A Novel Combined Technique to Assist with the Removal of Orbital Cavernous Venous Malformation of the Orbit Using High-Resolution Cone Beam Computed Tomography (Hr-Cbct) Imaging-Guided Embolization—Two Case Reports and a Literature Review

Abstract

Orbital cavernous venous malformations (CVMs) are the most common primary lesions in the orbit, characterized by slow growth and benign nature. CVMs that become symptomatic require intervention. Surgical management is guided by the expertise of the operating surgeon. Common surgical techniques include anterior orbitotomy (transconjunctival and transcutaneous), lateral and transcranial orbitotomy, and endoscopic transnasal approaches. Liquid agent embolization aids in easier lesion resection with reduced blood loss and potential prevention of recurrence. Our case reports detail the advantages and disadvantages of this approach, showcasing collaboration between neuroradiologists and orbital surgeons.

1. Introduction

Orbital cavernous venous malformations (CVMs) stand out as the most prevalent primary lesions within the orbit [1], comprising 4 to 6% of all intraorbital masses [1,2,3]. CVMs generally present with engorged vascular channels lined by a single layer of endothelial cells, with a diameter of 1 mm, tightly knit, and separated by fibrous septae [4]. Hongo et al. identified a somatic missense mutation, G121T (p.Gly41Cys), in the GJA4 gene part of the connexin family, in 96.2% of 26 CVM tissues. GJA4 encodes a transmembrane protein in vascular gap junctions and hemichannels. The mutation was found to be a gain-of-function mutation, resulting in the formation of a hyperactive hemichannel and loss of cellular integrity [5]. These lesions exhibit a benign nature, characterized by slow growth (with a yearly increase of 10% to 15%) [2,3,6,7,8,9], marked by thrombosis, neovascularization, and stromal hyperplasia [9]. Not all CVMs become symptomatic and require intervention. Notably, CVMs exhibit a predilection for women (60% of cases) [1,6] likely attributed to hormonal influences, notably estrogen and progesterone levels, alongside the presence of progesterone receptors in the epithelial cells of orbital CVMs [10,11,12]. While typically manifesting with benign progressive proptosis, in rare instances, CVMs may present acutely due to hemorrhage within the lesion [7]. Other common signs are the downward displacement of the eye, loss of vision, and signs of corneal exposure. Common symptoms include pain, reported variably (ranging from 6.5% to one-third of affected patients), alongside pressure sensation. Rare symptoms include diplopia, eyelid swelling, and the perception of a mass. Gaze-evoked amaurosis, though rare, may result from severe intraconal and extraconal orbital lesions, potentially attributed to transient axonal inhibition or optic nerve ischemia [1]. A fundus examination may observe compressive retinopathy/vascular damage and optic neuropathy. A study by Strianese et al. showed that choroidal folds were associated with tumors greater than 1100 mm³ [13]. Abnormal fundoscopy is significantly associated with decreased visual acuity. CT scans usually show no bone remodeling. Small tumors represent the majority of the cases, and tumor size and apical extension are associated with visual impairment [4]. A relative efferent pupillary defect is linked to both the lateral quadrant location and apical extension [13]. The classification of orbital vascular malformations adheres to the guidelines established by the International Society for the Study of Vascular Anomalies (ISSVA). According to this framework, which categorizes anomalies based on hemodynamic characteristics, CVMs are characterized by low flow and are non-distensible, indicating minimal communication with the venous system. These malformations can further be delineated based on their location within the orbit, including anterior, deep, combined, or complex lesions extending beyond the orbit [14]. Greater than 80% of orbital cavernous hemangiomas are situated in the intraconal space of the middle third of the orbit, positioned laterally to the optic nerve [1,7]. A rare presentation of an orbital CVM that extended along the maxillary division of the trigeminal nerve between the orbit and middle cranial fossa was described [15]. Diagnostic modalities such as ultrasound (US), high-resolution Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and digital subtraction angiography facilitate the precise localization of the lesion and greatly aid in surgical planning [16]. Ultrasound, in particular, offers a high degree of accuracy. The A-scan is a one-dimensional ultrasound technique that measures distances between eye structures by analyzing reflected ultrasound wave amplitudes, producing a graph with peaks representing tissue interfaces. It provides information on tumor echogenicity and nature.

In contrast, the B-scan is a two-dimensional technique that creates a cross-sectional grayscale image of the eye and surrounding structures by analyzing the brightness of reflected ultrasound waves, revealing different tissue types through varying shades of gray.

