ARMD

Question 1

Describe the layers of the retina?

Answer 1

• Differs from anatomy at fovea and macula
• Most posterior (from choroid) to anterior:
  o Choroid provides some blood flow to retinal structures
  o Retinal Pigment Epithelium (RPE) – 2 main functions:
   To provide vitamin A to photoreceptors
   Heavily pigmented to prevent scatter of light from photons (which are not incident on photoreceptors themselves
  o Rods/Cones:
   Away from macula have mixture of rods & cones with more rods further out in periphery and more cones present centrally on retina
  o Outer nuclear layer:
   Contains cell bodies of horizontal and bipolar cells
   When photon hits one of rods or cones it causes a transformation in the opsin proteins within the rods/cones – start of the nerve impulse travelling from rods and cones
• Start of the journey for photons creating an impulse which can then be decoded within brain as visual signal
   Once opsin has been transformed and signal transmits to horizontal and bipolar cells – first to cell bodies
  o Outer plexiform layer:
   Contains axons of horizontal and bipolar cells
  o Inner nuclear layer:
   Contains amacrine cells
  o Inner plexiform layer:
   Contains axons of bipolar and amacrine cells – as they then go onto synapse with ganglion cells
  o Ganglion cell layer:
   Contains ganglion cells
  o Retinal nerve fibre layer:
   Takes nerve fibres (axons of ganglion cells) to optic nerve
  o Inner limiting membrane:
   Most anterior structure in retina

Question 2

Describe the macula?

Answer 2

• One of key differences between macula and peripheral retina is proportion of cone cells to rod cells
• In periphery, much higher proportion of rod cells
• In central macula, densely populated area in central 0.15mm of retina (foveola) of cone cells
• As move away from central foveola, start to get a sharp decline in number of cone cells
  o & at same time, an increase in number of rod cells
• Trend continues out into far periphery
• In central foveola, absolutely no rod cells – only cone cells in that area
  o Cones important for detailed and colour vision
  Macula is AVASCULAR -> supplied solely by choroid (another reason for excellent vision as retinal BVs do not disrupt vision in this area at all)

Question 3

Describe the fovea?

Answer 3

• Distribution of photoreceptors in macula is quite different to surrounding retinal tissues
• Other differences too
• Macula lutea extends across from fovea into parafoveal region - ~2.5mm in diameter
• Fovea is ~1.5mm in diameter – encircling central foveola
  o Foveal pit of foveola is 0.15mm in diameter
  o Foveal pit quite different to rest of retina and even rest of macula – as it is almost devoid of the other layers of the retina aside from cone photoreceptors & RPE
  o At edge of foveal pit, start to see other cell layers appearing – some cell bodies (horizontal and bipolar cells) and some amacrine cell processes
• As go further out into macula area - ~0.35mm encircling foveola, start to see the first ganglion cell bodies

Question 4

Describe the foveola/foveal pit?

Answer 4

• Devoid of a lot of other layers you would expect in surrounding retina
• Concentrated density of cone photoreceptors – allows for really detailed vision and good colour vision in this area
• No rods
• When look at fovea, cone cells are extremely well packed – packed in hexagonal mosaic
  o Allows for detailed vision with high resolution and detailed colour vision

Question 5

Describe the fovea cellular structure?

Answer 5

• How the cone photoreceptors are packed within central foveola
• Regimented hexagonal pattern
• Majority of cone photoreceptors in this area are red and green photoreceptors
• Slightly larger cone photoreceptors highlighted with arrows (IN IMAGE) are the blue cone photoreceptors
• Allows for extremely detailed vision
  o High resolution of images which are projected onto fovea
  o Detailed colour vision

Question 6

What are the key features of the macula?

