AMD-age-related macular degeneration Flashcards
RFs for AMD?
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
define drusen
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.
what part of the eye is affected in AMD?
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
how is AMD classified?
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
what is early AMD?
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
what is intermediate AMD?
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%
what is advanced dry AMD?
geographic atrophy (depigmentation of RPE) and drusen extension to involve the FOVEA
central and paracentral macula degeneration
confluent drusen
non-exudative
gradual visual loss
what is advanced wet AMD?
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
common complaint of patients presenting with advanced dry AMD?
reading difficulty, progressing from small words to larger text
complaint of central vision deterioration if bilateral geographic atrophy involving the fovea
what mediates the progression of dry AMD to wet AMD?
VEGF, specifically VEGF-A
risk to other eye if patient presents with wet AMD affecting 1 eye?
50% likelihood patient will develop wet AMD in the other eye within 5 years
how does the presence of soft drusen cause a problem?
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
what can cause the RPE pigmentary changes that start in early AMD, and why are these changes a problem?
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.
what a major RFs for AMD progression?
numerous large hard and soft drusen in the macula, and extensive retinal pigment irregularities or de-pigmentation
what is seen over the macula on fundoscopy in advanced wet AMD?
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.
what conditions other than AMD can cause a painless loss of vision?
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
how does foveal atrophy appear in advanced dry AMD on fundoscopy?
visible choroidal blood vessels
symptoms of dry AMD?
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
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?
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
VEGF-A role in wet AMD?
drives the progression of wet AMD, stimulating new abnormal choroidal blood vessel growth and leakage
what mediates VEGF release in wet AMD? *
RPE oxidative stress
3 different classifications of wet AMD?
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
RFs for development of wet AMD in other eye after development in 1?
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%
management of patients with dry AMD?
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.
presentation of wet AMD?
sudden painless loss of vision over days-mnths with: loss of visual acuity reduced contrast sensitivity metamorphopsia central scotoma
treatment options for wet AMD?
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
complications of anti-VEGF injections for wet AMD?
INFECTION-endophthalmitis-severe inflammation of eyeball: anterior and/or posterior chambers, so patients must take Abx
stroke
vitreous floaters
raised IOP
how is ranibizumab administered in treatment of wet AMD?
0.5mg monthly intra-vitreal injection for 3 months, followed by monthly follow ups and treatment as required
NICE conditions for ranibizumab treatment of wet AMD?
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
most common investigation for AMD diagnosis?
OCT-optical coherence tomography
*looking closely for sub-retinal fluid (contrast to intra-retinal fluid being investigated for in diabetic retinopathy.)
AMD investigations?
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
examples of what can be provided to aid vision in patients with dry AMD?
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
why might wet AMD patients suffer visual hallucinations?
Charles Bonnet syndrome:
existing photoreceptor cells produce abnormal signals*
What might be used to assess vision of a patient with dry AMD quickly to determine if progressed to wet AMD?
Amsler grid
line wavyness or a central scotoma indicates wet AMD, and the need for urgent clinic r/f
4 pathological changes occurring in AMD?
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.
how does the risk of developing new onset AMD change when patients stop smoking?
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
complications of AMD?
visual impairment and blindness visual impairment complications: depression visual hallucinations-Charles Bonnet syndrome falls and fractures reduced mobility and AODL reduced QOL
conditions causing similar retinal signs to those seen in AMD?
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.
what can slit lamp investigation identify in AMD?
drusen
pigmentary, exudative, haemorrhagic or atrophic changes affecting the macula
and can detect retinal thickening or elevation due to wet/neovascular AMD
how many people with wet AMD can expect their vision to improve after intra vitreal injection anti-VEGF treatment?
1/3
most will retain vision at current level
about 10% will not respond
features of laser photocoagulation for wet AMD?
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
how does photodynamic therapy work in wet AMD treatment?
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
health balanced diet rich in leafy green vegetables and fresh fruit is good for what in AMD?
improving concentration of macular pigment in fundus
