SARS-CoV-2 Impairs Vision.

OBJECTIVES: Affection of the central nervous system and the eyes is increasingly recognized as manifestations of a SARS-CoV-2 infection (COVID-19). This review aims at summarizing and discussing recent advances concerning causes and locations of impaired vision because of an infection with SARS-CoV-2. METHODS: On a literature search through PubMed and ScholarOne, all available publications about COVID-19 patients with impaired vision were retrieved. RESULTS: Visual impairment in SARS-CoV-2-infected patients may be due to infection of lacrimal glands (dacryoadenitis), conjunctivitis, tonic pupils, vitritis, central retinal artery/venous occlusion, retinitis, retinal bleeding, panuveitis, anterior ischemic optic neuropathy, optic nerve stroke, optic neuritis, optic perineuritis, or occipital ischemic stroke. Visual impairment may be the initial manifestation of SARS-CoV-2. CONCLUSIONS: This mini review shows that impaired vision may be the initial manifestation of COVID-19, that all sections of the visual tract may be affected and causative for visual impairment in COVID-19 patients, and that SARS-CoV-2 manifests along the visual tract with ischemia, focal infection, and immunological reactions.

Neuro-Ophthalmic Visual Impairment in the Setting of COVID-19.

We set out to describe in detail the afferent neuro-ophthalmological complications that have been reported in association with coronavirus disease 2019 (COVID-19) infection. We describe and elaborate on mechanisms of disease, including para-infectious inflammation, hypercoagulability, endothelial damage, and direct neurotropic viral invasion. Despite global vaccination programs, new variants of COVID-19 continue to pose an international threat, and patients with rare neuro-ophthalmic complications are likely to continue to present for care.Afferent complications from COVID-19 include homonymous visual field loss, with or without higher cortical visual syndromes, resulting from stroke, intracerebral hemorrhage, or posterior reversible leukoencephalopathy. Optic neuritis has frequently been reported, sometimes along with acute disseminated encephalomyelopathy, often in association with either myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) or less commonly aquaporin-4 seropositivity or in newly diagnosed multiple sclerosis. Ischemic optic neuropathy has rarely been reported. Papilledema, resulting either from venous sinus thrombosis or idiopathic intracranial hypertension in the setting of COVID-19, has also been described.Observed afferent neuro-ophthalmic associations need to be confirmed though larger comparative studies. Meanwhile, the range of possible complications should be recognized by neurologists and ophthalmologists alike, to facilitate faster diagnosis and treatment of both COVID-19 and its neuro-ophthalmic manifestations.

Headache, Loss of Smell, and Visual Disturbances: Symptoms of SARS-CoV-2 Infection? A Case Report.

OBJECTIVE: The purpose of this case report is to describe the main components of the history and physical examination that led to idiopathic intracranial hypertension differential diagnosis, which initially was investigated as COVID-19. METHODS (CASE DESCRIPTION): A 28-year-old woman complaining of constant headache and loss of smell and taste was suspected as SARS-CoV-2 infection by her general practitioner. She underwent 3 molecular swab tests, all negative, then decided to seek her physical therapist for relieving headache. RESULTS: The full cranial nerve examination revealed impaired olfactory (CNI), abducens (CN VI), and facial (CN VII) nerves, leading the physical therapist to refer the patient to a neurosurgeon for a suspected central nervous system involvement. The neurosurgeon prescribed a detailed MRI and an ophthalmologic examination, which allowed for the final diagnosis of idiopathic intracranial hypertension. CONCLUSION: An urgent lumbo-peritoneal shunting surgery resolved the patient's symptoms and saved her sight. Despite the ongoing COVID-19 pandemic, health care professionals must pay attention to properly investigating patients' signs and symptoms using comprehensive clinical reasoning, considering the screening for referral to specialist medical attention. IMPACT: A thorough physical examination is required for every patient even if patients' signs and symptoms are in line with apparent common and widespread pathologies. Cranial nerve evaluation is an essential component of the physical therapist assessment and decision-making process. The ongoing pandemic highlighted the fundamental assistance of physical therapists toward physicians in the screening and management of musculoskeletal diseases.

