Coronavirus disease-2019 (COVID-19), which causes severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2), was first recognized and reported in December 2019 in Wuhan, China. Unfortunately, COVID-19 had evolved into a global pandemic infecting 70 million cumulative people and 1.6 million deaths globally till December 15, 2020. Ocular manifestations of this virus include conjunctivitis, corneal epithelial defect, subepithelial infiltrates, asymptomatic retinal lesions, and retinal microhemorrhages. Cavernous sinus thrombosis (CST) leading central retinal artery occlusion (CRAO) with eventual optic neuropathy in patient with COVID-19 has never been reported in the available literature to the best of our knowledge. Keeping this in view, we are reporting this case.
A 37-year-old man presented to us with the complaint of loss of vision in the left eye (OS). On enquiring about his past systemic and ocular history, patient revealed that he had suffered from COVID-19 infection 3 months back. He had shortness of breath, difficulty in breathing, generalized weakness, and fever with loss of smell and taste. He got tested for real-time reverse transcription-polymerase chain reaction (RT-PCR) for COVID-19 which came out to be positive and he was admitted in the hospital. Various investigations such as inflammatory markers erythrocyte sedimentation rate (ESR––160 mm/h normal range 1–13 mm/h), C-reactive protein (CRP––56.50 mg/L normal range 3.0 mg/L), D-dimers (>10,000 ng/mL, normal range <250 ng/mL), ferritin (370 ng/mL, normal range 20–250 ng/mL), interleukin-6 (560 pg/mL, and normal range 1.66 to 5.38 pg/mL) were significantly high. Electrocardiogram was normal. Computed tomography (CT) scan of the chest showed ground-glass opacities with reticulations in bilateral lungs consistent with viral pneumonia. Patient’s condition deteriorated on the fifth day of admission and was shifted to the intensive care unit (ICU) and intubated and got treated with the first intravenous (IV) injection of remdesivir in the dose of 200 mg followed by daily IV maintenance doses of 100 mg for next 5 days, azithromycin 500 mg/day IV infusion, and tocilizumab 400 mg IV once and one unit of plasma transfusion with other supportive care. After 9 days of stay in ICU, the patient recovered from pneumonia and was shifted to the ward where he developed sudden onset of swelling, foreign body sensation, drooping of upper eyelid, and diminution of vision of the left eye. An ophthalmological opinion was sought and records revealed no perception of light along with ptosis, proptosis, and complete ophthalmoplegia in the left eye. On fundus photography, it showed severe optic disc edema with cherry red spot and retinal whitening suggestive of CRAO without cilioretinal sparing [Fig. 1a]. Magnetic resonance imaging (MRI) brain and orbit showed CST with left diffuse pre-septal and retro-orbital edema with swollen optic nerve sheath secondary to CST [Fig. 1b]. CT venography demonstrated asymmetric bulging and filling defect of the left cavernous sinus. Axial images showed thickened and prominent left optic nerve sheath with ill-defined soft tissue infiltration at orbital apex between the medial rectus and optic nerve [Fig. 1c and d]. ESR and CRP were 85 mm and 49.14 mg/L, respectively. Patient was again admitted and managed with intravenous steroids, antibiotics, anticoagulant, and symptomatic care for a week. In the meanwhile, a biopsy was taken from the nasal mucosa to rule out any fungal infection (Asperigillosis) by Oto-rhinolaryngologist but reports were unremarkable. Despite this whole treatment, no visual recovery was noticed for left eye and the patient got discharged. Proptosis, ptosis, and ophthalmoplegia recovered completely within 1 month of treatment. Then patient presented to us with complaints of loss of vision in the left eye. On ophthalmological examination, the right eye revealed unaided visual acuity of 20/20 on Snellen’s chart with normal color vision. The left eye showed exodeviation of 15° on Hirschberg’s test. On swinging flashlight test, the left eye showed grade four relative afferent pupillary defect. Otherwise, anterior segment of both eyes was unremarkable on slit-lamp examination. On slit-lamp-biomicroscopy with 90 D, fundus examination revealed optic disc atrophy with gliosis and macular pucker in the left eye [Fig. 2a] but fundus of right eye was unremarkable. Intraocular pressure was 18 mm Hg and 16 mm Hg in right and left eye, respectively, with applanation tonometry. On spectral domain, optical coherence tomography OS showed loss of foveal contour with thinning measuring 142 mm, hyper-reflective internal limiting membrane with vitreomacular traction and few fluid pockets in parafoveal area [Fig. 2b]. Visual fields examination of right eye were unremarkable. On visual evoked potential (VEP), P100 latency and amplitude was normal in the right eye but it was nearly extinguished and no wave formation were seen in the left eye suggestive of left optic neuropathy [Fig. 2c].
On the basis of the all available records with the patient and the investigations which we did for him, diagnosis of CST with subsequent CRAO and optic neuropathy secondary to COVID 19 infection was made.
The cavernous sinus lying superior to the sphenoid sinuses collects venous drainage from the cranium, orbits, midface, and neck. This predisposes to the spread of infection via thrombophlebitis or septic emboli from these regions. Aseptic or noninfectious CST includes hypercoagulable disorders, malignancy, pregnancy, arteriovenous malformations, and inflammatoryconditions such as Tolosa–Hunt syndrome. CST is a complicated diagnosis that often presents with overlapping features with other more common ophthalmic conditions, including orbital cellulitis and orbital apex syndrome. Common symptoms include ptosis, proptosis, chemosis, ophthalmoplegia (cranial nerve III, IV, VI), and loss of sensation in the ophthalmic and maxillary divisions of the trigeminal nerve (V1 and V2). Rarely visual loss can occur in this entity due to optic nerve ischemia, retinal ischemia, and anterior ischemic optic neuropathy.
In the current case, the patient was young adult who lost his vision in the left eye due to CRAO secondary to CST within two weeks of getting positive for COVID-19 infection. COVID-19 is well known to increase the risk of developing venous thromboembolism. Therefore, patients with COVID-19 have been reported with cerebral venous sinus thrombosis. Additional posterior segment involvements in these conditions include retinitis, neuroretinitis, optic neuritis, panuveitis, and central retinal vein occlusion.
The mechanism responsible for increased risk of thrombosis, both in the venous and arterial circulations, includes excessive inflammation, platelet activation, endothelial dysfunction, and stasis. Angiotensin-converting enzyme 2 (ACE 2) receptor facilitates cell entry of SARS-CoV-2 expressed on mucosal surfaces of multiple organ systems (lung, liver, kidney, skin). Furthermore, ACE2 is present in arterial and venous endothelial cells and arterial smooth muscle cells. SARS-CoV-2 infection facilitates the induction of endotheliitis in several organs as a direct consequence of viral and of the host inflammatory response. Together with cytokine abnormalities, these contribute to vasoconstriction, inflammation, ischemia, and hyper-coagulopathy which eventually can lead to CRAO in COVID-19. Acharya et al. have reported an elderly case of CRAO secondary to COVID-19.
In view of significantly increasing rates of arterio-venous thrombosis in patients with COVID-19, particularly among those with severe disease requiring intensive care support, it is fundamental to carefully consider visual symptoms in order to pursue adequate ophthalmological management to avoid irreversible visual loss. Any kind of untoward ophthalmic manifestation without any other confounders should be suspected of COVID-19 whether symptomatic or asymptomatic and proper precautions should be implemented while examining such cases. Knowledge about these novel ocular manifestations should be disseminated among the physicians, health care workers and critical care fraternity to curb the eventual visual morbidity by early interventions.
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