FLUORESCEIN ANGIOGRAPHY BASIC PRINCIPLES AND INTERPRETATION

FLUORESCEIN ANGIOGRAPHYBASIC PRINCIPLES AND INTERPRETATION

Mr A Abumattar

MRCOphth

FLUORESCEIN ANGIOGRAPHY

Irvine Gass

American ophthalmologist (b. Aug. 2, 1928, Prince

Edward Island—d. Feb. 26, 2005, Nashville, Tenn.),

Gass was among the leading developers of

fluorescein angiography

Gass was a key figure in the discovery of the cause of

macular holes.

He was also among the first researchers to identify

the macular swelling that sometimes occurs after

cataract surgery, a condition called Irvine-Gass

syndrome.

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Fundal photography, performed in rapid

sequence following intravenous injection of

fluorescein dye.

It provides three main information:

The flow characteristics in the blood vessels as the

dye reaches and circulates through the retina and

choroid

Records fine details of the pigment epithelium and

retinal circulation that may not otherwise be visible

Give a clear picture of the retinal vessels and

assessment of their functional integrity.

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SODIUM FLUORESCEIN Ja

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Sodium fluorescein (C20H10O5Na2) is an organic water soluble dye.

Molecular weight is 376 daltons, and is 80% bound to plasma albumin. The remaining 20% is seen during angiography.

The dye absorbs light in the blue range of the visible spectrum, with absorption peaking at 490nm (blue). It emits light at 530nm (yellow).

ADVANTAGES OF DIFFERENT TYPES OF

ANGIOGRAPHY Ja

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Visible spectrum of

light 490nm 520nm

Shows fine retinal

vascular architecture

Does not pass through

RPE or pigment

Does not explore

choroidal lesions well

Infrared range.

805nm 835nm

Poor definition of

vascular tree

Bypass RPE and light

pigment including

blood

Improved view of

choroidal vessels

Fluorescein Indocyanine Green

FLUORESCEIN ANGIOGRAPHY Ja

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Confirm clinical

diagnosis

Plan management

Predict prognosis

Assist in follow up (↑↓)

Review outcome of

treatment

Following clinical

examination

Before discussing

diagnosis with patient

Remember to ask

patient if allergic to

any particular drug

Why do it? When to do it?

PHARMACOLOGICAL PROPERTIES OF

FLUORESCEIN Ja

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Safe (?)

Dose is 5ml of 20% of Sodium fluorescein

Warn diabetics not to adjust dosage based on Benedict’s test of urine

Give test dose in suspected cases (0.1 ml) 1/200,000 anaphylaxis, of

which 1/3000 death rate

Caution Pregnant / breast feeding

women Can be used in pregnancy

but not 1st trimester

Renal / hepatic failure patients

In Peritoneal dialysis patients the Dye takes weeks to clear

Previous allergy to fluorescein, iodine or contrast media

H/O Bronchospasm, Asthma, or chronic bronchitis

Recent MI

Congestive heart failure

Hay fever / Atopy

CHEMICAL PROPERTIES OF SODIUM FLUORESCEIN Ja

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Water soluble

Detectable at 1:100,000 dilution

Optimum fluorescence at 7.5 pH

Optimum absorption at 485-490nm and emission at 525nm

In circulation it binds to albumin

Coats RBCs but does not get inside

Metabolized by the liver and excreted by the kidneys.

Most dye is cleared within 24 hours

The skin stains yellow

Patient will urinate

bright yellow

fluorescent urine for

several hours after

administration.

ADVERSE EFFECTS Ja

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Nausea 4.6%

Vomiting 1.3%

Sneezing

Pruritus

Photosensitivity

Colour vision changes Last about 20 minutes

Inadvertent extravasation Warm sponges qds / 30 minutes each.

Review patient 1-2 days and be generous with pain killers

Mild

5-10% Transient, full recovery without medical treatment is

most likely.

ADVERSE EFFECTS Ja

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Urticaria skin rashes

Necrosis, abscess formation and, even

thrombophlebitis.

