Day 8 (2): Introduction to Fundus Fluorescein Angiography Flashcards
What is fluorescein?
- organic dye used as a fluorescent tracer
- 80% albumin-bound, 20% for fluorescence
- ideal pH: 7.4
- freely diffuses through choriocapillaris, Bruch’s membrane, optic nerve and sclera
- unable to cross:
1. Inner BRB: retinal blood vessels
2. Outer BRB: intact RPE tight junctions
3. LARGE choroidal vessels - metabolism: hepatic
- excretion: renal
- side effect: yellow urine for 24-36 hours
- absorbs BLUE light and emits YELLOW-GREEN light
What are the ophthalmologic applications of fluorescein?
- Fundus Fluorescein Angiography (FFA)
- Delineation of corneal abrasions, ulcerations and other epithelial defects
- RGP contact lens fitting
- Applanation tonometry
What is the blood supply of the retina?
Inner Retina: NFL, GCL, IPL, INL
- Central Retinal Artery and Vein <– Ophthalmic Artery and Vein (passing within the optic nerve)
Outer Retina: OPL, ONL, PRL, RPE
- Choriocapillaris <– Posterior Ciliary Arteries (piercing the posterior sclera)
- Vortex Veins
What is Fundus Fluorescein Angiography?
Purpose:
examines the competence and integrity of the blood-retina barrier
Apparatus: Fundus Camera
1. Blue Exciter Filter emits BLUE light (465 - 490 nm) absorbed by fluorescein
2. Fluorescein emits GREEN light (520 - 530 nm)
3. Passes through a Yellow barrier filter which allows only reemitted light to expose film
Risks: Dye hypersensitivity
- nausea and vomiting: due to diff. in dye and blood pH
- urticaria
- anaphylaxis (dyspnea, hypotension, cardiac arrest)
- precaution: SKIN TEST
- treatment: anti-histamines and epinephrine
Dose: 500 mg IV bolus (5 mL 10% sodium fluorescein)
- degree of fluorescence directly proportional to concentration but only within a narrow range of concentration (0.00001 - 0.01%)
What is the purpose of the Blood-Retina Barrier?
Controls the movement of fluid, ions and electrolytes from the intravascular space to the extravascular tissues of the retina
INNER Blood Retina Barrier
- tight junctions connecting the NON-fenestrated endothelial cells in the retinal arteries and capillaries
- prevents leakage of both bound and unbound intravascular fluorescein
- clear delineation of retinal blood vessels
OUTER Blood Retina Barrier
- tight junctions connecting the RPE
- impermeable to fluorescein
- RPE: acts as an optical barrier which masks the delineation of the choroidal circulation
What are the steps in doing FFA?
- Prerequisites: clear media and dilated pupils
- Begins with injection of sodium fluorescein into the antecubital vein
- Dye travels to the retina via the SHORT posterior ciliary arteries and the choroid
- Normal arm-retina time: < 10 seconds
Photographs
1. Early rapid sequence:
- 1-s intervals taken for 25–30 s
- more important than later shots
- only possible to do one eye at a time due to the time it takes to move the camera between eyes
2. Later shots:
- less frequent shots are needed
- alternating between the eyes for 5 - 10 min
- very late images may be taken at 10 - 20 min
What are the filling phases/stages in FFA?
Normal filling order:
1. Choroid
2. Cilioretinal vessels
3. Optic disc
4. Retinal vessels (artery, arterioles, capillaries, venules, vein)
4 Phases of FFA
- Choroidal Flush: 10 seconds PI
- choroidal filling; pre-arterial phase
- because choroid is fenestrated, fluorescein freely enters extravascular space
- mottled, patchy, lobular and mild hyperfluorescence of the choriocapillaris: due to variable lengths of the short PCA and variable optical blockade by the RPE
- ABSENT in macula: xanthophyll and lipofuscin absorbs blue light
- PRESENT in the optic disc: pre-laminar ON supplied by peri-papillary choroidal vessels - Arterial Phase: 12 seconds PI
- SIMULTANEOUS filling of retinal artery branches
- railroad track appearance:
+ due to laminar blood flow pattern: rapid flow along the vessel walls and slower towards the lumen due to increased density of RBCs
+ HYPERfluorescent walls
+ HYPOfluorescent lumen
- over in a few seconds after dye appearance
- look for: filling delays and defects
- duration altered by: cardiac diseases, blood viscosity, vascular diseases - Arterio-Venous Phase: 13 seconds PI
- dye in the retinal arterioles, capillaries and venules
- railroad track appearance - Venous Phase:
A. Early/Laminar Phase: 15 seconds PI
- majority of dye in the retinal venules
- railroad track appearance
B. Complete/Late/Peak Phase: 20 seconds PI
- most dye in the veins and less in the arterioles
- homogeneously HYPERfluorescent
- BEST time to see Foveal Avascular Zone: highlighted because choroid also homogeneously hyperfluorescent
C. Mid/Recirculation Phase: 50 - 60 seconds PI
- recirculation of dye with gradual decrease in fluorescence after excretion by the kidneys
D. Late Phase: 5 - 15 mins
- fundus devoid of fluorescence
- abnormalities: late leakage, accumulation of intraretinal dye, retinal tissue staining
Notes on the patterns of fluorescence in the different areas of the retina.
