valacyclovir and Keratitis--Herpetic

Ophthalmic herpes simplex viral keratitis is responsible for a range of ocular manifestations from superficial epithelial disease to stromal keratitis and endotheliitis. The Herpetic Eye Disease Study has guided the management of herpetic eye disease for almost twenty years, but newer medications such as valacyclovir are now available and are considered to have better bioavailability than acyclovir. In this review, we examine the existing evidence on the pathogenesis of different ophthalmic herpes simplex viral keratitis disease modalities and the role of oral and topically administered antiviral drugs in the treatment of herpes simplex viral keratitis.

Topics: Acyclovir; Administration, Oral; Administration, Topical; Antiviral Agents; Debridement; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Valacyclovir; Valine

A 25-year-old woman presented with redness, pain, and diminution of vision that occurred 2 weeks after microkeratome-assisted laser in situ keratomileusis (LASIK). On presentation, corneal edema, Descemet membrane folds, keratic precipitates, stromal infiltrates, and flap necrosis were observed. Delayed post-LASIK microbial keratitis was diagnosed. The patient had no history of ocular herpes. Culture and scraping showed no organisms. Immunofluorescence stain was positive for the herpes simplex virus antigen. The patient was started on oral valacyclovir, and progress was monitored through serial clinical photographs and anterior segment optical coherence tomography. Resolution began within 3 days of initiating treatment and was complete in 4 weeks.

Topics: Acyclovir; Administration, Oral; Adult; Antigens, Viral; Antiviral Agents; Corneal Stroma; Female; Humans; Keratitis, Herpetic; Keratomileusis, Laser In Situ; Myopia; Necrosis; Postoperative Complications; Simplexvirus; Surgical Flaps; Tomography, Optical Coherence; Uveitis, Anterior; Valacyclovir; Valine

Although many factors that trigger the herpes simplex virus (HSV) reactivation from latency have been reported, how HSV resides in a latent state in the normal human cornea still needs to be defined. We therefore conducted a series of studies regarding various aspects of HSV infections. To understand how patients subjectively perceived changes in their daily life that could have induced HSV reactivation, we first performed a comprehensive survey on the subjective factors in patients who had experienced recurrent herpetic keratitis. The result of our survey revealed that stress, lack of sleep, shoulder stiffness, and physical fatigue were the key factors. There were various causes for stress, and stress associated with reactivation often occurred between spring and summer. Regarding HSV latency in the normal cornea, we used real-time polymerase chain reaction (PCR) to determine the presence of HSV in the donor and host corneas. The findings showed that on average, those host corneas with a history of HSV keratitis had 1.6 x 10(4) copies/mg of HSV DNA, while the host corneas without a history and the donor corneas had 8.7 and 4.9 x 10(2) copies/mg of HSV DNA, respectively. Based on these observations, it is reasonable to infer that latent viruses could have resided in a normal cornea without a history and were transmitted to a host cornea through corneal transplantation. We also quantified the virus load in tears before and after ocular surgery (one week after corneal transplantation or the next day after vitreous surgery). Our results indicated that both the detection rate and the average copy number of HSV DNA had a tendency to increase postperatively. Moreover, we tried to differentiate the HSV strains that were involved in the recurrent lesions. In only one of the studied cases, could we find a single different nucleotide between two HSV strains. It seemed possible that two different strains of HSV had set off the same episode of reactivation. In recent years, chemokines have become known for their action in mediating inflammatory diseases. We suspected that chemokines might also play a role in the antiviral mechanism and examined the chemokine-derived antiviral activity. We used eight chemokines, including RANTES/CCL5, MIP-lalpha/ CCL3, and MIP-1beta/CCL4, in a murine HSK model with Vero cells. These chemokines directly bound to HSV and the chemokine-bound HSV was later resisted by the neutralizing antibody of envelope protein gB. Furthermore, by elect

Topics: Acyclovir; Animals; Antiviral Agents; Biomarkers; Chemokines; DNA, Viral; Dosage Forms; Humans; Keratitis, Herpetic; Recurrence; Simplexvirus; Surveys and Questionnaires; Valacyclovir; Valine; Virus Latency

The development of the antiherpetic therapeutical system was remarkable in the last decade. Nucleoside analogs (5-iodine-2-deoxiuridine, citodine-arabinotide, adenine-arabinotide), as well as specific inhibitors of viruses (Zovirax or Acyclovir) are active medicines for both local and wide-spread forms of the herpes virus infection.

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Bromodeoxyuridine; Cidofovir; Cytosine; Drug Combinations; Famciclovir; Foscarnet; Ganciclovir; Humans; Idoxuridine; Keratitis, Herpetic; Oligonucleotides; Ophthalmic Solutions; Organophosphonates; Treatment Outcome; Valacyclovir; Valine; Vidarabine

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.

Topics: Acyclovir; Administration, Oral; Adult; Antiviral Agents; Female; Humans; Keratitis, Herpetic; Male; Pilot Projects; Prodrugs; Prospective Studies; Secondary Prevention; Treatment Outcome; Valacyclovir; Valine

Thirty eyes of 28 patients with herpetic disease were included in the study. Group 1 patients (15 eyes of 15 subjects) received topical acyclovir (ACV) ointment. Oral valacyclovir (VACV) was prescribed to group 2 (15 eyes of 13 patients). The anterior segment of each eye was carefully examined by slit lamp and scored. Each patient was also instructed to grade his/her subjective symptoms. The corneal lesion healed significantly faster in the group 2 eyes compared to the group 1 eyes. Photophobia score on day 3 and slit-lamp score on day 10 were at significantly lower levels in group 2 compared to group 1. In herpetic keratitis, oral VACV can be a good alternative to ACV ointment therapy.

