acyclovir and Keratitis--Herpetic

BACKGROUND Herpes simplex virus (HSV) stromal keratitis with ulceration is one of the most serious forms of herpes corneal infection and is one of the most difficult conditions in terms of clinical management. We assessed the efficacy of intravenous acyclovir in the treatment of this condition. CASE REPORT Two cases of HSV stromal keratitis with ulceration were reported in terms of clinical presentation, investigation, treatment, and outcome.Diagnosis was confirmed by polymerase chain reaction (PCR) analysis. PCR testing of corneal scraping samples identified HSV-1 in the first patient and HSV-2 in the second patient. The first patient initially presented with herpes geographic epithelial keratitis and progressed to HSV stromal keratitis with ulceration during treatment with a prophylactic dose of oral acyclovir. Despite oral acyclovir therapy, the cornea lesion continued to worsen. The treatment was switched to intravenous acyclovir. The stromal infiltration gradually improved, and the epithelial defect closed. The second patient, who had undergone penetrating keratoplasty for 13 years, presented with extensive corneal infiltration and corneal melting. The laboratory work-up was positive for HSV-2, and intravenous acyclovir was prescribed. The patient's corneal infiltration improved, but a persistent epithelial defect was present. Then, 100% autologous serum was used until the epithelial defect closed. Prophylactic treatment with oral acyclovir was prescribed to both patients to prevent disease recurrence. CONCLUSIONS Intravenous acyclovir might be considered as an alternative treatment for patients with HSV stromal keratitis with ulceration who do not respond to oral acyclovir or those with an extensive infection on a corneal graft.

Topics: Acyclovir; Antiviral Agents; Corneal Transplantation; Herpesvirus 1, Human; Humans; Keratitis, Herpetic

Neonatal herpes simplex virus (HSV) is an uncommon but devastating infection in the newborn, associated with significant morbidity and mortality. The use of PCR for identification of infected infants and acyclovir for treatment has significantly improved the prognosis for affected infants. The subsequent use of suppressive therapy with oral acyclovir following completion of parenteral treatment of acute disease has further enhanced the long-term prognosis for these infants. This review article will discuss the epidemiology, risk factors and routes of acquisition, clinical presentation, and evaluation of an infant suspected to have the infection, and treatment of proven neonatal HSV disease.

Topics: Acyclovir; Antiviral Agents; Cesarean Section; Delivery, Obstetric; Disseminated Intravascular Coagulation; Encephalitis, Herpes Simplex; Extraction, Obstetrical; Extraembryonic Membranes; Female; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Keratitis, Herpetic; Labor, Obstetric; Liver Failure; Pregnancy; Pregnancy Complications, Infectious; Prognosis; Respiratory Insufficiency; Risk Factors; Skin Diseases, Viral; Time Factors

To review recent advancements in the management of herpes simplex virus (HSV) epithelial keratitis.. Trifluridine eye drop, acyclovir (ACV) ointment, ganciclovir gel, and oral ACV are still the main therapeutic agents. Cryopreserved amniotic membrane has been recently used as an adjuvant treatment. Resistance to ACV has become a concerning issue. The animal models of HSV vaccine are able to reduce HSV keratitis. New antivirals are under development.. Current cases of HSV epithelial keratitis are manageable with available medications, but new advancements are required to decrease disease burden in the future. HSV vaccine can be revolutionary.

Topics: Acyclovir; Administration, Oral; Animals; Antiviral Agents; Disease Models, Animal; Epithelial Cells; Epithelium, Corneal; Eye Infections, Viral; Ganciclovir; Humans; Keratitis, Herpetic; Ointments; Ophthalmic Solutions; Trifluridine

The purpose of this review is to discuss the options for, and recent developments in, the surgical treatment of herpes keratitis. Although the mainstay of treatment of herpetic keratitis is topical or oral antiviral agents, surgical intervention may be necessary for corneal melting or long-term complications such as scarring, lipid keratopathy, necrotizing keratitis, and neurotrophic keratitis.. There are a number of surgical therapies available for herpes keratitis. Preferred therapeutic modalities differ based on the size, causation, and location of the infection but consist of either replacement of the infected tissue or structural support of the tissue to allow healing. Incremental improvements in the existing treatment modalities have made them more effective, easier, and safer, whereas novel therapies such as corneal neurotization are starting to be described in ophthalmic literature.. Several options are available for surgically managing the complications of herpes keratitis. Ophthalmologists should select the optimal procedure based on the individual patient's situation. VIDEO ABSTRACT: http://links.lww.com/COOP/A28.

Topics: Acyclovir; Antiviral Agents; Eye Infections, Viral; Humans; Keratitis, Herpetic; Ophthalmologic Surgical Procedures

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

Ocular herpes is a viral infection of the eye caused by the herpes simplex virus (HSV), a double-stranded DNA virus. Corneal scarring caused by herpes simplex keratitis (HSK) is the leading infectious cause of penetrating corneal graft in high-income countries. Acyclovir is an antiviral drug known to have a protective effect against recurrences in herpetic eye disease. While there are some studies which have evaluated the effects of intervention with oral antiviral in preventing such recurrences in people with corneal grafts, a systematic review of all comparative clinical trials has not been previously undertaken.. To assess the efficacy of oral antivirals such as acyclovir in any dosage when taken for six months or more, in preventing recurrence of herpetic keratitis in people having corneal graft surgery for herpetic keratitis.. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2016), Embase (January 1980 to June 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 1 June 2016. We handsearched conference proceedings and contacted authors of the included studies and researchers active in the field.. We included randomised controlled trials (RCTs). People enrolled in these trials had corneal grafts for HSK. The intervention was oral antivirals for six months or more following the corneal graft surgery, and this was compared to no treatment or placebo.. Two review authors independently assessed trial quality and extracted data. We contacted trial investigators for any clarification or missing information. We graded the certainty of the evidence using GRADE.. We included three trials, involving 126 participants, comparing the use of oral acyclovir to no treatment or placebo. Two studies were conducted in single centres in Turkey and the USA, and one was multi-centred in the Netherlands. In general, the studies were poorly reported and it was difficult to judge the extent to which bias had been avoided.Oral acyclovir may reduce the risk of recurrence of herpetic keratitis (risk ratio (RR) 0.29, 95% confidence interval (CI) 0.13 to 0.64, 126 people, low-certainty evidence). Based on data from the included trials, this corresponds to approximately 23 fewer cases of HSK recurrence (95% CI 29 fewer cases to 12 fewer cases) per 100 corneal graft operations if oral acyclovir is used.Oral acyclovir may reduce the risk of graft failure (RR 0.40, 95% CI 0.16 to 0.97, 126 people, low-certainty evidence). Based on data from the included trials, this corresponds to approximately 13 fewer cases of graft failure (95% CI 18 fewer cases to 1 fewer cases) per 100 corneal graft operations if oral acyclovir is used.None of the studies reported any serious side effects of the antivirals necessitating stoppage or change. None of the trials reported outcomes over the long term (more than two years) or any data on quality of life.. Compared to placebo or to no treatment, oral antiviral (acyclovir) may reduce the risk of recurrence of herpetic keratitis in the first 12 months in eyes that have undergone corneal graft surgery.

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Corneal Transplantation; Humans; Keratitis, Herpetic; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention; Time Factors

Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) are highly prevalent viruses capable of establishing lifelong infection. Genital herpes in women of childbearing age represents a major risk for mother-to-child transmission (MTCT) of HSV infection, with primary and first-episode genital HSV infections posing the highest risk. The advent of antiviral therapy with parenteral acyclovir has led to significant improvement in neonatal HSV disease mortality. Further studies are needed to improve the clinician's ability to identify infants at increased risk for HSV infection and prevent MTCT, and to develop novel antiviral agents with increased efficacy in infants with HSV infection.

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Herpes Genitalis; Herpes Simplex; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Keratitis, Herpetic; Male; Pregnancy; Pregnancy Complications, Infectious

This objective of the review and analysis is to demonstrate that acyclovir (ACV) 3% ophthalmic ointment is superior to idoxuridine (IDU) in treating herpetic keratitis (HK) presenting as dendritic and geographic ulcer sub-types.. Publications in human subjects were identified by searching the Ovid MEDLINE database through April 2011, combining medical subject headings (MESH) "Keratitis, Herpetic/" AND "Acyclovir/" limiting by the key words "topical" OR "ointment" and also restricted to MESH "Administration, Topical/" OR "Ointments/". The results were cross checked with the references used in the Cochrane Database Syst Rev. 1:1-134, 2009 and GlaxoSmithKline clinical documents related to acyclovir.. Randomized, double-masked studies in subjects diagnosed with HK with head to head comparator arms of ACV ophthalmic ointment and topical IDU that had actual or calculable healing rates at Day seven.. Data independently extracted from identified articles by two authors of this manuscript.. Data from seven randomized, controlled trials (RCT) evaluating 432 subjects that met inclusion criteria (214 were treated with ACV and 218 were treated with IDU) and had Day seven healing rates calculable. All sub-classified lesions were identified as either dendritic ulcers (n = 185) or geographic ulcers (n = 35). The Cochran-Mantel-Haenszel (CMH) method in Biometrics 10:417-51, 1954 and JNCI 22:719-48, 1959, controlling for study, was performed as the primary analysis using SAS v9. Homogeneity was assessed using Breslow-Day-Tarone (BDT) test in IARC 1:1-32, 1980 and Biometrika 72:91-5, 1985. The analysis was performed with outliers removed to assess their impact.. ACV showed statistically significant greater odds of healing HK at Day seven in all subjects (Odds Ratio 3.95, 95% CI2.60, 6.00, p < 0.0001), in dendritic ulcers (Odds Ratio 4.22, 95% CI: 2.14, 8.32; p < 0.0001) and geographic ulcers (Odds Ratio 5.31, 95% CI: 1.09, 25.93; p = 0.0244).. ACV 3% ophthalmic ointment is a valuable intervention for dendritic and geographic corneal ulcers. ACV and IDU were generally well tolerated in the studies reviewed.

Topics: Acyclovir; Antiviral Agents; Follow-Up Studies; Humans; Idoxuridine; Keratitis, Herpetic; Ointments; Time Factors; Treatment Outcome

In Europe, herpes simplex virus type I (HSV) is a common cause of keratitis. The disease may be well treated if the ophthalmologtist is aware of the various types of clinical expressions of this typical unilateral chameleon, and treatment is adjusted accordingly. Types of expression include: (i) epithelial keratitis (dendritica/geographica), (ii) stromal keratitis (necrotising vs. non-necrotising = "interstitial keratitis"), (iii) endotheliitis (= "disciform keratitis"), (iv) so-called "metaherpetic keratitis" (= neurotrophic keratopathy), (v) (vascularised) corneal scars. In the acute phase, concomitant ocular hypertension should be treated predominantly without surgery (no prostaglandin analoga!). After keratoplasty and in cases of severe recurrences of herpetic keratitis, systemic aciclovir administration (2 × 400 mg/day) for at least one year is indispensable!

Topics: Acyclovir; Antiviral Agents; Diagnosis, Differential; Europe; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating

The treatment of patients with various forms of herpes requires a complex approach with using chemo- and immunotropic drugs. The use of Cycloferon, an interferon inductor (12.5% injection solution, 150 mg tablets or 5% liniment) was shown efficient. It had antiviral and immunotropic action in the mono- and combination therapy of herpes simplex of the skin and mucosa, genital herpes, ophthalmoherpes, herpes zoster, infectious mononucleosis. Cycloferon lowered the level and period of the disease clinical signs, prolonged the remission, corrected the immunity shifts, prevented the complications. The results of the study presented a conclusive proof for recommending such a use of Cycloferon in wide medical practice.

Topics: Acridines; Acyclovir; Antiviral Agents; Female; Herpes Genitalis; Herpes Labialis; Herpes Zoster; Herpesviridae; Humans; Immunity, Innate; Infectious Mononucleosis; Interferon Inducers; Keratitis, Herpetic; Male

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

To summarize the articles published in 2012 pertaining to the clinical presentation, diagnosis, and treatment of herpetic keratitis, with specific attention to pediatric population.. Liu et al. confirm prior literature that herpetic keratitis has higher recurrence rate in children than adults. Recurrences are more likely to occur as stromal disease. Vision loss in children is from corneal scarring leading to deprivation and/or refractive amblyopia. Acyclovir is safe and well tolerated as a treatment in pediatric population, and preferable to difficult and toxic eye-drop regimens.Immunochromatographic assay is an effective diagnostic tool to confirm diagnosis of herpes simplex virus-1 (HSV) in corneal scrapings with high specificity but poorer sensitivity.Real time PCR can be employed to follow changes in HSV viral load in patients where resistance is suspected.. Delays in treatment related to misdiagnosis, as well as resistance to current antiviral therapeutics, can lead to visually devastating corneal opacification. In the pediatric population, already at risk for amblyopia, this can be especially damaging. Children are unique with regards to the way in which they manifest herpetic keratitis, making rapid diagnosis and treatment even more challenging.

Topics: Acyclovir; Antibodies, Viral; Antiviral Agents; Child; Child, Preschool; Chromatography, Affinity; Herpesvirus 1, Human; Humans; Infant; Keratitis, Herpetic

Herpes simplex virus (HSV) keratitis is a common cause of ocular morbidity. Resistance to aciclovir is probably under recognized. We describe three cases of aciclovir-resistant herpes simplex virus keratitis treated with systemic foscarnet and present a review of the pharmacological options available to manage this condition.

Topics: Acyclovir; Administration, Oral; Administration, Topical; Aged, 80 and over; Antiviral Agents; Blindness; Drug Resistance, Viral; Humans; Keratitis, Herpetic; Male; Middle Aged; Treatment Outcome

The development of novel strategies to eradicate herpes simplex virus (HSV) is a global public health priority. While acyclovir and related nucleoside analogues provide successful modalities for treatment and suppression, HSV remains highly prevalent worldwide and is a major cofactor fueling the HIV epidemic. HSV is the predominant cause of genital ulcerative disease, and neonatal and sporadic infectious encephalitis. Asymptomatic shedding, which occurs more frequently than previously appreciated, contributes to viral transmission. Acyclovir resistance may be problematic for immunocompromised patients and highlights the need for new safe and effective agents. Ideally, vaccines to prevent infection, drugs to inhibit the establishment of or reactivation from latency, or vaginal microbicides to prevent sexual and perinatal transmission are needed to control the epidemic. This review summarizes current therapeutic options and strategies in development.

Topics: Acyclovir; Anti-Infective Agents; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Herpes Genitalis; Herpes Simplex; HIV Infections; Humans; Infant, Newborn; Keratitis, Herpetic; Male; Pregnancy; Stomatitis, Herpetic; Syndrome; Viral Vaccines

Ocular infection with herpes simplex virus (HSV) is usually acquired early in life, with 50% of people from higher and 80% from lower socioeconomic groups in the USA having antibodies by the age of 30 years. Attacks usually resolve spontaneously within 1-2 weeks, but 50% of people will experience a recurrence within 10 years.. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in people with epithelial keratitis? What are the effects of treatments in people with stomal keratitis? What are the effects of interventions to prevent recurrence of ocular herpes simplex? What are the effects of interventions to prevent recurrence of ocular herpes simplex in people with corneal grafts? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).. We found seven systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.. In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding oral aciclovir to topical corticosteroids plus topical antiviral treatment; adding topical corticosteroids to topical antiviral treatment; antiviral agents (topical); debridement; interferons (topical); and oral aciclovir.

Topics: Acute Disease; Acyclovir; Administration, Oral; Antiviral Agents; Debridement; Humans; Interferons; Keratitis, Herpetic; Recurrence

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

Topics: Acyclovir; Antiviral Agents; Humans; Interferons; Keratitis, Herpetic; Secondary Prevention

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

Topics: Acyclovir; Antiviral Agents; Debridement; Humans; Interferons; Keratitis, Herpetic; Prednisolone; Secondary Prevention

Topics: Acyclovir; Adolescent; Antiviral Agents; Child; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Infant, Newborn; Keratitis, Herpetic; Prognosis

Herpetic keratitis is characterized by spontaneous recurrences and a risk of vision loss, the latter being more serious when relapses are frequent and severe. Two clinical forms are commonly distinguished: epithelial keratitis, usually quickly resolved with topical antivirals, and stromal keratitis, which has a slower progression, even when both steroids and antivirals are used. Great strides have been made during the last 20 Years in the therapy of herpes keratitis, which is now considered and treated as a chronic disease. Randomized controlled studies definitively showed the decrease in spontaneous herpetic ocular events in patients treated with long-term oral acyclovir. The effectiveness of preventive treatment has also been shown during high-risk periods, especially ocular surgery, in patients with a history of herpes keratitis. However, the optimal duration and dosage of antiviral prevention have yet to be defined. We can also hope that in the future novel antiviral strategies such as vaccination will reduce the place of herpes keratitis as an indication for corneal graft.

Topics: Acyclovir; Antiviral Agents; Ganciclovir; Humans; Idoxuridine; Keratitis, Herpetic; Trifluridine

To describe the spectrum and recurrence of herpes simplex virus (HSV) keratitis in children and adolescents.. Retrospective cohort study.. Twenty-three patients younger than age 16 years were diagnosed with HSV keratitis at one institution.. All children presented with dendritic or punctate epithelial keratitis, and stromal keratitis occurred concurrently with epithelial keratitis in 14 patients (61%). Six patients (26%) had bilateral HSV keratitis. Eleven patients (48%) developed recurrent HSV keratitis at a median of 15 months after the first documented episode. Amblyopia occurred in three children.. Children with herpetic keratitis may have bilateral ocular involvement and are at risk for recurrent keratitis and amblyopia.

Topics: Acyclovir; Adolescent; Amblyopia; Antiviral Agents; Child; Child, Preschool; Cohort Studies; Corneal Stroma; Epithelium, Corneal; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Recurrence; Retrospective Studies; Trifluridine; Vidarabine

Topics: Acyclovir; Antiviral Agents; Debridement; Humans; Interferons; Keratitis, Herpetic; Prednisolone; Secondary Prevention

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Corneal Transplantation; Debridement; Humans; Interferons; Keratitis, Herpetic; Ophthalmic Solutions; Prednisolone; Secondary Prevention

Topics: Acyclovir; Administration, Oral; Administration, Topical; Adrenal Cortex Hormones; Antiviral Agents; Debridement; Drug Administration Schedule; Humans; Interferons; Keratitis, Herpetic; Randomized Controlled Trials as Topic; Treatment Outcome

The prognosis of herpetic keratitis has been dramatically improved during the past years because of a better understanding of their physio-pathologic phenomenons, and mostly because of the use of very efficient antiviral drugs. Superficial keratitis are easily cured in most cases; deep stromal keratitis, that often require corticosteroid treatment, are more difficult to heal. Prophylactic treatment of the recurrences by oral antiviral drugs represents a promising new concept for herpetic keratitis.

Topics: Acyclovir; Adrenal Cortex Hormones; Antiviral Agents; Clinical Trials as Topic; Contraindications; Corneal Transplantation; Endophthalmitis; France; Humans; Keratitis, Herpetic; Multicenter Studies as Topic; Recurrence; United States

Topics: Acyclovir; Administration, Oral; Administration, Topical; Adrenal Cortex Hormones; Antiviral Agents; Debridement; Drug Administration Schedule; Humans; Interferons; Keratitis, Herpetic

Herpes simplex virus (HSV) is a leading cause of chronic infectious ocular disease in the United States. The morbidity from recurrent herpetic episodes is high, and the resultant corneal scarring may require penetrating keratoplasty for visual rehabilitation. Effective treatments for acute episodes of HSV have been verified by early Herpetic Eye Disease Study (HEDS) trials. The recent HEDS trial on the efficacy of oral acyclovir as prophylaxis against recurrent stromal keratitis represents the first report of a treatment likely to reduce long-term scarring from herpetic disease. This article reviews all the HEDS trials and the implications of their findings for the management of patients with ocular HSV.

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Corneal Stroma; Humans; Iritis; Keratitis, Herpetic; Prednisolone; Randomized Controlled Trials as Topic; Recurrence; Trifluridine

Topics: Acyclovir; Antiviral Agents; Corneal Transplantation; Graft Rejection; Humans; Keratitis, Herpetic; Recurrence

Since the introduction of acyclovir in the last decade, the visual prognosis of herpetic keratitis has improved dramatically. Benefits with this superb agent include rapid resolution of epithelial keratitis, reduction of disturbances in ocular surface epithelia, and a decreased incidence of necrotizing keratitis or subsequent corneal melting. On the other hand, persistent superficial punctate keratopathy associated with topical usage, emergence of an acyclovir-resistant strain of herpes simplex virus, and a gradual increase in progressive corneal endotheliitis comprise the problems to be resolved.

Topics: Acyclovir; Administration, Topical; Animals; Antiviral Agents; Cornea; Humans; Keratitis, Herpetic; Ophthalmic Solutions; Prognosis; Simplexvirus; Visual Acuity

Topics: Acyclovir; Administration, Oral; Anti-Inflammatory Agents; Antiviral Agents; Clinical Trials as Topic; Humans; Keratitis, Herpetic; Multicenter Studies as Topic; Ophthalmic Solutions; Patient Participation; Prednisolone; Randomized Controlled Trials as Topic; Recurrence

Topics: Acyclovir; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating; Virus Latency

Topics: Acyclovir; Adolescent; Adult; Diagnosis, Differential; Humans; Infant; Kaposi Varicelliform Eruption; Keratitis, Herpetic

First, to characterize the histologic features of corneal buttons taken from two patients with chronic active herpetic stromal keratitis. Both eyes had suffered frequent and prolonged viral epithelial recurrences despite topical and systemic antiviral therapy and developed uniquely rapid deposition of chalklike stromal deposits. Second, to determine the clinical outcome of surgical intervention in eyes with such a pattern of herpetic disease.. Patients received topical antiviral medication and 200 to 400 mg of acyclovir five times daily for 2 or 5 months until penetrating keratoplasty. They received tapered doses of acyclovir after surgery. Corneal buttons were evaluated with light microscopy and electron microscopy.. Light microscopy of the specimens revealed calcium in the area of the chalklike deposits and a few cocci in the deep stroma. Electron microscopy showed numerous herpetic viral particles at various stages of maturity, including completely enveloped organisms, in the basal cells and keratocytes, and a few cocci in basal cells. Apart from one minor recurrence of a dendritic ulcer, both patients were free of herpetic disease at 13 and 22 months, required little to no medication, and had clear grafts.. Rapid calcium deposition in herpetic corneas may indicate disease of sufficient severity to warrant surgical intervention for removal of a stromal viral reservoir. Such intervention can stop further recurrences of keratitis that is poorly controlled by antiviral therapy. Such chronically diseased eyes may also harbor unsuspected bacterial infection.

Topics: Acyclovir; Aged; Aged, 80 and over; Calcinosis; Corneal Stroma; Drug Administration Schedule; Female; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating; Middle Aged; Ophthalmic Solutions; Recurrence; Simplexvirus; Virus Replication

Corneal transplantation is a common surgical intervention for restoring vision loss due to corneal damages. However, for cultural reasons, there is a huge shortage of donor corneas in China. Acellular porcine corneal stromas (APCSs) can be used as corneal substitutes in lamellar keratoplasty for corneal ulcers. This study was conducted to analyze the results of APCS use for herpes simplex keratitis (HSK).. The study involved HSK patients who underwent keratoplasty with APCSs from February 2016 to October 2017 in the second affiliated hospital of Zhejiang University. Patient data were collected at 7 days, 1 month, 3 months, 6 months, and at the last follow-up (7-25 months) postoperative. The corneal transparency, neovascularization, visual acuity, and graft stability were observed.. Thirteen patients with HSK including five patients with corneal perforation were included in this study, nine patients underwent deep anterior lamellar keratoplasty (DALK) and five perforation patients underwent double lamellar keratoplasty. There were nine men and four women with an average age of 62.5 ± 5.6 years old (ranging from 52 to 70 years old). The mean postoperative follow-up duration was 15.1 ± 5.8 months (ranging from 7 to 25 months). At the last visit, visual acuity improved in nine patients (69.2%) compared with preoperative (P = 0.008).The grafts of seven individuals (53.8%) were completely transparent or slightly opaque; their corneal transparency score had improved significantly compared with before the surgery (P = 0.010). Various degrees of neovascularization were present in 11 of the 13 patients (84.6%), most neovascularization gradually stabilized. Graft dissolution occurred in three eyes (23.1%) during the observation period, two underwent regrafting, the other one became stable after treatment. Three patients underwent second allograft transplantation, two of which encountered APCS graft dissolution and one of the patients requested a human donor allograft transplantation due to transparency issues despite the absence of adverse issues.. Acellular porcine corneal stroma seems to be effective in the treatment of HSK and can be used in HSK with corneal perforation by using double lamellar keratoplasty in an emergency.

Topics: Acyclovir; Aged; Animals; Antiviral Agents; Corneal Neovascularization; Corneal Opacity; Corneal Perforation; Corneal Stroma; Corneal Transplantation; Female; Humans; Keratitis, Herpetic; Male; Middle Aged; Ophthalmic Solutions; Postoperative Complications; Swine; Transplantation, Heterologous; Treatment Outcome

To validate photographic bioimaging for evaluating the severity of herpes simplex virus keratitis.. Stromal keratitis of patients in the Herpetic Eye Disease Study was clinically measured with a slitbeam micrometer and then photographed at trial entry. Calibrated images of 169 eyes were analyzed for the size, location, and density of stromal keratitis and endotheliitis, with shape factor as a function of area and perimeter. Validity was assessed by comparing clinical and computerized measurements and by correlating the keratitis area with visual acuity. Logistic regression explored characteristics associated with larger or denser corneal inflammation.. Stromal keratitis had a median area of 22.4 mm(2) (interquartile range, 12.8-31.6 mm(2)) with a median shape factor of 0.69 (interquartile range, 0.56-0.79); 126 eyes (75%) had their midpoint within 2 mm of the cornea's geometric center. Photoanalytical area estimates of herpetic stromal keratitis correlated closely with clinical measurements (correlation coefficient, 0.83). Eyes with larger stromal keratitis had worse vision (correlation coefficient, 0.32) and were more likely to have iritis (P = .01). Necrotizing stromal keratitis was significantly whiter (P = .02).. Image analysis validly assesses the disciform geometry of herpetic stromal keratitis and confirms that increased severity is associated with uveitis and reduced vision.

Topics: Acyclovir; Antiviral Agents; Corneal Stroma; Cross-Sectional Studies; Female; Humans; Image Processing, Computer-Assisted; Keratitis, Herpetic; Male; Microscopy; Middle Aged; Photography; Trifluridine

To investigate the long-term effect of oral acyclovir administered during the first 6 months after penetrating keratoplasty (PK) for herpetic eye disease (HED).. A 5-year follow-up was undertaken for a patient population from a placebo-controlled, randomized trial on acyclovir prophylaxis after keratoplasty. In this former study the effectiveness of oral acyclovir prophylaxis was significant during the first 2 years after keratoplasty. Prospective data such as graft survival, graft clarity, vascularization, infective events, and rejection episodes were obtained from the national keratoplasty follow-up registry. Additional clinical data were derived from the medical charts.. For 47 of the original 63 enrolled patients, the 5-year follow-up was completed. Comparing the acyclovir group with the placebo group, we found that with regard to the cumulative clinically evident recurrences, there was a statistically significant lower monthly event rate in the acyclovir group (P = 0.037). There were no statistically significant differences in visual acuity or in the use of oral aciclovir between the two treatment groups. The incidences of graft failure, vascularization, and medication or surgery for glaucoma were too low to analyze differences between the two groups.. The results of our study suggest that oral acyclovir prescribed during the first 6 months after PK for HED protects against clinically evident HED recurrences during the first 5 years following PK.

