Herpes Simplex DNA in Tears of Atypical Dendritic Keratitis and Multiple Punctate Subepithelial Stromal Opacity: A Case Report.

PURPOSE: To report an atypical presentation of herpes simplex virus (HSV) keratitis followed up using expression levels of HSV DNA in tears. METHODS: A 22-year-old Japanese woman with hyperemia and foreign body sensation in her left eye was diagnosed with atypical dendritic keratitis. A slit-lamp examination at presentation indicated the presence of a rush of dendritic lesions with a sparse branching pattern and poor development of terminal bulbs; follicular conjunctivitis was also observed. Positivity for house-dust-mite- and cedar pollen-specific IgE antibodies in her serum indicated atopic diathesis. The HSV DNA levels in her tears were measured by a real-time polymerase chain reaction. RESULTS: At the initial visit, the HSV DNA levels in tears were 6.4 × 10 copies/sample in the right eye and 1.6 × 10 copies/sample in the left eye. The keratitis improved after treatment with topical acyclovir ointment, 5 times a day for 7 days, and systemic valacyclovir 1000 mg/d for 5 days. Multiple punctate subepithelial opacities developed in her left eye on day 7, with undetectable HSV DNA in tears, bilaterally. CONCLUSIONS: We have successfully monitored the HSV DNA levels in tears using quantitative real-time polymerase chain reaction in HSV keratitis where the corneal findings progressed from atypical dendritic keratitis to multiple punctate corneal subepithelial opacities during the treatment period.

[Diagnostics and management of herpes zoster ophthalmicus]. / Diagnostik und Management des Herpes zoster ophthalmicus.

Herpes zoster (HZ, shingles) represents the secondary manifestation of an infection with varicellazoster virus (VZV). A reactivation of dormant VZV in the ophthalmic branch of the fifth cranial nerve leads to ophthalmic HZ (HZO). The predominantly older and immune compromised patients often present with eye involvement (approximately 50%) as well as characteristic skin changes. Clinical manifestations include the cornea and conjunctiva but anterior uveitis and (rarely) acute retinal necrosis may also occur. Associated sensory symptoms that range from paresthesia to severe pain may severely affect the quality of life. Particularly in immunocompromised and/or elderly patients, HZO is associated with complicated courses. Systemic antiviral treatment and an adequate pain medication are the mainstay of the recommended management. The present article provides an overview of the contents of the current consensus-based European guidelines on the management of HZ with a specific focus on HZO.

Herpes Simplex Virus Disease of the Anterior Segment in Children.

PURPOSE: To analyze the clinical presentation, characteristics, treatment, recurrences, and final outcomes and complications of herpes simplex virus (HSV) disease of the anterior segment in patients aged 17 years or younger. METHODS: This is an observational and retrospective study with review of the medical records of all the children diagnosed with herpes simplex infection of the anterior segment at an ophthalmologic referral center, from 2002 to 2012. The diagnosis was made on the basis of the history and examination of patients and in specific cases by viral culture and the polymerase chain reaction. Main outcome measurements included final visual acuity, bilateral disease, and recurrence. Recurrent disease was analyzed with Kaplan-Meier curves. RESULTS: A total of 103 patients were included with a median age at presentation of 9 years. Of them, 6 had bilateral and simultaneous disease. The median follow-up time was 18 months (range, 18 days-12 years). The most common clinical manifestations were epithelial dendritic keratitis in 42 eyes (38.5%) and interstitial keratitis in 39 eyes (35.7%), with 15 patients presenting multiple forms of HSV disease. The median final visual acuity in the group of patients was 20/40. Recurrent disease was evident in 42 (38.5%) of the eyes, with a median recurrence time of 15 months (95% confidence interval, 8.1-26.2 months). CONCLUSIONS: In this study, epithelial dendritic and interstitial keratitis were the most frequent forms of disease in the pediatric population with HSV of the anterior segment. A high rate of recurrent disease was present.

Treatment of pseudodendrites in herpes zoster ophthalmicus with topical ganciclovir 0.15% gel.

