Ocular manifestations of herpes simplex virus.

PURPOSE OF REVIEW: To review ocular manifestations and complications of herpes simplex virus (HSV) and discuss recent advancements in diagnostic and treatment strategy. RECENT FINDINGS: In-vivo confocal microscopy has expanded our understanding of corneal nerve degeneration, corneal dendritic cell activity, and changes in biomechanical properties in HSV keratitis. Although currently available only as a research tool, metagenomic deep sequencing has the potential to improve diagnostic accuracy beyond the well established PCR technology, especially in atypical cases. Development of an HSV vaccine has shown some encouraging results in a murine model. New treatment options for neurotrophic cornea offer promise, specifically cenegermin nerve growth factor. SUMMARY: Ocular herpes simplex infection and its complications continue to cause significant visual burden and decreased quality of life. Familiarity with its clinical features, wider adoption of viral PCR diagnostic technology, and recognition of the need for long-term maintenance medications for recurrent or chronic cases form the basis for effective management. Metagenomic deep sequencing, the development of a herpes vaccine, and cenegermin nerve growth factor offer promise as diagnostic, preventive, and therapeutic options, respectively.

Maxillary herpes zoster with corneal involvement in a HIV positive pregnant woman.

Corneal involvement in maxillary herpes zoster is very rare. This report presents the case of a 32 years old 7 months pregnant para2+1 female, who presented with vesiculopapular rashes with hyperpigmented crusts over the maxillary area of the face on the left side with periocular oedema, conjunctivitis and mild punctate keratitis in the left eye. She was HIV positive and was on treatment with the highly active antiretroviral therapy. She was treated with topical and systemic acyclovir with rapid resolution of the ocular features.

Neurological Manifestations of Dengue Infection.

Dengue counts among the most commonly encountered arboviral diseases, representing the fastest spreading tropical illness in the world. It is prevalent in 128 countries, and each year >2.5 billion people are at risk of dengue virus infection worldwide. Neurological signs of dengue infection are increasingly reported. In this review, the main neurological complications of dengue virus infection, such as central nervous system (CNS), peripheral nervous system, and ophthalmic complications were discussed according to clinical features, treatment and possible pathogenesis. In addition, neurological complications in children were assessed due to their atypical clinical features. Finally, dengue infection and Japanese encephalitis were compared for pathogenesis and main clinical manifestations.

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.

Risk and prognostic factors of postherpetic neuralgia and focal sensory denervation: a prospective evaluation in acute herpes zoster ophthalmicus.

OBJECTIVES: To determine the general risk and the prognostic factors of postherpetic neuralgia and focal sensory denervation in ophthalmic zoster disease. STUDY DESIGN: A prospective clinical study. SETTING: An ophthalmic practice participating in an eye-care network. PATIENTS: A cohort of 81 immunocompetent adult patients with herpes zoster ophthalmicus and referred by their general practitioner during the acute phase of the disease. METHODS: Various acute phase clinical parameters were determined via patient history and regular ophthalmic examinations. At a 2-month follow-up, the intensity of postherpetic neuralgia, rated on a 4-point verbal scale, and focal sensory denervation was determined. Skin tactile sensation within the ophthalmic dermatomes was tested with use of a cotton-wool tip, and corneal sensitivity was measured with use of a Cochet-Bonnet esthesiometer by comparing each eye. Statistical analysis was performed via chi2 analysis or Fisher exact test to identify prognostic factors of postherpetic neuralgia and focal sensory denervation at a 2-month follow-up. RESULTS: At a 2-month follow-up, pain of varying intensity was reported by 38 participants (47%). Of these patients, 25 patients (31%) rated their pain as mild, 8 patients (10%) rated their pain as moderate pain, and 5 patients (6%) rated their pain as severe. At that time, focal loss of normal skin or corneal sensation was detected in 49 patients (60%). Patient age, acute neuralgia score, manifestation and extent of acute skin rash, signs of ocular inflammation, and nontrigeminal cranial nerve involvement were all associated with prolonged pain and tactile sensory loss. CONCLUSIONS: The severity of acute skin rash, based on a specific manifestation of cutaneous herpes zoster eruptions, and the extent of infection to other neural pathways were clearly associated with postherpetic neuralgia and focal sensory denervation at a 2-month follow-up. These findings suggest that the inability of the immune system to control the spread of replicating varicella-zoster virus in the initial phase of the disease is an important factor in the pathogenesis of chronic zoster-related neuropathy.

