Common Features Between Stroke Following Varicella in Children and Stroke Following Herpes Zoster in Adults : Varicella-Zoster Virus in Trigeminal Ganglion.

The cerebral arteries are innervated by afferent fibers from the trigeminal ganglia. Varicella-zoster virus (VZV) frequently resides in the trigeminal ganglion. Reports of arterial ischemic stroke due to VZV cerebral vasculopathy in adults after herpes zoster have been described for decades. Reports of arterial ischemic stroke due to post-varicella cerebral arteriopathy in children have also been described for decades. One rationale for this review has been post-licensure studies that have shown an apparent protective effect from stroke in both adults who have received live zoster vaccine and children who have received live varicella vaccine. In this review, we define common features between stroke following varicella in children and stroke following herpes zoster in adults. The trigeminal ganglion and to a lesser extent the superior cervical ganglion are central to the stroke pathogenesis pathway because afferent fibers from these two ganglia provide the circuitry by which the virus can travel to the anterior and posterior circulations of the brain. Based on studies in pseudorabies virus (PRV) models, it is likely that VZV is carried to the cerebral arteries on a kinesin motor via gE, gI and the homolog of PRV US9. The gE product is an essential VZV protein.

Increasing hospitalisation of patients with herpes zoster ophthalmicus-an interdisciplinary retrospective analysis.

BACKGROUND: The occurrence of herpes zoster is rising globally. Future trends will be influenced by changes in population demographics and the growing number of patients at risk. Overall this poses a challenge for healthcare systems. METHODS: In our interdisciplinary, single-centre retrospective analysis, we aimed to assess the burden of the disease within the Department of Dermatology and the Eye Centre from the Medical Centre, University of Freiburg from 2009-2022. We obtained data from 3034 cases coded using the ICD-10 B02.x. Patients were characterised by sex, age, year of treatment, and type of treatment (inpatient vs. outpatient). RESULTS: Overall we observed a 200% increase in the number of herpes zoster patients over the 13-year period. Upon closer analysis, this was mainly due to a rise in inpatient treatment for herpes zoster ophthalmicus. CONCLUSIONS: If the incidence of herpes zoster ophthalmicus continues to increase at the current rate the number of hospitalisations of zoster ophthalmicus would double by 2040, assuming guideline-appropriate treatment. Overall, the results show a growing need for inpatient ophthalmological care.

Pediatric herpes zoster ophthalmicus: a systematic review.

PURPOSE: While typically affecting older adults and immunocompromised individuals, herpes zoster ophthalmicus (HZO) has been reported with varying manifestations and complications in children. In this review, we evaluate reported cases of pediatric HZO in the literature and discuss the epidemiology, risk factors, clinical presentation, treatment and outcomes. METHODS: A literature search on PubMed, Scopus, and Web of Science databases was performed using the terms "pediatric herpes zoster ophthalmicus" and "herpes zoster ophthalmicus children." Publications that were not specific to HZO or pediatric populations were excluded, as were publications that were not available to review or not published in the English language. RESULTS: Fifty-seven reports describing 130 cases of HZO or HZO-related complications were reviewed. Major risk factors for pediatric HZO included intrauterine exposure to varicella or primary varicella infection at a young age; HZO also occurred in patients who had received varicella vaccination. Both healthy and immunocompromised children were affected, with the majority of affected children being immunocompetent. The diagnosis of HZO is primarily clinical. Children appear to have good vision recovery and resolution of symptoms if they are treated promptly and if they adhere to treatment regimens, except for irreversible vision loss related to uncommon complications such as optic neuritis. CONCLUSION: HZO occurs in both healthy and immunocompromised children. Recognizing this treatable condition is essential for reducing ocular and systemic morbidity. Long-term follow-up and assessments of the impact on health in adulthood are lacking. More systematic study is needed to determine the incidence of HZO in children and appropriate diagnostic and treatment protocols for the care of pediatric patients with HZO.