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Drug Administration Schedule; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Kaplan-Meier Estimate; Keratitis, Herpetic; Keratoplasty, Penetrating; Postoperative Care; Postoperative Complications; Postoperative Period; Secondary Prevention; Treatment Outcome; Visual Acuity

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

To estimate the cost of treating herpes simplex virus (HSV) eye disease, and to evaluate the incremental cost-effectiveness of chronic suppressive antiviral prophylaxis for reducing ocular HSV recurrences.. An economic decision-tree model was used on follow-up data from 703 patients with prior ocular HSV disease who were enrolled in a Herpetic Eye Disease Study multicenter clinical trial that evaluated the prolonged use of oral acyclovir. Costs were based on wholesale drug prices, Medicare fees, and national health surveys. Incremental cost-effectiveness ratios for all patients and for patients with prior stromal keratitis were calculated as the additional net cost of acyclovir prophylaxis compared with the number of cases of ocular herpes prevented during 12 months. One- and 2-way sensitivity analyses evaluated the effect of different treatment costs and recurrence risks.. Approximately 17.7 US dollars million is expended annually to treat the estimated 59,000 new and recurrent episodes of HSV eye disease occurring among 29,000 individuals each year in the United States. Chronic suppressive oral acyclovir costs 8532 US dollars per ocular HSV episode averted. The incremental cost per infection averted would decline by up to 51% if antiviral prophylaxis were more effective and by up to 87% if patients had a higher recurrence risk. Targeting prophylaxis to patients with a history of stromal keratitis is not more cost-effective than providing oral acyclovir for patients with any prior HSV eye disease.. Herpetic eye disease is costly to treat and prevent. Because prophylactic oral acyclovir is not a cost-effective option for all patients with previous HSV eye disease, therapeutic decisions must be made on a case-by-case basis.

Topics: Acyclovir; Antiviral Agents; Cost-Benefit Analysis; Decision Trees; Drug Costs; Health Services Research; Humans; Keratitis, Herpetic; Models, Economic; Premedication; Secondary Prevention; United States

The main reasons for graft failure following penetrating keratoplasty in patients with herpetic eye disease are recurrence of herpetic disease and allograft rejection. In a randomised trial the effect of systemic acyclovir and mycophenolate mofetil (MMF) on these post-keratoplasty complications was evaluated.. Patients with typical clinical findings of recurrent herpetic keratitis were enrolled in this single-centre study after contraindications to systemic immunosuppression were ruled out. In a prospective randomised trial 30 patients were treated in three groups. In group A patients received acyclovir 200 mg five times/day for 3 weeks. In group B patients were treated with acyclovir 200 mg five times/day for 1 year, and patients in group C received acyclovir 200 mg five times/day in combination with MMF 1 g twice daily for 1 year.. In group A 3 patients experienced seven herpes recurrences. One patient had a moderate and one further patient a severe allograft rejection. In group B three severe allograft rejections were observed. Herpes recurrences did not occur while receiving acyclovir prophylaxis, but only once after the prophylaxis had been stopped. In group C no herpes recurrence was observed, and only two mild allograft rejections occurred while being under combined acyclovir-MMF therapy. Another mild and one moderate allograft rejection were observed after cessation of MMF.. These results demonstrate that systemic acyclovir protects the grafts from recurrences of herpetic disease as long as it is administered at efficient doses. Simultaneously administered mycophenolate mofetil does not trigger herpes recurrences and protects the graft from severe allograft rejections, but mild, less dangerous immune reactions may still occur while receiving MMF. The combination of systemic acyclovir and mycophenolate mofetil therefore is recommended for patients at high risk for herpes recurrence and allograft rejections.

Topics: Acyclovir; Aged; Antiviral Agents; Drug Synergism; Drug Therapy, Combination; Female; Graft Rejection; Herpesvirus 1, Human; Humans; Immunosuppressive Agents; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Middle Aged; Mycophenolic Acid; Pilot Projects; Postoperative Complications; Prospective Studies; Recurrence; Virus Activation

To determine the prophylactic effect of oral acyclovir on the recurrence rate of herpetic eye disease after penetrating keratoplasty.. A randomized, double-masked, placebo-controlled multicenter trial.. Sixty-eight consecutive patients (68 eyes) with corneal opacities due to herpetic eye disease who underwent penetrating keratoplasty.. Oral acyclovir 400 mg twice daily or placebo tablets for 6 months.. The recurrence rate of herpetic eye disease-related events and rejection episodes, proven by viral cell culture or polymerase chain reaction.. During the 2-year follow-up period, there were 3 culture-proven herpetic eye disease recurrences in the acyclovir group and 9 in the placebo group. Lifetime survival analysis of the probability of remaining free from recurrence revealed a significantly reduced risk of recurrent herpetic disease in the acyclovir-treated group.. This study suggests that oral acyclovir effectively prevents herpes-related recurrences after penetrating keratoplasty in herpetic eye disease.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Aged; Antiviral Agents; Corneal Opacity; Double-Blind Method; Female; Graft Rejection; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Middle Aged; Postoperative Complications; Secondary Prevention

To determine the clinical character of patients with keratoplasty after viral keratitis and comparison of pre- and postoperative visual acuity.. The study involved 24 patients treated using corneal graft after viral keratitis complications. Sex, age, permanent residence, duration of disease, previous pharmacological treatment, indications to corneal graft and postoperative functional results were evaluated.. In 24 cases 16 (66.7%) were males in age 38-75 years old. Eight (33.3%) of the 24 cases were females in age 12-78 years old. Visual acuity improvement after corneal graft was observed in 23 patients. There was no visual acuity improvement in one case with considerable degree of optic nerve lesion.. The results of these examinations showed, that keratoplasty after viral keratitis complications were more frequent in males, especially in 40-59 age range, professionally engaged. Statistical analysis of these cases showed good prognosis of visual acuity improvement after surgical treatment.

Topics: Acyclovir; Adult; Aged; Corneal Transplantation; Female; Humans; Keratitis, Herpetic; Male; Middle Aged; Premedication; Treatment Outcome; Visual Acuity

To evaluate the role of acyclovir in treatment and prevention of herpes simplex keratitis (HSK).. A total of 105 patients with HSK were divided into 4 groups. Group 1 consisted of 79 patients with HSV epithelial keratitis. Group 2 consisted of 20 patients with interstitial keratitis. Group 3 consisted of 6 patients with necrotizing keratitis. Group 4 consisted of 4 necrotizing keratitis patients with corneal perforation treated with conjunctival flap and corneal transplantation. All patients were treated with acyclovir systemically and topically. After full recovery, the patients with epithelial HSK and stromal HSK were randomly divided into two groups individually. One group was constantly treated with oral acyclovir at 300 mg/day for 1 year as a prophylaxis group. The other group was designated as control.. During the one-year treatment and follow-up, 5 cases with epithelial HSK recurred in the prophylaxis group and 14 cases in the control group, showing a statistically significant difference. One case of stromal HSK recurred in the prophylaxis group and 4 recurred in the control group.. Long term and low dose oral acyclovir for prophylaxis of recurrent epithelial herpes simplex infection and therapeutic doses of oral acyclovir reduce both the rate and duration of recurrences of infectious herpes simplex keratitis.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Child; Female; Humans; Keratitis, Herpetic; Male; Middle Aged; Recurrence

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.

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Blepharitis; Child; Conjunctivitis, Viral; Corneal Stroma; Epithelium, Corneal; Female; Herpesvirus 1, Human; Humans; Iritis; Keratitis, Herpetic; Male; Middle Aged; Recurrence; Risk Factors

Herpes simplex virus (HSV) infection is the most common cause of corneal blindness in developed countries. Penetrating keratoplasty is the only therapeutic option for visual rehabilitation in patients with severely scarred corneas. Recurrence of the underlying disease and allograft rejection (AR) are the common causes of graft failure. Systemic immuno-suppression with cyclosporin A is contraindicated due to the risk of HSV recurrence. The potent immunosuppressive properties of mycophenolate mofetil (MMF) have already been shown clinically. By reducing the intracellular guanosid-pool MMF inhibits the proliferation of lymphocytes. As these quanosin-nucleosides also act as competing substrates to acyclovir at the viral DNA-polymerase, a synergistic effect of MMF and acyclovir might be expected. The aim of this study was to evalute the efficacy and safety of a double-drug regimen with MMF and acyclovir in the prevention of acute allograft rejection and HSV recurrence following corneal transplantation.. Patients following penetrating keratoplasty due to herpetic eye disease have been treated with MMF 1 g twice dialy and acyclovir 5 x 200 mg/day for one year. Primary efficacy variables have been the number of acute AR and recurrence of herpetic disease per patient and time. The number of adverse events has been documented for safety analysis.. Fifteen patients have been enrolled. The average follow up period was 9.1 (+/- 5.2) months. No graft opacifications have been seen. With two AR and no recurrence of herpetic disease the efficacy ofthis therapeutic regimen was supperior compared with historical control groups.. In this first study on the efficacy and safety of a double drum regimen with acyclovir and MMF for the control of acute corneal AR and HSV-recurrenct following keratoplasty in patients with herpetic eye disease, the combination therapy has been shown to be a safe and highly efficient protocol for graft protection.

Topics: Acyclovir; Adult; Antiviral Agents; Drug Synergism; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Middle Aged; Mycophenolic Acid; Pilot Projects; Secondary Prevention; Survival Analysis; Treatment Outcome

To investigate the effect of oral acyclovir therapy for recurrences of herpes simplex virus (HSV) epithelial keratitis and stromal keratitis and to determine if certain patients derive differential benefit.. This randomized, double-masked clinical trial enrolled 703 immunocompetent patients with prior HSV eye disease within the preceding year; assigned 357 patients to receive oral acyclovir, 800 mg/d, and 346 to receive placebo; and followed up patients during a 12-month treatment period for the development of HSV eye disease.. The cumulative probability of a recurrence of any type of ocular HSV disease during the 1-year treatment period was 19% in the acyclovir group compared with 32% in the placebo group. Sixteen patients in the acyclovir group and 30 in the placebo group had more than 1 recurrence. A benefit was seen for preventing both epithelial keratitis (rate ratio, 0.62; 95% confidence interval, 0.39-0.97) and stromal keratitis (rate ratio, 0. 57; 95% confidence interval, 0.36-0.89). Although a relative benefit of treatment on preventing any type of recurrence was present in most subgroups, the magnitude of absolute benefit was greatest among patients with the highest number of prior episodes of ocular HSV disease. The benefit in preventing stromal keratitis was seen solely among patients with a history of stromal keratitis.. Long-term suppressive oral acyclovir therapy reduces the rate of recurrent HSV epithelial keratitis and stromal keratitis. Acyclovir's benefit is greatest for patients who have experienced prior HSV stromal keratitis. Arch Ophthalmol. 2000;118:1030-1036

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Aged; Antiviral Agents; Child; Corneal Stroma; Double-Blind Method; Epithelium, Corneal; Female; Humans; Keratitis, Herpetic; Male; Middle Aged; Secondary Prevention

In stromal keratitis induced by herpes simplex virus (HSV) the host's immune response contributes to corneal scarring and neovascularization. The purpose of this study was to analyze the efficacy of topically applied cyclosporin A (CsA) in patients with HSV keratitis.. The authors performed a prospective pilot study in patients with HSV stromal keratitis (n = 18). Eyes were treated with CsA eyedrops and acyclovir ointment. The drugs were tapered off gradually. Visual acuity, slit-lamp appearance, intraocular pressure and corneal sensitivity were evaluated monthly (follow-up 5.2+/-0.28 months, mean +/- SEM.. Keratitis resolved with CsA treatment in 10 of 14 patients with non-necrotizing keratitis and in 2 of 4 with necrotizing keratitis. As CsA was used topically, the corticosteroids could be withdrawn in all patients with non-necrotizing keratitis and in 1 of 3 with necrotizing keratitis. Under CsA therapy, persistent or progressive inflammation was noted in 6 of the 18 patients. These 6 patients with keratitis improved only with combined CsA/corticosteroids. Corneal ulcers healed in 4 patients with topical CsA, and corneal neovascularization improved in a further 8. Except for toxic epitheliopathy, no further CsA complications were noted.. The findings in this pilot study suggest that HSV stromal keratitis can be treated successfully with CsA eyedrops, especially in non-necrotizing disease. CsA may be particularly helpful in the presence of steroid glaucoma, herpetic corneal ulcers, and to taper off topical corticosteroids. Additional use of acyclovir may aid in suppressing the recurrence of epithelial HSV keratitis. A randomized study should be performed to evaluate the role of topical CsA in more detail.

Topics: Acyclovir; Antiviral Agents; Corneal Stroma; Cyclosporine; Drug Therapy, Combination; Female; Follow-Up Studies; Glucocorticoids; Herpesvirus 1, Human; Humans; Immunosuppressive Agents; Keratitis, Herpetic; Male; Middle Aged; Ointments; Ophthalmic Solutions; Pilot Projects; Prospective Studies; Treatment Outcome; Visual Acuity

To evaluate the efficacy of long-term and low-dose prophylactic oral acyclovir therapy in preventing the recurrence of herpetic infection and increasing graft survival in patients who undergo penetrating keratoplasty (PK) for herpes simplex keratitis (HSK).. Nineteen patients were included in the study, who underwent PK for herpes keratitis from July 1993 to November 1995, received oral acyclovir, and were followed at least 12 months. Group 1 included 12 patients with corneal scarring without perforation. These patients were free of inflammation for a mean of 4.1+/-2.2 months preoperatively, and received oral acyclovir 400 mg/day postoperatively for one year. Seven patients (Group 2) who developed corneal perforation due to necrotizing keratitis were treated with tissue adhesives, therapeutic contact lenses, and topical antiviral and oral acyclovir therapy for the resolution of active inflammation followed by PK after a mean of 3.8+/-2.1 months follow-up. They received oral acyclovir 400 mg/day postoperatively for one year in addition to standard postoperative therapy. The control group consisted of 16 patients (Groups 3 and 4) who underwent PK for herpes simplex keratitis and did not receive oral acyclovir. The indication for PK was corneal opacity and impaired visual acuity in 12 patients (Group 3) and corneal perforation in four (Group 4).. After an average of 25 months follow-up, there was only one recurrence (8.3%) in Group 1 and two cases (28.6%) of herpetic recurrence in Group 2. Recurrence occurred at two months in one patient while he was taking oral acyclovir. Two of these recurrences followed the withdrawal of oral acyclovir therapy after one year of therapy. In contrast, in control groups there were four cases of herpetic recurrence (33.3%) in Group 3 and two (50%) in Group 4 after a mean of 30.5 months postoperative follow-up. In the study groups, a rejection episode was seen in three patients (15.8%) which was successfully treated with medical therapy. One patient from Group 2 developed bacterial keratitis which subsequently resulted in graft failure. All grafts remained clear in the other patients (94.7%). In the control groups, rejection developed in seven patients. Three rejection episodes were treated successfully. The other four developed graft failure in spite of intensive medical therapy.. Our results suggest that postoperative oral acyclovir therapy is effective in preventing the recurrence of herpetic infection. However, the recurrence may develop after cessation of oral acyclovir therapy, especially in patients who underwent PK for corneal perforation due necrotizing HSK.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Aged; Antiviral Agents; Female; Follow-Up Studies; Graft Survival; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Middle Aged; Postoperative Complications; Recurrence; Retrospective Studies

The paper presents a study of the associated effect of acyclovir and a plant extract from Calendula officinalis, Actium lappa and Geranium robertianum. We studied a number of 52 patients suffering of herpetic keratitis. Better results in resolving complains and faster healing of ulceration were obtained using the associated treatment then the usual acyclovir treatment only.

Topics: Acyclovir; Adult; Antiviral Agents; Calendula; Drug Combinations; Drug Therapy, Combination; Female; Humans; Keratitis, Herpetic; Male; Phytotherapy; Plant Extracts; Plants, Medicinal; Romania

There were investigated 51 patients, 19 female and 32 male, with ages between 12 and 80 years, hospitalized in the Dept. Ophthalm. of the City Hospital of Arad, during 1995-1997. From these, 21 had the clinical diagnosis of superficial keratitis, typical form of dendritic ulcer, 7 had non-typical forms, and 4 had stromal keratitis; 19 patients recurred. The diagnosis of herpetic keratitis was established correlating the clinical aspect with the cytologic examination, made on conjunctivo-corneane smears. A number of 32 patients received a specific treatment with Acyclovir, in an ointment form in local applications and on general route orally; there were also associated mydriatics and epitelizants of the cornea. The evolution of the disease was evaluated by comparing results obtained in different groups of patients.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Child; Female; Humans; Keratitis, Herpetic; Male; Middle Aged; Recurrence; Time Factors

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Clinical Trials as Topic; Humans; Iritis; Keratitis, Herpetic; Recurrence

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.. 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.. 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<0.001). Among the 337 patients with a history of stromal keratitis, the most common serious form of ocular HSV disease, the cumulative probability of recurrent stromal keratitis was 14 percent in the acyclovir group and 28 percent in the placebo group (P=0.005). The cumulative probability of a recurrence of nonocular (primarily orofacial) HSV disease was also lower in the acyclovir group than in the placebo group (19 percent vs. 36 percent, P<0.001). There was no rebound in the rate of HSV disease in the six months after treatment with acyclovir was stopped.. 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.

Topics: Acyclovir; Antiviral Agents; Blepharitis; Conjunctivitis; Female; Humans; Incidence; Iritis; Keratitis, Herpetic; Male; Middle Aged; Secondary Prevention; Treatment Outcome

Ganciclovir is a broad-spectrum virustatic agent. Its efficacy and safety after ocular application have been demonstrated in studies of herpetic keratitis in rabbits. Two strengths of ganciclovir gel (0.05 and 0.15%) were compared with 3% acyclovir ointment in the treatment of superficial herpes simplex keratitis in humans.. Two multicenter randomized clinical trials were carried out in Africa (Trial 1) and Europe (Trial 2). Sixty-seven patients (Trial 1) and 37 patients (Trial 2) from herpetic ulceration were recruited.. The results showed no statistically significant difference between the treatment groups, although the healing rates tended to be better in the group receiving 0.15% ganciclovir gel, with healing rates of 85% (Trial 1) and 83% (Trial 2) as compared with 72% (Trial 1) and 71% (Trial 2) in the group receiving acyclovir ointment. Local tolerance was found to be superior with the gel formulation of ganciclovir with fewer complaints of discomfort (stinging, burning) or blurred vision after application of the drug. Systemic absorption of the drug was low. No hematologic changes were detected.. These findings support the efficacy of ganciclovir gel in the treatment of ulcerative herpes simplex keratitis and demonstrate its superior local tolerance when compared with acyclovir ointment.

Topics: Acyclovir; Administration, Topical; Adolescent; Antibodies, Viral; Antiviral Agents; Child; Cornea; Ganciclovir; Gels; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Ointments; Retrospective Studies; Safety; Treatment Outcome

To assess the benefit of adding oral acyclovir to a regimen of topical prednisolone phosphate and trifluridine for the treatment of iridocyclitis caused by herpes simplex virus (HSV).. Patients with HSV iridocyclitis were enrolled in a multicenter controlled clinical trial supported by the National Eye Institute, Bethesda, Md, and randomly assigned to receive a 10-week course of either oral acyclovir, 400 mg, 5 times daily, or oral placebo in conjunction with regimens of topical trifluridine and a topical corticosteroid. Follow-up examinations were performed weekly during the 10-week treatment period, every 2 weeks for an additional 6 weeks, and at 26 weeks after enrollment in the trial. Treatment failure was defined as a persistence or worsening of ocular inflammation, withdrawal of medication because of toxicity, or a request by the patient to withdraw from the trial for any reason. The trial was stopped because of slow recruitment after only 50 of the originally planned 104 patients were enrolled in more than 4 years.. A treatment failure occurred in 11 (50%) of the 22 patients in the acyclovir-treated group and in 19 (68%) of the 28 patients in the placebo group. Compared with the placebo group, the adjusted rate ratio for a treatment failure in the acyclovir-treated group during the 10-week treatment period was 0.43 (90% confidence interval, 0.18-1.02; P = .06, 1-tailed) and during the 16-week follow-up period (10-week treatment period plus 6-week observation period) was 0.60 (90% confidence interval, 0.29-1.25; P = .13, 1-tailed in a proportional hazards model). The treatment effect seemed slightly greater when only the patients with a persistence or worsening of ocular HSV disease were considered as treatment failures (ie, excludes terminations because of toxic effects of the drug and patients who requested to withdraw from the trial). By life-table analysis, similar results were obtained; the possible benefit of acyclovir became apparent after the first 3 weeks of follow-up.. While the number of patients recruited in this trial was too small to achieve statistically conclusive results, the trend in the results suggests a benefit of oral acyclovir in the treatment of HSV iridocyclitis in patients receiving topical corticosteroids and trifluridine prophylaxis.

Topics: Acyclovir; Administration, Oral; Administration, Topical; Anti-Inflammatory Agents; Antiviral Agents; Corneal Stroma; Female; Follow-Up Studies; Herpes Simplex; Herpesvirus 1, Human; Humans; Iridocyclitis; Keratitis, Herpetic; Male; Middle Aged; Ophthalmic Solutions; Patient Compliance; Prednisolone; Treatment Failure; Treatment Outcome; Trifluridine

Possible risk factors were evaluated for herpes simplex virus (HSV) epithelial keratitis in patients with stromal keratouveitis.. The study population included 260 patients who had active stromal keratitis and/or iridocyclitis without epithelial disease and who were enrolled in one of three clinical trials of the Herpetic Eye Disease Study. Study treatment involved a 10 week course of topical placebo, topical prednisolone phosphate, or topical prednisolone phosphate with oral acyclovir. All groups received topical trifluridine four times daily for 3 weeks then twice daily for another 7 weeks. Patients were examined for HSV epithelial keratitis for 16 weeks.. Dendritic or geographic epithelial keratitis occurred in 12 (4.6%) study patients. Adverse effects attributable to trifluridine prophylaxis were acute allergic blepharoconjunctivitis in 10 (3.8%) study patients and corneal epithelial erosions in 11 (4.2%) study patients. No significant difference in the occurrence of HSV epithelial keratitis was found among the study treatment groups: one (2.0%) of 49 topical placebo treated patients, nine (6.5%) of 138 patients treated with topical corticosteroids without acyclovir, and two (2.7%) of 73 patients treated with topical corticosteroids and oral acyclovir. Univariate exponential models suggested that patients with a history of previous HSV epithelial keratitis and non-white patients were more likely to develop HSV epithelial keratitis during treatment of stromal keratouveitis.. Individuals with prior HSV epithelial keratitis and certain ethnic groups may have a higher rate of recurrent epithelial keratitis during the acute treatment of HSV stromal keratouveitis.

Topics: Acyclovir; Anti-Inflammatory Agents; Antiviral Agents; Drug Therapy, Combination; Endothelium, Corneal; Female; Humans; Iridocyclitis; Keratitis, Dendritic; Keratitis, Herpetic; Male; Prednisolone; Recurrence; Risk Factors; Trifluridine

The management protocol for herpetic stromal keratitis (HSK) is still controversial. We have attempted to compare the relative efficacy of topical dexamethasone 0.01% and flurbiprofen 0.03% in combination with topical acyclovir 3% in HSK.. In this institutional, prospective, randomized, controlled, double-blind study, 45 clinically diagnosed cases of HSK were randomly distributed into three coded treatment groups--topical placebo, dexamethasone 0.01%, and flurbiprofen 0.03% each in tapering frequency and in combination with acyclovir 3% ointment five times per day for four weeks. Therapeutic response was assessed every third day for four weeks. Decoding of the treatment groups was done at the conclusion of the study and data analysed.. Four-week success rate was 93.3% (14 of 15) in the dexamethasone-acyclovir treatment group, 66.7% (10 of 15) in the flurbiprofen-acyclovir treatment group and 20% (3 of 15) in the placebo-acyclovir treatment group.. While dexamethasone in combination with acyclovir gives the best results in HSK with minimal side-effects, the role of topical flurbiprofen seems promising.

Topics: Acyclovir; Administration, Topical; Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antiviral Agents; Child; Corneal Stroma; Dexamethasone; Double-Blind Method; Drug Evaluation; Drug Therapy, Combination; Female; Flurbiprofen; Follow-Up Studies; Glucocorticoids; Humans; Keratitis, Herpetic; Male; Middle Aged; Ophthalmic Solutions; Prospective Studies; Treatment Outcome; Visual Acuity

Topics: Acyclovir; Adolescent; Adult; CD4 Lymphocyte Count; Child; Combined Modality Therapy; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunity, Cellular; Keratitis, Herpetic; Male; Middle Aged; Recurrence; Stomatitis, Herpetic; Vaccines, Inactivated; Viral Vaccines

To evaluate the efficacy of four antiviral agents--1% idoxuridine ointment (group 1), 2% trifluorothymidine ointment (group 2), 3% acyclovir ointment (group 3) and 1% bromovinyldeoxyuridine (BVDU) ointment (group 4)--in herpes simplex keratitis.. Randomized double-blinded clinical trial.. Tertiary care institution in New Delhi.. Eighty patients with uncomplicated herpes simplex keratitis of recent onset who had not previously received antiviral treatment.. Cure rate, frequency and severity of side effects.. Cure rates of 60%, 90%, 90% and 95% were obtained in groups 1, 2, 3 and 4 respectively. The average healing time was 13.4, 8.9, 8.5 and 7.5 days respectively. Side effects (follicular conjunctivitis, epithelial keratopathy and stinging) were more frequent in group 1 than in the other groups.. BVDU has a more pronounced therapeutic effect than idoxuridine, trifluorothymidine and acyclovir in uncomplicated epithelial herpetic disease of recent onset that has not previously been treated.

Topics: Acyclovir; Antiviral Agents; Bromodeoxyuridine; Double-Blind Method; Humans; Idoxuridine; Keratitis, Herpetic; Ointments; Treatment Failure; Trifluridine

We examined the recurrence rate of herpetic uveitis (HU) in 13 patients (group A) treated prophylactically with long-term systemic acyclovir (600-800 mg/day) and compared it with that of 7 patients with no prophylactic therapy (group B). HU was diagnosed on the basis of a history of dendritic or disciform keratitis accompanied by iridocyclitis and iris atrophy. The study population consisted of 12 men and 8 women with a mean age at onset of uveitis of 52.9 years (range 19-78 years). All patients were followed for at least 8 months. The mean follow-up time of patients on long-term oral acyclovir was 26.0 months. In this group, only one patient experienced a single recurrent episode of uveitis while on 600-800 mg/day of acyclovir therapy; two additional patients had recurrence of HU within 16.2 months after the acyclovir dose was tapered below 600 mg/day. In striking contrast, 16 recurrences occurred in the 7 patients of group B (p < 0.05). Of these, the initial recurrence occurred within an average of 4.3 months following cessation of therapy. There was a significant difference (p < 0.05) in the mean recurrence-free interval between patients in group A (24.6 months) and those in group B (3.4 months). Herpetic uveitis is a serious ocular disease in which recurrence of inflammation results in severe ocular complications. The long-term use of oral acyclovir may be of benefit in the prevention of recurrences, and hence may reduce the blinding complications of this disease. Efforts at completing a randomized, placebo-controlled trial on this matter by the Herpes Epithelial Disease Study Group were unsuccessful due to insufficient patient recruitment.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Oral; Adult; Aged; Antiviral Agents; Atrophy; Female; Humans; Iridocyclitis; Iris; Keratitis, Dendritic; Keratitis, Herpetic; Male; Middle Aged; Recurrence; Treatment Outcome; Uveitis; Visual Acuity

To evaluate the efficacy of oral acyclovir in treating stromal keratitis caused by herpes simplex virus (HSV) in patients receiving concomitant topical corticosteroids and trifluridine.. The authors performed a randomized, double-masked, placebo-controlled, multicenter trial in 104 patients with HSV stromal keratitis without accompanying HSV epithelial keratitis. Sample size was chosen so that a 5%, one-tailed test would have an 80% chance of detecting a doubling of the median time to treatment failure. Patients were randomized to receive a 10-week course of either oral acyclovir (400 mg 5 times daily, n = 51) or placebo (n = 53). All patients also received a standard regimen of topical prednisolone phosphate and trifluridine. Ophthalmologic examinations were performed weekly during the 10-week treatment period, every 2 weeks for an additional 6 weeks, and at 6 months after entry into the trial.. The median time to treatment failure (defined as worsening or no improvement of stromal keratitis or an adverse event) was 84 days (95% confidence interval, 69-93 days) for the acyclovir group and 62 days (95% confidence interval, 57-90 days) for the placebo group. By 16 weeks, 38 patients (75%) in the acyclovir group and 39 patients (74%) in the placebo group had failed treatment. Also by that time, the keratitis had resolved with trial medications, and there was no subsequent worsening in nine patients (18%) in the acyclovir group and ten (19%) in the placebo group. None of these results were significantly different between the two groups. However, visual acuity improved over 6 months in significantly more patients in the acyclovir group than in the placebo group.. There was no statistically or clinically significant beneficial effect of oral acyclovir in treating HSV stromal keratitis in patients receiving concomitant topical corticosteroids and trifluridine with regard to time to treatment failure, proportion of patients who failed treatment, proportion of patients whose keratitis resolved, time to resolution, or 6-month best-corrected visual acuity. Visual acuity improved over 6 months in more patients in the acyclovir group than in the placebo group.

