[Clinical assessment of oral ganciclovir capsules on the treatment of herpes simplex keratitis].

OBJECTIVE: To evaluate the clinical values of oral ganciclovir on the treatment of herpes simplex keratitis (HSK). METHODS: A randomized, controlled, single-blind and prospective study was carried out from May in 2008 to June in 2009 at Department of Ophthalmology, Eye Ear Nose and Throat Hospital of Fudan University. 60 patients (60 eyes) with HSK, including stromal keratitis and corneal endotheliitis, were enrolled in the study and were randomly arranged into two groups in average. Oral ganciclovir was orally administered 1000 mg 3 times per day for 8 weeks, 0.15% ganciclovir ophthalmic gel, 4 times per day, and 0.1% fluorometholone eye drops, 3 times per day, in the test group, meanwhile, the control group was adopted the same ophthalmic gel and eye drops without the oral capsules. The symptoms and signs were evaluated before and after the therapy 1st week, 2nd week, 4th week, 6th week and 8th day respectively with the side effects observed. RESULTS: There was no significant difference between the control and test group in the mean scores of symptoms (control 10.70 ± 3.61, test 11.87 ± 3.47) and signs (control 13.83 ± 3.74, test 15.27 ± 3.83) respectively before the treatment (Z = -1.269 and -1.419; P > 0.05). After the administration, the total scores of symptoms and signs in the test group were 8.37 ± 4.31, 2.70 ± 2.65, 0.70 ± 1.44, 0.33 ± 0.92 and 0.17 ± 0.65 respectively at each follow-up time point, which were obviously lower than those in the control group, 13.63 ± 7.64, 10.53 ± 7.18, 7.83 ± 6.49, 5.37 ± 5.33 and 4.37 ± 5.11 respectively (Z = -2.801, -4.895, -5.260, -4.758, and -4.292; P < 0. 05). The efficacy rates in the test group were all 100.0% after the administration, but those in the control group were 50.0%, 73.3%, 86.7%, 93.3% and 96.6%. Furthermore, the cure rates in the test group were 0.0%, 36.7%, 76.7%, 90.0% and 93.3% respectively at each follow-up time point, which were significantly higher than those in the control group with 0.0%, 3.3%, 16.7%, 30.0% and 43.3% respectively (χ(2) = 20.00, 16.433, 22.571, 22.636 and 17.330; P < 0. 001). There was no obvious discomfortableness and adverse reaction observed in the test group. Unfortunately, 5 patients in the control group and 3 patients in the test group underwent the recurrence of HSK after the course of treatment, but there was no significant difference between the groups in the recurrence rate. CONCLUSIONS: Oral ganciclovir can effectively assist to relieve the symptoms and signs and shorten the pathogenesis of herpes simplex stromal keratitis and corneal endotheliitis. And short-term oral ganciclovir has confirmed good safety.

Increased risk for herpetic eye disease in patients with allergic conjunctivitis.

PURPOSE: To evaluate the risk of ocular surface herpetic eye disease (osHED) in allergic eye disease. METHODS: We calculated the risk for osHED in 11,205 patients on antiallergic ocular topical agents compared with 453,069 controls based on filled prescriptions for topical acyclovir between 2001 and 2003. RESULTS: Significantly more allergic patients, of all age groups, received treatment for osHED (p < 0.01). The age and gender adjusted relative risk for allergic patients to suffer an osHED event was 2.31 (95% CI: 1.84-2.90), raising to 3.55 (95% CI: 2.0-6.4) in patients that filled > or = 4 antiallergic prescriptions. CONCLUSIONS: Patients treated for allergic eye disease have an increased risk of osHED.

Herpetic eye disease in diabetic patients.

PURPOSE: To study the incidence of herpetic eye disease (HED) of the ocular surface in diabetics. DESIGN: Observational historical cohort study. SETTING: A district of the largest health maintenance organization in Israel (the Central District of Clalit Health Services). PARTICIPANTS: We reviewed the electronic medical records of all patients older than 50 years (159634 patients) in the district, and of these, 22382 (14.0%) patients had diabetes mellitus. METHODS: All filled prescriptions for acyclovir eye ointment between January 1, 2001 and December 31, 2003 (1483 tubes) and all hemoglobin A1c laboratory tests during 2003 (41910 tests) were documented. An ocular surface HED event was defined when a patient consumed at least 1 tube of topical acyclovir per month, whereas no acyclovir use was documented 3 months before and 3 months after that event. MAIN OUTCOME MEASURES: Incidence of ocular surface HED events in diabetics compared with nondiabetics adjusted for age and gender. RESULTS: After age and gender adjustment, significantly more diabetics had ocular surface HED (5.21 per thousand) compared with nondiabetics (4.27 per thousand; P<0.0001). Stratification by age revealed a significantly higher prevalence of HED in diabetics, aged 60 to 79 years. Recurrent herpetic events occurred during the study period in 25.2% of HED-affected diabetics, and in 16.6% of HED-affected nondiabetics (P = 0.05). Diabetics with poor glycemic control (mean annual hemoglobin A1c > 9%) consumed significantly more ocular acyclovir (P = 0.01). Multivariate analysis revealed this effect to be independent of age, gender, place of birth, or place of residency. CONCLUSIONS: Ocular surface HED is significantly more common among patients with diabetes mellitus. Poor glycemic control correlates with increased consumption of ocular acyclovir in diabetic patients.