On A-scan, CVMs present a highly reflective, regularly structured lesion with moderate attenuation of echoes. On B-scan, CVMs typically exhibit a round shape with discernible topographic relationships with the globe, optic nerve, and orbital wall.

CT and MRI serve as complementary imaging tools for CVM diagnosis. On CT, they typically present as a homogeneous soft-tissue density with a variable pattern of contrast enhancement, ranging from focal enhancement in the early phase to heterogeneous and diffuse enhancement in intermediate and late phases, respectively.

On MRI, CVMs tend to appear isointense or slightly hypointense on T1-weighted sequences and hyperintense relative to muscles on T2-weighted sequences, with contrast enhancement progressing from patchy to a more uniform pattern. Arterial orbital angiography, once a mainstay in diagnosis, has been supplanted by advancements in other imaging modalities [1]. However, the hemodynamic assessment of CVMs reveals focal filling in the early phase of contrast injection, reflecting the vascular pedicle, and progressive filling in the venous phase imaging, indicative of minimal communication with inflow and outflow channels [14]. All these imaging techniques facilitate differentiation from other apical tumors such as schwannoma, meningioma, and hemangiopericytoma [17]. Effective initial screening is essential, especially in cases of decreased monocular vision, which does not respond to steroidal therapy for presumed optic neuritis [18]. Accurate diagnosis holds paramount importance for selecting effective treatment modalities, which have evolved to encompass less invasive approaches [10,16,19]. Surgical intervention becomes imperative for symptomatic CVMs, particularly for those causing optic nerve compression, proptosis, motility deficits, or visual impairment.

Surgical management is guided by the expertise of the operating surgeon, who determines the most suitable approach—whether neurosurgical, otolaryngological, or ophthalmological—based on the lesion’s anatomical location and its relationship with orbital structures. Common surgical techniques include anterior orbitotomy (transconjunctival and transcutaneous), lateral and transcranial orbitotomy, and endoscopic transnasal approaches [1,20]. Given the risk of hemorrhage during surgery, the complete removal of the malformed blood vessel may be challenging, leading to post-surgical complications and risk of recurrence (10 to 30%) [21]. In recent years, preoperative embolization has gained traction as a strategy for mitigating these risks [22]. In the following case reports, we delineate the advantages and disadvantages of this approach, involving the collaboration of neuroradiological and ophthalmological expertise.

2. Case Presentation Number 1

A 76-year-old man, with a medical history of hypertension, atrial fibrillation, and benign prostatic hypertrophy, as well as a history of bilateral cataract surgery, presented to our ophthalmological emergency service with right eye proptosis (Figure 1) associated with chemosis, conjunctivitis with abundant mucous discharge, binocular vertical diplopia, reduced visual acuity, and moderate retrobulbar pain. The best corrected visual acuity (BCVA) was 0.20 (logMAR) in the right eye (RE) and 0 (logMAR) in the left eye (LE); ocular motility showed RE hypotropia in primary gaze and preserved bilateral pupillary light reflex. Fundus examination in the RE revealed mild optic disk edema and hyperemia. High-resolution orbital contrast-enhanced computerized tomography (CT) scans revealed a densely hypervascular extraconal mass superomedially located in the right orbit, isodense with respect to the extraocular muscles, measuring 31 mm by 13 mm in width with well-defined margins. The lesion had clear contact with the medial margin of the optic nerve, with the posterior sclera, and dislocated the medial rectus muscle downward. Contrast-enhanced open 1.2T MRI showed a progressive enhancement transitioning from patchy to uniform on the orbital lesion (Figure 2). We unanimously decided to perform angiography prior to the surgery to identify collateral vessels and determine if the venous drainage of the tumor was connected to the significant venous drainage of the orbit and the eye. Additionally, angiography was conducted to understand the tumor flow, whether high or low, and to better characterize the lesion [23]. A transfemoral approach was employed to insert a 4F (4 French) guiding catheter into the left internal and external carotid artery. A biplane angiography unit (Siemens Biplane Artis q) was utilized. In the arterial phase, minute focal areas of contrast pooling in the lesional site were observed (Figure 3).

