Fluorescein Angiography (FA)

Key points at a glance

Key Points of This Test

• Fluorescein angiography (FA) is a test that dynamically images retinal and choroidal circulation by intravenous administration of sodium fluorescein.
• It is essential for diagnosis and treatment decisions in a wide range of fundus diseases, including diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration.
• It provides dynamic information such as fluorescein leakage due to breakdown of the blood-retinal barrier and filling defects due to vascular occlusion, which cannot be detected by OCT angiography (OCTA).
• The overall incidence of adverse reactions is 1.1–11.2%, most of which are mild, such as nausea and skin yellowing, and resolve spontaneously ⁴⁾.
• Severe anaphylaxis and death are extremely rare (death: approximately 1:200,000), but emergency response measures must be prepared before the test ³⁾.
• Administration to pregnant or breastfeeding women is generally contraindicated, and OCTA is recommended as an alternative ²⁾.
• OCTA can noninvasively visualize capillary-level vascular structures, but its ability to detect leakage is not a substitute for FA; the two are used complementarily.

1. Overview and Principles

Fluorescein angiography (FA) is a test in which sodium fluorescein, a fluorescent dye, is administered intravenously, and the fundus is photographed with a fundus camera equipped with special filters to dynamically image the blood circulation of the retina and choroid. It is excellent for evaluating retinal circulation dynamics and the state of the blood-retinal barrier, and is widely used for diagnosis and treatment planning of fundus diseases. It is useful not only for retinal vascular diseases but also for differentiating uveitis, choroidal tumors, and optic disc diseases.

History

In 1961, Harold R. Novotny and David L. Alvis first reported the original method of FA. Subsequently, from 1967, John Donald McIntyre Gass published systematic FA findings in various fundus diseases, leading to rapid expansion of clinical application.

Basic Principles

Sodium fluorescein emits yellow-green fluorescence (520–530 nm) when irradiated with blue excitation light (wavelength 465–490 nm). Scanning laser ophthalmoscopes (SLO) use a 488 nm blue laser. Sodium fluorescein is a water-soluble dye with a molecular weight of 376 Da, and its protein binding rate after intravenous administration is approximately 70–80%. The remaining approximately 20–30% is free form and emits fluorescence. Under normal blood-retinal barrier conditions, even the free form does not leak out of the vessels. When the barrier is disrupted, the dye leaks out of the vessels and is observed as characteristic hyperfluorescent findings.

The blood-retinal barrier (BRB) consists of two layers. The inner barrier is the tight junctions of retinal vascular endothelial cells, and the outer barrier is the tight junctions of retinal pigment epithelium (RPE) cells. When the BRB is disrupted, fluorescein leakage occurs, serving as a diagnostic indicator for various retinal diseases.

Excitation Light

Blue light with a wavelength of 465–490 nm is irradiated.

SLO uses a 488 nm laser.

An excitation filter cuts off unnecessary wavelengths.

Fluorescence Emission

It emits yellow-green fluorescence with an emission wavelength of 520–530 nm.

Free form (approximately 20–30%) is the main source of fluorescence.

Protein-bound form (approximately 70–80%) is less likely to fluoresce.

Barrier Filter

Only transmits fluorescence above 520 nm.

Blocks excitation light to sharpen the fluorescence image.

Extravasation is evidence of barrier breakdown.

Q When did fluorescein angiography begin?

A

It was first reported by Novotny and Alvis in 1961. After 1967, Gass systematized its application to various fundus diseases, and it became a standard diagnostic test for fundus examination worldwide.

2. Indications

Retinal avascular areas and fluorescein leakage seen on fluorescein angiography

Sun L, et al. ROP-like retinopathy in full/near-term newborns: A etiology, risk factors, clinical and genetic characteristics, prognosis and management. Front Med (Lausanne). 2022. Figure 3. PMCID: PMC9399493. License: CC BY.

