How to interpret fluorescein angiography: 6 types of defects

How does fluorescein angiography (FA) work?

Fluorescein is an organic dye. When blue light is shined on fluorescein, it fluoresces yellow-green. We do this commonly when looking at the cornea after instilling fluorescein. The same dye can be injected intravenously. A blue light camera can take pictures of the retinal circulation, and the emitted fluorescence is then passed through a yellow-green filter and sent to the camera for the final image.

In a normal eye, fluorescein can not permeate through the endothelial cells of the retinal blood vessels nor can it pass through tight junctions in the retinal pigment epithelium (RPE). The yellow-green wavelength is also heavily absorbed by the RPE so the choroidal fluorescence is blocked. This makes FA good for evaluating the retinal vasculature, not the choroidal vasculature.

In contrast with FA, indocyanine green (ICG) dye is great for evaluating the choroidal circulation. Almost all of the ICG molecules are protein bound, so they do not readily produce retinal leakage or staining. ICG fluoresces in the infrared wavelength and readily passes through the RPE (retinal pigment epithelium).

Phases of the angiogram

1. 9-15 seconds = Choroidal phase (AKA pre-arterial phase): The choroidal hyperfluorescence is present. A cilioretinal artery if there is one will fill in this phase. Delayed choroidal filling time happens in ocular ischemic syndrome (OIS).
2. 1-3 seconds later = Arterial phase: Arteries are bright, but the veins remain dark.
3. Arteriovenous phase: Laminar flow in the veins – the walls of the veins are bright while the center of the vein is still dark.
4. By 30 seconds = Venous phase: Complete filling of the veins.
5. 30 seconds – 10 minutes = Late phase: Dye has recirculated. Things that are going to leak or pool will have done so already.

Types of hyperfluorescence

There are 4 types of hyperfluorescence (brightness) in FA:

1. Leakage: Hyperfluorescence progressively enlarges with fuzzy borders. The dye permeates out of leaky, incompetent blood vessels in the setting of neovascularization, retinal vasculitis, vascular malformations, tumors, or disc edema (dye leaks from prepapillary capillaries).
2. Pooling: Hyperfluorescence progressively enlarges to fill the fluid cavity and then becomes fixed in size. Usually the dye fills a cavity like the subretinal space or sub-RPE space (in a PED).
3. Staining: Late hyperfluorescence due to accumulation of fluorescein dye. The hyperfluorescence gradually gets brighter, but the size stays the same. Usually a mild amount of fluorescence is seen, but it is never very bright. The optic disc always stains. Additionally, drusen and fibrosis will stain.
4. 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 before the arteries even fill in the early frames.

Leakage

Pooling

Staining

Window defect

Types of hypofluorescence

There are 2 major types of hypofluorescence:

1. Blocking: Blood or other opacities block the fluorescence. Blockage of the retinal fluorescence can happen due to preretinal or vitreous hemorrhage. Blockage of the choroidal fluorescence can happen due to nevi or melanomas, Stargardt’s disease (lipofuscin blocking choroidal flush leading to a “dark choroid”), or subretinal blood.
2. Filling defect – lack of retinal perfusion due to capillary dropout, retinal artery occlusion and other causes.

Blocking

Filling defect

Conclusion

1. Fluorescein angiography (FA) is a great way to evaluate retinal circulation.
2. Nowadays, OCT has greatly reduced the number of FAs performed, though FA still remains a very important modality for assessing many circulatory dysfunctions of the retina.
3. FAs can be evaluated based on distinct phases of dye circulation.
4. Various pathology can cause structures to be hyperflourescent or hypoflourescent. It is important to know generally what pathology correlates with what FA appearance.