Abstract
Purpose
To present a case series of percutaneous sclerotherapy of para-orbital and orbital venous malformations.
Method
Seven patients with venous malformations in the orbital and para-orbital region were reviewed. Puncture venogram was performed on all patients and image guided bleomycin injections using biplane digital subtraction in angiography suite.
Results
Average age of patients at the time of the procedure was 22 years old with the youngest being five years of age and the oldest being 50 years. Follow-ups ranged from 3 months to 18 months and the average follow-up duration was 13 months. The patients had no intraprocedural complications and reported symptomatic relief of pain as per the last follow-up. Patients have shown no symptoms or signs of recurrence of lesions with uneventful recovery so far.
Conclusions
Percutaneous sclerotherapy of orbital Venous Malformations with bleomycin is a safe and well-controlled procedure done in real time; it has no major systemic adverse side effects and higher efficacy than other sclerosing agents.
Introduction
The term orbital vascular malformation was defined in a consensus statement by the members of the orbital society in 1999. There are three types of orbital vascular malformations: no flow, venous, and arterial. 1 Orbital venous varix is a rare kind of lesion seen on the orbit and account for less than 1.3% of all orbital masses. Categorized as primary or secondary, a primary venous malformation presents in patients in their mid-20s to late 30s. The symptoms include periodic diplopia, visual acuity deterioration, proptosis, and retro-orbital pain. These lesions commonly cause spontaneous orbital hemorrhages. 2 Symptoms are known to flair when there is an increased pressure on the intraorbital region when intraabdominal pressure is increased or the patient remains in a prone position for too long. If there is a thromboses in the venous malformation, there is an acute exacerbation of symptoms. Imaging and diagnosis can easily be done with the patient in a resting state through a provocative valsalva maneuver or a prone position to elicit proptosis and engorgement of the varix. Orbital venous malformations can only be treated through a multidisciplinary approach. The biggest element in such collaboration is the imaging-guided sclerotherapy with percutaneous injection of ethanol or other sclerosing agents to treat the superficial and craniofacial orbital VMs. Bleomycin is an antineoplastic, antibiotic cytotoxin derived from Streptomyces verticillus and induces both single- and double-stranded DNA break down in endothelial sclerosants. We have found that among all other sclerosing agents bleomycin elicits the least inflammatory responses and can be helpful to treat intramuscular, orbital, and airway-related venous malformations where tissue edema can impair bodily functions. 3 Bleomycin should ideally be used in concentration of 1 unit/ml with a 0.5 unit/kg, maximum dose of 15 unit. 4 Lastly, it is recommended in literature to avoid giving bleomycin to people with compromised lung function tests and underlying chest pathology, thus in order to avoid such incidents, pre- and postoperative chest X-rays and lung function tests are advised. 5 Baseline vision testing and intraocular pressure measurements should also be performed. In the present study, we describe our experience and evaluate the efficacy and safety of intralesional injection with bleomycin for the treatment of orbital and para-orbital venous malformations.
