Fluorescein Angiography (FAN) & ICG PDF

Retinal Vasculature Review Retinal capillary beds ○ Supplies the inner ⅔ of the retina ○ Tight junctions, therefore no leaking should occur ○ Inner blood-retina barrier Choriocapillaries ○ Supply the outer ⅓ of the retina ○ Fenestrated, therefore...

Retinal Vasculature Review Retinal capillary beds ○ Supplies the inner ⅔ of the retina ○ Tight junctions, therefore no leaking should occur ○ Inner blood-retina barrier Choriocapillaries ○ Supply the outer ⅓ of the retina ○ Fenestrated, therefore NaFl permeates into extracellular spaces Located beneath the RPE ○ Circulation time is fast RPE ○ Outer-blood-retina barrier ○ Adherent together by zonule adherents (ZA) ○ Strongly adherent to Bruch’s Membrane (BrM) The tight junctions between RPE cells prevent that the NaFl in the extracellular space of the extracellular space of the choriocapillaries bed invades the retina and the RPE ○ RPE is loosely adherent to the sensory retina ○ Pigment acts as an optical barrier, obscuring the NaFl beneath (“Choroidal Flush”) The denser the pigment, less fluorescence is observed Arterial input Internal Carotid Artery (ICA), derives the Ophthalmic Artery which derive: ○ Central Retinal Artery (CRA) ○ Short and Long Posterior Ciliary Arteries (SPCA/LPCA) ○ Anterior Ciliary Arteries (ACA)  Blood flows from the CRA → Retinal Arterioles → Retinal Capillaries → Retinal Venules → CRV ○ No leakage of fluorescein should happen Venous Outflow Primarily by the Vortex Veins (VV) and the Central Retinal Vein (CRV) The CRV merge with the Superior and Inferior Ophthalmic Veins which drain into the Cavernous Sinus, the Pterygoid Venous Plexus and the Facial Vein ○ Then drain into the Jugular Vein Fluorescein Angiography (FAN) Asses choroid, RPE, retina, ONH, and vascular abnormalities ○ Delineates fundus vascularity Anterior segment blood and aqueous flow Requires an injection of sodium fluorescein (NaFl) and fundus photos Retinal vessels are clearly visible with fluorescein The choroidal fluorescence is reduced due to the intact RPE Disease that damage the ocular circulation, RPE or the blood-retinal barriers can all potentially be detected angiographically Uses ○ Useful to evaluate retinal and choroidal circulation, abnormal RPE changes, vascular disease and neoplastic disorders ○ Examples: Central Serous Chorioretinopathy Diabetic Retinopathy Disciform macular degeneration Retinal Vascular Occlusions RPE detachments Subretinal neovascular membranes Cystoid Macular Edema Sodium fluorescein is injected into the antecubital vein 70-85% of the circulating fluorescein binds to albumin and RBC NaFl in the bloodstream is excited by wavelengths of 465nm and emits a wavelength of 525nm  Metabolized into a weak fluorescent conjugate, which exhibits less plasma protein binding than fluorescein 10-15 seconds after injection the dye appears in the CRA NaFl absorbs blue light, with a peak excitation occurring at wavelengths between 465-490nm The resulting fluorescence occurs at the yellow-green wavelength of 520 to 530nm In broad-spectrum illumination, diluted NaFl appears bright yellowgreen. When illuminated with blue light, the yellow-green color intensifies Oral Fluorescein Angioscopy ○ 1g of fluorescein solution mixed with 200mL of liquid ○ Concentration peaks in 30 minutes ○ Used to study and document disorders characterized by late leakage of dye Ex: cystoid macular edema, RPE detachments, CSCR, Optic Disc Edema ○ Side effects are rare ○ But does not provide critical vascular details needed for photocoagulation A fundus camera fitted with an illumination source and barrier filters is used to selectively photograph the retinal and choroidal circulation ○ Blue and yellow filters In healthy eyes, fluorescein passes rapidly through the eye but the inner and outer blood-retinal barriers prevent staining of the retinal substrate Procedure ○ 5 mL of 10% or 3 mL of 25% solution is administered into the antecubital vein ○ ○ After injecting the dye into the antecubital vein, in ~10-15 seconds the dye should appear in the CRA ○ Dye enters the eye through the ophthalmic artery and there passes into the SPCA ○ Transition time (arm to retina time) in healthy subjects is ~12 seconds A delay in arm-to-retina time may indicate: Problem with the fluorescein dye injection Circulatory problems like heart and/or peripheral vascular disease  FAN IV Side Effects ○ About 10% of the