Impact of superior ophthalmic vein thrombosis: a case series and literature review

ABSTRACT

Purpose: To present nine new cases of superior ophthalmic vein thrombosis (SOVT) and compare these with the literature, and to assess the impact of SOVT for the clinician.

Methods: Using the data bases of the Department of Ophthalmology of the AMC, we searched for patients with radiologically evidenced SOVT between January 2006 and December 2014. In addition, a PubMed search, using the mesh term ‘superior ophthalmic vein thrombosis’, was done.

Results: We found nine patients with SOVT. In three patients, SOVT was related to dural arteriovenous fistulae. In one patient, it was caused by the acute reversal of warfarin by vitamin K. In two patients, an infectious cause was found. In three patients, the cause of SOVT was not found despite screening for coagulation and other disorders. All patients presented with eyelid swelling, proptosis, and/or motility impairment. We found complete recovery in four patients. Three patients had mild sequelae and two patients had severe visual impairment. In the literature, we found 60 cases reporting on SOVT with various aetiologies. Clinical presentation, treatment modalities, and outcomes were comparable to our findings.

Conclusion: Our case series and literature review show that SOVT can occur simultaneously with cavernous sinus thrombosis (CST) but can also be a separate entity. Clinical presentation can mimic orbital cellulitis (OC) or CST and when no signs of OC can be found, an alternative cause for SOVT should be sought. When timely and adequate treatment is conducted, the prognosis is predominantly favourable.

KEYWORDS:

• Arteriovenous fistula
• cavernous sinus thrombosis
• orbital cellulitis
• superior ophthalmic vein thrombosis

Introduction

Superior ophthalmic vein thrombosis (SOVT) is a clinical and radiologic diagnosis and its implications may not entirely be clear to the clinician. Apart from anecdotal case reports, systematic evaluations of SOVT are scarce. Causes of SOVT can be septic or aseptic. SOVT may present similar to, or occur together with, orbital cellulitis (OC) or cavernous sinus thrombosis (CST). Presenting signs of SOVT are caused by venous congestion and include eyelid swelling, proptosis, motility impairment, or even vision loss. We evaluated our own series and compared our findings with those described in literature.

Figure 2. Female, 62 years old. Left-sided SOVT caused by a small dural fistula. Treatment with anticoagulants. No coiling possible because of the small size of the fistula. Secondary macular oedema to some extent successfully treated with bevacizumab injections. Follow-up imaging showed a normal SOV.

(A) Clinical picture: ptosis and proptosis of the left eye, redness of the conjunctiva due to enlarged epibulbar veins.

(B) Funduscopy: papilloedema, tortuous retinal veins.

(C) Angiography, late arterial phase (via left internal carotid artery): early enhancement of venous structure; indicating small dural arteriovenous fistula. Blue arrow: internal catorid artery, red arrow; dural arteriovenous fistula.

(D) Angiography, late venous phase; dural arteriovenous fistula with filling of superior ophthalmic vein with stasis of contrast preluding thrombosis. Yellow arrow: sigmoid sinus, red arrow; dural arteriovenous fistula, purple arrow; superior ophthalmic vein.

Methods

We retrieved files from all patients in whom a diagnosis of SOVT has been made between January 1, 2006 and December 31, 2014 at the Department of Ophthalmology of the Academic Medical Center of the University of Amsterdam, a tertiary referral centre in the Netherlands (estimated population 17 million). We searched our electronic database for patients with a diagnosis of SOVT. A dedicated neuroradiologist (MMdW) reviewed all cases to confirm the diagnosis. Inclusion criteria were thickened or dilated superior ophthalmic vein (SOV) with a filling defect. All other cases were excluded. Charts were reviewed for demographic characteristics, ophthalmic examination, imaging results, and cause of SOVT. Use of antibiotic therapy, anticoagulation therapy (ACT), treatment of ocular hypertension, and surgical intervention were noted. Outcomes were evaluated for mortality, visual acuity, and eye movements.

In addition, on May 3, 2018, we searched in PubMed using the searchterm: ‘superior ophthalmic vein thrombosis’, and looked into the articles available in English containing case reports of SOVT.

Formal ethical approval was not required because the preexisting data had been anonymized. All investigations and treatments were carried out in line with accepted clinical practice.

