Vision Preservation in COVID-Related Cerebral Sinovenous Thrombosis With Optic Nerve Sheath Fenestration

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Vision Preservation in COVID-Related Cerebral Sinovenous Thrombosis With Optic Nerve Sheath Fenestration Andrew B. Johnston, MD, Asim F. Choudhri, MD, Violiza Inoa, MD, Lauren C. Ditta, MD A 21-year-old woman presented to the emergency department (ED) with a 1-day history of horizontal diplopia and headache. Three weeks before, she had been diagnosed with COVID-19 after reporting loss of taste and smell. Medical history was additionally notable for obesity (BMI 44.1). On initial ED examination, she had a right esotropia. The neurology service pursued neuroimaging, starting with head CT without contrast. This was followed by MRI of the brain without and with contrast, performed in conjunction with an MR venogram (MRV) of the head. MRV of the head revealed cerebral sinovenous thrombosis (CSVT) involving a majority of the superior sagittal sinus, including tributary cortical veins, the right transverse and sigmoid sinuses, and the right jugular bulb. The brain parenchyma was normal on CT of the head and MRI of the brain. Hematology was consulted, who started the patient on a heparin drip and admitted her to the neurointensive care unit. She had an embolic workup, which was unrevealing. She also had an extensive hypercoagulable workup, which was notable only for an elevated D-dimer (610 ng/mL). After initiation of anticoagulation, the patient remained stable, was transitioned to apixaban, and discharged home. A week later, headache and diplopia worsened. A community ophthalmologist evaluated the patient and found a right cranial nerve VI palsy and bilateral, highgrade optic nerve edema, prompting urgent ED referral. Head CT and CT venogram were performed, demonstrat- Departments of Ophthalmology (ABJ, LCD, AFC), Radiology (AFC), Neurosurgery (AFC), and Neurology (VI),; University of Tennessee Health Science Center, Hamilton Eye Institute, Memphis, Tennessee;; and Le Bonheur Neuroscience Institute (AFC, LCD), Le Bonheur Children’s Hospital Memphis, Tennessee; Semmes Murphey Clinic (VI), Vascular Neurology and Neurointerventional Radiology, Memphis, Tennessee; and Department of Ophthalmology (LCD), St. Jude Children’s Research Hospital, Memphis, Tennessee. The authors report no conflicts of interest. This case study was HIPAA compliant and performed after parental consent. Address correspondence to Lauren C. Ditta, MD, Le Bonheur Children’s Hospital Neuroscience Institute, 848 Adams Avenue, Memphis, Tennessee 38103; E-mail: [e-mail] Johnston et al: J Neuro-Ophthalmol 2022; 42: e463-e465 ing extensive CSVT, with a decrease in clot burden since the MRV. Lumbar puncture opening pressure was 40 cm H2O. She was started on acetazolamide (500 mg twice a day) and instructed to continue oral anticoagulation. She was then referred to our neuro-ophthalmology clinic. On examination, vision was 20/20 in both eyes. Pupils were equally reactive without an afferent pupillary defect (APD). She had a 12D right esotropia and 21 limitation to abduction of the right eye, consistent with a right sixth nerve palsy. She also had Frisen grade III papilledema (Fig. 1). Automated visual field (AVF) revealed paracentral areas of depression in the right eye and an enlarged blind spot in the left. Retinal nerve fiber layer (RNFL) global thickness was 259 mm in the right eye and 220 mm in the left eye. Treatment options were discussed, including continued medical therapy vs. surgical interventions. Given resolved headache, she elected to continue her medications at the current doses. The patient was re-examined within 1 week. Vision decreased to 20/30 in the right eye, there was a right APD, and AVF revealed an enlarged blind spot with superotemporal areas of depression in the right eye. The left eye remained stable. RNFL thickness increased to 274 mm in the right eye and 221 mm in the left eye. A plan was made for optic nerve sheath fenestration (ONSF) of the right eye the following day. The patient underwent an uncomplicated ONSF. At 3 weeks postoperatively, vision improved to 20/25 in the right eye. She had a residual, mild right APD. AVF showed only a stable enlarged blind spot. The RNFL in the right eye improved to 151 mm. The left eye remained stable (Fig. 2). At 2.5 months postoperatively, headaches resolved, vision improved (20/20 in both eyes), visual fields were full, diplopia had largely resolved, with a 12D esotropia in right gaze only, and RNFL global thickness improved in both eyes, without ganglion cell layer loss on OCT. MRV showed resolution of the right-sided clot with only residual clot in the superior sagittal sinus. She was continued on acetazolamide and apixaban. Cerebral sinovenous thrombosis (CSVT) is a relatively uncommon thromboembolic event within the general population (1). Although