ffa by suraj chhetri
TRANSCRIPT
FUNDUS FLUORESCEIN ANGIOGRAPHY
SURAJ CHHETRIB.Optometry16th batchMaharajgung medical campus , Nepal
PRESENTATION LAYOUT• Introduction to fluorescein
• Basic principle of fluorescence• Some terminologies • Anatomical considerations • Indication and contraindication of FFA • Procedure of FFA• Normal phases of FFA • FFA interpretation• FFA Vs ICG• Phenomenon of FFA
INTRODUCTION OF FLUORESCEIN
• Orange water soluble dye
• When injected IV , it remains largely intravascular and circulates in blood stream
• 70 – 85 % of fluorescein bind with blood serum albumin
• Rest of remain free i.e unbound form
• Sodium fluorescein : C20 H10 O5 Na2
CONTINUE…• Properties
-Non-expensive-Non-toxic-Flouresces at blood PH level 7.37 – 7.45 -Rapid diffusion
• Synthesized from the petroleum derivatives resorcinol and phthalic anhydride
Chemically related to Phenolphthalein
• Molecular weight : 376 daltons
BASIC PRINCIPLE OF FLUORESCENCE
• Absorption followed by release of the radiant energy in the form of visible light
• Fluorescent substance follows Stokes lawStokes law
• Fluorescent substances absorbs light • Molecular excitation• Electrons elevated to higher less stable state Returns
to stable lower energy form Releasing light of longer wavelength FLUORESCENCE
• Entire process – 10 – 8 sec.
BASIC PRINCIPLE OF FLUORESCENCE
• Absorption spectrum of fluorescein – 465 to 490 nm• Excitation peak 490nm (blue part of spectrum )• Emission spectrum of fluorescein – 520 to 530 nm • Emission peak 530 nm (green-yellow spectrum )
NOTEAbsorbed radiant energy > emitted energy
AND As energy – inversely proportional to –wavelength SO, λ of emitted wave > λ of absorbed wave
FILTERS FOR PROCEDURE• Two type • 1) blue barrier filter• 2) yellow green barrier filter • Blue barrier filter ensures that only the blue light enters the eye
• Yellow green barrier filter blocks the blue light reflects from the eye • It allows green light to pass through unimpaired, to be recorded on the
film
TERMINOLOGIES Fluorescence- ability of a compound to absorb light of
shorter wavelength and emit light of longer wavelength with in a very short interval
Hyper-fluorescence – an area of abnormally high fluorescence due to increase density of dye molecule
Hypo-fluorescence - an area of abnormally poor fluorescence
Auto-fluorescence – an inherent property of a lesion to spontaneously fluoresce even in absence of dye
( observed before injection of the dye)
Arm retina circulation time- from dye injection to first appearance in retinal arteries( 10-12 sec)
Pooling- accumulation of dye in closed space .e.g. RPE detachment, CSR
Leakage- dye escapes in open space e.g. vitreous space
Window defect- type of early hyper-fluorescence due to RPE atrophy
Control photograph –photo taken before dye given to detect auto-fluorescence
Staining- late hyperfluorescence due to adsorption of the dye by a tissue
Blocked fluorescence – hypofluorescence occurs by masking underlying retinal and choroidal tissue by blood , pigment etc.
