Age related macular degeneration: classification, risk factors and clinical investigation Flashcards
what is the outcome of end stage AMD in wet and dry
complete central scotoma
what is visual impairment of patients with AMD associated with
with increased risk falls and social isolation and problems performing tasks, and recognising faces
Prevalence of depression much higher in VI older adults
which part of the retina is affected by AMD and which 4 structures in particular
outer retina is affected
AMD primarily affects:
- Choroidal circulation
- Bruch’s membrane
- RPE
- Photoreceptors
what is the clinical classification of AMD currently used
VA almost unaffected. Often asymptomatic
No apparent ageing changes:
- No drusen
- No AMD pigmentary abnormalities
Normal ageing changes:
- Druplets (small drusen ≤ 63 µm)
- No AMD pigmentary abnormalities
Early AMD:
- Medium drusen >63 µm ≤ 125 µm
- No AMD pigmentary abnormalities
Intermediate AMD:
- Large drusen >125 µm and/or
- AMD pigmentary abnormalities
And
Central visual loss gradual (GA) or rapid (nAMD)
Late AMD:
Neovascular AMD (wet AMD)
and/or
Geographic Atrophy (dry AMD)
which 4 retinal signs = VA almost unaffected. Often asymptomatic
No apparent ageing changes
Normal ageing changes
Early AMD
Intermediate AMD
what are the 2 signs of normal ageing changes
Druplets (small drusen ≤ 63 µm)
No AMD pigmentary abnormalities
what are the 2 signs of early AMD
Medium drusen >63 µm ≤ 125 µm
No AMD pigmentary abnormalities
what are the 2 signs of intermediate AMD
Large drusen >125 µm and/or
AMD pigmentary abnormalities
what are druplets, what size are they and when is it seen
small size version of hard drusen
≤ 63 µm
seen in normal ageing changes
what are eyes that are classified as intermediate AMD at higher risk of
of getting late AMD
these patients can progress to wet AMD or geographic AMD or both together
what 2 things can AMD pigmentary abnormalities be referred to as
hyperpigmention: small clumps of pigment accumulation
or
hypo pigmentation: small clumps of pigment loss
what is drusen
Localised yellow/white deposits between basement membrane of RPE and Bruch’s membrane (outer layer of the retina)
They are waste material that the RPE can’t process from e.g. the photoreceptors
what are the clinical features of Early / Int AMD
- Hard drusen/druplets which are tiny yellow/white lesions (less than 63 um)
- in small numbers, part of normal ageing process
- when numerous, it is a risk factor for soft drusen and AMD
what is numerous hard drusen/druplets as seen in early/int AMD a risk factor for
soft drusen and AMD
which type of drusen is a hallmark sign/feature of AMD and how do they look
Soft drusen
larger in size
distinct or indistinct
may coalesce to form confluent drusen
what 2 clinical features is associated with a increased risk for progression onto advanced AMD
- Larger, increased no., and more confluent drusen
- Pigmentary changes
what are the clinical features of intermediate AMD
- focal hyper pigmentation
seen in eyes with or without soft drusen - focal hypopigmentation
seen as small patches of mottled pigment
what feature of AMD is seen with or without soft drusen
focal hyper pigmentation in intermediate AMD
what 3 things can focal hyperpigmenation be caused by
Increased melanin content of RPE
RPE cell profileration
RPE cell migration
what does the appearance of focal hyper pigmentation look like in flourescein angiography
as a dark patch, blocking the fluorescence of the choroidal circulation beneath
what 3 things can focal hypo pigmentation be caused by
Reduced melanin content of RPE cells
RPE cell atrophy
RPE layer thinning
what are the 5 clinical features of late AMD geographic atrophy
Sharply delineated, roughly round area >175µm of hypo or depigmentation, or apparent absence/atrophy of RPE
Increased visibility underlying choroidal circulation
Area of RPE death leads to photoreceptors loss and gradually the other retinal layers, causing visual loss (absolute scotoma)
Often starts in parafovea, sparing fovea until later (so first has scotoma around central vision)
Vision loss is gradual (as the retinal layers gradually die)
what is the clinical features of choroidal neovascularisation
Growth of new blood vessels from choroid to proliferate beneath RPE, or in sub retinal space (between RPE and retina)
May be seen as green/ grey lesion on fundus photograph
Fragile vessels mean sub- or intraretinal haemorrhages, hard exudates, intra-retinal fluid, sub-retinal fluid or pigment epithelial detachment common
Repeated leakage blood, serum and lipid stimulates formation of untreatable disciform scar
how will the growth of the new blood vessels from the choroid that proliferate beneath RPE, or in sub retinal space be seen as on a fund photograph
as green/grey lesions
what are the first symptoms of CNV wet AMD
recent onset distortion and deterioration of vision
therefore do an amsler test
what 5 things can commonly happen from the fragile vessels in wet AMD CNV
- sub- or intraretinal haemorrhages
- hard exudates
- intra-retinal fluid
- sub-retinal fluid
or - pigment epithelial detachment
in wet AMD what stimulates the formation of the untreatable disciform scar and what consequence does this lead to
Repeated leakage of blood, serum and lipid from a neovascular membrane which stimulates scar formation
