-cme

10/64

Riskfactor

8/7/2019 ARMD-cme

11/64

RiskFactors

Genetic

Race

GenderAge

Hypertension/Diabetes

Refractiveerror

Lensopacities

Sunexposure

Smoking

8/7/2019 ARMD-cme

12/64

RiskFactors

Genetic

Studieshavedemonstratedfamilialaggregation.

ABCRgene (linkedto Stargardts disease)has been

linkedtosomecasesofAMD. ComplementfactorHGene

ProteinsinCFH pathway foundindrusendeposits

Two- tofourfoldincreased riskifgenevariantisinheritedfrom one parent

Five- tosevenfoldincreased riskfrom 2 parents

8/7/2019 ARMD-cme

13/64

RiskFactorsRace NHANESIII reportedahigherfrequency in whitescompared with

blacks.

InBaltimoreEye SurveyAMDaccountedfor 30% ofblindnessamong whitesand 0% ofblindnessamong blacks.

Gender IntheBeaverDam study,only wetAMD wasshownto be more

frequentin women.

Age

8/7/2019 ARMD-cme

14/64

AMD Is Directly Related To Age

12%16%

30%

55 to 64 65 to 74 Over 75

1 Beaver Dam Study

Source: Yanoff: Ophthalmology, First Edition, 1999; Clinical Practice Guidelines, www.aoanet.org; www.allaboutvision.com

Incidence of AMD Increases With Age

8/7/2019 ARMD-cme

15/64

RiskFactors

Hypertension

Role remainsunclear

BeaverDam reportedthatsystolicBP wasassociated with

incidenceofRPEdepigmentation. MacularPhotocoagulation Study reportedanincreased

incidenceofwetAMDassociated withhypertension

Diabetes

BeaverDam showedno relation,however,literatureonthematterisotherwisescant.

8/7/2019 ARMD-cme

16/64

OcularRiskFactors

Refractiveerror

Increased risk withhyperopia

Lensopacities

BeaverDam revealednuclearsclerosisassociated with

increased riskofearlyAMD butnotlatestagesofthe

disease.

FESfoundno relationship.

Aphakia

Instudiesofunilateralaphakia,surgicaleyehad more

advanceddisease whencomparedtocontralateraleye.

8/7/2019 ARMD-cme

17/64

EnvironmentalRiskFactors

Sunexposure controversial riskfactor

Watermenstudy revealeda weakassociation between

advancedAMDandexposuretovisiblelight.

UVlightdidnotseem to be relatedintheBeaverDam,

WatermenandBlueMountainstudies.

8/7/2019 ARMD-cme

18/64

EnvironmentalRiskFactors

Smoking

Strong positiveassociation betweensmokingand

thedry and wetform.

IntheNursesHealth Study riskincreasedas pack

yearsofsmokingincreasedindicatingadose

dependent relationship.

8/7/2019 ARMD-cme

19/64

WHAT GOESWRONG IN ARMD?

8/7/2019 ARMD-cme

20/64


TYPES

Dry maculardegeneration

Wet maculardegeneration

Ref:NEJM, Vol. 342 (7):483-492

8/7/2019 ARMD-cme

21/64

ARMD : Etiology

Etiology iscomplexand poorly understood

Angiogenesisislikely to beanearly featureof

neovascularARMD

8/7/2019 ARMD-cme

22/64

DRYMACULARDEGENERATION

1. Accountsforabout 90% ofallcases

2. Alsocalledatrophic,nonexudative or

drusenoid maculardegeneration

3. As yet,thereisstillno proveneffectivetherapy

forthenon-neovascularform ofAMD

8/7/2019 ARMD-cme

23/64


Insufficientoxygenandnutrients

damages photoreceptor molecules

Withageing,theability ofRPEcellstodigestthese moleculesdecreases

Excessiveaccumulationofresidual bodies

(drusen)

RPE membraneandcellsdegenerateand

atrophy setsinandcentralvisionislost

BMJ326, 2003; 485-488

8/7/2019 ARMD-cme

24/64

DRUSEN

Drusen isanaggregationofhyalinemateriallocated betweenBruchsmembraneandRPE

Drusen arecomposedofwasteproductsfrom photoreceptors

Drusen > 63 micronsindiameterarestatistically associated withvisualpathology andaretermedearly

ARMDHypo/hyper pigmentationofRPEmay be present

NEJM, Vol 342 (7):483-492

8/7/2019 ARMD-cme

25/64

DRYMACULARDEGENERATION

8/7/2019 ARMD-cme

26/64

DRYMACULARDEGENERATION: VISUAL

8/7/2019 ARMD-cme

27/64

WETMACULARDEGENERATION

Accountsforabout10%

Alsocalledchoroidalneovascularization,subretinal

neovascularizationordisciform degenerationAbnormal bloodvesselsgrow beneaththe macula

Thesevesselsleak bloodandfluidintothe maculadamaging photo receptors

Progresses rapidly andcancauseseveredamagetocentralvision

http://www.blindness.org

8/7/2019 ARMD-cme

28/64


Alternatively the photoreceptorsand pigmentepithelium sendadistresssignaltochoriocapillaries to makenew vessels