Fluorescein angiography (FFA) findings of both eyes (A, B) in a case with FZD4 mutation, showing temporal avascular areas, brush-like peripheral retinal vessels, avascular areas in the peripheral retina, and fluorescein leakage indicated by red arrows. This corresponds to the fluorescein leakage discussed in the section “2. Indications”.

FA is widely used for visualization of the retinal vasculature. The main indications are listed below.

Retinal Diseases

• Diabetic retinopathy: Guidance for treatment of macular edema (CSME) and determination of laser photocoagulation sites, evaluation of unexplained vision loss, identification of neovascularization³⁾
• Retinal vein occlusion: Confirmation of occlusion site, assessment of capillary nonperfusion area, evaluation of macular edema characteristics
• Retinal artery occlusion: Identification of occluded vessels and ischemic area
• Retinal microaneurysm: Confirmation of aneurysm and leakage evaluation
• Macular telangiectasia (MacTel): Extent of telangiectasia and leakage pattern
• Coats disease, FEVR, retinopathy of prematurity (ROP): Evaluation of peripheral vascular abnormalities and neovascularization
• Retinal vasculitis, retinal hemangioma: Vascular wall leakage and inflammatory changes

Chorioretinal and Choroidal Diseases

• Central serous chorioretinopathy (CSC): Identification of leakage point from RPE
• Age-related macular degeneration (AMD): Detection and classification of CNV
• Myopic choroidal neovascularization (CNV), choroidal neovascularization associated with angioid streaks: Presence and extent of leakage
• Uveitis (Vogt-Koyanagi-Harada disease): Evaluation of choroidal vascular disorders and exudative changes

Optic Disc Diseases

• Optic disc vasculitis: Confirmation of leakage from disc vessels
• Anterior ischemic optic neuropathy: Evaluation of disc blood flow impairment

In macular edema following acute retinal necrosis (ARN), FA shows a petaloid leakage pattern, which has been reported to aid in the differential diagnosis of cystoid macular edema (CME) and assessment of treatment efficacy¹⁾.

Retinal vascular occlusion may occur during pregnancy, but from the perspective of placental transfer of FA, OCTA is recommended as an alternative examination²⁾.

3. Imaging Protocol and Procedure

Pre-examination Patient Explanation

Before the examination, explain the following and obtain written consent⁴⁾.

• An intravenous line will be placed, and contrast agent will be administered.
• Immediately after administration is a critical imaging point, and continuous imaging will be performed.
• After the examination, urine may appear yellow for up to the next day.
• Yellowing of the skin may persist for 2 to 3 hours.
• For dialysis patients, the dose should be halved, and dialysis is required after the examination.
• There is approximately a 10% chance of symptoms such as nausea, vomiting, itching, or hives due to the contrast agent.
• In severe cases, anaphylactic shock may occur.

Pre-examination preparation

According to the Japanese Ophthalmological Society’s Fundus Angiography Implementation Standards (Revised Edition), the following procedures are performed⁴⁾.

• Informed consent: Explain intravenously administered contrast agent, risk of side effects, and post-examination changes in writing, and obtain written consent.
• Medical history interview: Check for allergy history, presence of asthma/atopy. Also assess diabetes, hypertension, heart disease, liver/kidney disorders, cerebrovascular abnormalities. Special attention is needed for elderly, children, and pregnant women.
• Blood pressure measurement: Measure blood pressure before and after the examination.
• Intravenous line placement: Secure an intravenous line with an indwelling needle (antecubital vein) or winged needle (dorsal hand vein).
• Pupil dilation: Dilate the pupils sufficiently with mydriatic eye drops.
• Emergency preparedness: Keep the following equipment and medications readily available, and ensure the operator is familiar with the response procedures⁴⁾.
  • Oxygen, Ambu bag (airway management equipment)
  • Epinephrine (adrenaline) 0.3 mg intramuscular injection preparation
  • Ephedrine, dopamine
  • Atropine sulfate
  • Beta-2 agonists (bronchodilators), aminophylline 250 mg
  • Steroids (hydrocortisone, etc.)
  • Antihistamines
  • Lactated Ringer’s solution (fluid replacement)

Patients taking beta-blockers or alpha-blockers have an increased risk of side effects, so this should be identified in advance ⁴⁾. Skin reaction testing has limited utility, and even a negative result cannot completely rule out serious side effects ⁴⁾.

