AMD-age-related macular degeneration

Question 1

RFs for AMD?

Answer 1

SMOKING-for new onset AMD and progression to advanced AMD
increasing age
genetics-complement factor H, gene variant Y402H (linked to drusen formation) and FH-up to 3X increased risk if 1st degree relative with AMD
caucasian ethnicity
light iris, hypermetropia-also RF for angle closure glaucoma
CVD, HTN, CVS RFs-hypercholesterolaemia, DM, male, FH of CVD
?obesity, alcohol, sunlight, prev. cataract surgery and protective role of diet high in antioxidants and polyunsaturated fats

Question 2

define drusen

Answer 2

drusen is a collection of undigested cellular debris comprising lipid and protein material that forms due to the degeneration of the retinal pigment epithelium (RPE) that occurs as part of the normal ageing process, and undigested lipid products from photoreceptor cells which RPE is normally involved in processing and removing.
accumulates between the RPE and Bruch’s membrane (and within this membrane=innermost layer of choroid).
seen in early stages of AMD but small drusen also found in older people and not always assoc. with progression to advanced AMD and visual loss
soft and hard drusen, soft-larger and less well defined and increases risk of progression to advanced AMD.

Question 3

what part of the eye is affected in AMD?

Answer 3

tissues within the macular region of the retina
the macula is the region of retina with the maximum number of cone cells-mainly responsible for colour vision and reading-fine detail

Question 4

how is AMD classified?

Answer 4

dry and wet AMD, wet=advanced form of AMD which may result from progression of dry AMD or can in some cases present acutely with no prior dry AMD
dry is characterised by presence of drusen, and is split into early, intermediate AMD and advanced dry AMD.
advanced AMD can be advanced dry or wet

Question 5

what is early AMD?

Answer 5

few medium sized drusen
pigmentary abnormalities (RPE)- e.g. hypo or hyperpigmentation

can be combination of multiple small drusen, few intermediate sized, or mild RPE abnormalities

Question 6

what is intermediate AMD?

Answer 6

1 or more large drusen, or numerous medium (intermediate) sized drusen or
geographic atrophy (GA) NOT involving the fovea-this is a sharply demarcated area of partial or complete depigmentation of the RPE

risk of progression to advanced AMD over 5 years is 18%

Question 7

what is advanced dry AMD?

Answer 7

geographic atrophy (depigmentation of RPE) and drusen extension to involve the FOVEA
central and paracentral macula degeneration
confluent drusen
non-exudative
gradual visual loss

Question 8

what is advanced wet AMD?

Answer 8

exudative/neovascular
there is choroidal neovascularisation with new blood vessel formation beneath and within the retina, but these are more permeable so leak blood and fluid beneath and into the retina, invading through Bruch’s membrane to lead to retinal fibrous scarring-disciform scar with irregular borders, creating a blind spot in the patient’s central vision.
rapid visual loss over days/weeks

Question 9

common complaint of patients presenting with advanced dry AMD?

Answer 9

reading difficulty, progressing from small words to larger text
complaint of central vision deterioration if bilateral geographic atrophy involving the fovea

Question 10

what mediates the progression of dry AMD to wet AMD?

Answer 10

VEGF, specifically VEGF-A

Question 11

risk to other eye if patient presents with wet AMD affecting 1 eye?

Answer 11

50% likelihood patient will develop wet AMD in the other eye within 5 years

Question 12

how does the presence of soft drusen cause a problem?

Answer 12

it can separate the RPE from Bruch’s memebrane, causing hypoxia which leads to RPE atrophy, and inflammtion
soft drusen is more likely than hard to lead to promote progression to advanced AMD

Question 13

what can cause the RPE pigmentary changes that start in early AMD, and why are these changes a problem?

Answer 13

may be caused by:
age dependent phagocytic and metabolic insufficiency of postmitotic RPE cells
progressive accumulation of lipofuscin (or age pigment) granules
cytotoxic component with potential to damage lipids, proteins and DNA

RPE abnormalities are a RF for choroidal neovascularisation hence wet AMD-this presents acutely with a sudden painless loss of vision occurring over days-weeks, and can cause blindness within 3 mnths.

Question 14

what a major RFs for AMD progression?

Answer 14

numerous large hard and soft drusen in the macula, and extensive retinal pigment irregularities or de-pigmentation

Question 15

what is seen over the macula on fundoscopy in advanced wet AMD?

Answer 15

a thick yellow patch=disciform macular scar that occurs with fibrous scarring of the retina following new blood vessel invasion into the retina through Bruch’s membrane.

