DR WANI'S TALK ON Fundus fluorescein angiography for post graduates .pptx

FUNDUS
FLUORESCEIN
ANGIOGRAPHY
Dr.Vivek B Wani MS FRCSEd
Consultant Vitreoretina
KLES DR PRABHAKAR KORE HOSPITAL
AND MRC

61 yrs old, DV left eye 5 days,20/25
pseudophakic since one yr no CX in phaco sx
24 TH SEPTEMBER 2022 DR. VIVEK WANI KLE PG TALK FFA 2

FFA tells the story

OCT reinforces the diagnosis

Objectives of this talk
• At the end of lecture you should be able to know
-what is fluorescence
-how do we do the FFA procedure
-side effects of fluorescein
-what are blood retinal barriers and how they
decide FFA
-What is normal fluorescein angiography its
phases
-What are hypo and what is hyperfluorescence
-

What is FFA
• It is a diagnostic fundus photography
done in rapid sequence after we give
intravenous injection of fluorescein dye
• It provides information regarding
retinal circulation
choroidal circulation
integrity of outer and inner retinal barriers
6
DR. VIVEK WANI KLE PG TALK FFA
24 TH SEPTEMBER 2022

History
• 1871- Baeyer Synthesized - Sodium fluorescein
• 1959- Flocks -retinal circulation in cats after IV inj
of Sodium Fl
• 1960- MacLean and Maumenee studied choroidal
tumors on slit lamp with cobalt filter
•1961- First fluorescein angiography in
humans by Novotni and Alvis both
were medical students
7

What Is Fluorescence
Fluorescence is a property
of a substance to reach a
higher level of energy
after being excited by
light and then
immediately emit light and
return to the original level
of energy
The exciting light is of
shorter wavelength
(higher energy) than the
emitted light-Stokes law
of fluorescence
DR. VIVEK WANI KLE PG TALK FFA 8

What dye is used in FFA ?
Sodium fluorescein –
• yellowish red dye with
• molecular weight of 367.7 daltons-C20H10
O5 Na2
• Exciting light is blue light 465-490nm -485
nm peak wave length in human blood
• The emitted light is of 520-530nm
wavelength(green –yellow light) peak
wavelength 525 in human blood
9

How Do We Get Blue Light
•So a blue filter is placed in the path of
the flash light –white light- of camera
and hence only blue light enters the
eye (excitation filter)
•The blue light excites the fluorescein
in the fundus
10

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From Kanski text book

How Do We Get Green Light in the
camera
• The green light is emitted by excited Fl molecules
in retina and choroid
AND
• Some amount of blue light is reflected from retina
Both lights come out of the pupil to enter the
camera
• A green filter –Barrier filter -is placed in front of
the film to allow only green light to hit the film or
digital screen of camera
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Why Sodium Fluorescein
• Easily synthesized, cheap and relatively
inert
• Highly water soluble
• Its maximum fluorescence is at the blood
pH of 7.4
• The molecular size is large and does not
escape out of retinal capillaries and
between the RPE cells –It respects both
barriers
17

18

Why Sodium Fluorescein
While in blood the dye has
•peak excitation at 485nm
•peak emission at 525nm
•helps in using different filters to
separate the two effectively
19

What are other uses of Na fluorescein in
Ophthalmology
• Applanation tonometry
• To study ocular surface -corneal ulcers,
abrasions, or other epithelial defects
• Tear film breakup time
• Check the fit of contact lenses
• Verify the patency of lacrimal passageways
• Detect leakage of aqueous humor from corneal or
conjunctival wounds using the Seidel Test
20

Disadvantages Of Fluorescein
• It is bound in the blood to albumin
up to 80%
• Only 20% is available as free
fluorescein for FFA
PHOTOGRAPHY
• Choroidal circulation is difficult to
study because of diffuse leakage
from the choriocapillaris
• RPE pigments block the
fluorescence from choroid

Which drug do we use to study choroidal
circulation?

