It is very important to 

weiqing supply professional and honest service.

discuss any health conditions that you have, 

all the medications that you are taking, and 

especially any allergies to medications that you have had in the past. 

It is preferred that you bring this information as a letter from your doctor. 

If you have had a previous fluorescein angiogram, mention this as well. 

You do not need to fast for this test. 

Please advise the staff prior to the test being commenced if you are or suspect you may be pregnant. Fluorescein is reported to be safe in pregnancy but it is preferable to avoid this test in pregnant patients if possible.

Indocyanine green angiography (ICGA) provides improved imaging of choroidal vasculature compared to fluorescein angiography. Because of the excitation and emission properties of indocyanine green (excitation at 790 nm and emission at 835 nm), pathologies involving retinal and choroidal vascular systems can be imaged even in the presence of overlying melanin, serosanguinous fluid, xanthophyll pigment, or lipid exudations.

History

Indocyanine green (ICG) was developed in Kodack laboratories, and its physical and physiological properties were first described by Fox and Wood in .[1] Kogure and others first used ICG to visualize the fundus of an owl monkey in the s.[2] However, it was not routinely used in humans until s because of technological limitations of the fundus cameras. There was an uptick in ICGA administration in the s due to improvements in digital video angiography, scanning laser ophthalmoscopy, and optical systems of fundus cameras.[3][4] In addition, the advent of ICGA allowed for better detection of occult choroidal neovascularization (CNV), which in turn led to an increase in the number of eyes that were eligible for photocoagulation which, at the time, was the only treatment option for CNV.[5] Since the s, in the era of anti-vascular endothelial growth factor (anti-VEGF) therapy which does not require accurate localization of the CNVs, ICGA has been mostly limited to the indications summarized below.[6] However, ICGA, combined with FA, OCT, and OCTA, is still extremely useful in clinical practice.

Retinal angiomatous proliferation (RAP): 75-year-old patient with a decrease in visual acuity and metamorphopsia in right eye. This RAP lesion is focally hyperfluorescent in this late-phase FA (left) and hypocyanescent in midphase ICGA (right). Note the feeding and draining retinal arteriole and venule ending at the lesion. This image was originally published in the Retina Image Bank® website. Gabriela Lopezcarasa Hernandez, MD. Photographer Azucena Rios. Retinal Angiomatous proliferation. Retina Image Bank. ; . © The American Society of Retina Specialists.

75-year-old patient with a decrease in visual acuity and metamorphopsia in right eye. This RAP lesion is focally hyperfluorescent in this late-phase FA (left) and hypocyanescent in midphase ICGA (right). Note the feeding and draining retinal arteriole and venule ending at the lesion. This image was originally published in the Retina Image Bank® website. Gabriela Lopezcarasa Hernandez, MD. Photographer Azucena Rios. Retinal Angiomatous proliferation. Retina Image Bank. ; . © The American Society of Retina Specialists.

Properties

Two properties make ICG an effective dye for visualizing choroidal vasculature. First, indocyanine green&#;s affinity to circulating proteins is high (95%), limiting its leakage from vessel walls. Comparatively, more heavily leaking fluorescein (only 80% bound) from the retinal and choriodal vessels can obscure the details of adjacent retinal and choroidal vasculature. Another drawback of fluorescein dye in visualizing the choroid is that fluorescein molecule absorbs and emits shorter wavelength photons. Since the retinal pigment epithelium (RPE) also absorbs and emits photons around this wavelength, the resulting scatter from RPE can obscure the choroidal vessels. Indocyanine, however, absorbs and emits photons in the infrared spectrum, allowing the viewer to see the choroid through the retinal pigment epithelium or disease processes such as overlying hemorrhage.[7]

See &#;Dyes in Ophthalmology&#; for more information.

Uses

For a thorough review of the uses of indocyanine green, see Cohen et al.&#;s &#;Is indocyanine green still relevant?&#; editorial in Retina .[8]

In the era of anti-VEGF treatments, the localization of CNV is not absolutely necessary for managing exudative ARMD as it was in the past. However, ICGA is utilized by many clinicians in combination with other retinal imaging modalities to identify the subtype of CNV in AMD (type 1: sub-retinal pigment epithelium, type 2: subretinal, and type 3: intraretinal) and to differentiate ARMD lesions from simulating lesions.[8]

Polypoidal choroidal vasculopathy (PCV): The PCV lesion shows hyperfluorescence and hypercyanescence on intermediate-phase FA (left) and ICGA (right). This image was originally published in the Retina Image Bank® website. Gareth Lema MD, PhD. Photographer Sandra Boglione.Polypoidal Choroidal Vasculopathy - IVFA/ICGA. Retina Image Bank. ; . © The American Society of Retina Specialists.

