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Bleomycin sclerotherapy of a distensible orbital venous malformation without image guidance

  • Ying Chen
    Affiliations
    Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Fla.
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  • Catherine J. Choi
    Affiliations
    Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Fla.

    Division of Oculofacial Plastic and Reconstructive Surgery, Bascom Palmer Eye Institute, Miami, Fla.
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  • Bradford W. Lee
    Correspondence
    Correspondence to: Bradford W. Lee
    Affiliations
    Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Fla.

    Division of Oculofacial Plastic and Reconstructive Surgery, Bascom Palmer Eye Institute, Miami, Fla.
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Published:November 23, 2018DOI:https://doi.org/10.1016/j.jcjo.2018.08.016
      An orbital varix is a distensible venous malformation consisting of vascular channels that directly communicate with the systemic venous system. It can present with variable pain, proptosis, diplopia, spontaneous hemorrhage, or even vision loss, and these symptoms typically worsen with Valsalva maneuver. Treatments proposed include vascular clipping, endovascular glue embolization, endovascular coiling, surgical resection, or combination therapy.
      • Arat YO
      • Mawad ME
      • Boniuk M
      Orbital venous malformations: current multidisciplinary treatment approach.
      Recurrence is common, however, and devastating visual complications can occur with procedural interventions such as surgical resection and endovascular procedures.
      • Hwang CS
      • Lee S
      • Yen MT
      Optic neuropathy following endovascular coiling of an orbital varix.
      Previous reports of using bleomycin sclerotherapy to treat vascular malformations have focused on lymphatic venous malformations, cavernous hemangiomas, and high- and low-flow orbital venous malformations.
      • Yue H
      • Qian J
      • Elner VM
      • et al.
      Treatment of orbital vascular malformations with intralesional injection of pingyangmycin.
      • Jia R
      • Xu S
      • Huang X
      • et al.
      Pingyangmycin as first-line treatment for low-flow orbital or periorbital venous malformations: evaluation of 33 consecutive patients.
      There is only one previous case report of bleomycin sclerotherapy used to treat an orbital varix, and this case utilized angiography-guided catheterization through the cavernous sinus, a microcatheter balloon, and contrast-enhanced sclerotherapy mixed with bleomycin.
      • Vadlamudi V
      • Gemmete JJ
      • Chaudhary N
      • Pandey AS
      • Kahana A
      Transvenous sclerotherapy of a large symptomatic orbital venous varix using a microcatheter balloon and bleomycin.
      Here the authors describe the first reported case of non-image-guided bleomycin sclerotherapy for treatment of an orbital varix.

      Case Presentation

      A 35-year-old female presented with a 5-year history of progressively worsening left orbital pain with episodes of severe intractable pain, distensible orbital swelling, and headaches that were exacerbated by bending down and Valsalva maneuver. Examination showed normal vision and extraocular motility but was significant for mild enophthalmos and a visible purplish lesion overlying the medial bulbar conjunctiva (Fig. 1A,B). With Valsalva maneuver, the lesion enlarged with associated proptosis and periocular fullness (Fig. 1C,D). Magnetic resonance imaging (MRI) revealed a 3.3 × 2.2 × 0.9 cm lesion centered in the inferonasal orbit that enhanced with gadolinium, extended from the ocular surface to the orbital apex, and involved the medial and inferior recti and optic nerve without contiguous intracranial extension (Fig. 2A,B). Catheter angiography demonstrated a slow filling of the lesion without clear feeder vessels, consistent with a low-flow orbital varix. Under general anaesthesia, a traction suture was placed at the medial limbus to abduct the eye, thereby inducing improved access to the lesion. The traction suture induced slight retropulsion of the eye, reduced orbital venous outflow, and caused further engorgement of the lesion. Intralesional injection of 2 mL of 3 mg/mL bleomycin was administered transconjunctivally with a 27G 1.5 inch needle. Multiple retrograde injection passes were made along the medial orbit by advancing the needle into the orbit and only injecting medication while the needle was being withdrawn. The visible superficial portion of the lesion was also injected transconjunctivally. Postoperatively, the patient experienced complete resolution of orbital pain with disappearance of the superficial component of the lesion (Fig. 3A,B). Follow-up MRI obtained at 5 months showed a 53% reduction in size of the orbital component to 2.7 × 1.9 × 0.6 cm (Fig. 4A,B). The patient has remained asymptomatic at 2 years of follow-up.
      Fig. 1.
      Fig. 1External photograph at the time of presentation demonstrating a purplish lesion overlying the bulbar conjunctiva in primary gaze (A) and in abduction (B). Immediately after Valsalva maneuver, the lesion enlarged with associated proptosis as seen in primary gaze (C) and in abduction (D).
      Fig. 2.
      Fig. 2(A) Coronal and (B) axial images of T1-weighted, fat suppression postgadolinium MRI demonstrating a 3.3 cm × 2.2 cm × 9.4 mm enhancing lesion centered in the inferonasal orbit extending from the ocular surface to the orbital apex and involving the medial and inferior recti and optic nerve.
      Fig. 3.
      Fig. 3A, External photograph at presentation demonstrating a purplish intumescent lesion (varix) overlying the left medial bulbar conjunctiva. B, Six months after intralesional injection of 2 mL of 3 mg/mL bleomycin, the purplish lesion has completely resolved and is no longer visible, consistent with dramatic involution of the orbital varix.
      Fig. 4.
      Fig. 4(A) MRI gadolinium-enhanced T1 imaging before and (B) after intralesional sclerotherapy with bleomycin. (A) shows persistence of the enhancing vascular lesion along the medial orbit but with reduced size and anterior extent. In (B), orbital fat is visible along the medial orbit, which was not present before sclerotherapy.