Topics: Acyclovir; Administration, Oral; Administration, Topical; Adolescent; Adult; Aged; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Keratitis, Herpetic; Male; Middle Aged; Patient Compliance; Prednisolone; Prospective Studies; Regression Analysis; Treatment Outcome; Trifluridine; United States; Visual Acuity

Corneal graft survival in 13 patients (14 eyes) receiving oral acyclovir after penetrating keratoplasty for herpes simplex keratitis was compared with that in nine patients (nine eyes) who underwent penetrating keratoplasty for herpes simplex keratitis without postoperative acyclovir. Mean age, duration of disease, and time of follow-up did not differ in the two groups. There were no recurrences of herpes simplex keratitis in any patient receiving acyclovir during a mean follow-up of 16.5 months compared with a 44% (four of nine) recurrence rate in patients without acyclovir during a mean follow-up of 20.6 months (p < 0.01). Graft failure occurred in 14% (2 of 14) of acyclovir treatment eyes compared with 56% (five of nine) without acyclovir. Long-term prophylactic oral acyclovir significantly decreased the recurrence of herpes simplex keratitis and reduced corneal graft failure in patients who had a history of recurrent herpes simplex keratitis and who had undergone penetrating keratoplasty.

Topics: Acyclovir; Administration, Oral; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating; Middle Aged; Prevalence; Prospective Studies; Recurrence

The tolerability and efficacy of epidermal growth factor (EGF) in the topical treatment of herpetic corneal ulcers in addition to topical acyclovir have been evaluated in a double-blind, placebo-controlled, randomized study in two groups of patients. The time required for complete reepithelialization of the cornea was recorded, and the data obtained were analyzed statistically. In the EGF group, the reepithelialization was significantly faster than in the control group. Tolerability of EGF was always excellent. These results indicate that EGF is safe and effective in reducing the healing time of herpetic corneal ulcers.

Topics: Acyclovir; Administration, Topical; Adult; Aged; Corneal Ulcer; Double-Blind Method; Epidermal Growth Factor; Female; Humans; Keratitis, Herpetic; Male; Middle Aged; Ophthalmic Solutions

A double blind clinical investigation on the treatment of 100 cases of HSV keratitis with rHuIFN alpha-1 and acyclovir instillations was carried out in 8 institutions in Beijing and elsewhere. Both eyedrops proved about equally effective with cure rates of 88.1% and 82.9% respectively. Until recently, 128 cumulative cases of various types of HSV keratitis treated with rHuIFN alpha-1 demonstrated a cure rate of 82.0%, indicating that topical rHuIFN alpha-1 was an effective nonspecific remedy for HSV keratitis.

Topics: Acyclovir; Adult; Double-Blind Method; Female; Humans; Interferon Type I; Keratitis, Herpetic; Male; Ophthalmic Solutions; Recombinant Proteins; Single-Blind Method

Herpes simplex disciform keratitis is a difficult condition. The general feeling is that it is an immune disease, mediated by the virus, possibly located in the endothelial cells. It is frequently combined with inflammation in the trabecular meshwork and with uveitis. There is some controversy in relation to treatment and it has been suggested that anti-virals will control herpetic disciform keratitis, particularly if the patient has never had steroids previously. The authors of this paper have, in the past, published data which showed that Acyclovir, with corticosteroid, was necessary in the management of disciform keratitis. The data suggested that Acyclovir on its own was not effective. It remained to be answered whether Acyclovir on its own would be effective in patients who never had steroids for any reason previously. This paper demonstrates clearly that it is necessary, irrespective of whether patients have had steroids in the past or not, to combine corticosteroids with Acyclovir in the management of herpetic disciform keratitis. Acyclovir, on its own, is shown to be ineffective. It has also been suggested that Acyclovir is non-toxic. In a general way this is true, but the authors suggest that Acyclovir ointment does produce a punctate keratitis in patients with tear film disease, and that oral Acyclovir is preferable in such patients.

Topics: Acyclovir; Betamethasone; Double-Blind Method; Humans; Keratitis, Herpetic; Ointments; Patient Compliance; Placebos

Corneal graft survival in 13 patients (14 eyes) receiving oral acyclovir following corneal transplantation for herpes simplex keratitis was compared to that in nine patients (9 eyes) who underwent penetrating keratoplasty for herpes simplex keratitis without receiving postoperative acyclovir. Mean age, duration of disease, and time of follow-up did not differ in the two groups. There were no recurrences of herpes simplex keratitis in any patient receiving acyclovir during a mean follow-up of 16.5 months compared to a 44% (4/9) recurrence rate in patients without acyclovir during a mean follow-up of 20.6 months (p < 0.01). Graft failure occurred in 14% (2/14) of acyclovir treatment eyes and in 56% (5/9) of the grafts in patients not receiving acyclovir. Long term prophylactic oral acyclovir significantly decreased the recurrence of herpes simplex keratitis and reduced corneal graft failure in patients with a history of recurrent herpes simplex keratitis who underwent corneal transplantation.

Topics: Acyclovir; Administration, Oral; Female; Follow-Up Studies; Graft Rejection; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Middle Aged; Premedication; Prevalence; Recurrence

To report bilateral Herpes Simplex virus (HSV) keratitis in a patient on latanoprost for primi]k=8ary open angle glaucoma (POAG).. Case report.. A 76-year-old healthy male on latanoprost monotherapy for POAG polresented with sudden bilateral decreased vision. Examination showed bilateral dense corneal edema with loose epithelium. Aqueous fluid was positive for HSV-1 DNA on polymerase chain reaction (PCR). Latanoprost was discontinued, topical prednisolone acetate 1% eye, acyclovir 400 mg 5 times a day and combination of dorzolamide hydrochloride 2% and timolol maleate 0.5% twice daily were prescribed. The vision rapidly improved to 20/25 along with complete resolution of corneal edema within four weeks, with no recurrences over the next one year.. Bilateral simultaneous HSV endotheliitis is a rare condition and positive PCR test can help rule in the diagnosis. HSV keratitis is a known adverse event with Latanoprost use and can present atypically.

Topics: Acyclovir; Aged; Corneal Edema; Glaucoma, Open-Angle; Humans; Keratitis, Herpetic; Latanoprost; Male

Herpes simplex keratitis resistance to antiviral treatment presents a growing concern. The herpes simplex virus has many different mechanisms of resistance to antiviral treatment, which have been well described. Resistance to acyclovir occurs because of mutations in the viral thymidylate kinase and DNA polymerase that decrease this enzyme's affinity for its substrate. This article discusses factors that explain the prevalence of this resistance, the ability for recurrences in immunocompromised populations, current treatments for acyclovir-resistant herpes simplex keratitis, and novel therapies for this growing concern.

Topics: Acyclovir; Antiviral Agents; Humans; Keratitis, Herpetic; Simplexvirus

Thygeson's superficial punctate keratitis (TSPK) is a recurrent bilateral corneal epithelial disease. Typically, small, multiple discrete epithelial lesions occur in the central cornea. However, dendritic corneal lesions are rare. Herein, we report a rare case of TSPK in both eyes after a unilateral dendritic corneal lesion. A 42-year-old woman presented with decreased vision and foreign body sensation in her right eye that persisted for 1 month. Her uncorrected visual acuity and best-corrected visual acuity (BCVA) were 20/160 in the right eye. Slit-lamp microscopy revealed a dendritic lesion in the central cornea of the right eye. No abnormalities were observed in her left eye. Herpetic keratitis in the right eye was diagnosed and systemic acyclovir was prescribed, along with topical acyclovir ointment and steroids. After one week, most of the corneal lesions had disappeared, and the BCVA in the right eye had improved to 20/25. The corneal epithelium completely recovered after 2 weeks. However, 2 weeks later, the patient visited the hospital with decreased visual acuity in the right eye, and the BCVA decreased to 20/40. Multiple fine corneal lesions were observed under a slit-lamp microscope. The patient was diagnosed with TSPK of the right eye. Topical steroids were started, and after 7 days, the corneal condition improved. However, after 6 weeks, visual acuity decreased in the left eye, and a corneal lesion similar to that in the right eye was observed; therefore, the patient was diagnosed with bilateral TSPK. Short-term topical steroids and long-term topical cyclosporine A 0.1% were used in both eyes, and the disease was maintained without recurrence for 3 months. TSPK can appear as a unilateral dendritic corneal lesion similar to herpetic keratitis. Therefore, in case of unilateral dendritic corneal lesions, it should be considered that TSPK may develop later.

Topics: Acyclovir; Adult; Chronic Disease; Cornea; Female; Humans; Keratitis, Herpetic; Visual Acuity

The objective of this study is to evaluate the clinical features of pediatric herpes simplex virus keratitis, its recurrence rates, and its effects on visual acuity.. In this retrospective case series, records of pediatric patients (0-16 years) who presented with herpes simplex virus keratitis between January 2012 and September 2021 were evaluated. Data including age, gender, additional systemic diseases, the number of recurrences, recurrence time, treatment protocol, follow-up period, and presence of amblyopia were reviewed.. Twenty-four patients (16 females and 8 males) with a mean age of 6.6 ± 4 (1.1-15) years were included in the study. The mean follow-up time was 21 ± 19.9 (7-94) months. Four patients (16.6%) had bilateral keratitis. Including all 4 patients with bilateral involvement, a total of 10 (41.6%) patients had additional systemic diseases that cause immunodeficiency. After prophylactic antiviral treatment for at least 6 months (except for isolated epithelial keratitis), recurrence was detected in 5 (22.7%) patients, who were all immunodeficient. Among immunodeficient individuals, the recurrence rate was found to be 50%. Keratitis recurrence was significantly associated with immunodeficiency ( P = 0.03). However, type of keratitis ( P = 0.42), gender ( P = 0.47), and bilaterality ( P = 0.54) were not related with recurrence. 66.7% of the patients younger than 10 years developed amblyopia during follow-up.. In childhood, the most frequent corneal manifestation of herpes simplex virus is stromal keratitis that mostly progresses with corneal scarring, residual astigmatism, and amblyopia. The recurrence rate increases in the presence of immunosuppression. Close follow-up, rapid diagnosis, and treatment are critical for battling against amblyopia and achieving good visual prognosis.

Topics: Acyclovir; Amblyopia; Antiviral Agents; Child; Child, Preschool; Female; Humans; Keratitis, Herpetic; Male; Recurrence; Retrospective Studies; Simplexvirus

To retrospectively review the clinical characteristics of patients with herpes simplex virus type 2 (HSV-2) blepharokeratoconjunctivitis.. Laboratory-proven HSV-2 blepharokeratoconjunctivitis cases were reviewed between 1995 and 2021.. Ten of 725 (1.4%) patients had HSV-2 infection. Data were available for nine patients. Associated conditions included neonatal herpes (1/9, 11%), severe atopy (1/9, 11%), genital herpes (2/9, 22%), and systemic immune disorders (2/9, 22%). The most common presenting finding was pain and blurred vision (55.5%). Two patients (22%) had dendritic lesions and one patient (11%) had reduced corneal sensation. Complete resolution was reported in four patients (44.5%). Recurrence was noted in four patients (44.5%) despite antiviral prophylaxis. Corneal complications included scarring and neovascularization. The visual acuity at the last follow-up was 20/40 or worse in four patients (44.5%).. HSV-2 is an uncommon cause of keratitis. Dendrites and loss of corneal sensation were uncommon. Recurrence was noted despite antiviral prophylaxis.

Topics: Acyclovir; Antiviral Agents; Female; Herpesvirus 2, Human; Humans; Infant, Newborn; Keratitis, Herpetic; Retrospective Studies

To describe the clinical and virological profiles of patients with herpes simplex keratitis (HSK) caused by acyclovir-resistant (ACV. Multicenter retrospective case series.. HSV-1 resistance to ACV was confirmed using sequencing of genes encoding HSV-1 thymidine kinase (TK) and DNA polymerase (DNA pol). Data were collected on the number of HSK episodes before and after the diagnosis of resistance, ocular findings including the type of HSK, immune status of patients, antiviral treatments, and HSV-1 genotypic resistance profiles.. HSV-1 resistance to ACV must be suspected in HSK patients with recurrences despite AVP and/or in cases that respond poorly to a suppressive antiviral regimen. Immunocompromised patients and/or those with longstanding disease may be particularly at risk for developing resistance.

Topics: Acyclovir; Antiviral Agents; DNA-Directed DNA Polymerase; Drug Resistance, Viral; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Male; Recurrence; Retrospective Studies; Thymidine Kinase

Herpes simplex keratitis is an important infectious cause of blindness worldwide. The mainstay of antiviral therapy is treatment with long-established nucleoside analogues orally or topically. However, the emergence of resistant strains may become a major health concern in the future. Therefore, the development of backup antiherpetic medicines is urgently needed. Small molecule PDSTP is known to be active against herpes simplex type 1 strains in vitro, affecting early host-pathogen interactions. Here, we evaluated its preclinical efficacy in a rabbit model of herpes simplex epithelial keratitis. The mean course of keratitis and the corneal lesions in the 1.0% PDSTP gel group was statistically significantly less than in the negative control group and was comparable to that in the aciclovir group. These findings open up new opportunities for the development of antiherpetic drugs with an original mechanism of action.

Topics: Acyclovir; Animals; Antiviral Agents; Herpes Simplex; Keratitis, Herpetic; Rabbits

Ocular herpes simplex is usually caused by herpes simplex virus type 1 (HSV-1) and less commonly by the type 2 virus (HSV-2). Ocular manifestations of HSV include blepharitis, conjunctivitis, lacrimal system obstruction, corneal involvement, and uveitis. Corneal involvement is one of the causes of loss of vision and can be epithelial herpetic keratitis or stromal herpetic keratitis.. A significant population has a colonization of herpes viruses. Under certain circumstances, these viruses can reactivate with a significant ocular morbidity. Globally, COVID-19 vaccines are recommended; however, the vaccine safety data are limited.. Herein, we reported a case of herpetic keratitis reactivation that occurred 2 days after receiving SARS-CoV-2 mRNA vaccine. The patient is a 50-year-old man who underwent penetrating keratoplasty (PKP) in 2020 for corneal opacity caused by a previous herpes simplex keratitis in 2013. Herpetic keratitis was treated successfully with topical antiviral acyclovir along with topical moxifloxacin and artificial tears. After treatment, prophylactic oral acyclovir was started.. Both ophthalmologist and patients should be aware of this phenomenon. Long-term prophylactic antiviral treatment may be recommended for those patients.

Topics: Acyclovir; Antiviral Agents; COVID-19; COVID-19 Vaccines; Humans; Keratitis, Herpetic; Male; Middle Aged; mRNA Vaccines; Recurrence; RNA, Messenger; SARS-CoV-2; Vaccination; Vaccines, Synthetic

BACKGROUND Tyrosinemia Type II (TYRII) is a rare autosomal recessive inborn error of metabolism caused by deficiency of tyrosine aminotransferase (TAT), leading to hypertyrosinemia. TYRII patients often present in the first year of life with ocular and cutaneous findings, including corneal ulcers, pseudodendritic keratitis, and palmoplantar hyperkeratosis. The corneal involvement is often mistaken for herpes simplex virus (HSV) keratitis, which is a much commoner condition. CASE REPORT A previously healthy 10-month-old male infant was referred to Ophthalmology for acute onset photophobia. Bilateral dendritiform corneal lesions raised the suspicion for herpetic keratitis. Additionally, a papular, crusted lesion was found on his thumb after a few days of hospitalization, also raising concerns about HSV. The patient's clinical condition seemed to improve under intravenous acyclovir and supportive treatment. A conjunctival swab and crusted lesion on the thumb were tested for HSV using a polymerase chain reaction (PCR) technique, and both were negative. Nevertheless, given the clinical presentation and the favorable course of signs and symptoms, hospital discharge was planned with oral acyclovir. It was halted by an alternative diagnosis of autosomal recessive inborn error of metabolism, tyrosinemia type II, confirmed by elevated plasma tyrosine level and later by molecular analysis requested as a confirmatory investigation by the genetics medical team. CONCLUSIONS The corneal involvement in TYRII is often mistaken for HSV keratitis, and clinical course alone should not halt further investigations to rule out TYRII. Clinicians should suspect TYRII clinically when its characteristic ocular dendritiform lesions are present, namely in infancy or early childhood, and even in the absence of its typical cutaneous palmoplantar hyperkeratosis plaques.

Topics: Acyclovir; Administration, Intravenous; Child, Preschool; Corneal Ulcer; Humans; Infant; Keratitis, Herpetic; Male; Tyrosinemias

Moraxella nonliquefaciens (. Keratitis due to

Topics: Acyclovir; Aged, 80 and over; Anti-Bacterial Agents; Ceftazidime; Ciprofloxacin; Cyclopentolate; Female; Humans; Keratitis, Herpetic; Moraxella; Prednisolone; Vancomycin

An 82-year-old man with a history of herpes simplex keratitis 40 years previously presented with recurrence, 1 day following vaccination for novel COVID-19. His condition worsened despite topical treatment with ganciclovir gel. A diagnosis of herpetic stromal keratitis was made, requiring systemic aciclovir, topical prednisolone, moxifloxacin and atropine, and oral doxycycline. He improved clinically on treatment, with some residual corneal scarring. Visual acuity improved from 6/36 corrected at presentation, to 6/24 following treatment. Clearly, public and personal health benefits from vaccination are hugely important and we would not suggest avoiding vaccination in such patients. It is, however, important for ophthalmic providers to be aware of the rare potential for reactivation of herpetic eye disease following vaccination to enable prompt diagnosis and treatment.

Topics: Acyclovir; Aged, 80 and over; Antiviral Agents; COVID-19; Humans; Keratitis, Herpetic; Male; Prednisolone; SARS-CoV-2; Vaccination

To report two cases of herpes simplex virus keratitis reactivation following Pfizer-BioNTech COVID-19 (BNT162b2) mRNA vaccination.. Two patients (one male, age 42 years, and one female, age 29 years) who are known to have herpetic keratitis presented to our emergency room in a time frame between 4 days and 4 weeks of receiving the vaccine. One patient presented with necrotizing stromal keratitis; the other presented with endotheliitis and epithelial keratitis. PCR for herpes simplex virus (HSV) was obtained from the two patients, and all cases received systemic acyclovir.. PCR for HSV came positive in both cases. Patients responded well to the provided treatment.. Ocular herpetic infection may be activated by COVID-19 (BNT162b2) mRNA vaccine. Treating physician should be alert to such associations, and patients should be followed closely. No direct causality has been proven, but further reporting and investigating similar conditions is recommended.

Topics: Acyclovir; Adult; Antiviral Agents; BNT162 Vaccine; COVID-19; Female; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Latent Infection; Male; Polymerase Chain Reaction; SARS-CoV-2; Vaccination

To evaluate the long-term role of adherence to oral acyclovir prophylaxis in reducing the risk for recurrent herpes simplex virus keratitis (HSK) in children.. A retrospective cohort study was performed including all pediatric patients 16 years or younger) with their first HSK diagnosis and treatment at our center. Children were started on a standardized oral acyclovir prophylactic regimen after the acute phase. Adherence to prophylaxis was assessed monthly through parent interviews. The possible association between any recurrence (not only the first) and exposure to acyclovir prophylaxis was evaluated using random-effects multivariate logistic regression.. A total of 20 eyes of 17 patients (8 boys and 9 girls) were included. The mean follow-up time was 3.5 years. Adherence to acyclovir prophylaxis was registered in 100% of patients with no recurrences and in 36.4% of patients with 1 or more recurrences (P = 0.035). All other tested variables (time of follow-up, sex, age, infectious diseases, underlying hematological diseases, eye, and HSK type) did not differ between the 2 groups. The multivariate model confirmed the lower risk for recurrence in patients who were compliant to therapy (adjusted odds ratio 0.04, 95% confidence intervals 0.00-0.42, P = 0.008). No adverse effects were recorded during follow-up.. Oral acyclovir prophylaxis is a safe and an effective medical treatment for recurrent HSK and its long-term efficacy is associated with compliance to the therapy.

Topics: Acyclovir; Administration, Oral; Antibiotic Prophylaxis; Antiviral Agents; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Keratitis, Herpetic; Male; Medication Adherence; Reinfection; Retrospective Studies; Treatment Outcome; Visual Acuity

To report anti-viral therapy and outcomes for patients with herpes simplex keratitis (HSK) in a quaternary centre in Sydney, Australia.. A retrospective case review of patients who received anti-viral medications for any form of HSK was conducted. Cases were identified from pathology results, pharmacy records and hospital coding data from 2012 to 2013. Clinical details including initial anti-viral treatment and outcome were collated from the medical records. Outcome was determined from when initial anti-viral treatment was stopped or changed, and classified as either clinically resolved, partially resolved or worsened for therapeutic indication; or as either success or failure for prophylaxis.. Anti-viral therapy was given for therapeutic and prophylactic indications at presentation in 252 (85%) and 44 patients (15%), respectively. Topical aciclovir five times daily and valaciclovir in doses ranging from 500 mg to 1 g, one to three times daily were the preferred anti-viral therapies. One hundred and fourteen patients (n = 114/296, 38.5%) also received topical corticosteroids. An outcome was determined for 210/296 (71%) patients. For therapeutic indication, half of the patients (90/174) partially resolved within 8 days, with best outcomes achieved for endothelial HSK (8/11, 73%) and keratouveitis (21/36, 58%). Adverse events, observed in 20% (35/174) of patients, included corneal perforation (n = 8) and secondary bacterial keratitis (n = 6). Prophylaxis with antiviral therapy was successful in two-thirds of patients after 6 months.. Clinical and visual outcomes varied with the type of HSK and prescribed therapies. Diverse initial anti-viral therapies were identified; standardising them may improve outcomes.

Topics: Acyclovir; Antiviral Agents; Australia; Humans; Keratitis, Herpetic; Retrospective Studies

To report the outcomes of Descemet membrane endothelial keratoplasty (DMEK) with intensive antiviral therapy for corneal edema secondary to herpes simplex virus type 1 (HSV-1)-mediated endotheliitis.. All eyes with polymerase chain reaction positive for HSV-1 undergoing DMEK for endothelial decompensation between January 2014 and January 2018 were followed up prospectively at our tertiary referral center. All eyes had been free of active inflammation for a minimum of 9 months and were treated prophylactically with high-dose systemic and topical antivirals, which were continued for a prolonged period of time. Primary outcomes were the occurrence of immunological rejection and/or recurrence of endotheliitis, eventually resulting in graft failure. Secondary outcomes were best spectacle-corrected visual acuity and endothelial cell loss.. Four consecutive eyes of 4 patients were included with a mean (±SD) patient age of 68.5 ± 15.1 years. The postoperative follow-up averaged 22 months. No eyes exhibited any signs of immunologic rejection, recurrence of endotheliitis, or graft failure. Mean (±SD) decimal best spectacle-corrected visual acuity improved from 0.2 ± 0.1 to 0.7 ± 0.2 (P = 0.007), whereas mean (±SD) endothelial cell loss was 56% ± 10.2% at the final postoperative follow-up.. DMEK is an effective option to treat corneal edema secondary to HSV-1-related endotheliitis. Intensive antiviral prophylaxis may reduce the risk of recurrence and subsequent graft failure.

Topics: Acyclovir; Administration, Ophthalmic; Administration, Oral; Aged; Aged, 80 and over; Antiviral Agents; Combined Modality Therapy; Descemet Stripping Endothelial Keratoplasty; Endothelium, Corneal; Female; Ganciclovir; Graft Survival; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Male; Middle Aged; Retrospective Studies; Slit Lamp Microscopy; Tomography, Optical Coherence; Visual Acuity

Topics: Acyclovir; Adrenal Cortex Hormones; Humans; Keratitis, Herpetic

Although the clinical appearance of pediatric ocular herpes simplex virus (HSV) is similar in children and adults, there is evidence that stromal disease and recurrences are more common in pediatric patients. Misdiagnosis of these patients is common, and patients can develop corneal scarring and amblyopia.. This case series will review important clinical concepts on pediatric ocular HSV including differences in presentation and current treatment recommendations.. Three pediatric patients with HSV keratitis are presented: a 6-year-old girl who was treated for unilateral disease over the course of 3 years, a 7-year-old boy who presented with bilateral disease, and a 3-year-old girl in whom the diagnosis was not apparent initially. All patients were successfully treated with oral acyclovir and topical steroids. One patient was also treated with topical antivirals.. Pediatric HSV keratitis should be considered as a differential diagnosis in pediatric patients who present with keratitis. Accurate diagnosis of these patients is important so that amblyopia does not develop. Pediatric ocular HSV patients can be successfully treated with topical and/or oral medications, although their treatment duration may be 12 months or longer.

Topics: Acyclovir; Antiviral Agents; Child; Child, Preschool; Female; Humans; Keratitis, Herpetic; Male; Recurrence; Visual Acuity

A young lactating woman presenting to us with simultaneous bilateral corneal lesions was clinically diagnosed to have herpes simplex keratitis, which was confirmed by herpes simplex virus (HSV) PCR. The patient was administered topical and systemic acyclovir therapy and therapeutic penetrating keratoplasty was done in right eye. She was advised to continue breast feeding under strict hygienic conditions. Diagnosis and management of HSV keratitis in a lactating patient can be particularly challenging for both clinician and patient and adoption of a multidisciplinary approach is necessary to ensure safety of mother and child. At 3 months follow-up, the baby was clinically healthy, there were no side effects of acyclovir therapy in the mother or the baby and the patient showed no evidence of recurrence in either eye.

Topics: Acyclovir; Aftercare; Antiviral Agents; Breast Feeding; Corneal Diseases; Diagnosis, Differential; Female; Herpesviridae Infections; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating; Lactation; Rare Diseases; Treatment Outcome; Young Adult

We report here a case of an immunocompetent patient suffering from recurrent epithelial herpetic keratitis associated with the emergence of antiviral resistance. Indeed, the not previously described amino acid change L340R within herpes simplex virus thymidine kinase, was shown to confer acyclovir-resistance by recombinant phenotyping using bacmid technology.

Topics: Acyclovir; Adult; Antiviral Agents; Drug Resistance, Viral; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Male; Mutation; Phenotype; Recurrence; Thymidine Kinase

Epithelial keratitis is a common complication after cataract surgery. Many factors have been attributed to this clinical phenomenon.. An 82-year-old woman without previous herpes simplex keratitis (HSK) underwent an uncomplicated clear corneal phacoemulsification procedure in the right eye. In the late postoperative period, epithelial keratitis developed in this same eye.. An initial diagnosis of HSK was made clinically. The lesion was refractory to antiviral treatment and had progressed. After topical acyclovir cessation and vigorous lubrication, a diagnosis of toxic keratitis was finally made.. The corneal epithelial defect and dendritic lesion presented initially. Responding to antiviral treatment, this corneal lesion aggravated and revealed large epithelial erosion. After topical acyclovir cessation and initiation of vigorous lubrication, the toxic keratitis was completely resolved.. Epithelial keratitis following cataract surgery is a common complication and can be misdiagnosed early in its disease course. Physicians should be alert to the possibility of HSK. Polymerase chain reaction detection is helpful in diagnosing this disease.