Capillary nonperfusion – due to non filling of the retinal capillaries due to anatomical and function reasons
Artifacts- undesirable shadows that are seen following the development of the film
ANATOMICAL CONSIDERATION• Major choroidal vessels are impermeable to both bound and unbound
form of fluorescein BUT Choriocapillaries • Walls are extremely thin • Contains multiple fenestrations • Through which free molecules pass across Bruchs membrane
Choriocapillaries and Bruchs membrane both permeable to free and bound fluorescein molecules
CONTINUE….• Outer blood retinal barrier : tight junction between RPE cells prevent
passage of fluorescein
• Inner blood retinal barrier : tight junctins between endothelium cells of retinal blood vessels prevent passage of fluorescein
• Fluorescein pass from choriocapillaries also passes through bruch’s membrane but it encounter with tight junction intracellular complex zonula occludens of RPE cells and prevent passage
• Disruption of barrier leak both bound and free fluorescein molecules
BLOOD VESSLES IN RETINA
• For FFA interpretation sensory retina divided into two layers 1. Inners vascular half ( ILM – INL ) Here retinal blood vessels located in two separate planes large retinal arteries and veins located in nerve fiber layer Retinal capillaries located in inner nuclear layer
2. Outer avascular half (OPL – RPE )• when retina becomes edematous ,• it is the layer that fluid accumulate causing the cystoid space
PURPOSE OF FULUROSCEIN ANGIOGRAPHY
• Studying the normal physiology of the retinal and choroidal circulation,as well as disease process affecting the macula.
• Evaluation of the vascular integrity of the retinal and choroidal vessels • Check the integrity of the blood ocular barrier.
- Outer blood retinal barrier breaks in CSR
- Inner blood retinal barrier breaks in NVD, NVE
CONTINUE…
• It helps in clinical diagnosis
• To determine extent of damage
• To formulate treatment strategy for choroidal and retinal disease
• To monitor result of treatment
INDICATION OF FFARetinal vascular malformation and tumors
Retinal vascular disorders
Macular disorders
Choroidal disorders
Optic nerve disorders
Retinal diseases1) Diabetic retinopathy2) Retinal vein occlusions3) Retinal artery occlusion4) Retinal vasculitis5) Coats disease6) Familial exudative
vitreoretinopathy
Macular diseases1) Central serous retinopathy2) RPE detachment3) Cystoid macular edema4) Macular hole5) ARMD6) Cone rod dystrophy7) Epiretinal membrane8) Vitiliform dystrophies9) Stargardts dystrophy
Retinal vascular malformations and tumors
1) Capillary hemangioma of retina2) Cavernous hemangioma of retina3) Retinal AV malformation 4) Congenital tortuosity of retinal vasculature5) Congenital hypertrophy of RPE6) Angioid streaks7) Astrocytic hamartoma
Choroidal lesions1) Choroidal neovascular (CNV)2) Hemangioma3) Nevus4) Melanoma5) Choroiditis6) Choroidal folds
Optic nerve disorders1) Optic atrophy2) Papilloedema3) Ischemic optic neuropathy4) Optic disc pit5) Optic disc drusen6) Optic disc hemangioma7) Melanocytoma8) Myelinated nerve fibers
CONTRAINDICATIONS ABSOLUTE1) known allergy to iodine containing compounds.2) H/O adverse reaction to FFA in the past.
RELATIVE1) Asthma2) Hay fever3) Renal failure4) Hepatic failure5) Pregnancy ( especially 1st trimester)
MILD MODERATE SEVERE
Staining of skin, sclera and mucous membrane
Nausea and vomiting
Respiratory- laryngeal edema,bhroncospasm
Stained secretionTear, saliva
Vasovagal response
Circulatory shock, MI, cardiac arrest
Vision tinged with yellow
utricaria Generalized convulsion
Orange-yellow urine
fainting Skin necrosis
Skin flushing, tingling lips pruritis
periphlebitis
COMPLICATIONS
COMPICATIONS MANAGEMENT• Unavoidable minor side effects : treatment not needed
• Temporary tan skin colour, Red after image from the photoflash and discoloration of the urine
• Transient Nausea and vomiting (10%): treatment not needed
• Vasovagal syncope (1%) :treatment not needed
• In extreme bradycardia • IV atropine may be needed.
