All you need to know about AMD and the OCT – but were afraid to ask!

Talk summary

• The pathophysiology of AMD• OCT principles• Quiz and prize• Talk available on line

Attention span graph

A bit of confusing anatomy

Anatomy made simple

• Neuro-retina• Potential sub-retinal space• Retinal Pigment epithelium• Choroid

Neuro-retina• Nerve fibre layer

1.1 million fibres per eye

• Ganglion cells• Bipolar cells• Rods and Cones (photoreceptors)

Convert light into electrical impulses to transmit to the brain

Most energy dependent tissue in body

Retinal pigment epithelium

• Recycles material from rods and cones– Recycling needed to maintain efficient function

• Contains pigment to stop internal reflections– Prevents “glare” inside the eye– Melanin pigment

• Pumps water out of the neuro-retina and potential sub-retinal space to keep it “dry”

Choroid

• Supply oxygen and glucose to photoreceptors and RPE

• Highest blood flow per unit area of any tissue in the body

• Look what happens when you faint• Retina is always working very hard!

Important terminology• Outer retina

RPE and photoreceptors

Supplied by choroid

• Inner retinaNerve fibre layer

Ganglion cells

Bipolar cells

Supplied by central retinal artery

RPE and photoreceptors must not part company – they act

as a single unit

Is light bad for the eyes ?

• Form of electromagnetic radiation• Look what happens with excess sunlight on

the skin• Eye is an optical system that exposes retina

to radiation all the time• Light focused on the macula

What harm does light do to the retina?

• Reacts with fat in cell membranes• Produces reactive oxygen (free radicals)• Damages the DNA in the cells• Repair mechanisms

– Skin – repairs DNA all the time, new cells form– Brain – cannot create new cells as has to store

memory– Retina – part of brain so cannot create new cells

How does retina protect itself from light?

• Luteal pigment at macular protects against high energy blue light

• Rods and cones have “outer segments”• Although a “non dividing system” these outer

segment cell membranes are constantly shed then recycled by the RPE to form new cell membranes

How does macular degeneration start?

• Chronic damage to cells from high energy light– Damage to DNA (and cannot repair)

• Recycling becomes less effective with age– Accumulation of “waste products” (Drusen)

• Toxins– Smoking

• Genetic make up– Complement factor H

Wet AMD• Abnormal blood vessels grow upwards from

Choroid into Retina (Choroidal neovascular membrane)

• May remain under the RPE “Occult”• May grow through RPE into neuro-retina

“Classic”• VEGF driven• Treatment with anti-VEGF agents (Lucentis,

Avastin and Eylea)

Visual loss with wet AMD

• No treatment (natural history)– Loss of 5 lines of Snellen acuity in 2 years

• Most of the loss of vision will take place within the first 6 months

• Like a cut on the skin– First there is inflammation with swelling

and haemorrhage– Then a scar forms (disciform scar)

Fundus fluorescein angiography• Dye injected into vein in arm• Abnormal blood vessels leak the dye• Choroidal neovascular membrane (CNV)

retina

RPE

choroid

Occult CNV

Classic CNV

Choroid

Retina

RPE

Classic CNV – “ring of fire”

Damage to vision

• Classic– Disrupts RPE / photoreceptor partnership– More aggressive process– Significant and rapid visual loss

• Occult– RPE / photoreceptor partnership remains intact– May maintain better vision “low grade occult”

What is RAP?

• Choroidal neovascular membrane (CNV) are abnormal blood vessels growing upwards from Choroid into Retina (Occult and Classic)

• Retinal angiomatous proliferations (RAP) are abnormal blood vessels growing downwards from Retina into Choroid

• 15% of wet AMD is RAP and 100% bilateral within 3 years

RAP

• Multiple intraretinal haemorrhages at macular

• Can look like macular branch retinal vein occlusion but does not stop at horizontal midline

CNV haemorrhage is predominantly subretinal or sub RPE

Judah Folkman MD

• Prof of Paediatric Surgery at Harvard• 17 Honorary degrees• His lab discovered vascular endothelial growth

factor (VEGF) that stimulate blood vessel formation to allow tumour growth

• Anti-angiogenesis drugs inhibit tumour growth• Anti-VEGF treatment for AMD has developed

from his studies

Landmark Marina and Anchor studies

• Lucentis injected every month for 2 years• Average improvement of vision 10 letters• Maintained vision in most patients• If frequency of injections less than every

month reduced effect noted• Most UK practice is now 3 loading injection

over 3 months then as needed injections

Source: HORIZON data. Genentech.

