key: cord-0990681-c4hu1n7l authors: Khurram, Ruhaid; Naidu, Vishnu; Butt, Mohsin F.; Durnford, Luke; Joffe, Michael title: Superior ophthalmic vein thrombosis secondary to COVID-19: an index case date: 2021-03-03 journal: Radiol Case Rep DOI: 10.1016/j.radcr.2021.02.063 sha: f0a15d2a86cda0b8ba6626c6e890182c05e3ff9d doc_id: 990681 cord_uid: c4hu1n7l Superior ophthalmic vein thrombosis is a very rare condition, known to have a profound negative impact on vision and eye movement function and is usually associated with orbital infections, inflammation, tumors or carotid cavernous fistulae. There is an increased risk of arterial and venous thrombosis associated with COVID-19, the presence of which is related to a significantly increased risk of mortality. We report an index case of superior ophthalmic vein thrombosis in a 61-year-old male patient who was diagnosed with COVID-19 pneumonitis and a concomitant saddle pulmonary embolus. He was swiftly treated with low molecular weight heparin which led to the resolution of the thrombosis within 3 weeks. This case highlights the importance of considering this entity in the context of COVID-19 as well as providing prompt treatment to reduce the risk of complications. Abstract: Superior ophthalmic vein thrombosis is a very rare condition, known to have a profound negative impact on vision and eye movement function and is usually associated with orbital infections, inflammation, tumors or carotid cavernous fistulae. There is an increased risk of arterial and venous thrombosis associated with COVID-19, the presence of which is related to a significantly increased risk of mortality. We report an index case of superior ophthalmic vein thrombosis in a 61-year-old male patient who was diagnosed with COVID-19 pneumonitis and a concomitant saddle pulmonary embolus. He was swiftly treated with low molecular weight heparin which led to the resolution of the thrombosis within 3 weeks. This case highlights the importance of considering this entity in the context of COVID-19 as well as providing prompt treatment to reduce the risk of complications. The severe acute respiratory syndrome coronavirus 2 (SARs-COV-2 or COVID-19) is widely reported to be associated with increased risk of thromboembolic disease, likely secondary to hypercoagulability and/or a systemic inflammatory response associated with the infection. Large scale meta-analyses reveal that the pooled odds of mortality in COVID-19 positive patients who develop thromboembolism are 74% higher compared to those who do not. (1) The superior ophthalmic vein (SOV) originates from the superomedial angle of the orbital fossa and courses alongside the superior orbital artery within the intraconal space to ultimately drain into the cavernous sinus. SOV thrombosis is an extremely rare clinical phenomenon with an estimated incidence of 3-4 cases/million/year.(2) Its etiology is broadly categorized into septic and aseptic causes. Orbital cellulitis, sinusitis and septic cavernous sinus thrombosis account for common primary septic causes whereas facial trauma, hypercoagulability, aseptic inflammation, orbital neoplasms and Tolosa-Hunt syndrome account for the aseptic etiologies. (3)(4). The clinical features of SOV thrombosis can include painful proptosis, chemosis, conjunctival swelling, ophthalmoplegia, trismus and visual disturbance/loss. As such, timely diagnosis and identification of this condition is essential to prevent the profound visual complications and eye movement dysfunction. Herein, we present an index case of SOV thrombosis secondary to COVID-19 pneumonitis and a concomitant saddle pulmonary embolus. A 61-year-old man was admitted to hospital with a one week history of fever, muscle weakness and fatigue. His family contacts tested positive for COVID-19. His past medical history included: end stage renal failure with a renal transplant in 2009 (for which he was immunosuppressed), type 2 diabetes mellitus, cerebrovascular disease, sleep apnoea, orthostatic hypotension, benign prostatic hyperplasia (treated with transurethral resection of the prostate in 2009), and recurrent urinary tract infections. On clinical examination, his temperature was mildly elevated at 37.6℃, his pulse was 112 beats per minute and blood pressure was 111/74. Urinalysis was positive for leucocytes, nitrites and trace amounts of blood. He was initially admitted and treated in hospital for urosepsis, but began to develop low oxygen saturations and subsequently tested positive for COVID-19. He therefore received additional treatment with dexamethasone and tocilizumab. Unfortunately, despite one week of treatment on the ward, persistently poor oxygen saturations and limited urine output resulted in transfer to the intensive care unit where he was initially intubated and haemodialysed. Due to persistent fluctuating low oxygen saturations, a computed tomography pulmonary angiogram (CTPA) was performed 5 days following admission to intensive care. This demonstrated a saddle pulmonary embolus with extension into the segmental and subsegmental pulmonary artery branches of the right and left hemithoraces. This was on a background of bilateral ground-glass attenuation and patchy consolidation, consistent with severe COVID-19 pneumonitis ( Figure 1 ). Treatment with low molecular weight heparin (LMWH) was initiated following this finding. Three days following a diagnosis of a saddle pulmonary embulus, the patient was incidentally found to have bilateral edematous eyelids. An ophthalmology opinion was sought and an ocular examination revealed bilaterally fixed and constricted pupils (left eye, 2mm; right eye, 3mm). No exophthalmos was noted however there was asymmetrical right-sided conjunctival injection and chemosis. Visual acuity was difficult to ascertain at this point since the patient was unconscious and receiving invasive ventilation. A CT head with orbital imaging was performed which demonstrated an expanded and hyperdense right superior ophthalmic vein (SOV) as well as asymmetrical hyperdensity of the venous structures within the right masticator space. There was also swelling of the right pterygoid muscles and effacement of the fat planes. The findings were consistent with acute thrombosis of the right SOV and