Overview of Fluorescein Angiography
Fundus fluorescein angiography (or FFA) is a test used by eye doctors to examine the blood vessels in the back of the eye (the retina and choroid). It was created by two medical students, Herald Novotny and David Alvis. Previously, others had tried injecting a special dye called fluorescein into cats to study their eye blood flow. But, when they tried it on humans, their camera equipment wasn’t good enough to get clear pictures.
As technology improved, Novotny and Alvis used an updated camera and two types of filters to capture the first clear images of the dye glowing inside the eye’s blood vessels. They published their findings in 1961. The dye they used, sodium fluorescein, is an orange, water-soluble substance. It mostly attaches itself to proteins in the blood and does not freely move around inside the retina. But, it can freely move within the tiny blood vessels in the middle layer of the eye called choriocapillaris. This dye leaves the body within 24 to 36 hours through urine, which may cause a slight change in urine color.
The way FFA works is by taking a series of photos of both eyes after injecting the fluorescein dye into a vein, usually in the arm. As the dye flows through the blood vessels in the eyes, the camera captures images. Understanding these images helps doctors diagnose and evaluate various eye diseases and conditions. It’s important to realize that this test may have some risks and complications, like any other medical procedure. Patients undergoing FFA are typically monitored by a team of healthcare professionals for their safety and comfort.
Anatomy and Physiology of Fluorescein Angiography
The retina and choroid, parts of the eye that help us see, get their blood from the ophthalmic artery, one of the first offshoots of the internal carotid artery, a major blood vessel in the neck. This artery splits further into the posterior ciliary arteries, which nourish the back part of the eye, and the central retinal artery, which feeds the inner eye.
The retina, the part of our eyes that senses light and sends images to our brain, can be thought of in two parts. The inner part gets blood from the central retinal artery while the outer part, which doesn’t have blood vessels, gets its nutrients from the nearby blood vessels through a complex process called diffusion.
The central retinal artery further splits into two primary branches: the superior and inferior branches. These then break down into smaller branches that give blood to the inner layers of the retina. The retina has up to four layers of these tiny blood vessels, depending on the location. In some people (about 20% of us), there’s an extra blood vessel that comes from the area around the optic disc (where the optic nerve enters the eye) and provides blood to the central part of the retina responsible for sharp, central vision.
The choroid, the layer of the eye behind the retina, gets its blood supply from the posterior ciliary arteries. These arteries further branch out and connect with the arteries at the front of the eye to form a network. There’s a specific area called the choroidal watershed area where the blood supply from different arteries meets.
The fovea is the very central part of the retina responsible for sharp, central vision. It has many layers, and some of its unique features like a lack of blood vessels and presence of a specific pigment give it a dark appearance in certain eye tests known as angiography. There’s an area in the fovea that doesn’t have any blood vessels, this is called the foveal avascular zone (FAZ).
Finally, once the blood has delivered the necessary nutrients, it drains back toward the heart via the retinal veins, vortex veins, and larger veins in the eye orbit, eventually ending up in a large blood vessel called the cavernous sinus.
Why do People Need Fluorescein Angiography
If you’re having unexplained vision loss, it could be due to a range of conditions. One of these is diabetic retinopathy, which involves damage to the blood vessels in your eyes due to high blood sugar levels. Here, vision loss can result from poor blood flow to the macula, a small area in the middle of the retina responsible for sharp, central vision. Your vision may also be affected if you have swelling or fluid leakage in the macula, caused either by damaged capillaries or tiny bulges in the blood vessels called microaneurysms. Other potential causes of vision problems include not being able to see new blood vessels clearly, or different levels of disease in each eye.
Sometimes, there may be other factors at play, such as asteroid hyalosis, which is when small white opacity floats around in the vitreous humor, the gel-like substance filling the eye. Your doctor may need to investigate whether you have diabetic macular edema, which involves swelling in the macula, or Irvine-Gass syndrome, which affects vision after cataract surgery. Both of these conditions can exist at the same time.
Blocked blood vessels in the eye, or retinal vein occlusions, could also cause vision loss. Your doctor may wait for a few months to allow any existing hemorrhages to resolve before conducting angiography, a test that visualizes the blood vessels. This test can aid in identifying and confirming areas of the eye that aren’t getting blood supply because of the blocked vessels.
You could also be experiencing vision loss due to new blood vessels growing in your choroid, the vascular layer of your eye, a condition called choroidal neovascularization. This can occur due to age-related macular degeneration, among other retinal diseases. If you’re nearsighted, this condition might not be as evident, which means that a special type of imaging test may be required.
There are number of additional reasons you could be having vision problems, including being diagnosed with ocular ischemic syndrome, central serous chorioretinopathy, parafoveal telangiectasia, ischemic optic neuropathy, retinal vasculitis, uveitis, retinitis, posterior scleritis or dealing with intraocular tumors. Other disorders related to the blood vessels in the retina – including retinopathy of prematurity, commonly found in premature babies, and sickle cell retinopathy which affects people with sickle cell disease – may also affect your vision. Finally, any disturbances in the normal structures of the eye, including the cornea and iris, could be a factor in vision loss.
