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Fluorescein Angiography
- 1. Fluoroscein angiography- A journey through the vessels of the eye Dr.Shah-Noor Hassan FCPS,FRCS(Glasgow) Vitreo –Retina Unit Bangabondhu Sheikh Mujib Medical University
- 2. Introduction • The word Angiography - Greek angeion, "vessel" and graphien, "to write or record". • imaging of vessels, and the resulting pictures are angiograms. • in-vivo study of the retinal circulation
- 3. milestones 1871: Fluorescein is synthesized 1881: aqueous flow is examined with fluorescein sodium 1886-91: in vivo retinal photography of human subjects is attempted 1899: high quality fundus photograph are shown 1910: the choroid and retina are examined with fluorescein sodium 1926: fundus camera becomes commercially available 1930: filters are used to observe dye in retina 1939: dye flowing through the retinal vessels is described 1953: electronic flash tube technology is applied to fundus photography 1959: sodium fluorescein is photographed in the cat retina 1961: modern fluorescein angiography technique is described
- 4. Basic principle • luminescence- emission of light by excitation of atoms or molecules to higher energy levels • fluorescence- luminescence that is maintained by continuous excitation.
- 5. Cont…. • The emitted energy is often less than the absorbed energy, though of longer wavelength (stoke’s law) • Fluorescein absorbs blue light and emits yellow green light • Exciter filter (blue) and barrier filter (green)
- 6. • Properties of Flourescein Na
- 7. Chemical properties • Fluorescein sodium - synthesized from the petroleum derivatives resorcinol and phthalic anhydride • Low molecular weight • High solubility • Rapid diffusion through body fluids but not large enough to pass through tight junctions of retinal vessels, RPE and large choroidal vessels. • This is the basis for the diagnostic value of the test.
- 8. Optical properties • It absorbs blue light, with peak absorption and excitation occurring at wavelengths between 465-490nm. • Fluorescence occurs at the yellow-green wavelengths of 520 to 530nm
- 9. Pharmacological properties • 80% bound to serum proteins • also bound to blood cells • remaining is seen during angiography
- 10. pharmacokinetics • Metabolized by kidney, excreted from the body within 24 to 36 hrs • Small amounts are lost in bile. • Skin - a yellowish tinge for a few hours • Urine - yellow-orange color • dye is a biologically inert substance
- 11. Requirement
- 12. Relevant anatomy • Fluorescein cannot diffuse through tight cellular junctions present at two sites within the fundus: – retinal blood vessel endothelium (inner blood retinal barrier) – retinal pigment epithelium (outer blood retinal barrier)
- 13. • Angiography is composed of the superimposition of two separate circulations – Choroidal circulation - the fluorescein freely leaks out of the fenestrated choroidal capillaries, and from there through Bruch's membrane. – Retinal circulation - the retinal blood vessel endothelial cells are joined by tight junctions which prevent leakage of fluorescein into the retina.
- 14. Phases of normal angiogram • Arm to retina time: Normally 10-15 seconds elapse between dye injection and arrival of dye in the eye. • Retinal ciculation time: Transit of dye through the retinal circulation takes 15 to 20 seconds.
- 15. PHASES OF ANGIOGRAM 1. PREARTERIAL [ CHOROIDAL FLUSH ] – 10 sec 2. ARTERIAL – 12sec 3. ARTERIO-VENOUS - EARLY TRANSIT – 13 sec - MID TRANSIT – 16sec - LATE TRANSIT – 20 sec 3a. Peak phase – 25 sec 4. RECIRCULATION – 30sec 5. LATE FLURESCEIN TRANSIT – after 10 min
- 16. Choroidal phase • 1. Choroidal phase - - initial patching filing of lobules, - followed by a diffuse (flush) as dye leaks out of the choroidocapillaris.
- 17. - visualisation of choroid depends on retinal pigmentation - Cilioretinal vessels and prelaminar optic disc capillaries fill during this phase.
- 18. Arterial phase • the central retinal artery fills about 1 second later than choroidal filling
- 19. Venous phase • Early venous phase: filling of the veins is from tributaries joining their margins, resulting in a tramline effect (lamellar flow)
- 20. • Mid venous phase: veins are nearly filled • Late venous phase: veins are filled and arteries start to empty.
- 21. Late phase • after 10 to 15 minutes little dye remains within the blood circulation. • Dye which has left the blood to ocular structures is particularly visible. • it shows abnormal dye accumulations indicative of leakage or staining.