Answer 6

• Densely packed cone photoreceptors
• An absence of rods at the fovea
  o Rods are more important for night vision and not as important for detailed vision
• Fovea is avascular and in this area the retina is supplied with oxygen which diffuses from the choroid to the foveal retina
• Fovea 1.5mm across
• Foveola (foveal pit) 0.15mm diameter – cones most densely packed in this area
• Avascular zone (supplied purely by choroid – centred on foveola) 0.5mm diameter
• Half of the retinal nerves in the optic nerve serve the fovea
• Retina is thinnest at the fovea as retinal cell bodies and structures are displaced concentrically to the edge of the fovea to allow

Question 7

What is AMD and how many people have it in UK?

Answer 7

• AMD: long-term degenerative condition
• Leading cause of visual impairment in the UK
• ~600,000 people diagnosed (UK)
• AMD is relevant to optometrists as loss of sight can have impact on quality of life and emotional health

Question 8

What are the statistics for AMD (50 yos, 65 yos, 80 yos)?

Answer 8

• Prevalence estimates for UK by age groups (all types of AMD):
• 50+ y: 2.4 %
• 65+ y: 4.8 %
• 80+ y: 12.2 %
• Number of people with AMD predicted to rise
• 26,000 new cases each year (NICE estimate)
• Key reasons: aging population, increase in life expectancy
• Workload implications for HES

Question 9

How many people in UK are visually impaired from AMD?

Answer 9

• Visual impairment (6/18 or worse) from AMD affects
  o 4% of UK population > 75 years
  o 14% of UK population > 90 years
  o 1.6% have VA < 6/60 in population > 75 years
• ^Bilateral VA

Question 10

What are the Risk Factors for AMD from Nice Guidance?

Answer 10

• Diet low in omega 3 and 6 and carotenoids and minerals are a risk of AMD
• Lack of exercise
• Smoking – biggest modifiable risk factor
• Older age
• Hypertension
• Family history of AMD
• BMI of 30 kg/m2 or higher
• Presence of AMD in the other eye – monitor these pxs really carefully
• High fat diet

Question 11

What is dry AMD? Is it more or less common? How fast does it progress?

Answer 11

• More common presentation
• Slowly progressing
• No sudden loss of vision
• Managed by Optometrists in most cases
  Larger drusen more associated with disease progression

Question 13

Describe NICE Classification of dry AMD (normal eyes, early AMD (low, medium, high risk of progression), late AMD)

Answer 13

• Normal eyes
  o No signs of AMD.
  o Small (hard) drusen (<63 micrometres (1/2 a vein width (look at central vein))) only.
• Early AMD
  o Low risk of progression:
   Medium drusen (≥63 but <125 micrometres), or
   Pigmentary abnormalities.
  o Medium risk of progression:
   Large drusen (≥125 micrometres), or
   Reticular drusen, or
   Medium drusen with pigmentary abnormalities.
  o High risk of progression:
   Large drusen (≥125 micrometres) with pigmentary abnormalities, or
   Reticular drusen with pigmentary abnormalities, or
   Vitelliform lesion without significant visual loss (best-corrected acuity better than 6/18), or
   Atrophy <175 micrometres and not involving the fovea.
• Late AMD (dry)
  o Geographic atrophy (in the absence of neovascular AMD).
  o Significant visual loss (6/18 or worse) associated with:
   Dense or confluent drusen, or
   Advanced pigmentary changes and/or atrophy, or
   Vitelliform lesion.
  63um is half a vein width in diameter

Question 13

Describe reticular drusen (dry AMD)?

Answer 13

• Drusen are sub retinal pigment epithelium deposits of extracellular debris composed of lipids and proteins which sit just below the RPE, or between the RPE and bruchs membrane
• Reticular drusen are also known as pseudo-drusen or subretinal drusenoid deposits. Contrary to the drusen which lie below the retinal pigment epithelium (RPE), reticular drusen are located superficial to the RPE. They are yellowish subretinal lesions arranged in a network and indicate a greater risk of AMD progression
  Due to position, reticular drusen are much more strongly linked with progression of RPE

Question 14

Describe vitelliform lesion (dry AMD)?

