Ffa

ffa n icg presentation

1.   FLUORESCEIN ANGIOGRAPHY AND INDOCYANINE GREEN ANGIOGRAPHY DR. NIRAV B. DADIA FELLOW NANDADEEP HOSPITAL

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. Basic principle luminescence - emission of light by excitation of atoms or molecules to higher energy levels fluorescence - luminescence that is maintained by continuous excitation.

4. 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)

5. Properties of Flourescein Na

6. 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.

7. 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

8. Pharmacological properties • 80% bound to serum proteins • also bound to blood cells • remaining i.e. Unbound dye is seen during angiography

9. 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

10. Requirement

11. Relevant anatomy Outer blood retinal barrier Inner blood retinal Barrier   Fluorescein cannot diffuse through tight cellular junctions present at two sites within the fundus

12.  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.

13. 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.

14. 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

15. Choroidal phase - initial patching filing of lobules, - followed by a diffuse (flush) as dye leaks out of the choroidocapillaris .

16.  visualisation of choroid depends on retinal pigmentation - Cilioretinal vessels and prelaminar optic disc capillaries fill during this phase.

17. Arterial phase • the central retinal artery fills about 1 second later than choroidal filling

18. Venous phase • Early venous phase: filling of the veins is from tributaries joining their margins, resulting in a tramline effect (lamellar flow)

19. 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.

20. DARK APPEARANCE OF FOVEA The dark appearance of the fovea is caused by three factors: Absence of blood vessels in the FAZ. Blockage of background choroidal fluorescence due to the high density of xanthophyll at the fovea. Blockage of background choroidal fluorescence by the RPE cells at the fovea, which are larger and contain more melanin and lipofuscin than else where in the retina

21. SELECTION OF PATIENT • Not recommended : - History of allergy, severe urticaria or bronchial asthma - Patient with renal failure and poor general condition. • In pregnant women - it may be avoided. • Safe: In diabetics, hypertensives and history of previous cardiovascular disorders.

22. CONTRAINDICATIONS ABSOLUTE 1) Known allergy to iodine containing compounds. 2) H/O adverse reaction to FFA in the past. RELATIVE 1) Asthma 2) Hay fever 3) Renal failure 4) Hepatic failure 5) Cardiac disease – cardiac failure, Myocardial infarction 6) Previous mild reaction to dye. 7) Tonic- clonic seizures 8) Pregnancy ( especially 1st trimester

23. 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

24. 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 )

25. 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

26. 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

27. Hypofluorescence Transmission defect -blood, -pigment, -hard exudates -abnormal material ( eg , the yellow flecks in patient with Stargardt's disease etc)

28. pre-retinal opaque structures superficial to the retinal circulation will mask both the retina and choroidal circulation eg . - Preretinal hemorrhage , - myelinated nerve fibres

29. prechoroidal opaque structures deep to the retinal circulation but superficial to the choroidal circulation will mask only the choroidal circulation for example:

30. blood - retinal haemorrhages - subretinal blood from choroidal new vessels

31. 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 .

32. Leakage of dye  • occurs when there is breakdown of the tight junction of the RPE or the retinal endothelium.

33. 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

34. FFA patterns of some common diseases

35. 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

36. Wet ARMD • FA helps in determining the extent and the type of neo- vascularization . • Classified into classic and occult variety into extrafoveal juxtafoveal subfoveal

37. BRAO • Artery occlusion • Purtschners retinopathy- blocked fluoroscence partly due to ischaemia and intracellular edema - opacified edematous retina

38. CHOROIDITIS

39. Oral FA Indication: Psychologically or technically unsuitable for i /v injection especially children, obese pts. Dose: 1 gm Na fluorescein (5ml of 20% dye) (mixed in 200 ml of orange juice – Body weight 40kg. 1.5 gm in pts with a body wt 60 kg while 2.0 gm is given to pts over 60 kg

40.  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

41. Adverse events severity Adverse events percentage Mild Nausia , vomiting, 1-10 extravasation moderate Urticaria , 1-6 pyrexia, local tissue necrosis, nerve palsy severe Bronchospasm , 0.05 anaphylaxis, shock death 1/222,000

42. 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

43. 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

44. Limitations of FFA 1) Does not permit study of choroidal circulation details due to 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

45. INDOCYANINE GREEN ANGIOGRAPHY

46. INDOCYANINE GREEN ANGIOGRAPHY • Indocyanine green (ICG) angiography (ICGA) is fast emerging as a popular and useful adjunct to the traditional fundus fluorescein angiography (FFA) in the diagnosis of macular, choroidal and outer retinal disorders. • This technique was introduced in ophthalmology in 1973 by Flower and Hochheimer . • FDA approved the ophthalmic use of ICG dye in 1975. • It remained largely unpopular owing mainly to technical difficulties With the advent of videoangiogram recordings and the recognition of its potential in delineating occult choroidal neovascular membranes, the clinical use of ICGA has increased tremendously .

