Imaging the Microvasculature of Choroidal Melanomas With Confocal Indocyanine Green Scanning Laser Ophthalmoscopy

Mueller, A. J.

doi:10.1001/archopht.116.1.31

Cited by 90 publications

(51 citation statements)

References 27 publications

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“…A series of 18 patients with choroidal melanoma were studied prospectively with indocyanine green angiography using a confocal scanning laser ophthalmoscope (Heidelberg Retinal Angiograph, Heidelberg Engineering, Heidelberg, Germany) [11][12][13] ; two of these patients had their eyes removed following the angiogram. The eyes were fixed in 10% neutral buffered formalin for at least 48 hours, and opened via a coronal incision through the pars plana to allow for direct visualization of the tumor surface 14 and to enhance an accurate correlation with retinal landmarks by comparison with pre-enucleation fundus photographs and the confocal angiographs.…”

Section: Correlations With Indocyanine Green Angiographymentioning

confidence: 99%

“…Details of the prospective study and the angiographic-histological correlations were reported elsewhere. 13 …”

Section: Correlations With Indocyanine Green Angiographymentioning

confidence: 99%

“…The other patient had angiographic evidence of only large, preexisting choroidal vessels within the tumor (an absence of loops, Figure 1I) and showed only normal choroidal vessels histologically and no looping patterns ( Figure 1J). 13 Unlike cutaneous melanoma, which is usually accessible to biopsy without major morbidity, it is difficult to obtain representative quantities of tumor tissue from within the eye for histopathological analysis without risking compromise to vision. Thus, the ability of ophthalmologists to image prognostically significant microcirculatory patterns clinically in patients by confocal angiography or by ultrasound power spectrum analysis 36 provides noninvasive substitutes for biopsy.…”

Section: Histology Of the Melanoma Microcirculation Its Prognostic Smentioning

confidence: 99%

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Vascular Channel Formation by Human Melanoma Cells in Vivo and in Vitro: Vasculogenic Mimicry

Maniotis

Folberg

Hess

et al. 1999

The American Journal of Pathology

1,754

1,636

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Tissue sections from aggressive human intraocular (uveal) and metastatic cutaneous melanomas generally lack evidence of significant necrosis and contain patterned networks of interconnected loops of extracellular matrix. The matrix that forms these loops or networks may be solid or hollow. Red blood cells have been detected within the hollow channel components of this patterned matrix histologically, and these vascular channel networks have been detected in human tumors angiographically. Endothelial cells were not identified within these matrix-embedded channels by light microscopy , by transmission electron microscopy , or by using an immunohistochemical panel of endothelial cell markers (Factor VIIIrelated antigen , Ulex , CD31 , CD34 , and KDR[Flk-1]). Highly invasive primary and metastatic human melanoma cells formed patterned solid and hollow matrix channels (seen in tissue sections of aggressive primary and metastatic human melanomas) in threedimensional cultures containing Matrigel or dilute Type I collagen , without endothelial cells or fibroblasts. These tumor cell-generated patterned channels conducted dye , highlighting looping patterns visualized angiographically in human tumors. Neither normal melanocytes nor poorly invasive melanoma cells generated these patterned channels in vitro under identical culture conditions , even after the addition of conditioned medium from metastatic pattern- It is generally assumed that tumors require a blood supply for growth and metastasis. 1 The development of the tumor microcirculation compartment includes both the production of new blood vessels (angiogenesis) and their remodeling. 2 In fact, the number of vessels 3 and the patterning of the microcirculation 4 by remodeling events are used as histological markers of tumor progression. Although attention has been focused on factors that stimulate and suppress tumor angiogenesis, the molecular mechanisms underlying tumor remodeling remain enigmatic. It is therefore critical to investigate remodeling of the intratumoral microvasculature in various tumor models.Melanoma is among the better characterized tumor models with respect to prognostic staging of disease progression. The rising incidence of cutaneous melanoma makes this tumor an important public health problem. Melanoma of the interior of the eye, uveal melanoma, although much less common than cutaneous melanoma, poses a threat to vision and significant morbidity; nearly 50% of patients with uveal melanoma die from metastatic melanoma. 5 Cutaneous melanoma may disseminate through lymphatics or blood vessels. In contrast, the interior of the eye lacks lymphatics, and uveal melanoma, which develops in one of the most capillary-rich tissues of the body, is a paradigm for pure hematogeneous dissemination of cancer. 6 Therefore, the development of a tumor microcirculation in uveal melanoma is a rate-limiting step for hematological metastasis and serves as an important model for study of the cellular and molecular infrastruc-