Answer 14

• Accumulation of lipofuscin within the subretinal space
• Lipofuscin and extracellular deposit accumulation in drusen is below the RPE. Lipofuscin is is a heterogeneous material composed of a mixture of lipids, proteins, and different fluorescent compounds, the main fluorophore of which has recently been identified as a derivative of vitamin A
• Clinical course of patient 3.
  o (A) Vitelliform lesion in the left eye.
  o (B) FA showing staining and leakage of the vitelliform lesion without evidence of CNV.
  o (C) Vitelliform lesion in the left eye with associated SRF. Given the appearance of VM, the patient was observed without injection. Two years later
  o (D), the vitelliform lesion coalesced and the SRF resolved spontaneously.
  o (E) Five years after from presentation, the vitelliform lesion spontaneously collapsed

Question 15

Describe atrophy (dry AMD)?

Answer 15

• In early stages, may just have small patches of atrophy
• Geographic atrophy - loss of cells in the fovea - RPE and outer retina (rods and cones are lost)
• Geographic atrophy - Complete loss or RPE and outer retina if is at least 250 microns wide (2 vein widths in diameter - can be seen on any OCT- standard research definition
  o On OCT: when there is atrophy, start to lose form of RPE and start to lose some of the layers as the outer segments of the rods and cones start to decay

Question 16

What is the management of dry AMD?

Answer 16

• No treatment available
• Advise on lifestyle modifications
  o Smoking cessation is important
• Advise patients on nutritional supplements
• Educate about symptoms of progression and self-monitoring
• Aim: to slow down the progression

Question 16

What is the role of the optometrist in dry AMD?

Answer 16

• Make the diagnosis – think about NICE classification
• Give relevant advice (including advice on driving and smoking cessation)
• Counselling – diagnosis is often a shock
  o Speak in clear, simple language
  o Give them time to talk too
• Provide Information – needs to be accessible (e.g. large print)
  o Direct them to macular society – for support in their local area etc
• Monitor – disease progression
• Referral:
  o Low Vision Services
  o For SI or SSI Registration (Ophthalmology)
  o To Social Services

Question 17

Describe nutritional supplements - AREDS (age-related eye disease study)?

Answer 17

• Large scale, randomized, double-masked, placebo- controlled clinical trial (RCT)
• Looked at effectivity of supplements in delaying preventing onset progression of AMD
• AREDS 1 - Aim was to evaluate the effect of vitamins C (500 mg), E (400 mg), and beta-carotene (15 mg) with or without zinc (zinc oxide 80 mg) with copper (2 mg cupric oxide)
• AREDS 2 - Multicenter, randomized, double-masked, placebo-controlled clinical trial to evaluate
• Placebo, Lutein (10 mg)/zeaxanthin (2 mg), Omega 3 fatty acids (DHA 350 mg and EPA 650 mg), and Lutein/ Zeaxanthin and Omega-3 fatty acids combination
• In addition, participants were administered either the original AREDS formulation (vitamins C, E, and beta-carotene, and zinc with copper) or some modification of the AREDS formulation (either elimination of beta-carotene, lowering of the zinc, or the combination of the two)

Question 17

Describe the emerging treatments for dry AMD in the US?

Answer 17

• Complement Factor inhibitors
  o FDA approved
  o Intravitreal injections
  o Monthly or bimonthly
  o Utility has been shown in patients with severe dry AMD (Geographic atrophy)
  o Have been shown to increase risk of wet AMD
• If these are approved in UK, likely that they would first be used on patients with geographic atrophy away from the fovea to see if they slow down the progression and size of the atrophy

Question 18

Describe the outcome of AREDS and AREDS 2?

Answer 18

• Antioxidant supplements reduced the risk of AMD progression in those with moderate/ high risk of progression
• But, a systematic review showed that supplements had no effect in the prevention of AMD
• Omega-3 fatty acids may help prevent AMD
• Vitamin E and Beta-carotene are associated with increased risk of lung cancer in smokers and increased mortality

Question 19

Describe smoking cessation in dry AMD?

