Fluorescein Angiography

• Fluorescence: the property of emitting a longer wavelength light when stimulated by a shorter wavelength

• White light from the camera passes through a blue excitation filter

• Blue light (wavelength of 490nm) is transmitted to the fundus and is absorbed by the fluorescein molecules in the retinal and choroidal vasculature

• They are stimulated to emit yellow-green light (530nm)

• Macular xanthophyll may have a physiological role in limiting damage to the photoreceptors by protecting them from high energy short-wavelength light

• A yellow-green filter is placed to block blue light reflected from the eye
• The yellow-green light therefore reached the camera
• Fluorescein has a low molecular weight

• Can pass between endothelial cells in the choriocapillaris and other capillary beds in the body (therefore, in other tissues it does not stay intravascular)

• The RPE tight junctions normally prevent this leak into the neural retina (outer barrier)

• The tight junctions between retinal vascular endothelial cells also prevent leak normally (inner barrier)

• Fluorescein is 80-85% bound to serum protein (it is primarily hydrophilic)
• Leaks readily from fenestrated choriocapillaris
• 10% concentration fluorescein is used

• Anaphylactic shock: <1 in 100,000 (<0.001%)
• More common side effects
• Discolouration of skin and urine
• Nausea and vomiting
• Urticarial rash
• Flushing
• Photosensitivity 
• Itch
• Discomfort at injection site
• The diameter of retinal vessels on FFA is larger than that of a fundus photograph

• A photo only visualises the axial blood column whereas fluorescein reaches the peripheral blood in the vessel

Uses

• Diagnosis
• AMD
• CSR
• CMO
• Diabetic retinopathy
• Retinal vein occlusion
• Posterior uveitis
• Disc drusen
• Choroidal haemangiomas
• Management
• To guide laser in CNV, CSR, diabetic maculopathy and vein occlusion

Normal phases

• Choroidal: 10-12 seconds after injection in young patients but depends on vascular health

• Arterial: 1-3 seconds after the choroidal phase

• Neovascularisation of the disc (part of the retinal circulation) is visible during the early arterial phase

• The central retinal artery provides a circuitous route for the dye so it appears 1 or 2 seconds later than in the choroidal circulation

• Arteriovenous

• Demonstrates laminar flow: the veins are fluorescent near their walls and darker centrally

• Lasts for 1-2 seconds
• Venous
• Late phase
• Highlights cystoid macular oedema, CSR, or occult subretinal neovascular membranes
• Late staining of the optic disc is normal

Abnormalities

• Pooling: hyperfluorescence that increases in size and intensity as dye enters a closed space eg a pigment epithelial detachment

• Once the space is filled, the hyperfluorescence remains stable (cp leakage)

• Leakage: increases in size and intensity of hyperfluorescence over time (due to extravasation of dye)

• Incompetence of the inner or outer blood-retinal barriers
• Neovascularisation: defective inner barrier
• Defective choroidal circulation eg. AMD
• Window defect: unmasking of the normal choroidal fluorescence
• RPE atrophy
• Window defects are seen early
• Staining: hyperfluorescence appears late. Uptake of dye into structures
• Drusen
• Disciform scars
• Optic disc

• Pseudo-autofluorescence: overlap in the spectral transmission of the excitation and barrier filters

ICG

• Provides more information about the choroidal circulation

• ICG circulates 98% bound to plasma protein (it is amphiphilic, ie. both hydro- and lipophilic therefore binds lipproteins and phospholipids) so less leakage 

• Therefore provides information about the choroid that would be invisible to FFA due to extravasation of fluorescein from the choroid

• Takes longer than FFA
• Excreted by the hepatobiliary system: discoloured stool for several days
• Useful for
• Occult/poorly defined CNVM: can be more easily measured
• Polypoidal CNV
• Fibrovascular PEDs
• Medial opacities/vitreous haemorrhages
• Photophobic patients (they cannot see the infrared lights)

• Inflammatory disease: to identify possibly occult choroidal disease (crucial investigation for inflammatory disease)

Summary Table: FFA findings of important pathologies table