Topics: Acyclovir; Administration, Oral; Administration, Topical; Female; Humans; Keratitis, Herpetic; Male; Valacyclovir; Valine

Topics: Angiogenesis Inhibitors; Antiviral Agents; Diabetic Retinopathy; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Glucocorticoids; Humans; Intravitreal Injections; Keratitis, Herpetic; Macular Edema; Male; Middle Aged; Prednisolone; Ranibizumab; Uveitis, Anterior; Valacyclovir; Vascular Endothelial Growth Factor A

The objective of this study was to investigate the processability of hot-melt extrusion (HME) to formulate ocular inserts of valacyclovir hydrochloride and evaluate the in vivo bioavailability of the formulation. To optimize the formulation of this drug, different physical mixtures of the polymers and plasticizer were prepared. The physical mixture was extruded through a co-rotating twin-screw extruder, and the obtained ocular inserts were cut with dimensions of 4 mm × 2 mm × 1 mm to enhance the formulation instillation in the eye. Ocular inserts were evaluated for drug content, weight variation, uniformity of thickness, in vitro drug release, and in vivo drug bioavailability. The ocular inserts were thermally characterized using differential scanning calorimetry (DSC). The attributes observed for the ocular inserts were within the target specifications. The ocular inserts of valacyclovir hydrochloride were successfully prepared using the HME. They provided sustained drug release along with enhanced drug permeation when compared with the eyedrop solution and dissolve completely in 8 h. Additionally, the obtained results demonstrated that the formulation of ocular inserts of valacyclovir hydrochloride using HME was reproducible, robust, and effective method.

Topics: Administration, Ophthalmic; Antiviral Agents; Biological Availability; Calorimetry, Differential Scanning; Drug Compounding; Drug Implants; Drug Liberation; Hot Melt Extrusion Technology; Keratitis, Herpetic; Polymers; Valacyclovir

To report 2 cases of herpes simplex virus (HSV) stromal keratitis with epithelial ulceration that were managed using optical coherence tomography-generated pachymetric and corneal epithelial thickness maps.. Two patients with a history of HSV keratitis with nonhealing epithelial defects were referred to the Athens Vision Eye Institute. Anterior segment optical coherence tomography-generated pachymetric and corneal epithelial thickness maps showed subclinical stromal edema and irregular epithelium, thus indicating diagnoses of HSV stromal keratitis with epithelial ulceration. The patients were administered topical preservative-free dexamethasone and oral antiviral therapy. Steroid tapering was guided by pachymetric and corneal epithelial thickness maps at each follow-up visit.. Both patients experienced initial healing of the epithelium and resolution of stromal inflammation. One patient had a recurrence of HSV stromal keratitis with epithelial defect 3 months after initial improvement, with pachymetric and corneal epithelial thickness maps indicating subclinical stromal edema. He was reintroduced to topical steroid therapy, and the stromal edema and epithelial defect subsequently resolved. Both patients have had no recurrences in the past year.. Pachymetric and corneal epithelial thickness maps provide an objective assessment of stromal inflammation and the following 2 clinical advantages in the management of HSV stromal keratitis with epithelial ulceration: (1) they help differentiate it from HSV epithelial keratitis with geographic ulceration and neurotrophic keratopathy and (2) offer objective measurements to guide management with topical corticosteroids until resolution of stromal edema. Thus, treatment can be initiated in a timely manner, and the blinding complications of HSV stromal keratitis can be avoided.

Topics: Administration, Ophthalmic; Administration, Oral; Antiviral Agents; Corneal Pachymetry; Corneal Stroma; Corneal Ulcer; Dexamethasone; Drug Combinations; Epithelium, Corneal; Eye Infections, Viral; Female; Glucocorticoids; Humans; Keratitis, Herpetic; Male; Middle Aged; Tomography, Optical Coherence; Valacyclovir

Topics: Antiviral Agents; Debridement; Humans; Keratitis, Dendritic; Keratitis, Herpetic; Male; Middle Aged; Simplexvirus; Valacyclovir

Topics: Adolescent; Antiviral Agents; Corneal Opacity; Disease Progression; Female; Follow-Up Studies; Humans; Keratitis, Herpetic; Valacyclovir

Recurrence of herpes simplex virus (HSV) keratitis is a problem of keratoplasty and the prognosis is often poor in spite of oral acyclovir (ACV) prophylaxis. This 64-year-old woman was a known case of recurrent HSV endotheliitis with irreversible corneal oedema in the left eye for 2 years. She underwent Descemet membrane endothelial keratoplasty with intraocular lens implantation under perioperative oral ACV and prednisolone. After 4 weeks, her cornea cleared with the best-corrected vision of 6/9. After 2.5 months, she presented with sudden photophobia and visual loss. An increasing focal endothelial lesion was noticed even after oral ACV. Suspecting fungal interface infection, anterior chamber tap was done for PCR for panfungal and viruses. It was only positive for HSV. Oral ACV was changed to oral valacyclovir. The patient responded dramatically within 2 weeks, and after 12 weeks, the lesion disappeared completely, leaving behind a faint scar with 6/9 p vision. Oral valacyclovir, a prodrug of ACV, may work better than oral ACV.

