Distinguishing Features of Anterior Uveitis Caused by Herpes Simplex Virus, Varicella-Zoster Virus, and Cytomegalovirus.

PURPOSE: To determine distinguishing features of the clinical characteristics of anterior uveitis (AU) caused by herpes simplex virus (HSV), varicella-zoster virus (VZV), and cytomegalovirus (CMV). DESIGN: Retrospective, multicenter case series. METHODS: Consecutive patients with herpetic AU examined at 11 tertiary centers in Japan between January 2012 and December 2017 and who were followed for ≥3 months were evaluated. Diagnosis was made by polymerase chain reaction (PCR) for HSV, VZV, or CMV in the aqueous humor, or classical signs of herpes zoster ophthalmicus. RESULTS: This study enrolled 259 herpetic AU patients, including PCR-proven HSV-AU (30 patients), VZV-AU (50), and CMV-AU (147), and herpes zoster ophthalmicus (32). All HSV-AU and VZV-AU patients were unilateral, while 3% of CMV-AU patients were bilateral. Most HSV-AU and VZV-AU patients were sudden onset with an acute clinical course, while CMV-AU had a more insidious onset and chronic course. There were no significant differences for all surveyed symptoms, signs, and complications between HSV-AU and VZV-AU. However, significant differences were detected for many items between CMV-AU and the other two herpetic AU types. Ocular hyperemia and pain, blurring of vision, ciliary injection, medium-to-large keratic precipitates (KPs), cells and flare in the anterior chamber, and posterior synechia significantly more often occurred in HSV-AU and VZV-AU vs CMV-AU. In contrast, small KPs, coin-shaped KPs, diffuse iris atrophy, elevated intraocular pressure, and glaucoma surgery were significantly more frequent in CMV-AU vs HSV-AU and VZV-AU. CONCLUSION: This multicenter, retrospective study identified distinguishing features of HSV-AU, VZV-AU, and CMV-AU.

Herpes Zoster Ophthalmicus Clinical Presentation and Risk Factors for Loss of Vision.

PURPOSE: To determine the rate of moderate and severe vision loss following herpes zoster ophthalmicus (HZO) and to identify associated factors. DESIGN: Retrospective cohort study. METHODS: All subjects with acute HZO seen at a single center from 2006 to 2016 were included in the study. The primary outcome measure was the proportion of individuals with moderate and/or severe loss of vision following an acute episode of HZO. Secondary outcome measures included causes and factors associated with permanent loss of vision owing to HZO. RESULTS: A total of 869 patients with acute HZO were identified with a median follow-up time of 6.3 years (interquartile range 3.7-8.9 years). Ocular involvement of HZO was diagnosed at or within the first month of presentation in 737 individuals (84.8%). The most common sites of ocular involvement were conjunctivitis (76.1%), followed by keratitis (51.2%) and uveitis (47.6%). Moderate vision loss (≤20/50) secondary to HZO occurred in 83 eyes (9.6%) while severe vision loss (≤20/200) occurred in 31 eyes (3.6%). Causes of loss of vision included corneal scarring (94.0%), corneal perforation (4.8%), and secondary glaucoma (1.2%). Severe vision loss was associated with older age (hazard ratio [HR] 1.059, P = .001), immunosuppression (HR 3.125, P = .028), poor presenting visual acuity (HR 2.821, P = .002), and uveitis (HR 4.777, P = .004) on multivariate analysis. CONCLUSIONS: Among individuals with HZO, approximately 1 in 10 individuals may develop moderate or severe vision loss, primarily owing to corneal scarring. Older age, immunosuppression, and uveitis are associated with severe permanent loss of vision secondary to HZO.

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.

Aggregate health and economic burden of herpes zoster in the United States: illustrative example of a pain condition.

Our objective was to develop comprehensive national estimates of the total burden of herpes zoster (HZ) among U.S. adults, including direct (ie, medical costs) and indirect (ie, productivity losses) costs, as well as its psychosocial impact (ie, quality of life losses). Using a patient-level microsimulation model, we projected health and economic outcomes among U.S. adults aged 18 years and older using a 10-year time horizon. We conducted a comprehensive systematic literature review to generate parameter values and conducted simulation modeling to generate our outcomes, including numbers of cases of uncomplicated HZ, postherpetic neuralgia (PHN), and ocular complications, productivity losses, and losses in quality-adjusted life years (QALYs). We used a societal perspective for outcomes; the costing year was 2015. Projected outcomes for an unvaccinated population included 1.1 million HZ cases, 114,000 PHN cases, and 43,000 ocular complications annually, resulting in approximately 67,000 QALYs lost. HZ and its complications would incur costs of $2.4 billion in direct medical costs and productivity losses annually. Projected QALY losses were most sensitive to HZ and PHN health utility values in the model. Cost estimates were most sensitive to the probability of HZ and to the costs per episode of PHN. The national burden of direct, indirect, and psychosocial HZ costs is substantial. Our results can inform economic analyses for HZ vaccines. Comprehensive, national assessments of the total burden of other painful conditions would be very informative.

