Neuro-Ophthalmic Complications of COVID-19 Infection and Vaccination.

The COVID-19 pandemic has led to the identification of new disease phenotypes associated with infection by the SARS-CoV-2 virus. This includes multiple neuro-ophthalmological sequelae, which have been associated with COVID-19 infection and administration of COVID-19 vaccines. Some of these associations have a plausible pathophysiological link to the infection or vaccination but true causation has yet to be established. We review the literature for associations reported between COVID-19 infection or vaccination and neuro-ophthalmic sequelae and review the potential pathophysiological processes that may underlie these associations.

Post-COVID simultaneous onset of Graves' disease and ocular myasthenia gravis in a patient with a complex ocular motility impairment.

A 74-years-old man experienced severe diplopia one month after recovery from an uncomplicated SARS-CoV-2 infection. Neurological examination was normal whereas ophthalmological examination showed bilateral exophthalmos with a complex ocular motility disorder characterized by a pseudo-internuclear ophthalmoplegia after fatigue associated to impairment of elevation and infraduction. Antibodies against TSH and acetylcholine receptors were positive; subsequent hormonal tests, ultrasonography of thyroid gland, single fiber electromyography and orbit MRI confirmed the diagnosis of concomitant Graves Disease (GD) and Myasthenia Gravis (MG). The coexistence between MG and GD is not rare but simultaneous onset after viral infection is very unsual. The complex ocular disorder simulated a deficit of the oculomotor nerve nuclei, and on clinical examination it posed some problems in the diagnosis. We suggest that recent SARS-COV-2 infection may have triggered a complex autoimmune response.

An eye to the future: Acute and long-term neuro-ophthalmological and neurological complications of COVID-19.

COVID-19 has had a significant impact on the global population and has produced compelling evidence of non-pulmonary organ dysfunction, including the nervous system. It is vital that specialists in ophthalmology and neurology are informed of the potential complications of COVID-19 and gain a deeper understanding of how COVID-19 can cause diseases of the nervous system. In this review we detail four possible mechanisms by which COVID-19 infection may result in neurological or neuro-ophthalmological complications: (1) Toxic and metabolic effects of severe pulmonary COVID-19 disease on the neural axis including hypoxia and the systemic hyper-inflammatory state, (2) endothelial dysfunction, (3) dysimmune responses directed again the neuroaxis, and (4) direct neuro-invasion and injury by the virus itself. We explore the pathological evidence for each of these and how they may link to neuro-ophthalmological disorders. Finally, we explore the evidence for long-term neurological and neuro-ophthalmological complications of COVID-19, with a focus on neurodegeneration.

Impact of COVID-19 on Neuro-Ophthalmology in the United States: A National Survey.

PURPOSE: To evaluate the impacts of the COVID-19 on neuro-ophthalmology practice in the United States. DESIGN: Cross-sectional study. METHODS: The North American Neuro-ophthalmology Society distributed a survey on the impact of COVID-19 on neuro-ophthalmic practice to its members. The survey consisted of 15 questions regarding the impact of the pandemic on neuro-ophthalmic practice and perspectives. RESULTS: Twenty-eight neuro-ophthalmologists practicing in the United States responded to our survey. In this survey, 64% of survey respondents were male (n = 18), while 36% were female (n = 10). The average age of a respondent was 55 years old. According to 77% of survey respondents, various neuro-ophthalmic diseases were reported to have worsened during the pandemic including idiopathic intracranial hypertension, compressive optic neuropathy, optic neuritis, and giant cell arteritis. CONCLUSIONS: This survey represents one of the largest studies to describe the impact of the COVID-19 pandemic of neuro-ophthalmology. Given the underrepresentation of neuro-ophthalmology in the United States as described in the literature, this study strengthens the need for more neuro-ophthalmologists to provide timely care, particularly during the pandemic. Further interventions to incentivize the pursuit of neuro-ophthalmology training may help combat the effects of COVID-19 on neuro-ophthalmic conditions.

Ocular manifestations of COVID-19 in the pediatric age group.

