Introduction To Fundus Fluorescein Angiography (FFA)And Indocyanine Green(ICG)

- Dr HITESH SHARMA,

JR1 , DEPT OF OPHTHALMOLOGY,

IMS – B.H.U.

FUNDUS ANGIOGRAPHY

1. Fluorescein (FA)• Characteristics of Fluorescein & General principles• Excitation and emission

2. Indocyanine green (ICG)

• Filters• Photographic technique• Phases of normal angiogram• Causes of dark appearance of fovea• Causes of hyperfluorescence • Causes of hypofluorescence

• General principles

• Phases of normal angiogram

Characteristics of Fluorescein

• Nontoxic, 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 24 hrs.

General principles of FA

Fluorescein• 85% bound to serum proteins• 15% unbound ‘free’ fluorescein

• Impermeable to fluorescein

Outer blood-retinal barrier (zonula occludens)• Impermeable to fluorescein

Choriocapillaris• Permeable only to ‘free’ fluorescein

Inner blood-retinal barrier (retinal capillaries)

Excitation and emission

Filters

Photographic technique

1. Take red-free photograph2. Inject rapidly 5 ml of 10% solution3. Take photographs at 1 sec intervals between 5-25 sec after injection4. Take photographs after 10 min and 20 min, if appropriate

Normal FFA

• Arm-to-retina circulation time is 12-15 sec.• Five angiographic phases:

• Pre arterial• Arterial• Arteriovenous• Venous• Recirculation

Phases of normal FA

Arterial• Arterial filling

Arteriovenous (capillary) • Very early lamellar venous flow

Early venous • Marked lamellar venous flow

Mid-venous • Almost complete venous filling

Late venous • Complete venous filling

Late • Progressively weaker fluorescence• Staining of disc

Hyperfluorescence Hyperfluorescence

LeakLeak

Transmission increase Transmission increase

Abnormal vessels Abnormal vessels

LeakLeak

Pooling (in a space)Pooling (in a space)

Staining (in a tissue).Staining (in a tissue).

Pigment epithelial window defect Pigment epithelial window defect

Retinal Retinal

Subretinal Subretinal Tumors Tumors

Abnormal Vessels

Abnormal Vessels

Transmission increase

Transmission increase

Hyperfluorescence Hyperfluorescence LeakLeak

Pooling

(in a space)

Pooling

(in a space)

Staining

(in a tissue).

Staining

(in a tissue).

Retinal Retinal

Subretinal Subretinal

Retinal Retinal

Subretinal Subretinal

Cystoid edema Cystoid edema

Perivascular staining Perivascular staining

Retinal pigment epitheliumRetinal pigment epithelium

Noncystoid edema Noncystoid edema

DrusenDrusen

Scars Scars

Sclera Sclera

Lamina cribrosa Lamina cribrosa

Sensory retina detachmentSensory retina detachment

Hyperfluorescence Hyperfluorescence Transmission

Increase

Transmission

Increase

Pigment

Epithelial

Window

Defect

Pigment

Epithelial

Window

Defect

Atrophy Atrophy

Drusen Drusen

Hyperfluorescence Hyperfluorescence Abnormal

Vessels

Abnormal

Vessels

Retinal Retinal

Subretinal Subretinal

Tumors Tumors

Tortuosity and Dilation Tortuosity and Dilation

Neovascularization Neovascularization

Aneurysms Aneurysms

Telangiectasias Telangiectasias

Shunts and collaterals Shunts and collaterals

Vessels in scar Vessels in scar

MacroaneurysmsMacroaneurysms

Neovascularization Neovascularization

Retinal Retinal

Subretinal Subretinal

Angioma Angioma

Retinoblastoma Retinoblastoma

MicroaneurysmsMicroaneurysms

Hemangioma Hemangioma Melanoma Melanoma MetastasesMetastases

Hypofluorescence Hypofluorescence

Transmission Decrease

(blocking effect)

Transmission Decrease

(blocking effect)

