Learning Objectives Understand basic principles behind FA Fluorescein Explain common complications associated with FA Angiography Identify normal features of FA imaging Identify pathological patterns of hyperfluorescence and hypofluorescence Hannah Shinoda, OD, FAAO Assistant Professor Pacific University College of Optometry History Fluorescein Angiography Applications 1871: Fluorescein was synthesized by Nobel laureate Johann Baeyer Diabetic retinopathy Branch retinal artery occlusion 1881: Ehrlich observed fluorescence in the anterior chamber Age related macular Retinal arterial macroaneurysm after an injection of fluorescein degeneration Subretinal neovascular 1950s: Flock and co-workers investigated methods to Central retinal vein occlusion membrane determine retinal circulation times with various dyes, including fluorescein Branch retinal vein occlusion Choroidal tumors Central serous chorioretinopathy Chorioretinal inflammatory 1961: Fluorescein was introduced to ophthalmic imaging by conditions Novotny and Alvis (2 medical students) Cystoid macular edema Hypertensive retinopathy Central retinal artery occlusion Should only be performed if the findings are likely to influence management Excitation and Barrier filter What’s the Science? Two filter system: When light energy is absorbed into a luminescent material, Excitation filter: transmits 490nm which is free electrons are elevated into higher energy states. This the absorption peak of fluorescein excitation energy is then re-emitted by spontaneous decay of the electrons into their lower energy states. When this decay Barrier filter: transmits 520nm which is the occurs in the visible spectrum, it is called luminescence . emitted peak of fluorescein When choosing a camera, one should request Peak Absorption: 490nm the transmission curve of the filter combination to make sure that no significant overlap exists. Peak Emission: 520nm (otherwise other items would “fluoresce”) After several years, the filters become thin, emitting more light and increasing the incidence of pseudofluorescence. Quillen, David A., and James D. Strong. "Principles of Fluorescein Angiography." Albert & Jakobiec's Principles & Practice of Ophthalmology. By Timothy J. Bennett. 3rd ed., 2000.
Fluorescein Solution Complications Sodium Fluorescein C 20 H 12 O 5 Na Mild Reactions <5% Injection site reaction Orange-Red crystalline hydrocarbon Nausea When injected 80% is bound to protein, 20% remains in free Vomiting bloodstream Moderately Severe Reactions <1% Urticaria It is eliminated by the liver and kidneys within 24 hours, though traces Shortness of breath may be found in the body for up to a week Vasovagal reaction Available solutions: Skin necrosis 10mL of 5% fluorescein Life-threatening reactions Anaphylactic shock 5mL of 10% fluorescein (<0.001%) Seizure 3mL of 25% fluorescein Cardiovascular collapse The larger the volume, the longer the injection • Avoid angiography in pregnant women, especially in the first The smaller the volume, the more solution remains in the venous trimester dead space between the arm and the heart • Premedication with antihistamine and/or corticosteroids can be used Alternative if venous line could not be established or for patients with a history of moderately severe reactions. (depending injection is refused: on the situation) Oral administration of dose 30mg/kg • All units performing fluorescein angiography should have a crash Won’t see rush of fluorescein enter the eye cart available Pictures are taken 20-60 minutes following ingestion Procedure Complications Material: • Fundus camera and auxiliary equipment Extravasation of fluorescein under the skin • Matched fluorescein filters (barrier and excitation) • Digital photoprocessing unit (computer-based) and software user interface Accidental administration of fluorescein into the • 23 gauge scalp vein needle extravascular space/tissue around the infusion site • 5 mL syringe Side effects: • Needle to draw the dye • Armrest for fluorescein injection Can be extremely painful • Tourniquet Necrosis and sloughing of skin (rare) • Alcohol swabs Subcutaneous granuloma (rare) • Bandage Apply ice pack • Standard emergency equipment A common cause is the use of a large, long needle directly attached to Emergency Kit: Airway bag a syringe. *Use scalp vein needle instead Automated external defibrillator Oral or intramuscular antihistamines Autoinjectors for epinephrine Procedure Set up: Procedure Maximal dilation 6mm or more is best Explanation: PARQ Preparation of fluorescein and scalp-vein needle Identification photo Procedures Set up patient Color photos Alternatives Red free photos Filter in place, flash and camera ready Risks Check which eye is the transit eye Questions 1