Drug metabolism
• The dye is metabolized in the liver and
kidney
• Eliminated in urine in 24-36 hours
• Discoloration of urine, conjunctiva and skin
are seen in all patients
• Skin coloration for 6-12 hours(avoid
sunlight)
• Urine ( orange )for 24 hours
23

Toxicity
• Mild ( 5-8% of patients)
1. Nausea
2. Vomiting
3. Pruritis
24

Toxicity
• Moderate ( 1 in 62 patients)
1. Pyrexia
2. Urticaria
3. Syncope
4. Local tissue reactions –
thrombophlebitis,, extravasation –
necrosis, neuritis
25

From opsweb.org website---------- accidental intra-arterial inj.
26

Toxicity
• Severe --CARSD
1. Cardiac ( myocardial infarction,
cardiac arrest)
2. Anaphylactic shock
3. Respiratory( bronchospasm,
laryngeal edema)
4. Seizures
5. Death (1:221,781)
27

What precautions should be in place?
• IV line
• O2
• Inj.Hydrocortisone, adrenaline, antihistamine, IV fluids
• Cardiopulmonary resuscitation
CONTRAINDICATIONS
• Known allergy to Fluorescein
• Allergy to shell fish, iodine
• Unstable angina, recent MI, recent stroke, severe renal
impairment, pregnancy first trimester?
• SO ASK HISTORY !
28

Indications
• It is mainly a diagnostic tool
• Use when FFA can make difference in diagnosis or therapy
• Where baseline data is needed –study or long term FU
29

Examples of indications
• Macular disorders –CNV, hereditary disorders, DME, ME due to RVO,
CSR, uveitis
• Wet AMD -CNV- FFA is gold standard for diagnosis
• Macular edema due to DR –specifically to rule out ischemia
• Hereditary retino-choroidal disorders –Stargardt’s, cone rod
dystrophy, RP etc
• CME-uveitis
• CRVO, BRVO-to classify ischemic from non ischemic, diagnose CME
• CSR- if treatment is contemplated to identify the site of leak to laser
• Retinal tumors or choroidal tumors- may have specific patterns to aid
diagnosis
• ROP – identifies new vessels and abnormalities at periphery -
RETCAM

The Technique
• Informed consent-MUST
• Dilatation of pupils is must
• Take IV line
• Patient at the camera, focus and take
color photographs
red free photographs and
pre-injection photograph with filters on
• IV injection of 5 ml of 10% sodium fl or 3 ml of 25%
• Take photographs from 7 sec to 40 seconds every second
• Then late photographs are taken usually after 2, 5,
20minutes
31

IV fluorescein
From Duanes text book

Oral Fluorescein Angiography
Is indicated in cases where IV is impossible or
hazardous
• Quality of photographs- not good
• 1gm of Fl( 10 ml of 10%) mixed with orange juice
to mask the taste
• Photos are taken 20 minutes and later
• All the phases of FFA cannot be studied
• Only pooling or staining can be studied
• Severe allergic reactions can still occur but
nausea and vomiting are rare
33

INTERPRETATION OF FFA
Three basic facts decide the
appearance of the FFA
A. Inner blood retinal barrier –tight junctions
between endothelial cells of retinal vessels do
not allow Fl molecules to escape from them in
to the retinal extravascular space
So any extravascular Fl in the retina is
abnormal
34

Second basic fact- that decides the appearance of the FFA
B. Outer retinal barrier – the RPE cells have
zonula occludensa between them which do
not permit Fl molecules to escape from
chorio-capillaris in to the subretinal space
So any Fl in the subretinal space is
abnormal

Choriocapillaris with fenestrations in
endothelium
• From Duanes text book

From Kansky text book
37

C. RPE contain melanin pigments which partially filter the
fluorescence of the choroidal vasculature(choriocapillaris
leak Fl molecules normally because of fenestrated
endothelium)
The brightness of choroidal vasculature depends upon
pigmentation in RPE and in diseases that cause atrophy of RPE or
hypertrophy of RPE
Retina is transparent and only xanthophyll in macula acts
as a partial filter
Third basic fact to decide the appearance of the FFA

From Duanes text book
39

Field of area photographed
• Usually about 45-60 d
• So many times peripheral pathologies are not imaged
properly
• So ultrawide field FFA has come
• 200d field
• OPTOS

Normal Findings of FFA
I. Prefilling phase( pre-injection phase)
II. Transit phase
a) Choroidal phase
b) Arterial phase
c) Arterio-venous phase
d) Venous phase
III. Re-circulation
IV. Late phase(Elimination phase)
42

