Fluorescein angiography (FAG) for the diagnosis of retinal diseases

Angiography is a diagnostic imaging procedure used to visualize blood vessels. It is painless and carries low risk. Fluorescein angiography is a specialized form of angiography used in ophthalmology. It is used to visualize the structures of the fundus using a contrast agent.

The procedure is based on X-ray or MRI images. Typically, a contrast agent is injected into the blood vessels to improve visualization.

FAG is frequently used as a key diagnostic tool for retinal diseases. It allows for a better assessment of unclear changes in the retina and choroid.

The physician primarily examines the extent of diabetic changes in the retina. Furthermore, this procedure

• to determine the need for laser therapy,
• to classify age-related circulatory disorders of the macula, and
• to differentiate between arterial and venous occlusions.

FAG has been established in ophthalmology for many years; Achim Wessing had a lasting impact on modern retinal diagnostics with fluorescence angiography.

The retina during a fluorescein angiography © L. Bacud | Wikimedia Commons

Fluorescein angiography is particularly suitable for eye diseases caused by problems in the eye’s blood vessels. These include:

• diabetic retinopathy
• Anterior ischemic optic neuropathy
• age-related macular degeneration (AMD)
• Vascular occlusions in the eye caused by blood clots or tumors

Diabetic retinopathy

Diabetic retinopathy is a disease of the retina caused by diabetes mellitus. Diabetes also damages the small blood vessels in the eye. This leads to unnoticed damage to the retina.

As the condition progresses, it may eventually lead to blindness.

Treatment can slow the progression of the disease and, in the best-case scenario, halt it altogether. As a preventive measure, diabetes mellitus should be optimally managed.

Fluorescein angiography reveals whether there are leaky blood vessels, microaneurysms, or areas with poor blood supply. This is important for planning further treatment.

Anterior Ischemic Optic Neuropathy

Anterior ischemic optic neuropathy (AION) refers to an acute occlusion of an ocular artery in the Zinn-Haller circle, which supplies the optic nerve. This initially leads to insufficient blood flow to the optic disc. Consequently, the optic nerve becomes deprived of oxygen and nutrients.

AION is considered a medical emergency and is colloquially referred to as an “eye infarction.”

Age-Related Macular Degeneration (AMD)

Age-related macular degeneration (AMD) is a condition characterized by a loss of central visual acuity. The disease occurs in older adults and continues to progress.

Although visual acuity declines significantly, blindness is not expected even in the late stages. The loss of vision affects only the so-called macula (the central part of the eye’s retina). The rest of the retina remains unaffected by the disease. Visual acuity in the peripheral field of vision is therefore not impaired.

Despite AMD, people are therefore usually able to orient themselves in their surroundings without difficulty.

However, those affected can only perceive light-dark contrasts. This usually means the loss of the ability to read and drive. Those affected may also have difficulty recognizing the people around them.

The examination is particularly important when there is suspicion of abnormal new blood vessel growth in the macula.

Especially in cases of wet AMD, fluorescein angiography provides important information for decisions regarding further treatment.

Before performing the procedure, the doctor needs information about the patient’s general health, such as

• cardiovascular problems,
• allergies,
• kidney, lung, liver,
• metabolism and thyroid 
• nervous system

The patient is then given eye drops to dilate the pupils. The dilated pupils allow for better imaging of the retina. First, initial images are taken without contrast agent, followed by additional images under blue light.

In the next step, a dye is injected into a vein. The injection into the bloodstream is usually administered through a vein in the arm. A special camera or laser scanning system is then used to document how the dye spreads throughout the eye. This allows for a precise assessment of the retinal vessels and other structures.

The fluorescence angiography procedure essentially involves the following:

• Preparation with eye drops
• Initial photographic images
• Administration of the contrast agent
• A series of images to visualize the distribution

In everyday clinical practice, the procedure is often referred to as FAG.

Especially in patients with

• diabetes,
• circulatory disorders, or
• tumors

this is of particular importance. Diseases of the retina or blood vessels can also be diagnosed using fluorescein angiography.