Question 16

what conditions other than AMD can cause a painless loss of vision?

Answer 16

amaurosis fugax (central artery of the retina occlusion) and central vein of the retina occlusion
cerebrovascular disease-including amaurosis fugax, TIA and stroke
refractive errors
cataracts
some corneal diseases e.g. Fuch’s endothelial dystrophy
posterior vitreous detachment or retinal detachment or vitreous haemorrhage
some drugs e.g. isoniazid, ethambutol, tetracycline, isotretinoin, chloroquine and hydroxychloroquine
pituitary and other neurological tumours
diabetic maculopathy
primary open angle glaucoma

Question 17

how does foveal atrophy appear in advanced dry AMD on fundoscopy?

Answer 17

visible choroidal blood vessels

Question 18

symptoms of dry AMD?

Answer 18

early AMD often asymptomatic
loss of visual acuity
reduced contrast sensitivity, these both occur with loss of photoreceptor cells occurring with atrophy of RPE
abnormal dark adaptation-difficulty adjusting from bright to dim light

dry AMD progression:
gradual visual loss which is insidious over months/years
mild occasional metamorphopsia-visual distortion with straight lines appearing wavy e.g. lamp posts appearing bent.
central/paracentral scotomas-blind spots (grey or black patches) in an otherwise normal visual field

can be light glare, photopsia, visual hallucinations

Question 19

if wet AMD is much less common then dry AMD (10-15% of AMD cases vs. 85-90% of AMD cases), why is it such a concern?

Answer 19

responsible for 80% of severe vision loss in AMD
can cause blindness within 3 months of onset

importantly, it is a treatable disease in contrast to dry AMD, so important to have early detection and treatment to prevent unnecessary visual loss

Question 20

VEGF-A role in wet AMD?

Answer 20

drives the progression of wet AMD, stimulating new abnormal choroidal blood vessel growth and leakage

Question 21

what mediates VEGF release in wet AMD? *

Answer 21

RPE oxidative stress

Question 22

3 different classifications of wet AMD?

Answer 22

based on relationship of lesion to the fovea
subfoveal-most symptomatic
juxtafoveal-less than 200micrometres from the geometric centre of the fovea
extrafoveal-200 or more away from geometric centre of fovea

Question 23

RFs for development of wet AMD in other eye after development in 1?

Answer 23

more than 5 drusen
large (soft or confluent) drusen
pigment clumping in the RPE
systemic HTN

presence of all 4 RFs increases 5 year risk of developing wet AMD to 87%

Question 24

management of patients with dry AMD?

Answer 24

no definitive treatment, but can give lifestyle advice:
STOP SMOKING-assoc. with progression to advanced AMD
dietary advice: balanced diet, low in saturated fats but rich in omega 3 fats and green leafy vegetables, fruit, fresh fish and nuts to help prevent and slow down progression of AMD
ocular nutritional supplements e.g. zinc-risk of genitourinary conditions e.g. UTI and antioxidant vitamins e.g. vit E-but poss. increased HF risk in pts with DM or vascu disease, shown to delay progression in high risk patients, BUT should not be recommended for smokers as increased lung Ca risk assoc. with lutein (?and beta carotene-no longer recommended)
must monitor for progression to wet AMD: patients should self monitor each eye individually for visual distortion and reduction in visual acuity, and advise must seek urgent help if occurs, regular eye examinations-annually if over 55 and at risk
patient may require r/f for low visual aid assessment, blind/partial sight registration and social services involvement
if registered with sight impairment or severe sight impairment must be advised not to drive and to notify the DVLA.

Question 25

presentation of wet AMD?

Answer 25

sudden painless loss of vision over days-mnths with:
loss of visual acuity
reduced contrast sensitivity
metamorphopsia
central scotoma

Question 26

treatment options for wet AMD?

Answer 26

treatment should start within 2 weeks of presentation
anti-VEGF intra-vitreal injections e.g. ranibizumab (lucentis)-a monoclonal Ab that binds to all isoforms of VEGF-A so VEGF unable to bind to its receptors, and aflibercept (eylea), and bevacizumab (avastin)
photodynamic therapy with verteporfin-this is injected and activated by an argon laser beam, and once activated causes vessel thrombosis but spares the photoreceptors
thermal laser photocoagulation

Question 27

complications of anti-VEGF injections for wet AMD?