I. Prefilling Phase
• Photographs are taken with the filters placed and
before the dye is injected
• This helps to rule out pseudo fluorescence and
auto-fluorescence
• Pseudo-fluorescence is due to mismatching of
filters or decay in filters
• Auto-fluorescence is natural fluorescence of
some materials in the eye
• Seen with --Optic nerve drusen, astrocytic
hamartomas, lipofuscin pigments-drusens in the
retina, Best’s vitelliform and the aging human lens
43

Autofluorescence
• From Duanes’ text book
•

II. Transit Phase
• The first complete passage of the dye through
choroidal and retinal circulations(artery,
capillaries and veins)
• Normally within the first 30 seconds of the
injection
• Subdivided into
a) Pre-arterial OR choroidal
b) Arterial
c) Arteriovenous and
d) Venous phase
45

II) (a) Pre-arterial OR Choroidal Phase
• As choroid is nearer than retina for blood
circulation, fluorescein appears in choroid
one second earlier
• Choroid fills in a segmental and patchy
filling
• It is due to the lobular arrangement of the
chorio-capillaris
• The appearance of dye in choroid is known
as choroidal flush
46

Dr.Vivek Wani

49
Dr.Vivek Wani

CHOROIDAL FLUSH with ? artery
50
Dr.Vivek Wani

II.(a) Pre-arterial phase or Choroidal
Phase
• If cilioretinal artery + it fills up at the same
time
• Less pigmented fundus will show brighter
choroidal fl
53

II. Transit phase (b)Arterial Phase
• First appearance of the dye in the retinal
arteries marks the beginning of this phase
• Lasts till the dye fills up the arterial tree and
dye appears in capillaries- retinal
background fl
• The “arm to retina” time is the interval
between the injection of dye and its
appearance in retinal artery at the disc
• Normally 11-15seconds
• Delayed in – cardiac failure, carotid block,
Temporal arteritis, CRAO etc
55

56
Dr.Vivek Wani

I. Transit phase (c) Arterio-venous Phase
• Brief phase of retinal capillaries filling up
• Starts from filling up of retinal capillaries till first
evidence of laminar filling of the veins is seen
• The capillary filling gives the background
fluorescence seen in the retina
• It starts obscuring the choroidal flush to certain
extent
• Capillary fill up is seen best in the macular area
because of the background of dark RPE
57

58
Dr.Vivek Wani

Choroidal flush and retinal backgroud fluorescence add together
to make bright retina

II.(d) Venous Phase
• Starts when the lamellar flow is seen in
veins
• Lamellar flow is due to the blood reaching
sides of the veins first and non-turbulent
flow
• In 5-15 seconds the veins fill completely
and appear brighter than arteries
• When the veins fill completely the phase
ends
60

61
Dr.Vivek Wani

Venous phase
62
Dr.Vivek Wani

Venous phase
63
Dr.Vivek Wani

64
Dr.Vivek Wani

III. Recirculation Phase
• Occurs when blood returns to the eye after complete
circulation of the dye
• This usually occurs after 30 seconds after the injection
and lasts up to 3 minutes
• Fluorescence decreases in vessels as the concentration
of dye becomes less bcs it is uniformly distributed in the
tissues in the body
• Artery and veins are equally bright
• The contrast also is less due to staining of choroidal
tissues
• Leakage and staining start in this phase
65

66
Dr.Vivek Wani

IV. Late Phase
• Begins after 15 minutes of injection
• The retinal and choroidal vessels appear only
faintly
• Background fl due to choroidal and scleral
staining is seen
• ONH staining is seen
• Vitreous and aqueous leakage is seen
• Abnormal fl like pooling in spaces is seen in this
phase
67

IV. Late phase
68
Dr.Vivek Wani

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Dr.Vivek Wani

70
Dr.Vivek Wani

Special areas-Macula
• No capillaries in the fovea
• Lutein pigments-block choroidal fl-where
are they?
• Tall RPE with more pigments also block
choroidal fl
• It remains dark till the end
71

Macula
• From Duanes text book

Macula
73

Optic Disc
•ONH lights up with choroidal stage
•Further filling in arterial stage
•No leakage over the disc
•Peripapillary scleral staining is
common
74

ONH
76

IVF
I ) Preinjection phase
II) Transit phase which is divided into
a) Choroidal or prearterial
b) Arterial
c) Capillary or arteriovenous
d) Venous
III) Recirculation phase
IV) Late phase
77

THANK YOU
END OF PART I
78

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Dr.Vivek Wani

DR WANI'S TALK ON Fundus fluorescein angiography for post graduates .pptx

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