CONTINUE..• Anaphylaxis such as bronchospasm, urticarial skin rash and
hypotension (<1%). • Treatment is with chlorpheniramine (piriton) 10mg IV, hydrocortisone
100mg IV
• Hypotension and Bronchospasm • oxygen and adrenaline 1ml of 1:1000 IM
• Cardiac and respiratory arrest (<0.01%)• Treatment would involve cardiopulmonary resuscitation
EQUIPMENT AND MATERIALS NEEDED FOR ANGIOGRAPHY
Fundus camera and auxilliary equipment
Matched fluorescein filters ( barrier and exciter )
Digital photoprocessing unit ( computer based )
23 gauge scalp vein needle
5 ml syringe
5 ml of 10% OR 3ml of 25 % fluorescein solution
20 gauge , 1.5 inch needle to draw the dye
Armrest for fluorescein injection
Tourniquet
Alcohol swabs
Bandage
Standard emergency equipment
PROCEDURE Patient is informed of the normal procedures, the side effects and the adverse
reactions.
Dilating the pupil
Made to sit comfortable.
3-4 red free photographs taken. (control photographs)
5ml of 10% or 3ml of 25% NAF injected through the anticubital vein
Wait for 8 seconds for young and 12 seconds for older patients ( normal arm-retina time)
Photos are taken at 1 second interval for 10 seconds
Then every 2 seconds interval for 30 seconds
Late photographs are usually taken after 3 ,5 and 10 minutes.
CIRCULATION OF DYE
Dye injected from peripheral vein
venous circulation
heart
arterial system INTERNAL CAROTID ARTERY
Ophthalmic artery Short posterior ciliary artery) Central retinal (choroidal circulation.) ( retinal circulation)
NORMAL PHASES IN FFA• Early phase
• Choroidal(prearterial)• Arterial• Arteriovenous (capillary)• Venous
• Early• mid• Late
• Mid phase• Late phase
CONTINUE…• Normally 10 -15 secs elapse between dye injection and arrival of dye
in the short ciliary arteries
• Choridal circulation preceeds retinal circulation by 1 Sec
• Transit- if dye through the retinal circulation takes approximately 15-20 secs
EARLY PHASE
• Choroidal filling through the short ciliary arteries • Initial patchy filling of lobules followed by diffused blush as
dye leaks out of choriocapillaries• Cilioretinal vessels and prelaminar vessels and prelaminar
optic disc capilaries fill
Choroidal ( prearterial ) phase
FACTS OF PATCHY CHOROIDAL FILLING• Choriocapillaries has number of lobules
• The lobules fill independently from one another,
• giving a transiently patched or blotched appearance
ARTERIAL PHASE
• Begins with the first appearance of fluorescein in the arteries, and extends until the arteries are completely filled
• Posterior pole fills with dye earlier than the periphery
• Superior branches usually fill first
Arterial phase
ARTERIO-VENOUS PHASE(CAPILLARY PHASE)
• Complete filling of retinal arteries and capillaries.
• Early laminar flow in the veins in which dye is seen along the lateral wall of the vein
• Choroidal fluorescence increases as free fluorescein continues to leak from the choriocapillaries
Arteriovenous phase
VENOUS PHASE
• Gradually whole diameter of the veins is filled
• Earliest seen in the peripapillary and macular region
• Divided according to the venous filling and arterial emptying • Early• mid• Late
EARLY VENOUS PHASE• Arteries and capillaries are completely filled and marked lamellar
venous flow
MID VENOUS PHASE
• Some veins are completely filled• Some shows marked laminar flow
LATE VENOUS PHASE• All veins are completely filled and the arteries beginning to empty
MID PHASE• Known as recirculation phase
• 2-4 min after injection
• Veins and arteries remain roughly equal in brightness.
• Intensity of fluorescein diminishes slowly as• flourescein is removed from the blood stream on the first pass through
the kidneys.