Material and methods
A retrospective, noncomparative clinical study to evaluate the management of orbital venous malformation using bleomycin was conducted from October 2016 to May 2018. The study was approved by the concerned institutional review board and relevant patient data were identified from records and reviewed. The study included all patients with a VM in the orbital or para-orbital region who were given an intralesional bleomycin injection and were treated by a joint team venture of interventional radiologists and ophthalmologists. Postprocedurally the cases were managed in the ophthalmology ward. Patients with eye infections and those patients who had underlying pulmonary diseases were excluded from the study. All patients of orbital and para-orbital venous malformations which were clinically diagnosed by ophthalmologist and interventional neuroradiologists and supported by investigations such as MRI and Doppler were included in the study. Furthermore, all patients who had symptoms due to venous malformations were included in the study. All details of patient data and their results can be found in Table 1. The sclerosants were chosen to optimize treatment and minimize complications based on clinical experience. The interim outcome following each therapy session was determined based on the response of the malformation measured by reduction in size and lessening of symptoms. At each follow-up visit the size change was categorized on a 5-point scale; for symptoms they were categorized as less symptomatic, asymptomatic, and resymptomatic. The overall treatment outcome at 1.5–2 years was defined as a success if there was a complete or good response in terms of size change and the VM was asymptomatic following all treatment sessions. Sclerosant success rates were calculated by the relative number of times a sclerosant was associated with an overall successful outcome compared with a failed outcome. All patients were initially examined by the ophthalmology team and symptoms of orbital vascular lesions when identified were referred to the interventional radiology department. The patients underwent contrast enhanced MRI or CT and Doppler ultrasound to identify the lesions and a joint intervention strategy was planned and arranged at the angiography suite. Patient informed consent was obtained as was consent for the publication of nonidentifiable clinical photos pre- and posttreatment. If the lesion was multilobulated or large in size multiple punctures were needed and a dye mixture was injected to ensure complete sclerosis. Postoperatively patients were followed on day 1, week 1, month 1, month 3, month 6, 1 year, and 1 year and 6 months. Primary tool for measuring success was the palliation of symptoms and cosmetic improvement of disfigurement. Postprocedure side effects include ocular dysmotility, tissue necrosis, secondary hemorrhage, visual loss, swellings, and edema and all patients were evaluated for these outcomes.
Clinical and radiologic features of orbital and para-orbital venous malformations, treatment, and outcome.
CT: computed tomography; MRI: magnetic resonance imaging; OU: oculus uterque; VA: Visual Acuity.
Results
Seven patients including three males and four females underwent the procedure. All procedures were conducted under general anesthesia. The mean age of patients was 22 years with average follow-up time being 13 months. Patients saw a resolution of symptoms proptosis improved from up to 4 mm sustained and 10 mm on valsalva to 0, VA remained intact for all patients, and only two patients continued to have minor 2 mm proptosis on valsalva. As per the last follow-up with each patient there were no signs of recurrence and none of them suffered from visual loss. Lastly, no adverse event such as infection, tissue necrosis, or secondary hemorrhage was noted. The only side effect that did occur in all patients was eye redness, minor swelling, and edema.
Case reports
Case 1
A 32-year-old man was referred to our hospital for left orbital swelling arising from medial side of the eyelid. The lesion increased in size on valsalva associated with pain and discomfort. During history we found that over time the lesion had remained and grown in size with the patient suffering discomfort, orbital pain, and severe psychological disturbance. The contrast MRI showed a low flow infiltrative vascular lesion suggestive of a VM. Complete eye examination was carried out by the ophthalmologist prior treatment. His left eye proptosis was 4 mm sustained and 10 mm on valsalva and visual acuity was VA 6/9 OU. The procedure was carried out in the angiography suite. After first postoperative day VA was 6/9, proptosis was 0 mm on first postoperative day, on third month follow-up proptosis was sustained 2 mm and on valsalva it was 6 mm. Two sessions of percutaneous sclerotherapy done with eight months’ interval by injecting bleomycin percutaneously into the lesion. After second session VA 6/9 and proptosis was 0 mm on valsalva. Multiple injection site needed due to lobulated nature of venous malformation. At 15-month follow-up in total and 1 month after second session, the patient was seen to be experiencing no discomfort and no recurrence of proptosis. He was satisfied with the outcome.
Case 2
A 22-year-old man described a progressive proptosis left eyeball on valsalva since childhood. This was associated with mild discomfort. His vision and ocular motility remained normal. A MRI showed a vascular malformation extending from the lateral border to intraorbital region. His symptoms become gradually worsened. Complete eye examination was carried out in ophthalmology department. His VA was 9/24 OU and 6/9 OU with glasses, proptosis was 2 mm sustained and 8 mm on valsalva. Intraprocedure direct puncture venogram and bleomycin injection was given by interventional neuroradiologists. His visual acuity was 6/9 on first postoperative day and proptosis was 0 mm sustained and 2 mm on valsalva. After two sessions, six weeks apart, he was free of pain and proptosis and there was no evidence of recurrence at the recent follow-up after three months of second session (Figure 1).