The coronavirus disease 2019 (COVID-19) is now known to be associated with several ocular manifestations. The literature thoroughly discussed those that affect adults, with a lesser focus in the pediatric age group. We aim to outline the various pediatric ocular manifestations described in the literature. The manifestations may be divided into isolated events attributed to COVID-19 or occurring in the new multisystem inflammatory syndrome in children (MIS-C), a novel entity associated by COVID-19 infection. Ocular manifestations have virtually affected all ages. They manifested in neonates, infants, children, and adolescents. Episcleritis, conjunctivitis, optic neuritis, cranial nerve palsies, retinal vein occlusion, retinal vasculitis, retinal changes, orbital myositis, orbital cellulitis were reported in the literature with this emerging viral illness. Conjunctivitis was the most common ocular manifestation in MIS-C in nearly half of the patients. Other ocular manifestations in MIS-C were anterior uveitis, corneal epitheliopathy, optic neuritis, idiopathic intracranial hypertension, and retinitis. The clinical outcome was favorable, and children regain their visual ability with minimal or no deficits in most of the cases. Further follow-up may be warranted to better understand the long-term effects and visual prognosis.

Can Tele-Neuro-Ophthalmology Be Useful Beyond the Pandemic?

PURPOSE OF THE REVIEW: Neuro-ophthalmologists rapidly adopted telehealth during the COVID-19 pandemic to minimize disruption to patient care. This article reviews recent research on tele-neuro-ophthalmology adoption, current limitations, and potential use beyond the pandemic. The review considers how digital transformation, including machine learning and augmented reality, may be applied to future iterations of tele-neuro-ophthalmology. RECENT FINDINGS: Telehealth utilization has been sustained among neuro-ophthalmologists throughout the pandemic. Adoption of tele-neuro-ophthalmology may provide solutions to subspecialty workforce shortage, patient access, physician wellness, and trainee educational needs within the field of neuro-ophthalmology. Digital transformation technologies have the potential to augment tele-neuro-ophthalmology care delivery by providing automated workflow solutions, home-based visual testing and therapies, and trainee education via simulators. Tele-neuro-ophthalmology use has and will continue beyond the COVID-19 pandemic. Digital transformation technologies, when applied to telehealth, will drive and revolutionize the next phase of tele-neuro-ophthalmology adoption and use in the years to come.

MOG-IgG positive optic neuritis after SARS-CoV-2 infection.

BACKGROUND: Many neurologic complications have been described after severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) including atypical cases of optic neuritis (ON), positive to myelin oligodendrocyte glycoprotein (MOG) IgG. OBJECTIVE: To report a case of MOG-IgG-associated ON and discuss why SARS-CoV-2 infection could be a potential trigger. METHODS: Retrospective single case report. RESULTS: We report a case of ON with positive MOG-IgG developed 15 days after presentation of SARS-CoV-2 infection. CONCLUSION: This report suggests that SARS-CoV-2 infection may have triggered autoantibodies production against MOG leading to ON.

Optic neuritis following COVID-19 vaccination: Do autoimmune diseases play a role?

PURPOSE AND CONTEXT: We report two cases of optic neuritis following Pfizer-BioNTech COVID-19 vaccination in patients with autoimmune diseases. Post-vaccine optic neuritis, although rare, is reported in the literature and an autoimmune mechanism seems to be involved, especially in genetically predisposed subjects. METHOD: Report of two cases of optic neuritis following COVID-19 vaccination in patients with autoimmune diseases. KEY RESULTS: He novelty of this article is the fact that the two patients had a medical history of autoimmune diseases (Hashimoto thyroiditis and ankylosing spondylitis), a point of interest for research because it is not yet clear whether this could constitute a risk factor for adverse events after vaccination. CONCLUSIONS: The reactogenicity of COVID-19 mRNA vaccine in individuals suffering from immune-mediated diseases is yet to be elucidated and it is being increasingly investigated. Our paper supports the hypothesis that patients who are already affected or predisposed to autoimmune or autoinflammatory disorders should be carefully evaluated for the benefits and risks of COVID-19 mRNA vaccination.

Non-arteritic anterior ischemic optic neuropathy in COVID-19 infection - A case report.

Purpose: To report a case of a non-arteritic anterior ischemic optic neuropathy (NAION) in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Observations: A 60-year-old healthy female without any risk factors for vasculopathy, presented with an acute painless diminution of vision noticed in the lower half of the visual field in the left eye. She was diagnosed with NAION in the setting of a recent SARS-CoV-2 infection. Conclusions and importance: The purpose of this case report is to supplement our knowledge about the neuro-ophthalmological complications of COVID-19 in the form of NAION which might occur even in the early stages of the infection.

