Fluorescein angiography
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Fluorescein angiography (FA), fluorescent angiography (FAG), or fundus fluorescein angiography (FFA) is a technique for examining the circulation of the
retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...
and
choroid The choroid, also known as the choroidea or choroid coat, is a part of the uvea, the vascular layer of the eye, and contains connective tissues, and lies between the retina and the sclera. The human choroid is thickest at the far extreme rear ...
(parts of the fundus) using a
fluorescent Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation. It is a form of luminescence. In most cases, the emitted light has a longer wavelength, and therefore a lower photon energy, tha ...
dye and a specialized camera. Sodium
fluorescein Fluorescein is an organic compound and dye based on the xanthene tricyclic structural motif, formally belonging to triarylmethine dyes family. It is available as a dark orange/red powder slightly soluble in water and alcohol. It is widely used ...
is added into the systemic circulation, the retina is illuminated with blue light at a
wavelength In physics, the wavelength is the spatial period of a periodic wave—the distance over which the wave's shape repeats. It is the distance between consecutive corresponding points of the same phase on the wave, such as two adjacent crests, tro ...
of 490
nanometer 330px, Different lengths as in respect to the molecular scale. The nanometre (international spelling as used by the International Bureau of Weights and Measures; SI symbol: nm) or nanometer (American and British English spelling differences#-re ...
s, and an
angiogram Angiography or arteriography is a medical imaging technique used to visualize the inside, or lumen, of blood vessels and organs of the body, with particular interest in the arteries, veins, and the heart chambers. Modern angiography is performe ...
is obtained by photographing the fluorescent green light that is emitted by the dye. The fluorescein is administered intravenously in intravenous fluorescein angiography (IVFA) and orally in oral fluorescein angiography (OFA). The test is a
dye tracing Dye tracing is a method of tracking and tracing various flows using dye as a flow tracer when added to a liquid. Dye tracing may be used to analyse the flow of the liquid or the transport of objects within the liquid. Dye tracking may be either qu ...
method. The fluorescein dye also reappears in the patient urine, causing the urine to appear darker, and sometimes orange. It can also cause discolouration of the saliva. Fluorescein angiography is one of several
health care Health care or healthcare is the improvement of health via the prevention, diagnosis, treatment, amelioration or cure of disease, illness, injury, and other physical and mental impairments in people. Health care is delivered by health profe ...
applications of this dye, all of which have a risk of severe
adverse effect An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term complica ...
s. See fluorescein safety in health care applications. Fluorescein angiography does not involve the use of
ionizing radiation Ionizing radiation (or ionising radiation), including nuclear radiation, consists of subatomic particles or electromagnetic waves that have sufficient energy to ionize atoms or molecules by detaching electrons from them. Some particles can travel ...
. Fluorescein angiography was pioneered by German
ophthalmologist Ophthalmology ( ) is a surgery, surgical subspecialty within medicine that deals with the diagnosis and treatment of eye disorders. An ophthalmologist is a physician who undergoes subspecialty training in medical and surgical eye care. Followin ...
Achim Wessing, who published his findings in 1969.


Equipment

* Exciter filter: Allows only blue light to illuminate the retina. Depending on the specific filter, the excitation wavelength hitting the retina will be between 465 and 490 nm. Most only allow light through at a wavelength of 490 nm. * Barrier filter: Allows only yellow-green light (from the fluorescence) to reach the camera. Both filters are interference bandpass filters, which means they block out all light except that at a specific wavelength. The barrier filter only allows light with a wavelength of 525 nm, but depending on the filter it can be anywhere from 520–530 nm. *
Fundus camera Fundus photography involves photographing the rear of an eye, also known as the fundus (eye), fundus. Specialized fundus cameras consisting of an intricate microscope attached to a flash (photography), flash enabled camera are used in fundus phot ...
, either digital or with camera body containing black and white, or slide positive film.


Technique

* Baseline color and black and white red-free filtered images are taken prior to injection. The black and white images are filtered red-free (a green filter) to increase contrast and often gives a better image of the fundus than the color image. * A 6-second bolus injection of 2-5 cc of sodium fluorescein into a vein in the arm or hand * A series of black-and-white or digital photographs are taken of the retina before and after the fluorescein reaches the retinal circulation (approximately 10 seconds after injection). The early images allow for the recognition of autofluorescence of the retinal tissues. Photos are taken approximately once every second for about 20 seconds, then less often. A delayed image is obtained at 5 and 10 minutes. Some doctors like to see a 15-minute image as well. * A filter is placed in the camera so only the fluorescent, yellow-green light (530 nm) is recorded. The camera may however pick up signals from pseudofluorescence or
autofluorescence Autofluorescence is the natural emission of light by biological structures such as mitochondria and lysosomes when they have absorbed light, and is used to distinguish the light originating from artificially added fluorescent markers (fluorophores) ...
. In pseudofluorescence, non-fluorescent light is imaged. This occurs when blue light reflected from the retina passes through the filter. This is generally a problem with older filters, and annual replacement of these filters is recommended. In autofluorescence, fluorescence from the eye occurs without injection of the dye. This may be seen wit
optic nerve head drusen
or calcific scarring. * Black-and-white photos give better contrast than color photos, which aren't necessary because the filter transmits only one color of light.


