Overview of Indocyanine Green (ICG) Angiography
Indocyanine green angiography (ICGA) is a technique used for capturing pictures of the choroidal circulation, or the blood flow within a layer of the eye, and its abnormalities. Another tool, fundus fluorescein angiography (FFA), provides detailed images of retinal circulation, but is less effective at imagery of the choroidal circulation. This is due to the barriers from the retinal pigment epithelium, or the layer of cells that nourish the retinal visual cells, along with cloudiness of the eye and other obstructive material.
The nature of a dye called indocyanine green, or ICG, lets it be seen through these barriers. ICG can be best seen when illuminated at 790 to 805 nanometers, with maximum light emission at 835 nanometers. Because this wavelength is higher than that of fluorescein, the infrared rays to and from ICG can better penetrate through the barriers. Moreover, 98% of ICG is bound to protein in the blood, limiting its dispersion and keeping imagery of the choroid clear.
Approved for human use in the United States by the FDA in 1956, ICGA was first performed on the human choroid by R. W. Flower in 1972. Despite initial cloudiness, advances in technology have led to the development of high-resolution cameras capable of capturing clear ICGA images. With modern tools such as anti-vascular endothelial growth factor (anti-VEGF), a medicine to shrink abnormal blood vessels, and optical coherence tomography (OCT), a type of medical imaging technology, monitoring of the choroidal neovascular membrane, an abnormal blood vessel in the eye, has become easier.
Nevertheless, ICGA remains an essential tool in clinical practise for examining various eye disorders including idiopathic polypoidal choroidal vasculopathy (IPCV), retinal angiomatous proliferation (RAP), and central serous chorioretinopathy (CSCR), all conditions that affect the retina or choroidal circulation. It also helps in evaluating eye inflammatory conditions such as sympathetic ophthalmia (SO) and Vogt Koyanagi Harada syndrome (VKH), as well as eye tumors.
Anatomy and Physiology of Indocyanine Green (ICG) Angiography
The choroid, a part of your eye, gets its blood from the ophthalmic artery, a branch of the internal carotid artery, which is a major blood vessel in your neck. This artery branches out into different arteries, some short and some long, which go on to supply different parts of the choroid. The short arteries feed the back part of the choroid while the long ones take care of the front section, and a little bit of the back, too. These arteries work independently and do not mix their supplies.
The choroid is made up of several layers. The innermost layer, called the Bruch membrane, is made up of five sublayers—these include different types of protective and supportive tissue. Outside of the Bruch membrane are three layers of blood vessels varying in size and function—one being the choriocapillaris, a capillary network; a medium-sized arteriole layer, the Sattler layer; and then the layer of larger arterioles, called the Haller layer. These layers all have their own functional lobules, or sections, which work independently.
Each lobule is supplied by its own terminal choroidal arteriole and does not connect with its neighboring lobules. After supplying each lobule, the blood is drained through the vortex veins, each of which serves its own section without mixing with the others.
The rate of blood flow to the choroid is probably the highest in any tissue in the human body compared to its weight—ten times higher than that of the brain. This high blood flow helps maintain a higher level of oxygen in the choroid compared to the retina, which is useful as it allows for oxygen to diffuse, or spread, from the choroid to the retina. Most of the oxygen supply to the retina comes from the choroid circulation. This is particularly important in the dark when the photoreceptors in your eyes, which respond to light, are working extra hard. The walls of the choriocapillaris have small openings, or fenestrations, which allow for substances like glucose and other small molecules to pass through easily. Larger proteins, however, cannot pass through these openings.
For instance, ICG, a substance used in medical imaging, is 98% protein-bound; since it is made up mostly of large proteins, it mostly stays within the choriocapillaris. On the other hand, fluorescein, another substance used for the same purpose but is only 80% protein-bound, can easily spread out of the choriocapillaris.
Why do People Need Indocyanine Green (ICG) Angiography
Indocyanine green angiography (ICGA) is a special type of eye test that uses a colored dye to look at the blood vessels in your eyes. Doctors use this test to help them diagnose and monitor certain eye conditions. These include “wet” age-related macular degeneration, which is a common cause of vision loss in older people, and idiopathic polypoidal choroidal vasculopathy (IPCV or PCV), which causes abnormal blood vessels to form and leak in the back of the eye.
ICGA is also used for retinal angiomatous proliferation (RAP), a condition where blood vessels form in a particular layer of the retina, and central serous chorioretinopathy (CSCR), which causes fluid to build up under the retina. It can help doctors diagnose and monitor retinal arterial macroaneurysm (RAM), which is a bulge in the blood vessels in the eye, and different types of tumors in the eye including choroidal melanoma and choroidal hemangioma.