Case Report: Papilledema Secondary to Cerebral Venous Sinus Thrombosis after Severe COVID-19 Infection.

SIGNIFICANCE: This case highlights ocular adverse effects of a rare, potentially life-threatening complication from coronavirus disease 2019 (COVID-19). Papilledema can occur because of increased intracranial pressure caused by cerebral venous sinus thrombosis, the incidence of which may be more likely in patients with a history of COVID-19 because of an induced hypercoagulable state. PURPOSE: This case report presents a case of papilledema secondary to cerebral venous sinus thrombosis in a patient with a recent history of severe coronavirus disease (COVID-19). CASE REPORT: A 29-year-old man hospitalized with a complicated course of coronavirus disease (COVID-19) was referred to the ophthalmology department for episodic blurry vision of both eyes and intermittent binocular diplopia. Clinical examination revealed diffuse bilateral optic disc edema. Magnetic resonance venography of the brain during his admission revealed subtotal occlusion of the right transverse sinus by thrombosis. At the time of diagnosis, the patient was already taking systemic anticoagulation therapy for treatment of a recent pulmonary embolism also thought to be induced by COVID-19. After additional treatment with acetazolamide, there was improvement in his optic nerve edema. CONCLUSIONS: Cerebral venous sinus thrombosis, a serious and potentially life-threatening condition, can occur as a rare complication of COVID-19. In such cases, patients may develop increased intracranial pressure, papilledema, and subsequent vision loss. Magnetic resonance venography should be ordered in patients with suspected papilledema to help rule out the presence of cerebral venous sinus thrombosis.

Leber Hereditary Optic Neuropathy Gene Therapy: Adverse Events and Visual Acuity Results of All Patient Groups.

PURPOSE: To assess safety of gene therapy in G11778A Leber hereditary optic neuropathy (LHON). DESIGN: Phase 1 clinical trial. METHODS: Setting: single institution. PARTICIPANTS: Patients with G11778A LHON and chronic bilateral visual loss >12 months (group 1, n = 11), acute bilateral visual loss <12 months (group 2, n = 9), or unilateral visual loss (group 3, n = 8). INTERVENTION: unilateral intravitreal AAV2(Y444,500,730F)-P1ND4v2 injection with low, medium, high, and higher doses to worse eye for groups 1 and 2 and better eye for group 3. OUTCOME MEASURES: Best-corrected visual acuity (BCVA), adverse events, and vector antibody responses. Mean follow-up was 24 months (range, 12-36 months); BCVAs were compared with a published prospective natural history cohort with designated surrogate study and fellow eyes. RESULTS: Incident uveitis (8 of 28, 29%), the only vector-related adverse event, resulted in no attributable vision sequelae and was related to vector dose: 5 of 7 (71%) higher-dose eyes vs 3 of 21 (14%) low-, medium-, or high-dose eyes (P < .001). Incident uveitis requiring treatment was associated with increased serum AAV2 neutralizing antibody titers (p=0.007) but not serum AAV2 polymerase chain reaction. Improvements of ≥15-letter BCVA occurred in some treated and fellow eyes of groups 1 and 2 and some surrogate study and fellow eyes of natural history subjects. All study eyes (BCVA ≥20/40) in group 3 lost ≥15 letters within the first year despite treatment. CONCLUSIONS: G11778A LHON gene therapy has a favorable safety profile. Our results suggest that if there is an efficacy effect, it is likely small and not dose related. Demonstration of efficacy requires randomization of patients to a group not receiving vector in either eye.

A Case of Transient Visual Field Defect following Administration of Pfizer-BioNTech COVID-19 Vaccine.