Treated-Initial (n=388) Untreated (n=33)

ETD

RS

Lett

ers

-20

-15

-10

-5

0

5

10

15

3 6 9 12 15 18 21 24

HORIZON Study

+5.1

-6.7

+2.0

-6.9

24

MonthInitial baseline

Marina/Anchor Studies+10.2

-3.2

Average number of injections and costs

• 8 injections in the first year• 6 injections in the second year• Each injection costs £1,750 to the NHS

– £750 for Lucentis• The first 2 years cost the NHS £24,000• Average life expectancy from diagnosis

– 10 years

INJECTING

First nurse-delivered injections service in UK, 2008

• West of England Eye Unit, Exeter• NP’s Brian Kingett, Nicola Mann• 7,000 injections to date• Recently supported by Royal College of

Ophthalmologists and Macular Society

Problems with injections• Does not address fundamental cause of wet

AMD• Multiple injections for elderly patients• VEGF may be needed to help improve

circulation – Avoid if high risk of or recent stroke or heart

attack• Risk of injection itself

– Infection of eye (endophthalmitis) 1 in 1,000

How to reduce frequency of injections?

• Radiation damages proliferating cellsEndothelial cells, inflammatory cells, fibroblastsInternal beam (MERLOT study)External beam (INTREPID study)

• Longer acting anti-VEGF agentAflibercept (Eylea)

MERLOT study

• Finished recruiting, results awaited• Vitrectomy + beta irradiation from strontium

source

INTREPID study

• Similar to MERLOT but external beam irradiation

• X rays delivered via contact lens• IRay system from Oraya therapeutics Inc• Reduced injection rate by one third in study • Await “real world” results

Dry AMD• Build up of waste products due to poor

recycling (Drusen)• Changes in melanin pigment in the RPE• Geographic atrophy

What about dry AMD?

• Main treatment remains low visual aids• Stem cell treatment• Neuro-protection• Intraocular telescopes

– VIP IOL– Implantable miniature telescope– ARGUS II (digital camera in glasses

communicates with retinal chip)

What about diet and AMD ?

• Eat fresh fruit, dark green leaved vegetables• Vitamins supplements only if severe

Vitamins and AMD• Antioxidant treatments to “mop up” free

radicals• AREDS (Age related eye disease study)

– Vit C 500mg, E 400IU, beta carotene 15mg and zinc 80mg

– Decreased risk of progression of AMD with subgroup analysis

• AREDS 2 study results 5th May 2013– Lutein and zeaxanthin can safely replace beta

carotene (Lung cancer risk) and omega 3 fatty acids of no benefit

Principles of the OCT• Non invasive• Based on interferometry

– Interference between incident and reflected light• Like doing a vertical biopsy of the retina

– Use laser light rather than knife!• Good at showing swelling due to leakage• FFA still needed for showing blockage of

blood vessels

Optical coherence tomographyNormal anatomy

• Normal thickness = 200 microns• Thick retina > 250 microns

– Usually due to leakage• Thin retina < 150 microns

– Atrophic with poor function• Can be difficult to assess function on

thickness alone

Central macular thickness

The photoreceptor integrity line

• Junction between inner and outer segments• Barely visible in histological sections• Highly prominent with OCT• Due to difference in index of refraction of the

inner and outer segments

Assess retinal function• Normal thickness retina – how is it functioning?• Well demarcated IS/OS junction suggest good

photoreceptor function

Retina pathology often in layers

• Inner retina (retinal circulation)– Diabetic retinopathy – Retinal vein occlusion

• Outer retina (choroidal circulation)– AMD– CSR

OCT pathology often in layers• Retinal surface (mechanical problems)

– Vitreo-macular traction– Epiretinal membrane

• Inner retina (retinal circulation)– Diabetic retinopathy– Retinal vein occlusion

• Outer retina (choroidal circulation)– AMD – CSR

Retinal pathology in more than one layer

• Full thickness macular hole– All layers involved

• Lamellar hole– Usually surface and inner retina

• Severe retinal disease– Wet AMD (starts in outer retina)– Diabetic eye disease (starts in inner retina)– Retinal vein occlusions (starts in inner retina)

• Posterior vitreous pulling on macula• Wide range of severity• Treat with vitrectomy• Treat with Ocriplasmin injection (Jetrea)• If incidental OCT finding and patient

asymptomatic – do not refer

Vitreo-macular traction

Severe Vitreo-macular traction

0.5 LogMAR“Pointed - being Pulled”

Mild Vitreo-macular traction

Inner retinal cyst0.12 LogMAR

• Posterior vitreous usually detached• Sometimes associated with lamellar hole• Wide range of severity• If incidental OCT finding and patient

asymptomatic – do not refer

Epiretinal membrane

Epiretinal membrane

Mild epiretinal membrane

0.1 LogMARLoss of foveal pit

Lamellar macular hole with ERM

Note ERM with “saw tooth sign”Lamellar macular holeNote healthy IS / OS junctionVisual acuity is 0.12No symptoms