Topics: Acyclovir; Aged, 80 and over; Antiviral Agents; Cataract Extraction; Diagnosis, Differential; Female; Humans; Keratitis, Herpetic

To describe the clinical manifestations of herpes simplex keratitis (HSK) in a tertiary referral center in South Korea and to determine whether ascorbic acid treatment prevents recurrence of herpetic epithelial keratitis.. This retrospective cohort study included all consecutive patients with herpetic keratitis referred to our center from January 2010 to January 2015. Clinical features, ocular complications, and recurrences were recorded.. In total, 149 eyes of the 133 patients (72 male and 61 female) were followed for an average of 24.6 ± 13.2 months. Sixteen (12.0%) patients had bilateral HSK. The most frequent HSK subtype was epithelial keratitis (49.7%), which was followed by stromal keratitis (23.5%). Epithelial keratitis was the most likely subtype to recur. Complications occurred in 122 (81.9%) eyes. The most common complication was corneal opacity. Recurrences were observed in 48 (32.2%) eyes. The recurrence rates were lower in the prophylactic oral antiviral agent group (16 / 48 eyes, 33.3% vs. 49 / 101 eyes, 48.5%) and the ascorbic acid treatment group (13 / 48 eyes, 27.1% vs. 81 / 101 eyes, 70.3%) compared with the groups without medications. Univariate logistic regression analysis revealed that both factors significantly reduced the risk of recurrence (acyclovir: odds ratio, 0.25; 95% confidence intervals, 0.12 to 0.51; ascorbic acid: odds ratio, 0.51; 95% confidence intervals, 0.20 to 0.91).. This retrospective study described the clinical findings of HSK in a tertiary referral center in South Korea. Prophylactic oral antiviral agent treatment and oral ascorbic acid administration may lower the risk of recurrence.

Topics: Acyclovir; Administration, Oral; Adult; Aged; Aged, 80 and over; Antioxidants; Antiviral Agents; Ascorbic Acid; Drug Therapy, Combination; Eye Infections, Viral; Female; Follow-Up Studies; Humans; Incidence; Keratitis, Herpetic; Male; Middle Aged; Ophthalmoscopy; Recurrence; Republic of Korea; Retrospective Studies; Slit Lamp; Tertiary Care Centers; Time Factors; Treatment Outcome; Visual Acuity; Young Adult

To report a case of bilateral herpetic epithelial keratitis after bilateral intravitreal bevacizumab injections for the treatment of exudative age-related macular degeneration.. A 66-year-old man with diabetes and an extensive history of bilateral anti-vascular endothelial growth factor treatments for exudative age-related macular degeneration received an intravitreal bevacizumab injection in the right eye and triple therapy (bevacizumab, photodynamic therapy, and triamcinolone acetonide) in the left eye. After 4 days, he presented with pain, photophobia, tearing, and decreased vision in both eyes. Slit-lamp examination revealed bilateral dendritic epithelial lesions with terminal bulbs, and he was diagnosed with bilateral herpes simplex epithelial keratitis.. The patient was treated with ganciclovir ophthalmic ointment and oral acyclovir with resolution of signs and symptoms.. To our knowledge, this is the first documented account of bilateral herpetic epithelial keratitis after bilateral intravitreal bevacizumab injections.

Topics: Acyclovir; Aged; Angiogenesis Inhibitors; Antiviral Agents; Bevacizumab; Eye Infections, Viral; Ganciclovir; Humans; Intravitreal Injections; Keratitis, Herpetic; Male; Ointments; Ophthalmic Solutions; Postoperative Complications; Vascular Endothelial Growth Factor A; Wet Macular Degeneration

Topics: Acyclovir; Administration, Oral; Administration, Topical; Antiviral Agents; Humans; Keratitis, Herpetic; Simplexvirus

A 4-month-old female infant presented with a vesicular lesion on her left hand present since 1 day. A few days prior to presentation, she had a similar lesion on the lower lip. Two days after presentation, she returned with new lesions on her thorax and upper eyelid. PCR of the vesicle was positive for herpes simplex virus type 1. The transmission to her chest and face probably resulted from autoinoculation, caused by rubbing of the hand on other parts of the body. Transmission of herpes simplex through skin-to-skin contact is a common route of infection in people engaging in contact sports. Antiviral therapy was started because of the extensiveness and expansion of lesions and risk of developing herpetic keratitis. The patient completely recovered. This case shows that in an otherwise healthy infant, multiple herpetic skin lesions were not due to disseminated infection, but through autoinoculation.

Topics: Acyclovir; Administration, Intravenous; Antiviral Agents; Diagnosis, Differential; Disease Transmission, Infectious; Face; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant; Keratitis, Herpetic; Lip; Thorax; Treatment Outcome

To evaluate the therapeutic benefit of self-retained cryopreserved amniotic membrane in conjunction with oral antiviral therapy in herpetic epithelial keratitis.. Retrospective review of 4 patients with primary (1 eye) and recurrent (3 eyes) unilateral herpetic epithelial keratitis treated with cryopreserved amniotic membrane through the placement of the PROKERA Slim (PKS) (Bio-Tissue, Inc) in conjunction with oral acyclovir. Their symptoms, conjunctival inflammation, corneal staining, and visual acuity were compared before and after treatment.. Herpetic epithelial keratitis presented as dendritic (3 eyes) and geographic (1 eye) epithelial lesions. After epithelial debridement and placement of the PKS for 5 ± 3.7 days, all patients reported significant relief of symptoms, rapid corneal epithelialization, and reduction of ocular surface inflammation. The visual acuity was also improved in all eyes from 0.7 ± 0.7 to 0.4 ± 0.7 logarithm of the minimum angle of resolution (P = 0.2). They remained symptom-free during a follow-up period of 2.7 to 50.8 (20.3 ± 21.7) months.. The PKS in conjunction with oral acyclovir facilitates the ease of early intervention to accelerate restoration of a normal corneal epithelium in herpetic epithelial keratitis.

Topics: Acyclovir; Administration, Oral; Aged; Aged, 80 and over; Amnion; Antiviral Agents; Combined Modality Therapy; Cryopreservation; Debridement; Epithelium, Corneal; Female; Humans; Keratitis, Herpetic; Male; Middle Aged; Retrospective Studies; Visual Acuity

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

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Herpesvirus 1, Human; Humans; Keratitis, Dendritic; Keratitis, Herpetic; Simplexvirus

To describe a series of 5 patients with herpes simplex virus keratitis (HSK) and rheumatoid arthritis (RA) under immunosuppressive treatment.. Retrospective study. Detailed data were obtained regarding symptoms and signs at the initial evaluation, treatment, microbiological diagnostic tests, evolution, and outcomes.. Five patients with HSK and RA were identified. Bilateral involvement occurred in 2 patients (40%). Epithelial keratitis was diagnosed in 5 eyes. Three eyes showed severe melting with eye perforation. Gram-positive bacterial co-infections were common in the group with stromal keratitis. We did not find differences in the evolution of the disease based on anti-rheumatoid treatment.. The characteristics of HSK in patients with RA differed from HSK in immunocompetent patients. The stromal keratitis cases were very aggressive and difficult to manage, with perforation and gram-positive bacterial co-infection as frequently associated conditions. Prophylactic therapy at standard doses was unsuccessful to avoid recurrences.

Topics: Acyclovir; Aged; Antiviral Agents; Arthritis, Rheumatoid; Corneal Stroma; DNA, Viral; Female; Herpesvirus 1, Human; Humans; Immunosuppressive Agents; Keratitis, Herpetic; Male; Opportunistic Infections; Polymerase Chain Reaction; Retrospective Studies

To describe 3 cases of herpes simplex virus (HSV) vesicular blepharitis that progressed to infectious epithelial keratitis despite treatment with oral acyclovir, but responded to topical antiviral therapy.. Retrospective review of a small case series.. One adult and 2 children presented with unilateral HSV vesicular blepharitis without evidence of corneal involvement. Each patient was placed on a therapeutic dose of oral acyclovir. While taking oral antiviral therapy, the patients developed HSV infectious epithelial keratitis, which was treated with trifluridine 1% solution 9 times daily in the adult and ganciclovir 0.15% ophthalmic gel 5 times daily in the 2 children. All 3 cases showed resolution of epithelial keratitis within 3 to 10 days after initiation of topical antiviral treatment while oral acyclovir was continued.. Oral antiviral therapy alone may not adequately prevent progression of infectious ocular HSV blepharoconjunctivitis. Topical antiviral therapy appeared to enable resolution of HSV epithelial keratitis that arose during oral acyclovir treatment.

Topics: Acyclovir; Administration, Oral; Administration, Topical; Adolescent; Adult; Antiviral Agents; Blepharitis; Child; Conjunctivitis, Viral; Disease Progression; Epithelium, Corneal; Eye Infections, Viral; Female; Ganciclovir; Humans; Keratitis, Herpetic; Male; Retrospective Studies; Trifluridine

To evaluate the efficacy of systemic and topical antiviral therapy in the treatment of active herpes simplex virus (HSV) necrotizing stromal keratitis (NSK).. Prospective interventional case series.. Patients with a diagnosis of HSV NSK based on history and clinical findings were enrolled in the study. A standard protocol was used for microbiologic investigations. Ten weeks regime of systemic acyclovir and 2 weeks of topical acyclovir was given. Complete ophthalmic examination was performed at every visit. Outcome measures were a reduction in the area of infiltration and improvement in visual acuity.. Fifteen patients were enrolled in the study. The mean age of presentation was 51.53 years. The duration of symptoms at presentation ranged from 2 to 8 weeks. HSV1 DNA polymerase chain reaction was positive in 70% cases of those tested. Area of infiltration at trial entry and at the end of 2 weeks of antiviral treatment reduced significantly (P = 0.007). All patients showed a complete resolution of keratitis at the end of study.. Topical and systemic acyclovir for treatment of NSK facilitates healing of ulceration. Topical steroids after initial antiviral therapy are safe and decreases inflammation and improve visual recovery. Early initiation of therapy has better outcomes as compared to late presentations.

Topics: Acyclovir; Administration, Topical; Antiviral Agents; Cornea; DNA, Viral; Female; Humans; Keratitis, Herpetic; Male; Necrosis; Prospective Studies; Simplexvirus; Visual Acuity

We report the case of an immunocompetent male who presented with a limbal-adjacent scleritis and interstitial keratitis in the left eye. A few days later a new dendritiform ulcer in his right eye and bilateral progressive worsening with granulomatous uveitis in both eyes were observed. A thorough review of systems revealed positive serum IgM titles for herpes simplex virus.. In the context of a bilateral keratouveitis refractory to conventional treatment it is mandatory to rule out the herpetic origin based on the different forms of clinical presentation of this virus.

Topics: Acyclovir; Adult; Antibodies, Viral; Antiviral Agents; Corneal Opacity; Corneal Ulcer; Granuloma; Humans; Immunocompetence; Immunoglobulin M; Keratitis, Herpetic; Male; Scleritis; Simplexvirus; Uveitis; Virus Activation

Topics: Acyclovir; Adult; Antiviral Agents; Corneal Ulcer; Humans; Keratitis, Herpetic; Male

The increasing incidence of acyclovir (ACV) and multidrug-resistant strains in patients with corneal HSV-1 infections leading to Herpetic Stromal Keratitis (HSK) is a major health problem in industrialized countries and often results in blindness. To overcome this obstacle, we have previously developed an HSV-gB-specific monoclonal antibody (mAb 2c) that proved to be highly protective in immunodeficient NOD/SCID-mice towards genital infections. In the present study, we examined the effectivity of mAb 2c in preventing the immunopathological disease HSK in the HSK BALB/c mouse model. Therefore, mice were inoculated with HSV-1 strain KOS on the scarified cornea to induce HSK and subsequently either systemically or topically treated with mAb 2c. Systemic treatment was performed by intravenous administration of mAb 2c 24 h prior to infection (pre-exposure prophylaxis) or 24, 40, and 56 hours after infection (post-exposure immunotherapy). Topical treatment was performed by periodical inoculations (5 times per day) of antibody-containing eye drops as control, starting at 24 h post infection. Systemic antibody treatment markedly reduced viral loads at the site of infection and completely protected mice from developing HSK. The administration of the antiviral antibody prior or post infection was equally effective. Topical treatment had no improving effect on the severity of HSK. In conclusion, our data demonstrate that mAb 2c proved to be an excellent drug for the treatment of corneal HSV-infections and for prevention of HSK and blindness. Moreover, the humanized counterpart (mAb hu2c) was equally effective in protecting mice from HSV-induced HSK when compared to the parental mouse antibody. These results warrant the future development of this antibody as a novel approach for the treatment of corneal HSV-infections in humans.

Topics: Acyclovir; Animals; Antibodies, Monoclonal; Antiviral Agents; Chlorocebus aethiops; Corneal Stroma; Female; Glycoproteins; Herpes Simplex; Immunoglobulins; Keratitis, Herpetic; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Simplexvirus; Vero Cells

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

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.. 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.. 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).. 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.

Topics: Acyclovir; Administration, Oral; Administration, Topical; Adolescent; Anterior Eye Segment; Antiviral Agents; Child; Child, Preschool; DNA, Viral; Eye Infections, Viral; Female; Herpesvirus 1, Human; Humans; Infant; Keratitis, Dendritic; Keratitis, Herpetic; Male; Polymerase Chain Reaction; Retrospective Studies

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

We investigated thymidine kinase (tk) mutants isolated during multiple episodes of recurrent bilateral acyclovir resistant herpes simplex keratitis in an immunocompetent patient. From one eye, we found a single guanine insertion, previously shown to greatly reduce TK expression, and from the other, a previously unidentified substitution, which genetic experiments confirmed confers drug resistance. The substitution, although distant from substrate binding sites, reduced thymidine phosphorylation 10-20-fold, and acyclovir phosphorylation >100-fold. This phenotype should permit reactivation from latency to cause recurrent disease. The results may have implications for the prevalence and prevention of acyclovir resistance in patients with herpes simplex keratitis.

Topics: Acyclovir; Adult; Amino Acid Substitution; Antiviral Agents; DNA, Viral; Drug Resistance, Viral; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Male; Molecular Sequence Data; Mutant Proteins; Mutation, Missense; Phosphorylation; Point Mutation; Recurrence; Sequence Analysis, DNA; Thymidine; Thymidine Kinase; Viral Proteins

We report the case of a patient with suspected ulcerating necrotizing herpetic stromal keratitis who showed no improvement despite intensive (amongst others antiherpetic) topical and systemic therapy. The ulcer healed following amniotic membrane transplantation and penetrating excimer laser keratoplasty was performed to improve visual acuity. The excision showed deep stromal proof of herpes simplex virus (HSV) type 1 antigens.

Topics: Acyclovir; Aged; Amnion; Antiviral Agents; Biological Dressings; Combined Modality Therapy; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating; Laser Therapy; Male; Treatment Failure; Treatment Outcome

The objective of this study was to develop a clear, aqueous nanomicellar formulation and evaluate its in vitro ocular biocompatibility as a novel carrier for topical ocular delivery of biotinylated lipid prodrug for the treatment of herpetic keratitis.. Micellar formulation of Biotin-12Hydroxystearic acid-acyclovir (B-12HS-ACV) was prepared by solvent evaporation/film hydration method with two nonionic surfactants, vitamin E TPGS and octoxynol-40. The optimized formulation was characterized for various parameters including micelle size, polydispersity index (PDI), and zeta-potential and in vitro prodrug release. Human corneal epithelial cells (HCECs) were employed for studying the cytotoxicity of the formulation. Further, mRNA expression levels of various cytokines were also studied with quantitative real-time PCR (qPCR).. Average size was 10.46±0.05 nm with a PDI of 0.086 for blank nanomicelles, and 10.78±0.09 nm with a PDI of 0.075 for prodrug-loaded nanomicelles. Both unloaded and prodrug-loaded nanomicelles had low negative zeta potential. Prodrug encapsulation efficiency of mixed nanomicelles was calculated to be ∼90%. Transmission electron microscopy analysis revealed that nanomicelles were spherical, homogenous, and devoid of aggregates. B-12HS-ACV release from nanomicelles was slow with no significant burst effect. Results show a sustained release of the prodrug from nanomicelles over a period of 4 days. Neither the blank formulation nor the prodrug-loaded micellar formulation demonstrated any cytotoxic effects. Further, incubation of HCECs with blank and prodrug-loaded nanomicellar groups did not significantly alter the expression levels of IL-1β, IL-6, IL-8, IL-17, TNF-α, and IFN-γ.. In summary, a topical clear, aqueous nanomicellar formulation comprised of vitamin E TPGS and octoxynol-40 loaded with 0.1% B-12HS-ACV was successfully developed. B-12HS-ACV-loaded nanomicelles are small in size, spherical, and homogenous, without any aggregates. The micellar formulations were perfectly transparent similar to pure water. Ocular biocompatibility studies indicated that mixed nanomicelles were nontoxic and noninflammatory to corneal epithelial cells. Therefore, nanomicellar technology represents a promising strategy for the delivery of biotinylated lipid prodrugs of ACV.

Topics: Acyclovir; Administration, Ophthalmic; Antiviral Agents; Biotinylation; Cytokines; Drug Delivery Systems; Epithelium, Corneal; Gene Expression Regulation; Humans; Keratitis, Herpetic; Lipids; Micelles; Nanoparticles; Octoxynol; Particle Size; Polyethylene Glycols; Prodrugs; Real-Time Polymerase Chain Reaction; Surface-Active Agents; Vitamin E

To report a case of epithelial Herpes Simplex keratitis in a patient wearing daily disposable contact lenses.. Case report.. A 30-year-old female contact lens wearer presented to the emergency clinic with a painful, red left eye associated with an acute reduction of vision over 48 h. On examination, confluent dendritic ulcers were present on the cornea. Neither pertinent ocular nor medical history was obtained to explain such a dramatic clinical presentation.. Contact lens wear was the only risk factor identified, perhaps resulting in deviation of the immune response at the ocular surface, with consequent extensive dendritic ulceration.

Topics: Acyclovir; Administration, Ophthalmic; Adult; Antiviral Agents; Contact Lenses; Disposable Equipment; Equipment Contamination; Female; Humans; Keratitis, Herpetic; Treatment Outcome

Herpes keratitis (HK) remains the leading cause of cornea-derived blindness in the developed world, despite the availability of effective antiviral drugs. Treatment toxicity and the emergence of drug resistance highlight the need for additional therapeutic approaches. This study examined ataxia telangiectasia mutated (ATM), an apical kinase in the host DNA damage response, as a potential new target for the treatment of HK.. Small molecule inhibitor of ATM (KU-55933) was used to treat herpes simplex virus type 1 (HSV-1) infection in three experimental models: (1) in vitro--cultured human corneal epithelial cells, hTCEpi, (2) ex vivo--organotypically explanted human and rabbit corneas, and (3) in vivo--corneal infection in young C57BL/6J mice. Infection productivity was assayed by plaque assay, real-time PCR, Western blot, and disease scoring.. Robust ATM activation was detected in HSV-1-infected human corneal epithelial cells. Inhibition of ATM greatly suppressed viral replication in cultured cells and in explanted human and rabbit corneas, and reduced the severity of stromal keratitis in mice. The antiviral effect of KU-55933 in combination with acyclovir was additive, and KU-55933 suppressed replication of a drug-resistant HSV-1 strain. KU-55933 caused minimal toxicity, as monitored by clonogenic survival assay and fluorescein staining.. This study identifies ATM as a potential target for the treatment of HK. ATM inhibition by KU-55933 reduces epithelial infection and stromal disease severity without producing appreciable toxicity. These findings warrant further investigations into the DNA damage response as an area for therapeutic intervention in herpetic ocular diseases.

Topics: Acyclovir; Animals; Antiviral Agents; Ataxia Telangiectasia Mutated Proteins; Blotting, Western; Cells, Cultured; Disease Models, Animal; Drug Combinations; Enzyme Inhibitors; Epithelium, Corneal; Female; Herpesvirus 1, Human; Humans; Immunohistochemistry; Keratitis, Herpetic; Mice; Mice, Inbred C57BL; Morpholines; Organ Culture Techniques; Pyrones; Rabbits; Real-Time Polymerase Chain Reaction; Viral Plaque Assay; Virus Replication

We present the case of a 42-year-old man with AIDS who had lost complete vision of his left eye for the past 15 days. MRI and brightness scan ultrasonography were performed on his eyes that suggested of endophthalmitis with dendritic involvement in the left eye. Viral DNA PCR was performed in aqueous humour sample that confirmed the presence of herpes simplex virus and showed a negative result for cytomegalovirus. The patient was treated with a high dose of oral acyclovir for 10 days and long-term topical acyclovir. Neodymium-doped yttrium aluminum garnet procedure was performed to clear up the cornea, and intraocular pressure was controlled with brimonidine and timolol maleate. The patient was diagnosed to have disseminated tuberculosis (tuberculoma of the brain) and was started with antituberculosis therapy. His condition improved significantly after the treatment, and keratitis in cornea started to clean up.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antitubercular Agents; Antiviral Agents; Endophthalmitis; Humans; Keratitis, Herpetic; Male; Tuberculosis

Topics: Acyclovir; Animals; Antiviral Agents; Drug Resistance, Viral; Female; Herpes Simplex; Humans; Keratitis, Herpetic; Male

A 20-year-old man presented with a recurrent episode of herpetic keratouveitis in his right eye. The patient was treated with oral acyclovir and topical steroids. One week later the patient reported a sudden diminution of vision. Slitlamp biomicroscopy revealed the presence of a central anterior capsular defect and anterior subcapsular cataract. Dosage of steroids was temporarily increased and progression of cataract monitored. Subsequently, the anterior chamber reaction decreased and steroids were tapered.

Topics: Acyclovir; Adrenal Cortex Hormones; Anterior Capsule of the Lens; Antiviral Agents; Cataract; Herpes Simplex; Humans; Keratitis, Herpetic; Male; Recurrence; Uveitis, Anterior; Vision Disorders; Young Adult

Topics: Acyclovir; Adult; Antiviral Agents; Humans; Keratitis, Herpetic; Lasers, Excimer; Male; Photorefractive Keratectomy; Postoperative Complications; Simplexvirus; Treatment Outcome

Collagen crosslinking (CXL) has been proposed as a treatment for infectious keratitis. Given the insurgence of antibiotic-resistant microorganisms and frequent toxicity of topical medications, CXL may be a potential treatment for corneal infections. However, corneal infection is itself a possible complication of this treatment. We describe a case of severe corneal thinning and melting in a woman who had a CXL procedure as a treatment for herpetic keratitis.

Topics: Acyclovir; Antiviral Agents; Collagen; Combined Modality Therapy; Cornea; Corneal Perforation; Corneal Stroma; Cross-Linking Reagents; Female; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating; Middle Aged; Photochemotherapy; Photosensitizing Agents; Postoperative Complications; Riboflavin; Ultraviolet Rays

Herpes simplex virus type 1 (HSV-1) is a leading cause of corneal blindness. Acyclovir (ACV) constitutes the standard treatment of HSV infections including herpetic keratitis (HK). HSV resistance to ACV is mainly described in immunocompromised patients. We describe two cases of ACV-resistant corneal HSV-1 in immunocompetent individuals with recurrent HK.

Topics: Acyclovir; Aged; Aged, 80 and over; Amino Acid Substitution; Antiviral Agents; DNA-Directed DNA Polymerase; Drug Resistance, Viral; Exodeoxyribonucleases; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Male; Microbial Sensitivity Tests; Mutant Proteins; Mutation, Missense; Recurrence; Thymidine Kinase; Viral Proteins

Varicella-zoster virus (VZV) resistance to acyclovir (ACV) has only been reported in rare cases of immunocompromised patients. We report the first case of an immunocompetent patient with ACV-resistant VZV keratitis associated with a nucleotide deletion in the VZV thymidine kinase gene, leading to production of a truncated protein.

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Viral; Herpesvirus 3, Human; Humans; Immunocompromised Host; Keratitis, Herpetic; Male; Middle Aged; Mutant Proteins; Sequence Deletion; Thymidine Kinase

Topics: Acyclovir; Animals; Antiviral Agents; Drug Resistance, Viral; Female; Herpes Simplex; Humans; Keratitis, Herpetic; Male

Long-term acyclovir (ACV) prophylaxis, recommended to prevent recurrent herpes simplex virus type 1 (HSV-1) ocular disorders, may pose a risk for ACV-refractory disease due to ACV resistance. We determined the effect of ACV prophylaxis on the prevalence of corneal ACV-resistant (ACV(R)) HSV-1 and clinical consequences thereof in patients with recurrent HSV-1 keratitis (rHK).. Frequencies of ACV(R) viruses were determined in 169 corneal HSV-1 isolates from 78 rHK patients with a history of stromal disease. The isolates' ACV susceptibility profiles were correlated with clinical parameters to identify risk factors predisposing to ACV(R) rHK.. Corneal HSV-1 isolates with >28% ACV(R) viruses were defined as ACV(R) isolates. Forty-four isolates (26%) were ACV-resistant. Multivariate analyses identified long-term ACV prophylaxis (≥12 months) (odds ratio [OR] 3.42; 95% confidence interval [CI], 1.32-8.87) and recurrence duration of ≥45 days (OR 2.23; 95% CI, 1.02-4.87), indicative of ACV-refractory disease, as independent risk factors for ACV(R) isolates. Moreover, a corneal ACV(R) isolate was a risk factor for ACV-refractory disease (OR 2.28; 95% CI, 1.06-4.89).. The data suggest that long-term ACV prophylaxis predisposes to ACV-refractory disease due to the emergence of corneal ACV(R) HSV-1. ACV-susceptibility testing is warranted during follow-up of rHK patients.

Topics: Acyclovir; Aged; Animals; Antiviral Agents; Chemoprevention; Chlorocebus aethiops; Drug Resistance, Viral; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Male; Microbial Sensitivity Tests; Middle Aged; Prevalence; Risk Factors; Vero Cells

To investigate the efficacy of a combination treatment composed of the cationic, membrane-penetrating peptide G2, and acyclovir (ACV) in both in vitro and ex vivo models of herpes simplex virus 1 (HSV-1) ocular infection.. The antiviral activity of a combined G2 peptide and ACV therapy (G2-ACV) was assessed in various treatment models. Viral entry, spread, and plaque assays were performed in vitro to assess the prophylactic efficacy of G2, G2-ACV, and ACV treatments. In the ex vivo model of HSV-1 infection, the level of viral inhibition was also compared among the three treatment groups via Western blot analysis and immunohistochemistry. The potential change in expression of the target receptor for G2 was also assessed using immunohistochemistry and RT-PCR.. Statistically significant effects against HSV-1 infection were seen in all treatment groups in the viral entry, spread, and plaque assays. The greatest effects against HSV-1 infection in vitro were seen in the G2-ACV group. In the ex vivo model, statistically significant anti-HSV-1 effects were also noted in all control groups. At 24 hours, the greatest inhibitory effect against HSV-1 infection was seen in the ACV group. At 48 hours, however, the G2-ACV-treated group demonstrated the greatest antiviral activity. Syndecan-1, a target of G2, was found to be upregulated at 12-hours postinfection.. This study shows that G2-ACV may be an effective antiviral against HSV-1 (KOS) strain when applied as single prophylactic applications with or without continuous doses postinfection.