Topics: Antiviral Agents; Descemet Membrane; Descemet Stripping Endothelial Keratoplasty; Endothelium, Corneal; Female; Humans; Keratitis, Herpetic; Middle Aged; Recurrence; Simplexvirus; Treatment Outcome; Valacyclovir

Topics: Antiviral Agents; Drug Prescriptions; Eye Infections, Viral; Humans; Incidence; Keratitis, Herpetic; New Zealand; Risk Factors; Valacyclovir

Following Tx for facial blisters, our patient returned with what appeared to be viral conjunctivitis. Further evaluation revealed a missed tip-off to the proper Dx.

Topics: Anti-Bacterial Agents; Antiviral Agents; Conjunctivitis; Ear; Erythromycin; Female; Herpes Labialis; Humans; Keratitis, Herpetic; Lip; Middle Aged; Mouth; Nose; Otitis Media; Treatment Outcome; Trifluridine; Valacyclovir

A 36-year-old male, soft contact lens wearer was referred by his primary ophthalmologist for corneal ulcer of the right eye (OD), which was persistent despite topical fluoroquinolone therapy for 1 month. A ring-shaped infiltrate typically seen in Acanthamoeba infection was noted, and topical therapy with chlorhexidine and polyhexamethylene biguanide was initiated. However, the patient's condition deteriorated over the next several weeks; thus, diagnostic and therapeutic penetrating keratoplasty was performed. The postoperative immunohistochemical analysis suggested a diagnosis of herpes simplex virus (HSV) keratitis. The patient ultimately improved after initiation of oral valacyclovir following penetrating keratoplasty. We report a case of a commonly encountered clinical entity, HSV keratitis, with an atypical clinical presentation, masquerading as Acanthamoeba keratitis.

Topics: Acanthamoeba; Acanthamoeba Keratitis; Adult; Amebiasis; Antiviral Agents; Corneal Ulcer; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Simplexvirus; Treatment Outcome; Valacyclovir

Recurrent herpes simplex keratitis (HSK) is a leading infectious cause of blindness in industrialized countries. Antiviral prophylaxis (AVP) may fail to prevent recurrence of HSK due to viral resistance, inadequate dosing, or poor patient compliance. In this prospective multicenter study, we enrolled immunocompetent patients with recurrent HSK despite AVP. Ocular samples were tested by PCR for herpes simplex virus 1 (HSV-1). HSV-1 drug resistance was assessed with a genotypic assay based on UL23 and UL30 gene sequencing. After curative full dose valacyclovir (VACV) treatment was started, peak and trough acyclovir (ACV) plasma concentrations were measured, and patient compliance to AVP was assessed with a questionnaire. The study sample was comprised of 43 patients. Six (14%) patients were positive for HSV-1 using PCR, of whom 5 (83%) harbored genotypically ACV-resistant (ACV

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Child; Child, Preschool; Drug Resistance, Viral; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant; Keratitis, Herpetic; Male; Middle Aged; Polymerase Chain Reaction; Prospective Studies; Recurrence; Tears; Valacyclovir; Valine; Young Adult

Aciclovir (ACV), valaciclovir (VACV) and famciclovir (FCV) are used for systemic infections caused by herpes virus. In Japan, only topical ACV is permitted for use against herpetic keratitis. We investigated the effectiveness of topical ACV, oral VACV and oral FCV on mouse epithelial herpetic keratitis.. C57/BL76 mice were inoculated with HSV-1 McKrae strain in the cornea. Once infection was confirmed 4 days after inoculation, topical ACV, oral VACV and FCV were started and administered for 5 days. Control groups were given either topical or oral saline. On days 2, 4, 6 and 10 after medication started, tears, eyeballs, and trigeminal ganglia were examined using viral culture and real-time PCR.. Viral culture of tears detected no HSV in the topical ACV group on day 4 after administration start; with similar results for the oral VACV group on day 4; and the oral FCV group on day 6. Real-time PCR of the eyeballs showed significant decrease of HSV DNA copy number in the topical ACV group on days 4 and 6 compared to the topical saline group. Real-time PCR of the trigeminal ganglia showed significant decrease of HSV DNA copy number in the oral VACV group on days 4 and 6, and in the oral FCV group on day 6 compared to the oral saline group.. We suggest that 5-day administration of topical ACV, oral VACV and oral FCV are effective for mouse epithelial herpetic keratitis and sufficiently decrease HSV amounts in the ocular surface and eyeballs.

