Zhou N et al. (2021), Appearance of Tumor Vessels in Patients With Ch...

ECB-ART-50689

Front Oncol 2021 Nov 01;11:762394. doi: 10.3389/fonc.2021.762394.

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Appearance of Tumor Vessels in Patients With Choroidal Osteoma Using Swept-Source Optical Coherence Tomographic Angiography.

Zhou N , Xu X , Liu Y , Wei W , Peng X .

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OBJECTIVE: To report the morphologic characteristics of tumor-related vasculatures and their association with secondary choroidal neovascularization (CNV), subretinal fluid (SRF), choroidal thickness, retinal pigment epithelium (RPE) alterations, subretinal hemorrhage, and tumor decalcification in eyes with choroidal osteoma (CO), using swept-source optical coherence tomographic angiography (SS-OCTA). DESIGN: Cross-sectional observational study. PARTICIPANTS: We included 26 patients recruited from Beijing Tongren Hospital with a diagnosis of CO, based on the presence of yellow-orange mass deep to the RPE under indirect ophthalmoscopy and occupying the choroid with well-defined margins and bone density on ultrasonography or computed tomography and focal hyperfluorescent spots with no homogeneous pattern on fluorescein angiography/indocyanine green angiography (FA/ICGA). Data were collected from April 1, 2020, to April 1, 2021, and analyzed from April 30 through May 30, 2021. METHODS: Applying SS-OCTA systems operating at 1,050-nm wavelengths, eyes with CO were imaged. MAIN OUTCOME AND MEASURES: Tumor-related vasculature in eyes with CO was characterized using multimodal imaging that included fundus photography, FA/ICGA, SS-OCT, and SS-OCTA, and the images were anatomically aligned. CO thickness was manually measured as the distance between the upper boundary of the tumor and the underlying sclerochoroidal interface on the SS-OCT images. Subfoveal choroidal thickness was manually measured as the distance between the Bruch membrane and the sclerochoroidal interface on the SS-OCT images. RESULTS: Of the 26 Asian patients, 16 (62%) were women and 10 (38%) were men. The mean age was 26.8 years (median, 23; range, 8-45 years), and the mean best corrected visual acuity (BCVA) was 20/40. Thirty-three eyes underwent imaging and were diagnosed with CO. Indocyanine green angiography identified inhomogeneous hyperfluorescence due to tumor-related vasculature, and all corresponded to the structures that appeared as sea-fan vascular networks (SFVNs) combined with clusters of tangled vessels on SS-OCTA images. SFVNs were detected on SS-OCTA imaging in all eyes (100%), terminal tangled vascular structures in 32 of 33 eyes (97%), but not identified on ICGA. Of the 33 tangled vascular structures, 32 (97%) were located at the edge of or inside the tumor, and only 1 (3%) was associated with type 2 neovascularization. In addition, SS-OCT revealed SRF in 33 eyes (100%), 33 (100%) were located at the edge of CO, and only 1 was underlying macular. SRF with retinal edema was seen in 30 of 32 eyes (94%). CONCLUSIONS: In eyes with CO undergoing SS-OCTA imaging, tumor-related vasculature appears as SFVNs combined with tangled vascular structures or few type 2 neovascularization. The identification of actual tumor vasculature in patients with CO as SFVNs with inner or terminal vascular tangles rather than previously described CNV may help facilitate understanding of their pathogenesis, tumor control, and response to treatment.

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	Figure 1. (Patient 4) (A) Fundus examination revealed two orange-red lesions in the posterior fundus, one located at peripapillary with partial decalcification, another small lesion in the macula area. (B) FA/ICGA revealed that the hypofluorescent area observed in the early phase corresponds to the extent of osteoma but the borders may be difficult to demarcate, and diffuse mild hyperfluorescence in late phase. (C) On the SS-OCT, B-scan revealed a 376-μm-thick domed tumor and 619-μm-thick choroidal thickness, respectively. 16 mm B-Scan: white star: trabecular bone; green star: denser and striated cortical bone; long orange arrow: Haversian or Volkmann vascular channels; red arrowheads: hyperreflective dots; blue arrow: alteration of external retinal layers and RPE above the tumor; white arrow: the external choroid seems pushed toward the outside and compressed. (D) The SS-OCTA boundary segmentation showed that the SFVNs and terminal vessels appeared intertwined with tangled vascular structures that corresponded to a tumor vessel on B-scans. (E) The En-face Retinal Depth Encoded of the 6 × 6 mm SS-OCTA cube scan demonstrated two areas of quiescent tumor vasculatures with no exudative sign found on the B-scan. The vascular network is sea-fan-shaped with small vascular tangles, the terminal vessels of the vascular network are thinner, and the terminal vessels are thin, little showing angiomatous dilation. The tumor-related vasculature appeared to be composed of sea-fan vascular networks and numerous tangle vessels when the lesions were magnified, as outlined in our schematic drawing (F), which is consistent with the tumor-related vasculature on ICGA (B).
	Figure 2. (Patient 2) (A) Fundus examination revealed a yellowish-orange lesion located at peripapillary associated with a local SRF involved macular. (B) On the SS-OCT, B-scan revealed a 296-μm-thick flat osteoma in the early stage. 16 mm B-Scan: long orange arrows: Haversian or Volkmann vascular channels; blue arrow: alteration of external retinal layers and RPE above the tumor; white arrow: the external choroid seems pushed toward the outside and compressed. The trabecular bone, dense bone, and striated bone were not demonstrated in the early stage of the tumor. (C) The SFVNs and tangled vascular structures of tumor-related vasculature were clearly seen on SS-OCTA before and after anti-VEGF treatment. (D) Two months after the second ranibizumab (0.5 mg) injection, SS-OCTA showed regression of SRF, but no reduction of the terminal vessels in the tumor-related vasculature that appeared as a dilated vessel connected to the SFVN.
	Figure 3. (Patient 14) (A1, 2) Fundus examination revealed large diffused yellowish-orange lesions in the posterior fundus involved the macula, with partial decalcification. (B1, 2) SS-OCTA revealed SFVNs with tangled vascular structures that corresponded to the tumor-related vasculature seen on FA/ICGA (arrows). The En-face Montage images of the 23.5 × 17.5 mm SS-OCTA exhibited two large areas of quiescent tumor vasculature with no exudative sign found on the B-scan; the tumor-related vasculature appeared to be composed of sea-fan vascular networks and numerous tangle vessels when the lesions were magnified as 6 × 6 mm and 3 × 3 mm (B3–5), respectively. The caliber of tumor vessels is commonly one-eighth to one-quarter that of a major retinal vein at the disc margin, and occasionally they are as large as such veins. The tumor blood vessels frequently form networks that often resemble part or all of a carriage wheel. The vessels radiate like spokes from the center of the complex to a circumferential vessel bounding its periphery. SFVNs vessel networks may also be irregular in shape, without a distinct radial pattern.
	Figure 4. (Patient 3) (A) SS-OCTA showed SFVNs with tangled vascular structures that corresponded to the tumor-related vasculature seen on FA/ICGA ( eFigure 4B ). (B) Type 2 neovascularization and tumor-related vasculature were seen when the boundary layers on the cross-sectional SS-OCTA B-scan transitioned from the top of the lesion to choroid.

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