patients have an adverse reaction The most common nausea, sometimes followed by vomiting ○ Post-injection nausea may be related to the fluorescein concentration and speed of injection Lower concentration and slow injection decrease the nausea incidence ○ 50mg Promethazine (Phenergan) PO 1hr before FAN decreases the incidence of nausea ○ Allergic reactions/hypersensitivity ○ Laryngeal edema ○ Urticaria/pruritus ○ Temporary urine/skin discoloration ○ Headache ○ GI distress, vomiting ○ Extravasation and skin necrosis ○ Hypotension ○ Syncope ○ Respiratory effects ○ Bronchospasm ○ Basilar artery ischemia ○ Thrombophlebitis ○ Cardiac arrhythmia ○ Cardiac arrest ○ Death (1/250,000) FAN Contraindications ○ Hypersensitivity to active ingredients or component ○ Previous anaphylactic reaction ○ Severe renal impairment ○ Recent CVA, MI, or unstable angina ○ 1st trimester of pregnancy ○ Perform a good case history (Allergies) ○ Office that performs FAN must have epinephrine ampules 1:1000 dilution and emergency response system Defibrillators and CPR training Phases Pre-Arterial Phase: choroidal circulation is filled (choroidal flush), no dye has reached the retinal arteries ○ Very fast phase Arterial Phase: 1 second after the prearterial phase. It extends from the first appearance of dye in the arteries until the whole arterial circulation is filled  ○ CRA becomes white due to the fluorescein, but the CRV is still black Capillary Phase: complete filling of the arteries and capillaries ○ Retinal capillaries are visible, especially around the ONH and FAZ Venous Phase: subdivided according to venous filling and arterial emptying ○ Venous early stage (aka arterio-venous) Arteries and capillaries are filled and there is lamellar flow in the veins Retinal veins central lumen is dark and the walls have fluorescence ○ Venous mid-stage Veins nearly filled Complete vein filling occurs over the next 10 seconds with maximum vessel fluorescence occurring ~30 sec after injection Aka recirculation phase Occurs about 2-4 minutes after injection The veins and arteries remain roughly equal in brightness The intensity of the fluorescein is slowly diminishing ○ Venous late-stage Veins completely filled and the arteries are beginning to empty Veins have more concentration of dye than arterioles Dye starts to be excreted by the kidneys  Late phase demonstrates the gradual elimination of fluorescein from the retinal and choroidal vasculature Occurs 7-15 minutes after injection Late staining of the optic disc is a normal finding Any other areas of late hyper fluorescence suggest the presence of an abnormality FAN Expected Timing ○ 0 sec: Fluorescein is injected  ○ 9.5 sec: Posterior ciliary arteries fill ○ 10 sec: “Choroidal Flush”- background choroidal fluorescence ○ 10-12 sec: Retinal arterial phase ○ 13 sec: Capillary transition phase ○ 14-15 sec: Early Venous Phase ○ 16-17 sec: Venous Phase ○ 18-20 sec: Late Venous Phase FAN Delays ○ Choroidal flush can be delayed by conditions such as: Decreased cardiac output Congestive heart failure Hypertension Giant Cell Arteritis (creates a patchy choroidal flush) ○ Arterial stage ranges from 2-30 seconds depending on: Blood viscosity Vessel caliber Cardiac output Cardiac disease Autofluorescence or pseudofluorescence: Fluorescence prior to NaFl injection Something in the retina can produce autofluorescence (ex: ONH drusens) Macular hypofluorescence: Appear normally dark High concentration of RPE and xanthophyll blocks the choroidal flush Foveal Avascular Zone (FAZ): Free of retinal capillaries (500 microns) FAN Interpretation Healthy retinal vessels do not leak NaFl Retinal vessel walls are not fenestrated Healthy choriocapillaris are fenestrated and leak, creating a sponge-like tissue NaFl flush In a healthy retina, the choriocapillaris fluid is kept away from the sensory retina by an intact Bruch’s Membrane barrier RPE is also a filter, allowing for a partial showing of the choroidal glow ○ Dense RPE and xanthophyll mask the choroidal flush in the macular area ○ If there is absent or missing RPE, more glow will be seen ○ Hyperfluorescence Causes Transmission: window defect due to atrophy or absence of RPE ○ Will start with early hyperfluorescence, increasing in intensity and then fades w/o changing in size or intensity Ex: ARMD  Pooling: due to a breakdown of the outer-blood retinal barrier (RPE and zonula occludens) ○ Occurs in the subretinal space ○ Early hyperfluorescence, which then increases in size and intensity Ex: central serous chorioretinopathy (CSCR) ○ Leakage: from an abnormal choroidal vessel, CNVM, or breakdown of the inner blood-retinal barrier ○ Ex: cystoid macular edema or retinal neovascularization ○ Staining: due to prolonged fluorescein retention ○ Seen in the late phase ○ Hypofluorescence Causes Decreased or absent fluorescein due to an optical obstruction (masking) or inadequate perfusion Inadequate perfusion: ○ Blockage of retinal fluorescein  Pre-retinal lesions like blood: won’t see below because signal does not go through due to blockage Deep retinal lesions such as intraretinal hemorrhages or hard exudates which will block fluorescein ○ Blockage of background choroidal fluorescence: all conditions that block retinal fluorescence and those that block only choroidal fluorescence like: Increased RPE density (CHRPE: dense pigmentation of retina; associated to Gardner’s) Choroidal lesions (nevi) - can turn into melanoma Subretinal and sub-RPE lesions (blood) Filling defects: ○ Capillary closure ○ Retinal vascular occlusions Optical Barriers: ○ Pigment ○ Blood Choroidal nevus Causes hypofluorescence of the choroid, while the choriocapillaris are intact ○ Hypofluorescence due to blockage of background choroidal fluorescence by congenital hypertrophy of the RPE Pre-retinal hemorrhage Branch retinal vein occlusion  Subretinal hemorrhage Congenital hypertrophy of the RPE (CHRPE) Drusens: accumulation of lipfuschin Choroidal neovascularization ○ Diagram shows the abnormal vascular proliferation from the choriocapillaries dissenting under the RPE Subretinal hemorrhage ○ Early arteriovenous phase shows a lacy, irregular, nodular area of hyperfluorescence (NV) in the inferotemporal macula  ○ Late-phase-leakage from the patch of NV. Pooling of fluorescence under sensory retinal detachment Cystoid macular edema (CME) AV phase dilation of the capillaries around the fovea ○ Late phase hyperfluorescence ○ Malignant melanoma Geographic atrophy Full hypofluorescence- choroidal flush Indocyanine Green (used more for choroidal evals than retina but used for both) Non-toxic dye to corneal endothelial cells Stains diseased or dead endothelial cells Used for evaluation of donor corneal viability ICGA is used to observe vasculature of the choroid ICG ○ 98% of ICG is bound to protein (mainly albumin) Very little choriocapillaries leakage 2% excreted by kidneys and free-floating (be careful w/ impaired hepatic functions) ○ Excreted by the liver Patients with liver disease should avoid this test!!! ○ Is iodinated, so patients with allergy to iodine or shellfish should not undergo this test. CI to those allergic to shellfish! ○ Technique is similar to FAN, but image acquisition can continue to be taken up to 45 minutes ICGA ○ Fenestration of choriocapillaris are impermeable to larger protein molecules, most ICG is retained in choroidal vessels ○ ICG absorbs and emits light near the IR range  Better penetration of the RPE pigment, on exudates and thin layers of subretinal blood and choroid ○ Infrared light is scattered less than visible light. Therefore, ICGA is better for patients who have media opacities Clinical applications of indocyanine green ○ Fluorescent dye for retinal and choroidal angiography ○ Cataract surgery for staining of the anterior lens capsule ○ Vitreoretinal surgery to enhance visualization of the tissues on macular surface ○ Can be better than FAN for occult CNVM and those associated with a serous detachment Borders are easier to identify ○ ○ Limitations ○ Requires expensive imaging system ○ Quality of image is poor ○ Detailed capillaries are difficult to identify ○ Hopeful possibilities As ICG absorbs and emits in near IR spectrum, lasers which operate in this wavelength can possibly be used to accurately and selectively identify and ablate choroidal membrane Side effects ○ As safe as NaFl with fewer reactions ○ Severe allergic reactions have been reported ○ Nausea, vomiting and hives in few cases ○ ICG remains protein bound and rapidly metabolizes by the liver ○ Discoloration of the urine, skin or mucous membranes does not occur Contraindications ○ Iodine sensitivity or shellfish allergy  ○ Liver problems ○ Safety in pregnancy has not been established so it is not performed in pregnant women FAN vs ICGA for occult CNVM Normal ICGA MEWDS White-Dot Syndrome (has patchy choroidal appearance)