Comparison of optical coherence tomography angiography and fundus fluorescein angiography features of retinal capillary hemangioblastoma

Abstract

The aim of this study is to compare the optical coherence tomography angiography (OCTA) and fundus fluorescein angiography (FFA) features of retinal capillary hemangioblastoma (RCH). This is an observational case series of three patients with von Hippel–Lindau (VHL) disease and one patient with juxtapapillary RCH. All patients underwent FFA with a mydriatic fundus camera and OCTA with swept-source angio OCT. The FFA and OCTA characteristics of tumors were compared. In our series, FFA could identify tumors as small as the width of a third-order retinal artery, which was missed on clinical examination. OCTA identified these tiny tumors, but only those closer to the posterior pole. Both FFA and OCTA could identify the intrinsic vasculature and feeder vessel in juxtapapillary RCH. On OCTA, the tumors were better defined than in FFA. The depth of the lesion can be identified on OCTA. Feeder and the draining vessels could be identified precisely in OCTA than FFA, particularly in small tumors. OCTA can identify tumors in VHL missed on clinical examination. It can identify the feeder vessel and intrinsic vasculature of sessile juxtapapillary RCH and aids in its diagnosis. Tumors are better defined in OCTA than FFA due to the absence of leakage. However, FFA can identify nearly all the early tumors, but OCTA fails to image the peripheral tumors due to its smaller field and prolonged acquisition time. Technological advances and the development of wide-field OCTA in the future can be helpful in identifying all the unsuspected tumors in VHL disease.

Retinal capillary hemangioblastomas (RCH) are retinal vascular tumors composed of endothelial cells, pericytes, and foamy stromal cells.[1] RCH can occur as an isolated condition or can be the earliest manifestation of von Hippel–Lindau (VHL) disease. RCH can be seen in the peripheral retina or in the juxtapapillary region. RCH in the peripheral retina appears as orange-red circumscribed lesions with a dilated tortuous feeding arteriole and a draining venule. Juxtapapillary RCH can be endophytic, sessile, or exophytic.[2] The exophytic tumor appears as an orange-red lesion. However, the sessile and endophytic tumor does not show the characteristic fundus appearance and can be misdiagnosed with papillitis, unilateral papilledema, choroiditis, choroidal hemangioma, or choroidal neovascularization.[3] Sporadic cases are usually unifocal and those associated with VHL are frequently multifocal and bilateral. RCH can lead to vision loss due to submacular exudation from a peripheral tumor, tractional, or combined retinal detachment (RD) involving the macula.[4,5] Larger lesions, particularly those associated with VHL can be difficult to treat, and it is imperative to identify and treat these tumors when small. However, early lesions are not easily visible on clinical examination with slit-lamp biomicroscopy and indirect ophthalmoscopy. Fundus fluorescein angiography (FFA) may be necessary to detect these early lesions. Optical coherence tomography angiography (OCTA) has a role in characterizing retinal and choroidal vascular disorders and provides information comparable to FFA in a few disorders. We describe OCTA characteristics of RCH in comparison to FFA characteristics.

Methods

This is an observational case series of three subjects with VHL disease and one patient with juxtapapillary RCH. Institutional review board (IRB) approval was not sought as this was an observational case series. All patients underwent thorough ophthalmic evaluation with a slit lamp, slit lamp biomicroscopy with 78D lens and indirect ophthalmoscopy with 20D lens and FFA with a mydriatic fundus camera (Topcon TRC-50DX, Topcon Corporation, Japan.). FFA images consisting of posterior pole centered on the fovea, and eight peripheral images (50°) (superior, superotemporal, temporal, inferotemporal, inferior, inferonasal, nasal, and superonasal) were captured. OCTA images were captured with swept-source angio OCT (Topcon DRI OCT Triton, Topcon Corporation, Japan.) over the lesions detected on FFA. The FFA and OCTA characteristics of tumor were compared.

Results

Case 1

A 20-year-old male, a known case of VHL disease with cerebellar hemangioblastoma and bilateral multiple RCH presented to us for follow-up examination. Fundus evaluation revealed total RD in the right eye, whereas the left eye had an exophytic juxtapapillary RCH [Fig. 1a] and a regressed peripheral RCH (previously treated with laser photocoagulation).

Figure 1.

Case 1 – (a) Color photograph showing a retinal capillary hemangioblastoma located at disc, (b) fundus fluorescein angiography of disc retinal capillary hemangioblastoma showing its communication with inferotemporal major vessels and absence of leakage, (c) tiny retinal capillary hemangioblastoma identified on fundus fluorescein angiography, (d) optical coherence tomography angiography of disc retinal capillary hemangioblastoma showing communication with inferotemporal major vessels

In the early phase of FFA, a cigar-shaped hyperfluorescent lesion was seen at the inferior margin of optic nerve head [Fig. 1b]. The lesion was communicating with the major inferotemporal branch retinal vein and artery. Minimal dilatation of the artery at the point of communication with the lesion was seen. There was no evidence of leakage in the late phase. In addition to juxtapapillary RCH, an early peripheral RCH [Fig. 1c] was noted in the temporal mid-periphery which was not seen on clinical examination. On OCTA, a bright, well-defined lesion was seen in the inferior one-third of the disc in superficial and deeper sections [Fig. 1d]. In superficial sections, the lesion was seen to be communicating with the inferotemporal artery and vein, and minimal dilatation of artery was seen at the point of communication. The lesion was better delineated on FFA and OCTA than in color photograph. Deeper extension of the tumor was identified on OCTA. OCTA failed to capture the small tumor due to its peripheral location.

