4. Nerve layer (Neuro-retina)
• Rods and cones
– Converts light energy into electrical impulses to
transmit to the brain.
– Most energy dependent of all tissue in body
• Bipolar cells
• Ganglion cells
• Nerve fibre layer
– 1.1 million nerve fibres per eye
5. Pigment layer
• 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
• Single layer of cells
6. Blood vessel layer (choroid)
• Supply oxygen and nutrients to
photoreceptors and RPE (outer retina)
• Highest blood flow per unit area of any tissue
in the body
• Why vision goes just before you faint
• Retina is always working very hard!
7. 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
8. 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
9. How does retina protect itself
from light?
• Luteal (yellow) 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
10. 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” of metabolism
• Toxins
– Smoking
• Genetic make up
– Complement factor H
11. Demographics
• AMD - most common cause of visual loss in
patients over 55 in Western world
• Diabetic eye disease most common cause of
visual loss in patients under 55 in Western world
• Ageing population in UK – 20 million > age 50
12. Types of AMD
• Dry
– Most common form
– Gradual loss of central vision
– Not total blindness
• Wet
– 10-15% of AMD
– Sudden loss of central vision
– Not total blindness but often more severe central visual
loss
18. Wet AMD
• Abnormal blood vessels grow into retina from
choroid and haemorrhage and leak
• Vascular endothelial growth factor (VEGF)
stimulates this blood vessel growth
19. Fundus fluorescein angiography
• Dye injected into vein in arm
• Abnormal blood vessels leak the dye
• Choroidal neovascular membrane (CNV)
20. 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)
21. Injection treatments for wet AMD
• Developed from cancer research
• Vascular endothelial growth factor
– Produced by the retina
– Stimulates formation of abnormal, leaky blood
vessels
• Anti-VEGF
– Lucentis, Avastin, Eylea
– Blocks VEFG molecule therefore stops leakage
from the blood vessels
22. Judah Folkman MD
• Prof of Paediatric Surgery at Harvard
• 17 Honorary degrees
• His lab discovered angiogenesis molecules that
stimulate blood vessel formation to allow tumour
growth
• Anti-angiogenesis drugs inhibit tumour growth
• AntiVEGF treatment has developed from his
studies
23. 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
25. 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
29. 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
30. How to reduce frequency of
injections
• Radiation damages proliferating cells
– Endothelial cells (forming the abnormal blood
vessels
– Inflammatory cells (causing damage to tissue)
– Fibroblasts (causing scar tissue formation)
• Internal beam – Merlot study
• External beam – Intrepid study
31. MERLOT – first “portfolio study”
in WEEU, 2010
• Finished recruiting, results awaited
• Vitrectomy + beta irradiation from strontium
source
32. Intrepid study
• Similar to MERLOT but external beam
irradiation
• X rays delivered via contact lens
• IRay system from Oraya theraputics Inc
• Reduced injection rate by one third in study
• Await “real world” results
33. Eylea
• Anti-VEGF treatment
• Aflibercept
• May be more powerful than Lucentis
• Less frequent injection?
• Good for patients that have responded poorly
to Lucentis
34. 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)
35. What about diet and AMD ?
• Eat fresh fruit, dark green leaved vegetables
• Vitamins supplements only if severe
36. 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 only
• AREDS 2 study (ongoing)
– Investigating the benefits of lutein, zeaxanthin and
omega 3 fatty acid supplementation
37. Other macular degenerations
• Epiretinal membrane / Cellophane maculopathy
– Scar tissue on surface of macula
– Surgical treatment with vitrectomy and peel
• Vitreomacular traction
– Surgical treatment with vitrectomy
– New medical treatment with Ocriplasmin (Jetrea)
• Macular holes
– (Phaco)Vitrectomy with gas and limited posturing
– ? Jetrea in small holes