The PCV lesion shows hyperfluorescence and hypercyanescence on intermediate-phase FA (left) and ICGA (right). This image was originally published in the Retina Image Bank® website. Gareth Lema MD, PhD. Photographer Sandra Boglione.Polypoidal Choroidal Vasculopathy - IVFA/ICGA. Retina Image Bank. ; . © The American Society of Retina Specialists.

Type 1 macular neovascularization (MNV), with CNV network located under the RPE, is the most common form of exudative AMD. Type 1 CNV corresponds to &#;occult CNV&#; based on the Macular Photocoagulation Study and is identified as fibrovascular pigment epithelium detachment with a late stippled fluorescence or a late leakage from an undetermined source (LLUS). Often, clinical examination, OCT, and FA are sufficient for the diagnosis and follow-up; however, ICGA may be required when the lesion is covered with hemorrhage or if there is a question about the presence of accompanying type 3 MNV (retinal angiomatous proliferation &#; RAP) that is reported in about one fourth of the eyes with type 1 CNV. The presence of a RAP lesion has at least two clinical significances. First, RAP is shown to have a more aggressive clinical course that needs frequent and long-term injection of anti-VEGF agents. Second, it has been shown that RAP lesions respond better to treatment with anti-VEGF agents combined with photodynamic therapy (PDT). ICGA may delineate the presence of type 1 CNV usually around the perimeter of pigment epithelial detachment or show the feeder and draining vessels. RAP lesions are similarly seen as an interconnected retinal arteriole and venule branch.

Choroidal Hemangioma: (A) shows fundus photo (left), FA(middle), and ICGA (right). FA revealed leakage from an ill-defined lesion superotemporal to the disc, while the ICGA showed diffuse and intense hypercyanescence of choroidal vessels, consistent with a choroidal hemangioma. (B) shows OCT of the same eye with foveal detachment and choroidal elevation (star). (C) B-scan ultrasonography and A-scan ultrasonography. A Masquerade Case: Choroidal Hemangioma Misdiagnosed As Central Serous Retinopathy © by Lai L, Javier T, Lee S, Gallemore RP. is licensed under Creative Commons Attribution &#; Non-Commercial (unported, v3.0) License.

(A) shows fundus photo (left), FA(middle), and ICGA (right). FA revealed leakage from an ill-defined lesion superotemporal to the disc, while the ICGA showed diffuse and intense hypercyanescence of choroidal vessels, consistent with a choroidal hemangioma. (B) shows OCT of the same eye with foveal detachment and choroidal elevation (star). (C) B-scan ultrasonography and A-scan ultrasonography. A Masquerade Case: Choroidal Hemangioma Misdiagnosed As Central Serous Retinopathy © by Lai L, Javier T, Lee S, Gallemore RP. is licensed under Creative Commons Attribution &#; Non-Commercial (unported, v3.0) License.

Type 2 CNV known as &#;classic CNV&#; is located under the retina and above the RPE and is visualized nicely with ICGA as the network of abnormal vessels in the setting of improved delineation of retinal and choroidal circulations. This improved spatial and temporal visualization with ICGA allows identification of the feeding choroidal vessels into the type 2 CNV lesion. 

Aneurysmal type 1 MNV or polypoidal choroidal vasculopathy (PCV) is characterized by a growth of cavernous thin-walled vessels between the RPE and the Bruch&#;s membrane and is often associated with multiple, recurrent, serosanguineous detachments of the RPE and neurosensory retina secondary to leakage and bleeding from the polypoid lesions. ICGA delineates the polypoid or &#;bulging&#; capillaries through the overlying RPE and serosanguinous fluid with higher sensitivity and specificity and provides a better insight into the possible clinical course and prognosis. PCV polyps (that may be located in the peripapillary area or at the macula) start to fill before retinal vessels and continue to fill long after retinal vessels are filled. Thus, polyps are usually seen as early small hypercyanescence that leak slowly as the surrounding hypocyanescence become increasingly hypercyanescent. In later phases, dye gradually and uniformly &#;washes out&#; from the bulging polypoidal lesions.