Imaging Procedure

1. Connect a side tube with a three-way stopcock, and attach a syringe containing 5 mL of 10% fluorescein
2. Focus in the same way as for color fundus photography
3. Start the timer and simultaneously inject fluorescein rapidly intravenously
4. Insert the filter and maximize the observation light
5. Begin continuous shooting at a rate of one frame per second shortly before fluorescence appears (reaches the retina 6–8 seconds after injection via the cubital vein, 10–12 seconds via the dorsal hand vein)
6. Take images at high frequency from the arterial phase to the arteriovenous phase
7. Capture the arteriovenous phase of the contralateral eye 50–60 seconds after injection
8. Sequentially photograph from the posterior pole to the periphery
9. Take late-phase images at 5 and 10 minutes after injection

Dosage

Rapidly inject 3–5 mL of 10% fluorescein solution intravenously ⁴⁾. For children, a dose of 0.1 mg/kg is used as a guide, and for patients with renal impairment, the dose should be half or less of the usual amount ⁴⁾.

Q How long does a fluorescein angiography examination take?

A

Continuous imaging is performed for about 1 minute immediately after injection, followed by late-phase images at 5 and 10 minutes. Including the time for pupil dilation, the entire procedure takes about 15 to 20 minutes.

4. Normal Findings and Angiographic Phases

Fluorescein Angiography image

Ioannis Papasavvas; William R Tucker; Alessandro Mantovani; Lorenzo Fabozzi; Carl P Herbort, Jr. Choroidal vasculitis as a biomarker of inflammation of the choroid. Indocyanine Green Angiography (ICGA) spearheading for diagnosis and follow-up, an imaging tutorial. J Ophthalmic Inflamm Infect. 2024 Dec 4; 14:63. Figure 5. PMCID: PMC11618284. License: CC BY.

In MEWDS choriocapillary hypofluorescence is limited to dots isolated mostly non-confluent. The fundus color picture (top left) shows very faint discolorations. The early FA frame (top middle) shows choriocapillaris non-perfusion or perfusion delay (yellow arrows) which is also shown on the early ICGA frame (top right). On the late ICGA frame (bottom left) there are persistent hypofluorescent dots that correspond with certainty to choriocapillaris non-perfusion as they remain until the late angiographic phase. Bottom right, fundus hyper-autofluorescence typical of MEWDS, due to secondary loss of photopigment and/or accumulation of lipofuscin due to RPE dysfunction

FA is observed as multiple phases over time.

• Choroidal phase (early choroidal flush): Filling begins from the short posterior ciliary arteries, appearing 1–2 seconds earlier than the retinal circulation.
• Retinal arterial phase: Appears 1–3 seconds after choroidal filling (11–18 seconds after injection). The normal arm-to-retina circulation time is 10–15 seconds; prolongation suggests ophthalmic artery stenosis (ocular ischemic syndrome) or Takayasu arteritis.
• Capillary phase: The capillary network fills, and the foveal avascular zone (FAZ) has a diameter of approximately 500 μm. The capillary network surrounding the FAZ is visualized.
• Retinal venous phase: Early on, it is observed as laminar flow along the venous wall, becoming uniform fluorescence later. Venous filling is completed.
• Peak phase: Fluorescence intensity reaches its maximum approximately 30 seconds after injection.
• Late phase: Images are taken about 10 minutes after the start of angiography; the recirculation phase occurs at 3–5 minutes, and fluorescence fades by about 10 minutes.
• Normal macula: Background fluorescence is blocked by xanthophyll pigment and RPE pigment epithelial cells, making the FAZ appear dark.