the right pterygoid venous plexus ( Figure 2) . The left SOV also appeared dilated and this, in addition to the aforementioned findings, raised the suspicion of a bilateral caroticocavernous fistula (CCF). A multidisciplinary team decision was made to treat this abnormality with LMWH, which the patient was already receiving for the concomitant pulmonary embolism. The patient made excellent progress on intensive care and was fortunately extubated 3 weeks following the initial diagnosis of right SOV thrombosis. Repeat interval imaging at this point with a CT head ( Figure 3 ) and a CTPA (Figure 4 ) demonstrated complete resolution of the right SOV thrombosis and pulmonary embolism, with marked improvement in lung parenchymal appearances. We are pleased to report that the patient has now completely recovered from his illness and there were no residual abnormalities in relation to the SOV thrombosis. He has preserved range of movement in his eyes bilaterally, no diplopia and no deficiency in visual acuity. He is now undergoing speech and language therapy, physiotherapy and rehabilitation to improve his physical function after the prolonged hospital admission with COVID-19. This case report addresses the clinical characteristics of SOV thrombosis and the importance of considering this entity in COVID-19 patients with ocular impairment. To our knowledge, we are the first group to describe SOV thrombosis in a patient with COVID-19 pneumonitis. COVID-19 is thought to induce a systemic inflammatory response, endothelial dysfunction and a hypercoagulative state which predisposes patients to forming systemic thrombi.(5-8) Proposed molecular and cellular mechanisms include COVID-19 induced pyroptosis, the upregulation of platelet activation, coagulation cascade and proinflammatory cytokines such as interleukin-6 as well as a downregulation of fibrinolysis.(6)(8) All of the aforementioned factors are thought to be contributory to the formation of systemic emboli and/or immunothrombosis due to a delicate interplay between the immune system and haemostasis. (8) In our case, the patient also had a concomitant saddle pulmonary embolus which may have directly contributed to the development of SOV thrombosis secondary to distal embolic migration. Several institutions begin prophylactic anticoagulation in all hospitalized COVID-19 patients, whilst treatment dose anticoagulation is used in confirmed venous thromboembolism, for which there is evidence demonstrating improved clinical outcomes.(9) The attenuation of inflammatory pathways is postulated to have a dampening effect on the development of immunothrombi. Dexamethasone is associated with improved outcomes in hospitalized patients (10) and there is increasing research into the therapeutic utility of anti-cytokine agents such as tocilizumab (anti-IL6) and anti-complement agents.(11) Further research is required to clarify the optimum management of thrombosis in COVID-19, ensuring that a careful balance is struck between targeting the dysfunctional prothrombotic pathways, without impairing the host immune response against infection. SOV thrombosis in itself is a very rare entity and infrequently reported in the existing literature.(12)(13) Its etiology can be categorized into septic and aseptic causes, orbital cellulitis being the most commonly associated condition. (3)(14) It can also present either unilaterally or bilaterally and has an association with cavernous sinus thrombosis. The signs and symptoms of SOV thrombosis are usually due to impaired venous drainage from the affected orbit e.g. chemosis, painful eye movements, proptosis, eyelid swelling and visual disturbance.(4) There is considerable overlap and non-specificity of signs and symptoms when compared to other known ophthalmological conditions, which is why neuroimaging is necessary for a definitive diagnosis. CT or MRI venography are the modalities of choice, however the pathology can also be identified on a non-contrast cross-sectional studies. The primary findings include a dilated SOV with linear filling defects on CT or MRI venography or affected vessel hyperdensity in non-contrast examinations. (3) The management of SOV thrombosis has a focus on identifying and treating the underlying cause. Treatment options include anticoagulation, antibiotics or surgery and there is no definitive consensus and/or guidelines addressing its management. In general, published data suggests that aseptic, post-traumatic or incidental SOV thrombi have been treated with anticoagulation alone whereas septic cases have received additional antibiotics. Incidental and aseptic SOV thrombi are associated with a good prognosis and often respond to conservative/medical management. Septic SOV thrombi, secondary to orbital cellulitis or paranasal sinusitis, have a higher risk of complications such as abscess formation and therefore are likely to require surgical intervention and drainage. Thromboembolism risk of COVID-19 is high and associated with a higher risk of mortality: A systematic review and meta-analysis Venous anatomy of the orbit Superior ophthalmic vein thrombosis: What radiologist and clinician must know? Impact of superior ophthalmic vein thrombosis: a case series and literature review Incidence of thromboembolism in patients with COVID-19: a systematic review and metaanalysis Thrombosis and COVID-19 pneumonia: the clot thickens! Venous thromboembolism in patients with COVID-19: Systematic review and metaanalysis COVID-19, immunothrombosis and venous thromboembolism: biological mechanisms Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy Dexamethasone in Hospitalized Patients with Covid-19 -Preliminary Report Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts Spontaneous superior ophthalmic vein thrombosis: a rare entity with potentially devastating consequences Superior Ophthalmic Vein Thrombosis with Complete Loss of Vision as a Complication of Autoimmune and Infective Conditions Superior ophthalmic vein thrombosis developed after orbital cellulitis The authors of this manuscript have obtained written, informed consent from the patient to write up the case report and for the use of images pertinent to the case. We have ensured anonymity of all clinical and graphical data used.