Answer 19

• Smoking increases oxidative stress
• Second most important risk factor (after age)
• Most important modifiable risk factor
• Smoking
  o Slows down choroidal blood flow
  o Promotes ischaemia
  o Reduces macular pigment

Question 20

Describe other lifestyle modifications in dry AMD?

Answer 20

• Increased physical activity > No direct evidence
• Reduced alcohol consumption > Unclear whether moderate consumption is a risk
• Reduction of waist-hip ratio > Especially in obese – unclear?
• Diet rich in omega-3 polyunsaturated fatty acids > Evidence for decreased risk

Question 21

Describe education/self-monitoring and advice for dry AMD?

Answer 21

• Amsler
• Report changes to optometrist
• Ensure deterioration is investigated for progression to neovascular (wet) AMD
• Advice:
  o Every couple of days to once a week
  o Look at Amsler grid with best correction for near with right eye then left eye to see if any wiggly lines (ask them when they are in so you have baseline of what their Amsler looks like (as you will know they have no wet AMD that day)) – then they continue to monitor – is there a scotoma developing/is there wiggly lines?
  o If not issuing Amsler – ask px to look at bathroom tiles/door frames – is there any areas missing, are any of the lines wiggly?
  o If they notice change then they must report to you and you investigate for neovascular glaucoma, wet AMD or progression of dry AMD to point where they need additional support

Question 22

Describe the NICE Guidance Management for Dry AMD?

Answer 22

* Generally Dry AMD managed by community optometry * Refer people with late AMD (dry) to hospital eye services only: o for certification of sight impairment or o if this is how people access low-vision services in the local pathway (see recommendation 1.6.5) or o if they develop new visual symptoms that may suggest late AMD (wet active) or o if it would help them to participate in research into new treatments for late AMD (dry).

Question 23

What is the key point of the Royal College of Ophthalmologists treatment for dry AMD?

Answer 23

o “Treatment for non-neovascular AMD is limited and consists mainly of counselling, smoking cessation, visual rehabilitation and prescription of AREDS style vitamins to reduce risk of progression in those expected to benefit. Clinical trials of novel therapies are now taking place but are not currently available in clinical practice.”

Question 24

What are the benefits of registration for the patient with low vision as result of dry AMD?

Answer 24

o National Entitlement Card (NEC) o Scottish National Blind Persons Scheme o Disabled Persons Railcard o TV Licence discount o Blue Badge o May also be able to access monetary benefits from government if they are SSI o National Entitlement Card (NEC) o Scottish National Blind Persons Scheme o Disabled Persons Railcard o TV Licence discount o Blue Badge o May also be able to access monetary benefits from government if they are SSI

Question 25

Where are the low vision services (and where you may refer)?

Answer 25

* Local Hospital * Resource Centre – where they can choose the LVAs they need * LVA Qualified Optometrist

Question 26

Describe rehabilitation in dry AMD?

Answer 26

* Rehabilitation based on adaptation to vision loss * Advise on low vision services – which may allow them to try out various LVAs * Support patients in dealing with visual impairment o May involve occupational therapy coming out to their house to ensure they have everything they need * Direct to suitable information, e.g. Macular Society o https://www.macularsociety.org

Question 27

Describe referral to social services in dry AMD?

Answer 27

* RNIB * Eye Care Liaison Officer * Virtual or in person * Discuss diagnosis and assess needs * Macular Society * Sight loss and depression o The prevalence rates of depression in elderly populations with sight loss are between 25 per cent and 45 per cent. o The relative risk of depression is estimated to be around 3.5 times higher for those with sight loss compared to those fully sighted. o It is estimated that up to 30 per cent of those living with age related macular degeneration experience moderate to severe depressive symptoms due to vision loss. * Falls are a major cause of disability o 1.7x higher in people with sight loss o 47% of falls in low vision patients are due to their sight loss o The cost to NHS of falls associated with sight loss in Scotland is at least £1million per annum. * If someone has low vision – important that you make them aware of the limitations of their vision – including that falls may be a risk – get help to set up their home to minimise risk

Question 28

Describe vision support services?

