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Review Article

Intraocular Tumors: Angiographic Patterns

Bowen, Randy C. MD, MS; Raval, Vishal MD; Soto, Hansell MD; Singh, Arun D. MD

Author Information
Asia-Pacific Journal of Ophthalmology: September-October 2020 - Volume 9 - Issue 5 - p 449-460
doi: 10.1097/APO.0000000000000323
  • Open

Abstract

INTRODUCTION

Diagnosis of intraocular tumors is primarily clinical; however, ancillary tests such as ultrasonography and angiography are important aids to determine tumor size, composition of mass, and vascular patterns.1 Fluorescein angiography (FA) provides visualization of retinal tumors, whereas indocyanine green angiography (ICG) is most valuable for choroidal lesions due to deeper near-infrared penetration and 98% protein-bound particle, which highlights the choroidal vascular systems.2,3 Although optical coherence tomography angiography (OCTA) can provide excellent en face structural and static vascular information,4 it currently does not provide dynamic evidence regarding active leakage and staining and is particularly inadequate in assessing large choroidal vessels. Consequently, in this review, we focus on the angiographic patterns of FA and ICG of a variety of intraocular tumors.

FA OF RETINAL TUMORS

Retinal Capillary Hemangioma

Retinal capillary hemangioma (RCH) presents with an enlarged retinal arteriole entering the retinal tumor and an outgoing engorged venule which may have surrounding lipid exudate and subretinal fluid. RCH can present as peripapillary or peripheral lesion. Both can grow to considerable size producing exudate and subretinal fluid that threaten the macula. RCH may be associated with von Hippel-Lindau disease and should be referred for multisystem disease evaluation including cerebral, adrenal, renal, and other organs.5

FA is the most beneficial imaging modality for RCH. Wide-field FA has been shown to be more effective at identifying new smaller RCH compared to wide field fundus photography.6 FA demonstrates hyperfluorescence of the dilated feeder arteriole in early arterial phase angiography, followed by homogeneous filling of the fine capillary retinal tumor. The draining venule in the venous phase then becomes evident with subsequent filling, followed by progressive hyperfluorescence of the retinal tumor and leakage in the late-phase.7 The clear distinction of the feeder arteriole early-arterial phase assists to confirm the target vessel for laser photocoagulation (Fig. 1).8 Photodynamic therapy (PDT) in nonmacular regions has also demonstrated success at controlling tumor growth and reducing subretinal fluid while minimizing the risk of retinal hemorrhage.9 Cryotherapy is often selected for anterior tumors that are <4 mm.10 For larger >4 mm of peripheral lesions plaque brachytherapy is often used, due to the poor penetration of laser and cryotherapy, to prevent macula-threatening exudation and subretinal fluid.11

Figure 1
Figure 1:
Comparison of retinal capillary hemangioma (A–D), vasoproliferative tumor (E–H), retinal cavernous hemangioma (I–L), retinoblastoma (M–P), and astrocytic hamartoma (Q–T). Retinal capillary hemangioma (yellow arrow) with engorged retinal arterioles entering the retinal capillary hemangioma located at 6 o’clock with an engorged efferent venule (A). Fluorescein angiography (FA) during arterial phase demonstrates the enlarged arteriole (green arrow) entering the capillary hemangioma (B) followed by venous phase (C) and late phase which show leakage of capillary hemangioma (D). Inferotemporal, solitary, unilateral, vasoproliferative tumor (yellow arrow) with normal sized retinal vessels entering the lesion with increased intrinsic tumor vascularity. Surrounding lipid exudation and subretinal fluid with retinal atrophy (white arrow) due to prior chronic subretinal fluid (E). FA during arterial phase shows normal sized retinal vessels entering tumor (white arrow) with increased hyperfluorescence of the intrinsic vascularity within the tumor (F). Hyperfluorescence increases (G) with leakage in late phase (H). Retinal cavernous hemangioma demonstrating multiple “grape-like” clusters of dark encapsulated enlarged capillary saccules adjacent to a normal caliber venule (yellow arrows) (I). FA shows hypofluorescence in arterial phase (J) with gradual hyperfluorescent pooling in venous (K) and late phase (L). Images I–L are courtesy of Alexandra Rachitskaya, MD (Cole Eye Institute, Cleveland Clinic, OH). Retinoblastoma (yellow arrow) with dilated retinal arterioles entering the retinoblastoma with a dilated efferent venule (M). FA using RetCam III (Clarity Medical Systems, Pleasanton, CA) during early (<1 minute) phase demonstrates early hyperfluorescence (N) followed by increased hyperfluorescent staining of tumor during mid (1–2 minute) phase with dilated retinal arteriole and venule (green arrow) compared to normal retinal vessels (white arrow) (O) and mid-late (3 minutes) phase showing persistent staining of retinoblastoma (yellow arrow) (P). Astrocytic hamartoma involving the right optic nerve head (yellow arrow) (Q). Astrocytic tumor remains isofluorescent during early and late phases with increased surrounding hyperfluorescence temporal to the tumor (R–T).

