age-related macular degeneration Flashcards
risk factors for AMD
race - caucasian
age - increases with age
medical history - HTN, CVS disease, dyslipidaemia, diabetes mellitus
personal history - smoking
FH - complement factor H, gene variant Y402H
ocular characteristics
- light iris
- hyperopia
what is complement factor H
does the inflammatory part esp for the macular degeneration part
what is macula
5.5 mm in diameter with the fovea at its centre
what is the fovea
metabollically active - cone cells
what is RPE
provide nutrition and to metabolise the end products of the visual cycle
act as a choroid and retina barrier
Retinal pigmented cells rol
- outer blood retinal barrier - pumps put metabolic waste products
- facilitates photoreceptor turnover
- absorbs stray light
- storage, met and transport of Vit A in visual cycle
drusen?
• Undigested cellular debris from degeneration
of RPE cells as part of normal ageing process
accumulates as ‘drusen’
– Yellow/white material that builds up between the
RPE and Bruch’s membrane
yellow deposits
hallmark of dry ARMD
non degradable products from photoreceptors accumulate in the RPE - loads become toxic
RPE alterations are
hyperplasia - pigment clumping
atrophy
what is hard drusen
well defined
less than half a retinal vein width in diameter
little increased risk of visual loss
subretinal
what is soft drusen
bigger
less distinct
get bigger and coalesce into RPE - ‘‘drusenoid RPE detachment’
‘drusenoid RPE detachment” ?
soft drusen lift the RPE away from the Bruch’s membrane
- hypoxic state
- inflammation
what are the advanced stages of dry AMD
- confluent drusen
- central and paracentral degeneration of the macula
- atrophy og choriocapillaris, RPE and photoreceptors
end stage of dry AMD
geographic atrophy (GA) is a term used to describe advanced map-like area of atrophy (punched out) extending to foveal centre
differentiate between dry and wet
dry - atrophic
wet - neovasculairsation due to VEGF leaking ECF and blood whichc causes destructive scarring and visual loss
symptoms of AMD
- a reduction in visual acuity, particularly for near field objects
- difficulties in dark adaptation with an overall deterioration in vision at night
- fluctuations in visual disturbance which may vary significantly from day to day
- they may also suffer from photopsia, (a perception of flickering or flashing lights), and glare around objects
early - asymptomatic
- loss of visual acuity
- loss of contrast sensitivity - driving
- abnormal dark adaptation
progression of dry AMD
- gradual insidious vision loss over months/years
- mild occasional metamorphosia - change
- central/paracentral scotomas - gaps
classification of AMD
Early AMD
- non-exudative
- few medium sized drusen
- pigmentary abnormalities
- alterations to the RPE
intermediate AMD
- large druse/numerous
- geographical atrophy - does not extend to macular centre
late AMD - neovascularisation, exudative
Pathogenesis of AMD
VEGF A- abnormal vessels to grow and leak
pathophysiology of AMD
drusen
inflammation
monocytes/macrophages
RPE oxidative stress
inflammation increase in VEGF-A
inappropriate vessel growth
exudation and haemorrhage
disciform scar formation
disciform scar?
seen in wet AMD
its when scar tissue replaces the retinal tissue
represents the portion of the macula that has been permanently damaged
will cause a blind spot (scotoma) in the field of vision
classification of wet AMD
based in location in relation to fovea
- subfoveal
- juxtafoveal
- extrafoveal
what Ix we do to look for new vessels in eye
fundus fluorescein angiogram classification
risk factors to develop wet AMD in the second eye
- more than five drusen
- large (soft or confluent drusen)
- pigment clumping in the RPE
- systemic HTN
symptoms of wet AMD
- decrease in visual acuity
- decreased contrast sensitivity
- metamorphosia
- central scotoma
what is charles Bonnet syndrome
visual hallucinations - common in with wet AMD visual loss
Diagnosis of AMD
- patient history
- best corrected visual acuity
- amsler grid - look for distortion
- fundoscopy
- optical coherence tomography - subretinal spaces
- fluorescein angiogrpahy
test for AMD and other macular diseases
amsler grid
fundoscopy findings for dry AMD
- drusen
- hypo/hyperpigmentation of the RPE
- atrophy at the macula
fundoscopy findings for wet AMD
- exudate
- blood
- elevation of retina due to fluid
- cystic oedema of the sensory retina overlying the CNV
- advanced bug haem and exudation and fibrosis
treatment for dry AMD
stop smoking
diet advice
occular nutritional supplememtns - zinc and antioxidant vitamins
treatment for wet AMD
Photodynamic theraphy with verteperfin
Anti-VEGF therapy
- bevacizumab
- ranibizumab
what is AMD
degeneration of retinal photoreceptors that results in the formation of drusen which can be seen on fundoscopy and retinal photography.
