The Role of Coronavirus Spike Protein in Inducing Optic Neuritis in Mice: Parallels to the SARS-CoV-2 Virus.

BACKGROUND: Optic neuritis (ON), one of the clinical manifestations of the human neurological disease multiple sclerosis (MS), was also reported in patients with COVID-19 infection, highlighting one potential neurological manifestation of SARS-CoV-2. However, the mechanism of ON in these patients is poorly understood. EVIDENCE ACQUISITION: Insight may be gained by studying the neurotropic mouse hepatitis virus (MHV-A59), a ß-coronavirus that belongs to the same family as SARS-CoV-2. RESULTS: Mouse hepatitis virus-A59, or its isogenic spike protein recombinant strains, inoculation in mice provides an important experimental model to understand underpinning mechanisms of neuroinflammatory demyelination in association with acute stage optic nerve inflammation and chronic stage optic nerve demyelination concurrent with axonal loss. Spike is a surface protein that mediates viral binding and entry into host cells, as well as cell-cell fusion and viral spread. Studies have implicated spike-mediated mechanisms of virus-induced neuroinflammatory demyelination by comparing naturally occurring demyelinating (DM) and nondemyelinating (NDM) MHV strains. CONCLUSIONS: Here, we summarize findings in MHV-induced experimental ON and myelitis, using natural DM and NDM strains as well as engineered recombinant strains of MHV to understand the role of spike protein in inducing ON and demyelinating disease pathology. Potential parallels in human coronavirus-mediated ON and demyelination, and insight into potential therapeutic strategies, are discussed.

Optic neuritis following SARS-CoV-2 infection.

The most common neurologic symptoms in COVID-19 are headache, anosmia, and dysgeusia. Optic neuritis is an unusual manifestation of SARS-CoV-2 infection. We report a case of a patient who initially consulted for vision loss in the absence of respiratory symptoms. She was diagnosed with optic neuritis following SARS-CoV-2 infection. Delay in diagnosis of neuro-ophthalmic manifestations of COVID-19 may lead to irreversible optic atrophy. A mechanism in which viral antigens would induce an immune response against self-proteins, or direct SARS Cov-2 infection of the central nervous system, may be involved in optic nerve injury.

Pattern- and motion-related visual evoked potentials in HIV-infected adults.

PURPOSE: The goal of the current study was to explore visual function in virally suppressed HIV patients undergoing combined antiretroviral therapy (cART) by using pattern-reversal and motion-onset visual evoked potentials (VEPs). METHODS: The pattern-reversal and motion-onset VEPs were recorded in 20 adult HIV+ patients with a mean age of 38 years and CD4 cell counts ≥230 × 106 cells/L of blood. RESULTS: Nine out of 20 patients displayed VEP abnormalities. Pattern-reversal VEPs pathology was observed in 20% of subjects, and 45% HIV patients had impaired motion-onset VEPs. Five out of 16 neurologically asymptomatic HIV patients had prolonged motion-onset VEP latencies in both eyes. Four neurologically symptomatic patients displayed simultaneously abnormal motion-onset and pattern-reversal VEP latencies: monocular involvement was observed in two patients with Lyme and cytomegalovirus unilateral optic neuritis. Binocular involvement was noted in two patients with cognitive deficits. Correlation analysis between disease duration, CD4 cell count, HIV copies in plasma, MoCA and electrophysiological parameters did not show any significant relationships. CONCLUSIONS: The functional changes of the visual system in neurologically asymptomatic virally suppressed HIV patients displayed higher motion-onset VEP sensitivity than in standard pattern-reversal VEP examinations. This promising marker, however, has no significant association with clinical conditions. Further exploration is warranted.

Parainfectious optic neuritis: manifestations in children vs adults.

BACKGROUND: Parainfectious optic neuritis may appear at any age. The aim of our report was to compare the clinical manifestations and outcomes of this form of optic neuritis between children and adults. METHODS: The study sample consisted of all patients diagnosed with parainfectious optic neuritis evaluated by 2 neuro-ophthalmology services between 2005 and 2012. Data were collected retrospectively from the medical files. Findings were compared between patients aged 0-18 years and 19 years or older. RESULTS: Ten children (50% female) and 8 adults (50% female) met the study criteria. Mean duration of follow-up was 29.4 months (range, 2-72 months) in the pediatric group and 14.2 months (range, 5-80 months) in the adult group. Respective rates of bilateral disease were 50% and 38%, and all patients had optic disc swelling. The associated pathogen was identified in 60% of the pediatric group, mainly Mycoplasma pneumoniae, and 75% of the adult group, in which no microorganism predominated. The interval from the febrile illness to symptom onset was 6 days (range, 1-14 days) in the pediatric group and 19.5 days (range, 14-30 days) in the adult group. Acute disseminated encephalomyelitis (ADEM) was diagnosed in 40% (4/10) of the children and none of the adults. Final visual outcome was 20/30 or better in all patients. There was a higher frequency of bilateral disease in prepubescent vs postpubescent children. CONCLUSIONS: Parainfectious optic neuritis is associated with a favorable visual prognosis regardless of age. Children tend to manifest visual symptoms sooner after the antecedent infectious illness and more often bilaterally and in conjunction with ADEM. The causative agent is isolated less frequently in children compared with adults.

