fundus fluorescein Angiography ppt presentation

fundus fluorescein Angiography ppt presentation

1. Fundus Fluorescein Angiography Shivani Kochhar Medical Retina F ellow Dept. Of Ophthalmology University of Florida college of Medicine

2. Contents Definition Historic Background Basic Principle of FFA Dye used in FFA Purpose Indications Contraindications Technique Complications Phases Examples Other techniques

3. Definition FFA is an invasive diagnostic procedure. It refers to photographing the fluorescein dye in the retinal vasculature following intravenous injection of fluorescein sodium. It allows to study the anatomy, physiology and pathology of retinal and choroidal circulation by assessing the vascular integrity of retinal and choroidal vessels.

4. Why FFA? To confirm the elements already revealed by clinical examination Flow characteristics in the blood vessels as the dye reaches and circulates through the retina and choroid Gives a clear picture of the retinal vessels and assessment of their functional integrity To monitor the disease intensity and impact of therapy Provides guidance for application of focal laser in photocoagulation therapy To detect the leakages without clinical manifestation of edema.

5. Background 1882 – Ehrlich introduced Fluorescein into investigative ophthalmology 1940 – Gifford studied aqueous dynamics after injecting intravenous Fluorescein Therefore, earlier attempts were made with IV injection of fluorescein in humans to study the retinal circulation but because of insufficient lighting of the fundus camera and absence of barrier filters, they could not get serial images of the fundus to measure the circulation time. 1960 - Novotny and Alvis ( 2 medical students ) eventually used the new fundus camera with 2 different filters to image the fluorescence of the dye. They successfully got the first FFA in 1961.

6. Principle Fluorescence It is the property of certain molecules to emit light energy of longer wavelength when stimulated by a shorter wavelength. Sodium fluorescein dye absorbs light (excitation) in the range of 465nm -490 nm (blue light) and emits (emission) light in the range of 520-530 nm(green light).

7. Principle The dye does not diffuse out through the outer and inner retinal barrier therefore allows the study of retinal circulation. (inner and outer barriers control the movement of fluid, ions and electrolytes from the intravascular space to the extracellular space in the retina). It diffuses freely through choriocapillary and bruchs membrane therefore does not allow study of choroidal circulation.

8. Sodium Fluorescein Dye Fluorescein (C 20 H 12 O 5 ) refers to Fluorescein sodium (C 20 H 10 Na 2 ). Is a brown or orange-red crystalline substance first synthesized in 1871 in Germany by Von Baeyer An organic vegetable dye Highly water soluble and pharmacologically stable Molecular weight 376 Dalton Excited at 465-490 nm and fluoresces at 520-530 nm. Clearance Eliminated by liver and kidneys within 24 hours. Dose 10 ml of 5% 5 ml of 10% 3 ml of 25%

9. Purpose of FFA To evaluate the integrity of retinal and choroidal vessels And to evaluate the blood ocular barriers (outer and inner) iBRB is located in the inner retinal microvasculature and is made up of tight junctions between endothelial cells. oBRB is made up of tight junctions between RPE cells and regulates the exchange of material from the retina to the choroid.

10. Indications Retinal vascular diseases Macular disorders Retinal vascular malformations and tumors Choroidal diseases Optic Nerve diseases

11. Contraindications Absolute Known allergy to iodine containing compounds H/0 adverse reaction to FFA in the past Relative Asthma Hay fever Renal failure Hepatic failure Pregnancy (1 st trimester)

12. Side Effects Most Common Fluorescent discoloration of the urine Transient nausea (10%) no treatment needed Occasional vomiting Excessive sneezing Less Common Hives Asthmatic symptoms Syncope (1%) (if extreme bradycardia, IV atropine may be needed) Least Common Laryngeal edema Anaphylaxis to fluorescein (<1%) Myocardial ischemia Pulmonary edema Seizures Cardiorespiratory arrest: (<0.01%) (Treatment is with chlorpheniramine 10mg IV, hydrocortisone 100mg IV and give oxygen and adrenaline 1ml of 1:1000 IM for hypotension and bronchospasm)