Long-term outcomes of penetrating keratoplasty for corneal complications of herpes zoster ophthalmicus.

BACKGROUND/AIM: To review the long-term outcomes of penetrating keratoplasty (PKP) for corneal complications of herpes zoster ophthalmicus (HZO). METHODS: We reviewed the medical records of 53 eyes of 53 patients who underwent PKP due to corneal complications of HZO at the Kellogg Eye Center. RESULTS: The mean age of patients at the time of PKP was 68.0±16.4 years, with a follow-up of 4.0±3.8 years and quiescent period of 6.5±5.3 years from active HZO to PKP. Preoperatively, 25 (47.2%) eyes were completely anaesthetic, while 16 (30.2%) had deep corneal neovascularisation in four quadrants. Comorbid ocular disease, including cataract, glaucoma and macular disease, was present in 25 (47.2%) eyes. Twenty patients (37.8%) received acyclovir for the entire postoperative period. There were no recurrences of zoster keratitis in any eye. The most common complications were difficulty healing the ocular surface (12/53, 22.6%) and glaucoma (14/53, 26.4%). Thirty per cent of the eyes required one or more additional postoperative procedures, most commonly tarsorrhaphy (10/53, 18.9%) and amniotic membrane graft (6/53, 11.3%). At 1, 2-4 and ≥5 years, 94%, 82% and 70% grafts remained clear, respectively. Visual acuity improved at 1 year postoperatively (p<0.0001), but this improvement was not sustained. There was no significant benefit of long-term acyclovir on visual acuity (p=0.2132) or graft survival (p=0.241). CONCLUSIONS: Even in eyes with significant preoperative risk factors, PKP for the corneal complications of HZO can achieve favourable tectonic and visual results. Although most grafts remained clear, long-term visual potential may be limited by comorbid ocular diseases. Prophylactic postoperative oral acyclovir did not improve outcomes.

Varicella-zoster virus necrotising retinitis, retinal vasculitis and panuveitis following uncomplicated chickenpox in an immunocompetent child.

A 4-year-old girl presented with acute left visual loss 4 weeks after uneventful chickenpox. She was found to have left necrotising retinitis and profound retinal vasculitis and vitritis. Aqueous humour was PCR positive for varicella-zoster virus. Combined intravenous and intravitreal antiviral treatment led to rapid improvement with settled retinitis, no vascular occlusion and good recovery of vision. Her recent coinfection with Epstein-Barr virus may have acted to provoke the retinitis.

Electrophysiological characteristics of the frontal nerve in patients with herpetic ophthalmic neuralgia.

INTRODUCTION: The aim of this study was to explore a method for obtaining sensory nerve action potentials (SNAPs) of the supratrochlear (STN) and supraorbital (SON) nerves and evaluate the function of affected nerves in patients with herpetic ophthalmic neuralgia (HON). METHODS: Thirty healthy volunteers and 40 subjects with subacute HON participated in this study. RESULTS: The amplitudes and sensory conduction velocities (SCVs) that predicted HON were identified. The corresponding cutoff values for the amplitudes ranged from 11.10 µV to 12.45 µV. The corresponding cutoff values for the SCVs ranged from 43.14 m/s to 44.64 m/s. SCVs were markedly lower on the affected side compared with healthy volunteers (P < 0.05), and the amplitudes of SNAPs on the affected side were decreased by 36% compared with healthy volunteers (P < 0.05). DISCUSSION: SCVs of STN and SONs can be obtained with the 3-channel method and used to evaluate myelinated fibers in patients with HON. Muscle Nerve 57: 973-980, 2018.

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.

Treatment of Progressive Herpes Zoster-Induced Vasculopathy with Surgical Revascularization: Effects on Cerebral Hemodynamics.

