Indocyanine Green Angiography: Difference between revisions

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[[File:FA vs ICG in patient with Central Serous Chorioretinopathy .png|thumb|600x600px|Image comparing intermediate phase Fluorescein Angiography (FA) and Indocyanine Angiography (ICGA) in a patient with Central Serous Chorioretinopathy. '''A'''. FA photo '''B.''' ICGA photo (Choroid vasculature is more diffusely hyperfluorescent). University of Minnesota Ophthalmology, 2023 - Courtesy of Hossein Nazari, MD, PhD]]
[[File:FA vs ICG in patient with Central Serous Chorioretinopathy .png|thumb|600x600px|Image comparing intermediate phase Fluorescein Angiography (FA) and Indocyanine Angiography (ICGA) in a patient with Central Serous Chorioretinopathy. '''A'''. FA photo '''B.''' ICGA photo (Choroid vasculature is more diffusely hyperfluorescent). University of Minnesota Ophthalmology, 2023 - Courtesy of Hossein Nazari, MD, PhD]]
Indocyanine green angiography (ICGA) provides improved imaging of choroidal vascular circulation relative to other modalities such as [[Fluorescein Angiography|fluorescein angiography]]. Therefore, it allows better visualization of choroidal pathologies and can even allow viewing of this vascular system when there is an obstructing disease process in the retina (e.g. hemorrhage, drusen, etc.). ICGA can also help with diagnosis confirmation and management in choroidal disease processes.
Indocyanine green angiography (ICGA) provides improved imaging of choroidal vascular circulation relative to other modalities such as [[Fluorescein Angiography|fluorescein angiography]]. Therefore, it allows better visualization of choroidal pathologies and can even allow viewing of this vascular system when there is an obstructing disease process in the retina (e.g. hemorrhage, drusen, etc.). ICGA can help with diagnostic confirmation and management of choroidal disease processes.


= History  =
= History  =

Revision as of 07:53, August 6, 2023

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Image comparing intermediate phase Fluorescein Angiography (FA) and Indocyanine Angiography (ICGA) in a patient with Central Serous Chorioretinopathy. A. FA photo B. ICGA photo (Choroid vasculature is more diffusely hyperfluorescent). University of Minnesota Ophthalmology, 2023 - Courtesy of Hossein Nazari, MD, PhD

Indocyanine green angiography (ICGA) provides improved imaging of choroidal vascular circulation relative to other modalities such as fluorescein angiography. Therefore, it allows better visualization of choroidal pathologies and can even allow viewing of this vascular system when there is an obstructing disease process in the retina (e.g. hemorrhage, drusen, etc.). ICGA can help with diagnostic confirmation and management of choroidal disease processes.

History

The physical and physiological properties of indocyanine green (ICG) were first described by Fox and Wood in 1960.[1] ICG was first used in vivo in 1970 by Kogure and others to visualize the fundus of an owl monkey.[2] It was not routinely used in humans in the 1970s because of technological limitations, making it infeasible to use in the clinical setting. However, there was an uptick in its usage in the 1990s due to improvements in digital angiography, scanning laser ophthalmoscopy, optical alignment, and video monitors.[3][4] The advent of ICGA allowed for better detection of occult choroidal neovascularization (CNV), which in turn lead to an increase in the number of eyes that were eligible for photocoagulation which, at the time, was the only treatment for CNV.[5] However, when anti-vascular endothelial growth factor (anti-VEGF) was shown to improve mean visual acuity in patients with CNVs, there was a decreased need to use ICGA to pinpoint areas of occult CNV for phototherapy.[6]

Properties

There are two properties that make ICG an effective dye for visualizing choroidal vasculature. The first is that a high proportion of indocyanine binds to circulating proteins and the second is the wavelength spectrum at which it absorbs and fluoresces photos. Ninety-eight percent of indocyanine is bound to serum protein, causing the molecule to be sequestered inside the choriocapillaris instead of escaping through its fenestrations. Comparatively, leaking fluorescein (only 80% bound) from the choriocapillaris can obscure the details of the underlying choroidal vasculature. Another drawback of fluorescein dye in visualizing the choroid is that the molecule absorbs and emits photons of a shorter wavelength. This can be an issue because the retinal pigment epithelium also absorbs and emits photons around this wavelength and the resulting scatter from the epithelium can subsequently obscure the choroid. Indocyanine, however, absorbs and emits photons in the infrared spectrum, allowing the viewer to see the choroid through the retinal pigment epithelium or through disease processes such as 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 2011.[8]

