Age Related Macular Degeneration

80, 90

____% of pts have non-neovascular AMD, yet neovascular form is responsible for ____% of severe vision loss

increases

prevalence, incidence, & progression of AMD ______ with age

Caucasian

observations from the Barbados Eye Study, the Baltimore Eye Study & MPS suggest late-stage AMD is more prevalent in _______ individuals

European

meta-analysis in a systematic review reported higher prevalence of AMD in ________ individuals compared to Asian & African

1. age

2. northern European ancestry

3. genetic factors

4. smoking

5. HTN & CV disease (mixed results)

6. theoretically: hormonal status, sunlight exposure, alcohol use, vitamins B & D

what are the risk factors for AMD?

complement factors H (leads to defective regulation of alternative complement pathway)

what genetic component has been shown to have a strong association with higher risk of AMD?

1. RPE cells age & accumulate residual bodies with lipofuscin

2. decreased RPE function & changes in permeability of Bruch’s membrane may lead to drusen

3. drusen may initiate inflammatory cascade that can contribute to AMD progression

   1. disrupt RPE function

   2. loss of RPE & PRs

   3. dysfunction in Bruch’s

   4. VEGF

   5. CNVM

describe the pathogenesis of AMD

non-exudative

characterized by deep yellow deposits called drusen, RPE pigmentation changes, & atrophy

exudative

characterized by development of macular neovascularization which leak & bleed into surrounding tissue ultimately leaving a fibrovascular scar or disciform scar

drusen

• multilpe, discrete, round, slightly elevated, variable sized, yellow/white sub-RPE deposits in the macula & posterior pole b/t the RPE & Bruch’s membrane

• bilateral

• clustered in macular or paramacular area

• tend to increase in # & size but can fade from view & decrease in number

• change in size/shape/distribution/color/consistency w/ time

less than 63um

what are the size of small drusen?

63-125um

what is the size of intermediate drusen?

greater than or equal to 125um

what is the size of large drusen?

compare to the width of a major retina vein

how do you estimate the size of drusen?

hard drusen

• yellow, punctate, calcific

• can become crystalline in appearance or occasionally polychromatic or golden sparkling indicative of cholesterol deposits

• low risk of MNV

• FA shows early, well defined focal hyperfluorescence w/o leakage

• often clustered & can extend out of the vascular arcades & into the equatorial retina

soft drusen

• larger, pale yellow or gray-white, placoid or dome-shaped, less well-defined

• may coalesce to appear similar to a serous detachment of the RPE

• FA demonstrates early hyperfluorescence that does not leak & fades midway through

• increased risk of MNV

reticular pseudodrusen

• subretinal drusenoid deposits

• best imaged w/ AF, infrared reflectance, OCT

• appear to be a meaningful risk factor to GA

basal laminar drusen/cuticular drusen

• nodular thickening of the BM of the RPE

• uniformly small, discrete, round, slightly raised, yellow subretinal nodules that appear as early as early adulthood w/ equal frequency in blacks, Latinos, & whites

• can give an orange peel appearance when they cluster

• predispose pts to the development of the more typical drusen

younger, slower, higher, lower, better

how do basal laminar/cuticular drusen differ in regard to AMD?

onset is in ______(younger/older) pts, rate of visual loss is ____(slower/faster), incidence of GA is ______(lower/higher), risk of neovascularization is _____(lower/higher), & prognosis for retention of useful central vision is _____(better/worse)

large, soft, confluent

what type of drusen have been found to put pts at a higher risk for vision loss?

loss of choroidal vessels & fibrous replacement of choroid stroma

what can pseudodrusen indicate?

no AMD (AREDS category 1)

• AREDS severity scale

• characterized by no or few small drusen, aka drupelets

early AMD (AREDS category 2)

• AREDS severity scale

• characterized by a combination of multiple small drusen, few intermediate drusen or mild RPE abnormalities

intermediate AMD (AREDS category 3)

• AREDS severity scale

• characterized by numerous medium drusen or at least 1 large druse

advanced AMD (AREDS category 4)

• AREDS severity scale

• characterized by 1 or more of the following in 1 eye:

  • GA of the RPE fovea involving & not involving fovea

1

the presence of intermediate drusen in both eyes is __ risk factor

2

the presence of advanced AMD in 1 eye is __ risk factor

4

the contralateral eye to the eye of advanced AMD has large drusen & pigmentary changes is __ risk factors

geographic or central areolar RPE atrophy

• a form of dry AMD consisting of large areas of GA of the RPE

• histologic: the area of GA is associated w/ focal loss of the retinal receptor cells, RPE, & choriocapillaris

• 5-10% of pts w/ AMD lose central vision as a result of this form of AMD

• one or more sharply circumscribed geographic areas of atrophy of the RPE & retinal in the posterior pole

• central vision is slow & progressive as the atrophic concentric area enlarges

• bilateral, symmetric

• 20% of these pts will develop CNVM in the 2nd eye

• FA shows varying degrees of loss of the choriocapillaris w/in the area of GA

AREDS

double-masked clinical trial that studied the effects of zinc &/or antioxidants on pts w/ cataracts & those w/ varying stages & types of AMD

19

AREDS found that high levels of antioxidants & zinc can reduce the risk of vision loss from advanced AMD by about ____% in high-risk patients (pts w/ intermediate AMD or advanced AMD in 1 eye but not the other)

F

T/F: AREDS found that supplements do provide significant benefits to pts w/ minimal AMD

T

T/F: AREDS found that nutritional supplements do not prevent the initial development of AMD, nor do they improve vision already lost to AMD

F

T/F: AREDS found that nutritional supplements do seem to prevent cataracts & keep them from getting worse over time

1. vitamin C

2. vitamin E

3. beta-carotene

4. zinc

5. copper

what were the things included in the AREDS1 supplements?