Results

AMC-series

Over an 8-year span, we found nine patients with radiologically confirmed SOVT. Patient’s characteristics, presentation, imaging results, treatment, and outcome are summarized in Table 1. The median age was 56 (40–79), and we found four male and five female patients. The majority of the patients were aseptic (seven out of nine). In three patients, SOVT was caused by spontaneous thrombosing of dural arteriovenous fistula. One patient had SOVT caused by reversal of ACT by vitamin K. Two patients had a septic cause of SOVT; one was diagnosed with bacterial OC caused by paranasal sinusitis and another patient had OC due to a dental infection. In three patients, the cause was not found despite investigations for coagulation disorders by haematologists. One of these three patients, however, did have a history of Graves’ Orbitopathy. Two of the patients had SOVT and CST simultaneously. All patients presented with symptoms of orbital pathology: eyelid swelling, chemosis, proptosis, impaired ocular motility, reduced visual acuity and/or increased intraocular pressure. Visual acuity was impaired in four patients and one patient presented with no light perception at all. Treatment consisted of intravenous antibiotics, anticoagulants, eye pressure lowering medication, and/or surgical intervention. Seven out of nine patients were treated with anticoagulant therapy, and in none of these, haemorrhage complications occurred. There was no mortality. We found a complete recovery in four patients. One patient had persistent mild exophthalmos, and two patients had secondary cystoid macula oedema which was successfully treated with bevacizumab injections. The patient who presented with no light perception did not regain her visual acuity. The three other patients who presented with impaired visual acuity partially regained their vision.

Table 1. Case series, patient characteristics (CST: cavernous sinus thrombosis, SOV: Superior ophthalmic vein).

Age	Gender (M/F)	Etiology	CST yes/no	Laterality	Orbital symptoms	Treatment	Anticoagulation used	Outcome	Details
40	M	Unknown cause	Yes	Left	Ptosis, proptosis, motility impairment, diplopia, no visual impairment	Anticoagulation therapy	Fraxiparin	Complete recovery	No infective pathogen found, haematological work-up, and coagulation work-up revealed no abnormalities
58	F	Dural arteriovenous fistula of cavernous sinus	NO	Left	Proptosis, motility impairment, papilloedema, ocular hypertension	Ocular hypertension medication, spontaneous cure of fistula	None	Complete recovery	Follow-up scan: normal aspect of SOV
56	M	Dental infection, suspicion of orbital cellulitis (other hospital)	No	Left	Eyelid swelling, motility impairment	Antibiotics, anticoagulation therapy	Fraxiparin and Acenocoumarol	Complete recovery	Patient was sent in to our centre under suspicion of orbital cellulitis
56	M	Unknown cause	No	Left	Proptosis, eyelid swelling,	Anticoagulation therapy	Aspirin	Exophthalmus (Hertel 23–29 mm)	History of Graves orbitopathy, haematological, and coagulation work-up revealed no abnormalities
45	F	Unknown cause	No	Left	Proptosis, motility impairment, papilloedema, visual acuity 20/80	Anticoagulation therapy	Fraxiparin	Secondary cystoid macula oedema, treated with bevacizumab injections, with good effect. Visual acuity 20/25	Haematological work-up and coagulation work-up revealed no abnormalities
79	F	Reversal of anticoagulation therapy	No	Right	Eyelid swelling, proptosis, motility impairment, optic nerve involgement, ocular hypertension, visus: no light perception	Ocular hypertension medication, anticoagulation therapy	Fraxiparin	No light perception (right side)	History of anticoagulation therapy use because of atrial fibrillation. Because of an internal haemorrhage the anticoagulation was reversed by vitamin K
59	F	Dural arteriovenous fistula of cavernous sinus	No	Right	Eyelid swelling, proptosis, motility impairment, intraocular hypertension, optic nerve involvement, visual acuity 20/200	Ocular hypertension medication, no coiling because of progressive spontaneous thrombosis of the fistula	None	Visual acuity 20/80, no proptosis, normal motility
53	M	Sphenoid sinusitis and orbital cellulitis	Yes	Left	Eyelid swelling, proptosis, motility impairment, preexistent visual impairment	Antibiotics, anticoagulation therapy, endoscopic sinus surgery	Fraxiparin	Complete recovery (visual acuity not altered pre and post disease)	History of drugs abuse, which led to bilateral visual impairment
62	F	Dural arteriovenous fistula (internal carotid) Figure 2	No	Left	Eyelid swelling, optic nerve involvement, visual acuity 20/80	Anticoagulation therapy. No embolization possible because of anatomy.	Rivaroxaban	Secondary cystoid macula oedema, treated with bevacizumab injections, with moderate effect. Visual acuity 20/50	Follow-up scan after 6 months: normal flow through SOV