Aseptic meningitis after amenamevir treatment for herpes zoster ophthalmicus with oculomotor nerve palsy in a patient taking immunosuppressant.

A 79-year-old woman presented with vomiting after being prescribed amenamevir by her primary care physician. She had a medical history of rheumatoid arthritis and was administered prednisolone and methotrexate. She was finally diagnosed with herpes zoster ophthalmicus and aseptic meningitis, and intravenous antiviral therapy was initiated. However, the patient developed oculomotor nerve palsy on the 11th day of hospitalization. In this case, there was a time lag between the administration of antiviral drugs and clinical improvement. Our case suggests the necessity of selecting antivirals, especially in high-risk cases of CNS complications, to avoid the low intracerebral transferability of antiviral drugs, including amenamevir.

Orbital apex syndrome in herpes zoster ophthalmicus clinical features, treatment and outcomes: a case series and literature review.

Orbital Apex Syndrome (OAS) complicating Herpes Zoster Ophthalmicus (HZO) is associated with significant visual impairment. We present four patients with HZO OAS, to highlight clinical features and outcomes in order to promote earlier recognition and management of this potentially sight-threatening complication. CT and MRI imaging findings included expansion and enhancement of extraocular muscles and intraconal fat and involvement of the orbital apex and cavernous sinus. All patients received systemic steroid and antiviral therapy, but a standardised dosage and duration of treatment remains to be defined. Final visual acuity and extraocular motility outcomes were variable.

Approaching headaches and facial pains in eye care practice.

Headaches and facial pains are among the most frequent ailments seen in outpatient or emergency settings. Given the fact that some of the primary headaches and facial pains mimic the characteristic patterns seen in ocular diseases and related conditions, it is fairly common for these situations to be sent to an ophthalmology or optometry clinic and misdiagnosed as ocular headaches. This may result in a delay in starting an appropriate therapy, therefore extending the patient's illness. This review article aims to help the practitioners in understanding common causes of headaches and facial pains, approaching such cases in eye OPD and differentiating them for similar ocular conditions to impart an appropriate treatment or referral.

A Case Report of Herpes Zoster Ophthalmicus and Meningitis After COVID-19 Vaccination.

There are several reports that herpes zoster characterized by reactivation of varicella zoster virus (VZV) following coronavirus disease 2019 (COVID-19) vaccines can occur. Herein, we report VZV meningitis, herpes zoster ophthalmicus (HZO), and late neurotrophic keratitis after receiving a second dose of messenger RNA (mRNA) COVID-19 vaccine. A 74-year-old man developed a vesicular skin rash on the forehead, scalp, nose, and left upper eyelid with a severe headache. Five days earlier, he received a second dose of the BNT162b2 mRNA vaccine on his left arm. Ocular examination revealed conjunctival hyperemia and pseudodendrite in the peripheral cornea. VZV was detected in the cerebrospinal fluid using polymerase chain reaction. The patient was diagnosed with HZO and meningitis. The patient was treated with intravenous acyclovir and topical acyclovir ointment and levofloxacin 1.5% eye drops. One month later, he developed a central epithelial defect with a rolled margin, typical of a neurotrophic ulcer. Treatment with a therapeutic contact lens and a combination of topical recombinant human epithelial growth factor and ofloxacin ointment was initiated. At six months after vaccination, the slit-lamp examination findings were stable with a mild corneal superficial stromal haze.

Effectiveness of the Recombinant Zoster Vaccine for Herpes Zoster Ophthalmicus in the United States.