PCR assessment of HSV-1 corneal infection in animals treated with rose bengal and lissamine green B.

PURPOSE: In vivo, the ophthalmic dye rose bengal displays profound antiviral effects against herpes simplex virus (HSV)-1, thus limiting its utility in diagnosis of epithelial keratitis when used before viral culture is performed. In contrast, lissamine green B does not possess significant antiviral activity in vivo. To determine whether polymerase chain reaction (PCR) could successfully detect HSV-1 DNA in ocular samples that have been exposed to ophthalmic dyes, animal models were used to observe the presence of infectious HSV-1 and viral DNA in eyes treated with rose bengal or lissamine green B. METHODS: Animals were bilaterally infected with HSV-1 strain H129, and at daily intervals up to 16 days post infection (dpi) rose bengal or lissamine green B was instilled in the left eyes. The right eyes were not treated with dyes. Swabs of the dye-treated and untreated eyes were assayed by PCR for viral infectivity by culture and the presence of DNA specific for a fragment of the HSV-1 DNA polymerase gene. RESULTS: A statistically equivalent number of samples from lissamine green B-treated and untreated eyes were positive by both viral culture and PCR. In contrast, rose bengal significantly decreased the infectious virus present in ocular secretions. A total of 44% and 78% of the rose bengal-treated and untreated eye samples, respectively, were positive by culture from 1 through 16 dpi. PCR was more sensitive than culture for detection of HSV-1 in rose bengal-treated eyes, in that 74% of rose bengal-treated samples were positive by PCR compared with 44% that were positive by culture during the 16-day period studied. It was also noted that both rose bengal and lissamine green B treatments slightly prolonged the period during which viral DNA was detectable in ocular secretions by PCR, possibly because the singlet oxygen produced by these photoreactive dyes compromised ocular cellular, humoral, and nonspecific immune factors allowing viral DNA to persist for slightly longer periods. CONCLUSIONS: PCR can successfully detect HSV-1 DNA in ocular samples that are culture negative and contain rose bengal or lissamine green B. Visualization of ocular epithelial defects with lissamine green B does not interfere with detection of infectious virus or HSV-1 DNA.

Assessment trials of the therapeutic efficacy of the drug "Zovirax" in some recurrent ocular and genital herpetic infections.

In this work are reported the results of the researches performed by the authors more than a decade ago, aimed at assessing the clinical benefit of the introduction of the drug "Zovirax" in the treatment of recurrent herpetic infections with genital or ocular location. The results of the treatment carried out on a restricted group of patients were positive both in cases of genital herpes and of herpetic keratitis. The clinical benefit consisted in the reduction of the mean duration of the disease, in the shortening of the period of the infective virus elimination from the lesion, as well as in the decrease of the intensity and duration of the clinical symptomatology as a whole. With respect to these clinical parameters, the observations of the authors performed on a low number of cases are consistent with the data obtained by other authors in the framework of more extensive studies. The renewed discussion of these clinical and laboratory observations carried out by the authors during the first years after the introduction in our country of this drug in the therapeutic arsenal of herpetic infections is aimed at establishing a landmark for the comparison with more recent results of similar studies, starting from the idea of the opportunity of assessing periodically the sensitivity of herpes simplex virus strains, circulating among the autochthonous population, to the inhibitory action of some antiviral drugs. In other words, the in vitro testing of the susceptibility of these strains to the chemotherapeutic agents in current use is predictive for the efficacy degree of these drugs in the treatment of some forms of herpetic infections. This evaluation represents at the same time, undoubtedly, a useful epidemiological surveillance means of the circulation of human herpes viruses among the population. We refer especially to the risk of appearance of pharmacoresistant mutants, a risk possible under the conditions of the increased access of patients to the antiviral chemotherapeutic medication, which implicitly augments the probability of a fortuitous administration of treatments insufficient as regards the dose or the duration. In this work there are also shown the results regarding some experimental aspects related to the immune control mechanisms of the herpetic infection, which may complement the chemotherapeutic action. Under the treatment with acycloguanosine the synthesis of herpetic antigens is kept at a level sufficient for the circulating antibody synthesis induction and the HSV infected cells treated with the drug are recognized and lysed by effectors of the cell-mediated immune response of the host. Hence, it may be asserted that, in some clinical cases of recurrent herpes with frequent episodes, it is useful to perform immunostimulating treatments, able to potentiate the cell-mediated immune mechanisms possibly involved in the limitation of the herpetic infection at the peripheral level and of its spreading in the central nervous system.

Assessment of antiviral activity, efficacy, and toxicity of prostaglandin A2 in a rabbit model of herpetic keratitis.

Prostaglandin A2 (PGA2) inhibited the replication of herpes simplex virus type 1 in rabbit and human cornea stromal cells at concentrations of 1 to 5 microM while causing significant toxicity at 55 to 150 microM. Despite favorable therapeutic indices in cultured cells, PGA2 was not effective as a therapeutic agent in the treatment of herpetic keratitis in a rabbit model. The sequelae of disease appeared more severe in animals receiving PGA2 than in untreated or placebo-treated controls. The recovery of virus from tissues of latently infected rabbits was not affected by therapy. PGA2 therapy alone induced breakdown of the blood-aqueous barrier, indicating that pharmacologically active concentrations of drug were achieved in the eye. Thus, PGA2 had antiviral activity, but its proinflammatory effects appeared to be more detrimental than beneficial in the treatment of herpetic keratitis.