Fluorescein Angiography

The dye fluorescein is injected into the body through a catheter inserted into a vein in the arm or hand. The dye spreads throughout the body and appears in the eye’s blood vessels within just a few seconds.

During the examination, the patient sits behind a special camera or a laser scanning system. These systems digitally record the flow of the dye into the blood vessels of the eye as well as into other layers of the retina.

Due to the dye, the skin takes on a slightly yellowish tint after the examination. This discoloration fades after 4 to 6 hours, and the dye is excreted in the urine.

Fluorescein belongs to the group of xanthene dyes. In analytical chemistry, fluorescein is used as an indicator.

In addition to its use as a dye in ophthalmology, fluorescein has a wide range of applications. For example, it is used as a dye in soaps and bath extracts. Furthermore, fluorescein is also used in flow cytometry and fluorescence microscopy. Among other things, this allows for the detection of pathogens in

• cells,
• fluids, or
• tissues

. Fluorescein has a so-called high quantum yield of up to 93 percent.

Nevertheless, the dye also has disadvantages. For example, the intensity of the dye depends on the pH value. If the pH falls below 7, the intensity decreases. Furthermore, the fluorescence fades very quickly under illumination, and the fluorescence peak is not sufficiently sharp.

Fluorescein exists in two different structures:

• the open carboxylic acid form (stable, red crystals in the solid state) and
• the spiro-lactone form (unstable, forms a yellow compound).

After the examination, the skin may take on a slight yellow tint. The substance is also excreted in the urine. These changes are usually temporary.

Indocyanine Green Angiography

Indocyanine green angiography is performed in exactly the same way as fluorescein angiography. Indocyanine green (ICG for short) primarily highlights the choroidal vessels and the structures of the choroid. This procedure therefore allows for a deeper visualization of the layers of the retina.

Angiography using the indocyanine green dye requires specially designed laser scanning systems. Consequently, it is very equipment-intensive.

The dye is metabolized by the liver and excreted through the bile ducts. Indocyanine green is an iodine-containing dye that is well tolerated. For this reason, patients should not have any iodine intolerance.

In cases of

• advanced liver failure,
• allergy to iodine, and
• pregnancy

, indocyanine green angiography should not be performed.

If the patient has hyperthyroidism, treatment should only be administered after consulting the attending physician.

The dye indocyanine green (ICG for short) is also a fluorescent dye. It is primarily used in medicine as an indicator and has a half-life of about 3 to 4 minutes. After intravenous administration, it is eliminated from the body depending on liver function.

The so-called ICG sodium salt is available in powder form. This allows it to be used in a wide variety of solvents. Sodium iodide is added to the powder to improve solubility.

Fluorescein angiography is generally painless and complication-free for the patient. In most cases, the skin and urine turn yellow for a period of about one to two days after the procedure. This condition can last up to 24 hours, after which the dye is excreted by the kidneys.

During fluorescence angiography, the pupil is dilated. As a result, patients may experience additional side effects during and after the procedure:

• If you are highly sensitive to glare: sensitivity to light immediately after the examination. Please bring tinted glasses with you to the appointment for the trip home
• Deterioration of central vision, which limits your ability to drive and therefore makes driving a vehicle prohibited

Allergic reactions to the dyes fluorescein or indocyanine green are generally quite rare. If they do occur, however, the following may happen:

• skin rash,
• itching, or
• in the worst case, shortness of breath

. In such cases, depending on the severity of the symptoms, the patient is given

• an oral or injectable antihistamine or
• a corticosteroid preparation.

Nausea, vomiting, and dizziness may also occur in rare cases after the examination. However, these side effects are short-lived.

Very rarely, tissue irritation has occurred at the injection site

• tissue irritation,
• infections,
• scarring, or
• nerve damage

have been observed.

Following the examination, the findings are typically reviewed and discussed. This allows a further treatment plan to be developed together with the ophthalmologist.

As a general rule: Because the pupils are dilated, the patient must not drive a car for several hours after the examination.

Overall, fluorescein angiography is an important procedure for detecting changes in the eye at an early stage and for making targeted therapeutic decisions.