Eruption severity and characteristics in herpes zoster ophthalmicus: correlation with visual outcome, ocular complications, and postherpetic neuralgia.

INTRODUCTION: Herpes zoster ophthalmicus (HZO) is characterized by a typical vesicular eruption affecting the distribution of the ophthalmic division of the trigeminal nerve which can be of varying severity. The correlation of eruption severity and ocular involvement and subsequent visual loss is still to be established. In this prospective longitudinal study we evaluated the correlation of eruption severity with ocular complications, visual outcome and postherpetic neuralgia. METHODS: Patients with HZO underwent detailed ophthalmological and dermatological examination at presentation and follow-up on 1(st) , 2(nd) and 4(th) week and 3(rd) and 6(th) month. Eruption severity was graded as mild, moderate and severe based on the number of vesicles. The correlation of eruption severity and distribution with ocular complications, visual outcome and postherpetic neuralgia was statistically evaluated. RESULTS: Severe eruption was seen in 14(28%), moderate eruption in 21(42%) and mild eruption in 15(30%). Severe eruption was significantly associated with increased incidence and severity of ocular involvement (p = 0.04 and p = 0.04 respectively), occurrence of uveitis (p = 0.004), reduced visual outcome (p = 0.002) and the occurrence of PHN (p = 0.05). Lacrimal nerve involvement was also associated with increased incidence (p = 0.03) and severity (p = 0.02) of ocular complications and visual loss (p = 0.01). CONCLUSION: Increasing eruption severity is a good predictor of occurrence of ocular complications and subsequent visual loss in HZO. Presence of a severe eruption is an indication for early ophthalmic intervention. Nasociliary nerve and lacrimal nerve involvement are also good predictors of ocular complications.

Herpes zoster with progression to acute varicella zoster virus-meningoencephalitis.

BACKGROUND: Acute meningoencephalitis (ME) from varicella zoster virus (VZV) reactivation is a rare and serious complication of herpes zoster (HZ). OBJECTIVES AND METHODS: As early diagnostic detection is mandatory to prevent long-term sequelae, any clinical indication is helpful to identify patients that are at higher risk of the development of VZV-ME. In order to find such risk factors, the clinical data of 38 patients consecutively hospitalized for the treatment of HZ over a 1-year period were analyzed. RESULTS: Four of the 38 patients with HZ developed ME. Of these, three had involvement of the trigeminal nerve branch, one including an ophthalmic affection, and one presented with disseminated HZ. All were women with an average age of 83.5 years, in comparison with patients with HZ but without ME who had an average age of 69.3 years and a female preponderance of 60%. The first clinical signs of ME were rapidly progressing somnolence and meningism. Patients with HZ-ME were treated with intravenous acyclovir, oral glucocorticosteroids, and antiseizure therapy, and recovered almost completely without major residual symptoms. CONCLUSION: Progression of HZ to ME seems to occur more often than normally believed. Female patients above 80 years of age with either ophthalmic involvement or disseminated HZ are at a potentially high risk of the development of ME. The general recommendation of starting oral glucocorticosteroids from day 1 of antiviral treatment in older patients must be questioned, as it may stimulate VZV replication and dissemination.

Evaluation of the sensation in patients with trigeminal post-herpetic neuralgia.

BACKGROUND: Post-herpetic neuralgia (PHN) is one complication after herpes zoster infection, which may affect the facial superficial sensitivity. METHODS: Eighteen patients with PHN were interviewed and evaluated according to a systematized sensitivity approach, including mechanical, thermal and pain. RESULTS: The pain location was V1 in 15 patients. All trigeminal branches from both facial sides were evaluated; we compared the affected with the opposite side. There was a significant difference at V1 with cold (P=0.038), vonFrey (P=0.008) and pinpricks (P=0.022); at V2, the statistical difference occurred with cold (P=0.034), heat (P=0.019) and pinpricks (P=0.037); at V3, differences occurred with cold (P=0.042) and heat (P=0.036). Only V1 and oral mucosa (V2-3) presented pain threshold differences between both sides (P=0.001, P=0.021). CONCLUSION: Age, predominance of trigeminal PHN in V1 and continuous burning pain was common and similar to literature. Sensation was hampered with evident deficits of all sensory modalities in the affected trigeminal areas, especially V1.

