Recurrent Herpes Zoster Ophthalmicus in a Patient With a Novel Toll-Like Receptor 3 Variant Linked to Compromised Activation Capacity in Fibroblasts.

BACKGROUND: Herpes zoster ophthalmicus occurs primarily in elderly or immunocompromised individuals after reactivation of varicella zoster virus (VZV). Recurrences of zoster ophthalmicus are uncommon because the reactivation efficiently boosts anti-VZV immunity. A 28-year-old female presented to our clinic with a history of multiple recurrences of zoster ophthalmicus. METHODS: Whole-exome sequencing (WES), analyses of VZV T-cell immunity, and pathogen recognition receptor function in primary antigen-presenting cells (APCs) and fibroblasts were performed. RESULTS: Normal VZV-specific T-cell immunity and antibody response were detected. Whole-exome sequencing identified a heterozygous nonsynonymous variant (c.2324C > T) in the Toll-like receptor 3 (TLR3) gene resulting in formation of a premature stop-codon. This alteration could potentially undermine TLR3 signaling in a dominant-negative fashion. Therefore, we investigated TLR3 signaling responses in APCs and fibroblasts from the patient. The APCs responded efficiently to stimulation with TLR3 ligands, whereas the responses from the fibroblasts were compromised. CONCLUSIONS: We report a novel TLR3 variant associated with recurrent zoster ophthalmicus. Toll-like receptor 3 responses that were unaffected in APCs but diminished in fibroblasts are in line with previous reports linking TLR3 deficiency with herpes simplex virus encephalitis. Mechanisms involving compromised viral sensing in infected cells may thus be central to the described immunodeficiency.

Comparison of visual field defect progression in secondary Glaucoma due to anterior uveitis caused by three types of herpes viruses.

PURPOSE: To clarify the prevalence of secondary glaucoma (SG) and its speed of progression in patients with herpes simplex virus (HSV)-anterior uveitis (AU), varicella zoster virus (VZV)-AU, and cytomegalovirus (CMV)-AU. METHODS: In total, 170 patients with herpetic AU were enrolled in this retrospective observational case series. Patients with visual field (VF) defects and glaucomatous disc abnormalities were diagnosed with SG. Moreover, the speed of SG progression was defined as decreasing mean deviation (MD) values per year. SG prevalence and annual MD-value decrease were compared among the three types of herpetic AU. RESULTS: SG prevalence was 16%, 9%, and 72% in patients with HSV-AU, VZV-AU, and CMV-AU, respectively. Patients with CMV-AU had the highest SG prevalence (odds ratio = 3.15; 95% confidence interval = 1.15-8.65; P < 0.05). Furthermore, the annual MD-value change was significantly higher in SG caused by CMV-AU than in that caused by HSV/VZV-AU (-2.6 ± 2.4 dB/year and -0.45 ± 0.54 dB/year, respectively; P < 0.05). CONCLUSIONS: Our results demonstrated that patients with CMV-AU may have a higher risk and faster speed of progression of SG than patients with HSV/VZV-AU. Therefore, clinicians should monitor glaucoma onset and VF-defect progression in patients with CMV-AU.

BILATERAL ACUTE RETINAL NECROSIS: A Case Series.