Vasoproliferative Tumor

Vasoproliferative tumors (VPTs) are acquired and are usually sporadic, unilateral, solitary lesions predominantly found in the inferotemporal or superotemporal quadrants of the eye.12 The large majority (80%) are idiopathic primary VPTs; however, approximately 20% of cases are secondary VPTs with underlying ocular diseases such as intermediate uveitis or retinitis pigmentosa.13 Clinically they present with normal-sized retinal vessels entering the whitish-yellow mass with increased intrinsic tumor vascularity. Lipid exudation and subretinal fluid are signs of tumor activity.

FA easily distinguishes VPT from RCH due to the lack of enlarged feeder vessels, yet prominent intrinsic vascular tumor vessels that usually demonstrate hyperfluorescence and progressive leakage starting in arterial phase through late-phase angiography (Fig. 1).13 FA also assists in clarifying the extent of the actual tumor size compared to the exudate produced from the tumor, which is important when considering management.

Treatment depends on the location and size of the VPT. For posterior nonmacular lesions, PDT has shown reduction in VPT height, resolution of macular fluid, reduction of leakage from the lesion, and nonperfusion of VPT vascular channels verified at the 1-year follow-up.14 Additionally, the degree of collateral retinal scarring is minimal compared to cryotherapy. VPTs that are positioned more anteriorly are often treated with cryotherapy. Tumors that are thick (height >3.0 mm) or large in base (tumor diameter >7.5 mm) are often treated with episcleral plaque brachytherapy.15,16

Retinal Cavernous Hemangioma

Retinal cavernous hemangioma (RCavH) is a congenital, benign, nonprogressive vascular anomaly arising from the capillary bed that usually presents unilaterally and rarely is the source of intraocular hemorrhage.17 RCavH is clinically seen on the optic nerve or retina periphery as multiple confluent saccular vascular dilations around a retinal venule with layering of erythrocytes within the saccules.12,18,19 A key distinction from RCH and vasoproliferative tumor is the normal arteriole and venule entering the cavernous hemangioma and lack of exudation and subretinal fluid.

FA shows early blocking from pooling blood during early arterial phase followed by hyperfluorescence and layering of cells within multiple cluster-like vascular saccules arising from capillaries in later venous filling phase.12,19 The fluorescein caps on the saccules are a classic finding, which suggests sedimentation of erythrocytes. This results in a vivid fluorescein-stained saccular cap due to the supernatant plasma in conjunction with the inferior part of the saccule demonstrating blocking by the layered erythrocytes (Fig. 1).20

Treatment for RCavH is usually observation due to the benign effect. However, in rare cases of vitreous hemorrhage, photodynamic therapy and proton beam have been used successfully to collapse the saccules and stop the bleeding.21,22 Although RCavHs are often isolated findings, 14% of reported cases were associated with central nervous system cavernous hemangioma for which many had symptoms of seizures, transient visual disturbance, or headache. Consequently, neuroimaging is indicated for patients who present with RCavH.23