Answer 28

* The Vision Support Service provides vital emotional and practical support to anyone newly diagnosed with sight loss and provides a critical link between service users and support services. * Practical support is also viewed as an essential element for people living with sight loss, as well as their family or carers o To make sure a px is dealing with sight loss as best they can

Question 29

Describe wet AMD (is it common, how quickly does it happen)?

Answer 29

* Less common than dry AMD * Rapid onset – distortion and scotoma * Sudden loss of vision * Referral to Ophthalmology usually required

Question 30

What is the NICE classification of wet AMD (late AMD (wet active)) and late AMD (wet inactive))?

Answer 30

* Late AMD (wet active) o Classic choroidal neovascularisation (Choroidal Neovascularisation (CNV)). o Occult (fibrovascular Pigment Epithelium Detachment (PED) and serous PED with neovascularisation). o Mixed (predominantly or minimally classic CNV with occult CNV). o Retinal angiomatous proliferation (RAP). o Polypoidal choroidal vasculopathy (PCV). * Late AMD (wet inactive) o Fibrous scar. o Sub-foveal atrophy or fibrosis secondary to an RPE tear. o Atrophy (absence or thinning of RPE and/or retina) – geographic atrophy o Cystic degeneration (persistent intraretinal fluid or tubulations unresponsive to treatment).

Question 31

Describe the different aspects of late AMD (wet active)? What do these require?

Answer 31

Requires intervention and treatment * Classic choroidal neovascularisation (CNV) (FIRST IMAGE) o Neovascular lesion which is identified that extends from choroidal vessels through Bruchs membrane & RPE and grows in subretinal space o When look at outer retinal layers on angiography – there is signs on the early NaFl angiography of lacy areas where the leaky vessels are, just under the foveal area o If look at outer retinal images at later stage – can see extensive leakage o Fundus pic: can see change in colour at macula, secondary to the oedema and serous detachment that has occurred at the retina * Occult choroidal neovascularisation (CNV) (SECOND IMAGE) o Quite common o Neovascular lesion is located below RPE o Leakage as result of leaky vessels is underneath RPE rather than on top like in CNV above * Retinal angiomatous proliferation (RAP) (THIRD IMAGE) o Often seen more easily on fundus pics as can get punctate haemorrhages in area that is affected o Intraretinal neovascularisation – more superficial – why you can see punctate haemorrhages o OCT: can see retinal oedema within intraretinal area with cystic spaces often  Won’t see disruption of Bruch’s membrane or RPE

Question 32

Describe the aspects of late AMD (wet inactive)?