- 22. SELECTION OF PATIENT • Not recommended : - History of allergy, severe urticaria or bronchial asthma - Pt with renal failure and poor general condition. • In pregnant women -it may be avoided. • Safe: In diabetics, hypertensives and history of previous cardiovascular disorders.
- 23. The Consent Form • The name of the procedure • The name of the doctor ordering the procedure • A list of possible adverse reactions to the procedure • A warning that pregnant women should not have the test • The date • The patient's signature • A witness's signature
- 24. brief "patient friendly" explanation of the procedure • The reason for the test • A brief description of the procedure. • Possible side effects. • How long the procedure will take and • what will happen at the conclusion of the procedure.
- 25. preparation • make sure the patient is well dilated • Log the patient information • Injectable fluorescein dye comes in 5%(10cc) , 10% (5cc), and 20% (2cc or 3cc) solutions. • 20% solution is preferred because this larger bolus produces better photographic contrast and detail in the initial phases of the angiogram
- 26. •Interpretation
- 27. analysis – Sequential analysis - frame by frame. useful in analysing vascular disorders of the retinal and choroidal. – Anatomic analysis - observes each of the major layers of the posterior pole of the eye - the choroidal, RPE and neurosensory retina. – Morphologic analysis - considers overall patterns. (hyperfluorescent) or lighter (hypofluorescent)
- 28. reporting • Start with any striking abnormality and describe this in detail: - phase of angiogram – Hypo/hyperfluorescent components – Intensity of fluorescence and changes with time – Area of fluorescence and changes with time
- 29. Common abnormalities • Timing-arm to eye time and retinal circulation may be prolonged if the cardiac output is low or the carotid perfusion is reduced. • Abnormal dye distribution: hypofluorescence/ hyperfluorescence
- 30. FFA interpretation flow chart fluorescein angiogram normal abnormal artifact hyperfluorescence hypofluorescence Leakage pooling staining window blocked nonfilling defect
- 31. HYPO BLOCKED FILLING DEFECT RETINAL CHOROIDAL RETINAL DISC CHOROIDAL •DEEP RETINAL •SUBRETINAL •ARTERY •VEIN •CAPILARY •COMBINED •PHYSIOLOGIC •PC OCCLUSION •ABSCENCE
- 32. Hypofluorescence Transmission defect -blood, -pigment, -hard exudates -abnormal material (eg, the yellow flecks in patient with Stargardt's disease etc)
- 33. - pre-retinal opaque structures superficial to the retinal circulation will mask both the retina and choroidal circulation eg. -Preretinal hemorrhage, -myelinated nerve fibres.
- 34. • - prechoroidal opaque structures deep to the retinal circulation but superficial to the choroidal circulation will mask only the choroidal circulation for example:
- 35. blood - retinal haemorrhages - subretinal blood from choroidal new vessels
- 36. Filling defect due to abnormal circulation • arterial non-perfusion is seen in occlusion of the central retinal artery and its branches • capillary non-perfusion is an important sign of retinal ischaemia.
- 37. 46 Disturbance of choroidal circulation (occlusion of ciliary artery)
- 38. HYPER PRE INJ EARLY LATE AUTO PSEUDO RETINAL VESSELS CHOROID Vs OR WD VITREOUS DISC RETINAL CHOROIDAL •POOLING •STAINING •CME •NON CYSTOID
- 39. hyperfluorescence • Window defects of the RPE • In ARMD, fluorescein in the choroidal circulation appears brighter where the overlying RPE is atrophic. • most prominent in the choroidal phase
- 40. Leakage of dye • occurs when there is breakdown of the tight junction of the RPE or the retinal endothelium.
- 42. • t
- 43. CME
- 44. Leakage with staining • Impregnation into the tissue • The dye is derived from the choroidal circulation, and staining is most evident in the late phase.
- 45. Leakage from abnormal vessels • choroidal and retinal new vessels are structurally abnormal • tumors such as choroidal malignant melanoma, have their own blood supply which may leak.