Topics: Acyclovir; Animals; Anti-Infective Agents; Antimicrobial Cationic Peptides; Antiviral Agents; Blotting, Western; Cell Line; Chlorocebus aethiops; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Herpesvirus 1, Human; Immunohistochemistry; Keratitis, Herpetic; Vero Cells

Keratitis due to herpes simplex infection is a common cause of corneal damage resulting in impaired vision.. The aim of this study was to assess the outcome of penetrating keratoplasties in patients treated with systemic antiviral and immunosuppressive drugs.. The authors retrospectively analysed data of 12 patients who underwent penetrating keratoplasty. The average age at onset of the first keratitis preceding surgery was 18 years (between 5 and 40 years). The indication for surgery in 9 cases was to improve vision and in 3 patient to prevent corneal perforation. Nine patients were given both acyclovir and mycophenolate mofetil, as anti-viral agent and immunosuppressive treatment, respectively. Two patients were treated with anti-viral agent only while one patient received no systemic therapy. The average follow-up time was 53.1 months (between 16 and 84 months).. Of the 9 patients who underwent surgery for improving vision, 8 patients had transparent grafts during follow up without vascularization. All eight patients had been treated with acyclovir and mycophenolate mofetil. In one patient who had no systemic treatment recurrence and graft rejection was observed. Only one of the surgeries performed in acute stage of inflammation resulted in a properly healed transparent graft without recurrence and rejection. In this patient acyclivir and mycophenolate mofetil therapy had been given previously. In two cases the preventive - full or partial - systemic treatment had no effect. The visual acuity improved in all cases. In three patients visual acuity was influenced by some other factors as well.. The systemic acyclovir and mycophenolat mofetil therapy is fairly successful in perforating keratoplasty due to herpes simplex infection. Acyclovir decreases the risk of recurrence, while mycophenolate mofetil may prevent graft rejection. The timing of surgery is decisive; it leads to better results when performed in a scarred, noninflammatory state.. Bevezetés: A herpes simplex vírus által okozott szaruhártya-gyulladás a leggyakoribb oka a cornea centrumában kialakuló hegnek, amely látásvesztést okozhat. Célkitűzés: A szerzők célul tűzték ki a perforáló keratoplasztika eredményességének felmérését a szisztémás antiherpeses és immunszuppresszív terápia alkalmazásának tükrében. Módszer: Perforáló keratoplasztikán átesett 12 betegen végezték a retrospektív randomizált vizsgálatot. A műtéti beavatkozásig eltelt idő az első keratitis megjelenésétől számítva átlag 18 év volt (5–40 év). A műtéti indikáció 9 esetben a látás javítása, 3 esetben a cornea perforációjának megelőzése volt. Szisztémás kezelésként 9 beteg herpeszvírus elleni (acyclovir) és immunszuppresszív (mycophenolat mofetil), 2 beteg csak herpeszvírus elleni kezelést kapott, egy betegnél nem alkalmaztak szisztémás terápiát. Az átlagos követési idő 53,1 hónap volt (16–84 hó). Eredmények: A látásjavító célú 9 műtét közül 8 esetben a transzplantátum átlátszóan, ereződés nélkül gyógyult. Mind a 8 beteg acyclovir és mycophenolat mofetil kezelésben részesült. Egy esetben – amikor a beteg szisztémás kezelést nem kapott – recidíva és rejectio is fellépett. Az akut gyulladásos tünetekben végzett műtétek közül egyben gyógyult a transzplantátum átlátszóan, recidíva- és rejectiomentesen; a beteg acyclovir és mycophenolat mofetil terápiában részesült. Két esetben recidíva és rejectio is fellépett. Ezek közül egyben a beteg acyclovir és mycophenolat mofetil, egyben csak acyclovirkezelést kapott. A látóélesség minden esetben javult, 3 esetben a látást egyéb tényezők befolyásolták. Következtetések: A szisztémás acyclovir és mycophenolat mofetil terápia sikerrel alkalmazható herpes simplex keratitisben végzett perforáló keratoplasztikák után. Az acyclovir csökkenti a recidívák számát, a mycophenolat mofetil a transzplantátum rejectióját. A műtét időpontjának megválasztása döntő; a gyulladásmentes, heges állapotban végzett műtétek jobb eredménnyel kecsegtetnek. Orv. Hetil., 2013, 154(52), 2065–2070.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Female; Graft Rejection; Humans; Immunosuppressive Agents; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Middle Aged; Mycophenolic Acid; Postoperative Period; Retrospective Studies; Treatment Outcome; Visual Acuity

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

Herpes stromal keratitis is a serious condition and the most frequent cause of unilateral blindness. The real-time PCR is an accurate and fast diagnostic method for an analysis of infectious agents causing keratitis and keratouveitis. The aim of the study was to assess the relationship between clinical symptoms, treatment efficacy monitoring and viral quantity in corneal swabs determined by quantitative real-time PCR method. The real-time PCR method was used as well for the detection of other viral eye pathogens.. A total of 212 patients (136 men and 76 women) suspect of having herpes simplex virus (HSV) keratitis or keratouveitis were included in the study. The detection and quantitative analysis of the viral DNA were performed using the EliGene HSV1 RT kit, and the result was correlated with the clinical picture of the disease. The patients were routinely treated with acyclovir applied locally or, alternatively, in systemic administration. In a case of acyclovir treatment resistant keratitis, the patients were treated with local ganciclovir (Virgan gel ophth 0.15%).. A total of 636 analyses of the viral DNA were performed; 85 patients were positive for HSV1 (198 detected). There were 16 acyclovir resistant cases of keratitis (14%).. The real-time PCR appears as a fast and accurate method for an exact identification of the viral DNA in patients with herpes stromal keratitis. The introduction of the quantification is important for the treatment evaluation and for the specification of a so-called acyclovir resistant keratitis. A long-term systemic administration in maintenance doses may lead to the resistance and repeated, frequent relapses of the disease.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Child; Child, Preschool; DNA, Viral; Female; Ganciclovir; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Male; Middle Aged; Real-Time Polymerase Chain Reaction; Uveitis; Young Adult

To report five cases of new-onset herpetic eye disease with unusual presentation after ocular surgery.. Herpetic eye disease was suspected in five cases, three after cataract surgery and two after lamellar corneal transplantation surgery. Of these, four cases presented within 2-6 weeks of surgery. The clinical presentation was in the form of an epithelial defect, suspected epithelial down growth, graft oedema with unexplained anterior chamber inflammation and graft-host interface infection. A swab for viral detection with real-time polymerase chain reaction was performed in all the described cases.. Herpes simplex disease was detected in all cases. All cases responded to the antiherpetic medications.. Our study shows that new-onset herpetic eye disease may occur after cataract surgery and lamellar corneal transplantation, and a high index of suspicion may be necessary for the diagnosis in such cases.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Corneal Transplantation; DNA, Viral; Female; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Lens Implantation, Intraocular; Male; Middle Aged; Phacoemulsification; Polymerase Chain Reaction; Virus Activation; Visual Acuity; Young Adult

We have attached the antiviral drug acyclovir (ACV) to a xanthone photolabile protecting group (or photocage) through the O6 position of acyclovir, a procedure designed for the treatment of ocular herpes simplex virus infections. Acyclovir is photoreleased from the photocage, under physiological conditions, with a quantum yield (Φ(ACV release)) of 0.1-0.3 and an uncaging cross section (Φ·ε) of 450-1350 M cm(-1). We demonstrate that this photorelease method outcompetes alternative reaction pathways, such as protonation. Furthermore, complete release of the drug is theoretically possible given a sufficient dose of light . Surprisingly the acyclovir photocage, also showed some antiviral activity towards HSV-1.

Topics: Acyclovir; Antiviral Agents; Keratitis, Herpetic; Molecular Structure; Photolysis; Propionates; Ultraviolet Rays; Xanthones

The objective of this study was to determine current practices and opinions among cornea specialists for treating and preventing recurrences of herpes zoster ophthalmicus (HZO).. In November 2010, a survey of 15 questions was distributed to The Cornea Society listserv. Questions identified respondents' treatment practices for recurrent HZO and opinions regarding prolonged antiviral prophylaxis and zoster vaccine.. Of 100 respondents, the majority were cornea specialists (83 of 98, 85%). Eighty-seven percent (84 of 97) reported treating recurrent or chronic cases of HZO in the last year. The most common choice of treatment in the posed recurrent HZO clinical scenario was a combination of oral antiviral and topical corticosteroid (63 of 100, 63%), although significant variability existed in the duration of oral antiviral administration. Fifty-four respondents (56%) believed that prolonged acyclovir prophylaxis could reduce recurrent signs of HZO; 28% (27 of 98) believed that recurrences of HZO could be reduced after the period of acyclovir administration. For patients with a history of HZO, most respondents reported not recommending the adult zoster vaccine (63 of 98, 64%), but 46% (43 of 94) believed that the vaccine could reduce recurrent signs or did not know.. Many cornea specialists are managing recurrent or chronic cases of HZO, but there is variability in the use of topical corticosteroids and antivirals. Additionally, no consensus exists on the efficacy of prolonged antiviral therapy or the adult zoster vaccine to reduce chronic or recurrent disease. These results demonstrate the need for further systematic study of treatment and prophylaxis for recurrent and chronic HZO.

Topics: Acyclovir; Administration, Oral; Administration, Topical; Adult; Antiviral Agents; Attitude of Health Personnel; Chronic Disease; Drug Therapy, Combination; Glucocorticoids; Health Care Surveys; Herpes Zoster Ophthalmicus; Herpes Zoster Vaccine; Humans; Keratitis, Herpetic; Ophthalmology; Practice Guidelines as Topic; Practice Patterns, Physicians'; Recurrence; Surveys and Questionnaires; Treatment Outcome

To evaluate the therapeutic effect of deep anterior lamellar keratoplasty (DALK) in patients with herpetic stromal keratitis (HSK).. Forty-three eyes belonging to 42 patients with HSK, including 22 eyes in the active phase and 21 eyes in the quiescent phase, underwent DALK at the Shandong Eye Institute from January 2006 to December 2009. All patients with active disease had received intravenous acyclovir and amniotic membrane implants prior to DALK. Herpes simplex virus type 1 (HSV-1) antigens from excised corneal buttons were detected by immunohistochemistry.. The follow-up ranged from 1 to 4 years (mean, 29.1 months). Graft rejection occurred in one eye (2.3%) and was reversed. Among the other 42 survived grafts (97.7%), 37 remained clear at the last visit. The best spectacle-corrected visual acuity was 20/200 or better in 95.2% of eyes and 20/40 or better in 38.1% of eyes. Six eyes (14.0%) developed recurrent HSK, one of which received a second keratoplasty due to ineffective antiviral medication. There were no significant differences in endothelial cell density between 6 months and 12 months after the surgery. By immunohistochemistry, HSV-1 antigens were observed in the stroma of 18 of 32 corneal buttons.. DALK can not only remove the corneal lesions of HSK but also reduce latent or persistent viral loads in the cornea. In eyes with active or quiescent HSK but otherwise healthy endothelia, DALK seems to be safe and promising for its favorable visual outcome, graft survival rate, and low endothelial cell loss.

Topics: Acyclovir; Antigens, Viral; Antiviral Agents; Cell Count; Corneal Stroma; Corneal Transplantation; Endothelium, Corneal; Graft Survival; Herpesvirus 1, Human; Humans; Immunoenzyme Techniques; Keratitis, Herpetic; Recurrence; Retrospective Studies; Tomography, Optical Coherence; Visual Acuity

To investigate the role of in vivo confocal microscopy (IVCM) in the detection of inflammatory activity and follow-up of herpetic stromal keratitis (HSK).. Prospective observational cohort study.. Thirty-eight patients with active HSK.. Within 7 days after diagnosis of active HSK, both eyes of each patient were examined by slit-lamp biomicroscopy and white-light IVCM (Confoscan 4; Nidek Technologies, Padova, Italy). The HSK-affected eyes were followed up at 1, 3, 6, and 12 months, whereas the unaffected fellow eyes were reexamined after 12 months. Three patients did not complete follow-up and were excluded for data analyses. All IVCM examinations were assessed for morphologic alterations characteristic of inflammatory activity and for corneal backscatter. As secondary outcome parameters, best-corrected visual activity (BCVA), central corneal thickness (CCT), intraocular pressure (IOP), and endothelial cell density (ECD) were determined at each study visit. We used repeated-measures analysis of variance to assess changes during the 12-month follow-up period and paired t tests to compare HSK-affected eyes with fellow eyes.. Presence of dendriform cells, pseudoguttae, and keratic precipitates, and follow-up of mean corneal backscatter.. An increase of dendriform cells and pseudoguttae often accompanied stromal infiltration. Because these IVCM parameters were indiscernible or overlooked at slit-lamp examination, they proved to be excellent indicators of inflammatory activity. At 12 months' follow-up, mean corneal backscatter had decreased significantly by 36%, but still fell outside the normal range in 24 (69%) of the HSK-affected eyes. By using slit-lamp in conjunction with IVCM, we detected 17 recurrences in 14 of 35 patients (40%). Three of these recurrences were missed by slit-lamp, and 6 of these were missed by IVCM. At 12 months' follow-up, BCVA (-9 letters), CCT (-36 μm), and ECD (-313 cells/mm(2)) were significantly lower, whereas IOP (1.8 mmHg) was significantly higher, in HSK-affected eyes compared with fellow eyes.. The data presented demonstrate that IVCM is complementary to slit-lamp examination in the follow-up of HSK, particularly because of its power to detect early signs of intracorneal inflammatory activity. Therapy guidance based on morphologic assessment and corneal backscatter measurement by combined IVCM and slit-lamp examination may improve the outcome of HSK.. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Cell Count; Corneal Stroma; Dexamethasone; Drug Therapy, Combination; Endothelium, Corneal; Female; Follow-Up Studies; Glucocorticoids; Herpesvirus 1, Human; Herpesvirus 3, Human; Humans; Inflammation; Intraocular Pressure; Keratitis, Herpetic; Male; Microscopy, Confocal; Middle Aged; Prospective Studies; Visual Acuity; Young Adult

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 report long term visual outcomes, complications and graft survival of patients undergoing deep anterior lamellar keratoplasty (DALK) to treat corneal scarring secondary to herpes simplex virus (HSV) keratitis.. Retrospective, non-comparative case series. 18 patients who underwent DALK for HSV keratitis related corneal scarring between January 2004 and February 2007 were included. DALK was performed by Anwar's big bubble technique. Data collected for analysis included preoperative characteristics, intraoperative complications and postoperative acuity, complications and subsequent operations.. Mean best corrected distance visual acuity (LogMAR) improved from 1.51 ± 0.90 preoperatively to 0.82 ± 0.85 at the last follow-up (p=0.05). 27% of patients with more than 4 years follow-up had a best corrected distance visual acuity of 6/12 or better and 64% were 6/24 or better. Six patients (33%) experienced a recurrence of HSV keratitis and 9 (50%) experienced an episode of graft rejection. There were five cases (28%) of graft failure, four of whom had had a previous episode of graft rejection. Logistic regression did not find an association with graft rejection, HSV recurrence, any other observed postoperative host corneal vascularisation and any postoperative complication. The majority of patients underwent a second operation with 50% requiring cataract surgery.. DALK for the treatment of HSV related corneal scarring is associated with a high percentage of postoperative complications. DALK in this context is also associated with a large percentage of secondary operations. Patients should be aware of this when giving informed consent for DALK to treat HSV related corneal scars.

Topics: Acyclovir; Antiviral Agents; Cicatrix; Corneal Transplantation; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Intraocular Pressure; Kaplan-Meier Estimate; Keratitis, Herpetic; Male; Recurrence; Reoperation; Retrospective Studies; Risk Factors; Treatment Outcome; Visual Acuity

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Diagnosis, Differential; DNA, Viral; Drug Resistance, Viral; Female; Follow-Up Studies; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Male; Middle Aged; Real-Time Polymerase Chain Reaction

For the treatment of ocular keratitis acyclovir, as a highly specific inhibitor of herpes virus replication, is applied topically into the eye. The objective of this study was to design and evaluate freeze-dried, bioadhesive and biodegredable acyclovir ocular minitablets for prolonged local drug action. The sponge-like nature of the lyophilized ocular minitablets ensures rapid hydration and gelation of these tablets in the eye and thus would reduce the foreign body sensation. The polymers used were sodium carboxymethylcellulose (NaCMC), hydroxypropylmethylcellulose (HPMC), xanthan gum, chitosan and Carbopol 943P. The minitablets were evaluated for drug content, weight variation, bioadhesion, water uptake and in vitro drug release. In addition, the rheological characteristics of the polymers solutions were investigated. Rheological data revealed that all tested polymers exhibited pseudoplastic behaviour which is required to minimize interference with blinking. Drug release was found to be affected by the type and concentration of polymer. The order of sustainment was chitosan > xanthan > HPMC > Carbopol > NaCMC. Water uptake study, dissolution rate of the polymers and viscosity measurements could explain the different release profiles of the drug from the polymers. Chitosan minitablet was chosen for its significant sustained release and good bioadhesive property for in vivo study in rabbits. The tablet showed a good permeation into the cornea in comparison to the commercially available Zovirax(®) eye ointment. In conclusion, chitosan ocular minitablets containing acyclovir could be considered as a promising sustained drug delivery system for ocular keratitis treatment.

Topics: Acyclovir; Animals; Antiviral Agents; Chemistry, Pharmaceutical; Chitosan; Columbidae; Delayed-Action Preparations; Eye; Freeze Drying; Gels; Keratitis, Herpetic; Particle Size; Polymers; Rabbits; Simplexvirus; Tablets; Viscosity; Vision, Ocular

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

Recurrence of herpetic keratitis and immune reactions is the major cause of graft failures after penetrating keratoplasty as a consequence of herpes simplex keratitis. No treatment regimen is yet considered a standard of care. This retrospective study analyzes the effectiveness of combined systemic acyclovir and immunosuppressive therapy with cyclosporine A (CSA) or mycophenolate mofetil (MMF) after high-risk keratoplasty in herpetic keratitis.. A total of 87 high-risk keratoplasties treated with postoperative combined systemic acyclovir and immunosuppressive therapy with CSA or MMF were analyzed retrospectively according to the therapeutic regimen, the degree of preoperative corneal vascularization, and tissue matching of the graft. Endpoints included immunological graft rejection, recurrence of the herpetic keratitis, graft failure, and visual acuity.. There was an overall trend toward an improvement of visual acuity. Graft failure occurred in 13.1%, in all cases after termination of immunosuppression with MMF or CSA. In 4 of 11 cases, immune reactions caused graft failure. Patients with 3 to 4 quadrants of corneal vascularization showed significantly higher rates of graft rejection than patients with 1 to 2 quadrants vascularized or avascular corneas. Herpetic recurrence occurred in 31.8% and caused 18.2% of graft failure. In 7 of 23 cases, graft rejection was induced by herpetic recurrence.. Graft survival rate and functional outcome after postoperative antiviral and immunosuppressive treatment in cases of penetrating keratoplasties after herpetic keratitis are comparable with results of normal-risk keratoplasties, despite existing high risks for immune rejections or herpetic recurrences.

Topics: Acyclovir; Adult; Aged; Aged, 80 and over; Antiviral Agents; Cyclosporine; Drug Therapy, Combination; Female; Follow-Up Studies; Graft Rejection; Humans; Immunosuppressive Agents; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Middle Aged; Mycophenolic Acid; Postoperative Care; Retrospective Studies; Secondary Prevention; Visual Acuity; Young Adult

Neonatal herpes simplex virus (HSV) manifests as a disease limited to skin, eyes, and/or mucous membranes, central nervous system disease with/without skin involvement, or disseminated infection. Given the high morbidity and mortality of untreated neonatal HSV, early recognition and prompt treatment are important. We report two cases of unilateral HSV keratitis, after Cesarean section, in neonates whose twin had died. Both mothers denied history of HSV. Ophthalmic diagnosis led to full systemic workup and appropriate treatment.

Topics: Acyclovir; Adolescent; Antiviral Agents; Cesarean Section; Fatal Outcome; Female; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Infant, Newborn; Keratitis, Herpetic; Pregnancy; Pregnancy Complications, Infectious; Treatment Outcome; Trifluridine; Twins, Dizygotic; Young Adult

Topics: Acyclovir; Administration, Inhalation; Antiviral Agents; Blepharitis; Budesonide; Glucocorticoids; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Male; Middle Aged; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive

Using pharmacokinetics to explore the mechanism of honey to enhance the efficacy of acyclovir (ACV) treatment of herpes simplex keratitis (HSK), providing the basis for combination of the prescription of two drugs and dosage regimen designed.. Single dosages of 5% honey and 0% honey Meyasu eye ointment are injected into rabbit eyes. The aqueous humor of rabbit eye is measured at different times, specifically the content of ACV in aqueous humor by HPLC. Mathematical models are established, from which pharmacokinetic parameters are extracted and compared by mathematics and statistics methods.. Both the 5% and 0% honey Meyasu eye ointment in rabbit eyes are belong to a two-compartment model. The absorption half-life of the 5% Meyasu eye ointment in aqueous humor is as 2.30 times longer, the distribution half-life is 2.12 times longer, the peak concentration is 1.17 times longer, the peak time is 1.36 times longer, AUC is 1.41 times longer when compared to the 0% Meyasu eye ointment.. Honey can significantly increase the ACV concentration and bioavailability in the eye, extend the action time of ACV in target cells and increase the retention capacity of ACV in the target tissue; thereby improving treatment success.

Topics: Acyclovir; Animals; Antiviral Agents; Disease Models, Animal; Eye; Female; Honey; Humans; Keratitis, Herpetic; Male; Rabbits

To report a case of recurrent herpes simplex keratitis after verteporfin photodynamic therapy for corneal neovascularization.. A 69-year-old man who had lipid keratopathy with corneal neovascularization secondary to herpes simplex keratitis in the right eye and who was treated with topical steroid received photodynamic therapy with verteporfin. Six neovascular areas in the cornea were treated consecutively to occlude new vessels and reduce the risk of allograft rejection after subsequent keratoplasty.. Three days after verteporfin photodynamic therapy, there was evidence of vascular occlusion. However, a herpetic epithelial ulcer was detected in the cornea. Ten days after treatment, the lesion progressed to a geographic ulcer. After topical and systemic acyclovir treatment, the lesion healed. Five months after treatment, penetrating keratoplasty and postoperative antiviral prophylaxis were performed. During a follow-up period of 12 months, the graft remained clear with visual acuity of 20/40.. Herpes simplex keratitis can recur after verteporfin photodynamic therapy for corneal neovascularization.

Topics: Acyclovir; Aged; Antiviral Agents; Corneal Neovascularization; Humans; Keratitis, Herpetic; Male; Photochemotherapy; Photosensitizing Agents; Porphyrins; Recurrence; Verteporfin; Virus Activation; Visual Acuity

Topics: Acyclovir; Antiviral Agents; Corneal Diseases; Drug Resistance, Viral; Foscarnet; Humans; Keratitis, Herpetic; Treatment Failure; Treatment Outcome; Vidarabine

Topics: Acyclovir; Antiviral Agents; Cornea; Female; Herpes Zoster Ophthalmicus; Humans; Keratitis, Herpetic; Microscopy, Confocal; Middle Aged; Ophthalmic Nerve; Prednisolone; Sensory Receptor Cells; Treatment Outcome

To evaluate the success of cyanoacrylate tissue adhesive in the management of corneal perforations associated with herpetic keratitis.. Case records of 46 patients with microbiologically proven herpetic keratitis associated with corneal perforations that were treated with corneal gluing were analyzed retrospectively in a tertiary care hospital. N-Butyl cyanoacrylate tissue adhesive and bandage contact lens were applied in addition to antiviral therapy. The main outcome measure was preservation of the structural integrity of the globe.. Glue application could heal corneal perforations in only 17 eyes (37%). Therapeutic keratoplasty had to be performed in 26 eyes (57%) because of failure of the glue. Fourteen eyes (31%) required multiple applications of tissue adhesive, and 2 eyes had to be eviscerated. Location of perforation, additional anterior chamber intervention, and use of prophylactic acyclovir therapy had no statistically significant effect on the overall final outcome.. Corneal perforations associated with herpetic keratitis may not heal with glue application alone, and corneal transplantation surgery may be required to maintain the ocular structural integrity.

Topics: Acyclovir; Adult; Aged; Aged, 80 and over; Antiviral Agents; Corneal Perforation; Enbucrilate; Female; Humans; Keratitis, Herpetic; Male; Middle Aged; Retrospective Studies; Tissue Adhesives; Treatment Outcome; Wound Healing

Topics: Acyclovir; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antiviral Agents; Bevacizumab; Diabetic Retinopathy; DNA, Viral; Epithelium, Corneal; Herpesvirus 1, Human; Humans; Injections; Keratitis, Herpetic; Vascular Endothelial Growth Factor A; Vitreous Body

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.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Antiviral Agents; Blepharitis; Child; Child, Preschool; Conjunctivitis, Viral; Female; Follow-Up Studies; Humans; Incidence; Infant; Keratitis, Herpetic; Male; Middle Aged; Minnesota; Post-Exposure Prophylaxis; Risk Factors; Secondary Prevention; Sex Distribution; Treatment Outcome

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

Topics: Acyclovir; Administration, Topical; Antiviral Agents; Evidence-Based Medicine; Glucocorticoids; Health Knowledge, Attitudes, Practice; Health Personnel; Health Surveys; Humans; Information Dissemination; Keratitis, Herpetic; Ophthalmology; Public Health Practice; Randomized Controlled Trials as Topic; Surveys and Questionnaires

We report the case of a 34-year-old man who had uncomplicated cataract surgery in his left eye. Medical history was significant for atopic dermatitis, requiring oral immunosuppressive medications. Two days after the surgery, the patient presented with pain, photophobia, decreased vision, and a small corneal abrasion. On postoperative day 5, the patient returned with left upper lid vesicular lesions and 2 corneal dendrites. Corrected vision was 20/100 OS, with intraocular pressure of 18 mm Hg and 1+ pigmented cells in the anterior chamber. Cultures of the lid lesions revealed herpes simplex virus (HSV) type 1. The patient was placed on oral acyclovir 800 mg 5 times a day. By day 8, the dendrites had resolved, and by day 15, the lid lesions healed over. HSV keratitis is an uncommon complication after cataract surgery. Ophthalmologists should be aware of the possibility of developing HSV keratitis even after the most routine cataract extraction.

Topics: Acyclovir; Administration, Oral; Adult; Anti-Inflammatory Agents; Antifungal Agents; Antiviral Agents; Cataract Extraction; Drug Administration Schedule; Drug Therapy, Combination; Eyelid Diseases; Herpes Simplex; Humans; Keratitis, Herpetic; Male; Postoperative Complications; Prednisolone; Treatment Outcome; Wound Healing

Keratitis occurring in renal transplant patients are often severe, with difficult management. We describe the case of a renal transplant patient, 44 year-old man, with history of recurrent herpetic keratitis, which developed an impending corneal perforation. Conjunctival smear showed the presence of amoebic cysts. Anti-amoebic treatment was undertaken in addition with oral aciclovir, and a therapeutic penetrating keratoplasty was performed. An ulceration of the graft occurred within five months. Ocular samples showed the presence of Candida albicans. Despite aggressive antifungal therapy, he required a second therapeutic penetrating keratoplasty for graft perforation. One month later, we noted a recurrence of the ulcer with corneal thinning which evolved to perforation.

Topics: Acyclovir; Adult; Amebiasis; Animals; Antifungal Agents; Candida albicans; Conjunctiva; Corneal Transplantation; Humans; Keratitis, Herpetic; Kidney Transplantation; Male; Recurrence; Retinal Perforations

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 report a case of herpetic epithelial keratitis that developed after intravitreal bevacizumab (Avastin) injection.. A 63-year-old man with diabetes with proliferative diabetic retinopathy and macular edema received intravitreal injection of bevacizumab (Avastin) in his right eye.. Three days after the injection, the patient presented with foreign body sensation, redness, tearing, photophobia, and decreased visual acuity in the right eye. The cornea showed an arborizing dendritic epithelial lesion with terminal bulb typical of herpes simplex virus (HSV) epithelial keratitis. HSV-DNA was detected in corneal scrapings using polymerase chain reaction. A diagnosis for herpes simplex epithelial keratitis was made. Topical acyclovir ointment therapy was initiated with good resolution of HSV signs and symptoms.. Herpes simplex epithelial keratitis can be a possible complication of intravitreal bevacizumab (Avastin) injection. To our knowledge, this case is the first report of herpetic epithelial keratitis after intravitreal bevacizumab (Avastin) injection.

