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A summary of macular degeneration and how to assess macular problems with the OCT
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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