Herpes Simplex Virus Eye Disease Research Articles

Potential effect of decreased levels of folic acid and vitamin B12 on herpes simplex virus keratitis reactivation

Background/Aim. Most cases of herpetic keratitis present a recurrent disease as a result of herpes simplex virus type 1 reactivation from latency in the nearest sensory ganglia. Therefore, understanding the mechanisms of latency and reactivation of the latent virus is an important link in comprehending the onset of the recurrent eye disease itself. Epigenetic regulation of virus reactivation, as a result of the presence of transcriptionally active Latency-Associated Transcript (LAT) region in the latent viral genome, has already been demonstrated in several studies. The activity of the LAT region is directed to the chromatin arrangement. Epigenetic modulation of DNA methylation is associated with folate and vitamin B12 intake or their serum concentrations. To our knowledge, there is no report on the potential role of vitamin B12 and folic acid in herpes simplex virus keratitis reactivation. The aim of this study was to analyze the potential role of folic acid and vitamin B12 in the control of ocular herpes simplex keratitis reactivation. Methods. The study included 50 patients older than 18 years of age with recurrent herpes simplex virus eye disease. Levels of vitamin B12 and folic acid were measured in the acute phase of the disease. All patients were followed up for at least one year and episodes of recurrent herpetic eye diseases were recorded. Results. The recurrence rate of herpetic keratitis was statisticall significantly lower in patients with a higher blood level of vitamin B12. In addition, the recurrence rate of herpetic keratitis was lower in patients with a higher blood level of folic acid. However, statistical significance was lower in comparison with that for vitamin B12. Conclusion. The decreased levels of vitamin B12 and folic acid might have a vital role in herpes simplex keratitis reactivation.

Case-Control Study of Herpes Simplex Eye Disease: Bronx Epidemiology of Human Immunodeficiency Virus Eye Studies.

To determine whether human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS), diabetes mellitus, and atopic disease are associated with herpes simplex virus (HSV) eye disease and to examine the characteristics of patients with HIV infection and HSV eye disease. Retrospective case-control study. A hospital-based control group was matched to outpatient visits from June 1, 2010, through May 31, 2014, at Montefiore Medical Center (Bronx, NY). Inclusion criteria were a diagnosis of HSV eye disease during the study period and residency in the Bronx. Associations evaluated included age, sex, HIV/AIDS, diabetes mellitus, and atopic disease. HSV eye disease was confirmed in 70 patients, who were compared with 280 controls. Patients with ocular HSV had a greater prevalence of HIV/AIDS compared with controls (8.6% and 2.9%, respectively). Using multivariate analysis to control for age and sex, atopic dermatitis [odds ratio (OR) 3.08, 95% confidence interval (CI), 0.84-11.20] and diabetes with chronic complications (OR 2.25, 95% CI, 0.91-5.61) approached significance, whereas HIV/AIDS (OR 3.37, 95% CI, 1.09-10.40), an age less than 45 years (OR 2.89, 95% CI, 1.54-5.41), and male sex (OR 1.85, 95% CI, 1.07-3.18) were significant. In patients with HIV infection and HSV eye disease, 3 of 6 (50%) had confirmed AIDS at the time of ocular HSV diagnosis. Patients with HIV infection have more than a 3-fold increased risk of developing ocular HSV.

Management of patients with herpes simplex virus eye disease having cataract surgery in the United Kingdom

To standardize the management of patients with herpetic eye disease scheduled for cataract surgery, a questionnaire was sent to each fellow of the Royal College of Ophthalmologists registered as a consultant with a subspecialty interest in cornea. Most respondents agreed that disease stability was required before cataract surgery was offered; 62.3% would operate on patients in whom the disease had been quiescent for 3 to 6 months. The decision to prescribe prophylactic antivirals divided the respondents, with 58.8% in favor of starting antiviral treatment. Most respondents (72.46%) did not start topical antiviral treatment. In regard to changing topical steroid use postoperatively, 80.9% would not change their routine regimen. Oral acyclovir was the first line of treatment for 92.5%. The conclusions were that a significant period of inactivity should be considered before cataract surgery is performed in patients with herpes simplex virus eye disease. Oral antiviral prophylaxis is common clinical practice, but no change in routine postoperative steroid use is needed.

Incidence, Recurrence, and Outcomes of Herpes Simplex Virus Eye Disease in Olmsted County, Minnesota, 1976-2007

To provide an estimate of the incidence of herpes simplex virus (HSV) eye disease in a community-based cohort, and to investigate the effect of prophylactic oral antiviral therapy on HSV recurrences and outcomes. All Olmsted County, Minnesota, residents diagnosed with ocular HSV from 1976 through 2007 were retrospectively reviewed. The frequency of recurrences and adverse outcomes, such as vision loss or need for surgery, were compared between untreated patients and those treated prophylactically with oral antiviral medication. Three hundred ninety-four patients with ocular HSV were identified, yielding an annual incidence of 11.8 per 100,000 people (95% confidence interval [CI], 10.6-13.0). No trends in incidence or adverse outcomes were identified during the 32-year period. Oral antiviral therapy was prescribed in 175 patients. Patients were 9.4 times more likely (95% CI, 5.0-17.9) to have a recurrence of epithelial keratitis, 8.4 times more likely (95% CI, 5.2-13.7) to have a recurrence of stromal keratitis, and 34.5 times more likely (95% CI, 10.8-111.1) to have a recurrence of blepharitis or conjunctivitis if not being treated prophylactically at the time of the recurrence. Twenty patients experienced adverse outcomes, and 17 (85%) were not being treated with oral antiviral medications immediately preceding the adverse event. Oral antiviral prophylaxis was associated with a decreased risk of recurrence of epithelial keratitis, stromal keratitis, conjunctivitis, and blepharitis due to HSV. Patients with adverse outcomes due to ocular HSV were usually not being treated with oral antiviral prophylaxis.