PURPOSE: To examine the effectiveness of the recombinant zoster vaccine (RZV) for preventing herpes zoster ophthalmicus (HZO) in the general United States population. DESIGN: Retrospective, observational cohort study. PARTICIPANTS: Individuals enrolled in the OptumLabs Data Warehouse (OLDW; OptumLabs, Cambridge, MA) who were age eligible for herpes zoster (HZ) vaccination (≥50 years of age) from 2018 through 2019. The OLDW is a longitudinal, de-identified administrative claims and electronic health record database of patients in the United States with commercial insurance, Medicare Part D, or Medicare Advantage METHODS: Patients were required to have 365 days or more of continuous enrollment to be eligible. Those with a diagnosis code of HZ or an immunocompromising condition within 1 year before study inclusion were excluded. Vaccination with the RZV was ascertained by Current Procedural Terminology codes, and HZO was ascertained by International Classification of Diseases, Tenth Revision, codes. Cox proportional hazards regression models were used to estimate the hazard ratio of HZO associated with RZV, and inverse-probability weighting was used to control for confounding. Vaccine effectiveness was calculated from hazard ratios. MAIN OUTCOME MEASURES: Incidence of HZO in vaccinated versus unvaccinated person-times and vaccine effectiveness were assessed. RESULTS: From January 1, 2018, through December 31, 2019, a total of 4 842 579 individuals were included in this study. One hundred seventy-seven thousand two hundred eighty-nine (3.7%) received 2 valid doses of RZV. The incidence rate of HZO was 25.5 cases (95% confidence interval [CI], 17.4-35.8 cases) per 100 000 person-years in the vaccinated group compared with 76.7 cases (95% CI, 74.7-78.7 cases) in the unvaccinated group. The overall adjusted effectiveness of RZV against HZO was 89.1% (95% CI, 82.9%-93.0%). CONCLUSIONS: The effectiveness of RZV against HZO in individuals 50 years of age and older is high in a clinical setting. However, the low vaccination rate in this study highlights the public health need to increase HZV use. Ophthalmologists can play an important role in recommending vaccination to eligible patients.

Short-Term Peripheral Nerve Stimulation Relieve Pain for Elder Herpes Zoster Ophthalmicus Patients: A Retrospective Study.

OBJECTIVE: Ophthalmic postherpetic neuralgia (PHN) is the final stage of herpes zoster (HZ) ophthalmicus and a severe refractory neuropathic pain, thus there is no curative treatment that could alleviate pain and reduce the incidence of ophthalmic PHN now. The purpose of this study is to evaluate therapeutic efficacy of short-term peripheral nerve stimulation (PNS) for elder patients with HZ ophthalmicus. MATERIALS AND METHODS: We performed a retrospective study from March 2015 to August 2019 in our pain department. All the HZ ophthalmicus patients underwent supraorbital nerve short-term PNS were included. The patients' data, including numeric rating scale (NRS), 36-Item short form health survey (SF-36), and analgesic consumptions, were retrospectively analyzed. Severe side effects also were recorded. RESULTS: A total of 68 patients were enrolled in this study. The NRS scores were significantly decreased at different time points after short-term PNS compared to baseline (p < 0.001). The SF-36 scores, including general health, social function, emotional role, mental health, bodily pain, physical functioning, physical role, and vitality, were significantly improved at different time points after treatment (p < 0.001). The average dosages of tramadol and pregabalin administered (mg/d) were both significantly reduced compared to baseline (p < 0.001). There was no bleeding, infection, pain increase, and other side effects after treatment. CONCLUSIONS: Short-term PNS is an effective and safe therapeutic alternative for elder patients with HZ ophthalmicus and could reduce the incidence of ophthalmic PHN.

Chronic and Recurrent Herpes Zoster Ophthalmicus.