Filling defect

(delay and occlusion)

Filling defect

(delay and occlusion)

Hypofluorescence Hypofluorescence Transmission

Decrease (blocked)

Transmission Decrease (blocked)

Pigment Pigment

Exudates Exudates

Edema and transudate Edema and transudate

Other abnormal materials

Other abnormal materials

Melanin Melanin Hemoglobin Hemoglobin

Xanthophyll Xanthophyll

LipofuscinLipofuscin

HardHard

Soft Soft

Best`s disease Best`s disease Foreign bodyForeign body

Fundus flavimaculatusFundus flavimaculatus

Hypofluorescence

Hypofluorescence

Filling defect (delay and occlusion)

Filling defect (delay and occlusion)

Retinal Retinal

Subretinal Subretinal

Artery Artery

VeinVein

Capillary bed Capillary bed

Loss of tissueLoss of tissue

NonperfusionNonperfusion

DystrophiesDystrophies

DegenerationDegeneration

ChoroideremiaChoroideremia

Choroidal atrophy etc.Choroidal atrophy etc.

Myopia Myopia

Central areolar atrophy Central areolar atrophy

Causes of dark appearance of fovea

Avascularity

• Increased density of xanthophyll

• Large RPE cells with more melanin

Blockage of background choroidal fluorescence by:

Causes of hyperfluorescence ( 1 )RPE ‘ window’ defect

RPE atrophy (bull’s eye maculopathy

Pooling of dye

Under RPE (pigment epithelial detachment)

Under sensory retina (central serous retinopathy)

Causes of hyperfluorescence (2)

Leakage of dye Prolonged dye retention ( staining )

Into sensory retina (cystoid macular oedema)

From new vessels (choroidal neovascularization

Associated with drusen

Causes of hypofluorescence (1)

Blocked retinal or choroidal fluorescence

• Blood under retinal pigment epithelium

• Preretinal or intraretinal blood• Abnormal material• Increased pigment

Vascular occlusion

Capillary non-perfusion(venous occlusion)

Loss of vascular tissue

Choroideremia or high myopia

Causes of hypofluorescence (2)

Side Effects

• Minimal relatively safe drug

• Use of dilating drops

• Red after – images from the photoflash

• Temporary tan skin color

• Fl. Urine discoloration

• Interfere with serological tests

• 2-4% Transient nausea and occ. VOMITING

• Hives, asthmatic symptoms

• Laryngeal edema

• Rarely – Syncope, anaphylactic rxn, MI, resp. or Cardiac arrest

• Rx – oral or I.V. Benadryl or Cortisone

• A physician in the 1st few minutes

During Pregnancy and Lactation

• Controversial• Fl. Crosses the placenta• Has been done in pregnancy with no

adverse effect• Do it when necessary

General Principles of ICG Angiography

1. Binding• 98% bound to proteins

2. Fluorescence• Much less than fluorescein

• Less leakage from choriocapillaris

• Excitation peak 800 nm• Emission at 835 nm

3. Filters• Infrared barrier and excitation

4. Safer than fluorescein

Phases of normal ICG angiogram (1)Early (20 sec)

• Disc hypofluorescence• Poor perfusion of vertical (watershed) zone near disc• Prominent filling of choroidal arteries• Early filling of choroidal veins• Filling of retinal arteries but not veins

Early middle (3 min)

• Filling of watershed zone

• Fading of choroidal arterial filling

• Prominent filling of choroidal veins

• Filling of retinal arteries and veins

Phases of normal ICG angiogram (2)Late (21 min)

• Large choroidal and retinal vessels are empty

Late middle (6 min)

• Reduced filling of choroidal vessels• Diffuse hyperfluorescence due to diffusion of dye from choriocapillaris• Persistent filling of retinal vessels

• Diffuse background hyperfluorescence

Not all abnormal conditions of the ocular fundus will produce abnormal fluorescein angiograms.

FFA

Things to rememberThings to remember