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

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

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.

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.

Prophylaxis of herpesvirus infections in immunocompetent and immunocompromised older patients.

In older patients, prophylaxis of herpesvirus infections mainly involves preventing the recurrence of herpes simplex virus (HSV) and complications of herpes zoster in immunocompetent patients, while in immunocompromised patients it is more concerned with the prevention of opportunistic virus reactivation. HSV ocular infection is the most frequent cause of corneal blindness in the US. The effectiveness of aciclovir 400mg twice daily in preventing the recurrence of HSV eye disease in immunocompetent patients has been well demonstrated. The issue of treatment duration for patients with highly recurrent ocular herpes remains unresolved. Post-herpetic neuralgia (PHN) is one of the most common neuralgic illnesses worldwide. Some progress in prevention of PHN has been made with a combination of antiviral therapy (famciclovir or valaciclovir), started within 72 hours of onset of the rash, and analgesic treatment. However, the best prevention of PHN is the prevention of herpes zoster disease, and the varicella vaccine is an option which over the next few years will be tested in clinical trials. For immunocompromised patients of any age, restoring immunity prevents herpesvirus disease, as demonstrated for cytomegalovirus (CMV) in AIDS patients receiving highly active antiretroviral therapy. Specific antiviral therapy during the initial period after transplantation could prevent reactivation of HSV or CMV in seropositive recipients. Whether pre-emptive therapy or prophylaxis with ganciclovir is the optimal approach against CMV remains controversial, and the relative merits and limitations of each approach may guide the choice. In stem cell transplantation, pre-emptive therapy with foscarnet avoids the neutropenia and related complications associated with ganciclovir. In renal transplant recipients, universal prophylaxis of CMV infection with valaciclovir has the same efficacy as ganciclovir. Although it is relatively toxic, cidofovir should be further evaluated because of its in vitro activity against most DNA viruses.

Valacyclovir for the prevention of recurrent herpes simplex virus eye disease after excimer laser photokeratectomy

A variety of factors have been reported as inducing the reactivation of latent herpes simplex virus (HSV), among them stress, trauma, and UV radiation. Excimer laser photorefractive keratectomy (PRK) is a surgical procedure utilizing a 193 nm ultraviolet light to alter the curvature of the cornea and hence correct vision. Reactivation of ocular herpes simplex keratitis following such excimer laser PRK has been reported. All published cases of HSV reactivation following excimer laser treatment in humans are reviewed. The present study evaluates whether stress, trauma of the corneal de-epithelialization prior to the laser, or the excimer laser treatment itself to the stromal bed induces this ocular reactivation of the latent HSV, and whether a systemic antiviral agent, valacyclovir, would prevent such laser PRK-induced reactivation of the HSV.Forty-three normal 1.5- to 2.5-kg New Zealand white rabbits were infected on the surface of the cornea with HSV-1, strain RE. The animals were monitored until resolution, and then all animals were divided into 5 treatment groups: (1) de-epithelialization only, intraperitoneal (i.p.) saline for 14 days; (2) de-epithelialization plus laser, i.p. saline for 14 days; (3) de-epithelialization plus laser, valacyclovir 50 mg/kg per day i.p. for 14 days; (4) de-epithelialization plus laser, valacyclovir 100 mg/kg per day i.p. for 14 days; (5) de-epithelialization plus laser, valacyclovir 150 mg/kg per day i.p. for 14 days. Animals were evaluated in a masked fashion by clinical examination biweekly and viral cultures biweekly through day 28.The reactivation rates were as follows: group 1, 0%; group 2, 67%; group 3, 50%; group 4, 17%; and group 5, 0%. Viral titers were negative in animals that had no reactivation but persistently positive in those that had reactivation (day 6 through day 28).Excimer laser (193 nm) treatment can trigger reactivation of ocular herpes disease (67%) and viral shedding in the latently infected rabbit. De-epithelialization alone is not sufficient to cause reactivation or viral shedding. Prophylaxis with intraperitoneal valacyclovir decreases the recurrence rate in a dose-response fashion. At 150 mg/kg per day, there are no recurrences. The presence of persistent viral shedding in reactivated animals may correlate with cases of late HSV recurrence reported in humans undergoing excimer treatment. The data suggest that humans undergoing excimer laser procedures for correction of refractive errors or treatment of corneal scars with a history of herpetic keratitis are at increased risk for reactivation. Such patients, however, may appropriately be considered for prophylactic systemic antiviral medication at the time of the laser procedure in order to decrease the possibility of recurrence.

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.