Sclerotherapy for low-flow vascular malformations of the orbital and periocular regions: Systematic review and meta-analysis

Maria, Lucio De; Sanctis, Paolo De; Tollefson, Megha M.; Mardini, Samir; Garrity, James A.; Morris, Pearse; Bendel, Emily C.; Brinjikji, Waleed

doi:10.1016/j.survophthal.2019.08.003

Cited by 15 publications

(25 citation statements)

References 20 publications

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“…10,13,14 However, a recent systematic review of the literature, which analyzed 12 studies containing 142 patients with orbital VLMs, found that only 55% of patients experienced complete cure, with 45% experiencing partial cure. 22 Notably, the authors did not stratify the results between venous, lymphatic, and mixed lesions; thus, the success rate of treating venous-dominant lesions with sclerotherapy remains unclear. While 4 of 6 patients treated with sclerotherapy in the current study experienced temporary improvement in symptoms, all 6 lesions eventually recurred.…”

Section: Discussionmentioning

confidence: 99%

Recurrence of Distensible Orbital Venous-dominant Venolymphatic Malformations After Sclerotherapy Versus Embolization With Excision

Cohen

Goldberg²,

Rootman³

2021

Ophthalmic Plastic &Amp; Reconstructive Surgery

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Treatment for orbital venolymphatic malformations (VLMs) commonly includes 3 major options: sclerotherapy, surgery, and embolization followed by surgical excision. Each has certain advantages, although it is not clear whether all are effective. The authors characterize the clinical course for a series of patients with distensible orbital venous-dominant VLM treated with sclerotherapy and/or embolization with excision.Methods: In this cross-sectional cohort study, patients affected by distensible orbital venous-dominant VLM presenting to the orbital and ophthalmic plastic surgery service from 2014 to 2020 were identified. Patients were included if they presented with a moderate-flow, distensible venous-dominant malformation associated with Valsalva-related symptoms (e.g., pain, proptosis, and diplopia).Results: Six cases were treated with sclerotherapy. Four underwent multiple treatments, with a mean ± SD of 3.5 ± 2.3 (range 1-7). All patients in this group failed to improve or experienced recurrence of symptoms after sclerotherapy. Twelve cases were treated with embolization and excision. Resolution of symptoms in all 12 cases was noted and maintained for a mean of 3.4 ± 2.1 years. There have been no cases of recurrence. Patients treated with sclerotherapy were more likely to experience recurrence of symptoms compared to those treated with embolization and excision (p < 0.001).Conclusions: Treatment of distensible venous-dominant moderate-flow orbital VLM with sclerotherapy may provide temporary improvement in some cases. However, in the medium to long term, recurrence was universal in this series. Embolization with excision appears to provide more definitive management, avoiding recurrence in all cases for a mean follow-up of 3 years.

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Section: Discussionmentioning

confidence: 99%

Recurrence of Distensible Orbital Venous-dominant Venolymphatic Malformations After Sclerotherapy Versus Embolization With Excision

Cohen

Goldberg²,

Rootman³

2021

Ophthalmic Plastic &Amp; Reconstructive Surgery

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“…About 2x10 5 HUVECs were seeded on six-well plate overnight than transfected with lentiviral vectors expressing the GFP, TIE-WT, and TIE2-L914F in the presence of polybrene (8 mg/ml). After incubation for 48h, cells were treated with DMSO or rapamycin (MCE, Shanghai, China) for another 48h for subsequent experiments.…”

Section: Lentiviral Transfectionmentioning

confidence: 99%

“…Extensive VMs cause pain, bleeding, anatomic distortion and organ dysfunction [1][2][3]. Sclerotherapy is the traditional treatment, alone or in combination with surgical resection, but it has a series of side effects, such as skin necrosis, swelling and peripheral nerve de cits [2][3][4][5][6]. Current therapies are invasive and rarely curative as lesions tend to recur, so it needs to seek new therapies to alleviate clinical symptoms.…”

Section: Introductionmentioning

confidence: 99%

AKT/FOXO1 axis links cross-talking of endothelial cell and pericyte in TIE2-mutated venous malformations

