Ocular Herpes Simplex Virus Disease Research Articles

Cataract surgery in herpes simplex virus ocular disease.

To investigate the outcomes and complications associated with cataract surgery in eyes with herpes simplex virus (HSV)-related anterior segment ocular disease. Public tertiary center in Auckland, New Zealand. Retrospective observational cohort study. Clinical records of patients diagnosed with HSV-related keratitis and/or anterior uveitis who underwent subsequent cataract surgery in the affected eye were reviewed. Main outcomes measured were visual outcome, complications, and recurrence. 37 eyes of 37 patients were included. Intraoperative complications occurred in 1 patient (2.7%) with iris prolapse. Keratitis or uveitis recurred postoperatively in 17 patients (45.9%) 8 patients (22.5%); 22.5% experienced recurrences in the first year postoperatively. 1 case (2.7%) of postoperative cystoid macular edema and 1 (2.7%) postoperative endophthalmitis occurred. Corrected distance visual acuity at 3 months was >20/50 in 21 patients (70.0%), 20/50 to 20/200 in 4 patients (12.9%), and ≤20/200 in 6 patients (19.4%). Vision improved in 26 eyes (83.9%) and worsened in only 1 eye (3.2%). Risk for recurrent inflammation was associated with a greater number of recurrences prior to surgery (hazard rate [HR] 1.31), time quiescent prior to surgery (HR 0.48), and iris transillumination defect at preoperative assessment (HR 57.66). Cataract surgery in eyes with previous HSV disease may improve visual acuity for most of the eyes but, overall, carries a guarded prognosis, particularly in eyes with corneal scarring. There is a significant risk for recurrent inflammation in the first year postoperatively. If possible, surgeons should ensure a period of disease quiescence prior to surgery.

Herpetic eye disease study: lessons learned.

Ophthalmic herpes simplex virus (HSV) of the anterior segment is responsible for a range of corneal complications such as scarring, thinning, neovascularization, and severe loss of vision. This review provides current guidelines for treating anterior segment disease related to HSV. We first review findings from the Herpetic Eye Disease Study (HEDS) clinical trials, and then review new topical and antiviral therapies developed since the HEDS studies. The development of vaccines to prevent recurrent episodes of herpetic infection is briefly reviewed. New corneal surgical procedures, developed since HEDS, may put patients at risk for ocular HSV disease: cross-linking and excimer refractive surgery. HEDS established the standard of HSV ocular therapy and is still valid today. However, newer antivirals may provide easier compliance with improved bioavailability, efficacy, dosage, and tolerability. Further research is needed to prevent latency of HSV, decrease recurrences, and more effectively treat necrotizing keratitis associated with HSV.

Association Between Atopy and Herpetic Eye Disease

Immune dysregulation in patients with atopy has been hypothesized to increase susceptibility to viral infections. Herpetic eye disease (due to herpes simplex and herpes zoster) is a significant cause of visual impairment, and data on an association between this sight-threatening disease and atopy are limited. To assess the association between atopy and herpetic eye disease, including herpes simplex virus (HSV) ocular disease and herpes zoster ophthalmicus (HZO). Retrospective, population-based case-control study from January 1, 2006, through December 31, 2007, at Kaiser Permanente Hawaii, a multispecialty managed care organization serving approximately 15% of the general Hawaiian population. Participants were 217,061 patients enrolled in the Kaiser Permanente Hawaii health plan during the study period. Clinical diagnosis of HSV ocular disease or HZO during the study period determined by an initial search of the electronic medical record of Kaiser Permanente Hawaii and then confirmed through individual medical record review by a uveitis and cornea fellowship-trained ophthalmologist. Atopic disease status was determined based on International Classification of Diseases, Ninth Revision codes for patients with HSV ocular disease or HZO and 2 control groups, each randomly selected at a 4:1 ratio of controls to cases. One hundred fourteen patients with HSV ocular disease and 137 patients with HZO were identified. Using the age- and sex-matched controls, patients who had atopy had a 2.6-fold (95% CI, 1.6-4.2; P < .001) higher odds of having HSV ocular disease compared with patients who did not have atopy. Similarly, patients with atopy had a 1.8-fold (95% CI, 1.2-2.8; P = .01) increased odds of having HZO. Patients with 2 or more atopic conditions had an 8.9-fold (95% CI, 3.5-22.6; P < .001) higher odds of having HSV ocular disease and a 2.9-fold (95% CI, 1.1-7.7; P = .04) higher odds of having HZO. AND RELEVANCE The association between atopy and herpetic eye disease may be explained by various factors, including immunologic dysfunction in patients with atopy. Clinically, these results could help support the diagnosis of herpetic eye disease in these patients.