PURPOSE: To investigate the clinical characteristics and visual outcome of bilateral acute retinal necrosis. METHODS: The study included 30 patients (60 eyes) who were diagnosed with bilateral acute retinal necrosis. The medical records were reviewed. RESULTS: Twenty-five patients developed the disease in the contralateral eye within 5 months and 5 patients at >2 years after the initial onset. At presentation, 14 of 21 eyes suffered from retinal necrosis of more than 180° in the initially affected eye, whereas 3 of 22 eyes suffered it in the later-affected eye. Retinal detachment occurred in 23 of the 27 initially affected eyes and in 5 of the 27 later-affected eyes. The mean logarithm of the minimum angle of resolution best-corrected visual acuity decreased from 2.0 ± 1.1 (Snellen equivalent counting fingers) to 2.2 ± 1.0 (Snellen equivalent counting fingers) in the initially affected eyes after a follow-up of 34.1 ± 48.2 months (P = 0.529), and improved from 0.5 ± 0.4 (Snellen equivalent 20/66) to 0.3 ± 0.4 (Snellen equivalent 20/40) in the later-affected eyes after a follow-up of 21.2 ± 23.3 months (P = 0.005). CONCLUSION: Bilateral acute retinal necrosis usually occurs in the contralateral eye within a few months, but sometimes after several years. Inflammation and retinal necrosis are less severe in the later-affected eye, with less retinal detachment and a better visual outcome.

Case Report: Varicella-zoster Encephalitis with Acute Retinal Necrosis and Oculomotor Nerve Palsy.

SIGNIFICANCE: Varicella-zoster virus is a common cause of morbidity and vision loss in patients worldwide. It can affect any structure of the eye, from keratitis to acute retinal necrosis. Rapid diagnosis and treatment significantly improve clinical outcomes and quality of life. PURPOSE: The purpose of this study was to demonstrate a case where urgent referral to the emergency department was required to treat a patient with disseminated herpes zoster infection. CASE REPORT: This is a rare case of varicella-zoster virus encephalitis in a 70-year-old immunocompetent white man who initially presented to the eye clinic for vertical diplopia and floaters. He also had prior thoracic dermatomal rash, followed by new-onset headaches and cerebellar ataxia. Examination revealed a partial oculomotor nerve palsy in the right eye with bilateral optic disc edema and areas of retinitis consistent with acute retinal necrosis in both eyes. Polymerase chain reaction analysis of his aqueous humor and cerebrospinal fluid confirmed an active zoster infection. He received combination systemic and intravitreal antiviral medication until his retinitis resolved but required adjustments for recalcitrant disease and drug-induced nephrotoxicity. While on maintenance dosing of oral valacyclovir, he experienced reactivation in the form of bilateral vasculitis, which was successfully managed once restarting therapeutic oral dosing. CONCLUSIONS: This case describes a successful clinical course of acute retinal necrosis with strategies for its treatment in the setting of varicella-zoster encephalitis. Antiviral medication should be given as soon as possible, as prompt treatment has been shown to improve patient outcomes, although prognosis is typically poor in these cases. Multiple specialists are often needed to address different clinical challenges, including central nervous system involvement, viral strain resistance, disease reactivation, and drug toxicity.

Using natural language processing for identification of herpes zoster ophthalmicus cases to support population-based study.

IMPORTANCE: Diagnosis codes are inadequate for accurately identifying herpes zoster (HZ) ophthalmicus (HZO). There is significant lack of population-based studies on HZO due to the high expense of manual review of medical records. BACKGROUND: To assess whether HZO can be identified from the clinical notes using natural language processing (NLP). To investigate the epidemiology of HZO among HZ population based on the developed approach. DESIGN: A retrospective cohort analysis. PARTICIPANTS: A total of 49 914 southern California residents aged over 18 years, who had a new diagnosis of HZ. METHODS: An NLP-based algorithm was developed and validated with the manually curated validation data set (n = 461). The algorithm was applied on over 1 million clinical notes associated with the study population. HZO versus non-HZO cases were compared by age, sex, race and co-morbidities. MAIN OUTCOME MEASURES: We measured the accuracy of NLP algorithm. RESULTS: NLP algorithm achieved 95.6% sensitivity and 99.3% specificity. Compared to the diagnosis codes, NLP identified significant more HZO cases among HZ population (13.9% vs. 1.7%). Compared to the non-HZO group, the HZO group was older, had more males, had more Whites and had more outpatient visits. CONCLUSIONS AND RELEVANCE: We developed and validated an automatic method to identify HZO cases with high accuracy. As one of the largest studies on HZO, our finding emphasizes the importance of preventing HZ in the elderly population. This method can be a valuable tool to support population-based studies and clinical care of HZO in the era of big data.