LATE PHASE• After 10-15 minutes little dye remains in the blood stream
• This phase demonstrates• Gradual elimination of the dye from the retinal and choroidal
vasculature
• staining of optic disc , sclera is normal finding
• Any other hyperfluoresecence suggest the presence of abnormality
Late Phase
Phases of angiogram Time ( in seconds)Injection 0Posterior ciliary artery 9.5Choroidal phase 10Arterial 10 - 12Arterio venous 13Early venous 14 - 15Mid venous 16 -17Late venous 18 – 20Late ( elimination) 5 minutes
FLUORESCENCE IN FOVEAL REGION
• Dark appearance WHY? i) Avascularity in the FAZii) Blockage of the choroidal
flourescein because of• increased amount of xanthophyll
pigments at fovea• melanin in RPE
NORMAL ANGIOGRAM
• Patchy filling of choroid • Retinal blood vessels filling• Dark area of foveal avascular zone• But there is no hyper or hypofluroscence area • At the end of the transit phase, fluorescein dye remains in the choroid
and sclera due to leakage from the choroidal vessels• A small amount of fluorescein also remains in the optic nerve head and
retinal vessels, but there is no leakage• Any additional fluorescein in the eye should be regarded as pathologic
NORMAL ANGIOGRAM
STEPWISE APPROCH TO FFA• A fluorescein angiogram should be interpreted
systematically to optimize diagnostic accuracy as follows:-
• A ) Indicate whether images of right , left or both eyes have been taken.
• B)comment on the red free images
• C)indicate any delay in filling as well as hyper or hypo fluorescence
• D)indicate any characteristic features such as a smoke –stack or lacy filling pattern.
• E)indicate any evolution through the course of the angiogram in the area or intensity of fluorescence.
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FFA INTERPRETATION FLOW CHART Fluorescein angiogram
Normal Abnormal Auto/pseudofluorescence
Hyperfluorescence Hypofluorescence
Leakage Pooling Staining Window Blocked Non
defect filling
NOTE• Hyperfluorescence and hypofluorescence can alternate in same
location
• Especially in inflammatory disorder
• 1st hypofluorescence due to retinal oedema
• Later hyperfluorescence due to increased vascular permeability
AUTOFLUORESENCE• Emission of fluorescence light in the absent of fluorescein
Example : optic nerve head drusen , astrocytic hematoma , myelinated nerve fibers
Optic disc drusen Astrocytic hematoma
PSEUDOFLUORESCENCE• Occurs when nonfluorescence light passes through the entire filter system • Blue reflected light passes from green filter pseudofluorescence occurs
• It decrease contrast aswell as resolution of image
• To avoid pseudofluorescence filter combination to be sure that no significant overlap exists
• Over the time filter alter the range of light transmission so should be change in certain time . Auther recommend about 5 year time to change filter
WINDOW DEFECT• Focal RPE atrophy • Unmasking of normal background of choroidal fluorescence
• Characterized by early hyperfluorescence which increases in intensity then fade without changing shape and size
e.g. inflammation of RPE atrophy of RPE , drusen
EXTRAVASCULAR LEAK• Pooling and staining in choroid • Cystoid edema and noncystoid edema in retina • Neovascularization , inflammation and tumor vessels in vitreous • Disc staining
Cystoid oedema of macula
Pooling( accumulation of dye in a closed space)
-Early hyperfluorescence sub-retinal space Early hyperfluorescence sub RPE space increase in size ,intensity increase intensity only e.g. CSR e.g. PED
POOLING OF DYE
CSR( sub RETINAL space)PED( sub RPE space)
CSR increase in size and intensity
NVD
NVE
STAINING• Accumulation of fluorescence within a tissue
• Due to prolonged dye retention
• Minimum hyperfluorescence in early and midphase which increases in late phase
