Management of Orbital and Periocular Vascular Anomalies

Major Review

Management of Orbital and Periocular Vascular Anomalies Andrew W. Stacey, M.D.*, Joseph J. Gemmete, M.D.†, and Alon Kahana, M.D., Ph.D.* *Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, and †Department of Radiology, University of Michigan, Ann Arbor, Michigan, U.S.A.

Purpose: To review the treatment modalities available to clinicians who treat orbital and periocular vascular anomalies, with a focus on newer approaches. Methods: The authors’ experience, along with a literature review, was used to provide a concise summary of the available approaches to the treatment of periocular vascular anomalies. Emerging diagnostic tools and therapies are highlighted. Results: The treatment of orbital and periocular vascular anomalies, including vascular malformations and tumors, increasingly utilizes a multidisciplinary team and a combination of endovascular, percutaneous, and open surgical techniques. Conclusions: A growing reliance on new instrumentation and tools in a team-oriented approach to treatment may lead to better results with improved visual function and cosmesis and with reduced risk of complications. (Ophthal Plast Reconstr Surg 2015;31:427–436)

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ascular anomalies are a common finding in all age groups and have been reported in up to 1% of children.1 Classification of vascular anomalies is based on the system produced by The International Society for the Study of Vascular Anomalies.2,3 Under the current system, anomalies are divided into 2 groups: vascular tumors and vascular malformations. Vascular tumors represent anomalies with a significant component of cellular proliferation. Vascular malformations are anomalous channels of the arterial, venous, capillary, and/or lymphatic vascular system. Further characterization of vascular lesions by their flow rate aids in diagnosis and can help direct treatment. These characteristics are an important distinction for vascular anomalies in and around the orbit. Table 1 lists the periocular vascular anomalies based on The International Society for the Study of Vascular Anomalies categories of tumor versus malformation, adapted using flow characteristics, as recommended by the Orbital Society Consensus Statement.5 The authors find that for treatment purposes, the hemodynamic-based classification system is still quite useful, although it may not be as biologically rigorous. In a recent review, Rootman et al.6 describe the clinical and imaging tools that can help determine flow rate and lead to a proper diagnosis. Proper diagnosis of a vascular anomaly is absolutely critical for planning and executing a successful treatment. The current review focuses on the treatment of orbital and periocular vascular anomalies, based on the 27+ year combined Accepted for publication April 10, 2015. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, 1000 Wall St., Ann Arbor, MI 48105. E-mail: akahana@med. umich.edu DOI: 10.1097/IOP.0000000000000504

Ophthal Plast Reconstr Surg, Vol. 31, No. 6, 2015

experience of the senior authors as part of a vascular anomaly treatment team at a large academic medical center, summarizing lessons learned from treating approximately 100 periocular and orbital vascular anomalies in addition to hundreds of craniofacial and brain vascular anomalies. This review is not meant to be comprehensive but rather to highlight the newer concepts that are beginning to guide the treatment of these challenging lesions. Assessing the flow dynamic of a vascular lesion is a critical first step in assessing its etiology, and this has been reviewed elsewhere.6 In brief, flow dynamics can be assessed through history, clinical exam, and imaging studies. Useful clinical exam techniques involve orbital palpation, ocular auscultation, and clinical observation of a lesion with and without valsalva. Useful, noninvasive imaging studies include Doppler ultrasound, CT, and MRI. CT is excellent at evaluating for calcium and bone involvement, whereas MRI can provide exquisite soft tissue differentiation. CT and MRI can also be used for static angiograms (CT Angiography [CTA] and magnetic resonance angiography [MRA]) and venograms. Flow dynamics can be assessed via dynamic MRA, which is often referred to using the proprietary term of the manufacturer, e.g., TRICKS (GE Healthcare, Wauwatosa, WI), 4D-TRAK (Philips Healthcare USA, Andover, MA), or syngo TWIST (Siemens Corporation USA, Washington, D.C.).7 These are particularly useful for assessing flow through abnormal arterial channels as well as veins that may have arterial flow. The potential of a vascular anomaly to distend can be detected via a valsalva maneuver. More often, the authors prefer to compare imaging in the supine versus prone positions, which is not dependent on valsalva effort. Finally, digital subtraction angiography utilizes direct injection of contrast dye in the artery supplying the lesion, and provides excellent spatial and temporal resolution. The dynamic information obtained by performing an angiogram is particularly important in the evaluation of arteriovenus malformations (AVM). Treatment of periocular vascular malformations can be particularly challenging due to the risk of retrobulbar hemorrhage and the propensity of these anomalies to recur. Surgical excision can be difficult due to the propensity for certain malformations to bleed and due to the more invasive surgical approaches required for safe removal of vascular malformations in the orbital apex. Furthermore, treatment can be complicated by vascular malformations that are in close proximity to or frankly infiltrating important orbital structures including the globe, lacrimal system, extraocular muscles, and cranial nerves including the optic nerve. Fortunately, several recent advances in the medical and surgical treatment of vascular malformations have provided new options for treating even the most complex orbital and periocular lesions. Often, these treatment options require a multidisciplinary team that includes not only an oculoplastic surgeon but also interventional radiologists, cardiologists, neurosurgeons, and at times plastic surgeons and otolaryngologists. In this review, the authors will