Herpes zoster ophthalmicus: acute keratitis.

PURPOSE OF REVIEW: Herpes zoster is a common condition, and involvement of the trigeminal nerve results in herpes zoster ophthalmicus (HZO). Acute keratitis is one of the most common of these ocular complications associated with HZO. The findings associated with and the management of acute zoster keratitis will be reviewed. RECENT FINDINGS: The incidence rate of herpes zoster has been on the rise over the past several decades. At the same time, the average patient age at presentation is declining with similar trends also seen in HZO. The cause of these changes has yet to be determined. Our understanding of corneal involvement in HZO continues to evolve with new imaging demonstrating viral particles within keratocytes in a case of zoster stromal keratitis. New medications such as topical ganciclovir are also helping to better manage acute zoster keratitis that is unresponsive to oral antiviral therapy. SUMMARY: Acute zoster keratitis can lead to permanent vision loss. Early diagnosis and management may help reduce these potentially devastating complications. Oral and topical antiviral medications can play a role in managing the acute disease, and herpes zoster vaccinations are important for prevention of disease. Further research must be done to establish standards for treatment of anterior segment complications from herpes zoster.

Case Series: Herpes Zoster Ophthalmicus with Acute Orbital Inflammation.

SIGNIFICANCE: Herpes zoster ophthalmicus (HZO) has variable initial manifestations, and acute orbital inflammation may be the first sign without apparent zoster rash. This case series is significant for presenting diverse clinical features and treatment options of HZO with acute orbital inflammation. PURPOSE: To report a case series of patients diagnosed as HZO with acute orbital inflammation including two cases with unique presentations. CASE REPORTS: Medical records of four patients of HZO with acute orbital inflammation were reviewed. Two men and two women with a median age of 57 years (range, 32 to 69 years) were diagnosed as having HZO with acute orbital inflammation. Initial presentations included two cases of zoster rash and two cases of orbital pain preceding vesicles. Clinical orbital findings included proptosis, ptosis, ophthalmoplegia, and decreased visual acuity. Orbital magnetic resonance image showed enlarged extraocular muscle with enhancement and optic nerve sheath enhancement in all four patients, and unilateral dacryoadenitis in one patient. All four patients were administered with systemic steroid, three patients received intravenous acyclovir, and one patient received oral acyclovir. Orbital signs improved in all patients over several months. CONCLUSIONS: Herpes zoster ophthalmicus may initially present with orbital inflammatory signs, such as acute orbital myositis, perioptic neuritis, or dacryoadenitis, without zoster rash. Physicians should be aware of acute orbital inflammation as a presenting sign of HZO.

Herpes Zoster Optic Neuropathy.

BACKGROUND: Herpes zoster optic neuropathy (HZON) is a rare manifestation of herpes zoster ophthalmicus (HZO). The aim of our study was to better characterize the clinical features, therapeutic choices, and visual outcomes in HZON. METHODS: A retrospective chart review was performed at multiple academic eye centers with the inclusion criteria of all eyes presenting with optic neuropathy within 1 month of cutaneous zoster of the ipsilateral trigeminal dermatome. Data were collected regarding presenting features, treatment regimen, and visual acuity outcomes. RESULTS: Six patients meeting the HZON inclusion criteria were identified. Mean follow-up was 2.75 months (range 0.5-4 months). Herpes zoster optic neuropathy developed at a mean of 14.1 days after initial rash (range 6-30 days). Optic neuropathy was anterior in 2 eyes and retrobulbar in 4 eyes. Other manifestations of HZO included keratoconjunctivitis (3 eyes) and iritis (4 eyes). All patients were treated with systemic antiviral therapy in addition to topical and/or systemic corticosteroids. At the last follow-up, visual acuity in 3 eyes had improved relative to presentation, 2 eyes had worsened, and 1 eye remained the same. The 2 eyes that did not receive systemic corticosteroids had the best observed final visual acuity. CONCLUSION: Herpes zoster optic neuropathy is an unusual but distinctive complication of HZO. Visual recovery after HZON is variable. Identification of an optimal treatment regiment for HZON could not be identified from our patient cohort. Systemic antiviral agents are a component of HZON treatment regimens. Efficacy of systemic corticosteroids for HZON remains unclear and should be considered on a case-by-case basis.