- 46. Autofluorescence • Presence of hyperfluorescence in the fundus seen in pre-injection photographs. • optic disc drusen is the classic example. • Others: astrocytic hamartoma, large deposits of lipofuscin and exudates
- 47. FFA patterns of some common diseases
- 48. Diabetic retinopathy • Diabetic macular edema: • maculopathy and unexplained visual loss: • extent of capillary drop out areas in severe NPDR: delineated by FA
- 49. 1. Retinal Haemorrhage 2. Retinal ischaemia 3. Microaneurysms 4. NVE 5. IRMA 6. Venous bleeding DIABETIC RETINOPATHY
- 50. How will you differentiate between NVE / IRMA / Collaterals ? a) NVE – early hyper Fl. – Increase in size & intensity, profuse leak with Fussy margins. b) IRMAS : Hyper Fl. Starts in venous phase Mild staining & minimal leak no fussy margins. C) Collaterals – Connects nonperfused to perfused a) Staining of vessels b) No profuse leak.
- 51. ARMD • FA is not indicated in each and every case and in every visit • Indications • - possibility of finding CNVM metamorphopsia recent decrease in vision central or paracentral scotoma - undergone laser treatment
- 52. drusens • RPE is thinner over the surface of the hard drusen producing transmission defect • Myriads of small drusens- basal laminar drusens show starry sky appearance
- 53. Dry armd
- 54. Wet ARMD • FA helps in determining the extent and the type of nv • Classified into classic and occult variety into extrafoveal juxtafoveal subfoveal
- 55. classic • Classic: the vessels themselves are easily visible in the early phases of the angiogram, appear as cartwheel • These show prominent leakage during the course of angiogram • the vessels are often obscured by the overlying fluorescence leaked from the vessels.
- 56. occult • Occult- obscuration of the fibrovascular ingrowth by intervening tissue alters the appearance of lesion on FA. • we can observe the fuorescence characteristic of the vessel indirectly. • Two types - Fibrovascular PED - Late leakage of undetermined source
- 57. Venous occlusions • Advisable after 3 months • Blocked fluorescence: hemorrhages • Delayed filling and delayed emptying • CNP areas • Leakage from NVE
- 58. BRVO
- 59. CRVO
- 60. CRAO • Delay in retinal arterial filling Delay in A-V transit time • complete lack of filling of the retinal arteries is unusual • Choroidal filling is usually normal or a delay of 5 secs
- 61. FA can revert back to normal after varying period of time after the insultFA can revert back to normal after varying period of time after the insult
- 62. BRAO • Artery occlusion • Purtschners retinopathy- • blocked fluoroscence partly due to ischaemia and intracellular edema-opacified edematous retina
- 63. How to differentiate • Blocked fluorscence –abrupt cut off of the retinal vessels • Vascular filling defects-areas of hypofluoroscence surrounded by tortuous vessels with pruning
- 64. CSR • ≥ 1 hyperfluorescent leaks from RPE • Pattern: – Ink-blot – Smoke-stack – Point (< 1/5 DD) – Combinations – No definite leak
- 65. • Defines the location • Ink-blot (85%): – Even spread in all directions • Smoke-stack (10%): Rises superiorly ⇒ Expands laterally • Mushroom-like • Umbrella-like • No definite leak (5%): -Leaking point has healed -Lies outside macular area -Associated with ONP • PED may be detected if missed clinically
- 66. Eale’s disease • Active vasculitis: staining of vessel wall • CNP areas • NVE’s with leakage • Multiple BRVO • CRVO
- 67. FFA finding in vasculitis • Varing degrees of venous occlusion • Delayed filling • In acute stage – engorged capillary bed leak fluoroscein • Frank extravasation • Parallel sheathing by gliosis-does not show these features • CNP • NVE • Increased permeability at the disc
- 68. CHOROIDITIS
- 69. CHORIOEREMIA
- 70. Oral FA • Indication:Indication: Psychologically or technically unsuitable for i/v injectionPsychologically or technically unsuitable for i/v injection especially children, obese ptsespecially children, obese pts.. Dose:Dose: 1 gm Na fluorescein (5ml of 20% dye)1 gm Na fluorescein (5ml of 20% dye) (mixed in 200 ml of orange juice – Body weight 40kg.(mixed in 200 ml of orange juice – Body weight 40kg. 1.5 gm in pts with a body wt 60 kg.1.5 gm in pts with a body wt 60 kg. while 2.0 gm is given to pts over 60 kg wtwhile 2.0 gm is given to pts over 60 kg wt
- 71. Post-administration photographs taken after 15, 30, 45 and 60 minutes. Reserved - lesions resulting in late dye leakage and pooling like CSR, disciform disc degeneration etc. Not recommended when early circulation dynamics are to be studied
- 72. Adverse events severity Adverse events percentage Mild Nausia, vomiting, extravasation 1-10 moderate Urticaria, pyrexia, local tissue necrosis, nerve palsy 1.6 severe Bronchospasm, anaphylaxis, shock 0.05 death 1/222,000
- 73. EMERGENCY in FA Case • Allergic reaction: Local / Generalised Manifest: redness, itching, oedema & urticaria. • Stop dye injection. • Monitor Pulse , BP & Resp. • Inj. Avil 2ml IV • Inj Efcorlin 100mg IV • Normal Saline – wash the local site
- 74. 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.e.g. polycythemia weldenstrom macroglobulenaemia binding of fluorescein with excess Hb or protein Lack of freely circulating molecule