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TABLE 1. The periocular vascular malformations can be categorized as vascular tumors or vascular malformations Vascular tumors • Infantile hemangioma • Congenital hemangioma • Hemangioblastoma • Hemangiopericytoma

Vascular malformations High flow: • Arteriovenous malformation Mixed flow: • Arteriovenous fistula Low flow: • Venous malformation • Lymphatic malformation • Cavernous venous malformation

The vascular malformations can be further divided by the rate of flow through the anomalous channels in the lesion (a clinically useful approach) or based on the biological origins and anatomical complexity of the anomaly, i.e., simple vs. combined, as preferred by the ISSVA classification system. (The authors acknowledge the ISSVA classification, which is an important tool for research and serves to classify all vascular anomalies across the body. However, for an orbital surgeon, flow rate is of primary concern and is clinically useful for the treatment of orbital vascular anomalies in particular. Hence, the authors chose to provide an ISSVA-based classification that still utilizes the Orbital Society consensus statement.4,5) ISSVA, The International Society for the Study of Vascular Anomalies.

highlight the current and emerging treatment options for different subtypes of orbital and periocular vascular anomalies. High-Flow Malformations. Arteriovenus Malformations. An AVM is a congenital anomaly that consists of an abnormal nidus of vascular channels with feeding arteries and draining veins with no normal intervening capillary network. This is likely the result of abnormal cytokine release by diseased venous endothelium.8 Over time, the venous outflow veins of the lesion experience profound distention and dilation secondary to the high-pressure, pulsatile arterial flow with subsequent “arterialization” of the venous walls. Further expansion occurs as arterioles insert onto the pathogenic vein—the so-called nidus. The result of such expansion is a pulsatile mass with an increased risk of hemorrhage. Orbital AVMs can present clinically with proptosis, pain, diplopia, ecchymoses, and/or vision loss. The main risks of orbital AVMs are from mass effect and compartment syndrome, but they can also involve vascular “steal” away from normal tissues in and around the eye along with impairing venous drainage. Successful treatment of an AVM requires identification and treatment of the nidus as well as any residual abnormal venous endothelium. A key to treatment of AVMs is proper diagnosis and mapping of the arterial and venous components, including the feeding and draining vessels (Fig. 1). While invasive angiography is the gold standard for diagnosis of orbital AVM, noninvasive imaging techniques, such as CTA or contrast-enhanced dynamic MRA are playing an increasingly important role in the diagnosis and treatment planning for an AVM. Every major manufacturer of MRI instruments now has a protocol for dynamic MRA, and it is important that the orbital surgeon meet with neuroradiology counterparts to devise the appropriate imaging protocol for orbital AVMs.7 The goal of AVM treatment is to eradicate the AVM nidus and the diseased venous endothelium to prevent recurrence. This requires placement of a permanent agent within the nidus. In the authors opinion, surgical ligation or occlusion of the feeding artery with coils should not be performed because the lesion will develop collateral arterial feeders that will make treatment of the lesion even more difficult. Alcohol is the agent most often used for embolization of peripheral AVMs, given that it is permanent and probably the most effective. However, use of alcohol around the orbit should be considered with great