PCV can be misdiagnosed or confused with chronic central serous chorioretinopathy or with classic or occult CNV in the setting of AMD. Indeed, in some patients, a transitional phase between these two pathologies can contain PCV patholgies. PCV lesions are usually responsive to more frequent anti-VEGF treatment with or without photodynamic therapy. In this setting, ICGA can guide management primarily by:

1. Revealing the polypoidal lesions and the branching vascular networks.

2. Identify active PCV for selective treatment with photodynamic therapy (PDT)

3. Identify recurrences after PDT (seen as late geographic hypercyanescence).[9][10][11]

Central Serous Chorioretinopathy (CSCR): Mid-phase FA (right) shows a smokestack leak,age and ICGA (left) shows a pinpoint hypocyanescent spot corresponding to the leakage site and the adjacent hypercyanescent areas. This image was originally published in the Retina Image Bank® website. Hamid Ahmadieh, MD. Photographer Hamid Ahmadieh, MD. Acute Central Serous Chorioretinopathy. Retina Image Bank. ; 735. © The American Society of Retina Specialists.

Mid-phase FA (right) shows a smokestack leak,age and ICGA (left) shows a pinpoint hypocyanescent spot corresponding to the leakage site and the adjacent hypercyanescent areas. This image was originally published in the Retina Image Bank® website. Hamid Ahmadieh, MD. Photographer Hamid Ahmadieh, MD. Acute Central Serous Chorioretinopathy. Retina Image Bank. ; 735. © The American Society of Retina Specialists.

Choroidal tumors

ICGA and ultrasonography help identify choroidal hemangiomas and differentiate them from simulating tumors such as choroidal melanoma or metastasis. Choroidal hemangioma has a distinctive filling pattern on ICGA: progressive filling of abnormal choroidal vessels in the early phase, followed by an intense hypercyanescence at 2-4 minutes, with decreased cyanescence of the tumor at later frames compared to the rest of the choroid, known as the washout phenomenon.[12][13][14][15][16]

Although other choroid tumors do not have a characteristic ICGA feature, ICGA may still be used to differentiate them from simulating nontumor lesions such as peripheral exudative hemorrhagic chorioretinopathy (PEHCR). [8]

Choroidal hypervascularity in the pachychoroid spectrum of diseases such as central serous chorioretinopathy (CSCR) may be better delineated with ICGA. ICGA may show an area of choroidal hypervascularity larger than the leakage spot seen in FA and is especially helpful in guiding photodynamic therapy to include entire hypervascular and leaking areas.[17][18] In addition, chronic CSCR complicated with CNV with or without leakage and hemorrhage may be better delineated with ICGA.

Angioid Streaks: Late phase ICG angiography image of the left eye of a 59-year-old man with angioid streaks demonstrating hypercyanescence of the cracks in the Bruchs membrane. This image was originally published in the Retina Image Bank® website. Hamid Ahmadieh, MD. Photographer Hamid Ahmadieh, MD. Acute Central Serous Chorioretinopathy. Retina Image Bank. ; 951. © The American Society of Retina Specialists.

: Late phase ICG angiography image of the left eye of a 59-year-old man with angioid streaks demonstrating hypercyanescence of the cracks in the Bruchs membrane. This image was originally published in the Retina Image Bank® website. Hamid Ahmadieh, MD. Photographer Hamid Ahmadieh, MD. Acute Central Serous Chorioretinopathy. Retina Image Bank. ; 951. © The American Society of Retina Specialists.

ICGA may provide a clear view of the complications associated with pathologic myopia. CNV lesions associated with lacquer cracks (such as lesions underneath subretinal hemorrhages related to newly formed lacquer cracks) are better visualized with ICGA.[19]

Angioid streaks are typically visualized with ICGA more clearly, extensively, and prominently as compared to FA or fundus exam.[20]

Inflammatory

ICGA is helpful in the diagnosis of white dot syndromes, particularly if the fundus lesions are of an atypical appearance or have already faded away.[21] In MEWDS, ICGA shows numerous hypercyanescent dots scattered throughout the posterior pole and a hypocyanescent area surrounding the optic nerve. The hypocyanescent areas on ICGA disappear over time as the inflammation resolves. [22][23][24]

Multiple evanescent white dot syndrome (MEWDS): Late phase angiographic images from a patient with MEWDS; FA (left) and ICGA. ICGA shows hypocyanescent patches corresponding to MEWDS lesions. American Academy of Ophthalmology, , Accessed: 10/1/ https://www.aao.org/education/image/indocyanine-green-angiography