Risk of Stroke/Transient Ischemic Attack or Myocardial Infarction with Herpes Zoster: A Systematic Review and Meta-Analysis.

BACKGROUND: Accumulating evidence indicates that herpes zoster (HZ) may increase the risk of stroke/transient ischemic attack (TIA) or myocardial infarction (MI), but the results are inconsistent. We aim to explore the relationship between HZ and risk of stroke/TIA or MI and between herpes zoster ophthalmicus (HZO) and stroke. METHODS: We estimated the relative risk (RR) and 95% confidence intervals (CIs) with the meta-analysis. Cochran's Q test and Higgins I2 statistic were used to check for heterogeneity. RESULTS: HZ infection was significantly associated with increased risk of stroke/TIA (RR = 1.30, 95% CI: 1.17-1.46) or MI (RR = 1.18, 95% CI: 1.07-1.30). The risk of stroke after HZO was 1.91 (95% CI 1.32-2.76), higher than that after HZ. Subgroup analyses revealed increased risk of ischemic stroke after HZ infection but not hemorrhagic stroke. The risk of stroke was increased more at 1 month after HZ infection than at 1-3 months, with a gradual reduced risk with time. The risk of stroke after HZ infection was greater with age less than 40 years than 40-59 years and more than 60 years. Risk of stroke with HZ infection was greater without treatment than with treatment and was greater in Asia than Europe and America but did not differ by sex. CONCLUSIONS: Our study indicated that HZ infection was associated with increased risk of stroke/TIA or MI, and HZO infection was the most marked risk factor for stroke. Further studies are needed to explore whether zoster vaccination could reduce the risk of stoke/TIA or MI.

Herpes zoster ophthalmicus with associated vasculopathy causing stroke.

Varicella zoster virus (VZV) is an exclusively human, double-stranded DNA virus. Primary infection causes varicella (chickenpox); later the virus becomes dormant in the dorsal root, cranial nerve, and autonomic ganglia along the entire span of the nervous system, retaining the capacity to reactivate and cause a variety of dermal and neurological complications. Recently there has been increasing recognition, both clinically and epidemiologically, of the relationship between VZV and subsequent strokes. Herein, we describe a case of a previously healthy individual with reactivation of VZV causing herpes zoster opthtalmicus along with devastating multifocal vasculopathy. It is crucial for dermatologists to recognize the dermatomal vesicular eruption in this high risk area to aid in prompt diagnosis in an effort to improve clinical prognosis.

In Vivo Confocal Microscopy Use in Endotheliitis.

PURPOSE: The use of in vivo confocal microscopy has been valuable in detecting and managing corneal pathology. This case study documents endotheliitis using in vivo confocal microscopy where apparent resolution of endothelial edema on clinical examination resulted in the discovery of subclinical findings with confocal scanning. The purpose of this case study was to discuss a rare corneal pathology and the clinical value of confocal scanning. CASE REPORT: A 30-year-old Asian Indian woman presented with unilateral endotheliitis and trabeculitis of presumed varicella zoster virus etiology. She was treated successfully with oral antiviral and topical corticosteroid therapy. Subclinical endotheliitis was detected using in vivo confocal microscopy, prompting the continuation of prophylactic, low-dose, topical corticosteroid therapy and topical hyperosmotics. CONCLUSIONS: Further research is warranted to better understand the role of confocal microscopy in endotheliitis therapeutic management, endothelial cell count and morphology, and keratic precipitate characterization. To date, prophylactic oral antivirals and/or topical corticosteroids may play a role in immune suppression of the herpes virus, although prospective, randomized, controlled clinical trials have not focused specifically on endotheliitis cases.