Arteriovenous Communication of the Retina

Retinal racemose hemangioma is a congenital, retinal arteriovenous (AV) malformation which is often seen in Wyburn-Mason disease. The key differentiation from RCH is that although it presents with an enlarged and tortuous artery and vein, they fuse to form an anastomotic communication and do not lead into an angioma, as seen in RCH. Additionally, they do not cause exudation or accumulation of subretinal fluid.12

FA highlights the direct communication between arteriole and venule without a capillary network resulting in rapid fill of hyperfluorescence from arteriole to venule compared to the surrounding vasculature. Surrounding the retinal arteriovenous malformation, the vessels remain normal and no leakage or exudation is seen.24

Treatment of arteriovenous communication of the retina is usually not needed as it is mostly non-vision-threatening; however, a few cases of vessel occlusion, hemorrhage, and aneurysm have been reported.25–27 Most importantly, screening for concurrent orbital and cerebral vascular malformations with neuroimaging is indicated for patients where retinal AV malformations are identified.28

Retinoblastoma

Retinoblastoma is the most common intraocular malignancy in the pediatric population which presents as a white-gray endophytic (intra-retinal tumor invades inner retina and breaks through internal limiting membrane and grows toward vitreous, releasing retinoblastoma seeds) or exophytic (intra-retinal tumor grows in the direction of the subretinal space) lesion.29 Eyes with retinoblastoma can have large dilated or tortuous retinal feeder vessels, retinal or tumor nonperfusion, small vessel abnormalities, arteriovenous shunts, or intrinsic tumor vessels. Consequently, fluorescein angiogram provides a valuable comparison of the initial vascular condition compared to post-treatment status to guide treatment decisions.

Most fluorescein angiograms before 1980 were obtained with a portable fundus camera, whereas current day imaging is performed on wide-field contact fundus cameras, such as Retcam, during examinations under anesthesia.30 The clinically relevant findings in retinoblastoma are seen within the first 3 minutes of FA analysis; therefore, it is not advised to extend the evaluation beyond 3 minutes.30

FA presents a progressive hyperfluorescent staining of the retinoblastoma with possible leakage of tumor vessels in advanced cases (Fig. 1).31 However, other important features include hyperfluorescence of intraretinal microvascular abnormalities, arteriovenous shunts, and dilated feeder vessels that are seen at the site of direct retinoblastoma infiltration. Additionally, FA can demonstrate the degree of retinal and choroidal non- perfusion after intra-arterial chemotherapy, intravenous chemotherapy, intravitreal or local therapies.32,33 In advanced cases, iris neovascularization presents as patchy areas of hyperfluorescence in multiple iris sectors at 1 to 2 minutes.30 This is in contrast to iris neovascularization seen in diabetes mellitus or retinal vein occlusions which typically manifest neovascularization starting at the iris pupillary margin and extending peripherally over the iris surface.34

Astrocytic Hamartoma

Astrocytic hamartoma is a discrete, semitranslucent, gray white lesion located primarily in the nerve fiber layer (endophytic) but can also be seen in the subretinal space (exophytic). Astrocytic hamartoma often contains a fine capillary network. Over time, astrocytic hamartoma undergoes nodular calcific degeneration resulting in a stark white tapioca “mulberry” appearing retinal lesion that does not usually grow beyond 4 disc diameters.18 Although retinal astrocytic hamartomas are benign, slow-growing, non-neoplastic lesions, they can cause exudative retinal detachment and vitreous hemorrhage which can mimic retinoblastoma.35 These lesions have been associated with tuberous sclerosis and neurofibromatosis.36

FA pattern is variable, but typically shows mild to moderate early hyperfluorescence with increased hyperfluorescence and late staining or leakage; however, in some cases, only isofluorescence is noted. Feeder vessels are not dilated or tortuous which distinguishes them from RCH and retinoblastoma (Fig. 1).37

FA AND ICG OF UVEAL TUMORS

Uveal Melanoma

Uveal melanoma within the choroid, ciliary body, or iris presents as either a pigmented or amelanotic mass. Choroidal and ciliary body melanoma present a variety of clinical signs suggesting malignancy such as subretinal lipofuscin (orange pigment), subretinal fluid, and hemorrhage from a break through Bruch membrane resulting in a mushroom appearance. As melanomas enlarge, the intrinsic vasculature becomes more prominent particularly in amelanotic and highly elevated tumors.