Lamellar macular hole with ERM

0.1 LogMARAsymptomatic

Full thickness macular hole

Spontaneous improvement in a full thickness macular hole

OCT and dry AMD

Drusen“Lumpy bumpy” RPE

OCT and dry AMD

RPE atrophyHigh signal beneath RPEThin retina

OCT and leakage

• Wet AMD• Diabetic maculopathy• Retinal vein occlusions• CSR• Uveitis• Retinitis pigmentosa

Intraretinal fluid

What the vision?

Sub-retinal fluid

What is the vision?

Sub-RPE fluid (PED)

What is the vision?

OCT and wet AMD• Outer retina first involved (choroidal

circulation)• Fluid

– Sub RPE– Sub Retinal– Intra retinal if moderate or severe

• Usually previous dry AMD– Look at RPE line as rarely “pristine”

OCT and wet AMD

Sub RPE fluidSub retinal fluid

Intra retinal fluidNote previous dry changes

“Burnt out” Wet AMD

Disciform Scarring

OCT and exudative diabetic maculopathy

• Inner retina first involved (retinal circulation)• Fluid

– Intra retinal (including cystoid oedema)– Sub retinal if moderate or severe– No Sub RPE fluid

• Hard exudates– Highly reflective intraretinal spots

• RPE looks ok

OCT and exudative diabetic maculopathy

OCT and retinal vein occlusions

• Inner retina first involved (retinal circulation)• Fluid

– Intra retinal (including cystoid oedema)– Sub retinal if moderate or severe– No Sub RPE fluid

• Hard exudates– Less frequently seen than in diabetics

• RPE looks ok

Ozurdex in macular oedema from central vein occlusion

0.5 LogMARPre injection

0.3 LogMARPost injection

Where is pathology most disruptive to vision?

1. Outer retina (choroidal circulation)“Classic” Wet AMD

2. Inner retina (retinal circulation)Diabetic eye disease

Retinal vein occlusions

3. Sub-RPELow grade “Occult” Wet AMD / Chronic PED’s

Ask yourself

• Anything on the surface?• Is it mainly inner or outer retina or both?• How does the RPE look?• How well demarcated is the IS /OS

line?

Small BRVO or wet AMD at macula?

• BRVO– Inner retina– RPE normal– IS / OS may be preserved– Haemorrhage does not pass across the horizontal

midline• Wet AMD

– Outer retina– RPE abnormal– IS / OS disrupted– Haemorrhage may be on either side of horizontal

midline

What is this?

OCT and CSR

• Leakage from choroid through RPE• Fluid

– Sub Retinal• RPE

– May be small PED– Remaining RPE looks healthy

OCT and CSR

Uveitis

Retinitis pigmentosa

Pre – Sub Tenon’s steroid“Bell shape – from Below”

Post injectionNote thin retinaNo IS / OS junction

What is this?

Adult vitelliform dystrophy

0.0 LogMAR ODIntact IS / OS junction

What is this and what is the vision?

Macula schisis

0.1 LogMARIntact IS / OS junction

0.0 LogMARIntact IS / OS junction

What is this?

What is this?

Ruptured retinal macroaneurysm

What is this?

It was due to this !

Quiz

• Self marking• 8 questions• 1 tie break question if needed

Questions• What should never part company?• Classic CNV is where in the retina?• What can look like a macular BRVO

but is wet AMD?• What is the blood supply of the inner

retina?

Questions

• What can you look at to check retinal function on the OCT?

• All AMD patients should have vitamin supplements? True or False

• Fluid under the RPE is usually from vein occlusions? True or False

• Drusen are in the inner retina?

Questions• What should never part company?

– The photoreceptors and RPE• Classic CNV is where in the retina?

– In front of the RPE• What can look like a macular BRVO but is

wet AMD?– RAP lesions

• What is the blood supply of the inner retina?– Central retinal artery

Questions• What can you look at to check retinal function on

the OCT?– The IS/OS junction

• All AMD patients should have vitamin supplements? True or False

– False, only if high risk• Fluid under the RPE is usually from vein

occlusions? True or False– False, fluid will be intraretinal or if severe subretinal

• Drusen are in the inner retina? True or False– False, drusen are in the outer retina

Tie break question

• How many syringes were completely visible on the “Keep Calm and Carry On” slide?

INJECTING