A Comparison between Demyelinating and Omicron Variant Infection-Associated Optic Neuritis.

BACKGROUND: The connection between viral infection and the onset of demyelination has garnered considerable attention. Omicron, the most recent prevalent strain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised concerns. Optic neuritis (ON) associated with Omicron infection and spontaneous demyelinating ON may manifest distinct disease progressions. This study aims to contrast the features of these two distinct etiologies of ON. METHODS: This case-control study comprised fifteen patients (21 eyes) diagnosed with Omicron infection-related ON and fifteen patients (24 eyes) with demyelinating ON serving as the control group. Clinical characteristics, cerebrospinal fluid (CSF) analysis, treatment protocols, and outcomes were compared between the two groups. RESULTS: The Omicron-infected group exhibited a higher incidence of pain upon ocular movement (p = 0.023) and peripapillary hemorrhages (p = 0.046). In CSF analysis, there was an elevation in white cell counts (WCCs) (p = 0.004), with lymphocytes being the predominant cell type in the Omicron-related ON group. However, oligoclonal bands (OCBs), indicative of intrathecal synthesis, were significantly lower and lagged behind those of the demyelinating ON group (p = 0.021). SARS-CoV-2 RNA was not directly detected in the CSF of the Omicron-related ON group, and the degree of WCC elevation was closely linked with peripapillary hemorrhages (odds ratio = 0.029, p = 0.02). Additionally, the Omicron-related ON group displayed more pronounced ganglion cell loss following 3-month treatment (p = 0.02). CONCLUSION: Omicron-related ON is distinguished by more pronounced clinical symptoms and distinct CSF characteristics compared to spontaneous demyelinating ON. The absence of viral RNA sequence in the CSF of Omicron-associated ON supports the use of steroid monotherapy; however, varying treatment options and prognoses should be considered for these two types of ON.

New insights in the pathogenic mechanism of multiple sclerosis: Is Epstein-Barr virus associated with optic nerve involvement?

INTRODUCTION: There are no reports in the literature studying the possible relationship between Epstein-Barr virus (EBV) and optic nerve involvement in multiple sclerosis (MS). The aim of our study was to analyze the association between EBV antibodies titres and optical coherence tomography (OCT) and OCT angiography (OCTA) quantitative parameters. METHODS: We conducted a retrospective study. The study included 98 eyes of 49 patients with MS. Years of MS duration, relapse count, history of optic neuritis (ON), and immunoglobulin (Ig) G antibodies to the EBV viral capsid antigen (VCA) were recorded from each patient. Also, OCT analysis (including retinal nerve fibre layer (RNFL) thickness and ganglion cell-inner plexiform layer (GCIPL) thickness) and OCTA analysis (including perfusion density (PD) and flux index (FI) of the radial peripapillary capillary plexus) were performed in each participant. RESULTS: No significant associations were observed between anti-EBV antibody levels and OCT or OCTA parameters (p > 0,05). Correlation analysis between OCT and OCTA measurements showed a significant positive correlation between RNFL thickness and GCIPL thickness with peripapillary PD and FI (p < 0,035). Subgroup analysis revealed a significant diminution of RNFL thickness, GCIPL thickness and peripapillary PD and FI (p < 0,05) in the ON group. CONCLUSION: We were unable to demonstrate a significant association between anti-EBV VCA IgG antibody titres and OCT or OCTA parameters. Nonetheless, further longitudinal studies are needed to explore the possible association of EBV with optic nerve involvement in MS.

Presumed cytomegalovirus-associated retrobulbar optic neuritis in a patient after allogeneic stem cell transplantation.

A case of cytomegalovirus (CMV)-associated bilateral retrobulbar optic neuritis (ON) following haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is reported. Abrupt onset of bilateral decreased vision occurred in a 33-year-old man 7 months after haplo-HSCT. His cerebrospinal fluid (CSF) demonstrated pleocytosis with an absence of leukemic cells. CMV DNA was detected in his blood and CSF sample. Neither encephalopathy nor retinopathy was found in this patient. He was diagnosed with bilateral retrobulbar ON. Although he was given enough antiviral treatment against CMV and immunosuppression with high-dose methylprednisolone, the patient's vision showed no improvement, and he has almost total bilateral blindness. This is the first report, to our knowledge, of CMV-associated bilateral retrobulbar ON in allogeneic stem cell transplantation.