5. Interpretation of Abnormal Findings

FA findings are broadly classified into three categories: hypofluorescence, hyperfluorescence, and vascular morphological abnormalities.

Fluorescence Blockage (Hypofluorescence)

Definition: Hemorrhage, pigmentation, exudates, etc., block background fluorescence.

Features: Well-defined borders, no change in shape over time.

Representative diseases: Subretinal hemorrhage, hard exudates, choroidal nevus.

Filling Defect (Hypofluorescence)

Definition: No or delayed inflow of fluorescent dye due to vascular occlusion.

Features: Capillary non-perfusion areas remain dark throughout the entire course.

Representative diseases: Retinal artery occlusion, avascular areas in diabetic retinopathy.

Fluorescein Leakage (Hyperfluorescence)

Definition: Breakdown of the blood-retinal barrier causes dye to leak out of vessels.

Features: Enlarges over time, borders become indistinct. A petaloid pattern is characteristic of cystoid macular edema ¹⁾.

Representative diseases: Macular edema, CNV, retinal vasculitis.

Transmitted Fluorescence (Hyperfluorescence)

Definition: Choroidal fluorescence visible through a defect in the RPE (window defect).

Features: Does not change shape over time, but may show faint staining in the late phase.

Representative diseases: Geographic atrophy, confluent drusen, macular hole, angioid streaks.

Detailed Classification of Hypofluorescence

Hypofluorescence is further subdivided by cause as follows.

Type of Hypofluorescence	Cause/Mechanism	Representative Diseases
Blockage of Fluorescence	Hemorrhage, exudate, or nevus blocks background fluorescence	Subretinal hemorrhage, hard exudates, choroidal nevus
Filling Defect: Retinochoroidal Vascular Stenosis	Occlusion or stenosis of large vessels	Internal carotid artery occlusion, Takayasu arteritis
Filling defect: retinal vascular occlusion	Arterial/venous occlusion	Retinal artery occlusion (CRAO/BRAO), retinal vein occlusion
Filling defect: capillary occlusion	Peripheral circulatory disorder	Diabetic retinopathy (NPDR), Eales disease
Filling defect: choroidal circulatory disorder	Choroidal blood flow insufficiency	Vogt-Koyanagi-Harada disease, APMPPE, hypertensive choroidopathy
Chorioretinal atrophy	Loss of fluorescence due to tissue atrophy	Macular dystrophy, retinitis pigmentosa, atrophic AMD, pathologic myopia
Optic disc hypofluorescence	Ischemia/infiltration of optic nerve tissue	Ischemic optic neuropathy, melanocytoma

Detailed Classification of Hyperfluorescence

Hyperfluorescence is subdivided by cause as follows.

• Autofluorescence: Fluorescence observed before FA administration. Seen in vitelliform lesions, organized hemorrhage, drusen, optic disc drusen, and astrocytic hamartoma.
• Window defect: Choroidal fluorescence transmitted through RPE defects. Representative diseases: AMD, pathologic myopia, macular hole, angioid streaks.
• Pooling: Fluorescent dye accumulates in tissue spaces and intensifies over time.
  • Cystoid macular edema (CME) → diabetic macular edema, RVO, macular telangiectasia, uveitis, retinitis pigmentosa.
  • Serous retinal detachment (SRD) → central serous chorioretinopathy (CSC), Vogt-Koyanagi-Harada disease.
  • Retinal pigment epithelial detachment (PED) → AMD, CSC.
• Staining: Fluorescence increases while borders remain distinct. Observed in AMD, retinal arteriolar macroaneurysm, drusen, disciform scar, uveitis.
• Leakage: Borders become indistinct and expand over time.
  • Retinal and choroidal neovascularization.
  • Optic disc vascular leakage → papilledema, optic neuritis, ischemic optic neuropathy.

Classification of Vascular Morphological Abnormalities

The following morphological vascular abnormalities are observed.

