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.

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.

Bilateral Limbal Stem Cell Alterations in Patients With Unilateral Herpes Simplex Keratitis and Herpes Zoster Ophthalmicus as Shown by In Vivo Confocal Microscopy.

Purpose: The purpose of this study was to investigate the limbal changes in the palisades of Vogt (POV) in patients with herpes simplex keratitis (HSK) and herpes zoster ophthalmicus (HZO) with the application of in vivo confocal microscopy (IVCM). Methods: We enrolled 35 eyes of 35 consecutive patients with HSK and 4 patients with HZO in this observational study. Thirty-five participants were also recruited from a healthy population as the control group. All subjects were examined by IVCM in addition to routine slit-lamp biomicroscopy. The IVCM images of the corneal basal epithelial cells, corneal nerve, and the corneoscleral limbus were acquired and then were analyzed semiquantitatively. Results: The rate of absent and atypical POV was significantly higher in the affected eyes of patients with HSK than in the contralateral eyes and eyes of controls (88.57% vs. 65.71% vs. 17.14%, P < 0.01). In the HZO group, the rate of absent and atypical POV was 100% in the affected eyes and 50% in the contralateral eyes. When compared to the contralateral unaffected eyes and control eyes, the average density of the central basal epithelial cells and the sub-basal nerve plexus density and the total number of nerves in the central area of the affected eyes were significantly lower in the HSK group (1541 ± 704.4 vs. 2510 ± 746.8 vs. 3650 ± 746.1 cells/mm2, P < 0.0001). Spearman's rank correlation showed that the presence of absent and atypical POV had a significant negative correlation with central corneal basal epithelial cells (rs = -0.44979, P < 0.0001), the density of total nerves (rs = -0.49742, P < 0.0001), and the total nerve numbers (rs = -0.48437, P < 0.0001). A significant positive correlation was established between the presence of absent and atypical POV and HSK severity in affected eyes in the superior, inferior, nasal, and temporal quadrants (rs = 0.68940, rs = 0.78715, rs = 0.65591, and rs = 0.75481, respectively, P < 0.0001) and the contralateral eyes (rs = 0.51636, rs = 0.36207, rs = 0.36990, rs = 0.51241, correspondingly, P < 0.0001). Conclusions: Both eyes of patients with unilateral HSK and HZO demonstrated a profound and significant loss of limbal stem cells, which may explain the fact that HSK and HZO are risk factors for limbal stem cell deficiency (LSCD) in both eyes. The loss of LSCs was strongly correlated with the sub-basal nerve plexus and central basal epithelial cell alterations as shown by IVCM.

Clinical features and prognosis of herpetic anterior uveitis: a retrospective study of 111 cases.

To describe the clinical features and outcomes in patients with herpetic anterior uveitis. We reviewed the records of 111 patients with a clinical diagnosis of herpetic anterior uveitis seen at the Department of Ophthalmology, Istanbul Faculty of Medicine, from January 1996 to December 2006. Demographic and clinical features, recurrence rate, and visual outcome were analyzed. Fifty patients were male, 61 were female. Mean age at presentation was 39.2 ± 16.5 (6-74) years. Three atopic patients had bilateral involvement. Twelve patients had active or a past episode of herpes zoster ophthalmicus. Ocular findings were granulamatous anterior uveitis (93%), active keratitis or corneal scars (57%), elevated intraocular pressure (51%), iris atrophy (48%), distorted pupil (25%), and posterior synechiae (26%). Secondary glaucoma developed in two patients. None of the patients had posterior segment complications. The recurrence rate was 0.45/person-year. Topical corticosteroids and oral antiviral therapy were administered to all patients during active episodes. Long-term prophylactic oral acyclovir was used in 13%. Final visual acuity was worse than 0.5 in 17% of the involved eyes and was due to corneal scarring or cataract formation. Patients with iridocyclitis only had no permanent visual loss. Herpetic anterior uveitis is a recurrent granulomatous disease commonly associated with corneal involvement, iris atrophy, and transient intraocular pressure rise. Visual prognosis is good, especially in patients who have only anterior uveitis without corneal disease.