Case 2

A 14-year-old boy was noted to have a mid-peripheral RCH in the inferotemporal quadrant of the right eye on routine fundus evaluation. A suspicious lesion was seen in the superonasal quadrant. Magnetic resonance imaging of the brain and ultrasonography of abdomen were normal. Urinary vanillylmandelic acid was negative. On FFA, multiple RCH that were indistinct on clinical examination were identified in both the eyes (10 in the right eye and 8 in the left eye). Fluorescein leakage was seen in larger tumors in the late phase [Fig. 2a]. On OCTA, five tumors were identified in the right eye [Figs. 2b, d, 3b and d]. It failed to identify rest of the tumors due to their peripheral location. On OCTA, tumors were seen as well-defined bright lesions in the superficial retina. Feeder vessels could be identified. The margins were more distinct than in FFA [Fig. 2a and b]. In the deeper retinal sections of OCTA, signal void areas were seen in the deep capillary plexus around the tumor which corresponded to intraretinal cystic spaces on OCT.

Figure 2.

Case 2 – (a) Fundus fluorescein angiography of a large retinal capillary hemangioblastoma and small retinal capillary hemangioblastoma. The large tumor is ill defined due to leakage. Multiple hyperfluorescent satellite lesions around the large retinal capillary hemangioblastoma can be seen which would give a false impression of multiple tiny tumors, (b) optical coherence tomography angiography of the lesion in Figure 2a. Margins of the tumor are well defined compared to fundus fluorescein angiography. The small retinal capillary hemangioblastoma is identifiable even in optical coherence tomography angiography. Due to motion artifact duplication of tumor is seen, (c) fundus fluorescein angiography of a paired retinal capillary hemangioblastoma. The feeder and the draining vessels and communication between the tumors are seen, (d) optical coherence tomography angiography of the lesion in Figure 2c. The feeder and the draining vessels and the communication are more distinct than fundus fluorescein angiography

Figure 3.

Case 2 – (a and c) Fundus fluorescein angiography of cluster of tumors, (b and d) optical coherence tomography angiography of the lesions in Figure 3a and c. Individual tumor can be identified distinctly in optical coherence tomography angiography than fundus fluorescein angiography

Case 3

A 19-year-old boy with a family history of VHL disease presented with decreased vision in the left eye. Fundus evaluation of the right eye did not reveal any tumor. On fundus evaluation of the left eye, an RCH was seen in the superotemporal quadrant [Fig. 4a] with the presence of neurosensory detachment at the macula. On careful fundus evaluation, additional tumors were seen nasal to the optic disc and in the inferotemporal quadrant. On FFA, five tumors were identified in his left eye and three in the right eye. The larger tumor in the left eye showed leakage in the late phase [Fig. 4c and d] On OCTA, five tumors were identified in the left eye. Some of these lesions were better delineated on OCTA as compared to FFA with better visualization of the feeder and draining vessels [Fig. 4e, 5a and b]. OCTA of the tumors in the right eye could not be captured due to their peripheral location. In the deeper retinal sections of OCTA, signal void areas were seen around the tumor [Fig. 4f]. On OCT, these signal void areas corresponded to intraretinal cystic spaces in the inner and outer retina [Fig. 4b].

Figure 4.

Case 3 – (a) Color photograph of large retinal capillary hemangioblastoma with precisely identifiable feeder and draining vessel, (b) optical coherence tomography through the large tumor showing intraretinal cyst, (c) early phase fundus fluorescein angiography of large tumor with well-defined margins and feeder and draining vessel, (d) late phase fundus fluorescein angiography of tumor with blurring of margin due to leakage, (e) optical coherence tomography angiography of large tumor with well-defined margins and feeder and draining vessel, (f) Deeper retinal sections of optical coherence tomography angiography showing signal void areas in the deep capillary plexus around the tumor

Figure 5.

