Short-Term Supraorbital Nerve Stimulation and Pain Relief for Acute and Subacute Ophthalmic Herpetic Neuralgia: A Randomized Controlled Crossover Trial.

BACKGROUND: Herpes zoster ophthalmicus (HZO) is a kind of refractory disease, and treating it is important for preventing postherpetic neuralgia (PHN). But the evidence surrounding the current treatment options for these conditions is controversial, so exploring reasonable clinical treatment strategies for HZO is necessary. Neuromodulation is an excellent modality for the treatment of various neuropathic pain conditions. This trial was designed to evaluate the effectiveness of short-term supraorbital nerve stimulation (SNS) and the supraorbital nerve block (SNB) for HZO. OBJECTIVES: To determine whether short-term SNS relieves acute and subacute ophthalmic herpetic neuralgia. STUDY DESIGN: This prospective randomized controlled crossover trial compared short-term SNS to SNB. SETTING: The operating room of a pain clinic. METHODS: Patients with acute or subacute ophthalmic herpetic neuralgia were recruited. The patients were randomly assigned to receive either SNS or SNB. The primary outcome being measured was each patient's Visual Analog Scale (VAS) score at 4 weeks. The secondary outcomes under measurement were the proportion of patients who achieved ≥ 50% pain relief, sleep quality, medicine consumption, and adverse events. Crossover after 4 weeks was permitted, and patients were followed up to 12 weeks. RESULTS: Overall, 50 patients were included (n = 25/group). At 4 weeks, the patients who received SNS achieved greater pain relief, as indicated by their significantly different VAS scores from those of the SNB group (mean difference: -1.4 [95% CI, -2.29 to -0.51], P < 0.05). Both groups showed a significant decrease in pain level from the baseline (all P < 0.05). Overall, 72% and 44% of the SNS and SNB patients experienced ≥ 50% pain relief, respectively (OR: 0.31 [95% CI, 0.09 to 0.99], P < 0.05), and 68% and 32% of SNS and SNB patients, respectively, had VAS scores < 3 (OR: 0.22 [95% CI, 0.07 to 0.73], P < 0.05). Compared to the SNB group, the SNS group had better sleep quality, lower ophthalmic neuralgia, a lower proportion of further treatment, and lower analgesic intake. Overall, 18 patients received SNS alone, and 16 patients crossed over from SNB to SNS. The VAS scores, sleep quality, ophthalmic neuralgia, and trend of medicine intake were not significantly different between the groups (all P > 0.05). No serious complications occurred. LIMITATIONS: This study was nonblind. CONCLUSIONS: Short-term SNS is effective for controlling acute or subacute ophthalmic herpetic neuralgia. Combining SNS with SNB yields no additional benefits.

Radiofrequency regulation of the sphenopalatine ganglion in managing herpes zoster ophthalmicus neuralgia: A case series.

INTRODUCTION: Trigeminal herpes zoster, which comprises 10% to 20% of cases of herpes zoster, often leads to severe pain in the ophthalmic branches. Current treatments, including drug therapy and minimally invasive interventions, have limitations; accordingly, there is a need to explore alternative approaches. This study aimed to evaluate the efficacy and safety of computerized tomography (CT)-guided pulsed radiofrequency of the sphenopalatine ganglion in patients with intractable trigeminal herpetic pain. PATIENT CONCERNS: Three patients with intractable trigeminal ophthalmic zoster neuralgia were studied. All patients complained of bursts of headache, which occurred at least 10 times a day, usually in the periorbital and frontal regions. Conventional treatments, including oral medications and radiofrequency therapy targeting the trigeminal-semilunar ganglion and supraorbital nerve, could not sufficiently provide relief. DIAGNOSIS: Two patients were diagnosed with herpes zoster in the ocular branch of the trigeminal nerve with conjunctivitis, while one patient was diagnosed with postherpetic neuralgia in the ocular branch of the trigeminal nerve. INTERVENTIONS: This study employed a novel approach that involved CT-guided radiofrequency regulation of the pterygopalatine fossa sphenopalatine ganglion. OUTCOMES: In all three patients, pain relief was achieved within 1 to 3 days after treatment. During the follow-up, one patient had pain recurrence; however, its severity was ≈ 40% lower than the pretreatment pain severity. The second patient had sustained and effective pain relief. However, the pain of the third patient worsened again after 2 months. The average follow-up duration was 3 months. None of the enrolled patients showed treatment-related adverse reactions or complications. CONCLUSION: Our findings indicated that CT-guided radiofrequency regulation of the pterygopalatine fossa sphenopalatine ganglion was a safe and effective intervention for pain in patients with trigeminal ophthalmic zoster neuralgia, suggesting that it may be a therapeutic option if other treatments fail.

