Superior Ophthalmic Vein Thrombosis Secondary to Hyperhomocysteinemia

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Gour Wang, MD Superior Ophthalmic Vein Thrombosis Secondary to Hyperhomocysteinemia Lauren R. Schaffer, BA, Jill R. Wells, MD, Courtney E. Francis, MD S uperior ophthalmic vein thrombosis (SOVT) is an uncommon condition that typically presents with acute onset of orbital symptoms and has the potential to cause lasting visual impairment. Risk factors for SOVT include infection, coagulopathies, and inflammatory diseases (1). We present an unusual presentation of isolated SOVT in a 64-year-old woman with no ophthalmologic complaints and subsequent diagnosis of hyperhomocysteinemia. A 64-year-old woman presented to the emergency department for altered mental status and was found to be hypotensive and hypoglycemic. She had an extensive medical history, including idiopathic pulmonary hypertension, uncontrolled diabetes (hemoglobin A1c 15.3), rheumatoid arthritis, Sjögrens, chronic kidney disease stage III, and fibromyalgia. In addition, she reported a family history of blood clots but no personal history. Chart review revealed that she had been on long-term warfarin that had been discontinued by her hematologist 7 days before presentation due to no clear diagnosis warranting chronic anticoagulation and an increased risk of adverse events related to a history of frequent falls. A noncontrast head computed tomography (CT) was performed on admission and revealed an incidental finding of bilateral dilated superior ophthalmic veins (SOVs) with asymmetric hyperdensity in the right SOV (Fig. 1). To further evaluate hyperdensity, an MR venogram (MRV) was ordered and revealed a near total occlusive thrombus in the right SOV as well as a prominent left SOV, which was believed to be compensatory because there was no evidence of intraluminal thrombus on the left (Fig. 2). There was no propagation of the clot, cavernous sinus thrombosis, nor other venous sinus thrombosis. The patient denied any vision changes, pain, or redness but did endorse 3–4 months of headache in the right frontotemporal region that occasionally caused blurred vision. Ophthalmology was consulted and ocular examination revealed bilateral cataracts but was otherwise normal with intraocular pressure 14 mm Hg bilaterally, visual acuity 20/60 bilaterally, Department of Ophthalmology (LRS, JW), Emory University School of Medicine, Atlanta, Georgia; and Departments of Ophthalmology and Neurological Surgery (CEF), University of Washington School of Medicine, Seattle, Washington. Unrestricted University of Washington departmental grant from Research to Prevent Blindness. The authors report no conflicts of interest. Address correspondence to Courtney E. Francis, MD, Department of Ophthalmology, University of Washington, 325 9th Avenue, Box 359608, Seattle, WA 98104; E-mail: [e-mail] e312 no relative afferent pupillary defect, intact extraocular movements, and a normal dilated examination. A hypercoagulability and age-appropriate cancer workup was performed, including protein C, protein S, factor 5 Leiden, antiphospholipid antibodies, homocysteine, antithrombin III, mammogram, Papanicolaou test, and colonoscopy. Results were all negative except for an elevated homocysteine of 15.8 mmol/L (reference range: ,10.4 mmol/L). A diagnosis of hyperhomocysteinemia was made. As hyperhomocysteinemia is rarely diagnosed in the seventh decade of life, it is likely the patient had previously been diagnosed, which would explain why she had been on long-term warfarin therapy. However, the anticoagulation had been discontinued because the patient was unaware of the diagnosis and it had not been recorded in her FIG. 1. Axial noncontrast CT head demonstrating increased prominence of superior ophthalmic veins bilaterally and hyperattenuation within the right superior ophthalmic vein suggestive of an acute thrombus. CT, computed tomography. Schaffer et al: J Neuro-Ophthalmol 2021; 41: e312-e313 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 2. Axial MR venogram head and orbit demonstrating an enlarged right superior ophthalmic vein with a near total occlusive thrombus and compensatory prominence of the left superior ophthalmic vein. chart. The patient was subsequently restarted on anticoagulation with warfarin and a heparin bridge. The patient was referred to hematology, who decided that no further workup was required and that the patient should continue on warfarin indefinitely with a goal International Normalized Ratio of 2–3. One month later, a noncontrast