leading to a absolute central scotoma
what is the speed to vision loss in wet AMD and why
Vision loss may be rapid in AMD
due to exudates and haemorrhage, secondary cell death, and formation of scar tissue from the disciform form scar
what is the progression of CNV caused by
by hypoxia/inflammation in retina, leading to imbalance of inhibitory/stimulatory growth factors (e.g. PEDF, VEGF)
what does the untreated progression of CNV lead to
and what is there a high risk of with CNV
Untreated 1 line logMAR acuity loss in 3 months, 3 lines by 1 year
High risk in second eye in px with unilateral CNV - incidence in fellow eye of 12% by 12 months
in end stage CNV, where does the pigment epithelial detachment occur in the retina
which 2 different outcomes can it have
what does it usually leave behind
how much if associated with CNV
Between basement membrane of RPE and Bruch’s Membrane
May flatten over time, but may tear (in approx 1 in 10)
Usually leaves area of atrophy or sub retinal fibrosis
> 80% associated with CNV
what is a serous pigment epithelial detachment as seen in end stage CNV
how can it be viewed and how does it show up
shows elevation with accumulation of fluid beneath
seen with OCT - bright band is corresponding to RPE and fluid beneath seen as a dark region due to its low relative optical reflectivity
and dome shaped elevation seen in volk
apart from the leakage of new blood vessels causing the disciform scar and subsequent pigment epithelial detachment in CNV, what else can cause this
just having drusen
as this can disrupt the blood flow hence causing detachment of the RPE
(so theres not always blood vessels if theres PED)
what are the 2 theories/mechanisms of the pathogenesis of AMD down to
- oxidative damage
- inflammation
how is the mechanism of oxidative damage thought to be a part of the pathogenesis of AMD
Retina prone to oxidative damage
RPE is unable to break down products of oxidation accumulate (the lipids, carbohydrates and proteins) in RPE and Bruch’s membrane
so the oxidative damage causes changes to the molecules in the retina and this causes it to change their structure
how is the mechanism of inflammation thought to be part of the pathogenesis of AMD
Inflammatory cells e.g. macrophages found in eyes with drusen, CNV, RPE atrophy
Strong association between AMD and polymorphisms of CFH gene and other genes involves in immune response
so the waste material triggers off an inflammatory response and the long term low level of inflammation is causing damage to the retina = another mechanism for AMD
what is the biggest risk factor for AMD
age - which is not modifiable
list the 6 main risk factors of AMD
age ethnicity genetics smoking light exposure diet
what is the biggest modifiable risk factor of AMD
smoking
how is ethnicity a risk factor for AMD
Lower risk of (late) AMD in Black than White group
Prevalence similar in White and Asian groups
why is there found to be a lower risk factor of AMD in black than white people
because of the melanin having a protective affect from the oxidative/light damage
how is genetics a risk factor for AMD
Monozygotic twins have very high concordance for AMD, significantly greater than for dizygotic twins
First degree relatives with AMD provide up to 6–12 times higher risk than in the general population
by how much is smoking a risk factor for AMD
current smokers 4x risk late AMD compared to never smokers
After 10 years ex-smokers no more likely to develop AMD than never smokers (i.e. if quit smoking for 10 years)
which theory is the risk factor of light exposure of AMD based on
and how is this
based on the oxidative damage theory
Increased light exposure (esp blue light) throughout life has been associated with increased risk AMD
what improvements in diet, which is a risk factor for AMD, s thought to reduce the chances of getting AMD
Possible protective effect increased antioxidant intake
Reduced progression of AMD with high intake vitamins A, C, E and zinc (AREDS study), also if vitamin A (beta carotene) is exchanged for lutein and zeaxanthin (AREDS 2)
Protective effect increased omega 3 fatty acid and oily fish intake. Not supported by AREDS2
Protective effect increased xanthophyll (lutein, zeaxanthin) intake (green leafy vegetables e.g. kale, spinach, eggs). Weak evidence from AREDS2
why has the AREDS 2 study suggested that vitamin A should be replaced by lutein and zeaxanthin in a patients diet
because vitamin A is dangerous for smokers as it can cause a higher risk of cancer
list the 5 systemic conditions which seem to predispose towards an increased risk of AMD
Cardiovascular disease Hypertension High Body mass index (BMI) Diabetes Higher plasma fibrinogen
which gender is at a higher risk of having AMD
females
when carrying out a clinical investigation of AMD, what 5 things do you want to include in your basic evaluation
History and symptoms Refraction Visual acuity measurement (distance and near) Amsler chart Fundus examination
what 2 questions do you want to ask a older patient without AMD in your H and S
Family history of AMD?
History of smoking?
as these are risk factors
what 5 questions do you want to ask a patient with AMD in your H and S and why
asking to check for progression
(Worsened) symptoms distorted vision, or reduced vision?