47. PRINCIPLES OF ICG ICG fluorescence is only 1/25th that of fluorescein . So modern digital ICGA uses high-sensitivity videoangiographic image capture by means of an appropriately adapted camera. Both the excitation (805 nm) and emission (835 nm) filters are set at infrared wavelengths. Alternatively, scanning laser ophthalmoscopy (SLO) systems provide high contrast images, with less scattering of light and fast image acquisition rates facilitating high quality ICG video. The technique is similar to that of FA, but with an increased emphasis on the acquisition of later images (up to about 45 minutes) than with FA. A dose of 25–50 mg in 1–2 ml water for injection is used.

48. INDOCYANINE GREEN The indocyanine green (ICG) is a tricarbocyanine dye that comes packaged as a sterile lyophilized powder and is supplied with an aqueous solvent. Molecular weight :774.97 It contains less than 5% sodium iodide (in order to increase its solubility). It has a pH of 5.5 to 6.5 in the dissolved state, has limited stability, and hence must be used within 10 hours after reconstitution. 98% of the injected dye is bound to plasma proteins , with 80% being bound to globulins, especially alpha- 1 lipoproteins.

49. CLEARANCE The dye is secreted unchanged by the liver into the bile. There is no renal excretion of the dye It does not cross the placenta. The dye also has a high affinity for vascular endothelium, and hence persists in the large choroidal veins, long after injection.

50. ADVERSE EFFECTS Nausea, vomiting are uncommon. Anaphylaxis, approximately equal incidence to FA. Serious reactions are exceptionally rare. ICG contains iodide and so should not be given to patients allergic to iodine or possibly shellfish. iodine-free preparations such as infracyanine green are available.

51. CONTRAINDICATIONS ICGA is relatively contraindicated in liver disease (excretion is hepatic) In patients with a history of a severe reaction to any allergen. moderate or severe asthma significant cardiac disease. Its safety in pregnancy has not been established

52. PHASES OF ICGA Early – up to 60 seconds post-injection Early mid-phase – 1–3 minutes Late mid-phase –3–15 minutes Late phase – 15–45 minute

53. HYPERFLOURESCENE

54. HYPOFLOURECENCE  

55.   INDICATIONS OF ICGA Polypoidal choroidal vasculopathy (PCV) Exudative age-related macular degeneration (AMD) Chronic central serous chorioretinopathy . Posterior uveitis . Choroidal tumors may be imaged effectively Breaks in Bruch membrane If FA is contraindicated.

56. ADVANTAGES OF ICGA OVER FFA

57. RECENT ADVANCES IN INDOCYANINE GREEN ANGIOGRAPHY Wide-angle angiography: This is carried out by performing ICGA with the aid of wide angle contact lenses, such as Volk SuperQuad and a traditional Topcon fundus camera.This allows real-time imaging of a wide field of the choroidal circulation up to 160 degrees of field of view. Overlay technique: This technique allows lesion on one image to be traced on to another color or red-free image. Digital stereo imaging: Elevated lesions such as PEDs can be better imaged in this way. ICG as a photo sensitizer: It is considered to be a cheaper alternative to vertoporfin in photodynamic therapy of neovascular AMD& other disorders . Digital subtraction ICGA: It uses digital subtraction of sequentially acquired ICG images along with pseudo color imaging. It shows occult CNVM in greater detail and within a shorter time than conventional ICGA.

58. SUMMARY

59. Fundus fluorescein angiography ICG angiography For retinal circulation For choroidal circulation Dye used – sodium fluorescein Dye used – indocyanin green 80% plasma protein bound 98% plasma protein bound low MW high MW Light of visible spectrum used Infrared spectrum of light used Blue green filters used Infrared filters used More side effects Less side effects

60. FFA • Valuable in DR – Neovascularisation – CNP areas - Maculopathy • CNVM activity • CSR • Venous occlusion • Patient education

61. FUTURE APPLICATIONS OF INDOCYANINE GREEN ANGIOGRAPHY In the future, ICGA is expected to play a more important and wider role especially in the management of macular disorders. Identifying subclinical neovascular lesions in the other eye of patients with AMD. There are several reports that mention that 10% of such eyes with no clinical or fluorescein angiographic evidence of an exudative process harbor plaques of neovascularization evident on ICGA. ICG-guided feeder vessel photocoagulation: SLO high-speed ICGA can adequately image the feeding vessels of the CNVM which are 0.5 to 3 mm in length and are believed to lie in the Sattler’s layer of the choroid

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