High resolution vessel wall MRI and vasculopathy related to herpes zoster ophthalmicus.

Varicella zoster virus is a common viral infection with over 50% of patients over the age of 80 years infected with the virus. Following reactivation, some patients succumb to complications of VZV reactivation with neurologic and optic pathway pathology such as VZV vasculopathy resulting in transient ischemic attacks, strokes, aneurysms, as well as optic neuritis. We show that high resolution vessel wall magnetic resonance imaging can aid in the diagnosis of this condition with circumferential wall thickening and enhancement of the infected vessels. Prompt diagnosis is critical as this is a treatable condition that could result in substantial morbidity or mortality if not recognized early.

Immunopathology of Virus-Induced Anterior Uveitis.

Herpes simplex virus, varicella zoster virus, human cytomegalovirus, and rubella virus are the most common causes of virus-induced anterior uveitis. They can present in a variety of entities not only with typical but also overlapping clinical characteristics. These viral infections are commonly associated with ocular infiltration of T cells and B/plasma cells, and expression of cytokines and chemokines typical of a proinflammatory immune response. The infections differ in that the herpes viruses cause an acute lytic infection and inflammation, whereas rubella virus is a chronic low-grade infection with slowly progressing immunopathological responses. The outcome of an intraocular viral infection may largely be guided by the characteristics of the virus, which subsequently dictates the severity and type of the immune response, and the host immune status.

In Vivo confocal microscopic changes of the corneal epithelium and stroma in patients with herpes zoster ophthalmicus.

PURPOSE: To analyze the density and morphology of corneal epithelial cells and keratocytes by in vivo confocal microscopy (IVCM) in patients with herpes zoster ophthalmicus (HZO) as associated with corneal innervation. DESIGN: Prospective, controlled and masked cross-sectional study. METHODS: setting: Single-center study. PATIENTS: Thirty eyes with the diagnosis HZO and their contralateral clinically unaffected eyes, 15 eyes of 15 normal controls. intervention procedures: In vivo confocal microscopy and corneal esthesiometry of the central cornea. MAIN OUTCOME MEASURES: Changes in morphology and density of the superficial and basal epithelial cells and stromal keratocytes, and correlation with corneal sensation. RESULTS: The density of superficial epithelial cells in HZO eyes with severe sensation loss (766.5 ± 25.2 cells/mm(2)) was significantly lower than both healthy control eyes (1450.23 ± 150.83 cells/mm(2)) and contralateral unaffected eyes (1974.13 ± 298.24 cells/mm(2)) (P = .003). Superficial epithelial cell size (1162.5 µm(2)) was significantly larger in HZO eyes with severe loss of sensation, as compared to contralateral (441.46 ± 298.14) or healthy eyes (407.4 ± 47.2µm(2); all P < .05). The density of basal epithelial cells, anterior keratocytes, and posterior keratocytes did not show statistical significance between patients, controls, and contralateral unaffected eyes. Changes in superficial epithelial cell density and morphology correlated strongly with corneal sensation. CONCLUSIONS: In vivo confocal microscopy reveals profound HZO-induced changes in the superficial epithelium, as demonstrated by increase in cell size, decrease in cell density, and squamous metaplasia. We demonstrate that these changes strongly correlate with changes in corneal innervation in eyes affected by HZO.

Stroke after zoster ophthalmicus in a 12-year-old girl with protein C deficiency.

A 12-year-old girl who had zoster ophthalmicus 10 months earlier presented with hemiparesis and corresponding basal ganglionic infarction related to middle cerebral artery branch thrombosis ipsilateral to the zoster. Hematologic evaluation disclosed protein C deficiency. This represents the first zoster-associated stroke reported in childhood associated with protein C deficiency, with extension of the latency period between zoster and infarction, previously reported to be 6 months.

Ocular inoculation of monkeys with simian varicella virus: clinical and histopathologic observations.