Addressing corneal opacity after herpes zoster infection.

A 15-year-old boy was referred for corneal opacity evaluation. The patient had a previous herpes zoster virus (HZV) infection-varicella-zoster virus (VZV)-with ocular manifestation 1 year ago. After the infection, he developed a central corneal scar and decreased corrected distance visual acuity (CDVA) in the right eye. The slitlamp examination showed the right eye with central corneal opacity (involving anterior stroma), lacuna area between the haze, fluorescein negative, and no vascularization near the scar (Figure 1JOURNAL/jcrs/04.03/02158034-202406000-00019/figure1/v/2024-07-10T174224Z/r/image-tiff). The patient had been treated with oral valacyclovir and topical corticosteroids without any improvement of visual acuity or changes in opacity within the 1-year follow-up. His CDVA was 20/200 (-4.50 -0.75 × 25) in the right eye and counting fingers (-4.00) in the left eye. Intraocular pressure was 12 mm Hg in both eyes. Fundoscopy was normal in the right eye, but he had a macular scar in the left eye (diagnosed when he was 7 years). The left eye had no cornea signs. The patient has no comorbidity or previous surgeries. Considering this case, a corneal central scar in a 15-year-old boy, legally single eye only, and assuming it is an opacity in the anterior stroma, would you consider surgery for this patient? If so, which would you choose: Would you consider an excimer laser treatment of his ametropia while partially removing his opacity, a phototherapeutic keratectomy (PTK), or a PTK followed by a topography-guided treatment, femtosecond laser-assisted anterior lamellar keratoplasty (FALK), or deep anterior lamellar keratoplasty (DALK) or penetrating keratoplasty (depending on the scar depth)? Would you consider prophylactic acyclovir during and after surgery? Would you consider any other surgical step to prevent delayed corneal healing-persistent epithelial defect? Before the surgical approach, would you consider treating this patient with topical losartan (a transforming growth factor [TGF]-ß signaling inhibitor)? Would you first perform the surgery (which one) and then start the medication? Furthermore, if so, how long would you treat this patient? Would you consider treatment with another medication?

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.

Antiviral activity of salivary microRNAs for ophthalmic herpes zoster.

Ophthalmic herpes zoster is a common ocular infection caused by the varicella-zoster virus (VZV). Viral mRNA transcripts play a major role in the replicative cycle of the virus and current antiviral agents have little effect in preventing and treating the complications. Therapeutic use of saliva for certain painful ocular diseases such as ophthalmic herpes zoster is a well-known public practice in our region. We thought that antiviral activity of saliva may stem from salivary microvesicles and we aimed to look for molecules with antiviral activity in these vesicles. As a possible candidate for antiviral activity, salivary microvesicles contain at least 20 microRNAs (miRNAs), small noncoding RNAs, which suppress the translation of target mRNAs. miRNAs not only participate in maintenance of normal cell functions, but are also involved in host-virus interactions and limit the replication of certain virus types. Thus, miRNA gene therapy by targeting mRNAs required for VZV survival may find a niche in the treatment of ophthalmic herpes zoster. But, how could salivary microvesicles reach into the corneal cells to demonstrate their antiviral activity. We suggest that human salivary microvesicles can be effective carriers of miRNA for corneal cells, because they contain a molecular machinery for vesicle trafficking and fusion allowing them to be endocytosed by target cells. After binding to the plasma membrane, microvesicles seem to enter into the corneal cells through the clathrin-mediated endocytosis. In the cytosol, human salivary miRNAs base-pair with specific viral mRNAs and inhibit their translation, thus limiting the replication of the virus.