Topics: 2-Aminopurine; Acyclovir; Administration, Oral; Administration, Topical; Animals; Antiviral Agents; Disease Models, Animal; DNA Copy Number Variations; DNA, Viral; Epithelium, Corneal; Eye Infections, Viral; Famciclovir; Female; Herpesvirus 1, Human; Keratitis, Herpetic; Mice; Mice, Inbred C57BL; Real-Time Polymerase Chain Reaction; Tears; Trigeminal Nerve; Valacyclovir; Valine

Herpes simplex virus (HSV) ocular infection causes significant visual burden worldwide. Despite the fact that dendritic or geographic corneal ulcers are typical findings in HSV epithelial keratitis, conjunctival ulcer as a sign of HSV infection has rarely been reported. Although easily overlooked, this important sign could be enhanced by fluorescein staining. We report two cases of conjunctival geographic ulcers proven to be HSV infection by viral isolation and polymerase chain reaction (PCR). One patient had bilateral disease and blepharitis, and the other had unilateral involvement without skin lesions. With timely diagnosis and proper management, excellent visual outcome can be expected.

Topics: Acyclovir; Adult; Antigens, Viral; Antiviral Agents; Blepharitis; Conjunctival Diseases; DNA, Viral; Female; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Polymerase Chain Reaction; Ulcer; Valacyclovir; Valine

Topics: Acyclovir; Antiviral Agents; Aqueous Humor; DNA, Viral; Drug Therapy, Combination; Eye Infections, Viral; Gene Dosage; Glucocorticoids; Humans; Keratitis, Herpetic; Male; Middle Aged; Prednisolone; Real-Time Polymerase Chain Reaction; Simplexvirus; Uveitis, Anterior; Valacyclovir; Valine

To determine the efficacy of a new helicase-primase inhibitor, ASP2151, for treating herpetic keratitis.. Murine corneas were infected with herpes simplex virus type 1 (HSV-1). ASP2151 was administered orally or topically, and the severity of epithelial dendritic keratitis was determined. The effectiveness of ASP2151 was compared with that of acyclovir and valacyclovir. The reduction of the amount of HSV in tears, enucleated eyes and trigeminal ganglia was determined by real-time PCR or plaque assay.. Orally administered ASP2151 reduced the epithelial keratitis score significantly more than that of the vehicle-treated group (p<0.01). It also lowered the HSV-DNA levels in the tears significantly more than that by valacyclovir (p<0.01). ASP2151 ointment resulted in the same reduction of the keratitis score as acyclovir ointment, and lowered the HSV DNA in tears more than acyclovir ointment. Topical instillation of ASP2151 improved the herpetic dendritic keratitis score significantly and reduced the titre of HSV DNA in the tears in a dose-responsive way.. ASP2151 had significantly better anti-HSV activity against herpes simplex keratitis than valacyclovir and acyclovir after systemic or topical use. These findings indicate that ASP2151 should be considered as an alternative treatment for herpes simplex keratitis.

Topics: Acyclovir; Administration, Oral; Administration, Topical; Animals; Disease Models, Animal; DNA Helicases; DNA Primase; DNA, Viral; Herpesvirus 1, Human; Keratitis, Herpetic; Mice; Mice, Inbred BALB C; Oxadiazoles; Real-Time Polymerase Chain Reaction; Tears; Treatment Outcome; Valacyclovir; Valine; Viral Proteins

To report a case of bilateral Herpes simplex keratitis (HSK) masquerading as peripheral ulcerative keratitis (PUK).. A case of a 47-year-old female complaining of painful red eyes with a history of arthritis and anterior uveitis attacks with positive antinuclear antibodies (ANA). Biomicroscopy revealed PUK, stromal infiltrations and bilateral central corneal epithelial erosions. Slit-lamp examination disclosed +3 anterior chamber cells in both eyes.. Blood testing was positive for ANA. Herpes simplex virus (HSV) antigen was identified in both eyes using polymerase chain reaction (PCR). The management included topical prednisolone and acyclovir, as well as systemic valacyclovir. Improvement of epithelial corneal defects, PUK, and visual acuity was achieved gradually during the follow-up period.. Bilateral herpetic keratitis presenting as PUK is an extremely rare manifestation of herpetic disease. PUK can pose a diagnostic dilemma in cases with immune system dysregulation. Excluding infectious agents is mandatory for appropriate treatment.

Topics: Acyclovir; Antigens, Viral; Antiviral Agents; Corneal Ulcer; Diagnosis, Differential; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Keratitis, Herpetic; Middle Aged; Polymerase Chain Reaction; Prednisolone; Valacyclovir; Valine

To describe the clinical characteristics, treatment, and outcomes of herpes simplex virus (HSV) infections of the cornea and adnexae to raise awareness and to improve management of this important eye disease in children.. Retrospective case series.. Fifty-three patients (57 eyes) 16 years of age or younger with HSV keratitis (HSK), HSV blepharoconjunctivitis (HBC), or both in an academic cornea practice.. The following data were collected: age at disease onset, putative trigger factors, coexisting systemic diseases, duration of symptoms and diagnoses given before presentation, visual acuity, slit-lamp examination findings, corneal sensation, dose and duration of medications used, drug side effects, and disease recurrence.. Presence of residual corneal scarring, visual acuity at the last visit, changes in corneal sensation, recurrence rate, and manifestations of HSK were assessed in patients receiving long-term prophylactic systemic acyclovir.. The median age at onset was 5 years. Mean follow-up was 3.6 years. Eighteen eyes had HBC only; 4 patients in this group had bilateral disease. Of 39 eyes with keratitis, 74% had stromal disease. Thirty percent of HSK cases were misdiagnosed before presentation. Seventy-nine percent of patients with keratitis had corneal scarring and 26% had vision of 20/40 or worse at the last visit. Eighty percent of patients had recurrent disease. Six of 16 patients (37%) receiving long-term oral acyclovir had recurrent HSV, at least one case of which followed a growth spurt that caused the baseline dosage of acyclovir to become subtherapeutic.. In a large series, pediatric HSK had a high rate of misdiagnosis, stromal involvement, recurrence, and vision loss. Oral acyclovir is effective, but the dosage must be adjusted as the child grows.