FA of uveal melanoma is best understood by considering early retinal pigment epithelium alterations. As a result, when fluorescein enters the retinal and melanoma arterial supply, fine pin-point staining of drusen, exudate, and cellular debris on the tumor surface is seen. Of note, lipofuscin (orange pigment) causes blockage of fluorescence. Gradual increase of fluorescein intensity occurs through the venous and the late-phase. In cases of serous detachment overlying the melanoma, fluorescein rapidly passes through Bruch membrane into the subretinal pigment epithelial space to form a well-circumscribed pooling of hyperfluorescence. Likewise, fluorescein pools in associated cystoid macular edema.18 Uveal melanoma can also demonstrate hypofluorescence during the arterial phase when the tumor has invaded the outer retina. However, during later-phase angiography, mild hyperfluorescence often develops at a minimum around the tumor edge due to fluorescein staining of exudate from the exudative detachment.18

ICG on smaller uveal melanomas demonstrates hypocyanescence in early, mid, and late angiographic phases due to blocking. The uveal melanoma vascular supply becomes more apparent as the tumor enlarges and in amelanotic melanomas. Consequently, tumors have well-defined intrinsic vessels demonstrating hypercyanescence surrounded by tumor cells that show hypocyanescence. This provides a clear distinction from other tumors and mimickers such as subretinal hemorrhages as discussed below. Tumors that have broken through Bruch membrane will often have an even more engorged tumor vessel appearance due to the compressive effect.

Neither FA nor ICG is required for the diagnosis of uveal melanoma. However, they both can provide invaluable features to distinguish from mimicking diagnoses. Specifically, peripheral exudative hemorrhagic chorioretinopathy is often mistaken as a new onset of uveal melanoma. By obtaining ICG, the presence of a large choroidal tumor vessel on ICG rules out a sub-retinal pigment epithelium (RPE) or subretinal hemorrhagic lesion. On FA, during the arterial phase, the subretinal hemorrhages are completely hypofluorescent with sharply demarcated edges, which do not change throughout the angiogram study. Normal overlying retinal vessels are hyperfluorescent, but choroidal vessels are absent. This is in contrast to melanoma that will have some staining due to destruction of the RPE and presence of exudate (Fig. 2).18 In larger melanomas, choroidal vessels will be seen in pre-arterial phase, known as double circulation, and may even persist through venous phase if the tumor has broken through Bruch membrane.38 Additionally, the use of optical coherence tomography (OCT) and clinical examination will show a sharply demarcated edge of the retina and subretinal hemorrhage. Some small choroidal melanomas do not have visible choroidal vessels, so the absence of choroidal vessels do not rule out choroidal melanoma.1 In comparison, choroidal metastases rarely have prominent intrinsic vessels (Fig. 3). Polypoidal choroidal vasculopathy (PCV) can also mimic uveal melanoma due to secondary subretinal hemorrhage. ICG is better than FA for diagnosing PCV, because ICG angiography emits and absorbs near-infrared wavelengths, which pass through the RPE and penetrate into the choroid and associated hemorrhage, allowing for evaluation of choroidal lesions.39 PCV is distinguished by single or multiple hypercyanescent polyps during early-phase ICG angiography40 (Fig. 4), which assists in distinguishing PCV from uveal melanoma.