BACKGROUND: Herpes zoster ophthalmicus (HZO) is caused by reactivation of the herpes simplex virus in the trigeminal nerve. HZO-initiated cerebral vasculopathy is well characterized; however, there are no documented cases that report the efficacy of surgical revascularization for improving cerebral hemodynamics following progressive HZO-induced vasculopathy. We present a case in which quantitative anatomic and hemodynamic imaging were performed longitudinally before and after surgical revascularization in a patient with HZO and vasculopathic changes. CASE DESCRIPTION: A 57-year-old female with history of right-sided HZO presented with left-sided hemiparesis and dysarthria and multiple acute infarcts. Angiography performed serially over a 2-month duration revealed progressive middle cerebral artery stenosis, development of new moyamoya-like lenticulostriate collaterals, and evidence of fibromuscular dysplasia in cervical portions of the internal carotid artery. Hemodynamic imaging revealed right hemisphere decreased blood flow and cerebrovascular reserve capacity. In addition to medical therapy, right-sided surgical revascularization was performed with the intent to reestablish blood flow. Follow-up imaging 13 months post revascularization demonstrated improved blood flow and vascular reserve capacity in the operative hemisphere, which paralleled symptom resolution. CONCLUSIONS: HZO can lead to progressive, symptomatic intracranial stenoses. This report suggests that surgical revascularization techniques can improve cerebral hemodynamics and symptomatology in patients with aggressive disease when medical management is unsuccessful; similar procedures could be considered in managing HZO patients with advanced or progressive vasculopathy.

Prevalence of Ocular Manifestations and Visual Outcomes in Patients With Herpes Zoster Ophthalmicus.

PURPOSE: To investigate the prevalence of ocular manifestations and visual outcomes in patients with herpes zoster ophthalmicus (HZO). METHODS: Consecutive cases diagnosed with HZO who attended 2 hospitals between July 1, 2011, and June 30, 2015, were retrospectively reviewed. Patient demographics, clinical presentations, and management were reviewed. The logistic regression model was used to estimate the odds ratio of visual loss with ocular manifestations. RESULTS: A total of 259 patients were included. Of these, 110 (42.5%) patients were <60 years old and 149 patients (57.5%) were ≥60 years old. None of the patients had received zoster vaccination before presentation. Ocular manifestations were present in 170 (65.6%) patients with no difference between both age groups (P = 0.101). Conjunctivitis was the most common ocular manifestation, followed by anterior uveitis and keratitis. After resolution of HZO, 58.7% of patients had a visual acuity of 6/12 or worse. Epithelial keratitis and stromal keratitis were independent risk factors for visual loss after resolution of HZO (P = 0.003 and P = 0.004, respectively). The corresponding odds ratio was 6.59 [95% confidence interval (CI): 1.87-23.19] and 7.55 (95% CI: 1.88-30.30), respectively. The number of ocular manifestations was also associated with an increased risk of visual loss with an odds ratio of 1.49 (95% CI: 1.01-2.20; P = 0.043). CONCLUSIONS: A substantial proportion of patients with HZO were <60 years old in this study. The absence of zoster vaccination across the study cohort was noteworthy. Keratitis was the main reason for poor visual outcome in these patients.

[Clinical presentations of Herpes Zoster Ophthalmicus (diagnosis and therapy)]. / Klinicheskie proyavleniya Herpes Zoster Ophthalmicus (diagnostika i terapiya).