Multiple ocular manifestations in a patient diagnosed with herpes zoster ophthalmicus: case report.

Objective: Our purpose was to present a case of a patient diagnosed with herpes zoster ophthalmicus with multiple ocular manifestations. Case presentation: A 70-year-old Caucasian male presented to the hospital for headache and skin hyperesthesia on the scalp and forehead on the left side. The diagnoses of herpes zoster ophthalmicus and acute conjunctivitis were made for the left eye. The patient was followed up for 6 months and during that period the following diagnoses were made for the same eye: peripheral sterile corneal infiltrates, episcleritis, and hypertensive anterior uveitis. Discussions: Herpes zoster ophthalmicus occurs when the reactivation of the dormant virus involves the ophthalmic division of the trigeminal nerve. The most frequent ocular presentations are conjunctivitis, keratitis, uveitis, episcleritis, and scleritis. The standard therapy consists of antivirals, such as acyclovir, valacyclovir, and famciclovir to limit the replication of the virus. The patient's risk factors, the course of treatment, and the severity of the disease, all affect the prognosis, which is highly variable. Prevention of the disease consists of vaccination with one of the following two vaccines, Zostavax and Shingrix. Conclusions: Final visual acuity for the left eye remained 1 despite numerous manifestations of the disease. Abbreviations: VZV = Varicella-zoster virus, BCVA = best-corrected visual acuity, OU = both eyes, OD = right eye, OS = left eye, IOP = intraocular pressure, NCT = non-contact tonometer, ZVX = Zostavax vaccine.

Dermatologic Reactions Following COVID-19 Vaccination: A Case Series.

We describe 7 patients with various dermatologic reactions following COVID-19 vaccination, including herpes zoster (HZ) infection, herpes zoster ophthalmicus (HZO), herpes labialis, and urticaria. Although the reactions described here may be related to COVID-19 vaccination, continued vaccination is recommended, as it is the most effective way to protect against serious COVID-19 infection.

Risk of Herpes Zoster Ophthalmicus Recurrence After Recombinant Zoster Vaccination.

Importance: The recombinant zoster vaccine (RZV) is currently recommended for immunocompetent adults aged 50 years or older and immunocompromised adults aged 19 years or older and is effective in preventing herpes zoster ophthalmicus (HZO). However, questions about the safety of RZV in patients with a history of HZO remain. Objective: To evaluate whether there is an increased risk of HZO recurrence after RZV in patients with a history of HZO. Design, Setting, and Participants: This retrospective cohort study used medical and outpatient pharmacy claims data for commercial and Medicare Advantage enrollees from the Optum Labs Data Warehouse. Patients with incident HZO from January 1, 2010, to December 31, 2021, were identified; the study period ended on March 31, 2022. The vaccinated group consisted of patients with at least 1 dose of RZV more than 90 days following the initial HZO diagnosis. The unvaccinated group consisted of patients without any record of RZV in the study period. Vaccinated and unvaccinated patients were matched using exact k:1 matching without replacement. Exposure: Recombinant zoster vaccination. Main Outcomes and Measures: The main outcome was the number of HZO recurrences with and without RZV exposure. Results: A total of 16 408 patients were included in the matched analysis, of whom 12 762 were unvaccinated (7806 [61.2%] female; mean [SD] age at diagnosis, 68.8 [10.3] years) and 3646 were vaccinated (2268 [62.2%] female; mean [SD] age at diagnosis, 67.4 [9.8] years). Within the primary risk period of 56 days after the index date (ie, the start of follow-up for the outcome), the incidence of HZO recurrence after any RZV exposure was 37.7 per 1000 person-years compared with 26.2 per 1000 person-years in the unexposed group. After controlling for race and ethnicity, inpatient stays, emergency department visits, concomitant vaccines, and eye care practitioner visits, the association between vaccination status and HZO exacerbation in the primary risk period had an adjusted hazard ratio for any RZV exposure of 1.64 (95% CI, 1.01-2.67; P = .04). Conclusions and Relevance: In this study, RZV exposure was associated with a higher likelihood of HZO recurrence in patients with a history of HZO compared with no RZV exposure. These findings support consideration that patients with a history of HZO may benefit from monitoring after receiving RZV in case of HZO recurrence.