Zoster sine herpete causing facial palsy.

OBJECTIVES: The aims of this study were to verify the characteristics of zoster sine herpete (ZSH) causing facial palsy and the effects of different treatments and to confirm the difference from other etiologies. METHODS: From March 2010 to March 2011, a prospective study was performed on patients with ZSH with facial palsy. Patients were divided into a steroid-treated group and a steroid-antiviral combination group, and then the effects according to regimen of treatment were prospectively analyzed. Last, the difference between the ZSH group and patients diagnosed with Bell palsy and Ramsay Hunt syndrome in the same study period was confirmed retrospectively. RESULTS: Forty-five patients were diagnosed as having ZSH. Significant improvement was not observed in the ZSH group regardless of the treatment regimen during a 3-week period (P < .05). In patients with ZSH with accompanying typical pain, significant continuous improvement after 6 weeks was observed in patients with combination therapy (P < .05). Compared with patients with Bell palsy and Ramsay Hunt syndrome, there was a significant difference in recovery rate between patients with ZSH (accompanying pain) and those with Bell palsy (89.9%) (P < .05). CONCLUSION: The initiation of recovery in ZSH started later than that in other peripheral palsies, and slower recovery was shown in patients with ZSH with pain compared with those with Bell palsy. Steroid-antiviral combination therapy was a more effective regimen for treatment compared with steroid-only treatment. To improve the accuracy of ZSH diagnosis, confirming the presence of accompanying typical pain is necessary.

Comparison of rubella virus- and herpes virus-associated anterior uveitis: clinical manifestations and visual prognosis.

PURPOSE: To compare the clinical characteristics and visual prognosis of patients with anterior uveitis (AU) and intraocular fluid analysis positive for rubella virus (RV), herpes simplex virus (HSV), or varicella zoster virus (VZV). DESIGN: Retrospective, observational study. PARTICIPANTS: The study included 106 patients with AU and positive polymerase chain reaction (PCR) results, Goldmann-Witmer coefficients (GWCs), or both, for RV (n = 57), HSV (n = 39), or VZV (n = 10). METHODS: Clinical records of the included patients were analyzed retrospectively; demographic constitution, ophthalmologic characteristics, and visual prognosis were compared. MAIN OUTCOME MEASURES: Age, gender, and diverse clinical and laboratory characteristics, including course and laterality of AU; prevalence of positive results for PCR, GWC, or both; conjunctival redness; corneal edema; history of keratitis; presence of keratic precipitates; synechiae; heterochromia; and grade of inflammation. In addition, complications and visual acuity at 1 and 3 years of follow-up were recorded. RESULTS: All 3 types of viral AU were characterized by unilateral involvement (80%-97%). Rubella virus AU was characterized by younger age at onset and chronic course and typically was associated with cataract at presentation. Heterochromia was present in 23% of RV AU patients. Anterior uveitis associated with HSV or VZV occurred characteristically in older patients and frequently followed an acute course. Clinical features associated with herpetic AU included conjunctival redness, corneal edema, history of keratitis, and development of posterior synechiae. Herpes simplex virus AU often had severe anterior chamber inflammation, whereas the presence of vitritis was more common in RV AU and VZV AU. The prevalence of documented intraocular pressure (IOP) of more than 30 mmHg (25%-50%; P = 0.06) and development of glaucoma (18%-30%; P = 0.686) were similar in all 3 groups. Focal chorioretinal scars were seen in 22% of RV AU eyes, in 0% of HSV AU eyes, and in 11% of VZV AU eyes (P = 0.003). Visual prognosis was favorable for all 3 groups. CONCLUSIONS: These observations identify clinical differences between RV AU, HSV AU, and VZV AU and may be of particular value to ophthalmologists who are unable to carry out intraocular fluid analysis to discriminate between these types of viral AU. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.