PURPOSE: To report a case of transient visual field (VF) defect after coronavirus disease-19 (COVID-19) vaccination. CASE REPORT: A 38-year-old Caucasian, otherwise healthy female patient, presented with a complaint of vision loss in the outer quadrant in her left eye after the second dose of Pfizer®-BioNTech™ COVID-19 vaccine. The Snellen visual acuity was 20/20 in both eyes. She did not have relative afferent pupillary defect nor disturbance of color vision. Her intraocular pressures, slit lamp and fundus examinations were normal. In the VF test, a temporal hemifield defect in the left eye and a nasal peripheral VF defect in the right eye were detected. Other imaging characteristics and neurological examination were normal. She was followed without any treatment. One week later, the patient was re-evaluated and complete resolution of the VF defect was observed. CONCLUSION: Clinicians should be aware that patients can experience transient visual symptoms following COVID-19 vaccination.

Vision Loss Secondary to COVID-19 Associated Bilateral Cerebral Venous Sinus Thromboses.

A young, morbidly obese woman with recent SARS-CoV-2 infection requiring hospitalization presented with visual and neurologic complications secondary to bilateral cerebral venous sinus thromboses. With elevated intracranial pressure and severe papilledema, she rapidly progressed to complete bilateral vision loss despite anticoagulation, therapeutic lumbar punctures with lumbar drain, bilateral optic nerve sheath fenestrations, and endovascular thrombectomy. It is possible that obese patients with a SARS-CoV-2 infection may be at greater risk of hypercoagulable cerebrovascular complications. It is impossible to know if an even more rapid response would have led to a different outcome, but we report this case in the hope that publishing this and similar cases may result in improved treatment protocols to preserve vision.

Multiple evanescent white dot syndrome following vaccination for COVID-19: A case report.

RATIONALE: Multiple evanescent white dot syndrome (MEWDS) is an acute, usually unilateral, retinal disorder of unknown etiology that predominantly occurs in healthy young women. We report a case of bilateral asymmetric MEWDS that developed following the first vaccination for coronavirus-19 and worsened after a second vaccination. PATIENT CONCERNS: A 30-year-old Japanese woman was examined in an eye clinic for blurred vision in her left eye for 1 week duration. Thirteen days before her examination, she had received her first BNT162b2 mRNA SARS-CoV-2 vaccination. Her best-corrected visual acuity was 20/20 in both eyes. Fundus examination revealed multiple yellowish-white spots in the perifoveal area of both eyes. Visibility of the spots gradually decreased during the following week. She was then vaccinated with a second dose, and 3 days later, her vision worsened in her left eye. She was then referred to our hospital because of worsened vision and the appearance of white spots on other parts of the retina. Ophthalmological examination revealed a best-corrected visual acuity of 30/20 both eyes. DIAGNOSIS: The flare value in the anterior chamber was elevated in both the eyes. Fundus examination showed multiple white spots in the perifoveal area of both eyes, but they were more prominent in the left eye. Fundus fluorescein angiography revealed early hyperfluorescent spots located circumferentially around the fovea in both eyes. We concluded that the patient had MEWDS, which was most likely due to mRNA COVID-19 immunization. INTERVENTIONS: The patient was treated with topical betamethasone sodium phosphate/fradiomycin sulfate 0.1% thrice daily for 2 months. OUTCOMES: Two months after treatment, her blurry vision resolved with the disappearance of the fundus lesions. LESSON: Clinicians should be aware of potential adverse ocular events following similar vaccinations.

Persistent visual dysfunction following posterior reversible encephalopathy syndrome due to COVID-19: Case series and literature review.