Unilateral Acute Retinal Necrosis with Contralateral Non-necrotizing Herpetic Uveitis.

PURPOSE: The objective of this study is to report a case of unilateral acute retinal necrosis (ARN) with contralateral eye presenting as non-necrotizing herpetic uveitis. CASE REPORTS: Case 1: A 48-year-old female presented at our clinic with blurred vision in the right eye for 7 days. She was diagnosed with ARN in the left eye 2 weeks ago. Ophthalmic examination revealed reduced visual acuity in the right eye (20/33) with the presence of optic disc swelling and macular exudation without peripheral necrotic lesions. With systemic antiviral therapy, optic disc swelling of the right eye vanished gradually, and the visual acuity improved to 20/20. Loss of retinal nerve fiber layer (RNFL) and decreased retinal thickness in the corresponding area occurred during follow-up. CONCLUSION: Non-necrotizing herpetic uveitis may occur in the contralateral eye of unilateral ARN under rare conditions. Structure abnormities, including loss of RNFL and focal decreased retinal thickness, are irretrievable.

Viral Keratitis, Surgical Intervention in Viral Keratitis, Challenges in Diagnosis and Treatment of Viral Keratitis, HSV, HZV.

Viral keratitis is a significant cause of ocular morbidity and visual impairment worldwide. In recent years, there has been a growing understanding of the pathogenesis, clinical manifestations, and diagnostic modalities for viral keratitis. The most common viral pathogens associated with this condition are adenovirus, herpes simplex (HSV), and varicella-zoster virus (VZV). However, emerging viruses such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), and Vaccinia virus can also cause keratitis. Non-surgical interventions are the mainstay of treatment for viral keratitis. Antiviral agents such as Acyclovir, Ganciclovir, and trifluridine have effectively reduced viral replication and improved clinical outcomes. Additionally, adjunctive measures such as lubrication, corticosteroids, and immunomodulatory agents have alleviated symptoms by reducing inflammation and facilitating tissue repair. Despite these conservative approaches, some cases of viral keratitis may progress to severe forms, leading to corneal scarring, thinning, or perforation. In such instances, surgical intervention becomes necessary to restore corneal integrity and visual function. This review article aims to provide an overview of the current perspectives and surgical interventions in managing viral keratitis. The choice of surgical technique depends on the extent and severity of corneal involvement. As highlighted in this article, on-going research and advancements in surgical interventions hold promise for further improving outcomes in patients with viral keratitis.

The Infectious Uveitis Treatment Algorithm Network (TITAN) Report 1-global current practice patterns for the management of Herpes Simplex Virus and Varicella Zoster Virus anterior uveitis.