When a Person Should Avoid Fluorescein Angiography
Fluorescein angiography, a test that uses a special dye and camera to look at blood flow in the eye, is usually not recommended for pregnant women. This is because it’s rated as a category C drug, meaning we don’t have enough research to know if it’s entirely safe during pregnancy. Since the dye can also be found in breast milk for up to 3 days after the test, we’re still researching the effects on newborn babies who might ingest it, especially those receiving light therapy for certain conditions.
The risk of the dye causing skin damage after exposure to specific types of light, a condition known as phototoxicity, also needs more research. In neonates (newborn babies), it’s thought that additional factors like lack of certain antioxidants, lowered protein levels in the blood, increased risk of too much bilirubin in the blood (a condition that causes yellowing of the skin), and slow removal of the dye by the kidneys could also play a role in phototoxicity.
People with a history of severe allergic reactions should not get the dye at all. But those who’ve previously had a moderate allergic reaction to the dye might still be able to have the test if they take certain medications beforehand to prevent an allergic response. However, allergy skin tests aren’t very helpful in predicting whether someone will have an allergic reaction to the dye.
Having a history of heart or kidney disease doesn’t disqualify someone from having the test, but the medical team should be aware of these conditions, especially in managing any potential allergic reactions. Recent studies have shown that even patients with kidney problems and those undergoing dialysis can safely have the test as the kidneys can usually remove the dye in urine or during a dialysis session without any reported harm.
Equipment used for Fluorescein Angiography
To take special photographs of the eyes, a special camera, called a fundus camera, is needed. This camera comes with two filters: an excitation filter and a barrier filter. The blue excitation filter, which looks like cobalt blue, puts out a blue light between 465 and 490 nm. This is the right range for soaking up fluorescein, a special dye. The barrier filter lets through light in a range between 520 and 530 nm, just when the fluorescein gives off its light. Because technology has progressed, we also use a computer and some particular software to process the images the camera takes.
The dose of sodium fluorescein, the dye needed for adults, is 500 mg, given through a vein (intravenously). To get this dose, you’ll need a tiny vial of sodium fluorescein in different concentrations, such as 2 ml of 25%, 2.5 ml of 20%, 5 ml of 10 %, or 10 ml of 5 %. Additionally, other tools including a needle set for scalp veins (sized 23 gauge), a small 5 ml syringe with a needle to draw up the dye, an armrest, a tourniquet (a device used to control venous and arterial circulation), and an alcohol swab for cleaning are required. It’s also vital to have standard emergency equipment to handle a severe allergic reaction (anaphylaxis), prepared and ready to use before we start the procedure.
Who is needed to perform Fluorescein Angiography?
The procedure known as FFA (short for fluorescein angiography, a test to examine the blood flow in the back of the eye) involves a team of healthcare professionals. This includes nurses, an anesthetist (a specialist doctor who puts you to sleep or numbs parts of your body during surgery), and an ophthalmologist (an eye doctor). They all work together to make sure your test happens safely and successfully.
Preparing for Fluorescein Angiography
Before starting the medical procedure, it’s imperative that the patient understands what is happening and agrees to it. This is known as getting “informed consent”. The medical team will explain to the patient the benefits and risks involved with the treatment, and what the procedure entails. If the patient has any known allergies, especially to a dye called fluorescein used during the procedure, the healthcare team needs to know. In such cases, antihistamine or corticosteroid medications, which can help reduce allergic reactions, may be used. On the day of the procedure, it’s recommended the patient doesn’t eat anything for at least 2 to 4 hours prior.
In many instances, a 25% solution of fluorescein is used as it has been found to provide better-quality images. The quantity of this dye won’t affect the chances of side effects. For children, the amount of fluorescein used depends on their age and weight.
Before starting the procedure, the patient’s pupil needs to be well enlarged. The patient should also be informed about the possibility of feeling nauseous. The patient will be seated comfortably, with their arm on an armrest. They should be coached to look straight ahead and move their eyes according to the doctor’s instructions. This makes the procedure go quickly and smoothly.
A needle is inserted into the patient’s arm, and a small amount of blood is drawn to assure that it is positioned correctly. The eye area and specific location needing examination are confirmed. Images are taken before injecting the dye, and injection and timing start together. If the dye leaks out of the blood vessel (extravasation), this will be carefully monitored. Photographs are taken focusing on any specific areas as marked by the eye doctor. The healthcare team will watch for any early signs of faintness or severe allergic reaction. It’s important to keep the patient calm and informed throughout the procedure. After collecting some images of one eye, images are taken of the other eye.
Oral Fluorescein Angiography (FFA), where fluorescein is administered orally, can also be done after suitable precautions. Newer technologies like confocal scanning laser ophthalmoscope-based systems may provide better image quality than conventional digital camera-based FFA.