PURPOSE: To explore the possibility that inoculation of the eyes of African green monkeys with simian varicella virus (SVV) induces the symptoms of herpes zoster ophthalmicus (HZO), as seen in humans, and to develop a realistic and reproducible animal model of herpes zoster ophthalmicus for experimental studies. METHODS: In the first experiment, the right eyes of three African green monkeys were inoculated by intrastromal and subconjunctival injections with a suspension of SVV-infected Vero cells. In the second experiment, three additional monkeys were pretreated with intramuscular injections of methylprednisolone (41 mg/kg) for 7 days before ocular inoculation with SVV and for 3 weeks at 14 mg/kg after virus inoculation. The eyes were examined by slit-lamp biomicroscopy. Histologic, immunohistochemical, and electron microscopic studies were performed. RESULTS: In the first experiment, all three animals developed high titers of anti-SVV antibodies (IgG). Diffuse stromal opacity, with keratitic precipitates, stromal edema, and mild vascularization of the cornea, appeared 12 to 14 days after inoculation. The onset of ocular disease was correlated with the rise in serum antibody levels. There was no clinical evidence of a systemic viral infection resulting from the corneal inoculations in these monkeys. In the second experiment, all three animals treated with methylprednisolone developed severe ocular pathology within 1 week of inoculation. The clinical appearance of the diseased eyes strongly indicated that local viral infection had occurred. Dendritiform keratitis, corneal erosion, and stromal necrosis with vascularization of the cornea was seen in all the eyes. The disease resolved within 4 to 5 weeks of inoculation, leaving opaque, vascularized corneas. Histologic studies showed that inflammatory cells and viral antigens were widespread throughout the diseased corneas. A high titer of anti-SVV antibody (IgG) was detected in the immunosuppressed monkeys, but no evidence of systemic viral infection was observed. CONCLUSIONS: The authors propose that inoculation of the eyes of methylprednisolone-treated African green monkeys with simian varicella virus provides an appropriate animal model for studies of the virology and immunopathology of ocular varicella virus infection.

Herpetic corneal epithelial disease.

The clinical differentiation of corneal epithelial lesions due to herpes simplex or herpes zoster may be confusing. Practical clinical tests, including the use of topical ocular stains, are useful to differentiate corneal epithelial lesions caused by these two viruses. Two distinctive types of zoster corneal epithelial disease may be seen; an early dendritic form, and a delayed form characterized by corneal mucus plaques that may take a dendriform pattern. These plaques are composed of mucus that is adherent to swollen, degenerating epithelial cells. The clinical differentiation between these two viruses is essential since topically applied corticosteroids are contraindicated in epithelial herpes simplex and often are indicated in the management of epithelial herpes zoster.

Ocular varicella-zoster virus infection in the guinea pig. A new in vivo model.

Corneal intrastromal inoculation of guinea pigs with approximately 10(4) plaque-forming units of live, adapted varicella-zoster virus (VZV) resulted in reproducible, acute, superficial corneal disease in all animals. The culture-positive VZV ocular infection progressed to involve 30% to 40% of the corneal surface in a diffuse punctate keratitis and 10% to 15% of this surface with microdendrites, characteristic of VZV-induced ocular disease. Retrograde dissemination of VZV to the trigeminal ganglia, midbrain, cerebellum, and superior cervical ganglia was demonstrated by whole-cell coculture VZV recovery. Central nervous system VZV dissemination, manifested by transient neurologic symptoms and pneumonitis, was evident in 60% of the animals. Varicella-zoster virus spread to the trigeminal ganglion during acute and early-latent infection was evident by electron microscopy.

Optic chiasm, optic nerve, and retinal involvement secondary to varicella-zoster virus.

Immunocompromised patients are known to be at risk for varicella-zoster virus reactivation, often in atypical manners. We describe a 30-year-old man with simultaneous involvement of the retina, optic chiasm, and optic nerve with varicella-zoster virus who had a bitemporal visual field defect.