8 - Clinical assessment, classification and grading of AMD

Block 2

What are the two types of AMD?

• Wet aka active

• Dry aka inactive

What is AMD and what are its 2 main types?

AMD is a leading cause of visual impairment in people aged ≥50 in developed countries; wet/active AMD and dry/inactive AMD

What are the risk factors for AMD?

Increasing age; genetics; gender; lifestyle factors: smoking/diet/hypertension; myopia; CSR; cataract surgery; diabetes; inflammation

What does fundus autofluorescence (FAF) assess?

Lipofuscin fluoresces and indicates the presence of RPE; excess lipofuscin may occur when cells overlap due to early degeneration; oxidative stress = hyperfluorescence; RPE cell death = hypofluorescence

What is fluorescein angiography used for in AMD?

Investigates retinal leakage; the pattern of leakage can be used to classify the lesion

What is indocyanine green angiography used for?

Imaging the choroidal vasculature

What is OCT angiography (OCTA)?

Non-invasive imaging that detects blood flow and abnormal patterns of vascular flow

How does NICE classify normal/no AMD?

No signs of AMD or only small hard drusen <63 µm

What is NICE low-risk early AMD?

Medium drusen ≥63 to <125 µm OR pigmentary abnormalities

What is NICE medium-risk early AMD?

Large drusen ≥125 µm OR reticular drusen OR medium drusen with pigmentary abnormalities

What is NICE high-risk early AMD?

Large drusen ≥125 µm with pigmentary abnormalities; reticular drusen with pigmentary abnormalities; vitelliform lesion without significant visual loss (BCVA better than 6/18); OR atrophy <175 µm not involving the fovea

What is NICE late AMD (indeterminate)?

RPE degeneration/dysfunction with degenerative AMD changes and subretinal or intraretinal fluid without neovascularisation; OR serous PED without neovascularisation

What is NICE late AMD (wet active)?

Classic CNV; occult CNV including fibrovascular PED/serous PED with neovascularisation; mixed CNV; retinal angiomatous proliferation (RAP); polypoidal choroidal vasculopathy (PCV)

What is NICE late AMD (dry)?

Geographic atrophy without neovascular AMD; OR significant visual loss of 6/18 or worse associated with dense/confluent drusen; advanced pigmentary changes/atrophy; or a vitelliform lesion

What is NICE late AMD (wet inactive)?

Fibrous scar; subfoveal atrophy/fibrosis secondary to RPE tear; atrophy with absent/thinned RPE and/or retina; cystic degeneration with persistent intraretinal fluid/tubulations unresponsive to treatment

What are drusen?

Extracellular deposits between the RPE and Bruch's membrane due to incomplete processing of photoreceptor outer segments; largely composed of lipids; act as a barrier and are a precursor to atrophy and CNV

How does drusen prevalence change with age?

≈2% in ages 45–55; increases to ≈25% in those aged >75

What are the features of hard; intermediate and soft drusen?

Hard:

What are reticular pseudodrusen (RPD) and how can they be imaged?

Reticular pseudodrusen can be demonstrated using colour photography; IR imaging; FAF; and SD-OCT

What does the conversion-to-large-drusen graph show?

Risk of developing large drusen increases most when medium drusen are present in both eyes; lower with medium drusen in one eye; lower still with small/no drusen

What are the AREDS 5-year risk factors used to estimate AMD progression?

Large drusen and pigmentary abnormalities in each eye are assigned risk factors; additional risk factors are assigned when one eye already has late AMD

What is atrophy in AMD?

Associated with collapse of drusen; irreversible tissue loss; appears as a hypopigmented/depigmented area where choroidal vasculature becomes visible; geographic atrophy is end-stage

What is cORA?

Complete outer retinal atrophy: intermittent hypertransmission; continuous absence of ellipsoid/interdigitation zones with corresponding outer nuclear layer loss but intact RPE; usually after prolonged SRF or regression of subretinal deposit

What is iORA?

Incomplete outer retinal atrophy: detectable ellipsoid layer disruption and outer retinal loss; RPE remains intact; no hypertransmission

What is cRORA?