Answer 27

INFECTION-endophthalmitis-severe inflammation of eyeball: anterior and/or posterior chambers, so patients must take Abx
stroke
vitreous floaters
raised IOP

Question 28

how is ranibizumab administered in treatment of wet AMD?

Answer 28

0.5mg monthly intra-vitreal injection for 3 months, followed by monthly follow ups and treatment as required

Question 29

NICE conditions for ranibizumab treatment of wet AMD?

Answer 29

best-corrected visual acuity between 6/12 and 6/96
no permanent damage to central fovea
lesion size less than or equal to 12 disc areas in greatest linear dimension
evidence of recent presumed disease progression
cost of drug beyond 14 injections met by manufacturer

Question 30

most common investigation for AMD diagnosis?

Answer 30

OCT-optical coherence tomography

*looking closely for sub-retinal fluid (contrast to intra-retinal fluid being investigated for in diabetic retinopathy.)

Question 31

AMD investigations?

Answer 31

fundoscopy
fundus fluorescein angiography (FFA)-fluorescein dye injected into vein on back of hand and travels into retinal vessels, can observe choroidal capillary leakage producing stain indicating choridal neovascularisation in wet AMD, test used to assess suitability for treatment
OCT

Question 32

examples of what can be provided to aid vision in patients with dry AMD?

Answer 32

r/f to low visual aid clinic-will provide practical training and coping strategies and help with provision of:
magnifiers for near vision, telescopes for distance vision
large print books, talking tapes
gadgets to help with household tasks

Question 33

why might wet AMD patients suffer visual hallucinations?

Answer 33

Charles Bonnet syndrome:

existing photoreceptor cells produce abnormal signals*

Question 34

What might be used to assess vision of a patient with dry AMD quickly to determine if progressed to wet AMD?

Answer 34

Amsler grid

line wavyness or a central scotoma indicates wet AMD, and the need for urgent clinic r/f

Question 35

4 pathological changes occurring in AMD?

Answer 35

drusen formation
RPE abnormalities-hypo or hyperpigmenetation
geographic atrophy- RPE partial or complete depigmentation (atrophy) occurring with breakdown of light sensitive cells in the macula
neovascularisation-causes distortion and scarring of the retina, sub-retinal space invasion from choroid through Bruch’s membrane. some arise in macular retina, and the 2 can make contact forming chorio-retinal anastomoses.

Question 36

how does the risk of developing new onset AMD change when patients stop smoking?

Answer 36

smoking is the main modifiable RF

those who have stopped smoking for 20yrs or more have same risk of new onset AMD as non-smokers

Question 37

complications of AMD?

Answer 37

visual impairment and blindness
visual impairment complications:
depression
visual hallucinations-Charles Bonnet syndrome
falls and fractures
reduced mobility and AODL
reduced QOL

Question 38

conditions causing similar retinal signs to those seen in AMD?

Answer 38

diabetic maculopathy.
macular degeneration associated with high myopia (short-sightedness greater than -6 dioptres) - atrophic or neovascular changes usually occur at a younger age than AMD, and have a different natural history and response to treatment.
rare inflammatory syndromes causing choroidal neovascularization (for example presumed ocular histoplasmosis, punctate inner choroidopathy, multifocal inner choroidopathy). There are usually signs of active or previous uveitis that would not be present in AMD.
central serous retinopathy.
macular telangiectasia.
pattern dystrophy - these macular dystrophies may be inherited and are often symmetrical.
macular hole.

Question 39

what can slit lamp investigation identify in AMD?

Answer 39

drusen
pigmentary, exudative, haemorrhagic or atrophic changes affecting the macula
and can detect retinal thickening or elevation due to wet/neovascular AMD

Question 40

how many people with wet AMD can expect their vision to improve after intra vitreal injection anti-VEGF treatment?

Answer 40

1/3
most will retain vision at current level

about 10% will not respond

Question 41

features of laser photocoagulation for wet AMD?

Answer 41

treatment to destroy developing new blood vessels
patients will develop permanent scotoma-black or grey patch in their vision
lesions must not be very close to the fovea or risk of severe visual loss from laser damage of development of laser scar

Question 42

how does photodynamic therapy work in wet AMD treatment?

Answer 42

IV verteporfin-taken up selectively by proliferating vascular endothelial cells, and subsequent activation by laser produces damaged
and laser causes thrombotic occlusion of abnormally leaky vessels

Question 43

health balanced diet rich in leafy green vegetables and fresh fruit is good for what in AMD?

Answer 43

improving concentration of macular pigment in fundus