[Clinical study of optic neuritis combined with viral hepatitis].

OBJECTIVE: To investigate the clinical manifestation, management and prognosis of optic neuritis combined with viral hepatitis. METHODS: Retrospective study case series. Clinical data from twenty patients with optic neuritis combined with hepatitis who were hospitalized in Beijing Tongren Hospital neural eye ward from September 2003 to June 2010 were collected, the clinical characteristics and visual field changes in the group of patients were summarized, and comparison between the vision before and after treatment was made by the Wingerchuk vision classification. RESULTS: Among the twenty patients, eighteen patients had chronic hepatitis B and two patients had chronic hepatitis C. Thirteen (65%) patient were monocular, sixteen (80%) patients were single-phase course. Twenty-seven eyes were affected. Disc edema was very common which was found in 14 eyes (52%), severe vision impairment (Best corrected visual acuity worse than 20/200) were recorded in 19 eyes (70%). Lower altitudinal visual field impairment was more common which was found in 10 eyes (50%). All patients were followed for 3 months after steroid therapy, complete visual recovery or significant improvement was seen in only 3 eyes (11%) or 4 eyes (15%). Minor improvement was seen in 12 eyes (44%), while 8 eyes (30%) had no improvement. CONCLUSIONS: In this study, optic neuritis combined with hepatitis usually showed severe visual impairment. Although the vision of some patients could completely recover after steroid therapy, most of the patients had poor recovery. Combination of steroid and anti-viral therapy should be considered in the management of optic neuritis combined with hepatitis.

Optic neuritis caused by canine distemper virus in a Jack Russell terrier.

An atypical case of canine distemper (CD) was diagnosed in a vaccinated healthy adult dog. The patient was presented circling, seizuring, and blind. Postmortem examination resulted in a diagnosis of CD. Optic neuritis was diagnosed, a finding not previously described in the context of CD virus infection presenting solely with neurological signs.

Herpes zoster optic neuritis.

Herpes zoster (HZ) is an acute infection caused by reactivation of the latent varicella-zoster virus [1]. Herpes zoster ophthalmicus (HZO) occurs when inflammation spreads from the ganglion of Gasser to the ophthalmic branch of the trigeminal nerve. Optic neuritis, a very rare sequela of HZO [2-4], can occur simultaneously to the acute vesicular skin eruption or, more frequently, as a postherpetic complication. We report on a 74-year-old woman who presented with HZ optic neuritis 45 days after developing an incompletely treated bout of trigeminal HZ, characterized only by pruritus. It is important to value the non-specific manifestations of cutaneous HZ in the prodromal phase, so as to offer timely and appropriate treatment.

Vascular Damage May Mimic Retinitis and Optic Neuritis in COVID-19.

Ophthalmologic nvolvement in SARS-CoV-infected patients is variegated. One of the ophthalmologic pathologies is optic neuritis. Optic neuritis in SARS-CoV-infected patients may precede the classical pulmonary manifestations of COVID-19 and can be unilateral or bilateral. Optic neuritis has been repeatedly reported in COVID-19 patients and may occur with or without affection of other cranial nerves. Since cerebro-spinal fluid parameters can be abnormal in COVID-19 associated optic neuritis, these patients require a spinal tap. Before diagnosing SARS-CoV-2 associated optic neuritis various differentials need to be excluded. Since SARS-CoV-2 causes endothelial damage complicated by thrombus formation and thromboembolism, ophthalmologic vascular complication due to an infection with SARS-CoV-2 such as anterior ischemic optic neuropathy (AION), central retinal artery occlusion (CRAO), and retinal vein occlusion need to be excluded. CRAO may result from arterial hypertension, myocarditis, heart failure, Takotsubo syndrome, atrial fibrillation, or atrial flutter, frequent cardiac complications of COVID-19. Since CRAO can be accompanied by ischemic stroke, patients with SARS-CoV-2 associated optic neuritis need to undergo a cerebral MRI.

Post COVID-19 Ophthalmic Manifestations in an Asian Indian Male.

Introduction: The Ocular manifestations of coronavirus disease 2019 (COVID-19) reported include conjunctivitis, conjunctival hyperemia, chemosis, epiphora, episcleritis, retinal manifestations included cotton wool spots (CWS), micro-hemorrhages, papillophlebitis and neuro-ophthalmic manifestations.Purpose: To report post COVID-19 ophthalmic manifestations using multimodal imaging.Results: A 66-year-old Asian Indian male presented to us with bilateral blurring of vision, RE>LE, of 3 days following a diagnosis of COVID-19 disease. Corrected distance visual acuity were 20/2666 and 20/25 in the right (RE) and left (LE) eyes respectively. He had bilateral anterior chamber inflammation with a relative afferent pupillary defect in the RE. RE showed central retinal artery occlusion(CRAO) with CWS, few flame-shaped retinal hemorrhages and disc edema and hyperemia. LE had disc edema and hyperemia, few flame-shaped retinal hemorrhages, cystoid changes and CWS. A diagnosis of bilateral panuveitis and papillitis with CRAO in the RE was made.Conclusion: Our patient developed a vascular occlusion with panuveitis, which possibly represents an immune mediated event following COVID-19. Patients should be warned about possible ophthalmic sequelae even after recovery.