Complete RPE and outer retinal atrophy: hypertransmission with an area of RPE disruption >250 µm and evidence of overlying photoreceptor disruption

What is iRORA?

Incomplete RPE and outer retinal atrophy: hypertransmission with corresponding RPE disruption ± basal laminar deposits and evidence of overlying photoreceptor disruption

What does NICE recommend for referral of early AMD?

Confirm early AMD using slit-lamp biomicroscopic fundus examination alone; do not refer asymptomatic early AMD to hospital eye services for further diagnostic tests

When should late dry AMD be referred according to NICE?

Only for sight impairment certification; if hospital referral is the local route to low-vision services; if new symptoms suggest wet active AMD; or to enable participation in research into new dry AMD treatments

What OCT features should be assessed in AMD?

Subretinal fluid; intraretinal fluid; PED; hyper-reflective dots (HRD); subretinal hyper-reflective material (SHRM); double-layer sign (DLS); outer retinal tubulation (ORT)

What types of pigment epithelial detachment (PED) may occur?

Serous; drusenoid; fibrovascular; haemorrhagic

What are hyper-reflective dots (HRD)?

Possibly inflammatory/disrupted cells; can occur in all retinal layers; usually located around fluid

What can subretinal hyper-reflective material (SHRM) represent?

Haemorrhage; lipid; pigment; subretinal fibrosis; CNV itself can also be hyperreflective

What is the double-layer sign (DLS)?

Irregular elevation of the RPE from Bruch's membrane; can occur in CSR and AMD subtypes such as PCV and non-exudative CNV

What is outer retinal tubulation (ORT)?

Degenerative photoreceptors and Müller cells forming a hyper-reflective ring with a hypo-reflective centre; indicates chronicity and poor response to treatment

Where are the 3 types of CNV located?

Type 1 = below RPE; Type 2 = above RPE; Type 3 = intraretinal neovascularisation

What is non-exudative/quiescent CNV?

CNV with abnormal vascular flow detectable on OCTA but without the leakage detected by FA in exudative CNV; ≈20% risk of progression to exudative CNV within 1 year

How urgently should suspected wet active AMD be referred according to NICE?

Urgent referral to a macula service whether or not visual impairment is reported; normally within 1 working day; does not require emergency referral

What are the NICE anti-VEGF treatment criteria stated in the lecture?

BCVA 6/96–6/12; no permanent structural damage to the fovea; lesion ≤12 disc areas; features of recent progression

What are the main components of AMD assessment?

History; refraction; examination; Amsler; imaging

What should be established from the history in suspected AMD?

Reduced VA; distortion; whether unilateral or bilateral; duration and progression

How should refraction be approached in AMD?

Objective refraction may be more reliable; use changes appropriate to VA e.g. larger subjective steps if VA is poor; obtain a measurable VA as <6/60 is not ideal

How should the fundus be examined when assessing AMD?

Consider dilation with usual precautions; red-free may help; use low magnification; indirect/oblique illumination; contact lens examination where appropriate; examine both eyes

What is the role of the Amsler grid in AMD assessment?

Standard Amsler may not always be easy to administer; it can be useful for patient self-monitoring

What is the role of imaging in AMD assessment?

It complements clinical examination and helps identify AMD features

What happened in Case 1?

77-year-old woman with dry AMD for 10 years and progressive worsening; VA R 6/9-2 and L 6/12; developed stable right-eye distortion over several weeks; referred to macular clinic for assessment

What were the key details of Case 2?

Previously treated with anti-VEGF; last injection 4 weeks ago; VA stable at 6/48; fellow eye dry AMD with VA 6/7.5; no new symptoms; attending routine review

What OCT findings were considered in Case 2 and what were the management options?

New/recurrent intraretinal oedema/cysts with HRD versus degenerative cysts associated with damaged/defective RPE; options were re-inject; observe; or perform angiography

What are the key take-home points for assessment and referral of AMD?

AMD terminology/classification has evolved; dry AMD affects the majority but can convert; imaging is a useful adjunct; full evaluation is needed to determine diagnosis and management