• Can be seen in normal as well as pathologically altered tissue
examples
RETINALa. non-cystoid macular oedema
b. Perivascular staining
SUB RETINAL Drusens Sclera Lamina cribrosa scars
Drusens in ARMD
LATE HYPERFLUROSCENCE ALONG THE EDGE OF GEORAPHIC SCAR
FOCAL EXUDATIVE
• Circumscribed retinal thickening• Associated complete or incomplete circinate hard exudates
• Focal leakage on FA
Optic Disc Swelling
HYPOFLURESCENCE
• Reduction or absence of fluorescein
• Two causes
BLOCKED FLUORESCENCE
VASCULAR FILLING DEFECTS
BLOCKED FLUORESCENCE
• Optical obstruction (masking) of normal density of fluorescein• Caused by lesions anterior to retina
• Pre-retinal lesions eg.vitreous opacity,preretinal haemorrhage block all fluorescence
• Deep retinal lesions eg.intraretinal haemorrhage and hard exudates block only capillary fluorescence
• Increased density of RPE eg.congenital hypertrophy
• Choroidal lesions eg.naevus
EXAMPLE
FILING DEFECTS• Inadequate perfusion of tissue with resultant low fluorescein content
• Avascular occlusion of choroidal circulation or retinal arteries,veins and capillaries
• Loss of vascular bed eg.severe myopic degeneration – choroideremia
• Emboli
• arteriosclerosis
EXAMPLE
CRAOCRVO
LIMITATIONS OF FFA
1) Does not permit study of choroidal circulation details due to
a) melanin in RPE b) low mol. Wt. of fluorescein how to overcome ---- ICG
2) More adverse reaction
3) Inability to obtain angiogram in patient with excess hemoglobin or serum protein
INDOCAINE GREEN ANGIOGRAPHY
• FFA excellent method for demonstrating retinal circulation.
• But…• Not helpful in delineating choroidal circulation
• ICG –of particular value in studying choroidal circulation ,
• Can be useful adjunct to FA in investigation of macular diseases.
FFA Vs ICGPARAMETERS FFA ICG
1) Dye used Sodium fluorescein
Indocyanine green
2) Light used visible spectrum infrared
3) purpose study retinal vasculature
Choroidalvasculature
4) Filter used Blue- green Infra-red
5) expense lower higher
PHENOMENON OF FFA• All the process of occurrence of hyper or hypo-fluorescence can be
described under following 3 phenomenons
A. OPTICAL PHENOMENON
B .MECHANICAL PHENOMENON
C. DYNAMIC PHENOMENON
OPTICAL PHENOMENON• Normal neurosensory retina is transparent
• Normal RPE and Bruch’s Membrane are semitransparent
• Hence, we can see choroidal fluorescence
• BUT, this transparency can be pathologically increased or decreased
DECRESEING TRANSPARENCY • In case of blocked fluorescence , transparency is lost
• SO, WE DO NOT SEE CHOROIDAL FLUORESCENCE
Accumulation of blood haemorrhage
RPE hypertrophyChoroidal naevus
INCRESING TRANSPARENCY
• In case of staining due to drusens,angioid streaks ,scars and degenerative processes
Accumulation of drusens under RPE
MECHANICAL PHENOMENON• Related to adhesion of RPE to Bruch’s Membrane
• RPE firmly attached to Bruch’s membrane by hemidesmosomes
Absence of hemidesmosomes
RPE splits away from Bruch’s membrane
Fluorescein stained fluid accumulate in between them eg. PIGMENT EPITHELIAL DETACHMENT
DYNAMIC PHENOMENON• Related to diffusion of fluorescein in ocular tissue• Determined by inner and outer blood retinal barrier I.E DIFFUSION
BARRIER
RETINAL VESSELS• Normal retinal vessels do not leak fluorescein - due to zonula
occludents in between endothelial cells
• These zonula occludents open up during inflammatory process
Zonula occludents open up
normal
Endothelial cell is lost
Pores in endothelial cells
PERIVASCULITIS
DIABETIC MICROANEURYSM
PROLIFERATED RETINAL VESSELS
RETINAL PIGMENT EPITHELIUM• Normal RPE is tight
• zonula occludens seal portion of all the intercellular spaces of the pigment epithelial monolayer.
Cental serous chorioretinopathy
Haemorrhagic PED in wet ARMD
REFERENCES
INTERNATE
•Thank you