• Aneurysm: Retinal arterial aneurysm, capillary aneurysm (diabetic retinopathy, RVO, type 1 macular telangiectasia, hypertensive retinopathy).
• Telangiectasia: Coats disease, RVO, diabetic retinopathy
• Retinal neovascularization: Diabetic retinopathy, RVO, Eales disease, Behçet disease, ROP
• Choroidal neovascularization (CNV): AMD, pathologic myopia, angioid streaks, choroidal tumors

Limitations of FA

Choroidal vessels are difficult to evaluate because they are obscured by the RPE. ICG angiography (ICGA) is used complementarily to evaluate type 1 MNV (choroidal neovascularization) with fluorescein leakage.

6. FA Findings in Major Diseases

Diabetic Retinopathy (DR)

Microaneurysms, non-perfusion areas (NPA), and neovascularization are the main findings. FA helps determine the leakage pattern of macular edema (focal/diffuse/cystoid) and provides the basis for deciding laser photocoagulation sites ³⁾. In the late phase, marked leakage from neovascularization is observed. Ultra-widefield FA improves the accuracy of evaluating peripheral NPA.

Age-Related Macular Degeneration (AMD)

FA is essential for assessing CNV activity. Classic CNV (type 2) shows well-defined hyperfluorescence in the early phase and leaks in the late phase. Occult CNV (type 1) is located beneath the RPE and appears as stippled hyperfluorescence or fibrovascular PED in the late phase. Geographic atrophy appears as a window defect throughout the angiogram.

Retinal Vein Occlusion (CRVO/BRVO)

FA is used to evaluate delayed filling, venous dilation and tortuosity, capillary non-perfusion areas, and collateral circulation. An NPA of 10 disc areas or more is considered ischemic and indicates a risk of neovascular glaucoma. It is also important for understanding the leakage pattern of macular edema.

Central Serous Chorioretinopathy (CSC)

Characteristic inkblot or smokestack leakage points are seen at the level of the RPE. Multiple leakage points suggest chronic CSC. FA and ICGA are used together to determine the treatment area for photodynamic therapy (PDT).

Uveitis

In Vogt-Koyanagi-Harada disease, punctate hyperfluorescence due to multifocal choroidal leakage and dye pooling in areas of serous retinal detachment are observed. In Behçet’s disease, vessel wall staining of retinal vasculitis and non-perfusion areas (NPA) are seen. In Eales disease, peripheral NPA and neovascularization are characteristic.

7. Side Effects and Contraindications

Frequency of Side Effects

Data from the Japanese Ophthalmological Society’s Fundus Angiography Implementation Standards (Revised Edition) are shown ⁴⁾.

Side effects occur at the following frequencies according to severity.

Severity	Incidence
All side effects	1.1–11.2%
Mild	1.4–8.1%
Moderate	0.2–1.5%
Severe	0.005–0.48%
Death	0.0005–0.002%

Details of each side effect

Mild (often resolves spontaneously)

• Nausea: Most common, occurring in 3–15%³⁾. Easily induced by rapid intravenous injection.
• Vomiting: Approximately 7%
• Yellowing of skin and itching: Skin yellowing lasts 2–3 hours, urine yellowing lasts 1–2 days.
• Local pain and warmth: Transient symptoms at injection site.

Moderate

• Urticaria: Approximately 0.5%³⁾
• Thrombophlebitis: Possible local necrosis due to extravasation.
• Fever and syncope: Rarely occur.

Severe (extremely rare)

• Anaphylaxis: Mediated by IgE or immune complex mechanisms⁴⁾.
• Bronchospasm and cardiac arrest: Extremely rare.
• Death: 1:200,000 to 1:221,781³⁾

Diagnostic Criteria and Management of Anaphylaxis

The diagnosis of anaphylaxis is made when any of the following three criteria are met⁴⁾.

