Understanding Indocyanine Green Angiography
Indocyanine green angiography is a diagnostic imaging test that takes detailed pictures of the blood vessels in the choroid. The choroid is a layer of blood vessels located beneath the retina, the light-sensitive tissue at the back of your eye. During the test, a special dye called indocyanine green (ICG) is injected into a vein in your arm. As the dye travels through your bloodstream and into the choroidal vessels, a specialized camera captures images using infrared light.
The ICG dye was approved for human use by the Food and Drug Administration (FDA) in 1956 (FDA, via NIH). The first ICGA of the human choroid was performed by R.W. Flower in 1972. Since then, this test has become an important tool in retina care.
Another common eye imaging test is fundus fluorescein angiography (FFA). FFA does an excellent job of showing the blood vessels in the retina itself, but it has limitations with deeper structures. The retinal pigment epithelium (RPE), a layer of cells between the retina and the choroid, blocks much of the fluorescein signal. Media opacities and retinal exudates (fluid or deposits in the retina) also reduce FFA image quality of the choroid.
ICG dye works differently. It fluoresces in the near-infrared range, with an absorption peak at 790 to 805 nanometers and a peak emission at 835 nanometers. Infrared light penetrates better through the RPE, macular pigments, and other obstructions. This gives ICGA a much clearer view of choroidal blood vessels than FFA can provide.
Indocyanine green is a water-soluble cyanine dye with both hydrophilic (water-attracting) and lipophilic (fat-attracting) properties. After injection, ICG binds heavily to blood lipoproteins, particularly phospholipids. Up to the vast majority of the dye becomes protein-bound in the bloodstream (AAO, Basic and Clinical Science Course). This high level of protein binding means the dye leaks less from the tiny choroidal blood vessels compared to fluorescein dye. The choroidal vessels remain highlighted for a longer period, giving the retina specialist more time to study them.
When ICGA Is Recommended
ICGA is widely used to study choroidal neovascularization (abnormal new blood vessel growth beneath the retina) in patients with wet age-related macular degeneration (AMD). It helps identify occult choroidal neovascularization, a type of abnormal vessel growth that is difficult to see with standard fluorescein angiography. Finding and characterizing these vessels helps a retina specialist choose the most effective treatment plan.
Idiopathic polypoidal choroidal vasculopathy (IPCV) is a condition in which abnormal blood vessels beneath the retina develop bulging, polyp-like formations. These polyps can leak fluid or blood, causing vision loss. ICGA is considered essential for correctly diagnosing IPCV. It reveals the characteristic branching vessel network and polyps that other imaging methods may miss. Accurate diagnosis matters because IPCV may respond differently to treatment than other forms of wet AMD.
Retinal angiomatous proliferation (RAP) is another specific pattern of abnormal blood vessel growth associated with AMD. In RAP, new vessels grow from the retina downward into deeper tissue layers or from the choroid upward. ICGA helps retina specialists identify the exact location and stage of RAP lesions. This information influences treatment decisions.
Central serous chorioretinopathy (CSCR) is a condition in which fluid builds up under the retina. It often causes a blister-like detachment in the central vision area. ICGA helps reveal areas of choroidal vascular abnormality, including increased permeability and congestion, that contribute to fluid leakage. Recent research, including the CERTAIN Study, has used ultrawidefield ICGA to map choroidal vascular changes across a broader area of the eye in CSCR patients.
ICGA is also useful in evaluating ocular inflammatory conditions. In diseases such as sympathetic ophthalmia (a rare condition where inflammation in one eye triggers inflammation in the other), ICGA can detect choroidal inflammation not visible with other tests. This information helps guide treatment for complex inflammatory disorders affecting the back of the eye.
What Happens During the Test
Before ICGA, a retina specialist or technician will review your medical history. You will be asked about allergies, particularly to iodine or iodine-containing contrast agents, because the ICG dye solution contains sodium iodide. You will also be asked about any history of liver disease, kidney problems, or pregnancy. Your pupils will typically be dilated with eye drops so the camera can capture the best images.
A small needle is placed in a vein in your arm, usually in the hand or the inside of the elbow. The ICG dye is then injected into the vein. The dye concentration may vary depending on the camera system used. For fundus cameras, 25 milligrams of ICG dissolved in 5 milliliters of solvent is a typical dose. This may be increased to 50 milligrams in patients with small pupils or heavy eye pigmentation (AAO, Basic and Clinical Science Course).
As the dye circulates through the bloodstream and into the choroidal vessels, a special camera equipped with infrared filters takes a series of photographs. The camera captures images at different time points to show how the dye fills and flows through the choroidal blood vessels. The entire imaging session usually takes 20 to 30 minutes, though the dye injection itself is brief.
After the test, you may notice that your skin has a slight greenish tint. Your urine may appear darker or greenish for a day or two. These effects are normal and temporary as your body clears the dye. Your vision may be blurry from the dilating drops for several hours. It is a good idea to arrange for someone to drive you home if your pupils are dilated.