Case 3 – (a) Fundus fluorescein angiography of a small retinal capillary hemangioblastoma with blurring of margin due to leakage. Feeder and draining vessels are not seen, (b) optical coherence tomography angiography of lesion on Figure 5a with well defined margins. Feeder and draining vessel are precisely identifiable

Case 4

A 22-year-old boy was detected to have the abnormal optic disc in the right eye on routine fundus evaluation. A grayish white, horizontally oval, elevated lesion was seen inferior to the optic disc. The lesion was obscuring the inferior one-third of optic disc [Fig. 6]. There was no evidence of hard exudates or subretinal fluid around the lesion. OCT showed intact nerve fiber layer over the lesion. The lesion was not well defined. Few hyperreflective foci were seen within the lesion with shadowing. The retinal and the choroidal layers adjacent to the lesion were intact. On FFA, a retinal vessel was seen dipping into the lesion in the arterial phase suggestive of feeder vessel. Stippled hyperfluorescence within the lesion was seen in transit phase, and intense staining was seen in the late phase [Fig. 7a and b]. No lesions were seen in the retinal periphery in either eye. A diagnosis of juxtapapillary RCH was made in view of rich intrinsic vascularity with a retinal feeder vessel. OCT features were suggestive of sessile type.

Figure 6.

Case 4 – Colour photograph showing greyish, horizontally oval lesion obscuring the inferior one third of optic disc

Figure 7.

Case 4 – (a) Early phase fundus fluorescein angiography showing retinal feeder vessel (arrowhead) and stippled hyper fluorescence within the lesion, (b) late phase fundus fluorescein angiography showing intense staining of lesion, (c) superficial slabs of optical coherence tomography angiography showing feeder vessel (arrow) with its branches. The branches are not evident in fundus fluorescein angiography, (d) deeper slabs of optical coherence tomography angiography showing bright spots (dashed arrow) within the lesion suggestive of intrinsic vascularity (e and f) Corresponding b scans of c and d

On OCTA, the feeder vessel and the branching network of vessels were seen in the superficial slab. Intrinsic vasculature was seen as bright punctate spots in the deeper slabs [Fig. 7c-f].

Discussion

Early lesions of RCH are tiny and can be missed on clinical examination with slit lamp biomicroscopy and indirect ophthalmoscopy. FFA can identify subclinical tiny lesions, thereby enabling early treatment. In our series, FFA could identify tumors as small as the width of a third order retinal artery, which were missed on clinical examination. OCTA too identified these tiny tumors, but only those closer to the posterior pole. Peripheral tumors could not be captured on OCTA due to the limitations of current OCTA technology. Emerging OCTA technology that allows peripheral fundus screening would aid noninvasive screening of VHL patients.

Exophytic juxtapapillary RCH is orange-red and has an appearance similar to peripheral RCH and can be diagnosed easily. However, an endophytic or sessile juxtapapillary RCH can be misdiagnosed with papillitis, unilateral papilledema, choroiditis, choroidal hemangioma, or choroidal neovascularization.[3] FFA can identify the vascular nature of the tumor and aids in diagnosis. In our series, OCTA could identify the feeder vessel and the intrinsic vasculature of the sessile RCH (Case 4) comparable to FFA. Hence, OCTA can be used as a noninvasive diagnostic tool in the identification of juxtapapillary RCH.

On OCTA, tumors were seen in the superficial capillary plexus and in sections superficial to it, suggesting its origin in the superficial layers. Tumors were bright on OCTA due to their rich vascularity. Few dark spots were seen within the tumor, which would probably, represent intercapillary areas. In eyes with multiple tumors arranged in clusters, each tumor could be identified distinctly on OCTA as compared to FFA, an advantage attributable to its dye less imaging [Fig. 3]. Tumors captured in the early phase of FFA show well-defined borders, whereas tumors captured in late phase are ill-defined due to obscuration of margins by leakage of dye. The depth of the lesion can be identified on OCTA better than FFA. In larger tumors, color photograph can precisely identify feeder and draining vessels. However in small tumors, the feeder and the draining vessels can be identified precisely in OCTA, which can be missed on the color photograph and FFA. FFA gives better information about the activity of tumor by revealing leakage.

OCTA has been shown to be helpful in monitoring response to treatment and identification of harmless nonvascular lesions in VHL disease.[6]

OCTA has many disadvantages. The smaller field requires repeated imaging and patient co-operation. It prevents imaging of the mid-peripheral and peripheral retina. RCH are predominantly located in the mid-periphery and OCTA in the present era with limited scan length fails to image them. The presence of motion artifacts results in degradation of image quality and duplication of lesions [Fig. 2b]. Prolonged acquisition time is exhaustive. In Case 2 and 3, even a few accessible tumors located close to the posterior pole, could not be captured as repeated imaging exhausted the patients. However, additional details such as depth of the lesion, elevation from the retina, vitreous traction, and overlying retinal changes can be obtained by OCTA due to simultaneous acquisition of OCT.

Conclusion

OCTA can identify tumors in VHL missed on clinical examination. It can identify the feeder vessel and intrinsic vasculature of sessile juxtapapillary RCH and aids in its diagnosis. Tumors are better defined, localized in OCTA than FFA due to the absence of leakage. FFA can identify nearly all the early tumors, but OCTA fail to image the peripheral tumors due to its smaller field and prolonged acquisition time. Technological advances and development of wide-field OCTA in the future can be helpful in identifying all the peripheral lesions.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.