head CT scan showed a decrease in size of the SOV bilaterally with no evidence of the hyperdensity previously seen in the right SOV. Eighteen months after diagnosis, an MRI of brain with and without contrast revealed partial recanalization of the right SOV. The SOV is responsible for most venous drainage of the eye (1). Thrombosis of the SOV, especially isolated SOVT defined as SOVT without cavernous sinus pathology, is a rare condition (2). SOVT can be classified as either septic or aseptic. Septic SOVT can result from infections of the sinuses, orbit, face, or teeth (1,3). Causes of aseptic SOVT that have been reported include carotid cavernous fistula and orbital tumors. SOVT has also been reported in the setting of a number of systemic conditions, including hypercoagulable states such as antiphospholipid syndrome, systemic malignancy, sickle cell trait, and recent withdrawal of anticoagulation. In addition, many cases of SOVT have been associated with inflammatory diseases, such as systemic lupus erythematosus, ulcerative colitis, and Graves disease (1,2). Typically, patients with SOVT present acutely with pain, chemosis, proptosis, limited extraocular movements, and/or impaired vision. Imaging, either MRI or Schaffer et al: J Neuro-Ophthalmol 2021; 41: e312-e313 contrast-enhanced CT, should be performed to assist in making the diagnosis. Treatment depends on the etiology but can include antibiotics, anticoagulation, and steroids (1). Furthermore, additional workup should be performed for potential contributing systemic causes or risk factors, including ageappropriate cancer screening and hypercoagulability studies (proteins C/S, factor 5 Leiden, antiphospholipid antibodies, homocysteine, and antithrombin III) (1). To the best of our knowledge, this case represents the first reported case of SOVT associated with hyperhomocysteinemia. Hyperhomocysteinemia has been associated with many disorders, including dementia, osteoporosis, and increased risk of thrombosis (4). The pathophysiology of hyperhomocysteinemia and how it might increase the risk of thrombosis has been studied, and potential explanations suggest that hyperhomocysteinemia results in oxidative damage to the endothelium causing decreased nitric oxide production and impaired vasodilation. Furthermore, homocysteine may activate platelets, resulting in increased platelet aggregation and adhesion and thus a further increased risk of thrombosis (4). However, there is controversy regarding the association between hyperhomocysteinemia and venous thrombosis because there may be confounding factors contributing to the significantly increased risk of thrombosis that has been shown in previous studies (5). The patient we present also had numerous other risk factors for SOVT, including multiple inflammatory conditions (rheumatoid arthritis and Sjögren), in addition to recent cessation of long-term warfarin therapy. Furthermore, it is worth noting that unlike most of the previously reported cases, this patient did not present with any ocular complaints, and the diagnosis was made following an incidental finding on a CT scan. Moreover, the eye examination, both at time of diagnosis and followup, was normal and the only significant history was a chronic headache for a few months before presentation. Thus, this case serves as an example of how it is critical to keep SOVT on the differential if imaging reveals enlarged superior ophthalmic veins, even in the apparent absence of significant history and examination findings. This case also demonstrates that, although rare, hyperhomocysteinemia should be included on the differential when evaluating a case of SOVT. REFERENCES 1. van der Poel NA, de Witt KD, van den Berg R, de Win MM, Mourits MP. Impact of superior ophthalmic vein thrombosis: a case series and literature review. Orbit. 2019;38:226–232. 2. Rao R, Ali Y, Nagesh CP, Nair U. Unilateral isolated superior ophthalmic vein thrombosis. Indian J Ophthalmol. 2018;66:155–157. 3. Sotoudeh H, Shafaat O, Aboueldahab N, Vaphiades M, Sotoudeh E, Bernstock J. Superior ophthalmic vein thrombosis: what radiologist and clinician must know? Eur J Radiol Open. 2019;6:258–264. 4. Eldibany MM, Caprini JA. Hyperhomocysteinemia and thrombosis: an overview. Arch Pathol Lab Med. 2007;131:872–884. 5. Ospina-Romero M, Cannegieter SC, den Heijer M, Doggen CJM, Rosendaal FR, Lijfering WM. Hyperhomocysteinemia and risk of first venous thrombosis: the influence of (unmeasured) confounding factors. Am J Epidemiol. 2018;187:1392–1400. e313 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.