Treatment of ocular disease in eczema herpeticum

Individuals with atopic dermatitis are particularly susceptible to herpes simplex viral infection and may develop dissemination (eczema herpeticum). Additionally, they may develop severe and bilateral herpetic ocular disease. The keratitis is commonly complicated by stromal scarring and slow epithelial healing despite topical antiviral therapy. We treated three patients who had herpetic keratoconjunctivitis associated with eczema herpeticum. In all three cases the keratitis resolved promptly (48 to 72 hours) without residual scarring after treatment with systemic acyclovir and topical trifluridine. The combined use of systemic acyclovir and topical trifluridine may be of similar value in treating all cases of atopic herpetic keratitis.     

Oral acyclovir for the management of herpes simplex virus keratitis in children

PURPOSE: To evaluate the use of oral acyclovir in pediatric patients with herpes simplex virus (HSV) keratitis. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Seven pediatric patients seen at the University of Minnesota Hospitals and Clinics with herpes simplex virus (HSV) infectious epithelial keratitis between January 1992 and October 1998. Patient ages ranged from 6 weeks to 5 years at time of presentation with a median of 1.7 and mean of 1.9 years. INTERVENTION: All patients received oral acyclovir; six of seven patients also received topical antiviral medications. Three of seven patients had topical antiviral therapy fail before being placed on oral acyclovir, and the remaining four patients were placed on oral acyclovir primarily. RESULTS: All patients showed resolution of HSV infectious epithelial keratitis. Three patients have been maintained on prophylactic dosage of oral acyclovir because of recurrent disease or because they have been chronically treated with topical corticosteroids for immune stromal keratitis. All patients tolerated acyclovir well, and there were no adverse reactions. CONCLUSIONS: Oral acyclovir is useful in treating HSV infectious epithelial keratitis in pediatric patients. It is beneficial in treating infectious epithelial keratitis and prophylactically either while treating with topical corticosteroids for immune stromal keratitis or for preventing recurrent infectious epithelial keratitis.     

Dendritic keratitis caused by an acyclovir-resistant herpes simplex virus with frameshift mutation

PURPOSE: To report a case of acyclovir-resistant herpes simplex virus (HSV) keratitis after long-term, inconsistent use of topical acyclovir and fluorometholone. METHODS: A 70-year-old man with dendritic keratitis caused by an acyclovir-resistant HSV strain was examined. The 50% inhibitory concentration of different antiviral agents against the isolated virus and the DNA sequence of viral thymidine kinase were determined. RESULTS: The 50% inhibitory concentration of acyclovir and trifluorothymidine for the isolated HSV strain was 13.75 and 0.28 microg/mL, respectively, indicating that the virus was resistant to acyclovir. DNA sequencing of the viral thymidine kinase revealed that this virus had a frameshift mutant with a G insertion in the 7Gs homopolymer. Topical trifluorothymidine was effective, and the epithelial lesion was completely resolved within 2 weeks. CONCLUSION: A typical form of dendritic keratitis was caused by an acyclovir-resistant HSV with frameshift mutation in a 7Gs homopolymer region.     

Herpes simplex virus keratitis after laser in situ keratomileusis

PURPOSE: To report two cases of herpes simplex virus (HSV) keratitis after laser in situ keratomileusis (LASIK). METHODS: Interventional small case series. Two patients underwent uneventful LASIK. History of herpes labialis in one patient and herpetic eye disease > 10 years prior to intervention in the other patient was reported. Both patients developed stromal herpetic keratitis 6 weeks and 2 years after the procedure, respectively. RESULTS: Treatment consisting of topical steroid drops and topical and systemic antiviral therapy was administered. Recurrences of the herpetic keratitis were seen after tapering of the topical steroids; four and three recurrences were observed, respectively. Final visual acuity was > 6/9 in both cases. CONCLUSIONS: Herpetic keratitis after LASIK is an uncommon, possibly under-reported, entity. Even patients without history of herpetic eye disease can present with this complication. Oral antiviral prophylaxis may be appropriate when performing LASIK on patients with a history of ocular or systemic HSV infection.     

Immunoelectron microscopic localization of herpes simplex virus antigens in rabbit cornea with antihuman IgG-antiferritin hybrid antibodies.

Sheep antihuman IgG-antiferritin hybrid antibodies were used for the ultrastructural localization of herpes simplex virus (HSV) antigens in rabbit corneas from animals with herpetic keratitis. In animals with epithelial keratitis in which active viral replication is occurring (6 days after infection), viral antigen was found within nuclei, on nuclear membranes, and on cell surface membranes of epithelial cells. In animals with early necrotizing keratitis in which active viral replication cannot be demonstrated (14 to 21 days after infection), viral antigen was found in association with the cell surface of stromal keratocytes. Since lymphocytic cells in intimate contact with degenerating keratocytes have previously been identified in the cornea, these observations provide a basis for the view that cell-mediated immunopathogenesis is involved in the etiology of herpetic stromal keratitis.     

A comparison of local and systemic acyclovir in the management of herpetic disciform keratitis.