Answer 32

No new leakage from vessels, no new ongoing rapid damage * Fibrous scar (FIRST IMAGE) o Area of hypo and hyper pigmentation at foveal area o Striking on OCT – don’t get usual foveal contours, everything quite raised – not clear fluid appearance though, more lacy (fibrous material taken over in sub-RPE space) * Sub-foveal atrophy or fibrosis secondary to an RPE tear (SECOND IMAGE) o Sometimes when got so much stress on RPE as result of sub-retinal fluid, may get an RPE tear o On longer term basis, may get atrophy of over lying retinal layers or might start to get fibrotic changes underneath RPE in that area (where white arrow head is in image D)  Fibrotic change – area that is not clear fluid anymore, it’s changed & got bit of colouration * Atrophy (absence or thinning of RPE and/or retina) (THIRD IMAGE) o Late state consequence of atrophy o Can occur when px starts to get geographic atrophy following on from having wet AMD o Top pic of 3rd image: can see obviously still some fluid in sub-RPE space, some reflectivity below RPE as start to get RPE loss. Once fluid has dissipated in sub-RPE space o Middle pic of 3rd image: retina gone flatter as fluid dissipated, but become more flat than normal fovea due to loss of foveal layers – loss of foveal contours – hyperreflectivity beyond RPE as RPE starts to regenerate o NaFl Angiography on Left – see hypo-autoflurescence in lowest image – darker patch, widespread area of atrophy of retinal layers * Cystic degeneration (persistent intraretinal fluid or tubulations unresponsive to tx) (FOURTH & FIFTH IMAGE) o Sometimes persistent areas of fluid are seen as pseudo cysts – seen as hypo-reflective circular shaped lesions – can be mistaken for intra-retinal oedema which is secondary to leakage but they will not shift over time with tx  Pseudo-cysts do not leak when looking at them on NaFl angiography * Pseudo-cysts thought to be due to Muller cell degeneration – and getting reorganisation of intra-retinal layers o Outer retinal tubulations are similar – start to get rearrangement of photoreceptor layers – degenerating photoreceptors start to be arranged in a tubular fashion  get dark hypo-fluorescent areas (where have rearrangement of photoreceptor layer in outer retina) (white arrow points to outer retinal tubulation)

Question 33

Describe management of wet AMD?

Answer 33

* Urgent referral – if new presentation, someone now has fluid & 1st time being diagnosed with wet AMD * NICE guidance: o Make an urgent referral for people with suspected late AMD (wet active) to a macula service, whether or not they report any visual impairment. The referral should normally be made within 1 working day but does not need emergency referral.  Send it away within a day of seeing it so HES can make a judgement about when px needs seen and if tx required – but not emergency same day referral * Electronic (via SCI Gateway) o Via Macular Pathway o Not usually ‘letter in hand’ same day referral * Patient needs to be seen at Macular Clinic (where OCT and Fluorescein Angiography are available) o Differences seen in NaFl angiography between Wet active AMD and wet inactive AMD

Question 34

Describe the injections for wet AMD?

Answer 34

* Treatment usually with anti-VEGF injections * Course of 3 injections * Review/ monitoring period * May require further courses of injections – so long as it is working whilst monitoring their OCT and NaFl angiography

Question 35

Describe the role of the optometrist in wet AMD?

Answer 35

* Patients may be discharged back to community Optometry – specifically if not responding to tx * Optometrist to monitor for progression/ new fluid – be in talks with HES to say to them and determine if it is a true change or if they are quite aware of how things have progressed * OCT is required – best way to monitor if there is new fluid at the macula – hard with just fundus pic * Re-referral to HES * Involvement in anti-VEGF treatments – going forward this may become more of a thing

Question 36

Describe discharge of AMD pxs from hospital?

Answer 36

* Based on: o how stable the condition is and o if treatment will bring any further benefits to the patient * Discharged patients should see an optometrist or GP urgently if any new symptoms develop * Patients who have been treated for wet AMD in one eye and develop problems in the contralateral eye o Monitor this px very closely - & make sure they are aware of how to self-monitor too

Question 37

What is the aims of management in wet AMD?

Answer 37

* Prevent (further) vision loss * Halt progression of new vessels

Question 38

What are the types of anti-VEGF drugs?

Answer 38

* Ranibizumab (Lucentis®) Novartis AG * Bevacizumab (Avastin®) Roche Holding AG * Aflibercept (Eylea®) Beyer AG * Scottish Medicines Consortium has approved ranibizumab and aflibercept for use in NHS Scotland * NICE has approved ranibizumab for treating wet AMD * Bevacizumab is not used on the NHS, mainly for political and legal reasons

Question 39

Describe the Late AMD (indeterminate) stage?

Answer 39

* Late AMD (indeterminate) o Retinal pigment epithelial (RPE) degeneration and dysfunction (presence of degenerative AMD changes with subretinal or intraretinal fluid in the absence of neovascularisation). o Serous pigment epithelial detachment (PED) without neovascularism.