PURPOSE: There is no standard of treatment for epithelial pseudodendrites in herpes zoster ophthalmicus (HZO). The purpose of this study is to report the topical antiviral drug, 0.15% ganciclovir for treatment of these lesions. METHODS: This is a retrospective, interventional case series of 4 patients who were diagnosed with HZO epithelial pseudodendrites despite being given oral antiviral treatment and who underwent 0.15% ganciclovir gel topical treatment. Main outcome measures included epithelial healing time, visual acuity, and corneal sensation. RESULTS: All 4 patients were immunocompetent and had epithelial lesions unresponsive to antiviral treatment with oral valacyclovir. Treatment with topical 0.15% ganciclovir gel 5 times a day resulted in the lesions healing successfully within 7 days with improved visual acuity in 3 patients and an increase in corneal sensation in 2 of the 4 patients. CONCLUSIONS: Topical 0.15% ganciclovir gel, 5 times a day until pseudodendritic lesion healing and tapering to bid for 2 to 4 weeks thereafter, is an effective treatment for pseudodendrites in HZO-affected cases that are often a challenge to manage with other oral or topical antivirals.

Ganciclovir ophthalmic gel 0.15%: in acute herpetic keratitis (dendritic ulcers).

Dendritic epithelial keratitis is most commonly caused by infections of herpes simplex virus (HSV) type 1 (HSV-1), and less frequently by HSV type 2 (HSV-2). Ganciclovir, a guanosine nucleoside analogue, is a well established broad-spectrum antiviral agent that inhibits replication of viral DNA and is active against both HSV-1 and -2 and several other viruses. Ganciclovir ophthalmic gel 0.15% is a five-times-daily topical preparation that is indicated for the treatment of acute herpetic keratitis (dendritic ulcers). A randomized, open-label, phase III trial in immunocompetent patients with acute herpetic keratitis showed that ganciclovir ophthalmic gel 0.15% applied five times daily provided effective clinical resolution of dendritic ulcers following 7 days of treatment (primary endpoint). Moreover, a retrospective analysis of noninferiority showed that ganciclovir ophthalmic gel 0.15% was no less effective than aciclovir (acyclovir) ointment 3%. A pooled analysis of three randomized, single-masked, phase II multinational trials also showed high rates of dendritic ulcer healing at day 7 for eyes treated with ganciclovir ophthalmic gel 0.15% and aciclovir ointment 3%. Furthermore, in the individual phase II trials, most patients showed evidence of healed dendritic and geographic ulcers at day 14 in either treatment arm. Median healing times with either treatment ranged from 6 to 10 days. Ganciclovir ophthalmic gel 0.15% was generally well tolerated and was associated with a significantly lower incidence of visual disturbances than aciclovir ointment 3% in the phase III trial.

Late varicella-zoster virus dendriform keratitis in patients with histories of herpes zoster ophthalmicus.

PURPOSE: To describe the characteristics and course of late varicella-zoster virus (VZV) dendriform keratitis in patients with histories of herpes zoster ophthalmicus (HZO); to describe responses of corneal lesions to antiviral treatment; and to investigate risk factors for recurrence. DESIGN: Retrospective case series. METHODS: Included were patients known to have 1 or more episodes of dendriform lesions beginning at least 2 weeks after HZO in 2 academic practices. Epithelial lesions were evaluated for the presence of VZV DNA by a polymerase chain reaction assay. Demographic, medical, and ophthalmic data were collected for each episode. Responses to treatment with antiviral medications were evaluated. Cumulative risk of recurrence was determined using Kaplan-Meier analysis; potential risk factors for recurrence (age, systemic disease, lesion characteristics, corticosteroids) were evaluated using univariate Cox proportional hazard models. RESULTS: We identified 20 patients (14 women; median age, 65 years) who met inclusion criteria. Dendriform lesions were pleomorphic with thickened, opaque epithelium. Seven patients had systemic diseases characterized by altered immune function. VZV DNA was identified in 15 of 16 cases tested, and all lesions responded to antiviral therapy. The 1-year incidence of first recurrence was 95.8 lesions per 100 person-years of follow-up. Patients had multiple recurrences, but risk of recurrence appeared to decrease over time. No statistically significant risk factors for recurrence were identified. CONCLUSIONS: Late dendriform lesions associated with HZO are foci of productive VZV infection. Lesions can be treated effectively with topical or systemic antiviral agents. Patients can have multiple recurrences of dendriform lesions despite treatment.

Case of bilateral multiple herpetic epithelial keratitis manifested as dendriform epithelial edema during primary Kaposi's varicelliform eruption.

