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Is the Dye Used in Fluorescein and ICG Angiography Safe?

How Safe These Dye Tests Are, in Short

How Safe These Dye Tests Are, in Short

For most people these are routine office tests, and the common effects are temporary and predictable. Neither dye is an x-ray contrast agent, and neither contains radiation.

In a survey covering 221,781 fluorescein angiograms, a moderate reaction was reported about once in every 63 tests, a severe reaction about once in every 1,900, and a death about once in every 222,000.1 Moderate in that survey means a reaction that needed medical treatment and then resolved, which is a much smaller event than the word suggests. These figures come from a single large survey rather than a trial, so treat them as orders of magnitude rather than precise rates. The serious end of the range is genuinely rare, and it is also the reason your clinic keeps emergency drugs in the room.

The common effects are cosmetic and short lived. The most common reactions to fluorescein are skin discoloration, urine discoloration, nausea, vomiting and stomach upset; the skin usually returns to normal in 6 to 12 hours and the urine in 24 to 36 hours.2

Serious allergic reactions sit at the other end and are uncommon. They are also the reason the injection is given where staff and equipment are ready, rather than sent home with you in a tablet.

A few histories change the plan, and none of them are things staff can see. Tell the team before the needle goes in if any of these apply to you.

  • Any previous reaction to either dye, however mild it seemed.
  • Asthma, or a history of serious allergy of any kind.
  • Allergy to iodine or iodides, which matters for the green dye.
  • Pregnancy, or the chance of it, and breastfeeding.
  • Kidney or liver disease, or dialysis.

Most of these do not cancel the test. They change how the decision is made, and sometimes which dye is used. An iodine or iodide allergy is the one that can rule out the standard green dye, and even then there are routes around it, so it is information that changes the plan rather than ends it.

What the Two Dyes Are and Why They Differ

Fluorescein is a yellow dye that glows under blue light and maps the retinal circulation, the vessel layer at the surface of the retina. It is injected into an arm vein and photographed as it fills the vessels.

It is contraindicated only in people with known hypersensitivity to fluorescein sodium or another ingredient in the product, and caution is advised in anyone with a history of allergy or bronchial asthma.2 It is not iodine based, so an iodine allergy is not the issue with this dye.

The green dye answers a different question, which is why it is sometimes added rather than substituted. Indocyanine green binds to circulating proteins heavily, about 95 of every 100 molecules against about 80 of every 100 for fluorescein, so it leaks less from vessels; and it works in infrared light, which lets the camera see the choroid, the deeper vessel layer, through the pigment layer of the retina and even through overlying bleeding.3

It is most useful in polypoidal choroidal vasculopathy, central serous chorioretinopathy, choroidal hemangioma, and inflammatory conditions such as the white dot syndromes and Vogt-Koyanagi-Harada disease.3

This is the point where advice online diverges, so here is both halves of it. The manufacturer's label states that indocyanine green contains sodium iodide and should be used with caution in people with a history of allergy to iodides, because of the risk of anaphylaxis, and that deaths from anaphylaxis have been reported after it was given during cardiac catheterization.4

A specialist reference lists two absolute contraindications to the green dye: a previous allergic reaction to indocyanine green, and an iodine or iodide allergy. The same reference adds that a true allergic reaction to indocyanine green on iodine grounds is not considered biologically plausible, that it nonetheless advises avoiding the test where there is a history of iodine allergy, and that an iodine-free preparation of the dye is available for people who have an absolute contraindication to the standard one.3 The label separately notes that anaphylactic and hive-type reactions have occurred in people with and without a history of iodide allergy.4

So the reasoning behind the iodine warning is debated while the caution itself still stands. Report an iodine or iodide allergy before anything is prepared. That usually means the yellow dye alone, the iodine-free preparation, or a scan instead, rather than no imaging at all.

Getting Ready for the Test

Bring a written list rather than trusting recall at the desk. Include every drug allergy and what actually happened, since hives and a breathing problem are treated very differently in the planning.

List your medicines too, including eye drops and supplements, and let the team review them against the plan for the day. Mention any reaction to a previous dye test even if it was years ago and mild.

Most clinics let you eat and drink normally, and some suggest a light meal to reduce nausea. Follow the instruction your own clinic gives, because practices differ.

