NALIN NAYAN OPTOMETRIST

It is a medical imaging technique used to visualize the inside of blood vessels and organs of the body, with particular interest in the arteries, veins and the heart chambers.

traditionally done by injecting a radio-opaque contrast agent into the blood vessel and imaging using X-ray based techniques

The word itself comes from the Greek words angeion, "vessel", and graphein, "to write or record".

The film or image of the blood vessels is called an angiograph, or more commonly, an angiogram.

- Fundus Fluorescein angiography refers to photographing fluroscein dye in the retinal vasculature following intravenous injection of fluroscein sodium.

- Described in 1959 by MacLean and Maumenee

Fluorescein (C20H12O5) refers to Fluorescein sodium (C20H10Na2).

Is a brown or orange-red crystalline substance first synthesized in 1871 in Germany by Von Baeyer

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

Non toxic, inexpensive, safe Alkaline solution Highly fluorescent Absorbs blue light (480-500 nm) Emits yellow-green (500-600 nm [525

nm]) Effective at pH 7.37-7.45 Removal from blood by kidneys and

liver within 5 hrs.

Inner and Outer blood retinal 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

GENERAL PRINCIPLES:- -Fluorescein binding. -Inner blood retinal barrier. -Major choroidal vessels. -Outer blood retinal barrier. -Excitation peak. -Types of filters.

70-85% fluorescein molecules bind to serum proteins (mainly albumin) on entering the circulation.

The rest unbound molecules are referred to as free fluorescein.

At level of retinal capillary endothelium (tight junctions, non-fenestrated) and basement membrane

Prevents all leaks of free fluorescein and albumin-bound fluorescein.

in vascular permeability caused by changes in intravascular pressure or tissue hydrostatic pressure, or by change in capillary walls themselves, will permit leakage of both bound & free fluorescein molecules in extra vascular space.

-impermeable to both bound & free fluorescein molecules.

- walls of choricapillaries are extremely thin & contain multiple fenestrations through which free fluorescein molecules are able to escape into the extra vascular space & across Bruch’s membrane.

Composed of intact RPE (tight junctions b/w RPE cells).

Impermeable to free fluorescein. RPE presents an optical barrier to

fluorescein and masks choroidal circulation

490 nm (blue part of spectrum). represents maximal absorption of

light energy by fluorescein. Molecules stimulated by this

wavelength will be excited to higher energy level & will emit light of longer wavelength ( green portion of spectrum i.e. at 530 nm ).

2 types of filters:- - cobalt-blue excitation. - yellow-green barrier.Ensures blue light enters the eye &

only yellow green light enters the camera.

Light emitted from retinal camera passes through blue excitation filter, emerging blue light enters the eye & excites Fluorescein molecules in retinal & choroid circulation of longer wavelength (yellow green).

Yellow green barrier filter thus blocks any blue light that may leave eye, allowing only yellow-green light to pass through unimpaired to be recorded on film.

- Pupil should be dilated.TECHNIQUE:-- Patient seated in front of camera with one arm

out stretched.- Fluorescein 5 ml of 10% solution is drawn up

into syringe. In opaque media, 3 ml of 25% solution may be

preferred, because it gives better result.

- Red free photograph is taken.- Fluorescein injected rapidly into antecubital

vein.- Photographs are taken at approx 1 sec

interval between 5 & 25 sec after injection.- After transit phase has been photographed

in eye, control pictures are taken of opposite eye.

If necessary, late photograph can also be taken after 10 min & occasionally after 20 min if leakage is anticipated.

Red after image. Transient nausea. Flushing of skin. Itching. Hives. Excessive sneezing. Discolouration of urine & skin.

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

1) CHOROIDAL OR PRE-ARTERIAL PHASE:- -Choroidal circulation is filling, but no dye

has reached the retinal arteries.2) ARTERIAL PHASE:- -follows 1 sec after pre-arterial phase. -extends from first appearance of dye in the

arteries until whole arterial circulation is filled.

3)CAPILLARY OR ARTERIOVENOUS PHASE:- -characterized by complete filling of the

arteries & capillaries with early lamellar flow in the veins.

4) VENOUS PHASE:- - subdivided into early, mid & late stages according

to extent of venous filling & arterial emptying. early venous phase:- shows complete arterial &

capillary filling, & lamellar venous flow. mid venous phase:- shows almost complete venous

filling. late venous phase:- shows complete venous filling. -arteries are beginning to show decreasing fluorescence. -Recirculation of dye occurs within 3-5 min. -The intensity of fluorescence begins to diminish

so that arteries & veins appear equally fluorescent.

5) LATE PHASES:- - shows effects of continuous

recirculation, dilution & elimination of dye.

- with each succeeding wave, the intensity of fluorescence becomes weaker.