BACKGROUND: Bilateral herpetic keratitis has been reported in patients with atopy, measles, graft-versus-host disease, and altered immune status. We report a serologically verified case of primary, simultaneous onset, bilateral, atypical epithelial herpetic keratitis that manifested as dendriform epithelial edema during a generalized dermatitis incident. CASE: A 37-year-old man with chronic atopic dermatitis developed Kaposi's varicelliform eruption and bilateral dendritic epithelial keratitis with corneal epithelial edema. OBSERVATIONS: The pathogens isolated from both eyes were identified as herpes simplex virus type 1 (HSV-1) by a direct immunofluorescence method. Serological tests obtained on three different occasions over a 5-week period verified a primary HSV infection. CONCLUSIONS: With serological verification, we report a rare case of primary, simultaneous onset, bilateral, dendritic epithelial keratitis at a very early stage with complications of generalized herpetic disease in a patient with atopic dermatitis.

Herpes simplex keratitis after cataract surgery.

PURPOSE: Herpetic keratitis is a rare complication of cataract surgery. We describe 3 cases of herpes simplex keratitis after cataract surgery in eyes with no clinical history of this disease. METHODS: Three patients underwent uneventful phacoemulsification of cataract with intraocular lens implantation. All were treated postoperatively with topical steroids. On subsequent development of corneal dendritic epithelial lesions in the operated eyes, the corticosteroids were replaced by treatment with topical acyclovir. RESULTS: The first postoperative day was uneventful. Corneal dendritic epithelial lesions were observed 1-5 weeks postoperatively and healed without sequelae after topical acyclovir treatment. CONCLUSIONS: In view of the surgical trauma along with the topical corticosteroid treatment commonly prescribed after cataract surgery, physicians should be aware of the possible development of herpetic epithelial keratitis even in patients with no clinical history of this disease.

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.

"Steel wool keratopathy": a clinical sign of chronic inflammation.

PURPOSE: To introduce into the clinical nomenclature a sign frequently observed in our patients with persistent corneal inflammation associated with herpetic stromal keratitis. METHODS: Case reports and review of the literature. RESULTS: Four representative patients with herpesvirus stromal keratitis are presented. Herpes simplex virus-1 (HSV-1) was confirmed by culture in 1 case and by polymerase chain reaction in a second case. In the remaining 2 cases, the diagnosis was made based on characteristic clinical findings for herpes simplex virus and varicella zoster virus (VZV). On clinical examination, all 4 representative cases of stromal keratitis revealed a well-defined, localized region of intertwined, metallic-like, polychromatic material in the corneal stroma, a sign we have termed steel wool keratopathy. We have only rarely observed this finding in patients with stromal keratitis not caused by a herpesvirus. CONCLUSION: Steel wool keratopathy seems to represent a focal region of stromal degeneration or deposition associated with chronic inflammation. Although we most often observe this finding in patients with stromal keratitis secondary to HSV or VZV, we cannot exclude the possibility that this sign represents the sequelae of chronic/recurrent inflammation rather than a specific pathologic response to herpetic antigens.

Effect of oral valaciclovir on herpetic keratitis.

PURPOSE: To examine the efficacy of valaciclovir (VACV) oral formulation as an alternative to topical treatments in a case of herpetic keratitis. METHODS: The patient was a 61-year-old man who presented with dendritic keratitis in his left eye. After recognizing his difficulty in using eye ointment, we prescribed oral VACV 500 mg tablets twice daily for 7 days. We also describe our experiments with orally administered VACV in a mouse model of this disease. In this study, 143 Balb/c mice were inoculated with herpes simplex virus type 1 (HSV)-1 in each eye and treated with oral VACV 50 or 100 mg/kg twice daily, oral acyclovir (ACV) 50 mg/kg 5 times/d, 3% ACV eye ointment (ACV-O) 5 times/d, 3% ACV eye drops 5 times/d, or control for 5 days. RESULTS: After 7 days, the patient's lesion was observed healed. Corrected left visual acuity was also improved, and HSV DNA was below detectable level. In the mouse study, slit-lamp examination on days 3, 4, 5, and 7 revealed that all 5 ACV and VACV treatment groups were significantly more effective in improving symptoms of herpetic epithelial keratitis versus control (P < 0.05). Moreover, VACV 100 mg/kg was superior to other treatments. Viral titers in mouse eyeball and trigeminal ganglia were lowest in the VACV 100 mg/kg group versus other treatment groups. CONCLUSION: Our case example suggests that when frequent application, blurred vision, and foreign body sensation after ACV-O application cause difficulty for patients to follow treatment, oral VACV might be an effective and safe option for patients with herpetic keratitis.