Background and Objectives: This study sought to investigate the natural course, the chronicity and recurrence rate, and the risk factors of chronic and recurrent herpes zoster ophthalmicus (HZO). We also evaluated the effects of long-term treatment for HZO. Materials and Methods: Patients diagnosed and treated for HZO were included in the retrospective medical chart review. Multivariable-adjusted logistic and Cox regression models were used to show risk factors for chronic and recurrent HZO along with hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Among a total 130 of HZO patients, 31 patients (23.85%) had chronic disease and 19 patients (14.62%) had recurrent disease. The rate of chronic disease was higher in HZO with conjunctivitis, epithelial keratitis, and stromal keratitis. The recurrence rate increased in patients with chronic HZO (HR: 34.4, 95% CI: 3.6-324.6), epithelial keratitis (HR: 5.5, 95% CI: 1.3-30.0), stromal keratitis (HR: 18.8, 95% CI: 3.0-120.8), and increased intraocular pressure (IOP) (HR: 7.3, 95% CI: 1.6-33.2). Length of systemic antiviral therapy and anti-inflammatory eyedrop treatment were not associated with recurrent HZO (p = 0.847 and p = 0.660, respectively). The most common ocular manifestation for recurrent HZO was stromal keratitis. Conclusions: This study demonstrated a considerable frequency of chronic and recurrent HZO. Chronic HZO in the form of epithelial or stromal keratitis with increased IOP provoked a significant rise in the risk of recurrence.

Bihemisphere Ischemia Due to a Unilateral Lesion: A Case Report.

Bihemispheric ischemic strokes secondary to unilateral vessel disease are uncommon. We present the case of a 70-year-old man with multiple acute/subacute bilateral infarcts. The patient was found to have stenosis of the left internal carotid artery secondary to herpes zoster ophthalmicus vasculopathy, with involvement of the left proximal middle and anterior cerebral arteries. Angiographic studies also revealed A1 segment aplasia of the right anterior cerebral artery (ACA), thus indicating dependence on the left-sided circulation for perfusion of the bilateral ACA vascular territory. This case illustrates how A1 segment aplasia, an anatomic variant of the circle of Willis detected by angiographic studies, can contribute to bilateral infarction in the ACA vascular territory.

Ocular surgery after herpes simplex and herpes zoster keratitis.

PURPOSE: The recurrence of herpetic stromal keratitis (HSK) and herpes zoster ophthalmicus (HZO) has been reported after a variety of ocular surgeries. The aim of this study was to review the evidence on the preventive methods employed in the perioperative period in patients having undergone HSK/HZO. METHODS: The PubMed and Web of Science databases were the main resources used to conduct the medical literature search. An extensive search was performed to identify relevant articles concerning the prophylaxis against and risk of HSK/HZO recurrence in patients undergoing ocular surgery up to December 31, 2019. RESULTS: The disturbance of the corneal nerve plexus occurs during several ocular surgeries including penetrating keratoplasty, lamellar keratoplasty, corneal cross-linking, cataract surgery, as well as photorefractive and phototherapeutic procedures. Such trauma, as well as modulation of the ocular immunological response caused by steroids applied postoperatively, might engender the HSK/HZO reactivation which is not uncommon. There is strong evidence that oral prophylaxis should be recommended just after surgery in patients undergoing penetrating keratoplasty and having suffered from HSK/HZO. For other types of surgeries, the evidence is less compelling; nevertheless, a period of disease quiescence and oral prophylaxis should still be considered. CONCLUSIONS: Within the article, we discuss the available evidence for HSK/HZO prophylaxis in ocular surgery. Additional studies would be required to define the real risk of HSK/HZO recurrence following eye surgeries, and particularly cataract surgery, and to confirm the utility of perioperative HSK/HZO prophylaxis.

Isolated Internal Ophthalmoplegia Secondary to Herpes Zoster Ophthalmicus: A Rare Case Report.

Herpes zoster becomes latent in the sensory ganglia after the primary infection and may reactivate many years later to produce shingles in adults. Involvement of the ophthalmic branch of the trigeminal nerve with this virus is called Herpes zoster ophthalmicus (HZO). The eyelid skin, cornea, uvea, retina, optic nerve and other cranial nerves can be affected by HZO. Isolated internal ophthalmoplegia can rarely be seen. Clinicians should be aware of this condition and HZO must be kept in mind in the differential diagnosis of anisocoria.

[Acute retinal necrosis caused by varicella zoster virus]. / Ostryi nekroz setchatki, vyzvannyi virusom opoyasyvayushchego gerpesa.

