A Contrastive View Of 
Your Patient’s Problems

Fluorescein angiography can aid your diagnosis of various retinal and choroidal anomalies. Here’s a look at how this test works and how to interpret the results.

• Indocyanine green (ICG) angiography
• Indications for Angiography
• Suggested Picture Frames for FA

Then there’s the elderly patient with AMD. You can’t tell from the fundus photos if it’s the dry or wet form, and whether you should monitor the patient with an Amsler grid or refer the patient for immediate treatment. Again, fluorescein angiography can provide the answer.

These are just two examples of how fluorescein angiography can aid your diagnosis, help you determine the treatment plan and, perhaps, save the patient’s vision. These are good reminders that we should not overlook fluorescein angiography as a valuable diagnostic tool. 

Whether you refer patients to a retinal specialist for fluorescein angiography or are able do it yourself, you should understand this procedure. That way, you can educate your patients about the procedure, better understand the reports you receive and even be prepared for any future changes in scope-of-practice laws that might allow more optometrists to perform fluorescein angiography. 

Investigative Tool

Sodium fluorescein is a water-soluble, yellow-red dye that emits yellow-green fluorescence. When injected intravenously, it leaks from all vessels except those in the retina and central nervous system. Some 75-80% of the dye binds to plasma proteins such as albumin, while the remainder does not bind to any substances. This latter portion of fluorescein causes fluorescence during angiography.¹

Anatomical differences in various retinal tissues confine fluorescein dye within some compartments yet allow it to freely diffuse out of others. This difference in permeability allows for early detection and treatment of abnormalities within the sensory retina, choroid, RPE, sclera and optic nerve (see “Indications for Angiography”).²

Fluorescein angiography is indicated for proper diagnosis, to guide treatment or as a baseline.³ Many doctors use fluorescein angiography to identify areas that might benefit from laser treatment. 

Contraindications and Risks

Although fluorescein angiography is a safe diagnostic procedure, it does have a low rate of adverse reactions.⁵ The most common of these, which happens in nearly all patients, is yellowing of the skin, conjunctiva and/or urine. This temporary discoloration of the skin and conjunctiva usually lasts 6-12 hours, while the yellowing of urine can persist for 24-36 hours.⁶

Mild, transient reactions such as nausea, pruritus and vomiting occur in 3-15% of patients, while reactions such as urticaria, syncope and local tissue necrosis occur in 1-2% of patients.⁷ Serious reactions such as seizures, anaphylaxis and myocardial infarction occur in fewer than 0.05% of patients.⁷ The incidence of death following fluorescein angiography is extremely low—roughly 1 in 220,000.⁷

Orally administered fluorescein angiography is sometimes a viable alternative to the I.V. form, especially in patients who cannot tolerate injections, have inaccessible veins or have cardiovascular problems that contraindicate I.V. procedures.¹ T. Hara and M. Inami studied the efficacy and safety of oral fluorescein angiography and found that no patients suffered severe side effects such as anaphylaxis, myocardial infarction, or death, and that only 1.7% of patients experienced mild side effects such as itching or nausea.⁸

Technique

1. Obtain consent. Explain to the patient that you need to take photos of the back of the eye. Make sure the patient understands that this is not an X-ray, and that he or she will receive the fluorescein injection in the arm. (Many patients fear the injection will be in their eyes). Briefly explain the possible adverse reactions including both the mild and rare ones. 

2. Photograph the patient’s name, date and chart number. Enter this data by using the high-plus lens on the camera and a red-free filter.

3. Check for pseudofluorescence. Do this by removing the high-plus lens, and view the retina with both barrier and exciter filters in place. Mismatched filters will cause this, but it’s rare unless you’re using very old equipment. 

4. Take a stereo pair of red-free photos of each eye. These increase fundus contrast to help identify landmarks. The red-free photos also help identify areas of autofluorescence, which results from tissues that spontaneously emit light in the yellow-green spectrum when blue light illuminates them.⁹ Ocular conditions that demonstrate autofluorescence include astrocytic hamartomas, Best’s vitelliform lesions, lipofuscin deposits, flecks associated with fundus flavimaculatus and optic nerve head drusen.¹⁰

5. Using a butterfly-type needle in a bolus fashion, inject 5ml of 10% sodium fluorescein at a rate of 1ml per second.⁷ A faster rate causes increased cases of nausea and vomiting. A slower rate leads to poor early photos.

Since the first few seconds of the angiogram are often clinically significant, most practitioners perform the injection into the antecubital vein while the patient is seated at the fundus camera. If this vein is not usable, veins in the back of the hand or those on the thumb side of the wrist are viable alternatives.