3. Case Presentation Number 2

A 59-year-old woman with a medical history of hypothyroidism presented to our ophthalmological emergency service in May 2023 with moderate retrobulbar pain in her left eye, recurrent amnesia, and hearing loss over the past month. Her best corrected visual acuity (BCVA) was 0 (logMAR) in the right eye (RE) and 0.10 (logMAR) in the left eye (LE); she had normal ocular motility, preserved bilateral pupillary light reflex, an unremarkable fundus examination, and absence of proptosis. A high-resolution orbital CT scan revealed a left-sided space-occupying lesion, isodense with respect to the extraocular muscles, measuring 12 mm by 11 mm in diameter with well-defined margins. It was primarily located in the intraconal inferomedial portion of the orbital cavity and was in clear contact with the inferior margin of the optic nerve, without connections to the extraocular muscles. Contrast-enhanced open 1.2T MRI showed an intraconal lesion measuring 11.65 mm by 13.44 mm, with a progressive enhancement transitioning from patchy to uniform. The lesion appeared hypointense in T1 and hyperintense in T2. It was in contact with the superior profile of the inferior rectus muscle, posterior to the globe, causing minimal medial and superior deviation of the optic nerve, with a cleaving adipose plane (Figure 4). Angiography was executed through the selective catheterization of the internal and external left carotid and showed a little focal area of contrast pooling in the venous phase (Figure 5). A total-body CT scan revealed cavernous vascular malformations in the liver [24,25].

Indeed, hemangiomas are most frequently found in the central nervous system but can also occur in various other locations, such as the liver. Most CVMs are unifocal, although familial cases often develop multiple malformations [26].

4. Surgical Technique

Surgery in both cases was performed under general anesthesia. In case 1, a transcutaneous anterior orbitotomy approach was chosen because the lesion was larger than 2.0 cm and closer to the orbit wall. In case 2 (lesion < 2.0 cm), a transconjunctival anterior orbitotomy approach was used to expose the anterior surface of the vascular lesion. Thorough hemostasis of surrounding tissues was ensured using bipolar McPherson forceps to guarantee clear direct visualization. Percutaneous tumor puncture was performed with a 21-gauge spinal needle (Terumo, Tokyo, Japan) (Figure 6). Following puncture, a parenchymogram was obtained to confirm correct intratumoral needle positioning and exclude the extravasation of contrast material into normal parenchyma (Figure 7). After flushing the delivery system (a short tubing with a diameter of 1.2 mm from Braun, Melsungen, Germany, and the Terumo spinal needle) with Dimethyl sulfoxide (DMSO) to prevent precipitation, the slow injection of a non-adhesive liquid embolic agent (Squid 12, Emboflu, Gland, Switzerland) was initiated under continuous fluoroscopy. High-resolution cone beam CT (HR-CBCT) imaging (DynaCT, Siemens, Erlangen, Germany) confirmed the homogeneous distribution of the embolic agent throughout the lesion with no perilesional extravasation (Figure 8). CBCT (Cone Beam Computed Tomography) provided three-dimensional visualization of the vascular bed before and after treatment, reducing procedure time, contrast agent volume, and radiation dose [27]. The lesion was subsequently excised in the same manner in both patients by applying traction with forceps and separating the surrounding tissues (Figure 9 and Figure 10). Post-surgical recovery was uneventful, and no complications were reported. Postoperative CT demonstrated complete CVM asportation (Figure 11). Both patients exhibited recovery from the symptoms present prior to surgery. Patient number 1 experienced resolution of proptosis, conjunctival chemosis, and motility alterations at 3 months after surgery, with visual acuity improving to 0 logMAR. Patient number 2 no longer experienced ocular pain, never presented with proptosis, and exhibited no esthetic or functional changes following surgery.

5. Discussion

The treatment of CVMs typically varies based on their location. The most common management treatment is open surgery with no preoperative embolization [4].

Some authors suggest an anatomical approach to the clinical, surgical treatment of the orbit, dividing it into peripheral, posterior, and orbital apex sections: (1) the orbital apex is marked by the posterior ethmoid sinus; (2) the posterior part of the globe, by the anterior ethmoid sinus; and (3) the peripheral part of the orbit, before the posterior part of the globe. However, this method only considers the bony anatomy of the orbit. During surgery, both bony anatomical landmarks and soft-tissue landmarks, such as the globe and extraocular muscles, must be considered for accurate partitioning and treatment.

Anterior orbitotomy is commonly recommended for lesions situated in the anterior orbital cavity or at the base of the optic nerve, not involving the orbital apex [1,17].