Topics: 2-Aminopurine; Acyclovir; Administration, Topical; Adolescent; Age of Onset; Anterior Eye Segment; Antiviral Agents; Blepharitis; Child; Child, Preschool; Conjunctivitis, Viral; Eye Infections, Viral; Famciclovir; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant; Keratitis, Herpetic; Male; Ointments; Retrospective Studies; Trifluridine; Valacyclovir; Valine; Vidarabine

To describe an atypical case of cytomegalovirus (CMV) endotheliitis in a 74-year-old man who presented with chronic corneal edema without keratic precipitates (KPs) and intraocular pressure (IOP) elevation.. Case report.. A complete ophthalmologic examination was performed. Polymerase chain reaction was used to test for herpes simplex virus, varicella zoster virus, and CMV DNA in aqueous humor samples to rule out viral endotheliitis.. Severe bullous keratopathy was found in the temporal part of the cornea without KPs or elevated IOP. CMV DNA was detected. Corneal edema subsided with oral valganciclovior.. CMV endotheliitis may present as corneal edema that lacks typical features, such as KPs or elevated IOP.

Topics: Acyclovir; Aged; Antiviral Agents; Corneal Edema; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Endothelium, Corneal; Ganciclovir; Humans; Intraocular Pressure; Keratitis, Herpetic; Male; Prednisolone; Valacyclovir; Valganciclovir; Valine; Visual Acuity

Topics: Acyclovir; Administration, Topical; Antiviral Agents; Combined Modality Therapy; Corneal Stroma; Cyclosporine; Drug Therapy, Combination; Dry Eye Syndromes; Electrocoagulation; Eyelids; Glucocorticoids; Herpesvirus 1, Human; Humans; Immunosuppressive Agents; Keratitis, Herpetic; Lacrimal Apparatus; Secondary Prevention; Valacyclovir; Valine; Virus Activation

To report the clinical characteristics and visual outcomes of pediatric herpes simplex virus (HSV) keratitis.. The medical records of 29 patients younger than 16 years with HSV keratitis who were diagnosed and treated at Chang Gung Memorial Hospital, Taoyuan, Taiwan, between 1996 and 2004 were retrospectively reviewed. The diagnosis of HSV keratitis was proven by a positive viral culture and/or real-time quantitative polymerase chain reaction or by a clear history of dendritic keratitis or herpetic kerato-uveitis. Type of HSV keratitis, recurrence rate, and visual outcome were analyzed.. The average age at the entry into the study was 5.7 years (range: 7 months to 15 years). Mean follow-up time was 35.3 months (range: 2-69 months). Epithelial keratitis including dendritic and geographic ulcers was noted in 14 eyes, stromal keratitis in 2 eyes, stromal keratitis concurrent with epithelial keratitis in 8 eyes, and endotheliitis in 6 eyes. One patient had sequential involvement of both eyes. Thirteen patients (45%) developed recurrent HSV keratitis after the first documented episode. Female gender (but not age or the type of keratitis) was significantly associated with recurrences. Five patients who were maintained on oral valacyclovir prophylaxis up to 1 year had no recurrence during the period. Fifteen of 21 patients younger than 8 years of age had best-corrected visual acuity available at last follow-up, and 10 patients developed amblyopia.. Children with HSV keratitis are at risk for recurrent keratitis and amblyopia. Prolonged systemic antiviral prophylaxis may help to prevent such consequences.

Topics: Acyclovir; Adolescent; Antiviral Agents; Child; Child, Preschool; DNA, Viral; Female; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Infant; Keratitis, Herpetic; Male; Recurrence; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors; Valacyclovir; Valine; Virus Cultivation; Visual Acuity

To evaluate the efficacy of adjunctive treatments to decrease herpes simplex keratitis (HSK) recurrences in patients with simultaneous stromal HSK and dry eye disease.. This was a nonrandomized, single-center, retrospective, comparative analysis. Forty-two patients were diagnosed with unilateral HSK and dry eye disease. Of the 42 patients, 22 were treated with ipsilateral punctal occlusion by thermal cautery and 10 were treated with topical administration of cyclosporine, 0.05%, ophthalmic emulsion twice a day. Another group of 10 patients had previously undergone punctal occlusion and had cyclosporine ophthalmic emulsion twice a day added. All patients continued the use of oral acyclovir or valacyclovir hydrochloride and topical steroids. The frequency and duration of HSK recurrences were monitored for 1 year after initiation of treatment, and the rates were compared with those in the prior year.. The thermal cautery and topical cyclosporine groups experienced HSK recurrences for mean durations of 7.1 and 5.8 mo/y before treatment, respectively, and these were reduced to 1.1 mo/y after treatment in both groups. Topical administration of cyclosporine further reduced the duration of HSK recurrences in patients with prior thermal cautery from an average of 1.3 mo/y before the addition of cyclosporine to 0.8 mo/y after the addition of cyclosporine.. Permanent punctal occlusion by thermal cautery and the use of topical cyclosporine independently reduced recurrences of stromal HSK.