A history of cardiovascular or renal disease is not a contraindication to fluorescein angiography, and the test is not ruled out even in people on dialysis, because the dye is removed by hemodialysis.5 For the green dye, end-stage kidney disease and liver disease are listed as relative contraindications, which means the decision is weighed rather than automatic.3

Arrange for someone to drive you. Your pupils will be dilated for hours, which blurs near vision and makes daylight uncomfortable, and that alone rules out driving yourself.

Bring sunglasses, your glasses, and your medicine list. Wear a top with sleeves that push up easily, and if you know one arm gives better vein access, say so before they start.

What Happens During the Test

The whole visit is shorter than most people expect. The test is usually done in the ophthalmologist's office and often takes less than 30 minutes: drops dilate the pupils, the dye is injected into a vein in the arm, and it takes about 10 to 15 seconds to travel through the body before the camera starts.6

Nausea is the usual first-minute experience with fluorescein, and it is transient. Tell the photographer if you feel sick rather than trying to hold still through it, because they can pause.

You rest your chin on a support and look where you are told while the camera fires. The flash is bright and repeated, and your vision may look dark or tinted for a few minutes afterwards.

Early pictures come fast, then the team waits and takes late frames several minutes later. That gap is part of the test, not a delay, because leakage that appears late is often the finding that matters.

Knowing this in advance makes the rare event less frightening. The label instructs that an emergency tray should always be available, and reviews state that standard equipment to manage anaphylaxis should always be ready; an intradermal skin test may be performed beforehand where an allergy is suspected.25

Staff watch you during and after the injection for that reason. If you feel your throat tighten, your chest wheeze, or your skin come up in weals, say so immediately rather than waiting to see whether it settles.

The Hours After the Test

This is the effect that alarms people most and matters least. After fluorescein, the skin takes on a temporary yellowish tinge and the urine turns bright yellow; the skin usually clears in 6 to 12 hours and the urine in 24 to 36 hours as the dye is passed out by the kidneys.25

The green dye is not associated with this effect in any way you would notice. Drinking normally is sensible, and there is no need to force fluids.

Dilating drops leave vision blurry and eyes light sensitive for several hours.6 Plan a quiet afternoon rather than a return to work that needs sharp near vision.

Screens are uncomfortable rather than harmful, and larger text helps. Sunglasses outdoors are worth having even on a dull day.

Neither dye is used casually here, and both have a documented position. A clinical review of the test lists pregnancy, particularly the first trimester, and breastfeeding as relative contraindications to fluorescein, and reports that the dye can be found in breast milk for up to about 3 days after the injection.5 The green dye's label states it should be given to a pregnant woman only if clearly indicated.4

Relative means weighed, not banned. Tell your team, and ask what they would do differently, including whether the test can wait or whether expressing and discarding milk for a period is advised in your case.

What the Pictures Show, and What They Cannot

An optical coherence scan shows structure, meaning where fluid and layers sit. The dye study shows flow and leakage over time, which is a different question.

That is why both are often done at the same visit. A leak too small to change the anatomy yet can be the thing that decides whether treatment starts now.

It does not measure your vision, and it does not forecast it. It also cannot decide treatment by itself, since the pictures are read alongside your symptoms, your acuity and your scans.

A dramatic looking picture does not always mean a serious problem, and a quiet one does not always mean nothing needs doing. Ask your specialist what the images changed in the plan.

Many retina clinics review the images the same day, because the point of the test is often to decide on treatment during that visit. Others read them later and call you.

Ask before you leave which of those applies, and who will contact you. Ask for a copy or a look at the images too. Most retina specialists are glad to show you the leak they are treating.

The Real Risks, Put in Proportion

The numbers are worth seeing rather than imagining. In the survey of 221,781 angiograms, moderate reactions occurred about once in every 63 tests, severe reactions about once in every 1,900, and death about once in every 222,000; the overall reported incidence of death is about 1 in 222,000.15

Those come from survey and review data rather than randomized trials, so the exact figures carry uncertainty. Nausea, the most frequent effect by far, accounts for most of the moderate category.

The green dye's reported rates come from a smaller body of evidence. In a prospective series of 1,923 injections in 1,226 patients, mild reactions occurred in about 15 of every 10,000 injections, moderate reactions in about 20 of every 10,000, and severe reactions in about 5 of every 10,000.73 That is one series, so read it as the best available estimate rather than a settled figure.

Anaphylactic and hive-type reactions have been reported in people with and without any history of iodide allergy.4 In practice that means no history makes a reaction impossible, which is again why the injection happens in a staffed room.