Management of Herpes Simplex Virus Stromal Keratitis: An Evidence-based Review

Herpes simplex virus (HSV) stromal keratitis is a leading cause of corneal opacification and an important indication for penetrating keratoplasty. Based on several observational studies and clinical trials, the current standard of care includes topical corticosteroids and antivirals. However, corticosteroids have significant side effects, and antivirals are only beneficial if replicating virus is present. High-quality clinical trials investigating therapies for HSV stromal keratitis beyond corticosteroids and antivirals are lacking. Immune regulatory drugs, such as cyclosporine A, present attractive alternatives to managing HSV stromal keratitis, given the immune-mediated pathogenesis of stromal disease. Also, inhibiting viral reactivation in the latently infected ganglia through therapeutic vaccination will likely be the most efficient avenue to reduce recurrent HSV ocular disease. Our present aim is to review the current evidence-based treatment options for HSV stromal keratitis including and beyond the use of corticosteroids and antivirals and to cultivate insights into developing therapeutic vaccination strategies to inhibit HSV stromal keratitis recurrences.

Efficacy of Valacyclovir vs Acyclovir for the Prevention of Recurrent Herpes Simplex Virus Eye Disease: A Pilot Study

To compare the efficacy of one-year treatment with valacyclovir vs acyclovir in preventing recurrence of the herpes simplex virus (HSV) eye disease. Prospective, randomized, clinical trial pilot study. Fifty-two immunocompetent patients with a history of recurrent ocular HSV disease were treated at the Ocular Immunology Service, San Raffaele Hospital, Milan, Italy. Twenty-six patients were randomized to the valacyclovir group (one 500 mg tablet daily), and 26 patients were randomized to the acyclovir group (one 400 mg tablet twice daily). The recurrence rate of ocular HSV disease during 12 months of treatment and drug-related side effects were monitored. Recurrence of any type of ocular HSV disease during the 12-month treatment period was 23.1% in the valacyclovir group, compared with 23.1% in the acyclovir group. No difference between the two groups was observed regarding the nature, frequency, or severity of adverse events. The most frequent adverse events were nausea and headache. One-year suppression therapy with oral valacyclovir (500 mg tablet daily) was shown to be as effective and as well tolerated as acyclovir (400 mg tablet twice daily) in reducing the rate of recurrent ocular HSV disease.

Herpes Simplex Keratitis After Intravitreal Triamcinolone Acetonide

To report a case of recurrent herpes simplex virus (HSV) epithelial keratitis after intravitreal triamcinolone acetonide injection for the treatment of diabetic macular edema. Case report. We describe a case of a 59-year-old woman with a history of ocular HSV disease and severe proliferative diabetic retinopathy. She received an intravitreal injection of triamcinolone acetonide for macular edema in the right eye. One week later, she developed foreign body sensation, redness, and photophobia in the same eye. Slit-lamp examination revealed a corneal epithelial dendritic lesion. She was diagnosed with a recurrence of HSV epithelial keratitis and was treated with oral acyclovir 400 mg, 5 times a day, with good resolution of HSV signs and symptoms. Intravitreal triamcinolone acetonide injection may result in reactivation of HSV keratitis.

Atopic Disease and Herpes Simplex Eye Disease: A Population-Based Case-Control Study

To determine whether atopy is associated with herpes simplex virus (HSV) ocular disease. Retrospective, population-based, case-control study. Large, regional health maintenance organization (Northern California Kaiser Permanente). 1,042,351 people over a one-year period. Electronic database search for HSV ocular disease and subsequent chart review determined study eligibility. Two age-matched control groups (one population-based and one clinic-based) were randomly chosen. Medical record review determined the presence of atopy. Severe atopic disease was defined by diagnostic code or illness requiring an emergency room visit, hospitalization, or treatment with a systemic corticosteroid. Presence of HSV eye disease, presence of atopy, and characterization of atopy severity. HSV eye disease was found in 172 patients. HSV cases had a greater prevalence of atopy (34%, 58/172) than the clinic-based (25%, 43/172) or the population-based controls (21%, 36/172, odds ratio (OR) 1.5, 95% confidence interval (CI) 0.9 to 2.6 and OR 1.9, 95%, CI 1.1 to 3.3, respectively). The association of HSV ocular disease with severe atopy was even greater, with a history of severe atopic disease in 13% (22/172) of patients with HSV ocular disease as compared with 6% (11/172) of patients in the clinic control group and 3% (5/172) of patients in the population control group (OR 2.0, 95% CI 0.7 to 5.9 and OR 4.8, 95% CI 1.6 to 19.2, respectively). Patients with HSV ocular disease are more likely to have a history of atopic disease, especially severe atopic disease, than age-matched controls.