Topics: Acyclovir; Administration, Topical; Antiviral Agents; Combined Modality Therapy; Corneal Stroma; Cyclosporine; Drug Therapy, Combination; Dry Eye Syndromes; Electrocoagulation; Eyelids; Glucocorticoids; Herpesvirus 1, Human; Humans; Immunosuppressive Agents; Keratitis, Herpetic; Lacrimal Apparatus; Retrospective Studies; Secondary Prevention; Valacyclovir; Valine; Virus Activation

To compare the outcome of prophylactic oral valacyclovir (VAL) or oral acyclovir treatment (ACV) in patients having undergone penetrating keratoplasty for herpetic keratitis (HK).. All patients having received a penetrating keratoplasty for HK and being treated postoperatively with either oral VAL or oral ACV (inclusion period from 12/97 to 3/06 and 5/92 to 9/96, respectively) were retrospectively evaluated. Records were analysed for postoperative reactivation of recurrent HK, graft rejection, endothelial cell loss, central corneal thickness and visual acuity after a follow-up of up to 5 years.. Twenty patients received VAL and were compared with 19 patients being treated with ACV. Two patients developed clinical signs of recurrent herpetic disease in the VAL group compared with three patients in the ACV group. Two patients from both groups each developed an irreversible graft failure. Best corrected visual acuity improved in both treatment groups from baseline (logMAR) -1.97 (VAL), -1.47 (ACV) to -0.85, -0.72, respectively, at the 1-year follow-up and slightly deteriorated after 5 years in the ACV group (-0.71 VAL vs -1.14 ACV).. Prophylactic oral VAL treatment is at least as effective as ACV in preventing recurrence in patients who underwent corneal transplantation for HK. The tolerability of the two drugs is similar, but the dosing for VAL might be more comfortable for patients.

Topics: Acyclovir; Administration, Oral; Aged; Antiviral Agents; Corneal Opacity; Dose-Response Relationship, Drug; Female; Graft Rejection; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Valacyclovir; Valine; Visual Acuity

To describe archipelago keratitis, a presumed clinical variant of herpetic epithelial keratitis.. Case series.. A series of 6 patients with an unusual form of superficial keratitis.. History, including age, gender, clinical evolution, and treatment; slit-lamp biomicroscopy findings; in vivo confocal microscopy findings; and corneal epithelial scrapings were analyzed.. Clinical ocular examination, a diagnostic workup including corneal scraping for herpesvirus polymerase chain reaction, in vivo confocal microscopy, and therapeutic outcome.. The authors describe a series of 6 patients with keratitis consisting of foci of epithelial erosions associated with subepithelial nummular inflammatory infiltrates and disposed in a radial, centripetal, archipelagolike pattern originating from the limbus. All the patients had a past history of herpetic epithelial keratitis, herpetic vesicles on the ipsilateral lid, or both. Polymerase chain reaction-based screening for herpes simplex virus 1 and 2 in corneal scrapings demonstrated positive results in 2 patients. In vivo corneal confocal microscopy revealed focal areas of hyperreflective epithelial cells and hyperreflective subepithelial dendritic structures overlying activated keratocytes. All the patients improved with oral valacyclovir treatment followed by topical steroid therapy.. Archipelago keratitis may be a new clinical variant of herpetic keratitis, reflecting herpetic dissemination from the limbus to the center of the cornea.

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; DNA, Viral; Drug Therapy, Combination; Epithelium, Corneal; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Keratitis, Herpetic; Male; Microscopy, Confocal; Middle Aged; Polymerase Chain Reaction; Pregnadienes; Recurrence; Valacyclovir; Valine

To report the outcome of LASIK in patients with inactive herpetic keratitis in which perioperative antiviral prophylaxis was used to prevent the recurrence of ocular herpes.. We report an uncontrolled series of five patients with inactive herpetic keratitis for at least 1 year before surgery in whom LASIK was successfully performed. All patients showed normal topography, pachymetry, and corneal sensitivity with no central corneal scarring. Perioperative prophylaxis was used in each case with oral valacyclovir and topical acyclovir ointment.. None of the eyes developed reactivation of herpetic keratitis during follow-up.. This study suggests that perioperative antiviral prophylaxis may protect the cornea from herpes simplex virus reactivation after LASIK.

Topics: Acyclovir; Administration, Oral; Administration, Topical; Adult; Antiviral Agents; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Keratitis, Herpetic; Keratomileusis, Laser In Situ; Male; Myopia; Ointments; Perioperative Care; Prodrugs; Treatment Outcome; Valacyclovir; Valine

To examine the efficacy of valaciclovir (VACV) oral formulation as an alternative to topical treatments in a case of herpetic keratitis.. 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.. 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.. 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.

