Fluorescein Angiography

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Fluorescein Angiography

• Cathryn Edrich FRCS(Ed)
• Hull East Yorkshire Eye Hospital
• ( HEYEH )

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Brief history of Fluorescein

• 1871 Baeryer combined resorcinal phthalic acid
  anhydride
• C20H1005Na2
• Mwt 376 daltons
• 80 protein bound to albumin

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Brief History of Fluorescein

• 1882 Ehrlich introduced fluorescein into
  investigative ophthalmology
• 1940 Gifford studied aqueous dynamics after
  injecting intravenous fluorescein
• 1960 2 medical students Novotny Alwis
  experimented on each other and developed FFA

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Properties of Fluorescein

• 80 albumin bound 20 left for fluorescence
• Maximally fluoresces at pH 7.4
• Rapid diffusion through intra extracellular
  spaces
• Diffuses freely through choriocapillaris, Bruchs
  membrane, ON, sclera
• Cannot cross the retinal bvs, intact RPE
  larger choroidal vessels

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Properties of Fluorescein

• Stains skin mucous membranes yellow for 24
  36 hrs
• Metabolised by liver excreted via kidneys
  yellow urine for 24 36 hrs
• Absorbs light in blue range (490nm) emits in
  yellow range (530nm)

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Understanding FFA

• Inner and Outer blood retinal barriers are key!
• Both barriers control movement of fluid, ions
  electrolytes from intravascular space to
  extracellular space in retina
• FFA method of examining competence of blood
  retinal barriers and making permanent record

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Inner blood-retinal barrier

• At level of retinal capillary endothelium (tight
  junctions, non-fenestrated) and basement membrane
• Prevents all leaks of fluorescein and
  albumin-bound fluorescein
• Hence see clear picture of retinal bvs

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Outer blood-retinal barrier

• Composed of intact RPE (tight junctions b/w RPE
  cells). Impermeable to fluorescein
• RPE presents an optical barrier to fluorescein
  and masks choroidal circulation

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Photography

• Procedure, risks, contraindications (handout)
• Fundal camera built-in filters termed exciter
  barrier
• Retina illuminated via blue exciter filter
  (? 465-490nm) absorbed by fluorescein
• Fluorescein re-emits at ? 520-530nm (fluoresces
  green)
• Barrier filter (yellow-green) allows only
  re-emitted light to expose film

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The Normal FFA

• Baseline photos and red free
• 5 Phases of FFA
• Choroidal phase
• Arterial phase
• Capillary phase
• Venous phase
• Late phase

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Timings of the FFA Phases

• Arm to retina (ONH) 7-12s
• Posterior-ciliary artery fill 9s
• Choroidal flush, cilio-retinal artery 10s
• Retinal arterial phase 10-12s
• Capillary transition phase 13s
• Early venous/lamellar/a-v phase 14-15s
• Venous phase 16-17s
• Late venous phase 18-20s
• Late phase 5 15 mins

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15s early venous
12s arterial phase
20s venous phase
52s late phase
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Factors altering timing of phases

• Arterial phase may range from 2-30s may be
  affected by cardiac disease, blood viscosity,
  vessel calibre, CCF, GCA, ?BP, carotid artery
  stenosis
• Beware bolus of fluorescein passing around aortic
  arch missing carotids on 1st circulation time!

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Patterns of fluorescence

• Superior arterioles fill before inferior and
  temporal before nasal
• Choroidal scleral fluorescence depends on
  pigment density of RPE its integrity
• Macular hypofluorescence due to ?d density of
  RPE xanthophyll blocking choroidal fluorescence
• No retinal capillaries here FAZ 500µm foveola
  350µm

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Abnormal fluorescence

• Only 2 fundamental principles in FFA
• Things will either HYPERfluoresce or
  HYPOfluoresce!