Safety and Possible Side Effects
ICGA is considered a safe diagnostic procedure. With a typical ICG dose of 0.2 to 0.5 milligrams per kilogram of body weight, adverse events occur in fewer than 0.1% of patients (Frontiers in Surgery, 2019). When side effects do occur, they are usually mild. The most commonly reported reactions include brief episodes of low blood pressure, rapid heart rate, and hives.
The ICG dye preparation contains sodium iodide. Approximately 5% of the preparation by weight is iodide (AAO, Basic and Clinical Science Course). Patients with a known iodine allergy face a higher risk of a reaction. A 25 milligram ampoule of ICG contains about 0.93 milligrams of iodine. In rare cases, patients allergic to iodine or iodine-based contrast agents have experienced serious reactions. These can include difficulty breathing or anaphylaxis (a severe whole-body allergic reaction). A retina specialist will ask about iodine allergies before performing the test.
ICGA is not recommended for patients with significant liver disease because the liver is responsible for clearing the dye from the body. Patients with uremia (a buildup of waste products in the blood due to kidney failure) also face increased risks of side effects. According to FDA classification, ICG is a pregnancy category C drug. This means there are no adequate human studies to confirm its safety during pregnancy. A retina specialist will weigh the benefits against the risks before recommending ICGA in these situations.
How ICGA Fits into Modern Retina Care
Optical coherence tomography (OCT) is a noninvasive imaging tool that creates detailed cross-section images of the retina. In the era of anti-VEGF treatments and advanced OCT technology, monitoring many retinal conditions has become easier. However, ICGA continues to fill a unique role that OCT and fluorescein angiography cannot fully replace. Its ability to image the choroidal circulation through pigment, fluid, and exudates makes it irreplaceable for certain diagnoses.
The findings from ICGA often directly influence treatment choices. Correctly distinguishing between occult choroidal neovascularization, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation is critical. These conditions may require different treatment approaches. Anti-VEGF medications such as Eylea (aflibercept) or Vabysmo (faricimab) are commonly used for wet AMD. The specific pattern of disease seen on ICGA can help a retina specialist determine the best treatment protocol.
Researchers are exploring new ways to enhance ICGA. Simultaneous OCT, scanning laser ophthalmoscopy (SLO), and ICG imaging systems allow retina specialists to gather multiple types of data at the same time. Investigators have also interfaced ICG near-infrared imaging technology with neuroendoscopes (small cameras used in surgery). This helps visualize deep-seated blood vessel abnormalities that traditional ICGA cannot reach. Ultrawidefield ICGA is another advancement that captures a broader view of the choroidal vasculature in a single image.
Living with a Retinal Condition That Requires ICGA
If you have been diagnosed with a condition such as wet AMD, IPCV, or central serous chorioretinopathy, your retina specialist may recommend ICGA at different points during your care. The test may be performed at the time of initial diagnosis. It may be repeated later to evaluate how well your treatment is working or to look for changes in the choroidal blood vessels. The frequency of testing depends on your specific condition and how it responds to treatment.
ICGA is one of several tools a retina specialist may use to understand your condition. It provides information that complements other tests such as OCT and fluorescein angiography. If ICGA has been recommended for you, it means your retina specialist needs detailed images of the choroidal blood vessels that only this test can provide. Asking questions about why the test is being performed and what the results may mean can help you stay informed about your care.
When to See a Retina Specialist
Certain symptoms may indicate a serious retinal problem that requires imaging such as ICGA. If you experience any of the following, see a retina specialist or go to the emergency room immediately:
- A sudden increase in floaters (spots or lines drifting across your vision)
- Flashes of light in one or both eyes
- A curtain or shadow moving across your field of vision
- Sudden vision loss in one eye
If you have been diagnosed with age-related macular degeneration, central serous chorioretinopathy, or another choroidal condition, regular visits to a retina specialist are important. Even if your vision seems stable, changes in the choroidal blood vessels can occur without noticeable symptoms. Routine imaging, which may include ICGA, helps detect these changes early. This allows treatment adjustments before significant vision loss occurs.
Questions and Answers
The ICG dye is injected through a vein in your arm, similar to a standard blood draw. You may feel a brief pinch when the needle is inserted. The imaging itself is painless. Some people feel mild warmth or nausea as the dye circulates, but these sensations typically pass within a few minutes.
ICG dye is cleared from the body primarily through the liver. Most of the dye is eliminated within 24 hours. You may notice a greenish tint to your skin or urine for a day or two after the procedure, which is normal. Drinking plenty of water can help your body clear the dye.
Shellfish allergy is sometimes associated with iodine sensitivity, though the relationship is not straightforward. Because the ICG preparation contains sodium iodide, inform your retina specialist about any allergies to shellfish, iodine, or iodine-containing contrast agents before the test. Your specialist will determine whether ICGA is safe for you or whether an alternative approach should be used.
ICGA does not replace other eye tests. It provides specific information about the choroidal blood vessels that other tests, such as OCT or fluorescein angiography, cannot fully capture. In most cases, ICGA is used alongside these other tests to give your retina specialist a more complete picture. Each test has a unique role in diagnosis and treatment planning.