New vesselsgrow behindthe macula

BreakdownintheBruchs membrane

Bloodvesselsarefragile

Leak bloodandfluid

Scarringofmacula

Potentialfor rapidseveredamage

BMJ326; 2003:485-488

8/7/2019 ARMD-cme

29/64

8/7/2019 ARMD-cme

30/64

WetARMD

8/7/2019 ARMD-cme

31/64

SubretinalFibrosis

8/7/2019 ARMD-cme

32/64

WETMACULARDEGENERATION

8/7/2019 ARMD-cme

33/64

FFAINWETARMD

ClassicCNV (30%)

Welldefined membrane whichfluoresces brightly

andleaksintosubretinal space within1-2min

Classifiedas :

Extrafoveal : CNVis morethan200Um from thecentreof

FAZ

Juxtafoveal : CNViscloserthan200Um from thecentre

ofFAZ butdosent involvethat

Subfoveal : centreofFAZisinvolve

8/7/2019 ARMD-cme

34/64

8/7/2019 ARMD-cme

35/64

FFAINWETARMD

OccultCNV

Poorly definedless preciseonearly frame butgives

risetolate,diffusedor multifocalleakage

FibrovascularPED

CombinationofCNVandPED.TheCNVfluoresces

brighter (hotspot)thandetachment.InothercaseCNV may beobscured by the bloodorturbidfluid.

8/7/2019 ARMD-cme

36/64

8/7/2019 ARMD-cme

37/64

AMD: COURSEANDVISUALPROGNOSIS

Patients withonly drusen (inoneor botheyes)typically

donothave muchlossofvision, butthey make require

additional magnificationofthetextand moreintenselightingto readsmall point

Presenceoflargedrusen (> 63 micronsindiameter)is

associated witha riskofthelateform ofthedisease

Patients withlargedrusen areat relatively high riskfor

choroidal neovascularization (CNV)

8/7/2019 ARMD-cme

38/64

AMD: COURSEANDVISUALPROGNOSIS

Patients withCNVhavea rapiddeclineinvisionwithin weeks

OnceCNVhasdevelopedinoneeye,theothereyeisat relatively high riskforthesamechange

NEJM;Vol. 342(7); 483-492

8/7/2019 ARMD-cme

39/64

AMD: SYMPTOMS

Initialsymptoms

Blurry vision

Distortedvision

Straightlinesappear wavy

Objects may appearasthe wrongshapeorsize

Adarkempty areainthecentreofvision

http://www.kellogg.umich.edu/

8/7/2019 ARMD-cme

40/64

AMD: SYMPTOMSVISUAL

8/7/2019 ARMD-cme

41/64

8/7/2019 ARMD-cme

42/64

8/7/2019 ARMD-cme

43/64

AMD: EFFECTON QUALITYOFLIFE

8/7/2019 ARMD-cme

44/64

AMD:MANAGEMENT

8/7/2019 ARMD-cme

45/64

DRYAMD: MANAGEMENT

Low visionaids

Antioxidants

8/7/2019 ARMD-cme

46/64

AREDS STUDY

Aim

Toevaluatetheeffectofanti-oxidantvitaminsandzincon

the progressionofdryAMD. Thestudy wasinitiated byNationalInstitutesofHealth.

No.ofcentres

11

No.ofpeople

4767 participantsaged 55-80 years

8/7/2019 ARMD-cme

47/64

AREDS STUDY (contd.)

Patientsdividedinto4categories:Category1: littleornoAMD-> randomizedtoantioxidantsor placebotodetermineanyeffectonlens

changes

Category2: earlyAMDCategory3: intermediateAMD

Category4: advancedAMDinoneeye

Category2, 3and4 randomizedto receive:

1. Placebo

2. Antioxidantsalone3. Zinc alone

4. Antioxidants pluszinc (Vit. C: 500 mg,Vit.E: 400 IU,Betacarotene: 15 mg,Znoxide: 80 mg,Copper: 2mg)

Category2, 3,4 werefollowedforvisuallossforthedevelopmentofadvancedAMD

Patientsfollowedup: 6.3years

8/7/2019 ARMD-cme

48/64

AREDS STUDY (contd.)

Results

Forcategory 2,only 13% ofpatients progressedtoadvancedAMD.

Forcategories 3and4 (whoareatgreater riskfordevelopingadvancedAMD),it

wasfoundthatthecombinationofzincandantioxidants were mosteffectivein

reducingthe progressiontoadvancedAMD.

Conclusion

It was recommendedthat patients withintermediateoradvancedAMDshould

considertakingantioxidantvitaminsandzinc

8/7/2019 ARMD-cme

49/64

AREDSRecommendations

Supplement

IntermediateAMD

AdvancedAMD

Excellent Safety

Avoid betacarotenein

smokers

Encourageadherence

IntermediateAdvanced

Data on file, AREDS.