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Hyperfluorescence

• Transmitted fluorescence defects in RPE GA,
  FTMH
• Leaks MAs, IRMA, nvs, Capillary leaks
• Abnormal vessels RVOs, collaterals shunts
  (no leak), tumour feeder vessels (some leak)

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Hyperfluorescence

• Permeability defects cause pooling staining
• Pooling serous RPE detachment, SRF (? in size,
  shape intensity in later phases)
• Staining sclera, ON, drusen, vasculitis. (Leak
  into tissue rather than anatomical space)

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Hypofluorescence

• Blocked optical barriers e.g pigment blood
  egCHRPE, naevi, myelinated NFs, SRF, HEs
• Filling defects capillary closure, RVOs

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Autofluorescence

• Due to the 2 barrier filters not having mutually
  exclusive transmission spectra
• Light from bright fundal structures can pass
  through both filters expose film. e.g. ONH
  drusen, astrocytic hamartomas

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Autofluorescence

• Autofluorescence can be diagnostic
• FFA can exclude papilloedema
• Saves pt from invasive neuro diagnostic
  procedures!

Optic nerve head drusen
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Pseudofluorescence

• CB readily leaks fluorescein during aqueous
  production, into ocular fluids.
• Green light emitted when excited by blue light.
  Illuminates light coloured structures eg MNFs,
  white lesions

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Indications for FFA

• To aid diagnosis
• Decisions on whether to Rx or not
• Always study FFAs with other relevant
  investigations before making final diagnosis

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Interpretation

• Start by describing obvious abnormality
• Describe hypo/hyperfluorescent components
• Intensity of fluorescence with time
• Area of fluorescence changes with time

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Interpretation

• Run through anatomical list describing any other
  abnormalities affecting structures below
• Macula
• Disc
• Major arcades
• Capillaries

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Interpretation diabetic retinopathy

• Early venous phase
• HyperF NVD, mas
• HypoF blocked due to blood

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Interpretation - DR

• HypoF retinal haem 1 ischaemia 2
• HyperF mas 3, nvs 4
• IRMA 5
• Venous beading 6

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Post laser CSMO

• HyperF mas (leak) laser spots (stain)
• HypoF pigmented scars, blood, capillary drop out

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PRP laser for PDR

• HypoF massive retinal capillary dropout,
  pigmented laser scars
• HyperF laser scar staining

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Retinal Vein Occlusion

• HypoF retinal capillary closure, SRF, blood
• HyperF retinal vein damage staining collagen,
  leaking through damaged endothelial walls

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ST BRVO

• HyperF damaged veins staining and leaking, mas
• HypoF subretinal and preretinal haems

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Collaterals

• Collaterals dont
• leak!

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CRAO

• Non-perfusion of retinal vasculature. Vessels
  appear dark against light background
• No capillary perfusion, so empty veins
  (cattle-trucking)
• Choroidal perfusion intact (hence cherry red
  spot) C-R artery sparing in 15

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Transmission/window defects

• RPE atrophy allows choroidal fluorescence through
  with choroidal flush
• Does not change size or shape with time
• Fades with choroidal fluorescence

Red Free
Late
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Geographic Atrophy (GA)

• Large area of GA
• Clear view of choroidal vessels
• FFA shows unmasking of choroidal vessels

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Full thickness macular hole

• RPE show-through
• Loss of masking
• Early lighting up with choroid

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Leak and Pool - CSR

• Small defect in outer BR barrier
• F enters RPE defect fills serous retinal
  elevation blister (7 cases)
• HyperF - ?s in size intensity

Early
Late
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Leak Pool

• Breakdown of internal BR barrier
• Early leak from parafoveal retinal vessels
  hyperF, ? in FAZ
• Late pooling in classic petalloid appearance
  (NFL)

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Leak Stain

• Ischaemia vasculitis ?incompetent endothelial
  TJs
• F leaks into CT of bvs stains it. This
  persists
• Late disc staining is normal

ARN
Pars planitis
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Early late leaks classic SRNVMs

• Early lacey hyperF classic
• HypoF halo blood /or macula pigment
• Late leak, blurred margins apparent ? in size

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Late leaks occult SRNVMs

• Type I PED well-defined area of early hyperF,
  margins unchanged
• Type II late leak of undeyermined source not
  obvious from early phase

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Blocked fluorescence
Choroidal naevus blocking choroidal fluorescence
in arterial phase
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Blocked fluorescence

• Stargardts dark choroid (early)
• Lipofuscin deposition at RPE

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References

• Fluorescein Angiography, technique interpretation
  application, Max Nanjiani (OMP)
• www.mrcophth.com/ffainterpretation