- late staining of optic nerve is a normal finding.

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

12s arterial phase 15s early venous

20s venous phase 52s late phase

Arterial phase may range from 2-30s; may be affected by:

- cardiac disease - blood viscosity- vessel calibre- CCF- GCA - ↑BP- carotid artery stenosis.

Superior arterioles fill before inferior and temporal before nasal

Choroidal & scleral fluorescence depends on pigment density of RPE & its integrity

Macular hypo fluorescence – due to ↑’d density of RPE & xanthophyll blocking choroidal fluorescence

No retinal capillaries – FAZ 500μm; foveola 350μm

Only 2 fundamental principles in FFA

- HYPER fluorescence or HYPO fluorescence !

MAY BE CAUSED BY:- 1) AN RPE WINDOW DEFECT: -RESULTING FROM ATROPHY OF

OVERLYING RPE CELLS WITH UNMASKING OF NORMAL BACKGROUND CHOROIDAL FLUORESCENCE.

2) POOLING OF DYE:- -UNDER A DETACHMENT OF RPE OR

IN IN THE SUB RETINAL SPACE. - CAUSED BY A BREAKDOWN OF

OUTER BLOOD RETINAL BARRIER.

3) LEAKAGE OF DYE:- - into the sensory retina as a result

of breakdown of inner blood retinal barrier.

- may be:- ~from choroidal new vessels. ~from retinal new vessels. ~from the optic nerve head (in papilloedema).

4) STAINING OF TISSUES:- - as a result of prolonged retention

of fluorescence.

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)

May be caused by :- 1) BLOCKAGE OF FLUORESCENCE:- - by increased density of pigment (xanthophyll -sensory retina,

melanin- RPE) - deposition of abnormal materials ( hard exudates in sensory retina,

lipofuscin in Best’s disease) - Blood.

2)obstruction of retinal and choroidal circulation:-

- preventing access of fluorescein to the tissues.

3) loss of vascular tissues:- - in severe myopic degeneration or

choroideremia.

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

Autofluorescence can be diagnostic

FFA can exclude papilloedema

Saves pt from invasive neuro diagnostic procedures!

Optic nerve head drusen

CB readily leaks fluorescein during aqueous production, into ocular fluids.

Green light emitted when excited by blue light. Illuminates light coloured structures eg: MNF’s, white lesions

To aid diagnosis

Decisions on whether to Rx or not

Always study FFA’s with other relevant investigations before making final diagnosis

Start by describing obvious abnormality

Describe hypo/hyperfluorescent components

Intensity of fluorescence with time Area of fluorescence & changes with

time

Run through anatomical list describing any other abnormalities affecting structures below:

Macula Disc Major arcades Capillaries

Early venous phase

HyperF – NVD, ma’s

HypoF – blocked due to blood

HypoF retinal haem 1 ischaemia 2

HyperF ma’s 3, nv’s 4

IRMA 5 Venous beading 6

HyperF – ma’s (leak) & laser spots (stain)

HypoF – pigmented scars, blood, capillary drop out

HypoF – massive retinal capillary dropout, pigmented laser scars

HyperF – laser scar staining

HypoF – retinal capillary closure, SRF, blood

HyperF – retinal vein damage – staining collagen, leaking through damaged endothelial walls

HyperF – damaged veins staining and leaking, ma’s

HypoF – subretinal and preretinal haems

Collaterals don’t leak!

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%

RPE atrophy allows choroidal fluorescence through with choroidal “flush”

Does not change size or shape with time

Fades with choroidal fluorescence

Red Free

Late

Large area of GA

Clear view of choroidal vessels

FFA shows unmasking of choroidal vessels

RPE “show-through”

Loss of masking

Early lighting up with choroid

Small defect in outer BR barrier

F enters RPE defect & fills serous retinal elevation “blister” (7% cases)

HyperF - ↑’s in size & intensity

Early

Late

Breakdown of internal BR barrier

Early leak from parafoveal retinal vessels – hyperF, ↓ in FAZ

Late pooling in classic “petalloid” appearance (NFL)

Ischaemia & vasculitis incompetent endothelial TJ’s

F leaks into CT of bv’s & stains it. This persists

Late disc staining is normal

ARN

Pars planitis

Early lacey hyperF “classic”

HypoF “halo” – blood &/or macula pigment

Late leak, blurred margins & apparent ↑ in size

Type I – PED – well-defined area of early hyperF, margins unchanged

Type II – late leak of undeyermined source – not obvious from early phase

Choroidal naevus blocking choroidal fluorescence in arterial phase

Stargardt’s – “dark choroid” (early)

Lipofuscin deposition at RPE

Fluorescein Angiography, technique interpretation & application, Max Nanjiani (OMP)

www.mrcophth.com/ffainterpretation