Early phase Procedure CHOROIDAL FLUSH (8-12s) : choriocapillaris leaks dye freely through the space. Usually little detail as the RPE acts as an irregular filter that obscures view of choroid. When present, cilioretinal arteries fill at the same time. Establish a venous line 2 Start timer and inject 5mL of 10% Fluorescein rapidly (~10 sec) Make sure not to overload the vein and inject the fluorescein under the skin Fluorescein should start appearing in the eye in about 8-12 seconds 8 seconds for younger individuals 12 seconds for older individuals Take photos every 1.5-2 seconds in the transit eye for about 30 seconds until the initial transit is complete After, the fluorescein recirculates and the concentration of fluorescein begins to decrease Option of taking photos of fellow eye & periphery Wait (for late staining) ~3-5 minutes, take additional photo Option of taking 10 minute photo Early phase ARTERIAL PHASE (2s after the choroidal phase): Retinal arteries fill 2 Early phase ARTERIOVENOUS PHASE: When the retinal arteries, capillaries, and veins Ateriovenous phase contain fluorescein. The early part of this phase is the laminar phase when fluorescein is visualized in the walls of the larger veins. 2 Laminar phase when the fluorescein is in the laminar walls of the vein. 3
Early phase VENOUS PHASE (about 30 s after injection): as the fluorescein leaves Normal Macular Filling the arteries, the veins have an increase in fluorescein. Perifoveal capillary network best visualized during the venous phase. 2 2 Dark macula area: Taller, more pigmented RPE Xanthophyll pigment Absence of retinal capillaries in foveal center Late Phase Mid phase Late Phase: Gradual elimination of the dye from the retina and choroid. Mid Phase: Recirculation occurs 2-4 min after injection. The arteries and Staining of the optic disc is normal. Photos normally taken 7-15 min after veins are roughly equal in brightness. injection 2 2 Review of Vasculature Review of Vasculature Retinal circulation supplies the inner 2/3 of the retina Sodium Fluorescein readily diffused through the fenestrated Non-fenestrated vessels of the choriocapillaris but does not pass through Blood-retinal barrier via tight junctions healthy endothelial cells of non-fenestrated retinal vessels or through the RPE Choroidal circulation supplies the outer 1/3 of the retina Fenestrated, low resistance Blood-retinal barrier via tight junctions at the RPE 2
Hypofluorescence Hypofluorescence Reduction or absence of normal fluorescence BLOCKAGE Hemorrhage Pigment Preretinal VASCULAR FILLING DEFECT hemorrhage causing Absence of vascular tissue or by a complete hypofluorescent or partial obstruction of the vessels blockage of all retina and choroid Key: correlate the hypofluorescence on the angiogram with the fundus view. If the size/shape/location corresponds, its blockage. If not, it is a vascular filling defect. 1 Hypofluorescence Hypofluorescence Subretinal hemorrhage causing Intraretinal hypofluorescence. hemorrhage causing blockage. Blockage of the Hemorrhages choroid but no located in most of blockage of the retinal the layers of the vessels. retina 1 1 Hypofluorescence Hypofluorescence Reduction or absence of normal fluorescence BLOCKAGE Subretinal Hemorrhage hypertrophy of the Pigment retinal pigmented VASCULAR FILLING DEFECT epithelium. Absence of vascular tissue or by a complete or partial obstruction of the vessels Blocked choroidal fluorescence and Key: correlate the hypofluorescence on the normal retinal angiogram with the fundus view. If the fluorescence. size/shape/location corresponds, its blockage. If not, it is a vascular filling defect. 1
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