AIDS and optic neuritis in a rhesus monkey infected with the R5 clade C SHIV-1157ipd3N4.

A Chinese rhesus macaque infected with the pathogenic CCR5-tropic clade C simian-human immunodeficiency virus, SHIV-1157ipd3N4, had persistent viremia, depletion of CD4(+) T cells to <200 cells/µl, opportunistic infections, coagulopathy, and gradual development of bilateral blindness. MRI revealed marked thickening of both optic nerves. Histopathological evaluation showed diffuse cellular infiltration at necropsy and a focus of SHIV-infected cells. This is the first report of CNS pathology following chronic infection with an obligate R5 SHIV.

Herpes viruses in optic neuritis: Similar to Bell's palsy.

OBJECTIVE: Optic Neuritis (ON) might unfold either as a single intracranial neuritis or as multiple sclerosis, a widespread demyelinating disorder. Different herpes viruses have been proposed as potential participants in the etiology of multiple sclerosis (MS). To analyze the potential presence of herpes viruses in blood and subarachnoid area at the time of ON and contrast the findings according to long-term evolution either as intracranial neuritis or as progression to multiple sclerosis. PATIENTS AND METHODS: In a prospective investigation we searched the presence of DNA from 5 herpes viruses (HSV-1, HSV-2, VZV, EBV and HHV6) in CSF and blood lymphocytes from 54 patients with ON, patients were followed 62 ±â€¯3 months; those who developed MS were separated from those with ephemeral ON. Long-term prognosis of ON was related to DNA findings. RESULTS: As compared with controls, DNA from HSV-1 was significantly more frequent in CSF and blood from cases with ON; VZV and HSV-2 were found only in CSF; EBV was found only in blood samples (p < 0.006). CONCLUSIONS: Our results point out the potential participation of HSV, VZV and EBV in ON; suggesting the intervention of various herpes viruses as triggering agents of autoimmunity. However, the number of positive cases was minor than negative cases. Also, our results suggest that the etiological mechanisms in ON could be similar to those of neuritis of the facial nerve (Bell's palsy).

Experimental optic neuritis induced by a demyelinating strain of mouse hepatitis virus.

Optic neuritis (ON), an inflammatory demyelinating optic nerve disease, occurs in multiple sclerosis (MS). Pathological mechanisms and potential treatments for ON have been studied via experimental autoimmune MS models. However, evidence suggests that virus-induced inflammation is a likely etiology triggering MS and ON; experimental virus-induced ON models are therefore required. We demonstrate that MHV-A59, a mouse hepatitis virus (MHV) strain that causes brain and spinal cord inflammation and demyelination, induces ON by promoting mixed inflammatory cell infiltration. In contrast, MHV-2, a nondemyelinating MHV strain, does not induce ON. Results reveal a reproducible virus-induced ON model important for the evaluation of novel therapies.

Bilateral optic neuritis in acute hepatitis C.

A 34-year-old woman developed bilateral optic neuritis 2 weeks after the onset of acute hepatitis C. The strong temporal relationship between the initial clinical manifestations of hepatitis C and the development of optic neuritis provides a basis for thinking that the hepatitis caused the optic neuritis After corticosteroid treatment, the optic neuropathy markedly improved but left behind retinal nerve fiber thinning, as measured by optical coherence tomography, and optic disc pallor. Optic neuritis has been reported in conjunction with hepatitis A and B but not with hepatitis C.

A case of bilateral presumed chikungunya neuroretinitis.

Chikungunya fever is a relatively rare from of vector-borne viral fever caused by chikungunya virus and spread by bites of the Aedes aegypti and Aedes albopictus mosquito. Epidemics of chikungunya fever have been reported in the past from different parts of the world. Although the virus had been passive for quite some time, recent reports of outbreaks of chikungunya fever in several parts of Southern India have confirmed the re-emergence of this virus. Symptoms of this infection include abrupt onset of fever, chills, and headache, rash, severe joint pain, conjunctival injection and photophobia. Ocular manifestations have been recently reported with this infection. We report a case of a 48-year-old female patient, who presented with defective vision two weeks after a serology proven chikungunya infection. There was bilateral neuroretinitis with peripapillary cotton wool spots. These findings should be kept in mind as an ocular manifestation of chikungunya virus infection.