Pyrexia

Moderate

Transient, but some form of medical treatment is needed

ADVERSE EFFECTS Ja

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Anaphylaxis

Bronchospasm

Micro-embolisation Not dye particle

Plaques dislodge from carotid system

Cardiac arrest

Syncope

Death 1:222,000

Severe

Prolonged effects needs intensive medical treatment. Life

may be at risk

ADVERSE EFFECTS/ SYNCOPE Ja

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Keep IV line in situ

Head down or lay patient flat on floor

Maintain clear airway

Monitor BP and pulse

? IV steroids

IV or IM atropine if pulse rate is low

If in any doubt surely contact the crash team

Syncope is a transient loss of consciousness T-LOC due to

transient global cerebral hypoperfusion characterized by

rapid onset, short duration, and spontaneous complete

recovery.*

PHYSIOLOGICAL PRINCIPLES Ja

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Two Circulations within the fundus:

1. Choroidal circulation:The fluorescein

freely leaks out of the fenestrated Choriocapillaris, and from there through Bruch's membrane. however, tight junctions between (RPE) cells prevents dye reaching the retina

CHOROIDAL CAPILLARY

PHYSIOLOGICAL PRINCIPLES Ja

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2. Retinal circulation :

The retinal blood

vessel endothelial

cells are joined by

tight junctions which

prevent leakage of

fluorescein into the

retina. This

constitutes the blood

retina barrier.RETINAL CAPILLARY

OCULAR TISSUE RESPONSE TO FLUORESCEIN Ja

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Larger choroidal vessels are

impermeable to fluorescein

Choriocapillaris is very leaky

Extra-vascular fluorescein

stain the choroid and

connective tissues

Fluorescein permeates

through Bruch’s membrane

and binds to collagen and

drusen

Choroid Bruch’s membrane

Retinal pigment

epithelium

The tight junctions provided by zonulae occludentes prevents the dye getting into the retina except in pathological states

Retina

Retinal vessels prevent dye

escaping through the vascular

walls

OCULAR TISSUE RESPONSE TO FLUORESCEIN Ja

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Blood vessels of the ciliary body are freely permeable to the dye

Allows free flow between the posterior and anterior chamber

The superficial retinal vessels are impermeable

The deeper posterior ciliary vessels are permeable thus the optic nerve head shows mild staining during the late phase of the angiography

Ciliary body Optic nerve head

Vitreous

Takes several days for the

dye to be completely removed

from the vitreous

The anterior vitreous clears

through the forward diffusion

into the aqueous

Sclera

The inner surface of the

sclera stains from the leaked

dye from the Choriocapillaris.

This is seen in late phases

through window defects

NO STANDARD NOMENCLATURE FOR THE

VARIOUS PHASES

The time from when an injection of fluorescein is administered into an antecubital vein until the time that the dye first appears in the central retinal artery is called the arm-retina-time and it can vary significantly (between circa 7 to 15 seconds). It depends on a number of factors, including the size of the cubital vein, the speed of the injection, the blood pressure and cardiac output. It is shorter in young people and longer in the elderly. The dye appears first in the choroid and then shortly thereafter in the central retinal artery. There is no standard nomenclature for the various phases. Generally, though, an early phase is identified as the time to filling of the retinal arterioles (arterial phase), an intermediate phase (“arteriovenous phase”) that lasts up to the first appearance of the dye in retinal veins (and often subdivided into early, intermediate and late arteriovenous phases), and finally a late phase during which the fluorescence gradually fades away.

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PHASES OF A NORMAL FLUORESCEIN

ANGIOGRAPHY Ja

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Choroidal phase

10-15 seconds

choroidal filling via the

short ciliary arteries

results in initial patchy

filing of lobules, very

quickly followed by a

diffuse (blush) as dye

leaks out of the

Choriocapillaris.

