Indocyanine Green Angiography

Indocyanine green angiography is an imaging test of the choroidal circulation, the layer of vessels under the retina that feeds the outer retina. Indocyanine green dye is injected into a vein, and a camera sensitive to infrared light records the dye as it passes through the eye.

Infrared light passes through the retinal pigment epithelium, blood, fluid and mild haze better than the blue light used in fluorescein angiography, and the dye is bound to plasma proteins, so it leaks slowly from the choroidal vessels. These features give a clear view of the choroid.

The dye reaches the eye in about 10 to 20 seconds. Images are taken in the early phase (up to about 60 seconds), which shows filling of the choroidal arteries and veins, the middle phase (about 5 to 15 minutes), and the late phase (up to 30 to 45 minutes), which shows staining and washout.

A confocal scanning laser camera is the usual instrument, and it can be combined with fluorescein angiography and optical coherence tomography in one session. The test takes 30 to 45 minutes in total, after the pupils are dilated.

The test is an addition to, and not a replacement for, fluorescein angiography. It is most useful when the cause of fluid or haemorrhage under the retina is unclear.

It finds polypoidal choroidal vasculopathy in up to about 20 to 50% of patients of Asian and African ancestry with presumed neovascular macular degeneration, and it detects retinal angiomatous proliferation and occult neovascular membranes that fluorescein misses. Serious reactions are rare, and less common than with fluorescein (under about 1 in 10,000).

Indications.

• Polypoidal choroidal vasculopathy: polyps and the branching vascular network, and response to treatment.
• Age related macular degeneration with occult or unclear choroidal neovascularisation, or poor response to treatment.
• Central serous chorioretinopathy: choroidal hyperpermeability and dilated vessels, particularly in chronic or atypical cases, and before photodynamic therapy.
• Posterior uveitis and choroiditis: birdshot chorioretinopathy, multifocal choroiditis, sarcoidosis, tuberculosis, and Vogt-Koyanagi-Harada disease.
• Choroidal tumours and masses (haemangioma, melanoma, metastasis), and choroidal vascular abnormalities.
• Pathological myopia with choroidal neovascularisation, angioid streaks, and idiopathic neovascular membranes in the young.
• Unexplained visual loss, with subretinal fluid or haemorrhage of unknown cause.
• Planning of laser or photodynamic treatment, and follow up after treatment.

Not indicated when fluorescein angiography and optical coherence tomography angiography have given the diagnosis.

Contraindications and precautions.

• Previous allergic reaction to indocyanine green, or to iodide: the dye contains sodium iodide in many preparations, so a history of iodide allergy is a relative contraindication, and a preparation without iodide is used where available.
• Pregnancy: avoided unless the benefit is clear, since safety data are limited.
• Severe liver disease: the liver clears the dye, and the clearance is slow.
• Asthma, severe allergy, or earlier reaction to other contrast agents: caution, with resuscitation equipment ready.
• Renal impairment is not a contraindication, since the dye is cleared by the liver.
• Breastfeeding: advice is to avoid or interrupt breastfeeding for a short period, depending on local practice.
• Patients with poor venous access, or who cannot sit at the camera.
• Thyroid function tests and some radioiodine studies are affected by iodide in the dye, and the patient is told.

Preparation and technique.

The pupils are dilated, consent is obtained, and the patient's history of allergy, liver disease, pregnancy and medicines is checked. A cannula is placed in an antecubital vein, and baseline infrared images are taken. The dye is injected as a bolus, and flushed with saline, and the timer is started.

Images begin within seconds, with frames about every second in the early phase, then at intervals at 3 to 5 minutes, 10 minutes, 20 minutes and, when needed, 30 to 45 minutes. Both eyes can be imaged when needed. The patient is observed for about 30 minutes afterwards. Resuscitation equipment is kept ready.

Normal appearances.

The large choroidal arteries fill first, then the choroidal veins, and the retinal vessels are seen as dark or pale outlines against the choroid. The choroidal vessels are clear in the early and middle phases, and in late images the dye fades evenly from the vessels, leaving a uniform, mildly hazy background. There is no focal leakage, hot spot, or plaque.

Interpretation.