AIMS: To present current expert practice patterns and to formulate a consensus for the management of HSV and VZV AU by uveitis specialists worldwide. METHODS: A two-round online modified Delphi survey with masking of the study team was conducted. Responses were collected from 76 international uveitis experts from 21 countries. Current practices in the diagnosis and treatment of HSV and VZV AU were identified. A working group (The Infectious Uveitis Treatment Algorithm Network [TITAN]) developed data into consensus guidelines. Consensus is defined as a particular response towards a specific question meeting ≥75% of agreement or IQR ≤ 1 when a Likert scale is used. RESULTS: Unilaterality, increased intraocular pressure (IOP), decreased corneal sensation and diffuse or sectoral iris atrophy are quite specific for HSV or VZV AU from consensus opinion. Sectoral iris atrophy is characteristic of HSV AU. Treatment initiation is highly variable, but most experts preferred valacyclovir owing to simpler dosing. Topical corticosteroids and beta-blockers should be used if necessary. Resolution of inflammation and normalisation of IOP are clinical endpoints. CONCLUSIONS: Consensus was reached on several aspects of diagnosis, choice of initial treatment, and treatment endpoints for HSV and VZV AU. Treatment duration and management of recurrences varied between experts.

Risk of Herpes Zoster Ophthalmicus After COVID-19 Vaccination in a Large US Health Care Claims Database.

PURPOSE: Herpes zoster ophthalmicus (HZO) after COVID-19 vaccination has been reported in numerous case studies. However, no large-scale epidemiologic studies have been conducted to date. The purpose of this study was to determine whether COVID-19 vaccination is associated with an increased risk of HZO. DESIGN: Retrospective before-and-after risk interval analysis. METHODS: RESULTS: In total, 1,959,157 patients received a dose of a COVID-19 vaccine during the study period and met eligibility criteria. A total of 80 individuals without a prior history of HZO were included in the analysis because they developed HZO in the risk or control period. Patients had a mean age of 54.0 years (SD = 12.3 years). There were 45 cases of HZO in the risk interval after COVID-19 vaccination. There was not an increased risk of HZO after vaccination with BNT162b2 (IRR = 0.90, 95% CI: 0.49-1.69, P = .74), mRNA-1273 (IRR = 0.74, 95% CI: 0.36-1.54, P = .42), or Ad26.COV2.S (IRR = 0.50, 95% CI: 0.07-2.56, P = .42). CONCLUSIONS: This study found no evidence of increased risk of HZO after COVID-19 vaccination, providing reassurance for patients and providers who may be concerned about the safety profile of the COVID-19 vaccines.

The association of stroke with herpes zoster ophthalmicus.

BACKGROUND/OBJECTIVES: Studies have reported an association between herpes zoster ophthalmicus (HZO) and stroke. We sought to validate this association with rigorous controls for both medical comorbidities and social factors using a nationwide U.S. administrative medical claims database. SUBJECTS/METHODS: A two-step approach was taken: first a retrospective case-control study was performed, followed by a self-controlled case series (SCCS). For the case control study, cox proportional hazard regression with inverse proportional treatment weighting assessed the hazard for stroke. In the SCCS, incidence of stroke was compared prior to and after the diagnosis of HZO. RESULTS: For the case-control study, 25,720 cases and 75,924 controls met our eligibility criteria. 1712 (6.7%) and 4544 (6.0%) strokes occurred in the case and control groups respectively, conferring an 18% increased risk of stroke in the observed 1-year post-HZO period (HR = 1.18, 95% CI: 1.12-1.25, p < 0.001). SCCS analysis showed the risk for stroke was highest in the month immediately after HZO episode compared to any other time range (1-30 days after, relative risk 1.58, p < 0.001) and even higher when assessing time more distal time points prior to the HZO diagnosis (days 1-30 after HZO diagnosis had RR = 1.69 (95% CI: 1.38-2.07) and RR = 1.93 (95% CI: 1.55-2.39) compared with days -120 to -91 and -150 to -121 prior to index, respectively (p < 0.001). CONCLUSIONS: After accounting for stroke risk factors, our analysis confirms the association between HZO and stroke, with highest risk in the immediate month after an episode.

Bilateral herpes zoster ophthalmicus in an immunocompetent patient.