Age-Related Macular Degeneration (ARMD)

Polypoidal choroidal vasculopathy: A: Fundus photograph shows lipid exudation surrounding a hemorrhage and area of decreased pigmentation inferotemporal to the optic nerve. B,: ICGA shows the sub-RPE vessels affected by polypoidal choroidal vasculopathy. American Academy of Ophthalmology, 2023, Accessed: Polypoidal choroidal vasculopathy - American Academy of Ophthalmology (aao.org)

Although the identification of CNV is not as crucial for the management of ARMD patients as it was in the past, ICGA should still be utilized in cases of ARMD when there is doubt in the diagnosis.[8] If, after FA and OCT, one cannot exclude conditions such as central serous chorioretinopathy or idiopathic polypoidal choroidal vasculopathy, ICGA can provide additional objective information to differentiate these entities from CNV.[8]

Polypoidal Choroidal Vasculopathy (PCV)

One of the most important uses of ICGA is for patients with PCV. It can help guide treatment primarily in three ways:

1. ICG can help reveal the entire disease, particularly the polypoidal lesions and the branching vascular networks.

2. It can help identify active PCV for selective treatment

3. It can help identify any recurrences after photodynamic therapy (which is seen as persistence of late geographic hyperfluorescence).[9][10][11]

Choroidal tumors

Together with ultrasonography, ICGA is effective at identifying choroidal hemangiomas. This is because it has a very distinctive filling pattern on ICGA: In the early phase there is progressive filling of of abnormal choroidal vessels, followed by very intense hyperfluorescence at 2-4 minutes, with decreased fluorescence of the tumor at later frames compared to the rest of the choroid - this is known as the washout phenomenon.[12][13][14][15][16] ICGA has not proved particularly useful for the diagnosis of other tumors of the choroid.[8]

Central Serous Chorioretinopathy (CSCR)

Similarly to in cases of PCV, in CSCR ICGA can be used to help guide photodynamic therapy by identifying areas of choroidal vascular hyperpermeability.[17][18]

Pathologic Myopia

Using ICGA in the setting of pathologic myopia may be of use in getting a clearer view of the pathology. ICGA can be used to visualize CNV inside areas with lacquer cracks or underneath subretinal hemorrhages related to these newly formed lacquer cracks.[19]

Angioid Streaks

Angioid streaks are typically more clearly visualized, more numerous, and larger when using ICGA as compared to FA or fundus exam.[20]

Inflammatory

MEWDS: Late phase angiographic images from a patient with multiple evanescent white dot syndrome (MEWDS) A: fluorescein, B: ICGA. American Academy of Ophthalmology, 2023, Accessed: https://www.aao.org/education/image/indocyanine-green-angiography

Multiple evanescent white dot syndrome (MEWDS)

ICGA is helpful in the diagnosing of these white dot syndromes, particularly if the white retinal dots are of an atypical nature or have already faded away.[21] ICGA in these scenarios can show a hyperfluorescent area surrounding the optic nerve, and numerous hyperfluorescent dots scattered throughout the posterior pole.[22][23][24]

Acute Idiopathic Blind Spot Syndrome Enlargement

Similarly, with MEWDS, ICGA can be helpful as a diagnostic tool in this syndrome.[21][22][23][24]

Acute Posterior Multifocal Placoid Pigment Epitheliopathy

In this disease process, ICGA can show a unique fluorescence pattern in areas exhibiting white spots due to what is likely delayed choroidal filling.[25]

Vogt-Koyanagi-Harada disease

Differences (e.g. background can be dark in early phase with many hyperfluorescent lesions seen in the intermediate phase, suggesting a choroidal circulatory disturbance in the acute phase) in ICGA patterns in Vogt-Koyanagi-Harada disease can help distinguish between acute and chronic phases of this disease. ICGA can also be used to monitor if steroid treatment is effective.[26][27]