In the case of large lesions near the orbital apex or adhering to orbital structures (the lack of “black triangle” signs on CT scans may indicate tumor adherence to surrounding tissue) [17], lateral orbitotomy may be necessary to minimize postoperative complications [12]. This technique requires bone removal and carries the risk of prolonged surgery time [17] and lateral rectus trauma [4].

A CVM can occur in any part of the orbit, but those situated in the deepest parts, namely the annulus of Zinn and the optic canal of the orbital apex, are the most difficult to treat. Deep CVMs often occur at the common tendon ring in the extraocular muscle cone or the optic nerve sheath, placing them adjacent to vital structures like the optic nerve, extraocular muscles, and intraorbital blood vessels. Consequently, surgery in this area is challenging and risky.

An increasingly favored approach in recent times is the endoscopic endonasal approach (EEA), which does not require orbitotomy [12].

The CHEER staging system assesses tumor anatomy relative to adjacent orbital structures to determine which tumors are suitable for exclusively endonasal resection based on a plane of resectability (POR) [28].

While tumors in the inferomedial orbit and below the plane of resectability may be suitable for EEA, this approach is less ideal for superior or laterally located tumors. The EEA is possible on the orbital apex but requires advanced surgical skills. The EEA might not achieve complete resection when the tumor is located too close to the optic nerve or skull base [29].

More complex cases, like tumors located at the apex, can be approached with craniotomy. Craniotomy can fully expose the superior orbital fissure and optic nerve, remove the bones of the optic canal and superior orbital fissure, and completely expose the structures of the orbital apex area. It is often necessary to cut the common tendon ring structure, and the orbital periosteum of the orbital apex is typically incised using a lateral approach at the superior fissure. The trochlear nerve usually crosses over the tendon ring, so protecting the orbital apex structures, including the extraocular muscles and the optic, oculomotor, trochlear, and abducens nerves, is imperative to avoid postoperative orbital apex syndrome.

Other techniques developed to assist in excision include cryoextraction with an ophthalmic cryoprobe, fractionated stereotactic radiotherapy. When complete excision is not feasible due to the tumor’s location (deep lesions), piecemeal extraction is adequate, permitting the preservation of important orbital structures [4].

Alternative therapies like radiotherapy can be considered for treating inaccessible and non-resectable tumors. Traditional fractionated radiotherapy carries a substantial radiation risk to the optic nerve, as it receives nearly the same dose as the target lesion. In contrast, stereotactic radiosurgery (SRS) delivers high-dose radiation to the target in a single session with minimal collateral damage. Gamma Knife radiosurgery (GKRS), a form of SRS, is used for treating both intracranial and extracranial lesions, including orbital tumors. However, single-session radiosurgery often has an inadequate dose gradient for safely treating lesions near the anterior visual pathway.

Multisession GKRS combines the benefits of conventional fractionated radiotherapy and SRS, offering an increased therapeutic index and reduced risk to normal tissues. Ming Young et al. found that multisession GKRS significantly improved vision, visual field, proptosis, and diplopia, with a substantial decrease in tumor volume when treating orbital apex venous cavernous malformations.

Multisession radiosurgery delivers a high dose per fraction with high conformity and accuracy, resulting in a higher biologically equivalent dose to the target without increasing complication risks. In cases where surgical risks are high, multisession GKRS offers a beneficial alternative, shrinking tumor size, improving visual acuity, reversing RAPD, and resolving visual field defects without recurrence. It has been shown to be safe, with no GKRS-related complications or radiation-related visual morbidity [30].

Surgery for orbital hemangiomas poses inherent risks, including hemorrhage, profound vision loss due to optic nerve injury, limitation of ocular movement, ptosis, enophthalmos, blow-out fractures, sensory deficits, pupillary abnormalities, orbital apex syndrome, and loss of accommodation [12,21,28]. Pupillary abnormalities can occur in up to a quarter of patients after the excision of CVMs from intraconal lesions, especially those located inferotemporally or inferiorly, and in about half of apical lesions. Lateral or inferolateral orbital approaches, which disrupt the inferior intraconal fat, seem to carry a higher risk [31].

While these complications typically require close monitoring and are usually temporary (lasting up to 6 months) [17], about a third of those affected may experience a persistent tonic pupil [12].

Some studies have indicated that the choice of surgical approach may not significantly affect the complication rate, but ensuring a clear view remains a crucial factor in reducing postoperative complications [17].

Medical liquid agent embolization facilitates the molding and solidification of the lesion, enhancing the visualization of borders and separation from normal tissue, ultimately facilitating easier resection with reduced blood loss and potentially preventing recurrence [21,29].