1. Rapid onset of respiratory or cardiovascular symptoms accompanied by skin/mucosal symptoms (urticaria, flushing, edema)
2. Rapid onset of cardiovascular symptoms (hypotension, altered consciousness) after allergen exposure
3. Rapid onset of two or more of the following after known allergen exposure: skin/mucosal symptoms, respiratory symptoms, gastrointestinal symptoms, or cardiovascular symptoms

Anaphylaxis Management Flowchart:

1. Immediately discontinue contrast agent administration and place the patient in a supine position
2. Administer epinephrine 0.01 mg/kg (adult 0.3–0.5 mg) intramuscularly into the lateral thigh
3. Secure intravenous access and start fluid resuscitation with lactated Ringer’s solution
4. Administer H1 and H2 antihistamines
5. Administer corticosteroids (e.g., hydrocortisone 100–500 mg IV)
6. For refractory cases, use glucagon (in patients taking beta-blockers)
7. Prepare for emergency transport

Even after successful treatment, there is a risk of biphasic anaphylaxis (recurrence within 6–8 hours after symptom resolution), so observation for at least 8 hours is necessary, and hospitalization for 24 hours is recommended⁴⁾.

Differentiation from vasovagal reflex: Vasovagal reflex presents with bradycardia, hypotension, pallor, and cold sweat, but can be differentiated from anaphylaxis by the absence of skin findings (urticaria, flushing). For vasovagal reflex, supine positioning, leg elevation, and fluid resuscitation are effective⁴⁾.

Contraindications and Precautions

• Pregnancy: Fluorescein crosses the placenta, so it is generally contraindicated. Consider OCTA as an alternative²⁾.
• Breastfeeding: Avoid administration because fluorescein is detected in breast milk for 72 hours³⁾.
• Severe renal impairment: Reduce the dose (to less than half the usual dose) due to renal excretion⁴⁾.

Important Precautions for the Examination

• Patients taking beta-blockers or alpha-blockers have an increased risk of adverse effects. Be sure to check before the examination⁴⁾.
• If extravasation of the drug occurs, it may lead to local tissue necrosis. Proper fixation of the indwelling needle and confirmation during injection are important.
• Skin reaction testing has limited utility; a negative result does not completely rule out severe adverse reactions⁴⁾.
• Emergency medications (epinephrine for intramuscular injection, steroids, antihistamines) and equipment should be readily available, and the operator should be familiar with the response procedures.
• Measure blood pressure after the examination as well, and watch for prolonged adverse effects⁴⁾.

Q Is it okay if my urine turns yellow after fluorescein angiography?

A

This is a normal reaction due to fluorescein excretion by the kidneys, and there is no need to worry. Yellowing of the skin resolves in 2–3 hours, and yellow urine resolves by the next day.

Q Can I undergo this examination during pregnancy or breastfeeding?

A

Fluorescein crosses the placenta and is detected in breast milk for 72 hours, so administration is generally avoided in pregnant and breastfeeding women²⁾³⁾. If retinal vascular information is needed, non-invasive OCT angiography (OCTA) is recommended as an alternative²⁾.

8. Comparison with ICGA and OCTA

Pharmacological properties of fluorescein sodium

Fluorescein sodium is a yellow-red water-soluble dye with a molecular weight of 376 Da. When excited at wavelengths of 465–490 nm (488 nm with SLO), it emits yellow-green fluorescence at 520–530 nm. After intravenous administration, approximately 70–80% binds to plasma proteins (mainly albumin), and about 20–30% fluoresces as free form. It is excreted by the kidneys (cleared within 1–2 days), with minimal hepatic metabolism.

Comparison of FA and ICG angiography (ICGA)

Indocyanine green (ICG) angiography is used complementarily with FA. Their characteristics are shown below.

Parameter	FA	ICG angiography
Molecular weight	376 Da	775 Da
Protein binding rate	Approximately 70–80%	Approximately 98%
Main observation target	Retinal vessels	Choroidal vessels
Excitation wavelength	465–490 nm	Approximately 805 nm
Fluorescence wavelength	520–530 nm	Approximately 835 nm (near-infrared)
Excretion route	Kidney	Liver

ICG has a high protein binding rate of 98%, so it hardly leaks out of the choroidal vessels, making it suitable for evaluating choroidal blood flow. ICGA complements FA in the evaluation of polypoidal choroidal vasculopathy (PCV), choroidal hemangioma, and type 1 MNV.