Late phase angiographic images from a patient with MEWDS; FA (left) and ICGA. ICGA shows hypocyanescent patches corresponding to MEWDS lesions. American Academy of Ophthalmology, , Accessed: 10/1/ https://www.aao.org/education/image/indocyanine-green-angiography

Acute posterior multifocal placoid pigment epitheliopathy is a multifocal inflammation involving the choriocapillaris, and the resulting delayed and defective choroidal filling may manifest as a unique pattern of multifocal hypocyanescence in areas seen in the retinal examination as white spots.[25]

Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE): A 27-year-old male with APMPPE. In the fundus photograph, there are multiple yellow placoid lesions in the posterior pole of both eyes. ICGA revealed more lesions than those observed in fundoscopy. The OCTA segmented at the level of the choriocapillaris revealed areas of ischemia in close correspondence with the hypocyanescent lesions. The OCT with superimposed flow shows disruption and hyperreflectivity of the external retinal layers in the affected areas and the absence of flow in the choriocapillaris underneath. This image was originally published in the Retina Image Bank® website. Claudia Farinha. Photographer Pedro Melo. Acute Posterior Multifocal Placoid Pigment Epitheliopathy. Retina Image Bank. ; . © The American Society of Retina Specialists.

A 27-year-old male with APMPPE. In the fundus photograph, there are multiple yellow placoid lesions in the posterior pole of both eyes. ICGA revealed more lesions than those observed in fundoscopy. The OCTA segmented at the level of the choriocapillaris revealed areas of ischemia in close correspondence with the hypocyanescent lesions. The OCT with superimposed flow shows disruption and hyperreflectivity of the external retinal layers in the affected areas and the absence of flow in the choriocapillaris underneath. This image was originally published in the Retina Image Bank® website. Claudia Farinha. Photographer Pedro Melo. Acute Posterior Multifocal Placoid Pigment Epitheliopathy. Retina Image Bank. ; . © The American Society of Retina Specialists.

Although ICGA is not crucial for diagnosing VKH, active disease can be differentiated from completely treated and inactive VKH by the ICGA pattern. ICGA signs of acute VKH include early choroidal vessel hypercyanescence, intermediate to late phase fuzziness of choroidal stromal vessels, disc hypercyanescence, and hypocyanescent dark dots (HDDs).  ICGA is an excellent modality to detect subtle choroidal inflammation in subclinical VKH reactivation, thus helping to monitor adequate response to corticosteroid treatment.[26][27]

Deep, cream-colored lesions diffusely scattered throughout the fundus in Birdshot chorioretinopathy (BS) appear as round or oval hypocyanascent spots with a similar size spread across the fundus, particularly affecting the nasal quadrants. FA does not show these lesions well, and ICGA often shows more spots than clinical examination. Other ICGA features include an alteration of the vascular pattern of the choroid, with choroidal vessels appearing fuzzy and indistinct in the intermediate phases of the angiogram and a late diffuse hypercyanescence resulting from the ICG dye leaking through the inflamed choroidal vessels. In the chronic phase of the disease, the hypocyanescent dots persist in the late phases of the angiogram and correspond to chorioretinal scars. [28]

Choroidal Granulomas

Choroidal granulomatous diseases such as sarcoidosis and tuberculosis may manifest as hypocyanascent lesions that reflect filling defects in the areas occupied by a collection of granulomatous cells. [29][30]

Vogt-Koyanagi-Harada disease (VKH): Simultaneous early phase FA (left) and ICGA (right) images of a 42-year-old woman with VKH showing hypocyanescent dark dots corresponding to hypoperfused areas in choroid. This image was originally published in the Retina Image Bank® website. Claudia Farinha. Photographer Pedro Melo. Acute Posterior Multifocal Placoid Pigment Epitheliopathy. Retina Image Bank. ; . © the American Society of Retina Specialists.

Simultaneous early phase FA (left) and ICGA (right) images of a 42-year-old woman with VKH showing hypocyanescent dark dots corresponding to hypoperfused areas in choroid. This image was originally published in the Retina Image Bank® website. Claudia Farinha. Photographer Pedro Melo. Acute Posterior Multifocal Placoid Pigment Epitheliopathy. Retina Image Bank. ; . © the American Society of Retina Specialists.

ICGA can help to differentiate between active, inactive, and healed serpiginous choroidopathy (SC) lesions.[31][32][33] In subclinical and clinically active lesions, ICGA will typically show one of the two patterns: 1) early and late hypocyanescence with ill-defined margins, or 2) early hypocyanescence with increased cyanescence toward late-phase of ICGA. ICGA in healed SC lesions will show early and late-phase hypocyanescence with well-defined margins.