INTRODUCTION: Bilateral herpes zoster ophthalmicus (HZO) is rare. We report a case of an immunocompetent patient with nonsimultaneous attacks of HZO in both eyes. CASE DESCRIPTION: A 71-year-old female patient complained of blurred vision in the left eye for 1 week, which was treated with topical antiglaucomatous drugs due to elevated intraocular pressure. She denied any systemic diseases, but HZO had manifested as a rash with a crust over the right forehead skin 3 months earlier. Slit-lamp examination revealed localized corneal edema with keratin precipitates and mild anterior chamber reaction. Suspecting corneal endotheliitis, we performed aqueous tapping for detecting viral DNA, including cytomegalovirus, herpes simplex virus, and varicella zoster virus (VZV) DNA, through polymerase chain reaction (PCR) testing, but the PCR results were negative for all viruses. The endotheliitis resolved well after treatment with topical prednisolone acetate. However, the patient's blurred vision recurred in the left eye 2 months later. A dendritiform lesion on the left cornea was detected, and corneal scraping for PCR testing revealed VZV DNA. The lesion disappeared with antiviral treatment. CONCLUSIONS: Bilateral HZO is uncommon, particularly in immunocompetent patients. When in doubt, physicians should perform tests such as PCR testing to help establish a definite diagnosis.

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.

Practice Patterns in the Initial Management of Herpes Zoster Ophthalmicus in the United States.

PURPOSE: The aims of this study were to examine the trends in the initial management of herpes zoster ophthalmicus (HZO) in the United States from 2010 to 2018 and compare them with the treatment preferences of corneal specialists. METHODS: A retrospective, observational deidentified cohort study was conducted on individuals enrolled in the OptumLabs Data Warehouse who had a new diagnosis of HZO from 1/1/2010 to 12/31/2018. An online survey ascertaining HZO management perspectives was distributed to The Cornea Society listserv. The main outcome assessed was proportion of cases with systemic antiviral prescriptions, eye care provider involvement, and follow-up visits after the initial HZO diagnosis. RESULTS: Approximately 50% of patients received systemic antivirals the day of initial HZO diagnosis or within 7 days (45.6% and 53.7%, respectively). Most initial diagnoses were made by ophthalmologists (45.0%), followed by optometrists (19.2%). Referral rate to ophthalmology within a year of initial diagnosis was 38.6%. 48.7% cases had at least 1 follow-up visit with any type of provider within 30 days. Our survey of corneal specialists found 97% would prescribe systemic antivirals to those with ocular involvement, but 66% would prescribe antivirals to those without ocular or eyelid involvement. Seventy percent supported all patients having follow-up with an eye care provider within a month. CONCLUSIONS: HZO antiviral therapies seem to be underprescribed in the United States, referral rates to ophthalmology are low, and follow-up is suboptimal, which are not aligned with recommendations from corneal specialists. More research is needed to establish standardized guidelines for treatment, referral, and follow-up with ophthalmology for HZO.

Dual-neuromodulation strategy in pain management of herpes zoster ophthalmicus: retrospective cohort study and literature review.

BACKGROUND: Effective pain control of herpes zoster ophthalmicus (HZO) is not only essential to attenuate the clinical symptoms but to reduce the risk of postherpetic neuralgia development. Recently, neuromodulation therapy has been one promising option for neuropathic pain and increasingly applied in management of zoster-related pain. One key factor of neuromodulation treatment is the therapeutic site for the impaired nerves. In this study we aim to investigate one novel dual-neuromodulation strategy, targeting the level of the peripheral branch and trigeminal ganglion, in the pain management of HZO. METHODS: Dual neuromodulation strategy combining short-term peripheral nerve stimulation (PNS) with pulsed radiofrequency (PRF) of trigeminal ganglion was compared with single PNS treatment for HZO-related pain. Clinical recordings of patients were retrospectively reviewed. The primary outcome was the pain severity, assessed by the visual analogue scale (VAS) before and after neuromodulation therapy. RESULTS: PNS achieved significant relief of pain with or without PRF treatment before discharge, which provided enduring therapeutic effect up to 12-month follow-up. The mean reduction of VAS was 6.7 ± 1.4 in dual modulation therapy (n = 13) at last follow-up and 5.4 ± 1.5 in PNS subgroup (n = 20), respectively. Moreover, dual modulation strategy provided better control of pain compared with PNS therapy alone at each time point. CONCLUSION: It is feasible and effective to combine the PNS and PRF in pain management of HZO. This novel dual modulation strategy of trigeminal pathway may provide additional therapeutic effects of pain symptoms in HZO population.