Comparison of FA and OCT angiography (OCTA)

OCTA is a non-invasive test that analyzes the phase information of OCT to visualize the movement of red blood cells. It does not require contrast agents and can separate and depict the retinal vascular plexus into three layers at the capillary level ³⁾. Its usefulness as an alternative to FA in evaluating retinal vessels during pregnancy has been demonstrated ²⁾.

Item	FA	OCTA
Contrast agent	Required	Not required
Invasiveness	Venipuncture and side effects possible	Non-invasive
Dynamic information	Can evaluate leakage and filling delay	Cannot evaluate (structure only)
Depth resolution	Two-dimensional only	Layer-by-layer analysis possible
Imaging range	Wide angle (up to 200°)	Limited (3–12 mm)
Peripheral evaluation	Easy	Difficult

OCTA cannot detect fluorescence leakage outside blood vessels, so FA remains essential for assessing the activity of macular edema, determining CNV activity (presence of leakage), and evaluating vascular wall inflammation in retinal vasculitis. Using both complementarily enables more precise fundus evaluation.

Comparison of imaging devices

The observable field of view and characteristics differ depending on the imaging device used.

Device	Field of view	Main features
Fundus camera	55°	Standard, widely used
SLO/HRA	30–102°	High contrast, confocal
Optos	200°	Ultra-widefield single-shot imaging of periphery

The ultra-widefield imaging device (Optos) can capture the peripheral retina in a single shot, and is useful for evaluating peripheral lesions in diabetic retinopathy and retinal degenerative diseases.

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Latest Research and Future Perspectives

For patients: Please read carefully

The following content is currently at the research stage or under clinical trial, and is not standard treatment available at general hospitals. It is reference information for professionals regarding future medical developments.

Application of Fluorescein Leakage Patterns to Treatment Prediction

In cystoid macular edema after acute retinal necrosis, it has been suggested that the petaloid leakage pattern on FA may serve as a predictive biomarker for treatment response ¹⁾. Research is ongoing to quantify FA dynamic information and utilize it for predicting the efficacy of anti-VEGF therapy and photodynamic therapy.

Expanded Application to Pediatric and Special Populations

The introduction of RetCam3 has made FA feasible in children. It is expected to be applied for vascular evaluation in retinopathy of prematurity and pediatric retinal diseases.

Widespread Use of Ultra-Widefield FA

With the 200° ultra-widefield FA using Optos, the imaging time for peripheral lesions has been significantly reduced. Its utility has been demonstrated for evaluating peripheral capillary non-perfusion areas in diabetic retinopathy and for extensive assessment of congenital retinal vascular diseases (e.g., FEVR).

Q If OCT angiography is available, is fluorescein angiography unnecessary?

A

OCTA is non-invasive and can delineate capillary structures in detail, but it cannot detect fluorescence leakage outside blood vessels. FA is necessary for evaluating the activity of macular edema and confirming CNV leakage, and the two modalities complement each other’s information ³⁾.

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9. References

1. Rana V, Markan A, Arora A, et al. Cystoid Macular Edema Secondary to Acute Retinal Necrosis: The Role of Fundus Fluorescein Angiography in Guiding Treatment. Cureus. 2025;17(11):e96108.
2. Jurgens L, Yaici R, Schnitzler CM, et al. Retinal vascular occlusion in pregnancy: three case reports and a review of the literature. J Med Case Rep. 2022;16:167.
3. Flaxel CJ, Adelman RA, Bailey ST, et al. Diabetic Retinopathy Preferred Practice Pattern. Ophthalmology. 2020;127(2):P66-P145.
4. 日本眼科学会. 眼底血管造影実施基準（改訂版）. 日眼会誌. 2011;115(12):1101-1108.