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caution given the potential for significant swelling and tissue necrosis. Preoperative embolization with glue and/or Onyx can be useful in eliminating blood flow prior to surgical resection.9 In the case of periocular AVMs, percutaneous embolization can also be very useful (Fig. 1E). However, without excision of the nidus and diseased endothelium, the AVM will recur. Hence, postembolization excision is the standard of care. The keys to successful surgery are good exposure, meticulous hemostasis (some residual flow is almost always present even after embolization), and protection of vital structures. In the authors’ opinion, optimized exposure leads to improved access and better hemostasis. There are several good surgical approaches available for orbital surgery, and at times it can be tempting to use a narrower, less invasive approach. If no hemorrhage occurs, then such an approach is deemed successful. However, in the context of a sudden hemorrhage, poor exposure with limited access to the posterior feeding vessels can lead to untoward consequences and possibly tragic results. Hence, the surgeon should consider the flow rate, proximity of vital structures, and potential intraoperative complications, when choosing the best approach to orbital surgery for vascular anomalies. A lateral orbitotomy with a bone window is often considered standard of care in cases of larger lesions involving the lateral orbit. In addition, the authors experience of approximately 10 patients with infiltrative or compressive lesions that involve the superior orbit and apex, a transcranial orbitotomy (pterional for more lateral lesions, frontal for more medial lesions) performed in conjunction with a neurosurgeon, has provided ideal exposure and facilitated successful surgical treatment.10 The only complication encountered was temporal wasting in 1 patient who underwent a frontal craniotomy, requiring a plastic reconstructive procedure for correction. Mixed Flow Malformations. Arteriovenus Fistula. It can be congenital or acquired. When acquired, the connection between the arterial and venous system can be due to trauma or it can be idiopathic. The common etiology is damage to an arterial wall and subsequent connection to a venous system, bypassing the arteriolar and capillary networks. Arteriovenus fistulas are characterized as either high- or low-flow. The most common periocular arteriovenus fistulas is the carotid-cavernous sinus fistula (CCF). Most CCFs are high-flow connections between the internal carotid artery and the cavernous sinus and are usually the result of trauma. A less common form, the indirect CCF, is a low-flow fistula that results from a connection between a dural vein and a branch of the internal or external carotid artery, and is usually the result of systemic disease. Carotid-cavernous sinus fistula presents with proptosis, conjunctival vascular congestion, and conjunctival vascular dilation. An ocular bruit may be heard in high-flow states. Orbital imaging will reveal vascular congestion, enlarged extraocular muscles, enlargement of the superior ophthalmic vein, and possibly enlargement of the cavernous sinus. Treatment should be focused on closing the fistula connection. In low-flow states, this may occur spontaneously. When intervention is required, endovascular embolization from an arterial or venous approach is the preferred treatment for a CCF.11,12 On occasion, a dilated superior ophthalmic vein may be the best option for accessing the CCF. In such a case, an orbital surgeon can perform the orbitotomy to expose the dilated superior ophthalmic vein, which is best identified through a superior eyelid crease incision followed by careful blunt dissection along the lateral edge of the superior rectus muscle. Ideally, this procedure can be performed in a combined operating room/ endovascular suite. When such a combination suite is not available, the orbital surgeon should aim to secure an intravenous cannula in the superior ophthalmic vein and close the incision prior to transferring the patient to the endovascular suite.

© 2015 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.



Orbital and Periocular Vascular Anomalies

FIG. 1. Twenty-one-year-old male with a thrill over the left upper eyelid on palpation. A, Frontal photo shows swelling and erythema involving the left upper eyelid. B, Axial short tau inversion recovery (STIR) T2-weighted images shows multiple flow voids in the left superior aspect of the boney orbit and soft tissues of the upper eyelid. C, Frontal left internal carotid angiogram shows a large AVM over the left orbit with arterial feeders from the ophthalmic artery. D, Frontal left external carotid angiogram shows a large AVM with the left orbit with arterial feeders from branches from the internal maxillary and superficial temporal artery. E, Frontal fluoroscopic image shows the percutaneous injected glue cast within AVM. F, Postembolization frontal left internal carotid angiogram shows a decrease in the size of the AVM when compared with (C). AVM, arteriovenus malformation.

Low-Flow Malformations. Venous Malformations. It can occur in the orbit and are present at birth. They are not always clinically apparent and tend to grow in proportion to the growth of the child. Growth is most pronounced during puberty, and in woman also during pregnancy and menopause. These malformations can be solitary or associated with other malformations, small or large, deep or superficial, and well circumscribed or infiltrative, involving multiple tissue planes. They present clinically with proptosis, diplopia, vision loss, or periodic ecchymosis secondary to hemorrhage and thrombosis. Clinical examination should be completed at rest and again while the patient bends over (dependent position) or performs a valsalva maneuver, which can elicit an increase in proptosis due to increased venous pressure and venous malformations (VM) expansion. It has been suggested that an elevated D-dimer level is specific for a VM and can help distinguish VMs form lymphatic malformations (LMs).13,14 Distensibility is also a key feature of VMs.15 However, not all VMs are distensible, and in the authors’ experience, nondistensible VMs may be associated with more frequent episodes of hemorrhage.16 The authors hypothesize that this is because of the inability of the lesion to respond to changing pressure and flow dynamics. Most of the anterior and intraconal distensible lesions can frequently be identified by history alone—the patient will have likely noticed the change in pressure or lesion size with dependent position, straining, or exercise. Clinical exam can usually