Topics: Acyclovir; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antiviral Agents; Bevacizumab; Diabetic Retinopathy; DNA, Viral; Epithelium, Corneal; Herpesvirus 1, Human; Humans; Injections; Keratitis, Herpetic; Male; Middle Aged; Vascular Endothelial Growth Factor A; Vitreous Body

A 40-year-old woman presented with an unusual form of corneal herpetic reactivation 5 weeks after laser in situ keratomileusis. The cornea showed diffuse edema and a stromal ring infiltrate (disciform in appearance). Oral antiviral and topical steroids in tapered dosages were administered. The infiltrate disappeared within 6 weeks. Progressive improvement was also seen in all the parameters on Pentacam scans, including the pachymetry, keratometry readings, and elevation on the anterior float. Herpetic reactivation may occur in many forms after excimer laser ablation. Timely diagnosis and management is crucial to maintain good structural and visual outcomes. Pentacam analysis may serve as a useful adjunct in following the progression of herpetic reactivation cases.

Topics: Acyclovir; Adult; Antiviral Agents; Astigmatism; Cornea; Corneal Topography; Drug Therapy, Combination; Female; Glucocorticoids; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Keratomileusis, Laser In Situ; Lasers, Excimer; Myopia; Prednisolone; Virus Activation; Visual Acuity

We report a case of herpes simplex virus (HSV) epithelial keratitis that developed after a subtenon triamcinolone acetonide (TA) injection.. A 78-year-old woman with a branch retinal vein occlusion and diffuse macular edema in her left eye received a subtenon injection of 20 mg of TA.. Six days after the injection, the patient presented with a foreign body sensation, tearing, redness, and photophobia in the same eye. Slit-lamp examination revealed multiple corneal dendriform ulcers. She was diagnosed with HSV epithelial keratitis and treated with topical acyclovir ointment. The epithelial lesions healed after 1 week of therapy.. HSV epithelial keratitis can be a possible complication of a TA subtenon injection.

Topics: Acyclovir; Aged; Antiviral Agents; Epithelium, Corneal; Fascia; Female; Glucocorticoids; Herpesvirus 1, Human; Humans; Injections; Keratitis, Herpetic; Macular Edema; Retinal Vein Occlusion; Triamcinolone Acetonide; Virus Activation

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

Alternative therapies are needed for HSV-1 infections in patients refractory to treatment with Acyclovir (ACV) and its derivatives. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) are single-stranded DNA analogues that enter cells readily and reduce target gene expression through steric blockage of complementary RNA. When applied before or soon after infection PPMO targeting the translation-start-site regions of HSV-1 ICP0 or ICP27 mRNA reduced HSV-1 plaque formation by 70-98% in vitro. The ICP0 PPMO also reduced ACV-resistant HSV-1 (strain 615.9) plaque formation by 70-90%, while an equivalent dose of ACV produced only 40-50% inhibition when the treatment was applied between 1 and 3hpi. Seven daily topical treatments of 100microg ICP0 PPMO caused no gross or microscopic damage to the corneas of uninfected mice. Topical application of 10microg ICP0 PPMO to the eyes of HSV-1 infected mice reduced the incidence of eye disease by 37.5-50% compared to controls. This study demonstrates that topically applied PPMO holds promise as an antiviral drug candidate against HSV-1 ocular infection.

Topics: Acyclovir; Animals; Antiviral Agents; Base Sequence; Chlorocebus aethiops; Drug Resistance, Viral; Herpesvirus 1, Human; Humans; Immediate-Early Proteins; Keratitis, Herpetic; Mice; Molecular Sequence Data; Morpholines; Morpholinos; Ubiquitin-Protein Ligases; Vero Cells; Viral Proteins; Virus Replication

To identify whether histopathologic presence of neovascularization is predictive for allograft failure following penetrating keratoplasty for herpes simplex virus (HSV) keratitis.. Retrospective, interventional case series of 62 consecutive patients with HSV keratitis who underwent penetrating keratoplasty at the Kellogg Eye Center between 1990 and 2000. Reviews of the patients' clinical charts and the histopathologic slides of their excised corneal buttons were performed to identify associations between histopathologic neovascularization and clinical outcomes.. To determine whether histopathologic presence of neovascularization predicts allograft failure.. Histopathologic presence of neovascularization was present in 31% of corneal specimens and predicted subsequent allograft failure (P = 0.002) and HSV recurrence (P = 0.05).. Histopathologic presence of neovascularization is a risk factor for corneal allograft failure and HSV recurrence.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Child; Child, Preschool; Corneal Neovascularization; Drug Therapy, Combination; Female; Glucocorticoids; Graft Rejection; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Middle Aged; Prednisolone; Recurrence; Retrospective Studies; Risk Factors; Transplantation, Homologous

The incidence and clinical significance of herpes simplex virus type 1 (HSV-1) acyclovir resistance were determined in patients with recurrent herpetic keratitis (RHK).. Sequential corneal isolates (n = 39) from 15 immunocompetent patients with RHK were assayed for acyclovir susceptibility and genotyped by analyzing the hypervariable regions of the HSV-1 genes US1 and US12. The thymidine kinase (TK) gene of each isolate was sequenced, and the proportion of acyclovir-resistant viruses within isolates was determined.. Uniform acyclovir-resistant or acyclovir-sensitive sequential isolates were identified in 4 and 2 patients, respectively. Notably, the acyclovir susceptibility of sequential isolates changed from acyclovir sensitive to acyclovir resistant (5 patients) or from acyclovir resistant to acyclovir sensitive (3 patients). The acyclovir-resistant phenotype of the isolates correlated with the patient's unresponsiveness to acyclovir therapy. Combined analyses of the TK gene and genotype of sequential isolates showed that acyclovir-sensitive isolates contained multiple acyclovir-resistant variants of the same virus and that an identical acyclovir-resistant HSV-1 strain reappeared in the patient's cornea during RHK episodes.. Corneal HSV-1 isolates are mixtures of acyclovir-sensitive and acyclovir-resistant viruses that share the same genotype but have different TK sequences. Recovery of the same acyclovir-resistant virus during consecutive herpetic keratitis episodes suggests that acyclovir-resistant HSV-1 establishes latency and reactivates intermittently to cause acyclovir-refractory RHK.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Drug Resistance, Viral; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Male; Middle Aged; Prospective Studies; Virus Latency

To report an 81-year-old woman with corneal neovascularization secondary to herpetic stromal keratitis treated with subconjunctival bevacizumab and to discuss the role of this novel antiangiogenic treatment.. Case report and review of medical literature.. A dramatic regression of corneal vessels was observed 1 week after the injection. After a 3-month follow-up, there was no recurrence of corneal revascularization.. Bevacizumab may be a valid complementary treatment in patients with corneal neovascularization caused by herpetic stromal keratitis.

Topics: Acyclovir; Aged, 80 and over; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bevacizumab; Corneal Neovascularization; Corneal Stroma; Female; Humans; Keratitis, Herpetic; Treatment Outcome; Vascular Endothelial Growth Factor A

The prevalence and molecular characteristics of isolates from 173 immunocompetent patients with herpetic keratitis (HK) who were infected with acyclovir (ACV)-resistant (ACV(R)) corneal herpes simplex virus (HSV)-1 was determined. Isolates from 11 (6.4%) of the patients were ACV(R), and 9 of these 11 patients were refractory to therapy with ACV; the ACV(R) isolates from 5 and 1 of these 9 patients were cross-resistant to gancyclovir and to both gancyclovir and foscarnet, respectively. Of the 11 ACV(R) isolates, 10 had, in the thymidine kinase gene, mutations that presumably conferred the ACV(R) phenotype. These data demonstrate a relatively high prevalence of corneal HSV-1 ACV(R) isolates in patients with HK, which emphasizes the need to monitor for ACV susceptibility in patients with HK who are refractory to therapy with ACV.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Cohort Studies; Cornea; Drug Resistance, Multiple, Viral; Female; Foscarnet; Ganciclovir; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Male; Middle Aged; Prevalence; Thymidine Kinase

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 report a case of bilateral herpes simplex keratitis with unilateral secondary bacterial keratitis resulting in corneal perforation in a patient with pityriasis rubra pilaris.. Case report.. A 77-year-old female with pityriasis rubra pilaris was referred for a perforated corneal ulcer of the left eye. Cultures were positive in both eyes for Herpes simplex and in the left eye for Pseudomonas fluorescens and Staphylococcus aureus A microbiological cure was obtained with a combination of tectonic keratoplasty, fortified topical antibiotics, and systemic acyclovir.. Pityriasis rubra pilaris is a rare, inflammatory dermatologic disease that may predispose patients to bilateral Herpes simplex keratitis, secondary bacterial superinfection, and a tendency toward rapid stromal ulceration with risk of perforation.

Topics: Acyclovir; Administration, Oral; Administration, Topical; Aged; Anti-Bacterial Agents; Antiviral Agents; Bacterial Infections; Cefazolin; Ceftazidime; Corneal Transplantation; Corneal Ulcer; Female; Humans; Keratitis; Keratitis, Herpetic; Pityriasis Rubra Pilaris; Pseudomonas fluorescens; Pseudomonas Infections; Staphylococcal Infections

In vitro and in vivo studies demonstrated the antiviral efficacy of nerve growth factor (NGF) and its cyto-protective effect in herpes simplex virus (HSV)-infected cells. The aims of this study were to evaluate the role of endogenous NGF in HSV corneal infection, and the effects of topical NGF treatment on herpetic keratitis.. Herpetic keratitis was induced in 40 rabbits with the HSV-1 McKrae strain. Animals were divided into four groups, and treated with topical neutralizing anti-NGF antibodies, NGF, acyclovir or balanced salt solution (BSS) respectively. The clinical course of HSV keratitis was evaluated and scored by slit-lamp examination. In addition, biochemical (immunohistochemistry for glycoprotein D) and molecular (nested PCR for glycoprotein D) analyses were carried out to estimate viral replication.. Treatment with anti-NGF antibodies induced a more severe keratitis associated with increased biochemical and molecular markers of active viral replication. Two animals in this group developed lethal HSV encephalitis. Conversely, topical treatment with NGF induced a significant amelioration of clinical and laboratory parameters when compared to the BSS treated group (control). No significant differences were observed between NGF- and acyclovir-treated groups.. This study demonstrated the crucial role of endogenous NGF in herpetic keratitis. The comparable effects of NGF and acyclovir confirm the antiviral activity of NGF, and indicate a potential use of topical NGF in herpetic keratitis.

Topics: Acyclovir; Administration, Topical; Animals; Antibodies, Blocking; Antiviral Agents; Cytoprotection; Disease Models, Animal; Female; Herpesvirus 1, Human; Immunoenzyme Techniques; Keratitis, Herpetic; Nerve Growth Factor; Polymerase Chain Reaction; Prospective Studies; Rabbits; Viral Envelope Proteins; Virus Replication

Ocular infections resulting from herpes simplex viral infection can result in significant ocular morbidity. Crucial in preventing this complication is the need for appropriate diagnosis and initiation of treatment. In addition, most of the studies on herpes simplex viral infections involve adult populations. It is important to consider that children have a different progression of the disease process and may require an altered treatment regimen.

Topics: Acyclovir; Antiviral Agents; Child; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Keratitis, Herpetic; Ophthalmic Solutions; Sensory Deprivation; Severity of Illness Index; Trifluridine

To compare systemic vs topical acyclovir therapy for the prevention of recurrence of herpetic keratitis following penetrating keratoplasty (PK).. A retrospective observational study.. 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.. 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.. Systemic acyclovir is more effective than topical acyclovir in achieving better graft outcomes after PK for HED.

Topics: Acyclovir; Aged; Aged, 80 and over; Antiviral Agents; Female; Graft Survival; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Middle Aged; Recurrence; Retrospective Studies; Visual Acuity

To determine the efficacy of A-5021, a new analogue of acyclovir, on murine herpetic keratitis.. Herpes simplex virus type 1 (strain CHR3) was inoculated onto bilateral scarified BALB/c corneas. Clinical scores on the corneas treated with A-5021 eyedrops were compared with those obtained from the treatment with 3% acyclovir eye ointment by slit lamp microscopy. Virus titers of the trigeminal ganglia and eyeballs were quantitated on Vero cell monolayers. Mice treated with saline or a white petroleum jelly were used as controls.. A-5021 eyedrops significantly suppressed both corneal epithelial and stromal lesions at all concentrations used. Clinical scores on the epithelium and stroma treated with 0.1% A-5021 were equivalent to those with 3% acyclovir treatment. When compared with the non-drug-treated control mice, virus titers in the eyeballs and trigeminal ganglia in A-5021- and acyclovir-treated mice were significantly less than those in controls.. A-5021 eyedrops, which are easily applied onto the affected cornea, ameliorated clinical scores and suppressed virus growth. It is a promising alternative treatment of herpetic keratitis.

Topics: Acyclovir; Animals; Antiviral Agents; Chlorocebus aethiops; Disease Models, Animal; Female; Guanine; Herpesvirus 1, Human; Keratitis, Herpetic; Mice; Mice, Inbred BALB C; Ophthalmic Solutions; Trigeminal Ganglion; Vero Cells

To evaluate in vivo corneal absorption of the amino acid prodrugs of acyclovir (ACV) using a topical well model and microdialysis in rabbits.. Stability of L-alanine-ACV (AACV), L-serine-ACV (SACV), L-isoleucine-ACV (IACV), gamma-glutamate-ACV (EACV) and L-valine-ACV (VACV) prodrugs was evaluated in various ocular tissues. Dose-dependent toxicity of these prodrugs was also examined in rabbit primary corneal epithelial cell culture (rPCEC) using 96-well based cell proliferation assay. In vivo ocular bioavailability of these compounds was also evaluated with a combination of topical well infusion and aqueous humor microdialysis techniques.. Among the amino acid ester prodrugs, SACV was most stable in aqueous humor. Enzymatic degradation of EACV was the least compared to all other prodrugs. Cellular toxicity of all the prodrugs was significantly less compared to trifluorothymidine (TFT) at 5mM. Absorption rate constants of all the compounds were found to be lower than the elimination rate constants. All the prodrugs showed similar terminal elimination rate constants (lambda(z)). SACV and VACV exhibited approximately two-fold increase in area under the curve (AUC) relative to ACV (p<0.05). Clast (concentration at the last time point) of SACV was observed to be 8+/-2.6microM in aqueous humor which is two and three times higher than VACV and ACV, respectively.. Amino acid ester prodrugs of ACV were absorbed through the cornea at varying rates (ka) thereby leading to varying extents (AUC). The amino acid ester prodrug, SACV owing to its enhanced stability, comparable AUC and high concentration at last time point (Clast) seems to be a promising candidate for the treatment of ocular HSV infections.

Topics: Acyclovir; Animals; Anterior Chamber; Antiviral Agents; Aqueous Humor; Area Under Curve; Biological Availability; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Stability; Epithelium, Corneal; Keratitis, Herpetic; Male; Ophthalmic Solutions; Prodrugs; Rabbits; Toxicity Tests

To report the clinical course of a rare case of bilateral herpetic linear endotheliitis.. A 70-year-old man presented with bilateral circumferential bullous edema with stromal edema progressing centrally in the left cornea and bilateral sensorineural hearing impairment simultaneously. Serum immunoglobulin G (IgG) and IgM antibodies against herpes simplex virus type 1 (HSV1) were tested for, and aqueous humor from both eyes was examined separately using polymerase chain reaction for the presence of HSV1 DNA.. Serum antibody titers against HSV1 were positive. In the polymerase chain reaction, the aqueous humor showed HSV1 DNA in both eyes. Forty milligrams of prednisolone was given per day and 200 mg of oral acyclovir was given 4 times daily, but corneal edema progressed. After penetrating keratoplasty surgery in the left eye, recurrent herpetic endotheliitis also seemed to occur.. HSV-1 may cause bilateral corneal linear endotheliitis and hearing impairment simultaneously. Linear endotheliitis should be regarded as a manifestation of HSV1 corneal infection. There is a poor prognosis, and severe corneal edema can result if aggressive treatment is not used.

Topics: Acyclovir; Aged; Antibodies, Viral; Aqueous Humor; Disease Progression; DNA, Viral; Drug Therapy, Combination; Endothelium, Corneal; Hearing Loss, Sensorineural; Herpesvirus 1, Human; Humans; Immunoglobulin G; Immunoglobulin M; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Polymerase Chain Reaction; Prednisolone

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 a case of recurrent herpes simplex virus (HSV) epithelial keratitis after intravitreal triamcinolone acetonide injection for the treatment of diabetic macular edema.. Case report.. We describe a case of a 59-year-old woman with a history of ocular HSV disease and severe proliferative diabetic retinopathy. She received an intravitreal injection of triamcinolone acetonide for macular edema in the right eye. One week later, she developed foreign body sensation, redness, and photophobia in the same eye. Slit-lamp examination revealed a corneal epithelial dendritic lesion. She was diagnosed with a recurrence of HSV epithelial keratitis and was treated with oral acyclovir 400 mg, 5 times a day, with good resolution of HSV signs and symptoms.. Intravitreal triamcinolone acetonide injection may result in reactivation of HSV keratitis.

Topics: Acyclovir; Antiviral Agents; Diabetic Retinopathy; Female; Glucocorticoids; Herpesvirus 1, Human; Humans; Injections; Keratitis, Herpetic; Macular Edema; Middle Aged; Recurrence; Triamcinolone Acetonide; Virus Activation; Vitreous Body

To determine the effect of routine use of prophylactic oral acyclovir after penetrating keratoplasty (PK) for herpes simplex virus (HSV) keratitis on recurrence, rejection, and graft failure rates.. Records from 70 consecutive patients who underwent PK for HSV keratitis at the W.K. Kellogg Eye Center between August 1, 1990, and December 31, 2000, were reviewed. Data collected included preoperative disease activity, duration, host vascularity, pre- and postoperative vision, and antiviral use. Particular attention was given to all episodes of HSV recurrence, graft rejection, and failure.. Fifty-six patients (80%) were treated with prophylactic oral acyclovir after surgery. This cohort experienced fewer episodes of rejection (P = 0.006) and better overall graft survival (P = 0.04) than those who were not treated with prophylactic oral antivirals. There was no statistically significant difference in recurrence-free survival between the 2 groups (P = 0.22). Cox regression analysis failed to identify any single variable as a statistically significant predictor of recurrence, rejection, or graft failure.. Prophylactic oral acyclovir use after PK for HSV keratitis is associated with decreased episodes of rejection and improved graft survival.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Child; Child, Preschool; Female; Graft Rejection; Graft Survival; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Middle Aged; Postoperative Complications; Virus Activation

We report a case of herpetic epithelial keratitis that developed after intravitreal triamcinolone acetonide injection.. An 81-year-old man with diabetes with severe nonproliferative diabetic retinopathy and diffuse macular edema in both eyes received bilateral intravitreal injections of 0.4 mg/0.1 mL of triamcinolone acetonide.. Eighteen days after the injections, the patient presented with redness, tearing, foreign body sensation, and decreased visual acuity in the right eye. The cornea showed dendriform ulcers that exhibited positive fluorescein staining. Diagnosis for herpes simplex epithelial keratitis was made, and topical acyclovir ointment therapy was initiated. The epithelial lesions healed after 7 days of therapy.. Herpes simplex epithelial keratitis can be a possible complication of intravitreal triamcinolone acetonide injection. The course and response to conventional therapy was no different from that of the classical course of the disease.

Topics: Acyclovir; Aged, 80 and over; Antiviral Agents; Epithelium, Corneal; Glucocorticoids; Herpesvirus 1, Human; Humans; Injections; Keratitis, Herpetic; Macular Edema; Male; Triamcinolone Acetonide; Virus Activation; Vitreous Body

A 21-year-old woman had crosslinking for keratoconus in the right eye; the left eye was scheduled for penetrating keratoplasty. Five days postoperatively, she presented with geographic epithelial keratitis and iritis. Analysis of tear samples by polymerase chain reaction confirmed the diagnosis. The patient was treated with oral steroids and acyclovir, with significant improvement. Two months postoperatively, the visual acuity was improved and there was no evidence of herpetic disease recurrence. Crosslinking can induce herpetic keratitis with iritis even in patients with no history of herpetic disease. Early diagnosis and proper treatment are essential for a favorable outcome.

Topics: Acyclovir; Adult; Collagen; DNA, Viral; Drug Therapy, Combination; Female; Glucocorticoids; Herpesvirus 1, Human; Humans; Iritis; Keratitis, Herpetic; Keratoconus; Photosensitizing Agents; Polymerase Chain Reaction; Riboflavin; Tears; Ultraviolet Rays; Virus Activation; Visual Acuity

Herpes simplex virus ocular infections have been recognized as a major cause of corneal blindness in the developed world. The major signs of a primary infection are limited to the lids, conjunctiva, and cornea. Presence of a conjunctival dendrite without corneal involvement has been reported. Although conjunctival ulceration has been associated with recurrent attacks, it has not been documented as a manifestation of primary herpetic infection. We report a case of primary herpetic infection with geographic conjunctival ulcer with multiple corneal dendrites.

Topics: Acyclovir; Adult; Anti-Infective Agents; Antiviral Agents; Conjunctivitis, Viral; Herpes Simplex; Humans; Immunocompetence; Keratitis, Dendritic; Keratitis, Herpetic; Male; Ofloxacin; Ointments; Visual Acuity

Topics: Acyclovir; Antiviral Agents; Female; Fluorophotometry; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Keratomileusis, Laser In Situ; Limbus Corneae; Middle Aged; Myopia; Surgical Flaps; Virus Activation; Visual Acuity

To report a case of Alport syndrome with recurrent herpes simplex virus (HSV) keratitis.. Case report and review of the literature.. A 29-year-old man with Alport syndrome suffered from 4 consecutive episodes of HSV keratitis within 2 years. A type IV collagen defect in basement membranes plays an important role in the pathogenesis of Alport syndrome. The relationship between HSV keratitis and Alport syndrome is discussed. After remission from HSV keratitis, the patient underwent bilateral phacoemulsification and posterior-chamber intraocular lens implantation for anterior lenticonus and an anterior polar cataract. After surgery, the uncorrected visual acuity was 20/20 in both eyes.. We assume that the underlying basement membrane defects in Alport syndrome may account for the recurrent episodes of HSV keratitis in this patient. In addition, phacoemulsification and posterior-chamber intraocular lens implantation, rather than correction of refractive errors, provide a safe and efficient therapeutic choice for the management of anterior lenticonus, with or without associated cataract in patients with Alport syndrome.

Topics: Acyclovir; Adult; Antiviral Agents; Humans; Keratitis, Herpetic; Lens Implantation, Intraocular; Male; Nephritis, Hereditary; Phacoemulsification; Recurrence

The purpose of the study is to investigate whether analysis of specific antibody synthesis can aid the diagnosis of herpes keratitis.. Aqueous humor was collected from 39 patients with presumed recurrent herpes keratitis, including 23 consulting for keratitis and 16 patients scheduled for penetrating keratoplasty. Local antibody production was ascertained by analysis of paired aqueous humor/serum samples, using a modified micro-ELISA technique.. Local production of antibodies was found in 32 patients (82%): anti-herpes simplex virus (HSV) antibodies in 26 (67%) and anti-varicella zoster virus (VZV) antibodies in 11 (28%). Twenty of 23 patients with active keratitis (87%), and 12 of 16 undergoing keratoplasty (75%), tested positive. Five patients had local production of both anti-HSV and anti-VZV antibodies, whereas seven patients tested negative. Local antibody production was significantly associated with intraocular inflammation (P<0.05), corneal neovascularisation (P<0.05), and positive response to anti-viral treatment (P<0.05). No complications were encountered in sampling aqueous humor.. Assessment of local anti-HSV and -VZV antibody production is a safe and reliable diagnostic procedure for recurrent herpes keratitis. It might be particularly helpful in patients presenting with intraocular inflammation and neovascularisation since it discriminates between herpes and non-herpes pathologies and may therefore be useful for preventive and therapeutic strategies.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Viral; Antiviral Agents; Aqueous Humor; Corneal Neovascularization; Enzyme-Linked Immunosorbent Assay; Female; Herpesvirus 1, Human; Herpesvirus 3, Human; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Middle Aged; Recurrence; Risk Factors; Uveitis

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 evaluate the risk of ocular surface herpetic eye disease (osHED) in allergic eye disease.. 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.. 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.. Patients treated for allergic eye disease have an increased risk of osHED.

Topics: Acyclovir; Adult; Anti-Allergic Agents; Antiviral Agents; Conjunctivitis, Allergic; Databases, Factual; Drug Prescriptions; Female; Health Maintenance Organizations; Humans; Keratitis, Herpetic; Male; Middle Aged; Risk

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

Herpes simplex virus (HSV) infection can be devastating in the neonate. The disease most commonly presents as 1 of 3 clinical manifestations: disseminated visceral infection (with and without central nervous system involvement), isolated meningoencephalitis, and infection limited to the skin, eyes, and/or mucous membranes (SEM). Exposure leading to neonatal infection typically occurs as peripartum vertical transmission, most typically by direct contact with urogenital lesions or infected genital secretions, or as an ascending infection exploiting disrupted chorioamniotic membranes. We present a novel case of a newborn girl who developed HSV-2 keratoconjunctivitis despite being delivered via an elective, uncomplicated, repeat cesarean over intact chorioamniotic membranes in the absence of active clinical maternal HSV infection and despite having a negative medical history of previous orolabial or genital herpetic infection.

Topics: Acyclovir; Antiviral Agents; Cesarean Section; Conjunctivitis; Female; Herpes Simplex; Herpesvirus 2, Human; Humans; Infant, Newborn; Keratitis, Herpetic

This study aimed to evaluate the efficacy of topical ophthalmic aciclovir applied five times daily as a treatment for feline herpesvirus type 1 (FHV-1) keratitis in a group of cats in a first-opinion practice setting. Cats with ocular signs indicative of FHV-1 or Chlamydophila species infection, predominantly conjunctivitis and keratitis, were tested for FHV-1 antigen using an immunofluorescent technique on air-dried conjunctival swabs. They were first treated with topical chlortetracycline with efficacy against Chlamydophila species and then, in cases positive for FHV-1, with topical aciclovir. The time to recovery was determined and illustrated using a Kaplan-Meier plot. Three cats were infected with Chlamydophila species and showed a median time to recovery of 14 days (95 per cent confidence interval [CI] 10 to 18 days), while 30 cats infected with FHV-1 showed a median time to recovery of 12 days (95 per cent CI 10 to 14 days). The drug dose at which 50 per cent plaque reduction (ED50) occurred in a standard plaque reduction assay was determined in an in vitro study. This showed a mean (SD) ED50 of aciclovir of 25 (3.5) mg/ml compared with 0.4 (0.05) mg/ml for trifluorothymidine, a drug known to be efficacious against FHV-1. The study shows that even though aciclovir is generally considered to lack efficacy against ocular FHV-1 infection, when used frequently it can have a beneficial effect in FHV-1 conjunctivitis and keratitis.