- 75. Fluorescein Angioscopy • Indirect Ophthalmoscope along with its blue filter attachment, is used for viewing of the fundus periphery. • Pathology including Eales disease, sarcoidosis, retrolental fibroplasia and peripheral vasculitides, both in active inflammatory stage and later stage, are effectively visualised by F-scopy
- 76. SUMMARY • Valuable in DR - Neovascularisation - CNP areas - Maculopathy • CNVM activity • CSR • Venous occlusion • Patient education
Editor's Notes
- DR. HARSH
- Angiography is the , comes from the, facilitates the
- Since then the basic procedure has remained the same but the fundus imaging has been improved.
- excitation by electromagnetic radiation) Principle of FA is the application of phenomenon of
- According to the law of thermodynamics. Based on this fact. Integral parts of FA
- chemical compound is a highly fluorescent
- Hence it is necessary to inject large volume of fluorescein. The contrast of the dye is good in anemic patients as the free dye available in plasma is greater.
- Usual dose is 500 mg it requires 10%
- Infrared reflectance light and confocality Lasers used are 790,829,488 nm. 20micron 5micron compared to 15micron Field of view is narrower. FC gives up to 60 degree view while HRA 30degree. Montage does help in this.
- however, tight junctions between retinal pigment epithelium (RPE) cells prevents dye reaching the retina
- approximately
- Normal fluorescein angiogram of right disc and macula taken with a 60-degree camera. A, Red-free photograph. The disc and macula are normal. The reflex above and below the foveal area is normally seen in a young patient. B, The ground-glass fluorescence is the very early fluorescein filling of the choroid--the choroidal flush--which often occurs a few seconds before fluorescence within the retinal arteries, which in this photograph are just beginning to fill with fluorescein. C, Early arterial phase of angiogram. Note that the retinal arteries are filling, and the retinal veins have not yet begun to fluoresce. The choroid is almost completely fluorescent. The dark patches are areas of hypofluorescent choroid that have not yet received fluorescein; this is called patchy choroidal filling. D, Early arteriovenous phase of the angiogram. The retinal veins have begun to show fluorescein filling, as evidenced by the laminar flow within the veins. The patchy choroidal filling has mostly cleared, although still remaining are two patches faintly evident above the disc, one large patch below, and one nasally. E, Midarteriovenous phase of the angiogram. The choroid has completely filled with fluorescein, as have the retinal arteries and veins. The macula remains dark. F, Late phase of the fluorescein angiogram shows that fluorescein has faded from both the choroid and retinal vessels. There is very slight staining along the disc margin inferotemporally. The macula has remained dark.
- choroidal filling via the short ciliary arteries results in ,very quickly. If present
- as the underlying choroidal circulation is masked by luteal pigment in the retina and melanin pigment in the RPE. forming a rectangular pattern that can be seen surrounding he disc
- Mid phse: intensity of dye increases, reaching a stage in which veins are more hyperflourescent than arteries.
- Staining of the disc is seen. during this phase. Important because
- If the patient was already dilated before being asked to read and sign the consent form, you must read and/or explain the form to the patient. Notice that the &quot;presentation&quot; given to the patient was very similar to what is in the consent form
- A brief &quot;patient friendly&quot; explanation of the procedure This is a test of the retinal circulation that will give the doctor more information about your eye problem. This information is very useful and is not available from any other procedure &quot;We will take some color photos of your retina and then inject a dye in your arm and photograph the circulation of the dye in your eye.&quot; &quot;The dye will turn your skin yellowish and your urine orange for several hours after the test. A small percentage of patients experience nausea. If this happens to you, let me know and we can stop the test for a few minutes. The nausea usually passes quickly. There is a small chance that you may have a mild to moderate allergic reaction to the procedure. There is a very small chance that you may have a severe reaction to the dye. We are prepared to treat you if needed The test will take approximately 20 minutes and then the doctor will come in and review the photos with you and your wife.&quot;
- using whatever system is setup
- Thus there should be no light reaching the film except the fluorescent light from the retinal circulation. When you take a, with the filters in place
- Red free photos are useful for detecting superficial retinal abnormalitites at the level of the inner retinal laers, such as wrinkling of the ILM and foveal cysts. When lesions are at the level of choroid or RPE are being studied, green free or red light is preferred due to deeper penetration of red light.