In a study by Cohen et al., embolization with subsequent excision appeared to offer more definitive management, preventing recurrence in all cases over a mean follow-up period of 3 years [18]. In our study, even if anterior orbitotomy was not the more suitable technique (one lesion >3 cm, lacking the “black triangle” sign, lesion located near the orbital apex, in clear contact with the optic nerve), by combining excision with tumor embolization, we were able to successfully treat two patients. The safety of embolization is due to CVMs’ relative vascular isolation [14] and fluoroscopically guided puncture [12]. However, for deep orbital malformations, protecting surrounding structures and ensuring intratumoral injections is crucial. When dealing with sensitive areas like the optic nerve, applying the embolic agent in small amounts and possibly multiple sessions can help safeguard the eye’s blood supply [21]. Tumor embolization can be performed using different substances. In our study, we used Squid 12, which is a low-density embolic agent. It differs from glue because glue immediately collapses the vessels where it is injected. In contrast, Squid 12 acts slowly, being transported by the tumor’s flow and creating a gradual, controlled, and safe collapse of the tumor. Low-viscosity Squid formulations, such as Squid 12, penetrate more easily and result in significant embolization with less reflux [32,33]. Moreover, Squid 12 contains 30% less tantalum, improves fluoroscopic visualization, and reduces artifacts, making it easier to evaluate embolized vasculature and injected volumes [32]. In our study, CBCT was performed in the open field after embolization to check for any tumor residuals and, if necessary, immediately remove them before closing the surgical field and ending the procedure.

Smaller tantalum powder grains in Squid formulations enhance visibility during longer injections due to slower sedimentation [33]. Squid should be injected immediately after mixing to prevent poor visualization or microcatheter occlusion.

Intravascularly, the EVOH (ethylene-vinyl alcohol copolymer) copolymer and suspended tantalum in Squid create a spongy, coherent embolus. Both glues like Onyx and embolic agents like Squid solidify from the exterior to the interior, while PHILs (precipitating hydrophobic injectable liquids) solidify uniformly. Vessels embolized with Onyx or Squid may still have central perfusion, unlike PHILs, which completely blocks the vessel [34]. Because Squid is non-adhesive, the microcatheter can remain in place during slow injections [35]. However, there is a risk of microcatheter entrapment and bursting if excessive pressure is applied to clear solidified Squid.

The premature blockage of the microcatheter lumen by Squid can lead to the catheter tip becoming stranded during withdrawal. Squid extravasation during injection can cause subacute inflammatory responses, but vessel perforations sealed with Squid showed no post-procedural issues in a study. DMSO, used with Squid, can cause local toxic effects like vasospasms, vessel wall inflammation, or angionecrosis [36]. Hemorrhage during or after embolization is a serious risk, occurring in up to 17% of cases [37]. To mitigate this, it is recommended to limit devascularization extent per session and induce post-procedure hypotension [38,39].

We chose to use Squid 12 for its efficient radiologic visualization and the controlled, safe tumor collapse it induces. However, the choice should be tailored to the case and the surgeon’s needs.

It is worth noting that this procedure is not without risks. Indeed, the blood supply to the malformation may be provided dominantly by the ophthalmic artery (OA), a branch of the internal carotid artery. In this scenario, the microcatheterization of the OA is difficult and with risk of ophthalmic artery emboli, retinal ischemia, and visual loss. The direct puncture of the CVM after surgical exposure and injection of medical glue may reduce this risk.

Therefore, orbital and periorbital embolization procedures should be performed by an experienced neurointerventionist and assisted by high-resolution digital subtraction angiography [40].

6. Conclusions

In conclusion, we illustrated a possible approach involving anterior orbitotomy, the injection of a low-viscosity embolizing agent under fluoroscopic guidance, and CBCT intraoperative checks, even for large lesions located near the apex.

Tumor embolization offers several significant benefits, including reduced intraoperative bleeding and improved surgical visualization, which minimize postoperative complications. Additionally, it enhances cosmetic and functional outcomes. The low-density embolic agent allows for a gradual, controlled, and safe collapse of the tumor, and its radiopacity enables immediate intraoperative control of the lesion. After embolization, CBCT is performed in the open field, and if necessary, any remaining tumor is promptly removed before closing the surgical field and completing the procedure.

However, further research, including randomized controlled trials, is necessary to definitively establish the efficacy and safety of this approach.