Detection of varicella zoster virus DNA and viral antigen in human eyes after herpes zoster ophthalmicus

doi:10.1016/S0161-6420(98)97042-7

Ophthalmology

Volume 105, Issue 7, 1 July 1998, Pages 1323-1330

https://doi.org/10.1016/S0161-6420(98)97042-7 Get rights and content

Abstract

Objective

The purpose of the study was to identify varicella zoster virus (VZV) DNA and viral antigen in human eyes at various intervals after clinical onset of herpes zoster ophthalmicus (HZO).

Design

A retrospective case series.

Participants

There were 9 eyes and 4 corneal buttons surgically obtained from 13 patients with HZO at the University Eye Hospital of Erlangen-Nürnberg between 1984 and 1994. Specimens were examined at different timepoints after clinical onset of HZO (range, 1 day-19 years; median, 36 months).

Methods

Histopathologic evaluation was performed on formalin-fixed and paraffin-embedded tissue by routine histology, immunohistochemistry (5-B-7 murine monoclonal antibody to VZV; peroxidase-antiperoxidase method), and DNA-in situ hybridization (³⁵S deoxyadenosine triphosphate-labeled HindIII fragments [A and C] of VZV).

Results

Typical histopathologic changes associated with HZO were identified: vascularization of the corneal stroma (11 of 13), granulomatous reaction to Descemet’s membrane (8 of 13), fusiform-shaped ciliary scarring (5 of 9), optic neuritis (4 of 9), and perineuritis (8 of 9) and perivasculitis (8 of 9) of the long posterior ciliary nerves and arteries. VZV antigen was detected in two patients with acute infection 1 and 7 days after onset of HZO, respectively. VZV-DNA was identified in seven patients up to 10 years after onset of HZO in corneal epithelial cells (2 of 13), corneal stroma (5 of 13), inflammatory infiltrate of the anterior chamber (1 of 9), episclera (2 of 9), posterior ciliary nerves (1 of 9) and arteries (5 of 9), optic nerve (5 of 9), and adjacent leptomeninges (2 of 9).

Conclusion

Persistence of viral genomes, most likely accompanied by gene expression or slow viral replication, appears to be responsible for the often smoldering panophthalmitis and the chronic recurrent keratouveitis in patients with HZO. Localization of viral DNA in vascular structures suggests a role for vasculitis in the pathogenesis of some ocular findings associated with HZO.

Section snippets

Patients

Nine surgically enucleated eyes and four corneal buttons obtained after penetrating keratoplasty were studied from 13 patients who had a clinical diagnosis of HZO. The study included seven female and six male patients ranging in age from 19 to 86 years (median, 75 years). The interval between clinical onset of HZO and surgery varied from 1 day to 19 years (median, 36 months). Two patients (patients 1 and 2; Table 1) showed the clinical features of acute HZO 1 and 7 days after clinical onset,

Histopathologic analysis

The previously reported typical pattern of histopathologic changes in HZO16, 17 was confirmed in our series (Table 1). Major changes in the anterior segment of the eye included vascular corneal scarring (11 of 13) (Fig 2), granulomatous reaction to Descemet’s membrane (9 of 13) (Fig 2), and trabeculitis (8 of 9) (Fig 3). All eyes were diagnosed with a chronic nongranulomatous scleritis and episcleritis in combination with the typical segmental necrosis of iris stroma and anterior part of the

Discussion

Although the histopathologic features of HZO are well described,16, 17, 20, 21 the details of the pathogenesis and the pathomechanism of different ocular manifestations still are uncertain. The mechanism of a “smoldering” VZV infection with progressive destruction of the eye is discussed with special frequency. Some authors implicate different immunoreactions17 against inactive viral antigens or persisting viral replication,22 whereas others favor nerve damage,10 direct cytopathic effects of