- This clinical and research tool facilitates the in vivo study of the histopathologic characteristics of fundus disease. Before the advent of fluorescein angiography, conditions such as pigment epithelial detachment, cystoid retinal edema, and subretinal neovascularization could be evaluated and understood only histologically.
- the simultaneous use of colour picture is recommended it is examined , in the order that it was photographed In an abnormal angiogram, some areas may be darker
- It is seen in diabetic retinopathy and following retinal vein occlusion.
- the RPE behaves as a pigmented filter, reducing transmission of fluorescence. - areas of atrophy of RPE act as windows through which the fluorescence may be seen more brightly These areas of hyperfluorescence are, but persist through out all phases of the angiogram.
- fluid is present under the RPE
- which persists after dye has been cleared from the choroidal and the retinal circulations. collagen absorbs fluorescein dye causing staining
- and do not have intact endothelial tight junctions
- when both exciter blue and barrier green filters are used. Highly reflective material
- helps in distinguishing focal from diffuse edema, helps in assessing whether the loss of vision is due to ischemic maculopathy, DME or cystoid macular edema, and in Indian conditions will require PRP Based on which we decide iffocal laser treatment is needed or a grid laser treatment is required
- residual or new NV which may require supplemental photocoagulation
- In order to check if the lesion is completely treatment
- Early hyperfluorescence that remains stable during the course of examination
- Depending upon the distance from the central fovea
- In such lesions Because we do not see the vessels directly, rather inferring their presence through indirect effects this is called occult variety
- Of the involved vein
- occurs in less than 2% of cases, more prolongation is indicative of ophthalmic or carotid artery obstruction , as the retinal circulation tends to reestablish.
- Similar to CRAO but confined to affected segment
- Jet-like projection of fluid from RPE defect Diffusion & convection rather than net fluid influx Increased concentration of proteins in SRF Low density fluorescein rises by convection pit Leaking point has healed Lies outside macular area In presence of choroidal tumour Associated with ONH
- NVE at the junction of the perfused and non-perfused retina
- CNP areas Nve originate just proximal to the involved segment of the vein , with looping- leak fluoroscein in late venous phase The increased permeability at the disc or the proximal segment -forewarn the formation of the vascular proliferation inflamed wall stain with narrowed lumen- swelling and dilatation distal to the site of inflammation
- Choroideremia: total loss of retinal pigment epithelium (RPE) and choriocapillaris with much of the large choroidal vasculature remaining. A, Red-free photograph of right disc and macula. The large choroidal vasculature can be seen as pale irregular lines. There are some dark patches of pigment located in the macula and around the disc. B, Early arteriovenous-phase fluorescein angiogram of right disc and macula. The large choroidal vessels can be seen filling, as can the retinal arteries. The choriocapillaris is not seen. C, Midarteriovenous-phase fluorescein angiogram. The large choroidal vessels and retinal vessels can be seen, but the choriocapillaris (usually seen as ground-glass fluorescence) is not seen. D, Right disc and macula. Late-phase fluorescein angiogram shows no staining of the sclera; the large choroidal vessels and retinal vessels have become much less fluorescent as fluorescein has become diluted in the bloodstream. There is some late hyperfluorescent staining inferiorly where some islands of choriocapillaris have remained. COMMENT: This patient had a total loss of RPE and choriocapillaris in most areas of the fundus. The ground-glass choroidal fluorescence was absent from most areas. The large choroidal vessels could be seen. The large choroidal vessels do not leak fluorescein, and therefore the sclera did not stain in these areas.
- The Fluorescein Angiography Complication Survey has reported that one death occurs for every 222,000 ocular angio. It is generally recommended that a physician be present or available during angiography.
- It is one of the most fascinating yet immensely informative investigative procedure in ophthalmology