Monthly Recurrent Herpes Simplex Virus Blepharitis in a Boy for More Than 10 Years

Ocular herpes simplex virus (HSV) infection is generally accepted to be a unilateral disease and simultaneous bilateral recurrent ocular HSV disease is uncommon. Recurrent ocular herpes was generally thought to be characterized by corneal involvement. We here report an 11-year-old boy with monthly bilateral recurrent HSV type 1 blepharitis for more than 10 years. He had a general normal immunological examination. Only supportive or topical acyclovir ointment treatment proved adequate for controlling the monthly recurrent disease without corneal involvement or other sequelae to date. The case highlights the unusual presentation, general normal immune function, clinical course and treatment opinion for recurrent HSV blepharitis.

Recall bias in a prospective cohort study of acute time-varying exposures: Example from the herpetic eye disease study

Recall bias is possible in a prospective cohort study when exposure status is transient and must be periodically recalled, and ascertainment occurs after symptom onset. We know of no published demonstration of such bias at play in a prospective cohort study. In a substudy of a randomized clinical trial, 308 participants were prospectively followed to investigate potential acute triggers of ocular herpes simplex virus (HSV) recurrences. Participants reported on the presence of systemic infection or high psychological stress (exposures) on a home log that was completed weekly for up to 15 months and mailed to the study's coordinating centers. By protocol, exposure reporting was to occur on the last day of the week (Sunday) so that a prospective 1-week lag period between exposure and outcome in the following week could be assessed. The study outcome was development of a recurrence of ocular HSV disease documented by clinical examination. Using 35 weekly reports of exposure properly completed before the week of an outcome, there was no evidence of higher risk of HSV recurrence associated with systemic infection (rate ratio = 0.62, 95% confidence interval [CI]: 0.19–2.02) or high psychological stress rate (ratio = 0.0, 95% CI: 0.0–undefined). In contrast, when the analysis was based on 26 weekly reports of exposure improperly completed on or after the date of outcome, the risk of recurrence associated with systemic infection was estimated to be 4-fold (rate ratio = 4.07, 95% CI: 1.84–8.98), and there was a suggestion of a 2-fold risk associated with high psychological stress (rate ratio = 2.02, 95% CI: 0.69–5.91). Without real-time monitoring of exposure reporting, preservation of the temporal exposure–disease relationship—an implicit assumption of the prospective cohort study design—may be particularly tenuous when transient exposures are investigated longitudinally.

Predictors of Recurrent Herpes Simplex Virus Keratitis

Determinants of the natural history of recurrent herpes simplex virus (HSV) keratitis have not been consistently established. We assessed how previous HSV eye disease affects the risk of recurrent HSV keratitis and evaluated whether demographic and other variables play any predictive role. Three hundred forty-six patients in the placebo group of the Herpetic Eye Disease Study's Acyclovir Prevention Trial who had experienced an episode of HSV eye disease in the previous year were followed up for 18 months. Recurrences were categorized according to the type of involvement. Relative rates of recurrence were compared for categories of demographic variables, types and number of previous ocular HSV episodes, previous nonocular HSV infection, and month of the year. Fifty-eight (18%) of the 346 patients developed epithelial keratitis and 59 (18%) developed stromal keratitis during the 18 months of follow-up. Previous epithelial keratitis did not significantly affect the risk of epithelial keratitis (p = 0.84). In contrast, previous stromal keratitis increased the risk of stromal keratitis 10-fold (p < 0.001), and the risk was strongly related to the number of previous episodes (p < 0.001). Age, gender, ethnicity, and nonocular herpes were not significantly associated with recurrences, and no seasonal effects were observed. Among patients who experienced active ocular HSV disease in the previous year, a history of epithelial keratitis was not a risk factor for recurrent epithelial keratitis. In contrast, previous, especially multiple, episodes of stromal keratitis markedly increased the probability of subsequent stromal keratitis.