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Section: Correlations With Indocyanine Green Angiographymentioning

confidence: 99%

“…Details of the prospective study and the angiographic-histological correlations were reported elsewhere. 13 …”

Section: Correlations With Indocyanine Green Angiographymentioning

confidence: 99%

Section: Histology Of the Melanoma Microcirculation Its Prognostic Smentioning

confidence: 99%

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Vascular Channel Formation by Human Melanoma Cells in Vivo and in Vitro: Vasculogenic Mimicry

Maniotis

Folberg

Hess

et al. 1999

The American Journal of Pathology

1,754

1,636

View full text Add to dashboard Cite

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“…Digital images were stripped of all identifying (health protected) information and sent to the Department of Pathology at the University of Illinois at Chicago (RF and JL) for identification of vasculogenic mimicry patterns. The thickness of vasculogenic mimicry patterns was calculated from the 201 Â 201 angiograms using methods outlined previously by Mueller et al 13 Briefly, at a pixel resolution of 512 Â 512 pixels, one pixel equals 11 Â 11 mm for a 201 image.…”

Section: Methodsmentioning

confidence: 99%

“…5,11 These patterns have also been visualized in patients with posterior choroidal melanomas by laser scanning confocal ophthalmoscopy with indocyanine green (ICG). 12,13 The histological detection of looping vasculogenic mimicry patterns has been associated with an aggressive clinical course in multiple independent studies. [14][15][16][17][18][19] The presence of these patterns is associated with monosomy 3 20 (a cytogenetic marker of aggressive uveal melanoma behavior 20,21 ) and a gene expression signature that is associated with the development of metastatic uveal melanoma.…”

Section: Introductionmentioning

confidence: 99%

Demonstrating circulation in vasculogenic mimicry patterns of uveal melanoma by confocal indocyanine green angiography

Frenkel

Barzel

Levy

et al. 2007

Eye

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Purpose Vasculogenic mimicry patterns, formed by highly invasive melanoma cells, connect to endothelial cell-lined blood vessels and contain fluid in vitro and in vivo. This study was designed to determine if fluid leaks into vasculogenic mimicry patterns without circulation, or if fluid circulates in and clears from these patterns. Methods Indocyanine green (ICG) laser scanning confocal angiography (Heidelberg Retinal Angiograph (HRA); Heidelberg Engineering, Heidelberg, Germany) was performed on nine patients with posterior choroidal melanoma in an institutional setting. Blood was drawn before the ICG injection and from the contralateral arm of the ICG injection site and 1 min after the injection. Outcome measures include time to first filling of retinal vessels and vasculogenic mimicry patterns and the time at which no fluorescence could be detected by the HRA instrument. After fluorescence was no longer detected in vessels or patterns, the tubes containing the patient's blood was imaged by the Heidelberg HRA. Results Looping vasculogenic mimicry patterns were detected focally in five patients within 30 s after injection and were detectable up to 12 min post-injection. Blood drawn before ICG injection did not autofluoresce but ICG-containing blood pooled in the tube continued to fluoresce at 1-month postinjection. Conclusions Vasculogenic mimicry patterns are not part of the endothelial cell-lined vascular system and fluid enters these patterns through leakage. The rapid infusion of ICG into these patterns after injection and the disappearance of fluorescence detectable by the Heidelberg HRA suggest that fluid circulates in these patterns and does not accumulate as a stagnant pool.

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Evaluation of the Human Choroidal Melanoma Rabbit Model for Studying Microcirculation Patterns with Confocal ICG and Histology

Mueller

Folberg

Freeman

et al. 1999

Experimental Eye Research

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Imaging the Microvasculature of Choroidal Melanomas With Confocal Indocyanine Green Scanning Laser Ophthalmoscopy

Cited by 90 publications

References 27 publications

Vascular Channel Formation by Human Melanoma Cells in Vivo and in Vitro: Vasculogenic Mimicry

Vascular Channel Formation by Human Melanoma Cells in Vivo and in Vitro: Vasculogenic Mimicry

Demonstrating circulation in vasculogenic mimicry patterns of uveal melanoma by confocal indocyanine green angiography

Evaluation of the Human Choroidal Melanoma Rabbit Model for Studying Microcirculation Patterns with Confocal ICG and Histology

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