- Only 2 possible results:
1. HYPERfluorescence
2. HYPOfluorescence - Filling patterns:
+ Superior before Inferior
+ Temporal before Nasal - Choroidal fluorescence depends on:
1. RPE integrity: outer BRB acting as an optical barrier
2. Pigment density: xanthophyll, lipofuscin - Macula is HYPOfluorescent due to:
1. ABSENCE of choroidal flush:
+ High density of RPE
+ High levels of xanthophyll and lipofuscin: absorbs blue light
2. ABSENCE of retinal capillaries in the Foveal Avascular Zone
(central 500 um area)
What causes PSEUDOfluorescence?
- Defects in the filters of the fundus camera
- Should block out ALL light from other sources
What causes AUTOfluorescence?
- Fluorescence is observed PRIOR to injection of dye
- Comes from highly reflective intraocular structures:
1. Drusen
2. Asteroid bodies (asteroid hyalosis/synchysis scintillans)
3. Astrocytic hamartomas (tuberous sclerosis)
What are the different patterns of HYPERfluorescence seen in FFA?
Transmitted fluorescence/Window defect
- defects in the RPE (outer BRB) causing exposure of the underlying choroidal fluorescence
- macular hole, RPE atrophy
Dye leakage
- due to permeable or leaky vessels
- at disc: papilledema, optic neuropathy
- at macula: CME (petalloid), macular edema
- elsewhere: vasculitis, neovascularization, aneurysms
Permeability defects
1. Pooling:
- into a potential space (preretinal, subretinal space or subpigment space)
- detachment of the NSR from the RPE (CSR) or the RPE from the choroid (AMD)
2. Staining:
- into tissues (scars, drusen, sclera)
Vessel malformations
- vaso-occlusive diseases, tumors
- NO dye leakage: collaterals, AV shunts, vessel loops
- WITH dye leakage: tumor feeder vessels/neovascularizations
Autofluorescence
- visible without dye
- optic disc drusen, large lipofuscin deposits
What are the different patterns of HYPOfluorescence seen in FFA?
Blocked fluorescence
- due to optical barriers
1. PREretinal: blocks view of retinal and choroidal circulations
- vitreous opacities (granuloma, hemorrhage, degenerative)
- hemorrhage or fluid in the pre-retinal space
2. INTRAretinal: blocks view of capillary circulation, but larger retinal vessels seen
- dot and blot hemorrhages
- hard exudates
- myelinated nerve fibers
3. SUB-retinal/PRE-choroidal: blocks view of choroidal circulation, but retinal circulation seen
- subretinal hemorrhage
- pigmentation: nevus, RPE hypertrophy, melanoma
- deposits: drusen, lipofuscin, xanthophyll
Filling defects
- circulation abnormalities and non-perfusion
- disc: optic neuropathy
- arteriolar: arterial occlusion
- capillary: ischemia from DM or RVO
- choroidal: infarcts from uncontrolled hypertension
How to report a fundus fluorescein angiogram?
- Indication for the investigation
- Features on the red-free photograph
- Note phase, relative timing and delays in filling
- Describe the abnormality, hypo- or hyperfluorescent components and location of affected area:
- major vascular arcades
- retinal capillaries
- macula
- optic disc - Note changes in intensity or fluorescence over time
- Recommendations based on the results
FFA findings in DM retinopathy?
HYPERfluorescence:
- microaneurysms
- neovascularizations (fine blood vessels with florid leakage)
- intraretinal microvascular abnormalities
- venous beading
HYPOfluorescence:
- retinal hemorrhage
- ischemia
FFA findings in Post-Laser Clinically Significant Macular Edema
HYPERfluorescence
- microaneurysms: “stars in a dark sky”
- laser spots: stains/blotches of HYPERfluorescence in the periphery of laser spots (HYPOfluorescent)
HYPOfluorescence
- blot hemorrhages: dark spots
- capillary dropouts: areas of absence fluorescence