6. Start the camera timer as you begin the injection. Begin photography roughly 8-10 seconds after injection, when the fluorescein reaches the eye. (This time varies; it is a function of the speed of injection, the patient’s age and vascular system status.⁷) 

After the first photograph, take photos every 1-2 seconds for the initial 25-30 seconds (total 10-12 photos), then every 10-20 seconds for the next 1-2 minutes (6-10 photos), and then late angiography photos at 5-10 minutes.¹ Also photograph the area of interest and the entire posterior pole of both eyes during these late shots (see “Suggested Picture Frames for FA”).

These are only general guidelines. The exact sequencing routine often depends on the disease you suspect.

One additional note: You can document fundus images with black-and-white film or electronically. While film offers higher resolution, digital angiography lets you view the images instantaneously, edit the angiogram while it’s in progress, and immediately interpret the results and begin treatment.⁷ You can also manipulate the images electronically to highlight subtle details that can help you diagnose ocular pathology. Many doctors place monitors adjacent to the laser delivery system so they can use the angiography results to guide photo- coagulation treatment.³

Five Stages

However, fluorescein does not leak out of healthy retinal capillaries because of tightly bound endothelial cells, nor does it diffuse through the RPE. The RPE acts to limit the visualized choroidal flush depending on the level of melanin.¹
The five phases are: 
Pre-arterial (choroidal flush). The fluorescein dye travels to the choroid via the short posterior ciliary arteries. At first, this pattern is patchy and lobular. The intensity of the choroidal flush significantly decreases in the macular area due to the presence of melanin and fluorescent-absorbing xanthophyll pigment.¹

• Arterial. Fluorescein reaches the retina via the retinal arteriole. This phase of the study ends within seconds, when the entire arterial side of the retinal vasculature fills with the fluorescein dye.
• Arteriovenous. The dye spreads to the post-arteriolar, retinal and pre-venular capillaries. As the retinal veins begin to fill, the fluorescein stays against the vessel walls due to the faster flow of red blood cells in the central lumen. These columns become wider during the next 5-15 seconds. The arteriovenous phase ends when the entire lumen fills with dye and loses the laminar appearance.³
• Venous. There is equal intensity of fluorescein in both the arterioles and venules. 
• Late venous. This phase rapidly follows the venous phase. The concentration and intensity of fluorescein is now greater in the venules than in the arterioles

Shortly afterward, the dye begins to recirculate. This shows up as a continual reduction in fluorescence as the dye leaves the bloodstream via the kidneys.³

The late phase generally occurs about 5-10 minutes after injection. By now, the arterioles and venules are virtually devoid of fluorescein, and choroidal flush is minimal. 

The optic nerve is one of the few normal structures that hyperfluoresces during the late phase. Photographs taken at this point help identify fluorescein leakage and accumulation of intraretinal dye. Within 30 minutes, virtually all the injected fluorescein is gone from ocular circulation.⁷

Interpretation

Hypofluorescence has two basic causes: 
Blockage defects. These occur when an overlying opaque substance shields the fluorescence beneath it. Some examples: intrareti- nal and vitreal hemorrhages, intraretinal inflammatory cells, melanin, exudates, lipofuscin, fibrin, glial tissue, media opacities, congenital hypertrophy of the retinal pigment epithelium (CHRPE), retinal hyperplasia, or any condition that causes retinal hyperpigmentation.¹¹
Vascular filling defects. This signals vascular occlusion, retinal capillary nonperfusion, emboli or arteriosclerosis. 

Sectoral or complete hypofluorescence of the optic nerve head can be seen in ischemic optic neuropathy, optic nerve head colobomas, optic pits and sometimes in glaucomatous cupping.¹¹

Hyperfluorescence also falls into two categories: 

• Areas with increased intensity of normally present fluorescence. This results from the absence of overlying optical barriers. One of the most common causes of increased intensity of normal fluorescence is the absence of the usual “filtering” pigment from the RPE, which some refer to as a window defect.³ Other conditions that cause hyperfluorescence include geographic atrophy of macular degeneration, drusen, chorioretinal scars and full thickness retinal breaks.¹
• Areas that normally do not fluoresce. Hyperfluorescence that occurs due to retinal capillary leakage becomes larger and more intense in the late phases of angiog- raphy. Leakage can come from newly formed vessels, which are more fragile than normal ones, or from once-normal vessels that have become inadequate. 

Also, in cystoid macular edema, foveal capillaries become leaky, causing fluid to accumulate in cystic spaces of the outer plexiform layer (Henle’s layer). This shows up as a classic petaloid pattern of hyperfluorescence.³

Fluorescein angiography is a valuable diagnostic procedure that helps assess functioning in the back of the eye. By knowing when to order it, how it’s performed and how to interpret the results, we can educate our patients about the procedure. 

And, the next time that patient with diabetic retinopathy, AMD or another retinal anomaly presents to your practice, you might not find yourself with the same diagnostic dilemma.