Incidence of Herpes Zoster is relatively high. Herpes zoster ophthalmicus is one of the most common forms of the disease. Necrotising herpetic retinopathies (including acute retinal necrosis) are rare and usually these complications are presented in literature as individual cases. However, necrotising herpetic retinopathy can lead to complete loss of visual. The article reviews modern data on causation, diagnosis and treatment of acute retinal necrosis analyzing 40 open access articles from EBSCO published in 2011-2019, and describes the modern views on the prevalence and most important clinical features of herpetic acute retinal necrosis. Some contradictory opinions have been revealed concerning the diagnostic criteria and surgical treatment of acute retinal necrosis.

[Manifestations of herpes zoster ophthalmicus]. / Glaznye proyavleniya opoyasyvayushchego gerpesa.

The article reviews the main ocular features of Herpes Zoster Ophthalmicus (HZO) including Ramsay-Hunt and Tolosa-Hunt syndromes that involve III, IV and VI pairs of cranial nerves and I branch of the trigeminal nerve, and describes treatment methods of its active manifestations and postherpetic neuralgia, as well as herpes zoster vaccination practices.

Isolated optic neuritis with a concurrent abnormal trigeminal nucleus on imaging: case report of a rare complication of herpes zoster ophthalmicus.

BACKGROUND: Herpes zoster ophthalmicus (HZO) is an inflammation related to reactivation of the latent varicella zoster virus (VZV), involving the ophthalmic branch of the trigeminal nerve. Optic neuritis (ON), a rare ocular complication following HZO, has been reported in 1.9% of HZO-affected eyes. Most previous cases occurred simultaneously with other ocular complications, especially orbital apex syndrome. Moreover, detailed magnetic resonance imaging (MRI) with diffusion weighted imaging of the optic nerve and trigeminal nucleus in HZO-related ON has been rarely reported. We report a case of postherpetic isolated ON with a concurrent abnormal trigeminal nucleus on imaging. CASE PRESENTATION: A healthy 58-year-old female presented with sudden painful visual loss in her right eye for 2 days. Four weeks before the presentation, her right eye was diagnosed with HZO, and she received intravenous acyclovir for 10 days. Ophthalmic examination revealed a visual acuity of light perception and 20/20 in the right and left eyes, respectively. A relative afferent pupillary defect was present in the right eye. Neurological examination was significant for hypoesthesia in the area of the HZO. A clinical diagnosis of HZO-related right retrobulbar ON was made, and other causes of atypical ON were excluded. MRI showed enhancement and restricted diffusion of the right-sided optic nerve with linear hyperintense T2 of the right-sided spinal trigeminal nucleus and tract (STNT) along the brainstem. She received 14 days of intravenous acyclovir and 5 days of methylprednisolone. Both were switched to an oral route for 2 months. After the completion of treatment, the visual acuity was counting fingers and 20/20 in the right eye and left eye, respectively. Stable brainstem STNT abnormalities and resolution of ON were found radiologically. CONCLUSIONS: Isolated ON is a rare ocular complication following HZO. An abnormal high signal of STNT on a T2 weighted image may be present, which may be a clue for VZV-associated complications, such as HZO-related ON, especially in cases lacking an obvious history of HZO or other concomitant ocular complications. Prompt treatment with both acyclovir and corticosteroids should be started. Restricted diffusion of the optic nerve may be a predictor for poor visual recovery.

The Skin and the Eye - Herpes Zoster Ophthalmicus in a Healthy 18-month-old Toddler.

Herpes zoster, caused by reactivation of varicella-zoster virus, is uncommon in infancy. Even more uncommon is herpes zoster ophthalmicus, defined as herpes zoster of the ophthalmic branch of the fifth cranial nerve. Among healthy children, primary varicella-zoster virus infection during gestation as a result of maternal varicella or the first year of life is the major risk factor for development of herpes zoster in a relatively young age. Here we present an unusual case of herpes zoster ophthalmicus with dissemination in an immunocompetent toddler with favorable outcome. The child's mother contracted chickenpox in late pregnancy and her son was very likely infected with varicella-zoster virus in utero. During a two-year follow-up the child vision was normal and there was no evidence of post herpetic neuralgia.