Most people get nothing worse than a bruise. Fluorescein leaking out of the vein at the injection site can cause severe local tissue damage because of the high pH of the solution, with intense pain at the site and a dull aching pain in the arm.2

This is why you are asked to keep the arm still and to speak up at the first sting. Caught in the first seconds, the injection is stopped and the consequences are usually minor.

When to Call, and What to Watch For

These are the changes that need action the same day, not a wait to see. Tell the staff at once if you are still in the clinic, and call 911 or go to an emergency room if you are not.

  • Trouble breathing, wheezing, or a tight throat.
  • Swelling of the lips, tongue or face.
  • A widespread rash, or hives spreading quickly.
  • Faintness, a racing heart, or collapse.
  • Chest pain.

Reactions like these are uncommon, and they are treatable when they are treated fast. That combination is exactly why the test is done in a clinic rather than anywhere else.

Some tenderness and a bruise where the needle went in are ordinary and settle over a few days. Growing pain is not.

Call the clinic the same day for increasing pain, swelling, hardness, blistering or spreading redness at the injection site. Those are the signs of dye that leaked into the tissue rather than a normal bruise.

Contact the clinic if a rash or itching appears hours later, if nausea and vomiting persist beyond the day, or if urine is still deeply discolored after about two days.

Separately, contact your eye team for any new drop in vision, new floaters or flashes, or a curtain across your sight. Those relate to the retinal condition being investigated rather than to the dye, and they need the same-day attention they always would.

Common Questions About the Angiography Dyes

No to both. Fluorescein and indocyanine green are fluorescent dyes photographed with a camera, not x-ray contrast agents, and no radiation is involved. That also means the iodinated contrast reactions people remember from CT scans are a separate issue. The green dye does contain sodium iodide, which is worth reporting if you have an iodide allergy, but the two situations are not the same.

Shellfish allergy is an allergy to proteins in shellfish, which is not the same thing as an allergy to iodides. Report it anyway, along with every other allergy, because a history of significant allergy or asthma is itself a reason for extra caution with either dye, and reactions have been reported in people with and without any iodide allergy. Your team would rather have the information and decide it is irrelevant than not have it.

Yes, and the test is often more important in that situation rather than less, because the working eye is the one being protected. The dye is given into a vein and affects both eyes equally, so the test itself does not put the better eye at extra risk. Discuss the dilating drops and your transport home, since blurred vision in a single working eye is more disabling for the afternoon.

The needle stings like any blood draw, and the dye itself is not painful when it goes in correctly. A warm flush and brief nausea are common in the first minute with fluorescein. The bright repeated flashes are uncomfortable rather than painful. Sharp or increasing pain in the arm during the injection is the exception, and it should be reported immediately rather than tolerated.

You can always decline, and it is worth asking what the alternative costs you in information. Optical coherence scans, including the type that maps blood flow without dye, answer some of the same questions and not others, particularly about leakage over time. Ask your specialist what they would miss without the dye and how that would change your treatment, then decide with that in front of you.

There is no fixed limit, and people with active retinal disease may have several over the years. Fluorescein is passed out in the urine over about 24 to 36 hours5, so repeated tests do not stack up a dose the way repeated x-rays would; each one carries its own small risk instead. What usually limits repeats is whether the pictures would change the plan, so it is fair to ask what this one is expected to settle.

More Questions People Ask Before the Injection

Not on your own. There is no routine instruction to stop medicines before either dye test, and stopping something like a blood pressure drug or a blood thinner carries its own risk. Bring the full list, including eye drops and supplements, and let the team review it. Anything that matters becomes a note in your record rather than a reason to skip a dose.

Say so before anything is prepared, because it changes the planning rather than automatically cancelling the test. Options include pretreatment with antihistamines or steroids, switching which dye is used, or deciding a different test would answer the question. A previous severe reaction to a dye is a much stronger reason to avoid that same dye, and your team needs to know which of the two it was.

Age alone is not a barrier, and many people having these tests are in their seventies and eighties. What matters more is heart and lung health, allergy history, and mobility for the camera positioning. Tell the clinic if standing, transferring or holding a position is hard, since that is a practical problem they can solve in advance rather than on the day.

  • Which dye am I having, and what question is it meant to answer?
  • Does anything in my allergy, asthma, kidney or liver history change the plan?
  • Am I having both dyes at the same visit, and if so, why?
  • What will you do differently if I have had a reaction before?
  • Who reviews the pictures, and when will I hear the result?
  • What symptoms after I get home should make me call you the same day?