AREDS2

primary objective was to evaluate the effect of dietary xanthophylls &/or omega-3 on progression to advanced AMD

F

T/F: AREDS 2 found that there was a benefit from adding omega-3 fatty acids or a 5:1 mixture of lutein & zeaxanthin to the formulation

T

T/F: AREDS2 found that there was some benefit to pts who took an AREDS formulation with lutein & zeaxanthin but no beta-carotene

T

T/F: AREDS 2 found that there was no benefit to lowering the zinc dosage compared to AREDS1

1. vitamin C

2. vitamin E

3. lutein & zeaxanthin

4. zinc

5. copper

what was included in the new formulation of AREDS?

people at a high risk for developing advanced AMD:

1. intermediate AMD in 1 or both eyes

2. advanced AMD in 1 eye but not the other

who should consider taking a combination of antioxidants and zinc like those examined in AREDS & AREDS2?

drusen

drusen

hard drusen

soft drusen

soft drusen

soft drusen

soft drusen

reticular pseudodrusen

basal laminar/cuticular drusen

GA

GA

GA

GA

GA

1. maybe loss of vision, distortion, or blur

2. acute hemorrhage or insidious (fluid & PEDS) in onset

3. bilateral but often asymmetric

4. can have a hx of loss of vision in other eye

5. stable central scotoma in which VA falls below reading & legal driving level

6. peripheral vision retained

what are the signs/sx of neovascular AMD?

CNV

• ingrowth of new vessels extending from the choroid into sub-RPE space in one or more areas

• neovascular buds invade & penetrate the degenerated Bruch’s membrane & proliferate beneath the RPE

occult stage/Gass type 1

• initial blood flow is very slow through CNVM

• fibrovascular PED or late leakage of underdetermined source

• breaks through Bruch’s but staying sub-RPE

classic CNV/Gass type 2

• CNVM

• well defined hyperfluorescence

• cartwheel or sea fan appearance

• thought to break through RPE & staying sub-retinal

polypoidal choroidal vasculopathy (PCV)

• polypoid lesions

• more evident on ICG

• bridges AMD discussion & pachychoroid syndrome

1. growth of abnormal choroidal vessels

2. new vessels grow into & break through Bruch’s

3. new vessels continue to grow under RPE

4. drusen are resorbed

5. new vessels continue to grow under RPE

6. exudation due to vessels leaking fluid into sub-RPE space

7. fluid breaks into sub-retinal space through RPE

8. type 2 CNV develops which may show classic components or remain occult to FA depending on RPE cells’ migration to envelop the membrane

describe the development of wet AMD

under the pigment epithelium

describe type 1 CNVM on OCT

subretinal

describe type 2 CNVM on OCT

retinal angiomatous proliferation

describe type 3 CNVM on OCT

type 1 MNV

• fibrovascular PED

• late leakage from undetermined source (poorly defined neovascularization)

  • speckled hyperfluorescence

  • dye pooling late in study

  • poorly defined

PCV

similar to type 1 MNV w/ dilated vascular elements (polyps)

type 2 MNV

• MNV is now b/t neurosensory retina & RPE making the IVFA more obvious & well defined

• IVFA shows lacy, well-group area of neovascularization

  • hyperfluorescent early in study

  • late leakage

  • lacy early fill of the MNV during the choroidal & arterial filling phase

  • may have hypofluorescence corresponding to RPE hyperpigmentation & blood in the outline of the MNV

  • progressive hyperfluorescence throughout the FA w/o leakage of the margins of the MNV

type 3 MNV

macular NV originating from deep capillary plexus growing to the outer retina

subretinal hyperreflective material

• exudation into subretinal space

• composed of serum, fibrin, inflammatory cells

• may correspond w/ increased risk of GA

serous fluid

• type of PED

• dome-shaped detachment of RPE

• bright diffuse hyperfluorescence that does not spread

fibrovascular tissue

• type of PED

• irregular RPE w/ speckled fluorescence

hemorrhagic

• type of PED

• dark elevation of RPE

• blocked fluorescence

coalescence of drusen sub-RPE

• type of PED

• drusenoid

• staining w/ fading of fluorescence w/o leaking

1. RPE tear

2. hemorrhagic detachment of the RPE & retina

3. vitreous hemorrhage

4. subretinal scar tissue

what are the further complications of MNV

disciform scarring

• final stage of MNV in which there is progressive fibrosis & loss of the macular photoreceptors function

• seen less often now w/ anti-VEGF therapy

5, 15

over 5y, up to ___% w/ early AMD will progress to late stage, increasing to ___ over 15 years

hard

____ drusen is common & not associated w/ progression

6.5

soft drusen indicates ___% risk of progression to late AMD in 5y

7.1

RPE changes indicate a ___% risk of progression to late in 5y

47.3

if large drusen & pigmentation changes are present, there is a ___% risk of progression to late AMD in 5y

30

wet AMD is often bilateral w/ __% risk of 2nd eye involvement in 6y

exudative macular degeneration

fibrosis

PED

PED

PED

PED

MNV type 1

MNV type 1

MNV type 1

MNV type 1

MNV type 1

classic CNV

classic & occult CNV

type 2 MNV

MNV type 2

MNV type 2

MNV type 2

MNV type 2

MNV type 2