How is fluorescein angiography different from fundus photography?

Fundus photography captures a color image of the retinal surface using white light, showing structural detail. Fluorescein angiography uses intravenously injected fluorescein dye and a blue light source to photograph dynamic blood flow and vascular integrity. FA reveals leakage, ischemia, and neovascularization that are invisible on standard color fundus photography.

What are the phases of fluorescein angiography and what does each show?

The phases are: choroidal flush (patchy early choroidal filling at ~10-12 seconds), arterial phase (retinal arteries fill at ~12-15 seconds), arteriovenous phase (capillary network fills at ~15-20 seconds), venous phase (veins fill at ~20-30 seconds), and late phase (dye clears from normal vessels; leakage becomes visible as persistent bright areas in compromised tissue).

What are the common adverse reactions to fluorescein angiography?

The most common adverse reaction is nausea, occurring in up to 5-10% of patients. Other mild reactions include vomiting, temporary yellow-orange skin discoloration, and orange-tinted urine lasting 24-48 hours. Moderate reactions include hives and vasovagal syncope. Severe anaphylactic reactions are rare but require immediate treatment with epinephrine. Emergency equipment should always be available.

What does hypofluorescence indicate on fluorescein angiography?

Hypofluorescence (darker-than-normal areas) occurs for two main reasons. Blockage hypofluorescence happens when blood, exudate, or pigment blocks the fluorescence from underlying vessels. Non-perfusion hypofluorescence indicates ischemia, where capillaries are occluded and no dye reaches the tissue. Non-perfusion areas are clinically significant because they predispose to retinal neovascularization.

Fluorescein Angiography: Retinal Vascular Imaging

What Is Fluorescein Angiography?

Fluorescein angiography (FA) is a diagnostic imaging procedure that evaluates the retinal and choroidal vasculature by photographing the transit of fluorescein dye through the blood vessels of the eye. It provides dynamic, real-time information about vascular anatomy, blood flow, and the integrity of the blood-retinal barrier.

Unlike fundus photography, which shows surface structure, FA reveals vascular function. It can identify areas of vessel leakage, blockage, abnormal new vessel growth (neovascularization), and regions where perfusion is absent (ischemia). This functional information guides treatment decisions in conditions such as diabetic retinopathy, AMD, and retinal vascular occlusions.

The Procedure

Fluorescein dye is administered as an intravenous (IV) injection, typically into a vein in the antecubital fossa (inner elbow) or the back of the hand. The dye reaches the retinal circulation within approximately 10 to 15 seconds after injection. A fundus camera with a blue excitation filter (around 490 nm) is used to photograph the eye. The blue light excites the fluorescein molecules, causing them to emit a yellow-green fluorescence (around 530 nm) that the camera captures through a barrier filter.

Sequential photographs are taken rapidly during the transit of dye, then less frequently for several minutes as the dye gradually clears from the circulation. The full sequence captures the dynamic passage of dye through all vascular layers.

The patient should be warned before injection that the dye will temporarily turn their skin and urine orange or yellow. This is harmless and resolves within 24 hours, but it startles patients who are not expecting it.

Phases of Fluorescein Angiography

The FA sequence passes through distinct phases that correspond to vascular anatomy:

Phase	Timing	What Is Seen
Pre-arterial (Choroidal flush)	~10-12 sec post-injection	Patchy early filling of choroid; pseudopodial pattern
Arterial phase	~12-15 sec	Retinal arteries fill; veins still empty
Arteriovenous (capillary) phase	~15-20 sec	Capillary network fills; early venous laminar flow
Venous phase	~20-30 sec	Veins fully filling; arteries begin to recirculate
Late phase	Several minutes post-injection	Dye clearing from vessels; leakage visible if present

Leakage becomes most obvious in the late phase, when dye has cleared from healthy vessels but continues to pool in areas where the blood-retinal barrier is compromised. Early phases show anatomy; late phases reveal pathology.

Interpreting Fluorescein Angiography Findings

Hyperfluorescence

Hyperfluorescence means an area is brighter than expected on FA. There are several mechanisms:

Leakage: Dye escapes from abnormal vessels into surrounding tissue, causing progressive bright blurring in late frames. Seen in choroidal neovascularization (wet AMD), diabetic macular edema, and retinal vascular occlusions.
Pooling: Dye accumulates in an anatomical space, such as under the neurosensory retina in central serous chorioretinopathy.
Staining: Dye permeates fibrous tissue or drusen. Bright on late frames but does not expand like leakage.
Window defect: Loss of RPE cells allows the choroidal fluorescence to show through brighter than normal.

Hypofluorescence

Hypofluorescence means an area is darker than expected. This occurs due to:

Blockage: Blood, exudate, pigment, or other opaque material blocks the underlying choroidal or retinal fluorescence. Dense hemorrhages appear as very dark areas on FA.
Non-perfusion (ischemia): Areas where the capillary network is occluded and no dye reaches. These dark, non-filling zones indicate ischemia and are associated with risk of neovascularization in conditions like diabetic retinopathy and branch retinal vein occlusion.

Adverse Reactions

Most patients tolerate FA well, but adverse reactions can occur. They are generally categorized as:

Mild (most common): Nausea (most frequent, affects up to 5-10% of patients), vomiting, temporary skin yellowing, orange-tinted urine for 24-48 hours.
Moderate: Urticaria (hives), itching, vasovagal syncope.
Severe (rare): Anaphylaxis, bronchospasm, laryngeal edema. Requires emergency treatment (epinephrine, airway management).

All facilities performing FA should have emergency equipment and medications (epinephrine, diphenhydramine, oxygen) available. A history of prior fluorescein allergy is a contraindication or requires pre-medication consultation.

Fluorescein angiography uses sodium fluorescein dye, not the fluorescein from fluorescein strips used in tonometry. The dye amounts and routes are entirely different. Topical fluorescein does not provide angiographic data.

Key Takeaways

Fluorescein angiography uses IV-injected dye to image retinal vascular anatomy and function in real time.
The five phases are choroidal flush, arterial, arteriovenous, venous, and late phase.
Hyperfluorescence indicates leakage, pooling, staining, or window defects.
Hypofluorescence indicates blockage (hemorrhage, exudate) or non-perfusion (ischemia).
Common adverse reactions include nausea and skin discoloration; severe reactions (anaphylaxis) are rare but possible.