11 AMD and OCTA

Question 1

AMD epidemiology:

Answer 1

10% > 65yo
25% > 75yo
85% dry / 15% wet

Question 2

Dry AMD treatment:

Answer 2

No treatment availible
Recurrent Amsler check
Antioxidant supp. (Vit C/E)
Smoking cessation
BP/BMI management

Question 3

Dry AMD clinical presentation:

Answer 3

Soft sub-RPE drusen within macula (usually hard in periphery)
Lipofuscin lipid accumulation
RPE hyperpigmentation, atrophy, capillary loss

Question 4

Wet AMD clinical presentation:

Answer 4

Neovascularisation from choroid through bruchs membrane at macula
Retinal detachment
Haemorrhages
Yellow plaque membrane

Question 5

Risk factors for AMD

Answer 5

Age
Smoking
Mutation in CFH / ARMS2
Family, women, hyperopia, Caucasian, hypertension

Question 6

Causes of AMD

Answer 6

Stress from age
Oxidative damage (from light exposure)
Carcinogenic damage (smoking)
Blood dysregulation (fat/cholesterol)
Lack of antioxidant intake

Question 7

Stress effect on retinal cells:

Answer 7

Ganglion layer thinning
Microglial recruitment of inflammatory cells
Fatty acid buildup from photoreceptors
RPE lipofuscin (lipids) aggregation
Choroid growth factor dysregulation

Question 8

Drusen appearance

Answer 8

Small, yellow deposit between RPE basal lamina and bruchs membrane
Hard drusen coalesces to soft drusen in AMD

Question 9

Drusen composition:

Answer 9

Esterified cholesterol
Phosphatidylcholine
Proteins
Immune / complement components

Question 10

Drusen sizes

Answer 10

Small > 63um
Intermediate > 125um
Large < 125um

Question 11

Drusen shapes:

Answer 11

Hard > defined boarders
Soft > blurred boarders
Large/soft/continuous drusen > AMD

Question 12

Lipofuscin formation:

Answer 12

Condensation of 2x All-Trans-Retinal and Phoshatidylethanolamine
Forms Retinylidene-N-Retinylethanolamine (A2E) which cannot be removed from RPE
A2E accumulation decreases phagocytosis of outer photoreceptor segment and further builds up lipofuscin

Question 13

Lipofuscin pathophysiology:

Answer 13

Hypertension/carotid plaque/oxidative damage > Atherosclerosis (accumulation of cholesterol plaque) > altered choroidal circulation > incomplete digestion of outer photoreceptor shedding > accumulation in RPE

Question 14

Wet AMD treatments:

Answer 14

Photodynamic therapy: Injected verteporfin releases ROS under 690nm laser, damaging vessels
Anti-VEGFs: bind to VEGF, preventing its binding to VEGFR and subsequent angiogenesis

Question 15

Wet AMD Anti-VEGF treatments:

Answer 15

Macugen (pegaptanib, first treatment)
Ranibizumab (Lucentis)
Aflibercept (Regeneron)
Bevacizumab (Genentech)

Question 16

Anti-VEGF functions in AMD:

Answer 16

Ranibizumab: binds VEGF-A before binding VEGFR-1/2
Aflibercept: binds VEGF-A/B before binding VEGFR-2
Bevacizumab: binds VEGF-A/C/D before binding VEGFR-1

Question 17

Dry AMD pathophysiology:

Answer 17

Age/oxidative stress > outer photoreceptor shed / RPE processing dysfunction > Lipofuscin/drusen build-up > interrupted RPE processing > further buildup
Bruchs membrane deposit > local activation of complement > inflammatory influx > drusen growth > RPE ischemia

Question 18

Wet AMD pathophysiology:

Answer 18

RPE ischemia / inflammatory influx > Complement factor activation > PRE secretion of VEGF > Choroidal neovascularisation (CNV)

Question 19

AMD defence system in the eye:

Answer 19

Macula pigment prevents direct light oxidation
Antioxidants (retinoids) prevent oxidation from A2E accumulation

Question 20

AMD inflammation:

Answer 20

Lipofuscin / drusen > NLRP3 activation > Caspase-1 activation > IL B/18 synthesis > inflammatory cell influx

Question 21

OCTA basic principles:

Answer 21

Optical coherence tomography angiography
Continuous OCT scans over time to present blood flow

Question 22

OCTA devices:

Answer 22

Spectral domain: 840nm wavelength > Shallow RPE (drusen) imaging
Swept source: 1050nm wavelength > deep choroid imaging

Question 23

OCTA positive/negatives:

Answer 23

No need for injection
No information on dynamic leakage/lesions unlike fluorescein/indocyanine green angiography

Question 24

Choriocapillaris:

Answer 24

Vasculature under bruchs membrane
10um under fovea, 7um under periphery
Decreases in density with age and AMD