BACKGROUND AND PURPOSE: The full spectrum of neurological sequelae in COVID-19 is beginning to emerge. SARS-CoV-2 has the potential to cause both direct and indirect brain vascular endothelial damage through infection and inflammation that may result in long-term neurological signs and symptoms. We sought to illuminate persistent neuro-ophthalmological deficits that may be seen following posterior reversible encephalopathy syndrome (PRES) due to COVID-19. METHODS: We identified three individuals with PRES due to COVID-19 in our hospital system. One patient was identified on presentation to our neuro-ophthalmology clinic. The other patients were identified through internal records search. These cases were compared to published reports of PRES in COVID-19 identified through systematic literature search of PubMed/LitCOVID. RESULTS: All three patients were hospitalized with severe COVID-19 and developed altered mental status with new onset seizures that led to the recognition of PRES through diagnostic imaging. During recovery, two patients had persistent visual dysfunction including visual field deficits. One patient also experienced hallucinatory palinopsia and visual hallucinations. Literature search identified 32 other cases of PRES in the context of COVID-19. Visual disturbances were described in 14 cases (40%), with only seven cases (50%) reporting full recovery by the time of publication. CONCLUSIONS: As we learn about enduring neurological complications of COVID-19, it is possible that complications may be underrecognized and underreported. Understanding the range of complications can help in postcare evaluation and management changes in the critical care setting to potentially allow intervention before persistent deficits occur due to COVID-19.

Clinico-Radiological-Pathological Correlation of Visual Loss in COVID-Associated Rhino-Orbito-Cerebral Mucormycosis.

PURPOSE: To correlate the clinical, radiological, and histopathological features in Covid-associated Rhino-orbito-cerebral mucormycosis cases presenting with acute visual loss. DESIGN: Cross-sectional study. METHODS: Covid-associated Rhino-orbito-cerebral mucormycosis cases with unilateral visual loss, planned for exenteration, underwent orbital and ophthalmological ocular examination. The available radiological sequences, doppler ultrasonography and histopathology findings were correlated with clinical manifestations. RESULTS: The median age was 51 years and the male: female ratio was 3:1. All except one presented with unilateral ophthalmoplegia. The ocular media were hazy in 2 eyes. In 8 eyes, retinal changes were suggestive of occlusion of CRA (6), combined occlusion of CRA and central retinal vein (1), and myopic degeneration with hypertensive retinopathy (1). The contralateral eye showed retinal ischemic changes in one patient. Radiological imaging showed orbital apex involvement in the 10 affected eyes and one contralateral eye. Ipsilateral cavernous sinus thrombosis, diffusion restriction on MRI of optic nerve, internal carotid artery narrowing/thrombosis, and cortical watershed infarcts were seen in 8, 4, 4, and 2 cases, respectively. The blood flow in CRA and ophthalmic artery was absent or reduced in all the 10 affected eyes and in 1 contralateral eye. On histopathology, orbital fat necrosis, fungal hyphae, acute inflammation, granuloma formation, ischemic thrombosis of ophthalmic artery was observed in 10 specimens. CRA was patent in 9 and thrombosed in 1 eye. Optic nerve was ischemic in 8 and viable in 2 eyes. CONCLUSION: Acute visual loss in ROCM cases is associated with orbital apex involvement and thrombotic ischemia of ophthalmic artery. Cessation of flow in CRA possibly occurs secondary to ophthalmic artery thrombosis.

Pediatric Intracranial Hypertension: A Spotlight on Imaging, the Idiopathic Intracranial Hypertension Treatment Trial, and COVID-19 Associated Cases.

Primary intracranial hypertension (PIH) is characterized by clinical signs of increased intracranial pressure, papilledema, elevated opening pressure, and absence of mass lesion, hydrocephalus, or meningeal enhancement on neuroimaging. Visual changes are a common presenting feature and if untreated there is risk of irreversible vision loss. There have been recent proposed changes to the criteria for PIH along with studies looking at the differences in imaging characteristics between adult and pediatric PIH. The presence of transverse sinus stenosis alone was highly sensitive and specific for pediatric PIH. The Idiopathic Intracranial Hypertension Treatment Trial was an adult, multicenter study that examined the use of acetazolamide and weight loss on the course of PIH. The study confirmed many previously held beliefs including the most common presenting symptom in PIH is headache. Most patients present with bilateral papilledema with 58.2% of patients having symmetric Frisen scale grading and within one grade in 92.8%. Although diplopia is a common reported symptom, very few have evidence of cranial nerve palsy. Male gender, high-grade papilledema, and decreased visual acuity at presentation are risk factors for treatment failure. Acetazolamide use is associated with mild metabolic acidosis. During acetazolamide treatment, monitoring for hypokalemia or aplastic anemia is not recommended. Monitoring transaminases in the titration phase of treatment should be considered due to a case of transaminitis and pancreatitis with elevated lipase. Newer case reports have also seen associations of secondary intracranial hypertension with concurrent COVID-19 infection and MIS-C.