Topics: Acyclovir; Administration, Topical; Animals; Antiviral Agents; Cat Diseases; Cats; Female; Keratitis, Herpetic; Male; Treatment Outcome

To report 2 cases of herpes simplex keratitis misdiagnosed as rheumatoid arthritis (RA)-related peripheral ulcerative keratitis (PUK), where isolation of the herpes simplex virus (HSV) led to a complete modification in management.. This is a case report.. Two patients with RA presented with painful red right eyes. Ocular examination in both revealed an ulcer involving the peripheral cornea. The adjacent conjunctiva was infected, and the underlying sclera appeared inflamed. A diagnosis of corneal PUK secondary to RA was therefore made. The first patient had corneal scrapes taken for routine microbiological examination, which included polymerase chain reaction (PCR) for HSV. In the second patient, despite systemic immunosuppressive therapy, the ulcer progressed to involve deeper stroma and more central cornea. The conjunctiva adjacent to the ulcer was resected, and healthy conjunctival tissue was mobilized to cover the peripheral corneal ulcer. Resected conjunctival and corneal tissue was histopathologically assessed. In the first patient, PCR for HSV yielded a positive result. This prompted treatment with immediate systemic and topical acyclovir. The ulcer responded well to treatment. In the second patient, histopathological assessment and electron microscopy identified HSV. Treatment with topical trifluorothymidine and steroids was started, and a good recovery was made.. Treatment of PUK is with systemic immunosuppressive therapy, and such therapies have serious side effects. PUK may have an occult cause in RA, and a search for a secondary agent may be beneficial. In particular, occult HSV infection must be ruled out before commencing immunosuppressive therapy.

Topics: Acyclovir; Aged; Antiviral Agents; Arthritis, Rheumatoid; Cornea; Corneal Ulcer; Diagnosis, Differential; Diagnostic Errors; Female; Follow-Up Studies; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Male; Microscopy, Electron, Transmission; Middle Aged; RNA, Viral; Trifluridine

To study the incidence of herpetic eye disease (HED) of the ocular surface in diabetics.. Observational historical cohort study.. A district of the largest health maintenance organization in Israel (the Central District of Clalit Health Services).. 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.. 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.. Incidence of ocular surface HED events in diabetics compared with nondiabetics adjusted for age and gender.. 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.. 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.

Topics: Acyclovir; Aged; Aged, 80 and over; Antiviral Agents; Diabetes Mellitus; Drug Prescriptions; Drug Utilization; Female; Health Maintenance Organizations; Herpes Zoster Ophthalmicus; Humans; Incidence; Israel; Keratitis, Herpetic; Male; Middle Aged; Prevalence; Registries

To evaluate the efficacy of multilayer amniotic membrane transplantation (AMT) combined with antivirus and corticosteroid drug to treat necrotizing herpes simplex stromal keratitis.. Thirteen patients (13 eyes) of necrotizing stromal keratitis were referred to Shandong Eye Institute and Qingdao Eye Hospital between January 2003 and April 2004. The course of disease was 3 - 22 months (mean 15 months). Corneal inflammation persisted and corneal ulcer progressed despite topical and systemic antiviral treatment for over 1 weeks. Multilayer amniotic membrane transplantation was performed after excluding of bacterial and fungal infection by microbiologic studies including smears and cultures of necrotic corneal tissue and confocal microscope. Topical and systemic antiviral medications were given with adjuvant corticosteroid eyedrops postoperatively. We investigated the healing of corneal ulcer and improvement of stromal edema with slit lamp biomicroscope, the integrity of corneal defect with fluorescein staining, the migration of healthy corneal epithelial cells and transformation of amniotic membrane with confocal microscopy. All patients were followed up for 3 - 13 months (mean 10 months).. Corneal ulcer healed within 1 - 3 weeks postoperatively with negative fluorescein staining. Corneal stromal edema faded away within 1 month. Superficial amniotic membrane patches dissolved or shed on postoperative day 7 - 10, while the deeper grafts were adhered into the ulcer and fused with the surrounding fibroblasts. One of these grafts remained in situ more than 3 months. Confocal microscope examination indicated flat epithelial progenitor cells on the surface of residual amniotic membrane. Corneal transparence was achieved in 7 eyes, macula in 4 eyes and leucoma in 2 eyes 3 months after the operation. No recurrence of necrotizing stromal keratitis was occurred in 13 patients during the follow-up period.. Multilayer AMT combined with antivirus and corticosteroid treatment is an effective method to treat necrotizing herpes simplex stromal keratitis.

Topics: Acyclovir; Adult; Amnion; Antiviral Agents; Corneal Ulcer; Female; Follow-Up Studies; Glucocorticoids; Humans; Keratitis, Herpetic; Male; Middle Aged; Treatment Outcome

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

A 40-year-old woman underwent bilateral Laser In Situ Keratomileusis (LASIK) for the correction of myopia and astigmatism. The day after, four dendritic ulcers appeared in her left eye. She was treated with topical antiviral agents until complete recovery. She had a history of recurrent labial herpetic infection.. Reactivation of herpes simplex virus type 1 can occur, even without any previous history of corneal infection. Although this does not contraindicate surgery, all patients with a history of herpetic infection should be made aware of the complications related to this technique.

Topics: Acyclovir; Adrenal Cortex Hormones; Adult; Antiviral Agents; Astigmatism; Female; Herpes Labialis; Humans; Keratitis, Herpetic; Keratomileusis, Laser In Situ; Myopia; Postoperative Complications

We quantitated herpes simplex virus (HSV) DNA in tear film obtained from 2 patients who developed herpetic epithelial keratitis (HEK) during treatment with latanoprost and a beta-blocker.. The patient in case 1 is a 77-year-old woman with bilateral open-angle glaucoma who had been treated with latanoprost and timolol for 11 months. She developed HEK in the right eye followed by HEK in the left eye 1 month later. Both eyes healed with administration of acyclovir. Ten months later, HEK recurred in the right eye. The patient in case 2 is a 45-year-old man with bilateral normal tension glaucoma who had been treated with latanoprost for 2 years. After concurrent treatment with nipradilol for 5 months, typical dendritic keratitis developed in the left eye. In both cases, a real-time PCR assay was used to quantify HSV-DNA in the tear film.. In the patient in case 1, 71 copies of the HSV genome were detected in the tear film obtained from the right eye at the time of presentation with HEK. After 1 week of treatment with topical acyclovir ointment, the corneal epithelial defects healed and the number of HSV genome copies present in the tear film fell below the sensitivity limit of the assay. In the patient in case 2, 7.0 x 10 copies of the HSV genome were detected in the tear film from the left eye. After 3 days of topical acyclovir ointment, it healed and the HSV genome in the tear film became undetectable.. Herpetic keratitis may occur during treatment with latanoprost and beta-blockers. The amount of HSV DNA detected in the tear film paralleled with the activity of the corneal lesion.

Topics: Acyclovir; Aged; Antihypertensive Agents; Antiviral Agents; DNA, Viral; Epithelium, Corneal; Female; Gene Dosage; Genome, Viral; Glaucoma, Open-Angle; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Male; Middle Aged; Polymerase Chain Reaction; Virus Activation; Virus Latency; Virus Replication

To report recurrent herpetic keratouveitis following YAG laser peripheral iridotomy.. Case report.. A 64-year-old woman with a history of dendritic keratitis underwent Nd:YAG laser peripheral iridotomy and developed geographic epithelial keratitis with stromal keratouveitis. Culture of a corneal swab grew herpes simplex virus type I. Keratouveitis subsided with acyclovir and corticosteroid therapy.. Recurrent herpetic keratouveitis may be induced by YAG laser iridotomy.

Topics: Acyclovir; Antiviral Agents; Betamethasone; Cornea; Drug Therapy, Combination; Female; Glucocorticoids; Herpesvirus 1, Human; Humans; Iridectomy; Keratitis, Herpetic; Laser Therapy; Middle Aged; Recurrence; Uveitis, Anterior

A 38-year-old man was admitted to the Emergency Department suffering from an exacerbation of atopic dermatitis, fever and a burning sensation in the eyes. He was first treated with systemic corticosteroids. A subsequent dermatological and ophthalmological examination established the diagnosis of Kaposi-Juliusberg disease or eczema herpeticum with bilateral herpetic keratitis. Eczema herpeticum is an uncommon herpes simplex virus infection that occurs in patients with atopic dermatitis. Because it is a possible life-threatening condition, this disease must be recognized by all emergency physicians. The association with herpetic keratitis is not frequent but is a major ophthalmological problem. Treatment consists of the administration of high-dose intravenous acyclovir and acyclovir ophthalmic ointment.

Topics: Acyclovir; Adrenal Cortex Hormones; Adult; Antibodies, Viral; Dermatitis, Atopic; Emergencies; Emergency Medical Services; Fever; Humans; Kaposi Varicelliform Eruption; Keratitis, Herpetic; Male; Simplexvirus; Treatment Outcome

The purpose of this study was to examine the importance of considering the differential diagnosis for patients with sectorial keratitis and uveitis by case summary and literature review.. A retrospective review of patients with sectorial keratitis and uveitis seen at the Ocular Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary and a summary of the diagnoses of cases with similar ocular findings that have been reported in the literature.. Data on six patients with sectorial keratitis and uveitis were reviewed. Four patients were female and two were male, ages 21-50 years. All were eventually diagnosed with herpes simplex viral stromal sectorial keratitis. The corneal infiltrates were most common in the superior corneal quadrants, located in the posterior corneal layers. Anterior non-granulomatous uveitis was present in all cases. One case had bilateral ocular involvement. Five of the six patients responded to topical steroids and antiviral treatment. Immunomodulation with methotrexate, cyclosporine, and systemic prednisone was required in one patient. Glaucoma was a complication in six of the seven eyes. Five patients developed corneal scarring, localized in the anterior and mid-stroma.. The differential diagnosis of sectorial keratitis and uveitis is limited. The entities included in the differential are diverse; some of them threaten not only vision but also life. It is important for the ophthalmologist to be familiar with these entities, in order to pursue pertinent diagnostic investigations and arrive at an accurate diagnosis and institute appropriate management.

Topics: Acyclovir; Administration, Topical; Adult; Anti-Inflammatory Agents; Antiviral Agents; Corneal Stroma; Diagnosis, Differential; Female; Glucocorticoids; Humans; Keratitis, Herpetic; Male; Middle Aged; Prednisolone; Retrospective Studies; Uveitis, Anterior; Visual Acuity

To review the clinical characteristics and visual outcomes of patients with bilateral herpetic keratitis.. Retrospective, noncomparative, observational case series.. A retrospective review of medical records of 544 patients with herpes simplex virus (HSV) eye disease treated between January 1996 and September 2001 was performed at the Department of Ophthalmology, University of Minnesota. Seven patients (1.3%) with bilateral herpetic keratoconjunctivitis were identified.. In these seven patients, the age at the initial onset of corneal disease ranged from 7 weeks to 46 years, with a median of 18 years and a mean of 19.3 years. Five patients had systemic atopy, and two patients had severe ocular rosacea. Systemic immune disorders were noted in two patients. Recurrent blepharoconjunctivitis was noted in 8 eyes (57%), epithelial keratitis in 12 eyes (85.7%), stromal keratitis in 9 eyes (64.3%), necrotizing stromal keratitis in 5 eyes (35.7%), and progressive endotheliitis in 2 eyes (14.2%). Corneal complications included opacification, neovascularization, and corneal thinning or perforation. Penetrating keratoplasty was performed in 1 eye, in which endophthalmitis subsequently developed and which required enucleation. Four patients with continued use of oral antiviral prophylaxis (acyclovir 400 mg twice daily) since September 1999 showed significant decreases in recurrence. The average remission in these four patients was 1.7 years. The visual acuity at the last follow-up was 20/40 or worse in 6 eyes (42.8%).. In contrast to unilateral HSV keratitis, our patients with bilateral herpetic corneal infections had underlying atopy or immune deviations and evinced more protracted clinical courses. Long-term prophylactic antiviral treatment has reduced the incidence of recurrence in this group of patients.

Topics: Acyclovir; Adolescent; Adult; Age of Onset; Antiviral Agents; Child, Preschool; Corneal Neovascularization; Corneal Opacity; Corneal Stroma; Epithelium, Corneal; Female; Humans; Infant; Keratitis, Herpetic; Keratoconjunctivitis; Keratoplasty, Penetrating; Male; Middle Aged; Recurrence; Retrospective Studies; Visual Acuity

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

Topics: Acyclovir; Administration, Topical; Antiviral Agents; Eye Infections, Viral; Female; Humans; Keratitis, Herpetic; Middle Aged; Phototherapy; Virus Activation

In corneal recipients with herpes infection, acyclovir given for 1 year postoperatively prevents viral reactivation and improves graft outcome. The indication for prophylactic antiviral therapy relies on the preoperative diagnosis of herpes. However, many patients present with corneal scars featuring sequelae of herpes without a proven history of herpes. Here we report the results of a prospective study of anti-herpes simplex virus (anti-HSV) and varicella zoster virus (VZV) antibody testing in the aqueous humor at the time of corneal transplantation to refine the indication of the antiviral treatment.. The study involved 33 keratitis corneal graft recipients, 21 of whom had documented herpes keratitis. A control group was made with 11 cataract patients. An anterior chamber puncture was performed just before surgery. The micro-ELISA test was done on both aqueous humor and serum, and local anti-HSV or VZV antibody synthesis was acknowledged if the ratio of antibody concentrations was above 4.. Local antibody synthesis to HSV was detected in 22 cases, to VZV in 9 cases, to both HSV and VZV in 6 cases, and no synthesis in 8 cases. The sensitivity of the test was 65% in patients with a documented history of herpes (14 cases out of 21). Among non-herpetic patients, the test was positive in 9 patients, who thus benefited from postoperative antiviral therapy. No viral reactivation was encountered after a minimum follow-up of 1 year.. Antibody testing in the aqueous humor at the time of keratoplasty is a convenient, inexpensive diagnostic tool in corneal recipients. It provides useful information before prescribing a long and expensive postoperative antiviral therapy.

Topics: Acyclovir; Adult; Aged; Aged, 80 and over; Antibodies, Viral; Antiviral Agents; Aqueous Humor; Corneal Transplantation; Enzyme-Linked Immunosorbent Assay; Female; Herpesvirus 3, Human; Humans; Keratitis, Herpetic; Male; Middle Aged; Postoperative Complications; Simplexvirus; Virus Activation

To evaluate the effectiveness of more than 12 months of oral acyclovir therapy in reducing recurrences of ocular herpes simplex virus.. We retrospectively compared ocular herpes simplex virus recurrence in 2 groups of patients. In group 1, patients used oral acyclovir for at least 12 months and then discontinued the treatment. In group 2, patients received the treatment for at least 18 months. We compared recurrences when both groups were using acyclovir (period 1) and when only group 2 was receiving the drug (period 2). Statistical analysis was performed with the t test, chi2 test, and Kaplan-Meier method.. Group 1 had 18 patients and a mean +/- SD follow-up of 45.2 +/- 22.2 months. Group 2 had 22 patients and a mean +/- SD follow-up of 42.4 +/- 30.2 months. Six patients (33%) in group 1 and 4 patients (18%) in group 2 had recurrence in period 1 (P =.3). In period 2, 14 patients (78%) in group 1 and 8 patients (36%) in group 2 had recurrence (P =.01). Mean +/- SD recurrence-free survival in period 2 was 15.3 +/- 5.5 months in group 1 and 37.3 +/- 6.3 months in group 2 (P =.001).. Long-term oral acyclovir use seems to remain effective in decreasing the number of ocular herpes simplex virus recurrences beyond 12 months.

Topics: Acyclovir; Administration, Oral; Adult; Antiviral Agents; Blepharitis; Conjunctivitis, Viral; Disease-Free Survival; Female; Follow-Up Studies; Herpes Simplex; Humans; Iritis; Keratitis, Herpetic; Male; Middle Aged; Retrospective Studies; Secondary Prevention

Herpetic keratitis is manifested in various corneal disorders, for example, dendritic keratitis, persistent epithelial defect, disciform keratitis, and endotheliitis. In this paper, we report on the quantity of herpes simplex virus (HSV) genome in tears from patients with various types of herpetic keratitis in an attempt to understand the role of HSV in these conditions.. We collected tear samples from both eyes of 56 consecutive patients with herpetic keratitis who visited Kinki University Hospital between June 2000 and May 2002. All patients had unilateral herpetic keratitis: epithelial keratitis in 27 eyes; persistent epithelial defect in 6; active disciform stromal keratitis in 14; silent stromal keratitis in 6; and endotheliitis in 3. We measured levels of HSV genome in these tear samples using a real-time polymerase chain reaction (PCR) method.. In epithelial keratitis, HSV DNA was detected in all 27 samples from affected eyes (6.4 +/- 4.4 x 10(5) copies/sample). In persistent epithelial defect, HSV DNA was detected in all 6 samples from affected eyes (8.5 +/- 3.3 x 10(4) copies/sample). In active disciform stromal keratitis, HSV DNA was detected in 8 of the 14 affected eyes (1.4 +/- 1.1 x 10(5) copies/sample including zero values in negative samples). HSV DNA was not detected in samples from unaffected eyes or eyes affected by silent stromal keratitis or endotheliitis.. Real-time PCR is a useful method for quantifying HSV DNA in tear samples from patients with herpetic keratitis. Using this method, we demonstrate that HSV reproduction occurs in persistent epithelial defect and disciform stromal keratitis.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Computer Systems; DNA, Viral; Epithelium, Corneal; Female; Gene Dosage; Genome, Viral; Humans; Keratitis, Herpetic; Male; Middle Aged; Polymerase Chain Reaction; Simplexvirus; Virus Replication; Wound Healing

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

Herpetic keratitis is a common sequel of a corneal infection with herpes simplex virus (HSV)-1. Recrudescent herpetic keratitis (RHK) may result in irreversible damage to the cornea. Recurrences may be caused by reactivation of endogenous HSV-1 or reinfection with exogenous HSV-1. The objective of this study was to determine the incidence and risk factors involved of HSV-1 superinfection in patients with RHK.. From 30 patients with RHK, sequential corneal HSV-1 isolates were genotyped by PCR amplification of the hypervariable regions located within the HSV-1 genes US1, US10/11, and US12. The clinical data from the patients obtained retrospectively were: ophthalmologic history, clinical picture during recurrences, number and time points of penetrating keratoplasty (PKP), and steroid or acyclovir treatment.. Whereas the sequential corneal HSV-1 isolates of 19 (63%) of 30 patients had the same genotype (designated as group 1), the sequential isolates of 11 patients (37%) were genetically different (designated as group 2). Among the clinical data analyzed, only the time point of PKP was significantly different between the patient groups. Although no patients in group 1 had undergone transplantation between samplings, 4 of 11 patients in group 2 underwent PKP during the inter-recurrence period in the same eye from which the corneal HSV-1 isolates were obtained.. The data demonstrate that RHK is frequently associated with corneal reinfection with a different HSV-1 strain and suggest that PKP is a risk factor for corneal HSV-1 superinfection.

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Cornea; DNA, Viral; Female; Genotype; Herpesvirus 1, Human; Humans; Incidence; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Middle Aged; Polymerase Chain Reaction; Recurrence; Risk Factors; Superinfection; Virus Activation

To report a case of herpes simplex virus reactivation after starting bimatoprost treatment for glaucoma.. Interventional case report.. A 66-year-old woman had a herpes simplex keratouveitis reactivation that occurred within 1 month after starting bimatoprost. The herpes simplex had been inactive for more than 10 years.. Bimatoprost and prednisolone acetate 0.12% were discontinued; oral acyclovir, ofloxacin, and betaxolol 0.25% were initiated. Two weeks later, prednisolone acetate 1% was added. The reactivation resolved, and 1 month later, the best corrected visual acuity improved to 20/40.. Caution should be used in prescribing bimatoprost for patients with a history of herpes simplex virus keratitis.

Topics: Acyclovir; Aged; Amides; Anti-Infective Agents; Anti-Inflammatory Agents; Antihypertensive Agents; Antiviral Agents; Betaxolol; Bimatoprost; Cloprostenol; Drug Therapy, Combination; Female; Glaucoma; Herpesvirus 1, Human; Humans; Intraocular Pressure; Keratitis, Herpetic; Lipids; Ofloxacin; Prednisolone; Virus Activation; Visual Acuity

A twenty-eight year old woman with necrotitizing retinitis and herpes simplex virus type 1 isolated in aqueous humor with polymerase chain reaction (PCR). An Acyclovir and corticosteroid therapy was started with unsuccessful response, Foscarnet was added getting quiescence of lesions.. Acute Retinal Necrosis Syndrome (ARNS), induced by a virus of the herpes family, could develop in immunocompetent people. A characteristic clinical case with uveitis and vitritis, white retinitis areas and occlusive vasculitis is reported. Antiviral therapy with acyclovir and antiinflammatory treatment must be established quickly. Foscarnet can effectively treat ARNS in inmunocompetent patients. In spite of therapy, this is a potentially blinding retinal disease.

Topics: Acute Disease; Acyclovir; Adult; Antiviral Agents; Diagnosis, Differential; Drug Therapy, Combination; Female; Foscarnet; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Necrosis; Polymerase Chain Reaction; Retina; Retinal Diseases; Time Factors

To report a case of atypical herpes simplex keratitis initially diagnosed as bacterial keratitis, in a contact lens wearer.. Case report of an 18-year-old woman using contact lenses who presented with pain, redness and gradual decrease in vision in the right eye. Examination revealed a paracentral large stromal infiltrate with a central 2-mm perforation. Corneal and conjunctival scrapings were collected for microbiological investigations. Corneal tissue was obtained following penetrating keratoplasty. Corneal scraping revealed no microorganisms. Giemsa stained smear showed multinucleated giant cells. Conjunctival, corneal scrapings and tissue were positive for herpes simplex virus - 1 (HSV) antigen. Corneal tissue was positive for HSV DNA by PCR.. Atypical HSV keratitis can occur in contact lens wearers. A simple investigation like Giemsa stain may offer a clue to the diagnosis.

Topics: Acyclovir; Adolescent; Antigens, Viral; Antiviral Agents; Azure Stains; Conjunctiva; Contact Lenses, Hydrophilic; Cornea; Corneal Ulcer; DNA, Viral; Female; Giant Cells; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating; Polymerase Chain Reaction; Rupture, Spontaneous

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 examine morphological changes occurring in recurrent herpes simplex virus (HSV) epithelial keratitis after the application of topical acyclovir ointment 3%.. 7 patients examined with the slit lamp and photographed by non-contact in vivo photomicrography.. Within one day of treatment the lesions lost their typical herpetic features, and after about 2-3 days the morphology seemed to reflect only the sequelae: unhealthy epithelium and abnormal cells located at the level of the basement membrane. Two patients showed epitheliopathy compatible with the side-effects of the treatment.. The rapid loss of typical HSV features after drug application reflects a successful arrest of the virus replication, freeing the epithelial healing forces. At what point of time infectious virus is eradicated and the treatment can be safely stopped cannot be determined clinically. Healing in the sense of restitution ad integrum is a slow process showing individual variations. Abnormal intra-/subepithelial cells are last to disappear.

Topics: Acyclovir; Administration, Topical; Adult; Aged; Antiviral Agents; Epithelium, Corneal; Female; Humans; Keratitis, Herpetic; Male; Middle Aged; Ointments; Recurrence; Wound Healing

To report an unusual case of herpetic bullous keratitis misdiagnosed as a case of pseudophakic bullous keratopathy with secondary glaucoma.. A retrospective analysis of the case record of a 60-year-old man who had earlier undergone bilateral cataract surgery, was done. He presented with a complaint of decrease in vision in the right eye of 20 days duration. On examination, cornea showed epithelial bullae all over the surface with stromal and epithelial edema. Intraocular pressure was 30 mm of Hg in RE. He was treated with anti-glaucoma medications. Two dendritic lesions were seen in the cornea during a subsequent visit four days later. Virological investigations confirmed a diagnosis of Herpes simplex keratitis. He was treated with topical acyclovir.. This case highlights the fact that herpes simplex keratitis can present initially as a more diffuse corneal stromal and epithelial edema with epithelial bullae mimicking bullous keratopathy. Herpetic bullous keratitis, although unusual, should be considered in the differential diagnosis under such circumstances.

Topics: Acyclovir; Antiviral Agents; Cornea; Corneal Diseases; Corneal Edema; Corneal Stroma; Diagnostic Errors; Giant Cells; Glaucoma; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Male; Middle Aged; Pseudophakia; Retrospective Studies

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

To describe a unique case of retrocorneal membrane with large Descemet's detachment.. Case report of a 65-year-old man reported intermittent cloudy vision in his left eye. The patient underwent serial ocular examinations and slit-lamp photography over 6 weeks.. The patient had an inflammatory-appearing membrane that covered 60% of the posterior cornea, with a subtotal Descemet's detachment. Vision was stable at 20/20, and the cornea remained clear. The patient was empirically treated with topical neomycin/polymyxin/dexamethasone, sodium chloride, and oral acyclovir, and his symptoms improved; however, the retrocorneal membrane persisted.. This unusual clinical finding may represent reduplicated Descemet's membrane with partial Descemet's detachment secondary to occult deep herpes simplex keratitis. Other possibilities include spontaneous or traumatic Descemet's tear and detachment.

Topics: Acyclovir; Aged; Corneal Diseases; Descemet Membrane; Dexamethasone; Drug Therapy, Combination; Humans; Keratitis, Herpetic; Male; Neomycin; Polymyxins

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Acyclovir; Adjuvants, Immunologic; Antiviral Agents; Humans; Keratitis, Herpetic

Topics: Acyclovir; Anti-Infective Agents; Antiviral Agents; Ciprofloxacin; Corneal Stroma; Drug Therapy, Combination; Glucocorticoids; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Male; Middle Aged; Ofloxacin; Prednisolone

To evaluate the efficacy of penetrating keratoplasty (PKP) in treating active herpes simplex stromal keratitis.. PKP was performed on 59 patients with quiescent and 66 patients with active herpes simplex stromal keratitis. The results and complications of herpes simplex keratitis (HSK) in the quiescent group were compared with that of the HSK active group.. No clinical or statistical significant differences in visual outcome, graft transparent rate and recurrent rate of HSK after operation were identified between the active and quiescent groups.. When the pre- and intra-operative managements of PKP are properly performed on active HSK, the same results as that performed on quiescent HSK can be obtained, and it can reduce the complications and shorten the duration of the disease.

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Corneal Stroma; Female; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Middle Aged; Treatment Outcome; Visual Acuity

Topics: 2-Aminopurine; Acyclovir; Adult; Antiviral Agents; Dermatitis, Allergic Contact; Drug Hypersensitivity; Famciclovir; Female; Herpes Labialis; Humans; Keratitis, Herpetic

To evaluate the use of oral acyclovir in pediatric patients with herpes simplex virus (HSV) keratitis.. Retrospective noncomparative case series.. 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.. 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.. 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.. 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.

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Child, Preschool; Cornea; Female; Herpesvirus 1, Human; Humans; Infant; Keratitis, Herpetic; Male; Recurrence; Retrospective Studies; Treatment Outcome; Visual Acuity

Seven herpes simplex type-1 (HSV-1) isolates from herpes simplex keratitis (HSK) cases clinically resistant to acyclovir (ACV) were analyzed for the mechanism of ACV resistance in them. The purpose of the study was to focus the attention of ophthalmologists on the frequency of occurrence of ACV resistance in HSK and to characterize such a phenomenon. We employed in-vitro plaque reduction assay, thymidine kinase assay, polymerase chain reaction, single-strand confirmation polymorphism analysis and sequencing to detect any mutation(s) in thymidine kinase gene in this analytical study. Four of the seven HSV-1 isolates proved ACV resistant by plaque reduction assay and three of them showed reduced thymidine kinase activity. Altered mobility pattern indicative of mutation within 335 base pair PCR product bracketing the suggested homopolymer mutational hotspot (7 Guanosine) was detected in 2 of these 3 isolates. DNA sequencing showed a deletion at nucleotide position 336 from the tk gene transcription start in both the isolates. This mutation has generated the first TGA stop codon 27 nucleotides downstream in the tk open reading frame. Our study also suggests the need of clinical/molecular surveillance of ACV resistance in HSV types in a given geographic location for better management of HSV infections.