13. Anatomy Outer layers: Choriocapillaris Inner layers: Central retinal artery Outer plexiform layer: Watershed area It gets blood supply from both, the central retinal artery and choriocapillaris. The inner retina consists of the internal limiting membrane through to the external limiting membrane, and the outer retina consists of the photoreceptor layers through to the choroid

14. BLOOD SUPPLY Ophthalmic artery is the first intracranial subdivision of the internal carotid artery Occasionally (18% to 32% of eyes), there is a cilioretinal artery from the ciliary circulation, which irrigates the macula CRA supplies the inner 2/3rd of the retina. It is a terminal branch since it does not present significant anastomosis with other arteries. CRA divides into superior and inferior branches which further divide into their respective temporal and nasal branches. These branches rarely cross the horizontal raphe. Choriocapillaries supply the outer 1/3rd of the retina Choriocapillaries are a fine network of fenestrated and highly anastomosed capillaries beneath the RPE which allow for diffusion of blood to the photoreceptors and RPE The choroid constitutes the most vascularized tissue of the eyeball Histologically divided into 5 layers; 1 . Bruchs membrane 2. Choriocapillaries 3. Sattler layer 4. Hallers layer 5. Suprachoroidal layer

15. MACULA: Superior and inferior temporal branches of central retinal artery Cilioretinal artery FOVEA: Avascular area (500 µm) Mainly supplied by choriocapillaris VENOUS SUPPLY: Central retinal vein and its branches follows same pattern as CRA Empties into sup and inf ophthalmic veins Which drains into Cavernous sinus Blood Supply

16. PIGMENTS IN RETINA Retina has 4 pigments 1. Hemoglobin : present intravascularly 2. Melanin : present in RPE (also in choroid and iris) 3. Lipofuscin : present in RPE 4. Xanthophyll : present in OPL Hemoglobin: Absorb light in the green end of the visible spectrum, since emitted light from the fluorescein sodium is also green, it helps in CONTRAST of angiogram Melanin: Concentration is maximum at macula Acts as a natural block to the fluorescent dye, causing areas with high melanin to appear as hypofluorescence / dark areas on the angiogram (in AMD, due to RPE atrophy/ altered melanin density it can cause abnormal hyperfluorescence ) Xanthophyll Unique to the macular region Present in OPL Absorbs the blue excitation light hence dark color/relative hypo fluorescence of foveal region in normal angiogram. LIPOFUSCIN: Pigment is not visible with angiography Its presence is primarily assessed with the help of FAF which detects the natural fluorescence emitted by lipofuscin molecules.

17. Imaging Standard SEVEN field photographs Centered to disc centered to macula 30 temporal to macula with edge on macula Superior Temporal Nasal Inferior Red free image (FAF): shows retinal pathology Green free image shows choroidal pathology

18. Procedure Inject dye in the peripheral arm vein as a bolus and start timer Capture image exactly at start and finish of injection And again at 8 seconds in young and 12 seconds in adults after injection, at an interval of 1-2 seconds Shoot late pictures at 5 mins and 10 mins

19. Circulation of the dye Dye injected into the peripheral vein Venous circulation Heart   Arterial system Internal carotid artery Ophthalmic artery Short posterior ciliary artery central retinal artery Choroidal circulation retinal circulation Choroidal filling is 1 second prior to retinal filling

20. Phases of angiogram Consists of the following over lapping phases Choroidal phase Arterial phase Early late Arterial venous phase (capillary ) Venous phase Early Mid Late Late elimination phase

21. Normal circulatory filling 0 seconds — injection of fluorescein 9.5 sec — posterior ciliary arteries 10 sec — choroidal flush (or "pre-arterial phase") 10-12 sec — arterial phase 14-15 sec — arterio- venous phase/ early venous / lamellar flow 16-17 sec — mid-venous phase 18-20 sec — late venous phase 5 minutes — late staining

22. Choroidal phase 10-11 seconds Patchy filling is seen because of the lobular arrangement of choriocapillaries , followed by a diffuse flush as dye leaks out of the choriocapillaris typically described as “ground glass appearance”. Cilioretinal artery if present fills at the same time with choroidal circulation Pre laminar optic disc capillaries also fill during this phase No dye has yet reached the retinal arteries Choroidal flush can be delayed in decreased cardiac output, heart failure, giant cell arteritis, hypertension, etc.