confirm the distensibility of such a lesion. However, smaller and more posterior distensible lesions may not manifest on exam, and a high index of suspicion is required for their diagnosis. Imaging by CT or MRI, with contrast, in both supine and prone positions, can highlight the distensible component. In patients who require sedation, including children, the valsalva effect can be elicited by the anesthesiologist by increasing intrathoracic pressure. The importance of proper diagnosis cannot be overemphasized because the diagnosis often drives treatment options, and a distensible venous anomaly hidden within a LM can lead to very unpleasant surprises if surgical or sclerosis treatment is attempted. Observation of an orbital VM is a reasonable option if the lesion is relatively asymptomatic.16 Symptomatic VMs require treatment. The treatment options include excision, embolization, and sclerosis. Excision requires excellent exposure and control of the entire vascular channel to avoid intraoperative hemorrhaging. In the orbit, this can be difficult, particularly for smaller posterior lesions causing optic neuropathy or dysmotility. For a more anterior lesion, thrombosis with a thrombin/fibrinogen combination, such as Tisseel (Baxter) or Evicel (Ethicon) can be used to facilitate complete excision. Embolization with glue or Onyx (Covidien) leaves behind the abnormal endothelium, and creates a space-occupying mass that can cause a permanent mass effect. Combining embolization with excision has been a preferred approach for many years (Fig. 2).


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FIG. 2. Three-year-old boy with limited use of his left eye from an extensive lymphovenous malformation. A, Frontal photo shows apraxia of the left upper eyelid with bluish discoloration of the subcutaneous soft tissues. B, Intraoperative photo during debulking of the malformation following extensive embolization. C, D, Coronal contrast-enhanced CT images of the left orbit demonstrate enhancing tubular structures within the left upper eyelid extending posterior in the extra and intraconal compartments. E, F, Coronal STIR T2-weighted MRI images and (G, H) fat-saturation coronal T1-weighted contrast enhanced images show multiple high signal tubular structures within left upper eyelid which enhance and extend posterior into the extra and intraconal compartments. I, Intraoperative photo shows a butterfly needle in the venous malformation used for the injection of glue into the lesion under fluoroscopy prior to surgical resection. Antero-posterior fluoroscopic image (J) and lateral fluoroscopic image (K) shows the extensive glue cast within the venous malformation.

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The use of sclerosants in VMs has been limited because of the risk of drainage/leakage of the sclerosant into the vascular supply of the eye and/or cavernous sinus. However, the development of microballoons that can be floated into the varix from an endovascular approach has enabled the use of aggressive sclerosing treatment, followed by active decompression of the varix to promote collapse and permanent scarring (Fig. 3). Careful embolization can also be used to block outflow, although this is much trickier and not as well controlled. A percutaneous approach to the VM, or an open approach through an orbitotomy, represents additional options for accessing the VM for embolization and/or sclerosis (Fig. 4). Options for sclerosants include alcohol, sodium tetradecyl sulfate 3%, sodium morrhuate 5%, bleomycin A5, and doxycycline.6,17 A recent report has added pingyangmycin 1.5 mg/ml to the list of sclerosants used successfully in the orbit.18 The sclerosant can be enhanced through foaming, which is performed by mixing the sclerosant (e.g., sodium tetradecyl sulfate with air or bleomycin with albumin). The foam becomes space occupying, which means that care must be taken with regard to volume that is used in the treatment: 3 to 4 ml can usually be tolerated without a severe compartment syndrome. However, a compartment syndrome can lead to acute vision

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loss, and hence the surgical team should always be on the ready for emergent orbital decompression through lateral canthotomy and cantholyses. It is the authors protocol to have the orbital surgeon present when potentially larger volumes might be needed to treat orbital vascular lesions. Lymphatic Malformations. These are present at birth and are composed of abnormal, dilated lakes of lymphatic tissue that result from defective embryologic development of the primordial lymphatic channels. Lymphatic malformations can be classified radiographically as macrocystic (cysts ≥2 cm), microcystic (cysts