Ocular Infections

While posterior inflammation involving the choroid could be seen with ICGA in many infectious processes, ICGA often does not offer additional information to help with the diagnosis or management of ocular infectious conditions.[8]

Trauma

ICGA can reveal choroidal involvement as with traumatic choroidopathies such as choroidal rupture and traumatic ocular hypotony. However, since ICGA adds little diagnostic or prognostic information, it is rarely ordered in ocular trauma settings.[34][35] [36][37]

Procedure

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The standard dosing for ICG with scanning laser ophthalmoscopy camera systems is 25 mg of ICG dissolved in 3 ml of saline and 1 ml of the solution is injected. For combined FA and ICGA, saline is replaced with fluorescein sodium solution at 10, 20, or 25% concentrations. There  are three temporal phases for ICGA imaging, similar to fluorescein angiography:[7][38]

Birdshot Chorioretinopathy - ICG shows numerous scattered small hypocyanescent spots, not necessarily corresponding to lesions seen on FA or clinical examination This image was originally published in the Retina Image Bank® website. Armando L. Oliver, MD. Photographer Moises Castro. Birdshot ICG OD. Retina Image Bank. ; . © The American Society of Retina Specialists.

- ICG shows numerous scattered small hypocyanescent spots, not necessarily corresponding to lesions seen on FA or clinical examination This image was originally published in the Retina Image Bank® website. Armando L. Oliver, MD. Photographer Moises Castro. Birdshot ICG OD. Retina Image Bank. ; . © The American Society of Retina Specialists.

Early phase - within the first minute after injecting the eye, when larger choroidal arteries and veins are highlighted but retinal arteries are not filled.[38] Choroidal vessels start to fill from larger outer Haller&#;s layer vessels followed by intermediate Sattler&#;s layer. The choriocapillaris layer fills last but camera resolutions are not high enough to identify individual choriocapillaris. Thus, filling of choriocapillaris is usually seen as indistinct general haze, more evident in the posterior pole.

Middle phase - up to 5 to 10-15 minutes after injection. Retinal arteries and veins as well as the choroidal vasculature are filled.  Choroidal cyanescence will become more diffuse and less distinct in this phase as the choriocapillaris is filled.[38]

Late or recirculation phase - more than 10-15 minutes after the dye is injected. During this phase, a pathologic hypercyanescent lesion is more visible against the slowly fading background.[38]

Safety

ICGA is a safe and well-tolerated imaging study with extremely rare toxicity and allergic reactions such as nausea, vomiting, sneezing, and pruritus in 0.15% of the procedures, moderate allergic reactions such as urticaria and pyrexia in 0.2% of the patients, and severe reactions such as bronchospasm and anaphylactic reaction in 0.05% of the patients.[39] An editorial described four reports of patients who have experienced an adverse reaction out of 240,000 indocyanine intravenous injections, one patient had urticaria and three patients had anaphylactic reactions, with one resulting in death.[7][40]

Absolute contraindications

1. Prior allergic reaction to ICG

2. Iodine/Iodide allergy: Although prior allergy to contrast dyes containing iodine or allergic reaction to shellfish are traditionally mentioned as contraindications for ICGA, such &#;allergic reactions&#; against indocyanine green are not biologically plausible. Unlike x-ray contrast media, iodine containing disinfectant solutions, or iodine containing medications such as amiodarone where iodide is bound to the main large molecule and can be identified by immune system as antigen, the ICG molecule does not contain the ion iodide and small sodium iodide molecule that is added to stabilize ICG in saline solution, are not detectable by immune system as antigens. Nevertheless, it is a common agreement to avoid ICGA if there is a history of allergy to iodine. In addition, since up to 840μg of iodide can be administered with ICGA imaging, there is a risk of thyroid storm in individuals with uncontrolled hyperthyroidism. In these situations, ICG should be used with caution or not used at all. Infracyanine green is an iodine free preparation of ICG available for those with an absolute contraindication to ICG and can be given with some modifications in the administration techniques. [38]

Relative contraindications

1. End stage renal disease

2. Liver disease

3. Pregnancy (Category C: adequate safety studies have not been conducted)[7]

Summary

ICGA is a safe and important imaging modality that offers a better view of the choroidal vasculature and related pathologies. Although it is not used as often as before in managing choroidal neovascular lesions, ICGA is still helpful in guiding the treatment of PCV and CSC and diagnosing choroidal hemangiomas and ocular inflammations primarily affecting the choroid.

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