Approximately a quarter of the world's population at some point in life is at risk of developing shingles (Herpes Zoster). In 10-20% of cases the first branch of the trigeminal nerve gets involved (Herpes Zoster Ophthalmicus, HZO). Ophthalmic complications of HZO are able to cause a significant reduction in visual function. AIM: To study and summarize clinical features of HZO (including the rate of complications and their nature) and to determine the relationship between clinical and laboratory data from these patients. MATERIAL AND METHODS: The study included 133 patients with ophthalmic and neurological complications of HZO (group 1 (n=28) - retrospective analysis of outpatient records for the period 1995-2005; group 2 (n=95) - a prospective study for the period 2005-2015), who received a course of conservative treatment in either the Botkin City Hospital, branch № 1, or in the ophthalmic department of the Moscow herpes centre (Gerpeticheskiy Tsentr Ltd.). Laboratory tests were performed only in patients from group 2 and included: examination of biological fluids for six types of herpes viruses by polymerase chain reaction, examination of tears and urine for DNA of Chlamydia, Mycoplasma, and Ureaplasma, and serological blood testing for markers of herpes virus infection. Patients from group 1 were prescribed topical antiviral, antibacterial, and anti-inflammatory therapy, in rare cases - acyclovir per os. In group 2, the treatment included systemic antiviral medications and immune correction therapy. Anti-inflammatory therapy consisted of local and systemic non-steroidal agents (NSAIDs). RESULTS: The most common ophthalmic complications of HZO in both groups were stromal keratitis and keratoiridocyclitis, neurological - III and VI cranial nerves palsies. The duration of the disease in the first group ranged from 2 months to 3 years; in the second group, patients were divided into two subgroups: subgroup A with the disease duration of no more than one month (n=81) and subgroup B with the disease duration from 1.5 to 9 months (n=14). Varicella-zoster virus (VZV) DNA was present in tears and/or other biological fluids of patients from group 2 in more than 70% of cases (n=67). Particularly, in 27.4% of cases the virus was isolated in two fluids and in 7.4% of cases - in three fluids. The duration of virus production in tears and other biological fluids (saliva, blood, and urine) ranged from 10 days to 4 months. CONCLUSION: Topical non-steroidal anti-inflammatory drugs and systemic etiological treatment in case of intraocular inflammation in HZO patients may reduce the risk of severe consequences of VZV reactivation and help avoid recurrences later in life.

SUNCT headaches after ipsilateral ophthalmic-distribution zoster.

Nine days after left ophthalmic-distribution zoster, a 47-year-old man developed SUNCT headaches (short-lasting unilateral neuralgiform headache with conjunctival injection and tearing). In contrast to two prior cases of SUNCT that developed after varicella zoster virus (VZV) meningoencephalitis without rash, this case describes an association of SUNCT with overt zoster, thus adding to the spectrum of headache and facial pain syndromes caused by VZV reactivation.

Herpes zoster ophthalmicus and varicella zoster virus vasculopathy.

Herpes zoster (HZ) corresponds to the reactivation of varicella zoster virus (VZV). Among adults, the ophthalmic division of the trigeminal nerve is one of the most common sites of involvement. Vasculopathy caused by HZ is associated with significant morbidity and mortality, affecting structures such as the brain, which can lead to stroke. In this review, we analyzed the epidemiological and clinical aspects of the vascular involvement of VZV, focusing on the peculiarities of its association with ocular HZ. A review of the available literature indicated that ocular involvement of HZ was a risk factor for vasculopathy after adjusting for age, sex, body mass index, smoking, indicators of metabolic syndrome, and vascular and heart diseases. Considering the severity of this complication, vascular disease mediated by VZV requires early diagnosis and aggressive treatment. Finally, the anti-HZ vaccine has been recommended as a prophylactic measure in the elderly, but it should be used with caution in immunocompromised individuals.

Herpes zoster ophthalmicus and varicella zoster virus vasculopathy / Herpes zoster ophthalmicus e vasculopatia por vírus varicella zoster

ABSTRACT Herpes zoster (HZ) corresponds to the reactivation of varicella zoster virus (VZV). Among adults, the ophthalmic division of the trigeminal nerve is one of the most common sites of involvement. Vasculopathy caused by HZ is associated with significant morbidity and mortality, affecting structures such as the brain, which can lead to stroke. In this review, we analyzed the epidemiological and clinical aspects of the vascular involvement of VZV, focusing on the peculiarities of its association with ocular HZ. A review of the available literature indicated that ocular involvement of HZ was a risk factor for vasculopathy after adjusting for age, sex, body mass index, smoking, indicators of metabolic syndrome, and vascular and heart diseases. Considering the severity of this complication, vascular disease mediated by VZV requires early diagnosis and aggressive treatment. Finally, the anti-HZ vaccine has been recommended as a prophylactic measure in the elderly, but it should be used with caution in immunocompromised individuals.

RESUMO Herpes zoster (HZ) corresponde à reativação do vírus varicela zoster (VVZ) e, entre os adultos, o envolvimento da divisão oftálmica do nervo trigêmeo é um dos locais mais comuns A vasculopatia associada ao HZ é uma complicação dotada de grande morbimortalidade e afeta diferentes estruturas, favorecendo, inclusive o acidente vascular cerebral. Nesta revisão analisamos aspectos epidemiológicos e clínicos da vasculopatia mediada pelo VZV, bem como as peculiaridades relacionadas com o HZ ocular. De acordo com dados disponíveis na literatura, o acometimento ocular pelo HZ mostrou ser um fator de risco para vasculopatia após se ajustar para idade, sexo, índice de massa corporal, tabagismo, indicadores da síndrome metabólica, doença vascular e cardiopatias. Em face da gravidade dessa complicação, a doença vascular mediada pelo VZV requer diagnóstico precoce e tratamento agressivo. A vacina anti-HZ tem sido recomendada profilaticamente em idosos, mas deve ser usada com cautela em indivíduos imunocomprometidos.