23. Arterial phase 1 second after choroidal phase It's the filling of the central retinal artery about 1 second later than choroidal filling. Dollery et al. divided this phase into early and late. Early phase – the fluorescein rapidly spreads outwards along arteriolar tree. Late phase – an irregular narrow dark zone outlines on either side of the arteriolar blood column, which appears to be the thickness of the arteriolar wall Capillaries then quickly fill following the arterial phase making the perifoveal capillary network prominent at the macula.

24. Arteriovenous phase Arteries and capillaries are completely filled with laminar flow in veins. Early Venous phase - bright fluorescent line along the walls of vein confirming the “laminar flow”. Fluorescein dye enters the larger veins from smaller tributaries, causing the dye to initially flow rapidly along the vessel walls, creating a bright outline against a darker center due to the slower blood flow in the middle of the vessel. “ Laminar flow pattern” The laminar flow is not seen in venous segments after nipping by arterioles at their crossing as the flow becomes turbulent. ​

25. Venous phase Early – laminar flow in veins  dye completely fills the venous lumen Mid – some veins are completely filled and some show marked laminar flow Late – all veins are completely filled, and arteries begin to empty.

26. Late (elimination ) phase 7-15 mins mins from first appearance of the dye in the arterioles Gradual elimination of the dye from the choroidal and retinal circulation – arteries and veins are almost empty of dye and the choroidal flush is barely noticeable. Staining of the disc is a normal finding ( due to dye leaking from the choriocapillaris)

27. Time duration Arm to choroid      10-15 s     >30s abnormal Complete choroidal filling  3-5s        >5s abnormal AV transit         8-12s      >15 s abnormal

28. Why Autofluorescence It occurs when natural fluorophores emit light. In eye, the dominant source of fluorophores are Lipofuscin collagen elastin. Pseudofluorescence It occurs when non fluorescent structures ( hard exudates/ scar ) appear fluorescent due to limitations in the imaging filter system, essentially picking up light that shouldn’t be captured as fluorescence. To differentiate Auto F – present in both before and after injection images Pseudo F – present only in pre injection images

29. Causes of dark appearance of fovea Avascularity Blockage of background choroidal fluorescence due to increased density of xanthophyll large RPE cells with more melanin.

30. NORMAL DISC FLUORESCENCE ARTERIAL ARTERIOVENOUS EARLY VENOUS LATE PHASE

31. Late Extravascular Hyperfluorescence Considered Normal Fluorosence of Disc margins from surrounding capillaries Fluorosence of lamina cribrosa Fluorosence of Sclera at disc margin if RPE terminates away from disc as in Optic crescent Fluoresence of Sclera if RPE is lightly pigmented.

32. Interpretation of FFA Fluorescein angiogram Normal abnormal artifact Hyperfluorescence Hypofluorescence Leakage Pooling staining window defect blocked non filling

33. Hyperfluorescence - leakage Leakage – the dye permeates out of leaky incompetent blood vessels into the free space ( dye leaks from peripapillary capillaries) Frank hyperfluorescence that progressively enlarges with fuzzy borders In the setting of neovascularization, vasculitis, vascular malformations, tumors, disc edema etc Abnormal choroidal vasculature (CNV) Break in inner retinal barrier (CME) abnormal disc or retinal vasculature (NVD, NVE) Petaloid leakage from CME

34. Hyper fluorescence - Pooling Sub retinal space Early hyperfluorescence Increases in size and intensity (CSR) Sub RPE space Early hyperfluorescence Increases in intensity only (PED) Pooling – dye fills a cavity either in the sub retinal space or sub RPE space Hyperfluorescence progressively enlarges to fill the cavity and then remains fixed in size