Figure 2
Figure 2:
Comparison of melanocytic choroidal melanoma (A–H), peripheral exudative hemorrhagic chorioretinopathy (PEHCR) (I–P), and sub-retinal pigment epithelial hemorrhage (Q–T). Melanocytic melanoma, mildly visible orange pigment, subretinal fluid (white arrowheads) that has broken through Bruch membrane shows intrinsic tortuous vessels (yellow arrow) (A). Fluorescein angiography (FA) during arterial phase demonstrates tumor hypofluorescence with few early choroidal vessel hyperfluorescence (B). Increased hyperfluorescence of choroidal vasculature is seen illustrating “double circulation” from presence of tumor vessels and retinal vessels (C). Late phase shows staining and mild pooling on tumor surface (D). Malignant transformation of adjacent nevus (green arrowheads) with orange pigment, subretinal fluid, and hemorrhage secondary to break in Bruch membrane (E). Indocyanine green angiography (ICG) demonstrates hypocyanescence of tumor throughout the entire imaging with progressive hypercyanescence of tumor vessels (yellow arrow) (F-G) which fade in late phase (H). PEHCR is illustrated by the darkly pigmented, elevated, peripheral lesion that lacks orange pigment and drusen which has sharply demarcated edges (I). FA during arterial phase shows hypofluorescence of lesion with hyperfluorescence at leading exudative edge (J). Venous phase shows some retinal vessels (green arrow) overlying lesion (K), with late phase staining (L). Extramacular hemorrhagic chorioretinopathy with sharply demarcated edges with adjacent temporal RPE degeneration illustrating PEHCR (M). ICG shows hypocyanescence in area of PEHCR with normal choroidal vessels (N). Mid-vphase further illustrates normal choroidal vessels with faint outline of retinal vessels overriding lesion (green arrow) (O). Hypocyanescence persists into late phase (P). Hemorrhagic sub-retinal pigment epithelium with sharp demarcation at lesion edge (Q). FA shows sharply demarcated dense hypofluorescence of the lesion seen in arterial phase through late phase with no leakage (R–T).
Figure 3
Figure 3:
Comparison between amelanotic melanoma (A–G), choroidal hemangioma (H–N), and lung carcinoma choroidal metastasis (O–U). Medium size amelanotic melanoma on superior arcade with mild orange pigment and subretinal fluid (A). Fluorescein angiography (FA) during arterial phase demonstrates fine pin-point staining on tumor surface (B). Increase of fluorescein intensity is seen through venous and late phase (C–D). Indocyanine green angiography (ICG) shows hypocyanescence of the choroidal melanoma in early, mid, and late phase. Note the lack of choroidal vessels seen in this medium size melanoma that has not broken through Bruch membrane (E–G). Orange-white choroidal hemangioma with surrounding subretinal fluid (H). FA during the arterial phase exhibits a lacy hyperfluorescence, which intensifies in venous and late phase (I–K). ICG demonstrates early rapid hypercyanescence of choroidal vascular network (L) with intense hypercyanescence at approximately 1 minute (M). In the late phase, the dye fades from the tumor resulting in a “washed out” appearance (N). Amelanotic lung carcinoma choroidal metastasis superior to optic nerve with orange pigment and subretinal fluid (O). FA demonstrates mild hypo/isofluorescence of tumor (P) with gradual increased staining of exudate on tumor surface (Q–R). ICG shows hypocyanescence of tumor in early, mid, and late phases without tumor vascularity (S–U).
Figure 4
Figure 4:
Polypoidal choroidal vasculopathy of right eye which can mimic uveal melanoma (A). Multiple choroidal polyps seen between the fovea and optic nerve at the edge of the hypopigmentation with increasing hypercyanescence during early-phase angiography (B–D).