Corneal Reinnervation and Sensation Recovery in Patients With Herpes Zoster Ophthalmicus: An In Vivo and Ex Vivo Study of Corneal Nerves.

PURPOSE: To study corneal reinnervation and sensation recovery in Herpes zoster ophthalmicus (HZO). METHODS: Two patients with HZO were studied over time with serial corneal esthesiometry and laser in vivo confocal microscopy (IVCM). A Boston keratoprosthesis type 1 was implanted, and the explanted corneal tissues were examined by immunofluorescence histochemistry for ßIII-tubulin to stain for corneal nerves. RESULTS: The initial central corneal IVCM performed in each patient showed a complete lack of the subbasal nerve plexus, which was in accordance with severe loss of sensation (0 of 6 cm) measured by esthesiometry. When IVCM was repeated 2 years later before undergoing surgery, case 1 showed a persistent lack of central subbasal nerves and sensation (0 of 6). In contrast, case 2 showed regeneration of the central subbasal nerves (4786 µm/mm) with partial recovery of corneal sensation (2.5 of 6 cm). Immunostaining of the explanted corneal button in case 1 showed no corneal nerves, whereas case 2 showed central and peripheral corneal nerves. Eight months after surgery, IVCM was again repeated in the donor tissue around the Boston keratoprosthesis in both patients to study innervation of the corneal transplant. Case 1 showed no nerves, whereas case 2 showed new nerves growing from the periphery into the corneal graft. CONCLUSIONS: We demonstrate that regaining corneal innervation and corneal function are possible in patients with HZO as shown by corneal sensation, IVCM, and ex vivo immunostaining, indicating zoster neural damage is not always permanent and it may recover over an extended period of time.

Herpes Zoster Ophthalmicus.

Herpes zoster is a commonly encountered disorder. It is estimated that there are approximately 1 million new cases of herpes zoster in the United States annually, with an incidence of 3.2 per 1000 person-years. Patients with HIV have the greatest risk of developing herpes zoster ophthalmicus compared with the general population. Other risk factors include advancing age, use of immunosuppressive medications, and primary infection in infancy or in utero. Vaccination against the virus is a primary prevention modality. Primary treatments include antivirals, analgesics, and anticonvulsants. Management may require surgical intervention and comanagement with pain specialists, psychiatrists, and infectious disease specialists.

Outcomes of cataract surgery in eyes with previous herpes zoster ophthalmicus.

PURPOSE: To report the outcomes of cataract surgery in eyes with previous herpes zoster ophthalmicus (HZO). SETTING: Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, USA. DESIGN: Retrospective case series. METHODS: Eyes with a history of HZO that had phacoemulsification and intraocular lens implantation were reviewed. The information analyzed included the ophthalmologic history, visual acuity, preoperative and postoperative adjunct treatments, and complications. Analysis of the mean corrected distance visual acuity (CDVA) at 1 month, 1 year, and the last follow-up was performed. RESULTS: Twenty-four eyes were evaluated. The mean CDVA improved from 20/112 (0.75 logMAR ± 0.63 [SD]) preoperatively to 20/53 (0.42 ± 0.56 logMAR) 1 month postoperatively (P = .007) and 20/44 (0.34 ± 0.55 logMAR) at 1 year (P = .052) but decreased to 20/71 (0.55 ± 0.72 logMAR) by last follow-up (P = .605 versus preoperative CDVA). Eleven patients (45.8%) had recurrent keratouveitis after the first episode, 5 before cataract surgery and 6 after cataract surgery. Three had penetrating keratoplasty for worsening corneal opacification. Two patients had tractional retinal detachment from chronic uveitis and required vitrectomy and retinal repair. CONCLUSIONS: Visual recovery after cataract surgery in HZO might be compromised by chronic factors such as ocular surface disease and keratouveitis. Despite long quiescent waiting periods before surgery and aggressive preoperative and postoperative maintenance therapy, visual improvement might be hindered by the inherent pathology associated with HZO. Nevertheless, with careful patient selection, reasonable visual improvement can be achieved. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.