degeneration of the central retina bilateral
what is dry AMD
characterised by drusen - yellow round spots in Bruch’s membrane
what is wet AMD
characterised by choroidal neovascularisation.
Leakage of serous fluid and blood can subsequently result in a rapid loss of vision.
Carries worst prognosis
signs of AMD
- distortion of line perception may be noted on Amsler grid testing
- fundoscopy reveals the presence of drusen, yellow areas of pigment deposition in the macular area, which may become confluent in late disease to form a macular scar.
- in wet ARMD well demarcated red patches may be seen which represent intra-retinal or sub-retinal fluid leakage or haemorrhage.
Ix for AMD
- slit-lamp microscopy is the initial investigation of choice, to identify any pigmentary, exudative or haemorrhagic changes affecting the retina which may identify the presence of ARMD. This is usually accompanied by colour fundus photography to provide a baseline against which changes can be identified over time.
- fluorescein angiography is utilised if neovascular ARMD is suspected, as this can guide intervention with anti-VEGF therapy. This may be complemented with indocyanine green angiography to visualise any changes in the choroidal circulation.
- ocular coherence tomography is used to visualise the retina in three dimensions, because it can reveal areas of disease which aren’t visible using microscopy alone.
treatment for AMRD
the AREDS trial examined the treatment of dry ARMD in 3640 subjects. It showed that a combination of zinc with anti-oxidant vitamins A,C and E reduced progression of the disease by around one third. Patients with more extensive drusen seemed to benefit most from the intervention. Treatment is therefore recommended in patients with at least moderate category dry ARMD.
Vascular endothelial growth factor, (VEGF) is a potent mitogen and drives increased vascular permeability in patients with wet ARMD. A number of trials have shown that use of anti-VEGF agents can limit progression of wet ARMD and stabilise or reverse visual loss. Evidence suggests that they should be instituted within the first two months of diagnosis of wet ARMD if possible. Examples of anti-VEGF agents include ranibizumab, bevacizumab and pegaptanib,. The agents are usually administered by 4 weekly injection.
Laser photocoagulation does slow progression of ARMD where there is new vessel formation, although there is a risk of acute visual loss after treatment, which may be increased in patients with sub-foveal ARMD. For this reason anti-VEGF therapies are usually preferred.
contradictions for antioxidant dietary supplements
Beta-carotene has been found to increase the risk of lung cancer and hence antioxidant dietary supplements are not recommended for smoker
major risk factors of dry AMD
large hard and soft drusen in the macula
plus extensive pigment irregularities or de-pigmentation
what is the role of macula
specialised acuity of vision
high-resolution
central vision
what is the bruchs membrane
separates the RPE from choroid
pathophysiology of ARMD
when RPE secretions cant get into the bruchs membrane they start accumulating
RPE and photoreceptors cell layer ischaemia and atrophy
patients typically present with
subacute onset of visual loss with:
- a reduction in visual acuity, particularly for near field objects
- difficulties in dark adaptation with an overall deterioration in vision at night
- fluctuations in visual disturbance which may vary significantly from day to day
- they may also suffer from photopsia, (a perception of flickering or flashing lights), and glare around objects