      Discussion

      An orbital varix is a low-flow, thin-walled, and distensible venous plexus that is commonly intrinsic to the normal vascular circulation, while other orbital vascular malformations such as lymphatic venous malformations are isolated from the main circulation. Surgical resection is often not ideal due to the risk of orbital hemorrhage, components localized to the posterior orbit, potential damage to critical structures, and frequent recurrence. Other treatments such as laser therapy have limited utility, as they typically only address superficial lesions.
      • Arat YO
      • Mawad ME
      • Boniuk M
      Orbital venous malformations: current multidisciplinary treatment approach.
      Bleomycin is indicated as a systemic chemotherapeutic agent to treat various malignancies but has also been reported as an effective sclerosing agent.
      • Yue H
      • Qian J
      • Elner VM
      • et al.
      Treatment of orbital vascular malformations with intralesional injection of pingyangmycin.
      • Jia R
      • Xu S
      • Huang X
      • et al.
      Pingyangmycin as first-line treatment for low-flow orbital or periorbital venous malformations: evaluation of 33 consecutive patients.
      Bleomycin sclerotherapy acts by inducing inflammation and destruction of endothelial cells, resulting in fibrosis and thrombosis of vascular channels. Direct intralesional injection of bleomycin has been shown to be effective in the treatment of orbital lymphatic venous malformations. However, previous case series excluded distensible lesions like orbital varices and employed a different technique of aspiration and surgical orbitotomy with directly visualized injection of the deep components of the lesions.
      • Yue H
      • Qian J
      • Elner VM
      • et al.
      Treatment of orbital vascular malformations with intralesional injection of pingyangmycin.
      • Jia R
      • Xu S
      • Huang X
      • et al.
      Pingyangmycin as first-line treatment for low-flow orbital or periorbital venous malformations: evaluation of 33 consecutive patients.
      ,
      • Barnacle AM
      • Theodorou M
      • Maling SJ
      • Abou-Rayyah Y
      Sclerotherapy treatment of orbital lymphatic malformations: a large single-centre experience.
      In the one previously reported case of bleomycin sclerotherapy for treatment of an orbital varix, interventional radiology accessed the ipsilateral internal carotid artery via the contralateral common femoral artery to ensure absence of arteriovenous filling of the orbital varix. Next, the contralateral femoral vein was punctured and a catheter advanced into the ipsilateral cavernous sinus. A dual lumen balloon catheter was advanced through the ipsilateral petrosal sinus into the ophthalmic vein and varix. With the balloon inflated at the varix's outflow, bleomycin mixed with contrast was injected. In order to prevent bleomycin from flowing into the cavernous sinus and possibly causing cavernous thrombosis, the inflated balloon was left in place for 10 minutes. Imaging was performed to confirm filling of the orbital varix. The patient underwent the same procedure again 8 weeks later.
      • Vadlamudi V
      • Gemmete JJ
      • Chaudhary N
      • Pandey AS
      • Kahana A
      Transvenous sclerotherapy of a large symptomatic orbital venous varix using a microcatheter balloon and bleomycin.
      Although effective, endovascular sclerotherapy carries significant risks associated with endovascular catheterization and exposes patients to ionizing radiation and high procedural costs.
      • Vadlamudi V
      • Gemmete JJ
      • Chaudhary N
      • Pandey AS
      • Kahana A
      Transvenous sclerotherapy of a large symptomatic orbital venous varix using a microcatheter balloon and bleomycin.
      This case report demonstrates that bleomycin sclerotherapy can be effectively utilized to treat an orbital varix without extensive surgical exposure via orbitotomy, angiographic guidance, or complex endovascular procedures. In cases of deep lesions or those with an unclear diagnosis or suspicion for malignancy, an anterior orbitotomy can be performed with or without biopsy followed by directly visualized injection of the lesion without image guidance.
      • Yue H
      • Qian J
      • Elner VM
      • et al.
      Treatment of orbital vascular malformations with intralesional injection of pingyangmycin.