35. Hyperfluorescence – Staining Late hyperfluorescence due to accumulation of dye Hyperfluorescence usually gets brighter but stays the same in size Optic disc drusen Late staining of APMPPE lesions (acute posterior multifocal placoid pigment epitheliopathy)

36. Hyper fluorescence - Window defect Defect in the RPE allows transillumination of the choroidal hyperfluorescence. Remains  static in size and brightness  and becomes fluorescent with the choroidal phase even before the arteries fill in the early frames. Window defect from geographic atrophy

37. Hypofluorescence - Blocked fluorescence Hypofluorescence occurs by masking underlying retinal and choroidal tissue by blood, pigment etc.

38. Hypofluorescence – Filling Defect lack of retinal perfusion due to capillary dropout, retinal artery occlusion and other causes. Filling defect / non perfusion from capillary drop out

39. Fluorescein Angiogram can be analyzed as follow Sequential analysis Examining frame by frame in the order that it was photographed. The major vascular phases of the angiogram are emphasized. This method is most useful in analyzing vascular disorders of the retina and choroid. Anatomic Analysis Examining each of the major layers of the posterior pole of the eye; the choroid, RPE and neurosensory retina Morphologic analysis Examining the patterns of the angiogram; hyper and hypofluorescent

40. Describing an Angiogram Phase of the angiogram The hyper and hypo fluorescent structures Area of fluorescence and how it progresses with time in size, shape and brightness Run through the anatomical structures

41. Limitations of FFA Does not permit study of choroidal circulation due to Melanin in RPE Low mol wt of fluorescein Adverse reactions

42. Diabetic Retinopathy Early venous Phase Hyper F – NVD and Microaneurysms Hypo F – blocked F due to Blood

43. Diabetic retinopathy Hypo F Retinal hemorrhage ( blocked F) Ischemia ( filling defect/ non perfusion) Hyper F 3. Microaneurysms ( appear as small pinpoint hyperfluorescent dots typically in the early phase, might leak in the later phases) 4. Neovascularization ( Leakage) Other findings 5. IRMA (intra retinal microvascular abnormality) (typically donot leak on FA) 6. Venous beading (characteristic appearance of retinal veins where they appear dilated and segmented, resembling a "string of beads" often indicating underlying retinal vascular disease.

44. Post Laser in DR Hyper F Ma's (leakage) Laser spots ( Staining) Hypo F Capillary drop out areas ( filling defect/ non perfusion)

45. Post PRP laser for PDR Hypo F Massive retinal capillary drop out ( filling defect/ non perfusion) Pigmented laser scars ( blocking) Hyper F Laser scar ( staining)

46. ST BRVO Hyper F veins showing staining and leakage Ma's Hypo F Blocked F due to subretinal and pre retinal hemorrhage

47. Collaterals Collaterals don’t leak

48. CRAO No perfusion of retinal vasculature. Vessels appear dark against a light background No capillary perfusion – empty veins – "cattle tracking" Choroidal perfusion intact hence the "cherry red spot"

49. CCSR Smoke stack – starts as hyperfluorescent dot, progresses vertically till it reaches the edge of the detachment and then spreads horizontally like a mushroom or puff of smoke. Leak starts in AV phase or early venous phase. More commonly seen in acute CSCR Most common location – parafoveal Ink Blot – a small focal area of dye pooling that expands and intensifies over time. Indicates a localized area of RPE disruption causing fluid leakage into the subretinal space. MOST COMMON pattern seen in CSR on FA

50. Other techniques Fluorescein angioscopy – intravenous injection of dye followed by viewing the fundus using a cobalt blue filter over the illumination source of indirect ophthalmoscopy Oral fluorescein angiography – 10% sodium fluorescein is diluted to 2% - but it has limitations – unpleasant taste / staining of teeth/ not an ideal tool for detailed studying of retinal vasculature OCT angiography – non invasive / no dye/ limitation - because OCTA uses the principle that movement in the back of the eye represents blood flow, it is more prone to motion artifacts.

51. Thank you