Circumscribed Choroidal Hemangioma

Circumscribed choroidal hemangiomas (CCHs) occupy the choroidal space and cause changes in the RPE ranging from atrophy, focal proliferation with drusen formation, and fibrous transformation.41 CCHs can often be missed due to their low-profile, minimal elevation, and orange color that blends into the choroidal background which is in contrast to a metastatic lesion or uveal melanoma that are starkly evident on ophthalmoscopy. Choroidal hemangiomas are usually present in the posterior pole with an average height around 2 to 3 mm and cause vision reduction by the results of a hyperopic shift without fluid, or by subretinal fluid exudation, or by mechanical disruption of the foveal zone due to posterior elevation or tilting.42

FA during the arterial phase demonstrates mild lacy hyperfluorescence of the choroidal hemangioma's vascular network. The hyperfluorescence intensifies through the venous phase and into the late phase as the fluorescein stains the exudate and fibrous tissue that separates the tumor from the retina.18,43

Since indocyanine green is 98% bound to plasma protein,2 ICG angiography provides the best imaging to diagnose choroidal hemangiomas. Unlike choroidal melanoma, metastases, and choroidal granuloma, a choroidal hemangioma demonstrates rapid extreme hypercyanescence within the first minute, with persistent hypercyanescence of moderate intensity at 8 minutes followed by isocyanescence or hypocyanescence, a so-called “wash-out,” at 20 minutes during late phase (Fig. 3).43,44

Choroidal Metastasis

Choroidal metastasis almost always presents with symptomatic decrease in central or peripheral vision, photopsia, or pain. The appearance is usually a gray whitish-yellow choroidal mass that rapidly grows without significant blood vessels as seen in larger uveal melanomas. Growth is destructive to the RPE and results in associated serous exudation into the subretinal space.18 Metastasis can occur as a single solitary lesion (71%) or as multiple lesions (29%) which can be found at varying stages of growth. Most commonly, choroidal metastasis is located between the macula and the equator (80%) and are present bilaterally in approximately 20% of cases. The most common choroidal metastasis is from breast (47%) followed by lung (21%), gastrointestinal tract (4%), kidney (2%), cutaneous melanoma (2%), and prostate cancer (2%).45

On fluorescence angiography, metastatic lesions demonstrate hypofluorescence during arterial and venous phases. During semi-late and late phases pin-point hyperfluorescence develops as fluorescein stains exudate and fibrous tissue between tumor and retina, which is very similar in presentation to uveal melanoma on FA.18

ICG portrays hypocyanescence during early, mid, and late phase, which creates a stark difference from choroidal hemangioma (Fig. 3). In one study, only 13% of choroidal metastatic cases detected intratumor vessels compared with 89% of uveal melanomas for which tumor vessels were identified.46 If diagnostic ambiguity persists, then systemic work up including CT imaging of the chest, abdomen, and pelvis is indicated to either find a primary tumor or granulomatous infiltration (Fig. 5). If biopsy of the primary tumor or site of nonocular granuloma is not feasible, then fine needle aspiration biopsy of the intraocular mass is indicated for definitive diagnosis.

Figure 5
Figure 5:
Comparison of sarcoid choroidal granuloma (A–G) and choroidal osteoma (H–N). Gray whitish-yellow choroidal macular sarcoid granuloma with subretinal fluid in the macula (A). Fluorescein angiography (FA) during arterial phase demonstrates fine pin-point staining on tumor surface (B). Increase of fluorescein intensity is seen through venous and late phase (C–D). Indocyanine green angiography (ICG) shows hypocyanescence of the choroidal granuloma in early, mid, and late phases (E–G). Peripapillary whitish-pink choroidal osteoma with mild subretinal fluid at tumor edge (H). FA during arterial phase demonstrates fine pin-point staining on tumor surface (I) which intensifies during venous and late phase (J–K). ICG shows early phase hypocyanescence due to blockage of the osteoma (black arrows) (L). Mid phase is almost isocyanescent (black arrows) (M) and gradually increases intensity in late phase (black arrows) (N).

Choroidal Granuloma

Choroidal granuloma can arise from infectious or noninfectious etiologies.47 Choroidal granuloma presents as an amelanotic, gray whitish-yellow, unifocal or multifocal, elevated choroidal lesion, occasionally with posterior uveitis or sclerites, and often results in subretinal fluid causing symptomatic vision change, photopsia, and pain. Consequently, granulomatous lesions are often confused with choroidal metastasis or amelanotic melanoma.48

FA of a choroidal granuloma shows a similar presentation as a small uveal melanoma. During arterial phase, fine pin-point staining is seen on the surface of the granuloma. The staining remains hyperfluorescent into late phase and then fades.