Oral acyclovir suppresses recurrent epithelial and stromal herpes simplex.

THE NEW ENGLAND JOURNAL OF MEDICINE Acyclovir for the Prevention of Recurrent Herpes Simplex Virus Eye Disease The Herpetic Eye Disease Study Group . Background: Long-term treatment with antiviral agents has been shown to prevent recurrences of genital and orofacial herpes simplex virus (HSV) disease, but it is uncertain whether prophylactic treatment can prevent recurrences of ocular HSV disease. Methods: We randomly assigned 703 immunocompetent patients who had had ocular HSV disease within the preceding year to receive 400 mg of acyclovir or placebo orally twice daily. The study outcomes were the rates of development of ocular or nonocular HSV disease during a 12-month treatment period and a 6-month observation period. Results: The cumulative probability of a recurrence of any type of ocular HSV disease during the 12-month treatment period was 19 percent in the acyclovir group and 32 percent in the placebo group (P Conclusions: After the resolution of ocular HSV disease, 12 months of treatment with acyclovir reduces the rate of recurrent ocular HSV disease and orofacial HSV disease. Long-term antiviral prophylaxis is most important for patients with a history of HSV stromal keratitis, since it can prevent additional episodes and potential loss of vision. Arch Ophthalmol 1998;279:1820-1825.

THERAPY OF HERPES SIMPLEX VIRAL KERATITIS

Herpes simplex virus (HSV) eye infections are a major cause of corneal opacity and visual loss in developed countries. The main goals of the treatment of HSV keratitis are: 1To eradicate the live virus 2To promote healing of corneal tissues 3To minimize the scarring resulting from the associated inflammation To decrease the chance for future recurrence The successful management of HSV keratitis depends on clinical recognition of the specific tissue layers involved and the various immune components of the keratitis. Modulation of HSV ocular disease relies upon the appropriate application of antiviral and anti-inflammatory medications.

A Comparison of Enzyme Immunoassay and Polymerase Chain Reaction with the Clinical Examination for Diagnosing Ocular Herpetic Disease

The results of two laboratory diagnostic herpes simplex virus (HSV) tests, an enzyme immunoassay (improved Herpchek [iHC]) and the polymerase chain reaction (PCR), were compared with the clinical examination in the diagnosis of HSV. We determined when diagnostic laboratory tests provided the initial diagnosis of HSV ocular disease and when they were only confirmatory. The sensitivity and specificity of iHC and PCR were determined using 22 HSV culture-positive clinical samples, 10 adenovirus culture-positive clinical samples, 5 samples from normal conjunctivas, 4 bacterial samples, and 1 sample containing Varicella zoster virus. The medical history of the 22 patients with positive HSV cultures were reviewed to determine the initial diagnosis by clinical examination and the initial therapy. For typical presentations of ocular HSV disease, the clinical examination is as accurate as iHC (P = 0.99) and PCR (P = 0.24). However, for atypical presentations of ocular HSV disease, iHC (P = 0.000005) or PCR (P = 0.00006) were more accurate in detecting HSV infection than the clinical examination. Laboratory diagnosis of HSV from ocular samples was most useful to the clinician in atypical presentations of herpetic ocular disease.

Ocular Infection with Herpes Simplex Virus (HSV-1) in Vitamin A-Deficient and Control Rats

An experimental model was developed for studying ocular infections with herpes simplex virus (HSV) type 1 in vitamin A-deficient (-A) and pair-fed control (+A) rats. The severity and course of the disease was evaluated by clinical examination, slit lamp biomicroscopy and histopathologic observations. Experimental animals were in good health and were infected in the early stages of vitamin deficiency (either prior to or at the beginning of the weight plateau). In all trials the onset of herpetic keratitis was more rapid and the clinical disease more severe in -A rats compared to +A controls. Mean slit lamp scores (which assessed the severity of the corneal disease) increased from 3 to 10 d after infection and were higher (P < 0.002) in -A rats at all time points and doses of virus tested. The inflammatory response in the cornea and uveal tract of -A rats was significantly higher than that of +A animals. Since ocular HSV disease is a common cause of blindness, the availability of a rat model should be valuable in studies of the role of nutritional factors in host susceptibility and response to viral challenge. Mild vitamin A deficiency increased the severity of experimental corneal HSV infections and resulted in a high incidence of epithelial ulceration and necrosis.