Literature search

The initial search yielded 220 titles. Two authors separately screened the titles (KW and NP), for articles about SOVT and CST. Of the screened titles, 81 were considered to be eligible. Screening the abstracts, we found that 15 articles were not published in English and 9 articles did not contain a (new) case report of SOVT. Five articles were not available as full text, despite extensive efforts of our librarian. This resulted in a total of 52 articles containing 60 cases.

Of the 60 cases, 31 were female and 27 were male (in two cases, the gender was not specified). The median age was 53 (range 10 months–88 years). We found more cases caused by aseptic aetiology compared to septic disorders. Details on all cases can be found in supplementary data (supplementary table 1).

Discussion

The superior ophthalmic vein is a valve-less vein which is responsible for most of the venous drainage of the orbit. SOVT is caused by altered venous blood flow, which can be the result of stasis of blood flow, trauma to the vessel wall, or hypercoagubility disorders. Both septic and aseptic causes of SOVT are known. Aseptic causes of SOVT can be explained by alterations of blood flow due to anatomical or systemic causes. SOVT is seen in patients with flow alterations in the orbital vascular system, such as in dural arteriovenous fistulae in the direct vicinity of the cavernous sinus.^1–5 Facial trauma is another aseptic cause of SOVT, reported in literature.^6–8 Systemic diseases reporting SOVT in literature include Graves’ Orbitopathy, systemic lupus erythematosus, and ulcerative colitis.^9–13 Hematologic aetiologies include antiphospholipid syndrome and sickle trait.^14–17 Also, hormone therapies have been reported as a cause for SOVT (e.g. tamoxifen, oral contraceptive pill).^18–20 Other causes of aseptic SOVT include Tolosa-Hunt syndrome and idiopathic orbital inflammatory disease.^21,22 Not seldom, the cause remains unknown despite investigations for coagulation disorders or systemic diseases.^23–26 On the other hand, in some cases SOVT can be the first clinical sign of a new diagnosis such as arteriovenous fistulae or systemic disorders.^11,12

Septic causes of SOVT include infections of the paranasal sinuses, orbit, teeth, and face. In literature, paranasal sinusitis is the most common cause of septic SOVT.^13,27–33 In our series, the majority of cases were aseptic (77.8%). This corresponds to the literature, where we also found more aseptic SOVT (66.7%). The exact incidence of SOVT is not known but is often described as ‘rare’. This is reflected in the literature by the fact that we only found 60 cases since 1975.^14,18

For an overview of SOVT aetiology in literature, see Table 2.

Table 2. Literature review. Aetiology of cases in literature (total number of cases: 60).

Aseptic		#cases	Septic		#cases
Vascular malformations	Embolization dural arteriovenous fistula	2	Sinusitis	Sphenoidal sinusitis	3
	Carotid-cavernous fistula	3		Ethmoidal sinusitis	2
	Dural arteriovenous fistula of cavernous sinus, gamma knife radiosurgery	1		Pansinusitis	3
	Posttraumatic carotid-cavernous fistula	1	Orbital infections	Dacryocystitis-induced orbital cellulitis	1
Auto-immune/systemic	Graves’ orbitopathy	2		Orbital cellulitis, ethmoid sinusitis	2
	Systemic lupus erythematosus	2	Dental infections	Dental infection	1
	Ulcerative colitis	1		Dental infection and orbital cellulitis	2
Trauma	Facial trauma	3		Dental infection with pansinusitis	1
Haematological	Autoimmune haemolytic anaemia	1	Facial infections	Facial cellulitis and orbital cellulitis	2
	Antiphospholid syndrome	2		Nasal furunculosis	1
	Sickle trait	1		Masticator space abscess	1
	Hereditary haemorrhagic telangiectasia (HHT)	1	Other	Lemierre syndrome/otomastoiditis	1
	Cessation of anticoagulation therapy (warfarin) for history of DVT	1
Malignancies/neoplasms	Adenoid cystic carcinoma of the nasal mucosa	1
	CML, antifibrinolytic and thrombopoietin receptor agonists	1
	Left cavernous sinus meningioma	1
Hormonal	Minestrine (hormone therapy for menopause)	1
	Tamoxifen for breast cancer	1
	Oral contraceptive pill	2
Other	Diabetes	1
	Injection of heroin intraorbital	1
	Idiopathic orbital inflammatory disease	1
	Tolosa-Hunt syndrome	1
	Idiopathic	6
	Not specified	1