Since when? Sudden onset? (treatment implications)
Both eyes/one eye? (in patient with unilateral AMD, need to ask if they have noticed changes in good eye)
Increased difficulty with tasks e.g. reading, cooking, mobility, shopping? (refer to social services)
Taking any dietary supplements? (if not, then advise then to)
when carrying out refraction and best corrected VA distance and near
which chart should you use
when is va not and is affected by AMD
Use ETDRS logMAR chart if possible
VA is relatively unaffected by early AMD, but may be substantially reduced by advanced AMD
give 3 reasons for why measuring VA in your clinical investigation of AMD is important
Measure of disease progression
NICE guidelines for seeing is suitable for Lucentis treatment (VA 6/12-6/96)
Guidelines for registration (severely) sight impaired
- if va less than 6/96 - still refer but not as urgent as cannot treat with lucentis
- if long standing AMD - should still refer if theyre not registered as sight/severely sight impaired
if a patient with AMD va is fine, what else may determine if a patient might benefit from a low vision assessment/advice advice on practical solutions to help with VI
the patient’s contrast sensitivity
can give advice on improving lighting around the house or high contrast gadgets
what about driving standards do you need to consider when assessing a patient with AMD
and when must you inform the DVLA for group 1 and groups 2 drivers
Ensure spectacles enable 6/12 binocularly
Must inform DVLA if:
AMD in one eye (bus, coach, lorry drivers)
AMD in both eyes (car drivers)
must tell the DVLA of AMD if it is still good enough to drive, as can monitor it and the DVLA can get information from the optom about the patient’s level of vision
what is the purpose of using an amsler chart on a px with AMD or suspect AMD
what may the amsler chart have the potential to do
therefore what is it more useful for
what is the instructions of the amsler chart very important for
To plot areas of distortion and scotomas which may indicate the presence of underlying neovascular changes
Potential to miss scotoma (‘filling in’ effect)
More useful for detecting distortions associated with the conversion to wet AMD
Instructions are very important for self-monitoring using Amsler chart
why is monitoring a patient who already has AMD with an amsler chart useful
Monitoring scotomatous areas is also useful in patients with established AMD and vision loss, as it helps the practitioner to give guidance on maximising the use of residual vision, for example using an eccentric viewing strategy
what is the best way to carry out a fundus examination when investigating AMD
Dilated indirect fundus examination essential e.g. Volk
Stereoscopic view needed to detect presence of sub retinal fluid (an elevated area of retina)
Fundus photography and OCT can be very useful
list 5 further functionals tests you will want to carry out alongside your main clinical tests in investigating AMD
- contrast sensitivity
- reading speed/accuracy
- macular photostress test
- colour vision
- microperimetry
what test should be used to measure contrast sensitivity
why is it useful to carry this out
what is contrast strongly related to
Pelli Robson
Useful in people with established AMD (i.e. not used for diagnosis)
Strongly related to performance e.g. reading with magnifier, recognising faces, driving, mobility
Practical advice can help those with poor C.S. e.g. improve lighting in house etc
why is reading speed/accuracy measured in AMD investigation as a functional test
because the patient may be able to read N5, but with difficulty and taking a long time = an implication for referring for an LV assessment
how is the macular photostress test carried out as a functional test for investigating AMD
how is the results different in someone with AMD
30 secs bleach with ophthalmoscope
>60 secs to recover to within 1 line of baseline VA = abnormal
Px with AMD = their dark adaptation is impaired so takes longer to recover from bright light
how is colour vision affected in someone with AMD and so how should it be measured in these patients
Primarily B/Y in early AMD, therefore Ishihara not appropriate
New computer-based tests available e.g CAD test
colour vision is not a good diagnostic test for AMD as many factors can affect colour vision with age
which 3 imaging techniques is useful in investigating AMD
- fundus photography
- optical coherence tomography
- flourescein angiography
what is a advantage and disadvantage of using fundus photography is investigating AMD
useful for monitoring progression and for recording the presence of haemorrhage and exudates
but non-stereoscopic cameras will not provide information on retinal elevation
how does drusen appear in an OCT image
White blobs
it is lumps of waste material pushing the RPE up
how does intraretinal fluid appear in an OCT image
large dark ‘bubbles’ in the inner retina
due to lack of reflection of the light
how does sub retinal fluid appear in an OCT image
the dark area is beneath the retina, but inner to the RPE
how does a Choroidal Neovascular Membrane appear in an OCT image
an area of new vessel growth shown as a lump under the RPE (this causes sub retinal fluid)
how does geographic atrophy appear in fluorescein angiography
enhanced visibility of the underlying glow from the choroidal circulation
how does geographic atrophy appear in an OCT image
The OCT light goes right through, described as a window effect (as the laser is going through the RPE and illuminating the choroid behind)
when the RPE is not present to absorb/reflect the light, it is able to penetrate more deeply into the underlying choroidal vasculature
how does geographic atrophy appear in fundus photography
can see the choroidal blood vessels more easily as theres no RPE to mask them
describe how a flourescein angiography shows up in 2 types of wet AMD
CNV membrane may be classic or occult
Classic: well defined on FFA, becoming large and indistinct in late stage due to leakage. Caused by CNV between RPE and retina
Occult: is less well defined, and less prone to leakage out into it’s surroundings. Caused by CNV between RPE and Bruch’s
= growth of new blood vessels lower down into the retina