Topics: Acyclovir; Administration, Oral; Animals; Antiviral Agents; Cornea; Disease Models, Animal; DNA, Viral; Gene Dosage; Herpesvirus 1, Human; Humans; Keratitis, Dendritic; Keratitis, Herpetic; Male; Mice; Mice, Inbred BALB C; Middle Aged; Polymerase Chain Reaction; Prodrugs; Valacyclovir; Valine

To compare the efficacy of oral antiviral prophylactic treatment for herpes simplex virus (HSV) recurrences in patients with and without self-reported atopy.. Retrospective cohort comparative study.. setting: Cornea Service, Wills Eye Hospital. study population: Patients who presented with previously diagnosed ocular HSV between March 2003 and March 2004. From 244 patients invited, 54 patients (58 eyes) were included. One hundred and ninety patients were excluded according to exclusion criteria: no active episode during follow-up, immunosuppression, less than one year of follow-up, or previous history of penetrating keratoplasty. The Questionnaire regarding history of atopic disease, considers: presence of allergic rhinitis, asthma or atopic dermatitis, and chart review of ocular history. main outcome measures: Incidence of all types of HSV recurrences with and without antiviral prophylaxis within each group and between groups. HSV episodes were classified into infectious, inflammatory, and mixed for analysis.. Atopic/nonatopic (P value): mean follow-up without prophylaxis 8.1 (+/- 8.2)/7.3 years (+/- 8.6) (P = .71); mean follow-up with prophylaxis 2.9 (+/- 2.3)/2.6 years (+/- 2.2) (P = .51); the effect of prophylaxis significantly reduced the all recurrences in both groups except in the inflammatory recurrences in the atopic group and in the mixed recurrences in both groups. Prophylaxis decreased infectious episodes by 44% in nonatopic and 76% in atopics and decreased inflammatory manifestations by 69% in the nonatopic group and 8% in the atopic group.. Antiviral prophylaxis for HSV recurrences was more effective in reducing infections in atopics and less effective in reducing inflammatory episodes in atopics versus nonatopics.

Topics: 2-Aminopurine; Acyclovir; Administration, Oral; Antiviral Agents; Famciclovir; Female; Follow-Up Studies; Herpesvirus 1, Human; Humans; Hypersensitivity, Immediate; Keratitis, Herpetic; Male; Middle Aged; Prodrugs; Retrospective Studies; Secondary Prevention; Surveys and Questionnaires; Valacyclovir; Valine

A woman with a history of recurrent herpes simplex keratitis in the left eye developed endothelial and stromal keratitis after cataract extraction. Because of the resultant corneal distortion a high regular astigmatism appeared. An arcuate keratotomy was performed to improve her visual acuity.. Corneal astigmatism can appear after herpetic keratitis. An arcuate keratotomy was effective in this case to decrease astigmatism and improve her vision. Keratitis reactivation is possible so antiviral prophylaxis is advisable. Our good results show that arcuate keratotomy can be a useful technique for these patients.

Topics: Acyclovir; Antiviral Agents; Astigmatism; Dexamethasone; Drug Therapy, Combination; Female; Humans; Keratitis, Herpetic; Lens Implantation, Intraocular; Middle Aged; Ophthalmologic Surgical Procedures; Phacoemulsification; Postoperative Complications; Tobramycin; Valacyclovir; Valine; Virus Activation

The time course for delivery and transport of two major proteins of herpes simplex virus (HSV) has been determined for mature mouse retinal ganglion cell axons in vivo. Twenty-four hours after intravitreal injection of HSV, valacyclovir was introduced into the drinking water of the mice to inhibit subsequent viral replication. Without treatment, viral spread and replication in periaxonal glial cells confound study of axonal transport. At 2 to 5 days after infection, the animals were sacrificed and contiguous segments of the optic pathway were removed. Immunofluorescence microscopy indicated that the number of infected astrocytes was reduced in the proximal optic nerve and eliminated in the optic tract. Western blots of the retina with antibodies for envelope and capsid components, glycoprotein D (gD) and VP5, respectively, revealed that both components were expressed in retinal homogenates by 2 days. Results of reverse transcription-PCR indicated that there was no gD mRNA present in the treated optic tract 5 days after infection. Therefore, we conclude that gD is transcribed from viral mRNA in the retinal ganglion cell bodies. The gD accumulated in the proximal ganglion cell axon by 2 days and reached the most distal segment after 3 days. The VP5 first appeared in the proximal axons at 4 days, about 48 h after the appearance of gD. Thus, gD entered the axon earlier and independent of VP5. These finding confirm the subassembly model of viral transport in neurons and suggest that there is a 4- to 5-day window for initiation of effective antiviral treatment with valacyclovir.

Topics: Acyclovir; Animals; Antiviral Agents; Astrocytes; Axonal Transport; Capsid Proteins; Immunohistochemistry; Keratitis, Herpetic; Male; Mice; Mice, Inbred BALB C; Optic Nerve; Retina; Retinal Ganglion Cells; Simplexvirus; Valacyclovir; Valine; Viral Envelope Proteins; Virus Replication