White Dot Syndromes are a group of conditions that cause white spots to appear on the retina, they include Birdshot chorioretinopathy (BSCR), multifocal choroiditis, multiple evanescent white dot syndrome (MEWDS), and serpiginous choroidopathy. Other conditions include acute posterior multifocal placoid pigment epitheliopathy (APMPPE), punctate inner chorioretinopathy (PIC), acute zonal occult outer retinopathy (AZOOR), and chorioretinal atrophy.
ICGA can also help in diagnosing ocular inflammatory diseases, which are a group of conditions that cause inflammation in different parts of the eye, like sympathetic ophthalmia (SO) and Vogt Koyanagi Harada syndrome (VKH).
Apart from diagnosing eye conditions, this test can also be used to check the liver function, blood supply to the liver, and cardiac output, which is the amount of blood your heart pumps each minute. It’s also used during brain surgery to help manage intracranial aneurysms, which are bulges in the blood vessels of your brain that can be life-threatening if they burst.
When a Person Should Avoid Indocyanine Green (ICG) Angiography
ICG is a type of dye that’s generally safe and doesn’t cause many issues when used in eye health procedures. However, there are a few situations where it shouldn’t be used. For instance, if a patient has an allergy to iodide or shellfish, they should not be given ICG. It’s also not suitable for patients who have uremia, which is a condition where waste substances build up in the blood, or a history of severe allergic reactions.
ICG is only released from the body through the liver. So, it’s not advisable to use it in patients with liver disease. According to food and drug regulations, ICG is categorized as a ‘pregnancy category C’ drug. This means that we aren’t sure it’s completely safe for use in pregnant people because not enough studies have been done.
Once mixed with water, the ICG solution should be used within 6 hours. Also, if a patient needs a test that involves the uptake of radioactive iodine, they should wait at least a week after their ICG procedure.
Equipment used for Indocyanine Green (ICG) Angiography
A fundus camera, which has special filters that help it take clear pictures, is used to photograph the back of your eye. There are two types of fundus cameras. The first is a digital flash camera (made by companies like Zeiss and Topcon) that uses regular white light. This type of camera has special filters for letting through specific light wavelengths – between 640 and 780 nanometers for the excitation filter and between 820 and 900 nanometers for the barrier filter.
The second type is a confocal scanning laser ophthalmoscope (made by companies like Heidelberg, Nidek, and Optos) that uses a single-color laser light for taking pictures. For example, the Spectralis by Heidelberg uses a diode laser (at 790 nanometers) and has a barrier filter of 830 nanometers. This camera can also capture 12 to 15 images in a second, allowing for real-time monitoring.
For the process, a standard dosage of a chemical called ICG is injected into an adult’s vein. It’s usually 25 milligrams of ICG mixed in 5 milliliters of solvent. To do this, additionally, a 23 gauge vein needle set, a 5 ml syringe with a needle, alcohol swab, tourniquet (a tightly wrapped band around your arm to make your veins bulge out), and armrest are needed. And just in case, a standard emergency kit to manage severe allergic reactions (called anaphylaxis) should always be ready before starting.
Who is needed to perform Indocyanine Green (ICG) Angiography?
If you have to go through a medical procedure called ICGA (which stands for Indocyanine Green Angiography, a type of eye test), there will be a team of health care professionals there to take care of you. This team includes an ophthalmologist, who is a doctor specializing in eye disease, along with a technician who operates the special equipment. There’s also an optometrist – another type of eye doctor who often focuses on eye tests and glasses, nursing staff to assist, and an anesthetist – a doctor or nurse who manages your pain and might make you sleep during the procedure. This way, you’re well looked after at every step.
Preparing for Indocyanine Green (ICG) Angiography
Before starting a particular medical procedure, it is essential to get the patient’s understanding and agreement. This is known as informed consent. The doctor should explain to the patient in easy-to-understand language the benefits and risks associated with the procedure. Before the procedure, doctors also need to gather detailed information from the patient about any allergies and existing health conditions they may have. It’s suggested that patients stop eating or drinking anything two to four hours before the procedure.
During the procedure, the medical team might use a special dye (ICG) to help them see better. For adults, the typical dosage is 25 mg of this dye, mixed into 5 ml of liquid. If a specific kind of imaging system called SLO is used, the same amount of dye is dissolved in less liquid (3 ml), and only 1 ml of this is injected. After injecting the dye, they will give a 5 ml saline wash to ensure that all the dye was delivered to the right place.
The medical team will take precautions to ensure the patient’s comfort and safety during the procedure. They will ensure the patient’s pupils are well dilated, which helps them see inside the eyes more clearly. They’ll take a few test pictures of the inside of the eye to make sure they’re focused and clear. Patients will be seated comfortably, with their arm on a rest and their chin on a chin rest. They’ll explain to the patient that they’ll be taking pictures while your eyes are looking straight ahead (primary gaze) and then at different angles (different gazes).