Jiang

Si²,

Huang

et al. 2020

Preprint

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Background: Venous malformations (VMs), most of which associated with activating mutations in the endothelial cells (ECs) tyrosine kinase receptor TIE2, are characterized by dilated and immature veins with scarce smooth muscle cells (SMCs) coverage. However, the underlying mechanism of interaction between ECs and SMCs responsible for VMs has not been fully understood.Methods: Here, we screened 5 patients with TIE2-L914F mutation who were diagnosed with VMs by SNP sequencing, and we compared the expression of platelet-derived growth factor beta (PDGFB) and α-SMA in TIE2 mutant veins and normal veins by immunohistochemistry. In vitro, we generated TIE2-L914F-expressing human umbilical vein endothelial cells (HUVECs) and performed BrdU, CCK-8, transwell and tube formation experiments on none-transfected and transfected ECs. Then we investigated the effects of rapamycin (RAPA) on cellular characteristics. Next we established a co-culture system and investigated the role of AKT/FOXO1/PDGFB in regulating cross-talking of mutant ECs and SMCs.Results: VMs with TIE2-L914F mutation showed lower expression of PDGFB and α-SMA than normal veins. TIE2 mutant ECs revealed enhanced cell viability and motility, and decreased tube formation, whereas these phenotypes could be reversed by rapamycin. Mechanically, RAPA ameliorated the physiological function of mutant ECs by inhibiting AKT-mTOR pathway, but also facilitated the nuclear location of FOXO1 and the expression of PDGFB in mutant ECs, and then improved paracrine interactions between ECs and SMCs. Moreover, TIE2 mutant ECs strongly accelerated the transition of SMCs from contractile phenotype to synthetic phenotype, whereas RAPA could prevent the phenotype transition of SMCs.Conclusions: Our data demonstrate a previously unknown mechanistic linkage of AKT-mTOR/FOXO1 pathway between mutant ECs and SMCs in modulating venous dysmorphogenesis, and AKT/FOXO1 axis might be a potential therapeutic target for the recovery of TIE2-mutation causing VMs.

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“…Extensive VMs cause pain, bleeding, anatomic distortion and organ dysfunction [1][2][3]. Sclerotherapy is the traditional treatment, alone or in combination with surgical resection, but it has a series of side effects, such as skin necrosis, swelling and peripheral nerve deficits [2][3][4][5][6]. Current therapies are invasive and rarely curative as lesions tend to recur, so it needs to seek new therapies to alleviate clinical symptoms.…”

Section: Introductionmentioning

confidence: 99%

AKT/FOXO1 axis links cross-talking of endothelial cell and pericyte in TIE2-mutated venous malformations

Huang

et al. 2020

Cell Commun Signal

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Background: Venous malformations (VMs), most of which associated with activating mutations in the endothelial cells (ECs) tyrosine kinase receptor TIE2, are characterized by dilated and immature veins with scarce smooth muscle cells (SMCs) coverage. However, the underlying mechanism of interaction between ECs and SMCs responsible for VMs has not been fully understood. Methods: Here, we screened 5 patients with TIE2-L914F mutation who were diagnosed with VMs by SNP sequencing, and we compared the expression of platelet-derived growth factor beta (PDGFB) and α-SMA in TIE2 mutant veins and normal veins by immunohistochemistry. In vitro, we generated TIE2-L914F-expressing human umbilical vein endothelial cells (HUVECs) and performed BrdU, CCK-8, transwell and tube formation experiments on none-transfected and transfected ECs. Then we investigated the effects of rapamycin (RAPA) on cellular characteristics. Next we established a co-culture system and investigated the role of AKT/FOXO1/PDGFB in regulating cross-talking of mutant ECs and SMCs. Results: VMs with TIE2-L914F mutation showed lower expression of PDGFB and α-SMA than normal veins. TIE2 mutant ECs revealed enhanced cell viability and motility, and decreased tube formation, whereas these phenotypes could be reversed by rapamycin. Mechanically, RAPA ameliorated the physiological function of mutant ECs by inhibiting AKT-mTOR pathway, but also facilitated the nuclear location of FOXO1 and the expression of PDGFB in mutant ECs, and then improved paracrine interactions between ECs and SMCs. Moreover, TIE2 mutant ECs strongly accelerated the transition of SMCs from contractile phenotype to synthetic phenotype, whereas RAPA could prevent the phenotype transition of SMCs. Conclusions: Our data demonstrate a previously unknown mechanistic linkage of AKT-mTOR/FOXO1 pathway between mutant ECs and SMCs in modulating venous dysmorphogenesis, and AKT/FOXO1 axis might be a potential therapeutic target for the recovery of TIE2-mutation causing VMs.

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Sclerotherapy for low-flow vascular malformations of the orbital and periocular regions: Systematic review and meta-analysis

Cited by 15 publications

References 20 publications

Recurrence of Distensible Orbital Venous-dominant Venolymphatic Malformations After Sclerotherapy Versus Embolization With Excision

Recurrence of Distensible Orbital Venous-dominant Venolymphatic Malformations After Sclerotherapy Versus Embolization With Excision

AKT/FOXO1 axis links cross-talking of endothelial cell and pericyte in TIE2-mutated venous malformations

AKT/FOXO1 axis links cross-talking of endothelial cell and pericyte in TIE2-mutated venous malformations

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