8/7/2019 ARMD-cme

50/64

14 SuperFoods

Blueberries

Sardine

Citrus

Pumpkin

Yogurt

Oats

Legumes

Spinach

Turkey Breast

Broccoli

Walnuts

Tomato

GreenTea

Soy

Daily sunlight and/or 1000 IU vitamin D daily

also is very important for general health

8/7/2019 ARMD-cme

51/64

WETAMD: MANAGEMENT

Photodynamictherapy

Anti-angiogenic therapy

Intravitreal steroid Anti-vascularendothelium growthfactor (anti-VEGF)

Surgery

Submacularsurgery Maculartranslocation

8/7/2019 ARMD-cme

52/64

ThePrincipleofPhotodynamictherapy

Incontrast withtheconventionalhotlaser

PDThelpstoselectively closeoffsubretinalnew

vessels

twostagetreatment

Injectingthe photosensitiserdrug

Applyingcoldlasertoactivatethedrug Releasesthesingletoxygen moleculethatdamagesthe

endothelium

Thrombosisofthecapillaries

8/7/2019 ARMD-cme

53/64

PHOTODYNAMICTHERAPY

PDT forAMDisatwostage processcomprisinga10

minuteintravenousinfusionof6 mg/kgverteporfin

followed by activation 5 minuteslater by 689nm diodelaserfor83secondsat 503/cm2

The photosensitiveverteporfinisselectively takenup by

rapidly proliferatingendothelialcells withinthetarget

CNV reachingits peakconcentrationat15 minutesCytotoxic reactiveoxygenintermediatesdamage

cellular proteinsandcause microvascularthrombosis

8/7/2019 ARMD-cme

54/64

8/7/2019 ARMD-cme

55/64

Wormald R

The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews

2009 I

Objectives

The aim of this review was to examine the effects of PDT in the

treatment of neovascular AMD.

STUDY SIZE

1022 participants.

Auth

os' c

onclu

sion

s Photodynamic therapy in people with choroidal neovascularisation due

to AMD is probably effective in preventing visual loss though there is

doubt about the size of the effect. Outcomes and potential adverse

effects of this treatment should be monitored closely. Further

independent trials of verteporfin are required to establish that the

effects seen in this study are consistent and to examine importantissues not yet addressed, particularly relating to quality of life and cost.

However, the advent of new interventions for AMD make this unlikely

1

8/7/2019 ARMD-cme

56/64

Intravitreal steroid

Triamcinolone mayb usealoneoradjuncttoPDT

May improve retinalthicknessanddecreasevascularexudation

Anti-angiogenic therapy

8/7/2019 ARMD-cme

57/64

ANTI-VEGF FACTORS IN ARMD

8/7/2019 ARMD-cme

58/64

Intravitreal bevacizumab (Avastin) for age-related macular

degeneration: a critical analysis of literature

S JyothiEye advance online publication 14August 2009

PURPOSE: This study was undertaken to review the current literatureon bevacizumab for age-related macular degeneration and itsvalue in determining best clinical practice

Conclusions

There is sufficient scientific and statistical evidence to advocate the effective use ofOCT-guided administration of intravitreal bevacizumab for neovascular AMD. This isreflected in our study outcome measures that are comparable to findings publishedfrom recent well-conducted RCTs on intravitreal ranibizumab at the same time point.

5

8/7/2019 ARMD-cme

59/64

Purpose:To compare 1-year functional and anatomic outcomes ofintravitreal bevacizumab (IVB) & photodynamic therapy +intravitrealtriamcinolone (PDT+IVTA) combination in patients with neovascular age-related macular degeneration (AMD).

STUDY SIZE

28 patients.

Conclusions:Patients treated with IVB showed a significant better VAoutcome compared with the PDT+IVTA group despite the fact that bothmodalities showed equal potency in reducing CRT during a 12-monthperiod.

14

S Sacu

Eye advance online publication, 23 January

2009

8/7/2019 ARMD-cme

60/64

INVESTIGATIONALTREATMENTS

Submacularsurgery

Retinaltransplantationandtransplantationof

RPE

Retinaltranslocation

Genetherapy

Angiogenesisinhibitors: likecytochalasinE,

Anecortaveacetate,Prinomastat

8/7/2019 ARMD-cme

61/64

SUBMACULAR SURGERY

The technique for CNV removal

After complete pars plana

vitrectomy

CNVM is removed from subretinalspace by making retinotomy

temporal to fovea & inducing

localized retinal detachment.

Fluid-air exchange is performed at

the end of surgery and gas

tamponade is given.

8/7/2019 ARMD-cme

62/64

8/7/2019 ARMD-cme

63/64

TIPSFORARMDPATIENTS

Monitorvision monthly withanAmslergrid

Takea multi-vitamin withzinc

Incorporatedarkleafy greenvegetablesintoyourdiet

Always protect youreyes withsunglassesthat

haveUV protectionQuitsmoking

Exercise regularly

8/7/2019 ARMD-cme

64/64

Thank you

armd-cme

Documents