[Zona of the cranial nerves. Current aspects]. / Zona des nerfs crâniens. Aspects actuels.

Recurrence of the chickenpox virus, herpes zoster localizes in cranial nerves in 30% of cases, with a predilection for the ophthalmic nerve. In young patients, clinicians must search for a herpes zoster-HIV association as well as oculomotor proprioception impairment in herpes zoster ophthalmicus. Enhanced MRI allows good objective view of the facial nerve lesions in herpes zoster facial paralysis. Finally, the gravity and aftereffects of cephalic herpes zoster can be decreased by an appropriate therapeutic approach.

Tracking the spread of a lacZ-tagged herpes simplex virus type 1 between the eye and the nervous system of the mouse: comparison of primary and recurrent infection.

The spread of herpes simplex virus type 1 (HSV-1) during primary ocular infection and after reactivation of latent infection in the trigeminal ganglion (TG) was examined in the mouse using a genetically modified virus containing the lacZ reporter gene under the control of the immediate-early 110 promoter. Whole tissue mounts of the eye and lids, their sensory nerves, and TG with the attached dorsal root entry zone (DRE) into the central nervous system (CNS) were stained for beta-galactosidase. Sixteen hours after inoculation of the cornea by scarification, staining was found in the scarified epithelium of the cornea and in the unscarified conjunctiva. By 24 h, staining was also seen in a few TG neurons and by 96 h their number had greatly increased and their distribution was more widespread. Stained cells (identified as Schwann cells by their staining for glial fibrillary acidic protein [GFAP] or S-100) in the TG were first seen close to stained neurons at 40 h, and by 48 h lines of such cells extended partway toward the periphery and toward the DRE. By 72 h, these lines had reached the periphery and the DRE where the adjacent CNS was also stained. In the cornea, stained cells with the morphology and arrangement of Schwann cells were seen from 40 to 120 h. After reactivation of latent infection, 10 of 22 samples had positively stained neurons. In eight samples, corneal and lid epithelial cells were stained. No stained Schwann cells were seen in the TG; however, branched networks of such cells were present in the cornea and the lids. This detailed sequential analysis has provided new information on the involvement of Schwann cells in the pathogenesis of primary and recurrent HSV-1 disease in the TG and the cornea.

Prognostic value of Hutchinson's sign in acute herpes zoster ophthalmicus.

PURPOSE: To determine the prognostic value of nasociliary skin lesions (Hutchinson's sign) for ocular inflammation and corneal sensory denervation in acute herpes zoster ophthalmicus. METHODS: A longitudinal observational study with a 2-month follow-up was performed involving 83 non-immunocompromised adults with acute herpes zoster ophthalmicus, with a skin rash duration of less than 7 days, referred by their general practitioner. All skin lesions at the tip, the side and the root of the nose, representing the dermatomes of the external nasal and infratrochlear branches of the nasociliary nerve, were documented by taking photographs and marking anatomical drawings. Ocular inflammatory signs were observed by slit-lamp biomicroscopy, and corneal sensitivity was measured with the Cochet-Bonnet esthesiometer at 2-month follow-up. RESULTS: Hutchinson's sign was a powerful predictor of ocular inflammation and corneal denervation in herpes zoster ophthalmicus [relative risks: 3.35 (CI 95%: 1.82-6.15) and 4.02 (CI 95%:1.55-10.42), respectively]. The manifestation of herpes zoster skin lesions at the dermatomes of both nasociliary branches was invariably associated with the development of ocular inflammation. CONCLUSION: Clinicians should be alert for early skin lesions within the complete nasociliary dermatome, because they are a reliable prognostic sign of sight-threatening ocular complications in acute herpes zoster ophthalmicus.