Preoperation, operation prep and post-procedure images. In the second row we can see an MRI of the eye, DSA image of blush during procedure, and a DSA image postprocedure where blush is clearly gone.
Case 3
A seven-year-old girl had a right upper and lower lid vascular lesion since birth. She was unable to open right eye due to swelling. She received no treatment in the past. Subsequently, she was noted to have progressive ptosis. MRI of her orbit showed a contrast-enhancing extra-conal mass at anterior and posterior aspect of her globe. It displaced the right lateral rectus muscle and the globe. Her visual acuity was 6/6. She received percutaneous injection of bleomycin intralesionaly. In view of the extensive lesion size, repeated venograms with bleomycin injections under fluoroscopic guidance were given after 4–6 weeks’ intervals. After multiple sessions the ptosis improved and the visual acuity remained 6/6 and there was no clinical recurrence with satisfactory cosmetic outcome.
Case 4
A 50-year-old female presented to us with a para-orbital vascular lesion that she had for the last 30 years. Patient history showed the mass to have increased in size over the years resulting in disfigurement and significant pain. The MRI showed a multiloculated intraorbital lesion that was at the supro-medical of the left orbit. The lesion suggested a slow flow orbital VM and was managed collaboratively by the interventional and ophthalmology team. Her visual acuity was 6/6 prior intervention. Contrast injection followed by bleomycin injection under fluoroscopy was performed through percutaneous puncture of lesion with butterfly needle. After single session there was no clinical recurrence noted and visual acuity remained within normal limits,18 months after the first session, although follow-up MRI orbit showed residual venous malformation.
Case 5
A five-year-old girl presented with right upper and lower lid mass since she was three years of age. The mass caused mechanical ptosis and periocular discomfort but there was no proptosis or ocular dismotility. Her visual acuity was 6/6. Because of the cosmetic disfigurement and inability to see percutaneous bleomycin injection was given. Initially direct puncture venogram was performed with contrast injection followed by bleomycin injection under fluoroscopy to avoid spillage of bleomycin into normal draining venous channels. Six sessions were given due to large size of the lesion. There was significant improvement in symptoms and cosmetics after injection sclerotherapy. There was no decline in visual acuity on follow-ups.
Case 6
A 21-year-old female presented with upper and lower eyelid swelling since childhood. The mass caused ptosis and conjunctival redness. She was surgically treated by excision two times prior presenting to our department. Histopathology revealed dysplastic venous channels in report. Subsequently, she again developed ptosis right upper and lower lid. MRI head and face showed a contrast-enhancing extra-orbital mass involving upper and lower lid with infiltrating lesion of right cheek. Her vision was intact. She received percutaneous injection sclerotherapy with bleomycin. After 10 sessions in both cheek and para-orbital lesion, there was significant reduction in size of lesion as well as improvement in cosmetics.
Case 7
A 20-year-old male described a progressive proptosis left eyeball on valsalva for six months; there was slight discomfort and pain but no other significant symptoms. There was also a history of left supra-clavicle swelling which was pulsatile in nature for the past year. This case was unique as patient presented with a dual diagnosis. A MRI orbit showed enhancing vascular malformation extending from lateral border to superior border; this mass was also extending up to retrobulbar region posteriorly compressing the optic nerve. Complete eye examination was carried out by ophthalmologist. His visual acuity was 6/6, proptosis was 2 mm sustained, and increases up to 5 mm on valsalva. Extraocular movements were intact and pupil was reactive to light and for accommodation. Digital subtraction angiogram of chest and head was performed to evaluate any abnormal draining channels which revealed left supra-clavicle arteriovenous malformation. However, DSA head was unremarkable. Direct puncture venogram performed and almost 6 unit of bleomycin injection was given in concentration of 2:1. His visual acuity was 6/6 first operative day and proptosis was 0 mm on valsalva. First follow-up was done after three months, he was free of proptosis and there was no recurrence of symptoms till last follow-up.