Cilioretinal vessels and

prelaminar optic disc

capillaries fill during

this phase


ANGIOGRAPHY Ja

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Arterial phase

The central retinal

artery fills about 1

second later than

choroidal filling


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Early arteriovenous phase

The fluorescein dye from the smaller venules enters the vein along their walls resulting in a laminar flow of the dye in the vein.

As the vascular flow is faster in the centre of the vessel than on its side ,the fluorescein dye sticks to the walls of the vein another contributing factor for laminar flow


ANGIOGRAPHY Ja

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Arteriovenous phase

The dye completely fills the lumen of the vein.

Perifoveal capillary network is best visualized at 20 to 25 seconds after the injection when the concentration of the dye is maximum.

The fovea appears hypofluorescent because of: Absence of the blood vessels

in the foveal avascular zone (FAZ)

Blockage of the background choroidal fluorescence by the increased pigment in the tall RPE cells at the fovea


ANGIOGRAPHY Ja

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Venous phase

The whole diameter of

the veins is filled


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Late phase

After 10 to 15 minutes

little dye remains

within the blood

circulation. Dye which

has left the blood to

ocular structures is

particularly visible

during this phase

MAIN INDICATIONS FOR FLUORESCEIN ANGIOGRAPHY Ja

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Detecting any significant macular oedema which is not clinically obvious.

Locating the area of oedema for laser treatment

Differentiating ischemic from exudative diabetic maculopathy.

Differentiating between IRMA and new blood vessels if clinical differentiation is difficult

Determining the integrity of the foveal capillary bed and the extent of macular oedema following branch retinal vein occlusion

Differentiating collaterals from neovascularization

Less commonly it is used purely to determine the extent of retinal ischaemia (as this can be done clinically)

Diabetic patients: Retinal vein occlusion:

MAIN INDICATIONS FOR FLUORESCEIN ANGIOGRAPHY Ja

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Locate the subretinal

neovascularization

and determine its

suitability for

treatment

Locating subretinal neovascularmembrane in various conditions (high myopia, angioid streaks, choroidal rupture and chorioretinitis)

Locating abnormal blood vessels (for example idiopathic retinal telangietasia, retinal retinopathy etc)

Looking for break down of RPE tight junctions (central serous retinal retinopathy) or the blood retinal barrier (cystoid macular oedema)

Help with diagnosis of retinal conditions (for example Stargardt's disease gives a characteristic dark choroid).

Age-related macular

degenerationOther indications:


INTERPRETATION

A systematic approach to angiogram will ensure that maximum information is gained.

Colour fundus photograph and relevant clinical information is essential for meaningful interpretation.

Follow an abnormal feature through a sequence of angiogram photographs, then analyse each photograph separately.

Start with any striking abnormality and describe this in detail:

Hypo/hyper fluorescent components

Intensity of fluorescence and changes with time

Area of fluorescence and changes with time

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UO

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INT

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PR

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Color (A) and

red-free (B)

photographs

of a fundus

with soft

drusen and

hyper-

pigmentation.

Soft drusen

hyper-

fluoresce

during the

early phase of

angiography

(C) and stain

in the late

phase (D)

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FLUORESCEIN ANGIOGRAPHY INTERPRETATION

CAUSES OF HYPOFLUORESCENCE

1. Decreased transmission

Blockage may be caused by:

Pre-retinal opaque structures superficial to the retinal

circulation will mask both the retina and choroidal

circulation e.g. Preretinal haemorrhage or Myelinated

nerve fibres.

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CAUSES OF HYPOFLUORESCENCE

Opaque structures deep to the retinal circulation but

superficial to the choroidal circulation will mask only the

choroidal circulation for example:

1. Retinal haemorrhages in diabetic retinopathy

2. Retinal vein occlusion

3. Subretinal blood from choroidal new vessels

4. Hard exudates

5. Cotton wool spots

6. Melanin in choroidal naevus

7. Xanthophyll pigment - in the area of the macula

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CAUSES OF HYPOFLUORESCENCE Ja

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2. Filling defect due to

abnormal circulation

Arterial non-perfusion is

seen in occlusion of the

central retinal artery and

its branches

Capillary non-perfusion is

an important signs of

retinal ischaemia.