Atypical presentation of juvenile multiple sclerosis in a patient with COVID-19.

PURPOSE: To report our experience with a case of a very atypical clinical onset of multiple sclerosis in a young boy during a COVID-19 infection. CASE REPORT: A 16-year-old boy was referred to our ophthalmology clinic with a complete isolated bilateral horizontal gaze palsy. The condition had onset suddenly 2 weeks prior and he had no associated symptoms, as well as no significant medical history. His corrected visual acuity was 0.0 logMAR in both eyes. While hospitalized, he was found infected with COVID-19. Subsequent brain MRI showed multiple lesions typical of a yet undiagnosed MS, as well as an active pontine plaque which was highly probable the cause of the horizontal gaze palsy. High-dose steroid treatment was initiated 1 week later, after the patient exhibited negative COVID-19 test results. CONCLUSION: Clinical manifestations of MS are rarely seen in male teenagers and only a few cases of isolated bilateral horizontal gaze palsy have been reported as the initial manifestation, but never during concomitant COVID-19 infection. We presume that the presence of COVID-19 may have been a neuroinflammatory trigger of underlying MS.

Post-COVID Wernicke's presenting as bilateral vision loss.

PURPOSE: This case report represents poor nutritional intake and vomiting secondary to COVID-19 resulting in Wernicke's syndrome and blindness. OBSERVATIONS: We report the case of a 36 year old with a post-COVID episode of acute-subacute onset bilateral blindness ultimately diagnosed as Wernicke's syndrome based on MRI findings and clinical response to high dose IV thiamine supplementation. CONCLUSIONS AND IMPORTANCE: Given this patient's dramatic presentation of no light perception vision in both eyes and resolution of symptoms with treatment, it is reasonable to consider thiamine deficiency in any individual who presents with acute-subacute onset vision loss, particularly when the history is suggestive of potential nutritional deficiency.

How to Manage a Strabismus Clinic During the COVID-19 Pandemic; What is Really Urgent, What is Not?: A Single-Center Case Series from Turkey

Objectives: To evaluate the management of the pediatric ophthalmology and strabismus clinic when strict quarantine conditions were adopted during the coronavirus disease 2019 (COVID-19) pandemic in Turkey. Materials and Methods: The study presents a review of the patients examined during the quarantine period. All patients were assessed with the highest possible level of personal protection. Results: Ten patients (6 girls, 4 boys) with a mean age of 9 years (range: 2-16) were evaluated. The patients presented 3-20 days after symptom onset. Ocular misalignment and diplopia were the main symptoms. Four of the 10 patients were diagnosed with sixth cranial nerve palsy and three patients were diagnosed with acute-onset comitant esotropia. Six patients had significant cranial magnetic resonance imaging findings. Conclusion: Acute-onset neurological conditions are more common during the COVID-19 pandemic. These reports will contribute to global experience and understanding of COVID-19.

Chapter 8 - Tele-Neuro-Ophthalmology

Tele-neuro-ophthalmology has gained significant adoption worldwide since 2020, largely precipitated by the COVID-19 pandemic. This trend may improve access to neuro-ophthalmic care, which is a scarce resource. Evaluation of many neuro-ophthalmologic conditions may benefit from telehealth due to their reliance on patient history and ancillary testing and less dependence on the physical exam. Formalized asynchronous telehealth modalities such as interprofessional consultation may allow neuro-ophthalmologists to provide rapid point-of-care advice to referring providers without the barrier of long referral wait times. There are multiple techniques and applications available to aid the evaluation of the neuro-ophthalmic patient. Deep machine learning algorithms may also eventually supplement neuro-ophthalmic care.

Papillophlebitis in a COVID-19 patient: Inflammation and hypercoagulable state.