Normal circulatory filling

''times are approximate'' * 0 seconds – injection of fluorescein * 9.5 sec – posterior ciliary arteries * 10 sec –
choroid The choroid, also known as the choroidea or choroid coat, is a part of the uvea, the vascular layer of the eye, and contains connective tissues, and lies between the retina and the sclera. The human choroid is thickest at the far extreme rear ...
al flush (or "pre-arterial phase") * 10–12 sec – retinal arterial stage * 13 sec –
capillary A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...
transition stage * 14–15 sec – early venous stage (or "laminar stage", "arterial-venous stage") * 16–17 sec – venous stage * 18–20 sec – late venous stage * 5 minutes – late staining Fluorescein enters the ocular circulation from the
internal carotid artery The internal carotid artery (Latin: arteria carotis interna) is an artery in the neck which supplies the anterior circulation of the brain. In human anatomy, the internal and external carotids arise from the common carotid arteries, where these b ...
via the
ophthalmic artery The ophthalmic artery (OA) is an artery of the head. It is the first branch of the internal carotid artery distal to the cavernous sinus. Branches of the ophthalmic artery supply all the structures in the orbit around the eye, as well as some st ...
. The ophthalmic artery supplies the choroid via the short posterior ciliary arteries and the retina via the
central retinal artery The central retinal artery (retinal artery) branches off the ophthalmic artery, running inferior to the optic nerve within its dural sheath to the eyeball. Structure The central retinal artery pierces the eyeball close to the optic nerve, sendin ...
, but the route to the choroid is typically less circuitous than the route to the retina. This accounts for the short delay between the "choroidal flush" and retinal filling.


Pathologic findings

Pathologic changes are recognized by the detection of either hyperfluorescence or hypofluorescence. Causes of hyperfluorescence: :window/transmission (filling) defects :leaking defects (i.e. capillary leakage,
aneurysm An aneurysm is an outward bulging, likened to a bubble or balloon, caused by a localized, abnormal, weak spot on a blood vessel wall. Aneurysms may be a result of a hereditary condition or an acquired disease. Aneurysms can also be a nidus (s ...
,
neovascularization Neovascularization is the natural formation of new blood vessels ('' neo-'' + '' vascular'' + '' -ization''), usually in the form of functional microvascular networks, capable of perfusion by red blood cells, that form to serve as collateral circu ...
) :pooling defects :staining :abnormal vasculature Causes of hypofluorescence: :blocking defect (i.e. blood) :filling defect (capillary nonperfusion/blockage) Fluorescein angiography is used by physicians specializing in the treatment of eye diseases (
ophthalmologists Ophthalmology ( ) is a surgical subspecialty within medicine that deals with the diagnosis and treatment of eye disorders. An ophthalmologist is a physician who undergoes subspecialty training in medical and surgical eye care. Following a medic ...
) to evaluate the vasculature of the
retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...
,
choroid The choroid, also known as the choroidea or choroid coat, is a part of the uvea, the vascular layer of the eye, and contains connective tissues, and lies between the retina and the sclera. The human choroid is thickest at the far extreme rear ...
,
optic disc The optic disc or optic nerve head is the point of exit for ganglion cell axons leaving the eye. Because there are no rods or cones overlying the optic disc, it corresponds to a small blind spot in each eye. The ganglion cell axons form the ...
, and
iris Iris most often refers to: *Iris (anatomy), part of the eye *Iris (mythology), a Greek goddess * ''Iris'' (plant), a genus of flowering plants * Iris (color), an ambiguous color term Iris or IRIS may also refer to: Arts and media Fictional ent ...
. Among the common groups of ophthalmologic disease, fluorescein angiography can detect
diabetic retinopathy Diabetic retinopathy (also known as diabetic eye disease), is a medical condition in which damage occurs to the retina due to diabetes mellitus. It is a leading cause of blindness in developed countries. Diabetic retinopathy affects up to 80 perc ...
(
neovascularization Neovascularization is the natural formation of new blood vessels ('' neo-'' + '' vascular'' + '' -ization''), usually in the form of functional microvascular networks, capable of perfusion by red blood cells, that form to serve as collateral circu ...
), vein occlusions,
retinal artery occlusion Ocular ischemic syndrome is the constellation of ocular signs and symptoms secondary to severe, chronic arterial hypoperfusion to the eye. Amaurosis fugax is a form of acute vision loss caused by reduced blood flow to the eye; it may be a warn ...
s, edema of the optic disc, and tumors. Additionally, the transit time (the period between injection of the dye and when it appears in the examined blood vessels) can provide an objective measurement of the rate of blood flow through the imaged blood vessels.


See also

*
Fundus photography Fundus photography involves photographing the rear of an eye, also known as the fundus. Specialized fundus cameras consisting of an intricate microscope attached to a flash enabled camera are used in fundus photography. The main structures that ...
*
Laser Doppler imaging Laser Doppler imaging (LDI) is an imaging method that uses a laser beam to scan live tissue. When the laser light reaches the tissue, the moving blood cells generate doppler components in the reflected ( backscattered) light. The light that comes ...


References


Additional references

* * * Manfred Spitznas: ''Understanding fluorescein angiography = Fluoreszeinangiografie verstehen.'' (German, English, Spanish) Springer, Berlin/Heidelberg/New York 2006, . * Achim Wessing (1969). ''Fluorescein angiography of the retina.Textbook and atlas.'' Saint Louis: Mosby, {{Medical imaging Diagnostic ophthalmology Optical imaging