Discussion
No standardized treatment modality for orbital venous malformations has yet been agreed on. A number of various treatment types are used such as CO2 laser ablation, percutaneous ethanol sclerotherapy, and endovascular treatment with platinum Guglielmi detachable coil embolization. 2 It is difficult to manage lesions in the orbit or airways as swelling from sclerotherapy can result in compartment syndrome or compromise the airway. In such cases a less inflammatory sclerosant like bleomycin is more effective. 6 Bleomycin involves the apoptosis of quickly dividing cells and inhibits DNA synthesis and involution by fibrosis by inducing inflammation. This combined with local anesthetic decreases postoperative discomfort and improves the uptake of bleomycin in cells by disrupting the membrane. Other possible sclerosants include ethanol. Ethanol acts as a sclerosant by causing hypertonic dehydration of cells, protein denaturation, thrombosis, and vessel occlusion. However, this leads to an intense inflammatory response causing swellings. Other complications of ethanol sclerotherapy include tissue necrosis, nerve damage, pain, deep vein thrombosis, and cardiopulmonary failure. 7 Yet another commonly used sclerosant is STS; it acts on endothelial lipid molecules causing surface damage and collagen exposure and leading to an inflammatory response that results in fibrosis, scarring, and shrinkage of the VM with minimal thrombus formation. Endothelial damage to the vein occurs 15 min after sclerosant injection and adhesion between the thrombus and wall happens within 2–5 h of therapy. Complications include skin necrosis, motor sensory pain injuries, deep vein thrombosis, pulmonary embolus, and cardiopulmonary collapse. 8 While no major side effects are reported with the intralesional use of bleomycin, postinjection inflammation is seen in all sclerosants and bleomycin is thought to have better results than other such as sodium morrhuate and sodium tetradecyl sulfate. The systematic side effect of bleomycin includes fever, nausea, vomiting, loss of appetite, pulmonary toxicity and weight loss, and injection site skin necrosis. Our study, however, did not see any of these reactions and it is considered that pulmonary fibrosis happens only when cumulative dose exceeds 400 mg. 9
Conclusion
In the late 2000s and up to 2010 orbital venous malformations were most commonly treated surgically or through ozone laser treatment. Sclerotherapy is a relatively newer treatment modality that shows more promising results and is easier to conduct. Both ozone therapy and surgery are more difficult to conduct as well as being less effective and costly. Sclerotherapy is a more effective, easy and less complicated alternative through which palliation can be achieved faster and safer. There is lower recurrence rate through sclerotherapy and complete obliteration is achieved in certain cases. However, sclerosing agent and therapy techniques still need to be universally agreed on after vast rigorous trials and until that time it is our hope that this article will pave the way to that.
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: There are no major/minor funding sources to declare for this paper. Study was conducted in a government institution by the authors themselves. While the review board gave their approval no funding was provided and all technical and logistical services were paid for out of pocket by the authors.
Ethical approval
The Institutional Review Board (IRB) gave their consent for the study and all patients mentioned herein gave informed consent to partake. Data of any patients who did not wish to be a part of the study were not included. In the case of minors informed consent was taken from an adult parent or guardian.
Guarantor
Punjab Institute of NeuroSciences, a branch of Lahore General Hospital falling under the department of Health Government of Punjab Pakistan is the chief guarantor of this study. All data used in the study are from patients who were taken into PINS institute and jointly treated by the neuroradiology and ophthalmology departments. This was the first such interdepartmental collaboration in the province.
Contributorship
This paper was written by SA, however FKA was a great help in the ophthalmology department. He prepped all patients and did pre- and post-op examinations as well as helped in gauging the success of all procedures.
Acknowledgements
We would like to acknowledge Mian Faizan and his organization Team Online for all the help in the project management, logistics of research, and the formatting and editing of this paper. He also contributed greatly toward the structure and design of this study and report.