Forty-three patients with active herpetic disciform keratitis were entered into an open study to compare the efficacy of oral acyclovir (400 mg) with acyclovir ophthalmic ointment (3%) to inhibit viral replication during treatment with 0.05% prednisolone eye drops. All patients, regardless of the mode of therapy, were treated five times a day until they were healed. The mean time to heal in the oral group was 25.9 days and in the topical group was 25.3 days. Resolution of lacrimation was significantly faster in the oral group (12.1 days versus 27.6 days). The patients on tablets also showed a greater improvement in visual acuity. No statistically significant differences were found between the two groups in the incidence of recurrences over a three-year post-treatment period. It is concluded that oral acyclovir treatment is an effective alternative to ophthalmic ointment in the management of herpetic disciform keratitis.     

Evidence-based treatment of herpes simplex virus keratitis: a systematic review

Herpes simplex virus (HSV) keratitis is a common cause of ocular and visual morbidity. In this article, we systematically review published randomized clinical trials (RCTs) for HSV epithelial and stromal keratitis in order to establish a rational evidence-based foundation for treatment of these disorders. Articles for review were identified in the MEDLINE database from January 1, 1966, to May 30, 2006. Our review criteria stipulated that each study be performed in prospective, randomized, and double-blinded fashion, that it be controlled, and that it rely on specific clinical criteria for diagnosis and outcome. Of articles thus identified in the English language press, 38 articles met our review criteria, 30 for HSV epithelial keratitis and 8 (comprising 7 RCTs) for HSV stromal keratitis. From these studies, we concluded that the best evidence from treatment trials on HSV epithelial keratitis supports the use of topical trifluridine and topical or oral acyclovir, and suggests a possible additional benefit for topical interferon. The best evidence from RCTs for HSV stromal keratitis supports the use of topical corticosteroids given together with a prophylactic antiviral to shorten the duration of active HSV stromal keratitis, and the use of long-term suppressive oral acyclovir therapy to reduce the incidence of recurrent HSV keratitis.     

Evaluation of 80 virologically-confirmed cases of ocular herpes. Study of the correlation between the type of virus and the epidemiologic characteristics of the disease

80 strains were isolated from patients with herpetic ocular infection during the period May 1979 to May 1981: 17 patients with herpetic blepharitis, 40 patients with superficial keratitis and 23 with deep stromal keratitis or kerato-uveitis. Among 63 patients treated with antiviral agents, clinical resistance to the drug was observed in 17 cases. The strains were typed as HSV 1.1, 1.2 or 2.2 by seroneutralization and thermosensitivity in cellular cultures. No relationship between the viral types and the patient age, previous history of corticosteroid therapy and the response of ocular lesions to antiviral treatment were detected. It appeared that there was a relationship between the viral type and the clinical type of infection: 70% of herpetic blepharitis and 83% of superficial keratitis were due to HSV 1.1 while 71% of stromal keratitis were due to HSV 1.2. No HSV 2.2 was isolated. These results seem to support the hypothesis that genetic differences between herpetic virus strains may determine their virulence.     

In Vivo Observations and Electron Microscopy of Treatment of Experimental HSV Keratitis with Anti-HSV Monoclonal Antibodies

Purpose: To study the antiviral activity of monoclonal antibodies (McAb) in vivo and identify their effects on experimental herpetic keratitis.Methods: Topical use of anti-HSV monoclonal glycoprotein antibodies was carried out on acute herpetic keratitis of rabbits infected by HSV-1 SM44. The application of the eye drops in each group was five times per day for 14 days by double-blind method. In vivo observation and electron microscopy were performed during the whole procedure. The anti-HSV McAb's solution was mixed up of five monoclonal antibodies with high neutrilization titers and/or high ADCC activity. Results: Compared with placebo-treated eyes, anti-HSV McAb treatment made statistically significant reduction of herpetic corneal epithelial lesion on rabbits from day 3 to day 14 postinnoculation (P<0. 01). Punctate and short dendritic lesion were the main patterns. The area of involvement was also limited. Electron microscopic analysis showed ultrastructural changes of herpetic corneal infection. Th     

Acyclovir therapy in prevention of recurrent herpetic keratitis following penetrating keratoplasty

PURPOSE: To compare systemic vs topical acyclovir therapy for the prevention of recurrence of herpetic keratitis following penetrating keratoplasty (PK). DESIGN: A retrospective observational study. METHODS: Patients who underwent PK for herpetic eye disease (HED) and prophylactically received acyclovir therapy postoperatively, either systemically (26 eyes) or topically (29 eyes), were analyzed. The main parameters evaluated were recurrence of herpetic keratitis, graft rejection, visual acuity, and graft survival rate. RESULTS: Mean average follow-up period was 24.7 +/- 3.6 months and 23.5 +/- 2.3 months in the systemic and topical group, respectively (P = 0.73). The average duration of prophylactic antiviral therapy in systemic group was 16.1 +/- 4.8 months and in topical group was 15.1 +/- 3.5 months (P = .59). Recurrence of herpetic keratitis was seen in 12% in the systemic group compared to 55% in the topical group (P < .001). More eyes in topical group 15 (52%) had rejection episodes than in the systemic group 5 (19%) (P < .001). A best-corrected visual acuity of > or = 20/40 was achieved in 31% and 7% eyes in the systemic and topical group, respectively, at the end of two years (P = .002). The clear graft survival rate in the systemic and topical acyclovir receiving group was 96.2% vs 86.2% at 12 months, and 88.5% vs 65.5% at 24 months, respectively. CONCLUSION: Systemic acyclovir is more effective than topical acyclovir in achieving better graft outcomes after PK for HED.