Birdshot Chorioretinopathy

Differences (e.g. dark hyperfluorescent dots persist throughout the late phases of ICGA in the chronic form of the disease, but not in the active form) in ICGA imaging in the intermediate phase and late phase of birdshot chorioretinopathy can help to monitor treatment effects by visualizing the presence and resolution of active disease.[28]

Sarcoidosis

Early Phase ICGA: Patient with Central Serous Chorioretinopathy, image on left is early phase fluorescein angiography and image on the right is early phase indocyanine angiography for comparison. University of Minnesota Ophthalmology, 2023 - Courtesy of Hossein Nazari, MD, PhD

ICGA can reveal choroidal involvement and help with disease classification for monitoring sarcoidosis.[29][30]

Infections

While posterior inflammation involving the choroid could be seen in many infectious processes, it does not help with the diagnosis or management of many of the conditions.[8]

Other

Serpiginous Choroidopathy

ICGA can allow for clearer differentiation between active and healed lesions.[31][32]

Fundus Flavimaculatus

ICGA commonly shows hyperfluorescent curvilinear areas forming a reticular pattern in this dystrophy, therefore ICGA could be useful in making a discrepancy between typical and atypical flavimaculatus.[8][33][34]

Trauma

Middle Phase ICGA: Same patient as above with Central Serous Chorioretinopathy, image on left is middle phase fluorescein angiography and image on the right is middle phase indocyanine angiography for comparison. University of Minnesota Ophthalmology, 2023 - Courtesy of Hossein Nazari, MD, PhD

ICGA can reveal choroidal involvement as with ocular traumatic choroidopathy, choroidal rupture, and traumatic ocular hypotony.[35][36] [37][38]

Procedure

ICG is injected at a loading dose of 25 mg either immediately after fluorescein injection or as a mixture of both fluorescein and ICG. There are three temporal phases for ICG imaging, similar to fluorescein angiography.[39][40] The three phases are:

Early phase - 1 minute after injecting the eye, this is when larger choroidal arteries and veins are highlighted, as the dye is still making its way through the choriocapillaris.[39]

Middle phase - 5 to 15 minutes after injection, at this time the choroidal vasculature is now more diffuse and less distinct.[39]

Late Phase ICGA: Same patient with Central Serous Chorioretinopathy, image on left is late phase fluorescein angiography and image on the right is late phase indocyanine angiography for comparison. University of Minnesota Ophthalmology, 2023 - Courtesy of Hossein Nazari, MD, PhD

Late phase - >15 minutes after dye injection, during this phase a hyperfluorescent lesion is more visible against the slowly fading background.[39]

Safety

An editorial described that there were four reports of patients who have experienced an adverse reaction out of a total of 240,000 indocyanine intravenous injections.[40][41] One patient had urticaria and then three with anaphylactic reactions with one resulting in death. Another study looked at 1923 patients with ICG angiograms and only one had a severe adverse reaction (a decrease in blood pressure without anaphylaxis).[40][42]

Absolute contraindications

1. Prior allergic reaction to ICG

2. Iodine allergy (ICG is dissolved in an aqueous sodium iodide solvent).[39]

Relative contraindications

1. End stage renal disease

2. Liver disease

3. Pregnancy (Category C)[40]

Summary

Overall, ICGA is a safe and important imaging modality that differs from fluorescein angiography in that its properties allow better view of the choroidal vasculature and related pathologies. Although no longer used as often in cases of AMD, ICGA is still particularly helpful in guiding treatment in PCV and CSC and for the diagnosis of choroidal hemangiomas.

References

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  2. Kogure K, David NJ, Yamanouchi U, Chromokos E. Infrared absorption angiography of the fundus circulation. Arch Ophthalmol 1970; 83: 209-14.
  3. Hayashi K, Hasegawa Y, Tokoro T. Indocyanine green angiography of central serous chorioretinopathy. Int Ophthalmol 1986; 9: 37-41.
  4. Scheider A, Schroedel C. High resolution indocyanine green angiography with a scanning laser ophthalmoscope. Am J Ophthalmol 1989; 108: 458-9.
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  37. Kohno T, Miki T, Shiraki K, Kano K, Hirabayashi-Matsushita M. Indocyanine green angiographic features of choroidal rupture and choroidal vascular injury after contusion ocular injury. Am J Ophthalmol 2000;129:38–46.
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