11 AMD and OCTA Flashcards
AMD epidemiology:
10% > 65yo
25% > 75yo
85% dry / 15% wet
Dry AMD treatment:
No treatment availible
Recurrent Amsler check
Antioxidant supp. (Vit C/E)
Smoking cessation
BP/BMI management
Dry AMD clinical presentation:
Soft sub-RPE drusen within macula (usually hard in periphery)
Lipofuscin lipid accumulation
RPE hyperpigmentation, atrophy, capillary loss
Wet AMD clinical presentation:
Neovascularisation from choroid through bruchs membrane at macula
Retinal detachment
Haemorrhages
Yellow plaque membrane
Risk factors for AMD
Age
Smoking
Mutation in CFH / ARMS2
Family, women, hyperopia, Caucasian, hypertension
Causes of AMD
Stress from age
Oxidative damage (from light exposure)
Carcinogenic damage (smoking)
Blood dysregulation (fat/cholesterol)
Lack of antioxidant intake
Stress effect on retinal cells:
Ganglion layer thinning
Microglial recruitment of inflammatory cells
Fatty acid buildup from photoreceptors
RPE lipofuscin (lipids) aggregation
Choroid growth factor dysregulation
Drusen appearance
Small, yellow deposit between RPE basal lamina and bruchs membrane
Hard drusen coalesces to soft drusen in AMD
Drusen composition:
Esterified cholesterol
Phosphatidylcholine
Proteins
Immune / complement components
Drusen sizes
Small > 63um
Intermediate > 125um
Large < 125um
Drusen shapes:
Hard > defined boarders
Soft > blurred boarders
Large/soft/continuous drusen > AMD
Lipofuscin formation:
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
Lipofuscin pathophysiology:
Hypertension/carotid plaque/oxidative damage > Atherosclerosis (accumulation of cholesterol plaque) > altered choroidal circulation > incomplete digestion of outer photoreceptor shedding > accumulation in RPE
Wet AMD treatments:
Photodynamic therapy: Injected verteporfin releases ROS under 690nm laser, damaging vessels
Anti-VEGFs: bind to VEGF, preventing its binding to VEGFR and subsequent angiogenesis
Wet AMD Anti-VEGF treatments:
Macugen (pegaptanib, first treatment)
Ranibizumab (Lucentis)
Aflibercept (Regeneron)
Bevacizumab (Genentech)
Anti-VEGF functions in AMD:
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
Dry AMD pathophysiology:
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
Wet AMD pathophysiology:
RPE ischemia / inflammatory influx > Complement factor activation > PRE secretion of VEGF > Choroidal neovascularisation (CNV)
AMD defence system in the eye:
Macula pigment prevents direct light oxidation
Antioxidants (retinoids) prevent oxidation from A2E accumulation
AMD inflammation:
Lipofuscin / drusen > NLRP3 activation > Caspase-1 activation > IL B/18 synthesis > inflammatory cell influx
OCTA basic principles:
Optical coherence tomography angiography
Continuous OCT scans over time to present blood flow
OCTA devices:
Spectral domain: 840nm wavelength > Shallow RPE (drusen) imaging
Swept source: 1050nm wavelength > deep choroid imaging
OCTA positive/negatives:
No need for injection
No information on dynamic leakage/lesions unlike fluorescein/indocyanine green angiography
Choriocapillaris:
Vasculature under bruchs membrane
10um under fovea, 7um under periphery
Decreases in density with age and AMD