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There are a number of autoimmune disorders which can affect visual function. There are a very large number of mechanisms in the visual pathway which could potentially be the targets of autoimmune attack. In practice it is the retina and the anterior visual pathway (optic nerve and chiasm) that are recognised as being affected in autoimmune disorders. Multiple Sclerosis is one of the commonest causes of visual loss in young adults because of the frequency of attacks of optic neuritis in that condition, however the basis of the inflammation in Multiple Sclerosis and the confirmation of autoimmunity is lacking. The immune process is known to be highly unusual in that it is not systemic and confined to the CNS compartment. Previously an enigmatic partner to Multiple Sclerosis, Neuromyelitis Optica is now established to be autoimmune and two antibodies – to Aquaporin4 and to Myelin Oligodendrocyte Glycoprotein – have been implicated in the pathogenesis. The term Chronic Relapsing Inflammatory Optic Neuropathy is applied to those cases of optic neuritis which require long term immunosuppression and hence are presumed to be autoimmune but where no autoimmune pathogenesis has been confirmed. Optic neuritis occurring post-infection and post vaccination and conditions such as Systemic Lupus Erythematosus and various vasculitides may cause direct autoimmune attack to visual structures or indirect damage through occlusive vasculopathy. Chronic granulomatous disorders such as Sarcoidosis affect vision commonly by a variety of mechanisms, whether and how these are placed in the autoimmune panoply is unknown. As far as the retina is concerned Cancer Associated Retinopathy and Melanoma Associated Retinopathy are well characterised clinically but a candidate autoantibody (recoverin) is only described in the former disorder. Other, usually monophasic, focal retinal inflammatory disorders (Idiopathic Big Blind Spot Syndrome, Acute Zonal Occult Outer Retinopathy and Acute Macular Neuroretinitis) are of obscure pathogenesis but an autoimmune disorder of the post-infectious type is plausible. Visual loss in autoimmunity is an expanding field: the most significant advances in research have resulted from taking a well characterised phenotype and making educated guesses at the possible molecular targets of autoimmune attack.
Herpes zoster ophthalmicus: Comparison of disease in patients 60 years and older versus younger than 60 years
2011, Ophthalmology
To study the clinical course of herpes zoster ophthalmicus (HZO) and to compare the demographics, treatments, and outcomes in patients aged <60 years versus patients aged ≥60 years at the time of diagnosis.
Retrospective chart review of all 112 patients presenting for management of HZO from January 1, 2008 to December 31, 2008.
A total of 112 patients (58 aged <60 years and 54 aged >60 years) at the time of HZO onset.
Anterior segment complications, treatments, and surgical procedures were documented at 3 months, 6 months, and 1 year, and then annually for the remainder of the follow-up period.
Intraocular pressure, inflammation, steroid use, surgical procedures, anterior segment complications, post-herpetic neuralgia, and delayed herpes zoster pseudodendrites.
Equal numbers of patients were affected with HZO in the younger and older age groups (51.8%, n = 58 vs. 48.2%, n = 54, respectively, P = 0.69). The most common decade of HZO onset was between 50 and 59 years. Younger patients were more likely to be healthy compared with older patients (P = 0.05). Delayed herpes zoster pseudodendrites were more common in the younger patients (36.7% vs. 16.7%, P = 0.03). The mean number of flares per patient-years was significantly higher in the younger patients (z test, P = 0.024). Post-herpetic neuralgia, neurotrophic keratopathy, and secondary infectious keratitis were more frequent in the older patients (P = 0.05). Prevalence of corneal perforation, corneal thinning, cataract formation, and glaucoma was similar between the 2 groups. Most patients in both groups (84.2% of younger patients and 89.5% of older patients) were taking topical steroids 3 years after referral for HZO.
Herpes zoster ophthalmicus affects individuals aged younger than and older than 60 years in similar numbers, with the most common decade of onset between age 50 and 59 years. Younger patients had more episodes of delayed pseudodendritiform keratitis and flares of inflammation compared with older patients, who had more problems related to neurotrophic keratopathy.
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1999, Mayo Clinic Proceedings
Herpes zoster is a cause of considerable morbidity, especially among elderly patients, with a suggestion of a slight increase in incidence among female patients. Substantial research on the biology of the varicella zoster virus has led to advances in our knowledge of the pathophysiology of the disease along with more successful therapy for the acute episodes of herpes zoster. Ophthalmic zoster is more common than zoster in other cranial nerves and is associated with pronounced suffering. This article reviews the epidemiology, biology, and latency of herpes zoster, discusses the pathophysiology of the disease, and describes treatment options with antivirals and corticosteroids. The pathophysiology and treatment options for postherpetic neuralgia are also addressed. The varicella vaccine is now available, and initial results suggest that this may lessen the effect of herpes zoster in the future.
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¹: The authors have no proprietary interest in any instrument, drug, or piece of equipment mentioned in this article.

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Detection of varicella zoster virus DNA and viral antigen in human eyes after herpes zoster ophthalmicus1

Abstract

Objective

Design

Participants

Methods

Results

Conclusion

Section snippets

Patients

Histopathologic analysis

Discussion

Am J Ophthalmol

Am J Ophthalmol

Ophthalmology

Am J Ophthalmol

Surv Ophthalmol

Am J Ophthalmol

Ophthalmology

Ophthalmology

Am J Ophthalmol

J Neurol Sci

Virology

Am J Ophthalmol

Pediatr Neurol

Hum Pathol

A clinical report on herpes zoster frontalis ophthalmicus (shingles affecting the forehead and nose)

Royal London Ophthalmic Hospital Report

Herpes zoster ophthalmicusreport of cases and review of literature

Arch Ophthalmol

Natural history of herpes zoster ophthalmicuspredictors of postherpetic neuralgia and ocular involvement

Br J Ophthalmol

Cutaneous eruption with or without ocular complications in patients with herpes zoster involving the trigeminal nerve

Graefes Arch Clin Exp Ophthalmol

True posterior ischemic optic neuropathy associated with herpes zoster ophthalmicus

Optom Vis Sci

Herpes zoster optic neuritis in human immunodeficiency virus infection

Arch Ophthalmol

Detection of varicella zoster virus DNA and viral antigen in human eyes after herpes zoster ophthalmicus¹