How is Fluorescein Angiography performed
A fundus camera, which is used for eye examination, employs two filters. One, the excitation filter, only allows blue light to enter the structure of the eye to interact with the particles of a special dye called fluorescein. The other, the barrier filter, lets in only the green light emitted by the dye, keeping out any other light bouncing back from the eye. The timing of injecting the dye aligns well with the process of snapping pictures. The initial photos are captured every 1 to 2 seconds and are then followed by shots of the other eye. Subsequent photos can be captured at a more gradual pace based on the specific condition of the eye decorum.
Now let’s talk about the usual phases observable during a Fluorescein Fundus Angiography (FFA).
The last phase is the Venous phase which consists of three stages: early, middle, and late, and is based on how the dye fills up the part of the circulation. During the early stage, a laminar flow is visible. It progresses to full vein filling in the mid-stage and then a reduced dye concentration in the arteries in the late stage. During the peak of this process, the small blood vessels around the fovea, a part of the retina, can be clearly seen.
After the Venous phase, the concentration of dye in the vessels starts to decrease, and it is completely cleared out approximately 10 minutes after the injection. During this last phase, known as the Recirculation phase, certain structures in the eye such as the optic disc, Bruch’s membrane, choroid, and sclera start to take up the dye.
Possible Complications of Fluorescein Angiography
Extravasation, or leakage of a substance into areas where it’s not supposed to go, is a serious side effect of some medical procedures that involve injecting a dye under the skin. This leakage can cause a lot of pain and may even cause skin death or necrosis. Putting an ice pack on the area where the substance has leaked can help reduce the pain. Some people may experience nausea, which is the most common side effect, but this sensation doesn’t last long. Vomiting is less common.
Patients who have had nausea and vomiting before can prevent it from happening again by taking a medication called promethazine hydrochloride (25 to 50 mg) one hour before the procedure. Fainting, or vasovagal syncope, can also happen in people who are very scared. This can make them pass out for a few minutes, but they will recover.
In more serious cases, patients may experience bradycardia (a slow heartbeat) and hypotension (low blood pressure). In these situations, the person is laid down and their feet is elevated. Regular blood pressure monitoring will be done.
Allergic reactions are usually mild, like hives or itching, and can be treated with antihistamines which reduce allergy symptoms. However, more serious allergic reactions can also occur, including difficulties in breathing due to bronchospasm, swelling of the larynx, or even severe heart conditions such as a heart attack. These are emergencies and must be treated immediately. Rarely, death caused by an intravenous injection has been reported. To prepare for such emergencies, equipment and medicines, including adrenaline, steroids, and bronchodilators like aminophylline, should always be ready. These substances can help treat severe reactions, like bronchospasms and severe allergic reactions.
Overall, deaths caused by these procedures are very rare, with one occurrence in 222,000 cases reported.
What Else Should I Know About Fluorescein Angiography?
Fluorescein angiography is a test used to examine blood flow in the back of your eye. For the test to make sense, you need to understand some key terms:
Hyperfluorescein refers to parts of the eye that show up very brightly on the test. This happens for different reasons:
1. Preinjection Fluorescence: Some parts of the eye can glow without any fluorescein dye because they contain substances that emit light – like lipofuscins or porphyrins. Some conditions, like optic disc drusen (a type of eye disease), also glow because they contain a lot of these substances.
However, sometimes the glow isn’t due to fluorescein or these substances – this is called pseudofluorescence. This happens because of the light reflecting from structures in the eye.
A type of hyperfluorescence called transmitted fluorescence happens when healthy cells in the eye (RPE) aren’t present and we see the glow from the underlying layer. This only changes with time if the dye leaks or collects in particular spaces.
Hypofluorescence is the opposite – it refers to parts of the eye that don’t glow or are darker on the test.
This can happen because there’s something blocking the glow from the layers beneath (like bleeding), or there’s no blood flow to light up – either completely or just partially.
Finally, let us look at some conditions and what their results on this test mean:
Epiretinal Membrane (ERM): A type of eye disease where we may see irregular blood vessels and leakage. There may also be a bright spot in the center of the eye due to fluid build-up.
RPE Rip: Another eye condition where on observation, a bright section is seen because of underlying tissue is exposed. Areas where the cells have rolled underneath will not glow.
Drusen: These are yellow deposits under the retina, we may see areas that glow because of underlying tissue exposure or staining (cells retaining dye).
Serous PED: This refers to a form of eye disease. The test reveals a glow that enhances over time and is well-defined.
Choroidal Neovascular Membrane (CNVM): This is a major cause of vision loss. On the test, you may see a well-defined bright network, enhancing over time. The exact source of brightness might be hard to pinpoint for some forms of CNVM. ICGA, another eye test, may be better for those instances.
These are just a few examples. The key thing to remember is that the brightness on the test results can tell doctors a lot about what’s happening in your eyes. If your doctor recommends this test, they’re trying to get a better look at your eye’s blood flow and tissue condition. Understanding these terms can help you interpret the results along with your doctor.