Acute reduction of visual acuity and visual field after Pfizer-BioNTech COVID-19 vaccine 2nd dose: a case report.

Long-term and rare adverse effects of COVID-19 vaccines are unknown. Hence, it is important to report them to improve the safety profile of the vaccines and enhance their use worldwide. Here, we describe a case of acute visual impairment after Pfizer-BioNTech vaccine second dose.

Intracranial hypertension and visual loss following COVID-19: A case report.

A 40-year-old woman presented with headache, bilateral optic disc edema, and visual loss. She had been diagnosed with COVID-19 (coronavirus disease 2019) 15 days ago. Her cerebrospinal fluid opening pressure was 410 mmH2O, and cranial imaging was normal. She had obesity as a risk factor but had not experienced any ophthalmic complaints before. COVID-19 could be a causative or precipitating factor for intracranial hypertension especially in high-risk groups even in the late phases of the disease and has not been discussed in the literature as such. This should be studied further and kept in mind to prevent permanent loss of vision.

Posterior reversible encephalopathy syndrome (PRES) associated with COVID-19.

The novel human coronavirus disease (COVID-19) has been associated with vascular and thrombotic complications, some of which may result from endothelial dysfunction, including the posterior reversible encephalopathy syndrome (PRES). We report a case series of 8 patients with COVID-19 and PRES diagnosed at two academic medical centers between March and July of 2020. The clinical, laboratory and radiographic data, treatment, and short-term outcomes were retrospectively analyzed. The mean age was 57.9 ± 12 years, and 50% were women. Four patients had previous vascular comorbidities. All the patients suffered from severe pneumonia, requiring intensive care unit admission. Five patients were not hypertensive at presentation (all SBP < 127 mmHg). Neurologic symptoms included seizures in 7 patients; impaired consciousness in 5 patients; focal neurological signs in 3 patients; and visual disturbances in 1 patient. All patients underwent brain magnetic resonance imaging which indicated asymmetric T2 prolongation or diffusion changes (50%), extensive fronto-parieto-occipital involvement (25%), vascular irregularities (12.5%) and intracranial hemorrhage (25%). Four patients were treated with tocilizumab. Three patients were discharged without neurologic disability, 2 patients had persistent focal neurologic deficits and 2 expired. One patient's prognosis remains guarded. Together, these data support the relationship between PRES and endothelial dysfunction associated with severe COVID-19. In patients with severe COVID-19, PRES can be triggered by uncontrolled hypertension, or occur independently in the setting of systemic illness and certain medications. Like other infectious processes, critically ill patients with COVID-19 may be at greater risk of PRES because of impaired vasoreactivity or the use of novel agents like Tocilizumab.

Monocular visual loss as the presenting symptom of COVID-19 infection.

BACKGROUND AND IMPORTANCE: Additional time is needed to determine the exact impact of COVID-19 on acute cerebrovascular disease incidence, but recently published data has correlated COVID-19 to large vessel occlusion strokes. CLINICAL PRESENTATION: We report the first case of central retinal artery occlusion (CRAO) as the initial manifestation of COVID-19 infection. Subsequent neuroimaging revealed a large thrombus extending into the internal carotid artery. CONCLUSION: This case illustrates the need to suspect COVID-19 infection in patients presenting with retinal arterial occlusion, including individuals who are asymptomatic or minimally symptomatic for COVID-19 infection.