Dual neuromodulation strategy for pain management of herpes zoster ophthalmicus is proposed, with regard to stimulation site (peripheral and trigeminal ganglion) and apparatus (electrical nerve stimulation and pulsed radiofrequency).Superior clinical outcome was associated with novel neuromodulation therapy with dual therapeutic targets, when compared with peripheral nerve stimulation in treatment of herpes zoster ophthalmicus.We conducted literature review to compare distinct pattern of neuromodulation (peripheral nerve stimulation and radiofrequency) in treatment of trigeminal neuropathic pain caused by herpes zoster.

Effectiveness of the live zoster vaccine during the 10 years following vaccination: real world cohort study using electronic health records.

OBJECTIVES: To assess the effectiveness of live zoster vaccine during more than 10 years after vaccination; and to describe methods for ascertaining vaccine effectiveness in the context of waning. DESIGN: Real world cohort study using electronic health records. SETTING: Kaiser Permanente Northern California, an integrated healthcare delivery system in the US, 1 January 2007 to 31 December 2018. POPULATION: More than 1.5 million people aged 50 years and older followed for almost 9.4 million person years. MAIN OUTCOME MEASURE: Vaccine effectiveness in preventing herpes zoster, postherpetic neuralgia, herpes zoster ophthalmicus, and admission to hospital for herpes zoster was assessed. Change in vaccine effectiveness by time since vaccination was examined using Cox regression with a calendar timeline. Time varying indicators were specified for each interval of time since vaccination (30 days to less than one year, one to less than two years, etc) and adjusted for covariates. RESULTS: Of 1 505 647 people, 507 444 (34%) were vaccinated with live zoster vaccine. Among 75 135 incident herpes zoster cases, 4982 (7%) developed postherpetic neuralgia, 4439 (6%) had herpes zoster ophthalmicus, and 556 (0.7%) were admitted to hospital for herpes zoster. For each outcome, vaccine effectiveness was highest in the first year after vaccination and decreased substantially over time. Against herpes zoster, vaccine effectiveness waned from 67% (95% confidence interval 65% to 69%) in the first year to 15% (5% to 24%) after 10 years. Against postherpetic neuralgia, vaccine effectiveness waned from 83% (78% to 87%) to 41% (17% to 59%) after 10 years. Against herpes zoster ophthalmicus, vaccine effectiveness waned from 71% (63% to 76%) to 29% (18% to 39%) during five to less than eight years. Against admission to hospital for herpes zoster, vaccine effectiveness waned from 90% (67% to 97%) to 53% (25% to 70%) during five to less than eight years. Across all follow-up time, overall vaccine effectiveness was 46% (45% to 47%) against herpes zoster, 62% (59% to 65%) against postherpetic neuralgia, 45% (40% to 49%) against herpes zoster ophthalmicus, and 66% (55% to 74%) against admission to hospital for herpes zoster. CONCLUSIONS: Live zoster vaccine was effective initially. Vaccine effectiveness waned substantially yet some protection remained 10 years after vaccination. After 10 years, protection was low against herpes zoster but higher against postherpetic neuralgia. TRIAL REGISTRATION: ClinicalTrials.gov number NCT01600079; EU PAS register number EUPAS17502.

Case Report.

Cavernous sinus thrombosis is a rare life-threatening complication of herpes zoster ophthalmicus (HZO). This case highlights the importance of at least considering the diagnosis in all cases of HZO, as the consequences of missing it can be disastrous.