Genetic analysis of varicella-zoster virus in the aqueous humor in uveitis with severe hyphema.

BACKGROUND: Genetic variations have been identified in the genome of varicella-zoster virus (VZV) strains using vesicle fluid, varicella scabs and throat swab samples. We report a rare case of VZV-associated uveitis with severe hyphema, which was immediately diagnosed by polymerase chain reaction (PCR) using the aqueous humor, in which we were able to analyze the VZV genotype for the first time. CASE PRESENTATION: A 16-year-old Japanese boy was referred to our hospital with a 20-day history of unilateral anterior uveitis and 11-day history of hyphema. At presentation, details of the iris, the iridocorneal angle, and the fundus were not visible due to the severe hyphema. Serum anti-VZV IgG and anti-VZV IgM were elevated, and 1.61 × 109 copies/mL of VZV-DNA were detected by real-time PCR using the aqueous humor. As there were no eruptions on his face or body, we diagnosed zoster sine herpete and started intravenous administration of prednisolone and acyclovir. The hyphema completely disappeared 2 weeks after presentation, while sectorial iris atrophy and mild periphlebitis of the fundus became gradually apparent. Anterior inflammation and periphlebitis gradually improved and VZV-DNA in the aqueous humor was reduced to 1.02 × 106 copies/mL at 4 weeks after presentation. Examination by slit lamp microscope revealed no inflammation after 5 months, and VZV-DNA could no longer be detected in the aqueous humor. Serum anti-VZV IgG and anti-VZV IgM also showed a gradual decrease along with improvement in ocular inflammation. The genetic analysis of multiple open reading frames and the R5 variable repeat region in the VZV genes, using DNA extracted from the aqueous humor at presentation, showed that the isolate was a wild-type clade 2 VZV strain (prevalent in Japan and surrounding countries) with R5A allele and one SNP unique to clade 1 (both are major types in Europe and North America). CONCLUSIONS: VZV-associated uveitis may develop hyphema that obscures ocular inflammation, thus PCR analysis using the aqueous humor is the key investigation necessary for the diagnosis. The measurement of VZV-DNA copies by real-time PCR would be useful for evaluation of therapeutic effects. We could amplify and analyze VZV genotype using the aqueous humor including a very large number of VZV-DNA copies (1.61 × 109 copies/mL).

Early- and late-stage ocular complications of herpes zoster ophthalmicus in rural South Africa.

OBJECTIVES: To describe the spectrum of ocular complications of herpes zoster ophthalmicus (HZO) in rural South Africa. METHODS: Patients presenting with visual complaints and active or healed HZO at the ophthalmology outpatient department of three hospitals in rural South Africa were included in this study. Demographic and clinical data were collected, and HIV status was determined for all participants. RESULTS: Forty-eight patients were included, and 81% were HIV infected. Poor vision was reported by 94% of patients, painful eye by 79% and photophobia by 63%. A diverse spectrum of ocular complications was observed with corneal inflammation and opacification in 77% followed by anterior uveitis in 65%. The majority (65%) presented with late-stage ocular complications associated with irreversible loss of vision whereas early-stage complications, such as punctate epithelial keratitis and anterior uveitis, were less common. Blindness of the affected eye was observed in 68% of patients with late-stage complications. There was a considerable delay between onset of symptoms and first presentation to the ophthalmology outpatient department (median time 35 days; range 1-2500 days), and longer delay was associated with late-stage ocular complications (P = 0.02). CONCLUSIONS: HZO patients present with relatively late-stage ocular complications, and blindness among these patients is common. The delayed presentation to the ophthalmology outpatient department of hospitals in our rural setting is of concern, and efforts to improve ocular outcomes of HZO are urgently needed.