Diabetic retinopathy and

Retinal vein occlusion.


CAUSES OF HYPERFLUORESENCE Ja

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1. Window defects

of the RPE

Like in RPE

atrophy or

Macular hole

Hyperfluoresence

in the macula due

to RPE window

defect allowing

choroidal

fluorescein to

show through

brightly.



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2. Leakage of dye

Neovessels with

leakage

Microaneurysms

Note the

Hypofluorescence

from dot and blot

haemorrhages



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3. Leakage with

pooling

1) RPE detachment

2) Central serous

retinopathy CSR

3) Cystoid macular

oedema CMO

Cystoid macular

oedema with petalloid

pattern in late phase



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4. Leakage with

staining

Collagen absorbs

fluorescein dye causing

staining which persists

after dye has been

cleared from the

choroidal and the

retinal circulations.

Profound ischaemia

and vasculitis both

lead to incompetence of

retinal endothelium

tight junction.

Par planitis showing

staining of the

blood vessels

and dye leakage at the

optic disc



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5. Drusen present in

age-related

maculopathy

becomes stained by

absorbing dye from the

choroidal circulation

6. Leakage from

abnormal vessels

Fundal tumours such

as choroidal malignant

melanoma, have their

own blood supply

which may leak.

Late phase.

Leaking subretinal

neovascularization and

staining of the drusen.



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7. Autofluorescence of optic nerve head drusen.

(A) Pre-injection photograph of the optic nerve in a patient with optic nerve head drusen. Both barrier and exciter filters are in place.

(B) Same patient after filling of retinal vessels


ABNORMAL DYE DISTRIBUTION SUMMARY Ja

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Decreased fluorescence

Decreased

transmission

Filling defect due

to abnormal

circulation

Increased fluorescence Window defects of

the RPE

Leakage with pooling

Leakage with staining

Drusen present in age-related maculopathy

Leakage from abnormal vessels

Autofluorescence of optic nerve head drusen

Hypofluorescence Hyperfluoresence

FLUORESCEIN ANGIOGRAPHYBASIC PRINCIPLES AND INTERPRETATION

Quiz

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DIABETIC MACULOPATHY

RIGHT FFA, VENOUS PHASE, HYPO, HYPER Ja

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NPDR RIGHT FFA, VENOUS PHASE, HYPO, HYPER, MA, DOTS, BLOTS

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CSRLEFT FFA, LATE PHASE, HYPER, POOLING, SMOKE STALK J

an

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BRVORIGHT FFA, VENOUS PHASE, HYPO, HYPER, LASER SCARS, NON PERFUSION

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NVDLEFT FFA, EARLY VENOUS PHASE, HYPER WITH BRANCHING FINE

VESSELS, MASKING Ja

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STARGARDT’SRIGHT FFA, VENOUS PHASE, CHOROID FLUORESCEIN ABSENT, DARK CHOROID

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ANGIOID STREAKS

RIGHT FFA, VENOUS, HYPER, RADIATES OUT FROM DISC

IF CNV DEVELOP VISION WELL BE SEVERELY AFFECTED

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WET AMD

RIGHT FFA, EARLY VENOUS, HYPO, HYPER, EARLY LACY PATTERN

CONSISTENT WITH SRNVM, SUBRETINAL HGE

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CHOROIDAL MELANOMA Ja

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Early FFA of choroidal melanoma showing

intrinsic vascularity

Late FFA showing early diffuse staining

Colour photograph of a dome-shaped choroidal

melanoma.

CHOROIDAL MELANOMA Ja

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Early FFA of choroidal melanoma showing

intrinsic vascularity

Late FFA showing early diffuse staining

Colour photograph of a dome-shaped choroidal

melanoma.

B-scan ultrasound showing acoustic

hollowing and uveal excavation

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ph

y B

asic P

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A A

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58

FLUORESCEIN ANGIOGRAPHY BASIC PRINCIPLES AND INTERPRETATION

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