      • Jia R
      • Xu S
      • Huang X
      • et al.
      Pingyangmycin as first-line treatment for low-flow orbital or periorbital venous malformations: evaluation of 33 consecutive patients.
      ,
      • Barnacle AM
      • Theodorou M
      • Maling SJ
      • Abou-Rayyah Y
      Sclerotherapy treatment of orbital lymphatic malformations: a large single-centre experience.
      When sclerosing a varix, there is a risk that the injected bleomycin could pass into the systemic venous circulation without adequate contact time for sclerosis of the varix. There is also a risk of orbital hemorrhage, cavernous sinus complications, and inflammation and fibrosis of orbital structures. The chance of vision loss with sclerotherapy injection, however, is low. Theoretically, vision loss can occur due to accidental globe perforation with the needle, accidental intraocular injection of sclerosant, or with injection of sclerosant into the arterial circulation with retrograde flow and subsequent anterograde flow into the ophthalmic or central retinal artery.
      • Arunakirinathan M
      • Walker RJ
      • Hassan N
      • Ameen S
      • Younis S
      Blind-sided by cosmetic vein sclerotherapy: a case of ophthalmic arterial occlusion.
      • Sio WS
      • Lee SH
      • Liang IC
      Orbital infarction syndrome after multiple percutaneous sclerotherapy sessions for facial low-flow vascular malformation: a case report and literature review.
      Sclerosing the varix via the multiple retrograde injection technique as performed in this case may minimize the risk of inadvertent arterial injection and can allow for sclerosis of a low-flow varix without isolating the lesion from the systemic circulation via an endovascular balloon catheter. With respect to systemic absorption and toxicity of bleomycin, the dose used in this case was similar to those reported for sclerosis of orbital lymphatic venous malformations using bleomycin.
      • Yue H
      • Qian J
      • Elner VM
      • et al.
      Treatment of orbital vascular malformations with intralesional injection of pingyangmycin.
      • Jia R
      • Xu S
      • Huang X
      • et al.
      Pingyangmycin as first-line treatment for low-flow orbital or periorbital venous malformations: evaluation of 33 consecutive patients.
      No systemic toxicities such as pulmonary fibrosis have been reported with sclerosing orbital lesions, since the doses used are far below those at which pulmonary fibrosis occurs with systemic chemotherapy, which approach 300 to 400 grams. Bleomycin remains the authors’ preferred choice of sclerosing agent as it has been shown to be the most effective sclerosant to date in the treatment of orbital venous malformations.
      • Yue H
      • Qian J
      • Elner VM
      • et al.
      Treatment of orbital vascular malformations with intralesional injection of pingyangmycin.
      • Jia R
      • Xu S
      • Huang X
      • et al.
      Pingyangmycin as first-line treatment for low-flow orbital or periorbital venous malformations: evaluation of 33 consecutive patients.
      ,
      • Barnacle AM
      • Theodorou M
      • Maling SJ
      • Abou-Rayyah Y
      Sclerotherapy treatment of orbital lymphatic malformations: a large single-centre experience.
      Although longitudinal follow-up and serial imaging will be helpful in determining the long-term efficacy and risk of recurrence for this treatment paradigm, preliminary clinical findings remain positive at 2 years follow-up. Compared with angiography-guided sclerotherapy, nonimage-guided sclerotherapy has the advantages of reduced cost and procedural time, lack of ionizing radiation, ability to be performed in a standard operating room by an ophthalmologist, and reduced risk of endovascular complications.

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        Optic neuropathy following endovascular coiling of an orbital varix.
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        Pingyangmycin as first-line treatment for low-flow orbital or periorbital venous malformations: evaluation of 33 consecutive patients.
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        Transvenous sclerotherapy of a large symptomatic orbital venous varix using a microcatheter balloon and bleomycin.
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