• Polypoidal choroidal vasculopathy: early focal hyperfluorescent nodules (polyps) at the end of a branching vascular network, which leak or wash out in the late phase. A late hyperfluorescent halo around the polyp (washout) is typical.
• Neovascular macular degeneration with occult membranes: a late hyperfluorescent plaque or a focal hot spot, with the lesion shown more clearly than on fluorescein.
• Retinal angiomatous proliferation: a hot spot at the site of a retinal choroidal anastomosis, with an intraretinal component.
• Central serous chorioretinopathy: dilated choroidal veins, patchy hypofluorescence in the early phase, and multifocal hyperfluorescence in the middle phase from choroidal hyperpermeability.
• Choroiditis and inflammation: hypofluorescent dark spots in the middle and late phase (from non-perfusion or blockage by inflammatory lesions), seen in more places than are visible on examination. Birdshot lesions and sarcoid granulomas show as dark dots.
• Choroidal tumours: haemangioma shows rapid filling with late washout, melanoma shows double circulation, and metastasis shows hypofluorescence.
• Choroidal neovascularisation in pathological myopia and angioid streaks: focal hyperfluorescence at the edge of lacquer cracks or streaks.
• Results are read together with fluorescein angiography, colour images, and optical coherence tomography.

Critical values and findings needing immediate action.

• Anaphylaxis (hypotension, wheeze, laryngeal oedema, urticaria): stop the injection, call for help, and give adrenaline, oxygen, fluids and airway support.
• Active choroidal neovascularisation or polypoidal lesions with haemorrhage: urgent referral for treatment, within days.
• Tumour features (a mass with abnormal vessels): urgent referral to an ocular oncology service.
• Findings of active posterior inflammation with visual loss: urgent specialist review for treatment and investigation of systemic causes.
• Extravasation with pain: stop the injection, elevate the arm, and observe.

Limitations and artefacts.

• The image of the retinal vessels and fine detail of the retinal layers is poorer than with fluorescein angiography, and it does not show retinal oedema well. The test does not show the retinal layers, which optical coherence tomography does.
• The late phase has pseudo hyperfluorescence from dye in dilated choroidal vessels, and staining of drusen and scars can mimic leakage.
• Media opacities, small pupils, poor fixation, a slow or incomplete injection and wrong timing of images reduce quality.
• Dye extravasation at the injection site reduces the quantity reaching the eye.
• Subretinal blood and dense pigment block the view, although much less than with fluorescein.
• Interpretation needs experience, and many findings are not specific to a single disease.
• Optical coherence tomography angiography now shows many choroidal and neovascular features without dye, and in some centres replaces the test.

Complications.

• Nausea and vomiting (about 1 to 3%), usually mild.
• Mild itch, hives, or local pain at the injection site (about 1 to 2%), and vasovagal reactions.
• Severe allergic reactions, bronchospasm, hypotension and anaphylaxis (very rare, about 1 in 10,000 to 1 in 40,000).
• Extravasation with local tissue irritation (rare).
• A false result in thyroid uptake studies and some other tests for a short time after the injection.

Special groups.

• Patients of Asian and African ancestry with macular degeneration: a higher proportion have polypoidal disease, so the test has a higher yield.
• Patients with central serous chorioretinopathy: useful before photodynamic therapy.
• Pregnancy: avoided, and non-contrast options such as optical coherence tomography and optical coherence tomography angiography are used.
• Patients with iodide allergy: an iodide free preparation, or other imaging.
• Patients with liver disease: slow clearance, with caution.
• Children: rarely used, with sedation or anaesthesia in selected cases.
• Regions: the test needs a scanning laser camera and trained staff, and is available in few centres. Polypoidal disease and chronic central serous chorioretinopathy are common in many regions, and are often treated without it using clinical findings, optical coherence tomography and fluorescein angiography. Infective and inflammatory choroiditis (tuberculosis, syphilis, toxoplasmosis) are important causes of visual loss.

Follow up tests.

• Fluorescein angiography and optical coherence tomography angiography.
• Optical coherence tomography for fluid, thickness and structure.
• Fundus autofluorescence and colour fundus photography.
• Ocular ultrasound for tumours and thick choroids.
• Blood tests and chest imaging for systemic causes of choroiditis (tuberculosis, sarcoidosis, syphilis, autoimmune screen).
• Repeat imaging after treatment to check for polyp closure and activity.
• Referral to a retina or ocular oncology service.