there has not been an increase in the reported number of CSVT cases during the 2020 e463 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. High-grade, bilateral papilledema at the time of presentation to the neuro-ophthalmology clinic. COVID pandemic, there is emerging evidence of COVID19-associated coagulopathy (1–4), with CSVT as a complication with neuro-ophthalmologic implications (1,5,6). Although the pathophysiology remains unknown, there is a growing consensus that viral infections may lead to profound dysregulation between inherent procoagulant and anticoagulant mechanisms, leading to endothelial dysfunction, inhibition of fibrinolysis, increased blood viscosity, and septic-associated coagulopathy (7,8). Patients with COVID-19 have been found to have anticoagulant dysregulation resulting in elevated D-dimer levels and fibrinogen (9). These patients are therefore at a higher risk for thromboembolic events, such as CSVT and other sequelae. Papilledema is often a consequence of venous hypertension from CSVT. Early detection and treatment are critical in preventing vision loss. The mainstay of treatment for CSVT is anticoagulation to prevent further clot formation and promote clot dissolution (10). Management of CSVT sequelae, such as papilledema, is an important consideration. Mild papilledema can often be managed with anticoagulation and oral carbonic anhydrase inhibitors (acetazolamide). Severe cases, at high risk of vision loss, may require serial lumbar punctures; however, they are also treated with ONSF and other cerebrospinal fluid diversion procedures (e.g., ventriculoperitoneal and lumboperitoneal shunt) (11). Several endovascular interventions have been reported for the treatment of CSVT: thrombolysis, thrombectomy, stenting, or a combination of these. The efficacy of these treatments has not been established, and most endovascular treatments have been deemed as salvage therapies for refractory CSVT (12). We present a woman with CSVT, elevated ICP, highgrade papilledema, sixth nerve palsy, and reduced vision, after a symptomatic COVID infection. This is a timely and interesting case because of increasing recognition of thrombotic events associated with COVID infections. Several studies have reported significantly increased rates of venous and arterial thromboses in patients with COVID-19, but most of these events have been in hospital settings, particularly the ICU (2,13–15). CSVT has only rarely been reported in the context of COVID-19, especially in the outpatient setting. Unique to this case is our patient having only mild COVID symptoms yet remaining at risk for hypercoagulable events, given her elevated D-dimer—which has been shown to not only predict likelihood of venous thromboembolism but also stratify risk (14). Although evidence for direct oral anticoagulant (DOAC) use in CSVT is limited, FIG. 2. Reduced papilledema in the right eye 3 weeks after ONSF (image on left). ONSF, optic nerve sheath fenestration. e464 Johnston et al: J Neuro-Ophthalmol 2022; 42: e463-e465 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence there is a growing tendency to consider DOACs for the treatment of hypercoagulable states, including CSVT. Apixaban was the preferred (DOAC) in this case (16,17). Her high-grade papilledema, despite imaging signs of decreased clot burden, placed her at risk for permanent vision loss. Therefore, it is important to consider this vision-threatening condition in COVID-positive patients who also present with visual or neurologic complaints, even in ambulatory settings. This case also highlights the importance of monitoring patients with known idiopathic intracranial hypertension (IIH) or IIH risk factors closely because acquiring COVID could exacerbate symptoms resulting from CSVT. ONSF was pursued because of worsening vision, highgrade papilledema, and field defects. ONSF is particularly useful for vision preservation in patients with intractable papilledema in the setting of CSVT to prevent optic nerve damage in the acute setting, while allowing time for clot dissolution. In this way, patients are protected from vision loss while also avoiding more invasive procedures with permanent implanted devices. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: A. B. Johnston, A. F. Choudhri, V. A. Inoa, and L. C. Ditta; b. Acquisition of data: A. B. Johnston, A. F. Choudhri, V. A. Inoa, and L. C. Ditta; c. Analysis and interpretation of data: A. B. Johnston, A. F. Choudhri, V. A. Inoa, and L. C. Ditta. Category 2: a. Drafting the manuscript: A. B. Johnston, A. F. Choudhri, V. A. Inoa, and L. C. Ditta; b. Revising it for intellectual content: A. B. Johnston, A. F. Choudhri, V. A. Inoa, and L. C. Ditta. Category 3: a. Final approval of the completed manuscript: A. B. Johnston, A. F. Choudhri, V. A. Inoa, and L. C. Ditta. REFERENCES 1. 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