INTRODUCTION: Papillophlebitis is a rare condition characterized by venous congestion and optic disc edema, which has been suggested to occur as a consequence of inflammation of the retinal veins or, possibly, the capillaries of the optic disc, leading to venous insufficiency and compression of the central retina vein. The disease affects healthy young adults and commonly has a benign course, however, if complications such as macular edema or ischemia appears, treatment should be instituted immediately to avoid poor prognosis. CASE REPORT: A 40-year old white male patient consulted for a slight decrease in the sensitivity of the visual field in his left eye (OS). Visual acuities (VA) were 20/20 in both eyes. OS fundus examination showed dilated and tortuous retinal vessels, disc edema, and retinal hemorrhages. The patient was diagnosed with papillophlebitis. OS VA decreased to 20/200 due to macular edema, and he was treated with a intravitreal dexamethasone implant. An exhaustive and interdisciplinary exploration process was performed, identifying a recent disease and recovery of Covid-19 as the only factor of inflammation and coagulation alteration. Other systemic diseases were excluded. We also describe a rapid decrease in disc and macular edema after intravitreal dexametasone injection, which could support the inflammatory hypothesis. CONCLUSION: The importance of this case lies in the possible association of papillophlebitis with the new Covid-19 disease. We believe that the inflammatory reaction and the coagulation alteration present in our patient due to Sars-Cov2 coronavirus may have acted as risk factors for the development of papillophlebitis.

Simultaneous new onset of neuromyelitis optica spectrum disorder in identical twins.

OBJECTIVE: To present a case of two identical twins presenting concurrently with symptoms and subsequent initial diagnosis of neuromyelitis optica spectrum disorder (NMOSD). METHODS: Clinical, laboratory and MRI findings for both twins were reviewed and presented here. RESULTS: Twin A presented with right eye pain and subsequent blurred vision in right eye. MRI of the brain and spine demonstrated pre-chiasmal right optic nerve enhancement and T2 hyperintense lesions in the spinal cord at T7 and T9 levels. Cerebrospinal fluid (CSF) analysis was remarkable for NMO/aquaporin-4 (AQP4) fluorescence-activated cell sorting (FACS) titre of 1:32 and a serum NMO/AQP4-IgG positive titre of 1:10 000. Twin B presented with diplopia. MRI of the brain and spine demonstrated T2 hyperintense lesions in the periventricular cerebral white matter, in the periaqueductal white matter of the pons, in the midbrain and the cervical spinal cord. Neurological examination findings revealed incomplete right trochlear palsy, rotatory nystagmus, an incomplete left internuclear ophthalmoplegia and hyper-reflexia. CSF analysis was remarkable for NMO/AQP4 FACS titre of 1:256 and a serum NMO-IgG positive titre of 1:10 000. Both twins responded well to intravenous steroid therapy. There was no adverse environmental exposure present. CONCLUSION: We present an interesting and rare case of identical twins presenting concurrently and for the first time with NMOSD.

Tolosa-Hunt Syndrome Presenting After COVID-19 Vaccination.

Coronavirus disease 2019 (COVID-19) infection is associated with a plethora of neurological complications. Newly developed vaccinations targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral spike protein represent a great epidemiological promise with respect to the resolution of the pandemic. However, vaccinations are not without side effects and, in rare cases, have even been implicated in various autoimmune phenomena. In this report, we describe a case of Tolosa-Hunt syndrome (THS), a granulomatous inflammatory process of the cavernous sinus, occurring in a patient one week after getting COVID-19 vaccination. This rare diagnosis of exclusion must be considered in patients presenting with painful ophthalmoplegia.

Unilateral inferior altitudinal visual field defect related to COVID-19.

Ocular manifestations of COVID-19 are still being studied. Posterior segment involvement in viral entities is either direct viral involvement or a delayed immune response to the antigen. A 22-year-old woman presented with history of perceiving absolute inferior scotoma in the right eye for 4 days and history of fever and sore throat 10 days ago. Fundus examination revealed disc edema and vessel tortuosity. Humphreys Field Analyzer confirmed inferior field defect and Optical Coherence Tomography showed superior, nasal and inferior retinal nerve fiber layer thickening in the right eye. Patient was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription polymerase chain reaction (RT-PCR) testing. Patient received three doses of injection methylprednisolone over 3 days. There was subjective resolution of scotoma reported 3 weeks posttreatment. We bring forward the first reported case of parainfectious optic neuritis associated with COVID-19.

Neuro-ophthalmologic complications of coronavirus disease 2019 (COVID-19).

Multiple neuro-ophthalmological manifestations have been described in association with COVID-19. These symptoms and signs may be the result of a range of pathophysiological mechanisms throughout the course from acute illness to recovery phase. Optic nerve dysfunction, eye movement abnormalities and visual field defects have been described.