ICG for choroidal granuloma presents very similarly to small uveal melanomas and most choroidal metastases by demonstrating hypocyanescence in early phase that represents blocking that persists through middle- and late-phase angiography and then fades (Fig. 5). There is no vascular supply as is seen in larger uveal melanomas or rarely metastases (Fig. 2). Additionally, these tumors are easily distinguished from choroidal hemangiomas due to lack of hypercyanescence on ICG. These lesions will benefit from OCT and Bscan imaging for further clarification of diagnosis. Similar to suspicion for metastases, systemic work up is required including syphilis panel, QuantiFERON gold, ACE, lysozyme, erythrocyte sedimentation rate, C-reactive protein, computed tomography-chest. If infectious panel is negative, a trial of steroid with a response of mass reduction facilitates the diagnosis of granuloma; otherwise, fine needle aspiration biopsy is indicated.48

Choroidal Osteoma

Osteomas are benign ossifying tumors that form from the vascular choroidal layer located primarily in the peripapillary region. They most commonly present in females during their 20 to 30s. Clinically, the tumor color ranges from normal orange to yellow-white with orange-red peripherally, which reflects the degree of retinal pigment epithelial destruction overlying the tumor.49,50 Approximately, 50% of osteomas will grow to varying degrees which may result in vision loss by direct proximity to the fovea or by development of a choroidal neovascular membrane which occurs in approximately 30% of cases. With time, osteomas undergo decalcification and reduce in size.51

FA of choroidal osteomas show early, patchy, pin-point hyperfluorescence of the tumor that progresses to more intense staining in late-phase angiography.50 If a neovascular membrane is present, then early lacy hyperfluorescence with early leakage followed by late staining around the lesion is typical.52

ICG on early phase shows hypocyanescence due to blockage of the osteoma. Due to peripheral choroidal vessels entering the osteoma, during the mid and late phases, the osteoma becomes isofluorescent (Fig. 5).53 Although neither ICG nor FA is diagnostic of osteoma, ICG illustrates only mild blocking compared to the intense hypocyanescence seen with uveal melanoma, metastasis, and granulomas. Additionally, FA helps to determine whether a choroidal neovascular membrane has formed and is leaking.

Uveal Lymphoma

Uveal lymphoma is predominantly a low-grade B-cell non-Hodgkin lymphoma, most commonly extranodal marginal zone lymphoma. Patients present clinically with yellow-white choroidal infiltrates distributed usually in a diffuse or superotemporal pattern, often anterior to the arcades.54,55 Vitreous cell is usually not seen in uveal lymphoma given that vitreous cell is associated with high-grade diffuse large B-cell lymphoma causing vitreoretinal lymphoma; however, high-grade lymphoma has been reported in uveal lymphoma.56

FA provides little benefit in the diagnosis of uveal lymphoma; however, ICG angiography provides insightful patterns. During early-phase ICG angiography, there is hypocyanescence in the areas of clinically yellow-white choroidal lymphoma infiltrates. As the choroidal dye fades during mid-late phase, the blocking becomes more apparent (Fig. 6).54 However, birdshot, sarcoidosis, MEWDS, TB, and syphilis can have similar findings and consequently infectious and rheumatological work up followed by biopsy is indicated for management. OCT imaging will commonly present with an irregular lumpy and bumpy choroid. Ultrasonography further evaluates for thickened choroid and for extrascleral involvement which is seen in approximately 75% of uveal lymphoma cases.54

Figure 6
Figure 6:
Uveal lymphoma (A-D). Speckled yellow-white choroidal infiltrates distributed in the posterior pole and mid-periphery (A). Indocyanine green angiography shows hypocyanescence of corresponding choroidal infiltrates in early, mid, and late phases (B–D).