The medical professional will insert a small tube called a ‘scalp vein set’ into a blood vessel on the underside of the forearm to administer various medicines or fluids as required during the procedure. To ensure it’s correctly placed inside the vein, they may draw a small amount of blood or use a saline solution for flushing. They’ll always have an emergency kit on hand for any unexpected situations that may arise.
How is Indocyanine Green (ICG) Angiography performed
When taking images of the eye, the patient’s chin is carefully placed on a chin rest and their head is held steady to prevent any movement. As soon as a special dye is injected, pictures are automatically taken every 1.5 to 2 seconds. Once the dye has filled the blood vessels in the back of the eye, photos are taken more slowly to capture detailed images.
It’s also important to take pictures of the other eye for comparison. These pictures help doctors see if there is normal flow of blood through the eyes.
There are different stages we look at when examining these images:
1. Early Phase – This phase happens immediately after the dye is injected and lasts for about 3 minutes. It is subdivided into three stages, detailed below:
- Stage 1: Starts 2 seconds after the dye is injected. This is marked by a quick filling of the tiny blood vessels in the back of the eye with the dye while the main blood vessels of the eye and an area known as the watershed zone stay dark.
- Stage 2: Occurs three to five seconds post injection where the dye starts filling the larger veins in the eye and the small arteries in the eye.
- Stage 3: Starts 6 seconds post injection and lasts up to 3 minutes. At this stage, the “watershed zone” gets filled with the dye and the visibility of the bigger veins and arteries starts to reduce.
2. In the Middle Phase (between 3 to 15 minutes post injection), the dye in the blood vessels of both the eye and the back part of the eye starts to fade.
3. In the Late Phase (between 15 to 60 minutes post injection), the dye starts to stain the tissue just outside the layer at the back of the eye, making it appear that the blood vessels in the back of the eye are not displaying the dye as much when compared to the tissue around them. Also, during this phase, the blood vessels of the eye are not noticeable.
Possible Complications of Indocyanine Green (ICG) Angiography
Side effects of a medical test called Indocyanine Green Angiography (ICGA) are less likely compared to those from another test called Fluorescein Angiography (FA). One side effect could be a stinging sensation if the dye used in the test leaks out of the blood vessel. About 0.15% of patients might feel mild effects like nausea and vomiting. Other effects, which are seen in around 0.2% of patients, include hives (also known as urticaria) and fainting spells (known as vasovagal events). Hives can be treated with antihistamines, which are medicines used to treat allergies.
The occurrence of severe side effects is rare, happening in only 0.05% of patients. However, serious allergic reactions known as anaphylaxis can occur in patients who are allergic to iodine. It’s also important to note that these side effects are more common in patients with a condition called uremia – a state of high level of wastes in the blood, compared to the general population.
What Else Should I Know About Indocyanine Green (ICG) Angiography?
Exudative Age-Related Macular Degeneration (exudative AMD or wet AMD)
Exudative age-related macular degeneration (wet AMD) is a condition where new blood vessels grow in the back of the eye, which can lead to vision loss. A test called ICGA helps doctors see these new blood vessels. ICGA can show three different patterns of new blood vessels: a specific spot of growth (hot spot), a larger area (plaque), or a mix of the two. Each type of growth can affect your vision differently, and may need different treatments.
Doctors can also use ICGA to see if these new blood vessels have caused a bump or detachment in the back of the eye, and what type of new blood vessels are present. The test can help differentiate between immature and mature vessels, which is crucial for choosing the appropriate treatment.
A subgroup of these new blood vessels, retinal angiomatous proliferation (RAP), leads to about 20% of cases of wet AMD. ICGA can also help them separate RAP from other growths by spotting unique signs. If identified early on, the treatment response for RAP is likely better with combined treatment options.
Another condition that can be identified with ICGA is polypoidal choroidal vasculopathy (PCV). PCV is an abnormality in the blood circulation in the back of the eye and appears as a reddish-orange bulge on examination. This test is specifically recommended to rule out PCV in certain circumstances such as a massive spontaneous hemorrhage, or after unsuccessful treatment with a type of medication called anti-VEGF.
It is critical to differentiate PCV from other new blood vessel growth because the treatment is different. A combined therapy of light treatment and anti-VEGF medication works more effectively than only using anti-VEGF for PCV.
ICGA is also useful for spotting unusual circulation conditions in the eye like central serous chorioretinopathy (CSCR), a disease where fluid builds up under the retina. The ICGA result in CSCR is distinct and helps differentiate it from PCV and detect other underlying conditions.
Overall, ICGA is a crucial tool in diagnosing and treating various conditions associated with unusual blood vessel growth and circulation in the eye.