A dipeptide prodrug of the antiviral nucleoside acyclovir (ACV), val-val-ACV (VVACV), was evaluated in vivo as a potential drug candidate for improving antiviral efficacy against herpetic epithelial and stromal keratitis.. The effect of 1% VVACV on epithelial keratitis induced by inoculation of HSV-1 strain McKrae (25 microL of 10(5) plaque-forming units [PFU]) in the scarified rabbit cornea and stromal keratitis induced by intrastromal injection of HSV-1 strain RE (10 microL of 10(5) PFU) was compared with that of 1% trifluorothymidine (TFT) and balanced salt solution as the vehicle control. Both eyes of 10 rabbits were used in each treatment group. Lesions were evaluated by slit lamp examinations over a 2-week period after infection. Aqueous humor samples and corneas were analyzed for drug concentrations at the end of each experiment. Cytotoxicity of VVACV in comparison with val-acyclovir (VACV), ACV, and TFT was evaluated in cellular proliferation assays.. The dipeptide prodrug VVACV demonstrated excellent activity against HSV-1 in the rabbit epithelial and stromal keratitis models: 1% VVACV was as effective as 1% TFT. The prodrug was also less cytotoxic than TFT, which is the only effective drug currently licensed and routinely used for topical treatment of ocular herpes infections in the United States.. The less cytotoxic and highly water-soluble prodrug VVACV, which showed excellent in vivo activity against HSV-1 in rabbit epithelial and stromal keratitis, is a promising drug candidate for treatment of ocular HSV infections.

Topics: Acyclovir; Animals; Antiviral Agents; Aqueous Humor; Biological Availability; Chlorocebus aethiops; Cornea; Corneal Stroma; Disease Models, Animal; Drug Evaluation, Preclinical; Epithelium, Corneal; Herpesvirus 1, Human; Keratitis, Herpetic; Prodrugs; Rabbits; Trifluridine; Valacyclovir; Valine

Mouse models of herpes simplex virus type 1 (HSV-1) infection provide significant insights into viral and host genes that regulate disease pathogenesis, but conventional methods to determine the full extent of viral spread and replication typically require the sacrifice of infected animals. To develop a noninvasive method for detecting HSV-1 in living mice, we used a strain KOS HSV-1 recombinant that expresses firefly (Photinus pyralis) and Renilla (Renilla reniformis) luciferase reporter proteins and monitored infection with a cooled charge-coupled device camera. Viral infection in mouse footpads, peritoneal cavity, brain, and eyes could be detected by bioluminescence imaging of firefly luciferase. The activity of Renilla luciferase could be imaged after direct administration of substrate to infected eyes but not following the systemic delivery of substrate. The magnitude of bioluminescence from firefly luciferase measured in vivo correlated directly with input titers of recombinant virus used for infection. Treatment of infected mice with valacyclovir, a potent inhibitor of HSV-1 replication, produced dose-dependent decreases in firefly luciferase activity that correlated with changes in viral titers. These data demonstrate that bioluminescence imaging can be used for noninvasive, real-time monitoring of HSV-1 infection and therapy in living mice.

Topics: Acyclovir; Animals; Antiviral Agents; Disease Models, Animal; Female; Genes, Reporter; Herpes Simplex; Herpesvirus 1, Human; Keratitis, Herpetic; Luciferases; Luminescent Measurements; Mice; Organ Specificity; Time Factors; Valacyclovir; Valine

Topics: Acyclovir; Administration, Oral; Adrenergic beta-Antagonists; Antiviral Agents; Drug Resistance, Microbial; Drug Therapy, Combination; Glaucoma; Humans; Intestinal Absorption; Keratitis, Herpetic; Latanoprost; Prostaglandins; Prostaglandins F, Synthetic; Recurrence; Simplexvirus; Valacyclovir; Valine; Virus Activation

To determine whether the systemic administration of valacyclovir (Valtrex) reduces ocular shedding of herpes simplex virus type 1 (HSV-1) after laser in situ keratomileusis (LASIK) in the New Zealand White (NZW) rabbit latency model.. Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.. New Zealand White rabbits latently infected with HSV-1 W strain were divided into 3 groups. The first received 100 mg/kg/day of valacyclovir; the second, 200 mg/kg/day of valacyclovir; and the third (control), saline. One half the total dose of valacyclovir was delivered via intraperitoneal injections twice daily for 7 days beginning with 1 dose before LASIK. The HSV-1 ocular shedding was determined from eye cultures for 7 days after LASIK.. The administration of both 100 mg/kg/day and 200 mg/kg/day of valacyclovir significantly reduced the number of eyes (1/16 in both groups) and the total number of HSV-1 shedding days (1/122 and 2/122, respectively) from which HSV-1 was recovered compared to the control group (7/16 [P =.0396] and 14/129 [P <.007], respectively).. Systemic administration of valacyclovir significantly reduced HSV-1 ocular shedding after LASIK in the NZW rabbit latency model. The clinical implications of this study suggest that patients with a history of recurrent ocular herpes may be able to safely have LASIK with less risk of a recurrent herpetic episode while on valacyclovir antiviral prophylaxis.

Topics: Acyclovir; Animals; Antiviral Agents; Cornea; Female; Herpesvirus 1, Human; Injections, Intraperitoneal; Keratitis, Herpetic; Keratomileusis, Laser In Situ; Rabbits; Valacyclovir; Valine; Virus Activation; Virus Shedding

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; HIV-1; Humans; Keratitis, Herpetic; Male; Middle Aged; Prodrugs; Purpura, Thrombotic Thrombocytopenic; Recurrence; Valacyclovir; Valine

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.

Topics: Acyclovir; Animals; Antiviral Agents; Female; Keratitis, Herpetic; Lasers, Excimer; Photorefractive Keratectomy; Postoperative Care; Rabbits; Secondary Prevention; Simplexvirus; Valacyclovir; Valine; Virus Activation