Presentation

The clinical presentation of SOVT can be explained by congestion of the orbit due to the impaired venous drainage. Patients usually present with pain, chemosis, eyelid oedema, proptosis, limited ocular motility, with or without fundus findings, and impaired visual acuity. These symptoms are similar to the symptoms of CST and OC, and thus those entities can be hard to be distinguished clinically. Moreover, SOVT, CST, and OC can occur together.

In our series, we found SOVT to be a unilateral disease in all cases. In our literature review, 85% of cases presented with unilateral complaints. In patients with CST, however, patients usually have an onset with unilateral ophthalmic signs, with rapid development to bilateral signs and symptoms.³⁴

If patients present themselves without septic symptoms and there is no suspicion of OC, one must look for another underlying condition. Imaging can rule out or demonstrate vascular abnormalities. Laboratory examinations should be performed for systemic and hypercoagulable disorders.

Imaging

The diagnosis of SOVT is assessed by imaging, preferably contrast enhanced CT or MR imaging. On a contrast-enhanced CT-scan, SOVT is characterized by a thickened SOV with an indistinct outer border due to perivascular oedema compared to the other side. A filling defect can be seen within the SOV itself, or a thin lining can be present close to the vessel wall, either due to vessel wall enhancement or a small lumen in between the clot and the vessel wall.³⁵ In case of a chronic SOV thrombosis, the central thrombus can also show enhancement opposite to the acute stage. MRI shows enhancement of intraorbital fat and swelling and enhancement of the eye musculature due to the venous congestion. Similar to contrast enhanced CT, MRI can show intra-luminal filling defects in the SOV, as shown in Figure 1. Secondary signs include proptosis and thickening of the extraocular muscles.²³

Figure 1. Contrast enhanced MRI (3D T1GE; E-THRIVE); showing dilated right superior ophthalmic vein with filling defect.

Management

If an underlying cause is found, a targeted treatment is possible. Treatment may include antibiotics, steroids, ACT, and/or surgery. The choice of antibiotics should be based on the pathogens usually found in the suspected source of infection, while waiting for culture. There is no consensus on duration of antibiotic therapy. No aggregated evidence is available for the use of steroids in SOVT.

ACT was initially disputed because of fear for haemorrhagic complications. More recent literature shows that the risk of haemorrhages is acceptable in most patients and that the use of anticoagulants promotes a smooth instead of an abrupt transition to normal flow conditions. In a recent review, Weerashinghe et al. concluded ACT to be associated with reduced mortality in CST patients.³⁶ However, their conclusion is based on a review of case reports with a great heterogeneity of patients and treatment schemes. Although current reports favour ACT, the optimal dose and duration is not known. Surgery may be necessary for an underlying cause of SOVT like sinusitis, orbital abscess, or dental infection.

Prognosis

Early detection of SOVT is crucial to prevent progression to CST and its severe effects. In the case reports we found, SOVT mostly resolved without any serious sequelae. However, 3 out of 60 literature cases died and 7 of the cases did not regain any visual acuity after presenting with no light perception. The majority of cases fortunately reported complete recovery.

Conclusion

We present 9 new cases of SOVT and an overview of 60 previously described cases in literature. We found a variation in both septic and aseptic causes of SOVT, and both in our cases as in literature, the majority of SOVT was caused by aseptic disorders. Patients clinically present with typical orbital symptoms, which can also mimic OC and CST. Thus, especially in patients presenting with OC without sinusitis or other signs of inflammation, SOVT should be considered. Underlying pathology should be sought for, such as systemic diseases or haematological disorders.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Supplementary data

Supplemental data for this article can be accessed at https://doi.org/10.1080/01676830.2018.1497068