FA OF IRIS TUMORS

Iris Melanoma

Iris melanoma presents as a pigmented or amelanotic, multipattern, iris stromal lesion. The large majority has feeder vessels and increased tumor vascularity.57 Metastatic tumors to iris also present with increased vascularity and have poorly defined borders.

Anterior segment FA of iris melanoma demonstrates hyperfluorescence of radial feeder vessels in early phase followed by pin-point tumor staining. Increased tumor hyperfluorescence is seen at mid-late phase. During late phase, the tumor becomes iso- or hypofluorescent with mild hyperfluorescence at tumor edge (Fig. 7).58 The feeder vessel hyperfluorescence is characteristic of malignancy and can help differentiate from iris melanocytoma, granuloma, iris pigment epithelial, or stromal cyst.

Figure 7
Figure 7:
Comparison of iris melanoma (A–E), iris arteriovenous malformation (F–J), and iris cavernous hemangioma (K–O). Iris melanoma with intrinsic vascularity and feeder vessels causing corectopia (A). Fluorescein angiography (FA) during arterial phase demonstrates hyperfluorescence of radial feeder vessels (B) followed by pin-point staining on tumor surface (C) with increased fluorescence through venous phase (D) with dye fading in late phase (E). Mid-dilated pupil with iris arteriovenous communication at 4 o’clock (white arrow) (F). FA shows rapid filling hyperfluorescence of both the artery and vein during arterial phase, illustrating the direct communication (G). Hyperfluorescence persists beyond 5 minutes without leakage. No evidence of mass or feeder vessels (H–J). Flocculi from 12-5 o’clock. Iris cavernous microhemangioma within iris floccule at 12 ’clock (K). Hypofluorescence in the early phase (L), followed by increasing circumscribed hyperfluorescent saccule without leakage (M and N) with subsequent fading of dye in the late phase (O).

Iris Arteriovenous Communication

Iris arteriovenous malformation illustrates a congenital anomaly resulting in abnormal vascular anastomosis which bypasses the iris capillary bed which presents as engorged vascular loops along the iris.59 Iris arteriovenous communications are benign in nature; however, anterior segment ultrasound is still indicated to rule out an underlying malignant tumor.

FA demonstrates early hyperfluorescence of the large caliber vascular loop, illustrating lack of additional feeder vessels that would be concerning for an underlying tumor.59 During late phase, the fluorescence fades (Fig. 7).

Iris Cavernous Hemangioma

Iris cavernous hemangiomas can be found in the iris stroma or iris margin and have been associated with spontaneous recurrent anterior segment hyphema.60

FA in iris cavernous microhemangioma presents similarly to RCavH by revealing hypofluorescence in the early phase followed by circumscribed hyperfluorescent cap with hypofluorescent base suggestive of sedimentation of erythrocytes.61 Leakage is usually absent, but when present, hyphema occurs. These lesions can be surrounded by iris pigment epithelium or within an iris pigment epithelial floccule (Fig. 7).

CONCLUSIONS

Understanding the fluorescein and ICG angiographic patterns for intraocular tumors provides critical diagnostic signs to facilitate distinction between intraocular tumors while ruling out mimickers (Table 1 ). Overall, FA provides the most benefit for retinal tumors by evaluating retinal tumor vessel diameter and intrinsic tumor vascularity and leakage (Fig. 1). Conversely, ICG angiography provides the most benefit in distinguishing between the characteristic vascular differences seen in uveal tumors of varying size. Additionally, ICG provides key vascular distinction between choroidal melanoma and peripheral exudative hemorrhagic chorioretinopathy (Fig. 2).

TABLE 1
TABLE 1:
Angiographic Patterns of FA and ICG in a Variety of Intraocular Tumors
TABLE 1 (Continued)
TABLE 1 (Continued):
Angiographic Patterns of FA and ICG in a Variety of Intraocular Tumors

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Keywords:

angiographic patterns; choroidal hemangioma; fluorescein angiography; indocyanine green angiography; intraocular tumors

Copyright © 2020 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.