Topics: Acyclovir; Antiviral Agents; Base Sequence; Developing Countries; Drug Resistance, Microbial; Herpesvirus 1, Human; Humans; India; Keratitis, Herpetic; Microbial Sensitivity Tests; Molecular Sequence Data; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Sequence Analysis, DNA; Thymidine Kinase; Viral Plaque Assay

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

A case of an 8-year-old girl with immune ring is presented. Immune reaction in the cornea after the second assault of the same antigen, probably HSV, produced immuno-complexes deposited in the cornea as a ring-shaped lattice. In our case the girl was admitted to hospital because of blurred vision, corneal deposits in the shape of a ring with keratomycosis suspicion in the eye. 3 months before she suffered from a minor injury to this eye (corneal abrasion with a finger while playing). Immune ring was recognised. Following Missoten's recommendations the girl was treated mainly with topical steroids (ophticor) every 15 minutes on the first day until the afternoon, subsequently with dexamethasone 4 times a day--for 10 days with decreased frequency continuously in an amount stopping the immune reaction. After 3 days the regression of deposits and the visual acuity improved. I believe this disease is not rare but rarely recognised and my aim is to approach this problem more thoroughly.

Topics: Acyclovir; Antiviral Agents; Child; Cornea; Female; Humans; Keratitis, Herpetic

To evaluate the contribution of molecular methods for the diagnosis of an acyclovir-resistant HSV-1 bilateral keratitis in an AIDS patient and to report a new point mutation in the nucleotide sequence of the thymidine kinase (tk) gene involved.. A 31 year old HIV-positive female presented with severe, active, bilateral and sight-threatening keratitis of 6 months duration, which was treated unsuccessfully with acyclovir. After corneal biopsy, samples were analysed by standard virological procedures, in situ hybridization, and PCR. The tk gene was cloned and subsequently sequenced.. Conventional virological methods remained inconclusive. However, in situ hybridization and PCR rapidly confirmed the diagnosis of HSV-1 keratitis. The tk gene sequence revealed the presence of five variations previously described in two reference strains, but also a new point mutation at nucleotide position 431 which leads to an amino-acid change at position 144 that supported the hypothesis of a putatively altered functional form of the enzyme. Intravenous foscarnet treatment in an induction regimen was effective and cicatrization occurred within 3 weeks.. PCR and in situ hybridization are effective and powerful techniques when other virological procedures are non-contributive, particularly in immunocompromised patients previously treated with antiviral drugs. The new point mutation identified in the tk gene may be associated with resistance to acyclovir.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Amino Acid Sequence; Antiviral Agents; Base Sequence; Drug Resistance, Microbial; Female; Foscarnet; Herpesvirus 1, Human; Humans; In Situ Hybridization; Keratitis, Herpetic; Molecular Sequence Data; Point Mutation; Polymerase Chain Reaction; Thymidine Kinase; Treatment Outcome

To describe presumed activation of herpetic keratouveitis after argon laser peripheral iridotomy.. Case report.. A 68-year-old man developed chronic, unilateral, anterior uveitis associated with decreased corneal sensation, focal keratitis, and increased intraocular pressure after argon laser peripheral iridotomy. Treatment with oral acyclovir and discontinuation of topical latanoprost resulted in prompt and continued control of both the intraocular inflammation and pressure.. Herpetic keratouveitis may occur after argon laser iridotomy, and it should be considered when postoperative inflammation persists despite appropriate use of topical corticosteroids, particularly in patients with a history of herpetic eye disease.

Topics: Acyclovir; Aged; Antiviral Agents; Chronic Disease; Glaucoma; Herpesvirus 1, Human; Humans; Intraocular Pressure; Iris; Keratitis, Herpetic; Laser Therapy; Latanoprost; Male; Prostaglandins F, Synthetic; Uveitis, Anterior; Virus Activation

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

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Corneal Stroma; Epithelium, Corneal; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Randomized Controlled Trials as Topic; Secondary Prevention; Virus Activation

To report an eye with corneal endotheliitis and increased intraocular pressure in which the trabeculum demonstrated immunoreactivity for herpes simplex virus.. Case report. A 62-year-old man presented with increased intraocular pressure, keratic precipitates, and corneal stromal edema in his left eye. The tissue excised during trabeculectomy was immunohistochemically examined for herpetic viruses.. Immunoreactivity for herpes simplex virus was identified in the trabeculum.. Herpes simplex virus may cause trabeculitis and increased intraocular pressure in patients with corneal endotheliitis.

Topics: Acyclovir; Antibodies, Viral; Antigens, Viral; Antiviral Agents; Corneal Edema; Endothelium, Corneal; Herpesvirus 1, Human; Humans; Immunoenzyme Techniques; Intraocular Pressure; Keratitis, Herpetic; Male; Middle Aged; Trabecular Meshwork; Trabeculectomy; Visual Acuity

Topics: Acyclovir; Antiviral Agents; Drug Utilization; Herpes Labialis; Humans; Keratitis, Herpetic

To investigate cytokine mRNA expression and the influence of acyclovir and tetrandrine on that expression in the corneas of mice infected with herpes simplex virus type 1 (HSV-1).. Male BALB/c mice were infected in the right cornea with HSV-1. The corneas were harvested from control normal mice and from untreated, acyclovir-treated and tetrandrine-treated mice 14 days after infection. The infected corneas of each group were divided into inflamed and uninflamed depending on clinical observation. After total mRNA extraction from the corneas, gene expression of interleukin 1 beta (IL-1 beta), IL-6, tumour necrosis factor alpha (TNF-alpha) and transforming growth factor (beta (TGF-beta) was analysed by reverse transcription polymerase chain reaction.. No mRNA expression of the cytokines was found in normal corneas. IL-1 beta and TNF-alpha mRNA was seen in inflamed corneas, while mRNA expression of IL-6 and relatively weaker TGF-beta mRNA expression were found both in inflamed corneas and in infected but uninflamed corneas treated with acyclovir. TNF-alpha mRNA was present in the uninflamed corneas of tetrandrine-treated mice. No influence of either agent was found on TGF-beta gene expression.. The results suggest that local IL-1 beta and TNF-alpha gene expression is required for corneal inflammation, whereas IL-6 and TGF-beta may exert antiviral and inflammation regulatory activities in HSV corneal infection.

Topics: Acyclovir; Alkaloids; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antiviral Agents; Benzylisoquinolines; Cornea; Cytokines; Electrophoresis, Agar Gel; Gene Expression; Keratitis, Herpetic; Male; Mice; Mice, Inbred BALB C; Polymerase Chain Reaction; RNA, Messenger

To compare trifluridine eyedrops, cidofovir eyedrops, and penciclovir ophthalmic ointment for the treatment of herpes simplex virus type 1 keratitis.. New Zealand white rabbits were infected with the McKrae strain of herpes simplex virus type 1. Three days after viral inoculation, the rabbits were randomly assigned to treatment with 1% trifluridine, 0.2% cidofovir, 3% penciclovir ointment, or phosphate-buffered saline (for control) on various schedules. The severity of keratitis was graded in a masked manner.. Treatment with any of the antiviral drugs resulted in significantly less severe keratitis than treatment with phosphate-buffered saline. There was no statistically significant difference between eyes given trifluridine 2, 4, or 7 times a day and eyes given cidofovir 2 times a day (P=.06, P=.43, and P=.19, respectively, using the F test of the analysis of variance). Cidofovir given twice a day was significantly more effective than penciclovir given either 2 or 4 times a day (P<.001 and P=.002, respectively). Even with once-a-day dosage, all 3 drugs were significantly more effective than phosphate-buffered saline (P<.001 for all). There was no significant difference between once-a-day trifluridine and cidofovir treatments (P=.17). Trifluridine administered 5 times a day was as effective as 1% cidofovir. A similar degree of punctate keratitis was seen after 4 to 5 days in eyes treated with trifluridine at the highest frequency, 1% cidofovir, or penciclovir ointment.. Trifluridine treatment was highly effective in this rabbit model, even when given only once a day. Treatment with cidofovir was as effective as that with trifluridine.. Cidofovir and penciclovir treatments may prove to be effective against epithelial keratitis. Clinical trials of trifluridine, cidofovir, and penciclovir with lower treatment frequencies appear to be warranted.

Topics: Acyclovir; Animals; Antiviral Agents; Cidofovir; Cornea; Cytosine; Disease Models, Animal; Female; Guanine; Herpesvirus 1, Human; Keratitis, Herpetic; Male; Ointments; Ophthalmic Solutions; Organophosphonates; Organophosphorus Compounds; Rabbits; Trifluridine

Topics: Acyclovir; Antiviral Agents; Humans; Keratitis, Herpetic; Secondary Prevention

Drug-resistance of herpes simplex virus (HSV) is caused most frequently by mutation of the viral thymidine kinase (TK) gene. To elucidate the significance of detecting nucleotide changes of the TK gene for screening drug-resistant viruses, the frequency and variation of the genetic polymorphisms in the whole coding region of the TK gene were studied in 14 acyclovir-susceptible HSV type 1 (HSV-1) clinical isolates from 14 patients with epithelial herpetic keratitis. Two reference HSV-1 laboratory strains, McKrae and PH, and two acyclovir-resistant variants of the PH strain were also studied as controls. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct sequencing detected nucleotide differences at 24 positions, and amino acid substitutions at 12 codons in the TK gene of the examined viruses. Nucleotide diversity of 0.0029 per base (the average number of nucleotide substitutions of 3.3 per 1,131 base pairs) in the TK gene in the clinical isolates was comparable to 0.0037 per base of the whole HSV-1 genome in Japanese isolates reported previously. PCR-SSCP analysis of the acyclovir-resistant strains easily detected aberrantly shifted bands by comparing them with those of the parental strain, followed by the quick determination of mutated sequences. These results suggest that detection of nucleotide changes of the TK gene is useful for serial observation of persistent or recurrent HSV infection as observed in immunocompromised hosts, but that it is not useful for screening drug-resistant viruses from nonepidemic clinical isolates because of the comparable genetic polymorphisms in the TK gene as in the whole HSV-1 genome.

Topics: Acyclovir; Amino Acid Sequence; Animals; Antiviral Agents; Base Sequence; Chlorocebus aethiops; Cornea; DNA, Viral; Drug Resistance, Microbial; Genes, Viral; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Microbial Sensitivity Tests; Molecular Sequence Data; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Single-Stranded Conformational; Thymidine Kinase; Vero Cells

Topics: Acute Disease; Acyclovir; Adult; Anti-Inflammatory Agents; Antiviral Agents; Dexamethasone; Diagnosis, Differential; Female; HLA-B27 Antigen; Humans; Intraocular Pressure; Iridocyclitis; Keratitis, Herpetic; Methylprednisolone; Mydriatics; Rheumatic Diseases; Toxoplasmosis, Ocular; Uveitis, Anterior

Topics: Acyclovir; Aged; Antiviral Agents; Cataract Extraction; Female; Humans; Keratitis, Herpetic

Topics: Acyclovir; Antiviral Agents; Humans; Keratitis, Herpetic; Randomized Controlled Trials as Topic

We treated a number of 141 patients suffering of herpetic keratitis--34 were treated with Acyclovir in the first 72 hours the symptoms started, 42 were treated with Acyclovir after this interval and 65 were treated with IDU. We compared visual acuity after six month and we proved that those that were treated with Acyclovir had the same or better visual performances in most cases. Recurrence rate was 0% in the first year and 2.94% in the second year for those witch were treated with Acyclovir in the first 72 hours symptoms started and 2.94% in the first year and 14.71% in the second year for those treated with Acyclovir after this interval. Patients treated with IDU had suffered 23.53% recurrences in the first year and 41.18% recurrences in the second year. Acyclovir treatment and its precociousness protect patients sight and reduce number of recurrences.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Drug Evaluation; Humans; Idoxuridine; Keratitis, Herpetic; Recurrence; Time Factors; Visual Acuity

There were studied 33 patients admitted with clinical diagnosis of superficial herpetic keratitis, typical form of dendritic ulcer. In all these cases there were performed smears from the level of cornea and conjunctiva, that were stained with rapid blue polycrome tanin Dragan staining method. Smears were performed before and during the evolution of the disease, in patients specifically treated with antiviral drugs and also in cases treated unspecifically. There are described some cytological particularities which have a relative specificity for the diagnosis: a high number of lymphocytes with cytoplasmic blebs, giant multinucleated cells, and epithelial cells with degenerative lesions (nucleocytoplasmic inclusions, vacuoles, chromophobe halo around nucleus). Such lesions were not observed in patients with non herpetic keratitis. Modifications noticed in epithelial corneal cells could suggest the diagnosis, which can be associated with clinical examination, in order to administer a specific therapy. Dynamic cytological evolution shows early regression of specific cellular modifications in patients treated by Acyclovir.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Conjunctiva; Cornea; Disease Progression; Female; Humans; Keratitis, Herpetic; Male; Middle Aged

The authors have made a retrospective study of 161 cases of herpetic keratitis. 121 cases of them have been superficial herpetic keratitis and 40 of them discoid forms. 72 cases of superficial keratitis have been the first manifestation and 49 have relapsed. 53 cases of superficial herpetic keratitis and 39 cases of relapsed herpetic keratitis have been treated with specific antiviral medication. This treatment decreased significantly the hospitalisation period of first superficial attack herpetic keratitis. In relapsed and discoid forms the number of the hospitalisation days have not been influenced by the antiviral treatment, needing the association of nonsteroid anti-inflammatory drugs and vitamins.

Topics: Acyclovir; Administration, Topical; Adolescent; Adult; Anti-Bacterial Agents; Antiviral Agents; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Idoxuridine; Infant; Infant, Newborn; Keratitis, Herpetic; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Trifluridine

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Humans; Keratitis, Herpetic; Longitudinal Studies; Recurrence

Immunological factors play an important role in the development of herpetic stromal keratitis. T lymphocytes are the principal cells involved in this immunologic reaction. We therefore investigated the efficacy and safety of topical cyclosporin A 2 % solution in herpetic stromal keratitis.. Ten patients with herpetic stromal keratitis received topical cyclosporin A 2% 4 times daily for 2 months. Acyclovir 3% ointment 5 times daily and cycloplegic eyedrops 2 times daily were used in conjunction with cyclosporin A solution in the 1st month of treatment. Topical steroids were not used. The patients were followed for 6-9 months. Treatment efficacy was evaluated according to two parameters: resolution of stromal infiltrates and neovascularization and increase in visual acuity by two or more Snellen lines. Serum cyclosporin A levels were measured with high-performance liquid chromatography.. In all the patients, the stromal infiltration resolved completely after 2 months of treatment. Visual acuity increased by two or more Snellen lines in 8 out of 10 patients. In the remaining 2 cases, stromal scarring that was present before cyclosporin A treatment prevented vision increase. There were no serious complications from the cyclosporin treatment but 4 cases complained of severe burning upon instillation of the drug. This complication was temporary and did not result in discontinuance of the drug. Serum levels of the drug were always below toxicity levels.. While this is a noncontrolled study, our results show that topical cyclosporin can be a valuable adjunct to acyclovir treatment in herpetic stromal keratitis. Use of topical cyclosporin in dendritic herpetic ulcers and necrotic stromal keratitis has not been investigated in this study.

Topics: Acyclovir; Administration, Topical; Adolescent; Adult; Aged; Antiviral Agents; Chemotherapy, Adjuvant; Corneal Stroma; Cyclosporine; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Keratitis, Herpetic; Male; Middle Aged; Ointments; Ophthalmic Solutions; Visual Acuity

Topics: Acyclovir; Adult; Antiviral Agents; Drug Resistance, Microbial; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Male; Wiskott-Aldrich Syndrome

We have previously shown that basic fibroblast growth factor (FGF-2) enhances corneal epithelial healing in different experimental models in vivo. In order to study the healing effect of this growth factor in pathological conditions of the cornea, we investigated whether topical application of FGF-2 could affect herpes keratitis in rabbits. Since HSV-1 infection is prevented in vitro by incubation with heparin, we also topically applied heparin and suramin, considering the similar interaction of herpes simplex virus and FGF-2 with cell membrane-anchored heparan sulfate.. After virus inoculation with a human BEY.2 strain, rabbits were treated with either FGF-2 (200 ng to 2 micrograms/application), heparin (250 micrograms/application) or suramin (250 micrograms/application) 4 times daily until day 14. Acyclovir and placebo administrations served as controls (n = 48 rabbits). Computerized ulcer surface analysis, clinical observations and virus recovery assays were performed.. Topical FGF-2, heparin and suramin treatment revealed a significant reduction in peak ulcer sizes, and complete epithelial healing was achieved earlier than in placebo-treated corneas. However, no significant antiviral effect of FGF-2, heparin and suramin was detectable in plaque assays from conjunctival swabs.. These experiments demonstrate that FGF-2 is effective in promoting herpetic epithelial ulcer healing, either due to its proliferative effects on epithelial cells or indirectly by occupying the sites on cell surface heparan sulfate necessary for the attachment of the virion. The latter mechanism of action is presumably the reason for the similar effect of heparin and suramin.

Topics: Acyclovir; Administration, Topical; Animals; Corneal Neovascularization; Corneal Opacity; Drug Therapy, Combination; Epithelium, Corneal; Eye Infections, Viral; Female; Fibroblast Growth Factor 2; Follow-Up Studies; Heparin; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Ophthalmic Solutions; Rabbits; Suramin; Tears; Wound Healing

We have been investigating the potential of a new class of antiviral compounds. These peptidomimetic derivatives prevent association of the two subunits of herpes simplex virus (HSV) ribonucleotide reductase (RR), an enzyme necessary for efficient replication of viral DNA. The compounds disclosed in this paper build on our previously published work. Structure-activity studies reveal beneficial modifications that result in improved antiviral potency in cell culture in a murine ocular model of HSV-induced keratitis. These modifications include a stereochemically defined (2,6-dimethylcyclohexyl)amino N-terminus, two ketomethylene amide bond isosteres, and a (1-ethylneopentyl)amino C-terminus. These three modifications led to the preparation of BILD 1351, our most potent antiherpetic agent containing a ureido N-terminus. Incorporation of the C-terminal modification into our inhibitor series based on a (phenylpropionyl)valine N-terminus provided BILD 1357, a significantly more potent antiviral compound than our previously published best compound, BILD 1263.

Topics: Animals; Antiviral Agents; Cells, Cultured; Dipeptides; Enzyme Inhibitors; Keratitis, Herpetic; Magnetic Resonance Spectroscopy; Mice; Oligopeptides; Ribonucleotide Reductases; Simplexvirus; Stereoisomerism; Structure-Activity Relationship; Urea

Sixteen patients with relapsing or chronic HSV keratouveitis were treated during a new attack by acyclovir 15 mg/kg/day by the i.v. route for 5 days with local combination of acyclovir 3% ung. and steroids. In all 16 patients improvement of signs of keratouveitis occurred on the fourth day of therapy, in 10 patients with improvement of visual acuity. In 5 patients perforating keratoplasty was performed on account of turbidity of the cornea. The authors observed four relapses of the disease in the course of 12 months after termination of treatment.

Topics: Acyclovir; Administration, Topical; Adult; Aged; Antiviral Agents; Chronic Disease; Female; Humans; Infusions, Intravenous; Keratitis, Herpetic; Male; Middle Aged; Recurrence; Uveitis

Topics: Acute Disease; Acyclovir; Adult; Antiviral Agents; Astigmatism; Cornea; Eye Foreign Bodies; Eyelids; Follow-Up Studies; Humans; Image Processing, Computer-Assisted; Keratitis, Herpetic; Male; Visual Acuity

The efficacy of combined acyclovir and steroid therapy in the treatment of herpetic stromal disease was evaluated by clinical evaluation of disease, the rebound of disease following termination of therapy, and the recovery of virus and viral DNA from corneas in a rabbit model. Therapy with acyclovir alone produced a significant reduction in corneal thickness in 10% of eyes. Addition of steroid to acyclovir therapy decreased the severity of stromal disease as measured by corneal thickness and increased the frequency of response to treatment to 63% of eyes. All eyes receiving acyclovir alone experienced rebound of disease following termination of therapy. Combined therapy increased the severity of rebound of corneal disease. Virus was recovered from cell cultures established after recovery from rebound in 50% of untreated and treated eyes. Viral DNA was detected by PCR in five of the nine corneal cultures which did not produce infectious virus.

Topics: Acyclovir; Animals; Antiviral Agents; Corneal Stroma; DNA, Viral; Drug Therapy, Combination; Glucocorticoids; Herpesvirus 1, Human; Keratitis, Herpetic; Male; Ophthalmic Solutions; Polymerase Chain Reaction; Prednisolone; Rabbits; Random Allocation; Recurrence; Trigeminal Ganglion; Virus Activation; Virus Shedding

To evaluate the efficacy of long-term oral acyclovir therapy in reducing recurrences of dendritic or geographic herpes simplex keratitis (HSK).. Thirteen patients with a history of frequently recurring HSK were followed before (mean, 27 months) and during long-term systemic acyclovir, and eight were followed after the acyclovir was discontinued.. Treatment ranged from 8.5 to 62 months (mean, 34 months). During treatment, the number of recurrences per month decreased from 0.15 to 0.03, and the average duration of relapses decreased from 12.6 to 7.8 days. Recurrences correlated with daily doses of oral acyclovir of 800 mg or less, intraocular surgery within 6 weeks of initiating treatment, and discontinuation of therapy against medical advice.. The results of this small study appear to demonstrate the efficacy of long-term oral acyclovir in prophylaxis of recurrent epithelial herpes simplex infection: therapeutic doses of oral acyclovir reduce both the rate and duration of recurrences of infectious herpetic keratitis. A multicenter, double-masked, placebo-controlled study is indicated.

Topics: Acyclovir; Administration, Oral; Adult; Aged; Aged, 80 and over; Antiviral Agents; Cataract Extraction; Child; Female; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating; Lenses, Intraocular; Longitudinal Studies; Male; Middle Aged; Recurrence; Visual Acuity

Topics: Acyclovir; Administration, Topical; Adult; Anesthetics, Local; Antiviral Agents; Cornea; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Male; Ophthalmic Solutions; Procaine; Recurrence; Remission Induction; Substance-Related Disorders; Virus Activation

Topics: Acyclovir; Adult; Antiviral Agents; Drug Therapy, Combination; Endothelium, Corneal; Glucocorticoids; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Male; Ophthalmic Solutions; Prednisolone; Trifluridine

Keratitis, retinitis and secondary cataract are well known complications of ocular herpes simplex infection. We report on a case of herpetic keratouveitis and cataract. Acute and inflammatory pathogenesis of cataract formation resemble a phacoanaphylactic reaction.. A 15-year-old girl with recurrent herpes keratitis was referred for acute spontaneous cataract formation accompanied by iridocyclitis and hypotony. Visual acuity was decreased from 0.4 to light projection. During cataract extraction the anterior chamber was tabbed for immunological analysis. The thickened anterior lens capsule was examined by light microscopy. We found a significant local synthesis of herpes antibodies in the aqueous. Histologically the lens capsule depicted a defect and a granulomatous inflammatory infiltrate towards the basal membrane material. The specimen was not suitable to judge on eventual additional phacoanaphylaxis. After cataract extraction and systemic acyclovir and corticosteroids the keratouveitis subsided. Visual acuity improved to 0.4, but was limited by the disciform corneal scar.. The granulomatous response towards lens capsule shown here, resembles the granulomatous reaction towards Descemet's membrane in advanced herpetic corneal ulcer. We speculate on the pathogenesis of the lens capsule defect as a, so far unknown, herpes-associated autoimmun response against the basal membrane material of the lens. The acuteness of cataract formation may be a consequence of contact of aqueous with lens fibres. Additional phacoanaphylaxis combined with secondary glaucoma is possible.

Topics: Acyclovir; Adolescent; Anterior Chamber; Antibodies, Viral; Antiviral Agents; Aqueous Humor; Cataract; Cataract Extraction; Combined Modality Therapy; Cornea; Female; Humans; Iridocyclitis; Keratitis, Herpetic; Lens Capsule, Crystalline; Simplexvirus

Two patients with previous corneal transplants developed unusual rejection-like episodes of the grafted cornea. Both had a migrating line of keratic precipitates and stromal edema involving both the donor and recipient corneas. Intensive steroid treatment attained little effect, but oral acyclovir treatment dramatically suppressed the disease process. The facts suggest that a virus-related immune mechanism against both the donor and recipient endothelia, rather than simple allograft rejection, may have been responsible for the clinical presentations. Oral acyclovir therapy might be considered in patients with steroid-nonresponsive corneal endotheliitis mimicking allograft rejection.

Topics: Acyclovir; Administration, Oral; Adult; Corneal Edema; Corneal Stroma; Corneal Transplantation; Endothelium, Corneal; Female; Graft Rejection; Humans; Keratitis; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Middle Aged; Postoperative Complications

The treatment of herpes simplex keratitis has ranged from simple debridement to the use of prototypic antiviral agents specific to the herpes family, such as acyclovir. The various treatment modalities for dendritic keratitis, for the most part, have been effective. However, in recent years numerous reports of antiviral-resistant strains of herpes simplex have appeared, particularly in immunocompromised patients receiving chronic acyclovir. Interferon has been proposed as a possible treatment adjunct in these cases. We report the case of a 46-year-old man on chronic immunosuppressive and acyclovir therapy after a renal transplant who developed ulcerative keratitis due to a strain of herpes simplex virus that was resistant to multiple antiviral agents both in vivo and in vitro. After 7 weeks without improvement on multiple treatment regimens, including trifluridine, vidarabine, debridement, and topical and systemic acyclovir, interferon alpha-2a was added to topical acyclovir therapy, and the keratitis quickly resolved. Topical interferon alpha-2a appears to be an effective treatment adjunct for refractory herpes simplex keratitis in patients with cell-mediated immune dysfunction and subsequent lack of endogenous interferon. Its value in nonimmunocompromised patients remains to be determined.

Topics: Acyclovir; Administration, Oral; Administration, Topical; Antiviral Agents; Cornea; Corneal Ulcer; Drug Resistance, Microbial; Drug Therapy, Combination; Herpesvirus 1, Human; Humans; Immunocompromised Host; Immunosuppression Therapy; Interferon alpha-2; Interferon-alpha; Keratitis, Herpetic; Male; Middle Aged; Ophthalmic Solutions; Recombinant Proteins

Lactoferrin inhibits bacterial growth in the conjunctival sac. However, its antiviral function particularly in ocular tissue has not been reported in the literature. We studied whether lactoferrin inhibits infection of herpes simplex virus type-1 (HSV-1) in vitro using Vero cell monolayer. We also tested the inhibitory effect of lactoferrin on HSV-1 infection in the mouse cornea. Lactoferrin prevented HSV-1 plaque formation. Administration of topical 1% lactoferrin prior to the virus inoculation suppressed infection on ocular tissue, however it did not inhibit propagation of the virus.

Topics: Acyclovir; Administration, Topical; Animals; Chlorocebus aethiops; Cornea; Female; Herpesvirus 1, Human; Instillation, Drug; Keratitis, Herpetic; Lactoferrin; Mice; Mice, Inbred BALB C; Vero Cells; Viral Plaque Assay; Virus Replication

Herpes simplex virus lesions recur in 8-30% of infants who receive a course of parenteral antiviral therapy for an initial infection. Long-term acyclovir is used by some clinicians to prevent recurrent Herpes simplex disease. We describe nine infants who were treated with doses of oral acyclovir which were chosen to achieve 2-h post-plasma concentrations of > or = 2 micrograms/ml. Eight infants had Herpes simplex encephalitis and one had multiple recurrences of dermal and ocular disease. The target plasma concentration was chosen in order to attain acyclovir cerebrospinal fluid distribution (< or = 50% plasma) for an estimated ID30 of Herpes simplex II strains of 0.1-0.5 microgram/ml. One of nine patients failed to achieve the target plasma acyclovir concentration. One of nine patients developed symptomatic recurrence of the central nervous system disease and none of the remaining eight patients experienced recognized dermal or neurologic recurrence of Herpes simplex disease. Renal and neurologic status were routinely monitored and no signs of acyclovir toxicity were observed. Plasma concentration of acyclovir > or = 2 micrograms/ml may be achieved with average oral doses of 1340 mg/m2/dose (1000-1740 mg/m2/dose) given at 12-h intervals.

Topics: Acyclovir; Administration, Oral; Dose-Response Relationship, Drug; Drug Administration Schedule; Encephalitis, Viral; Female; Follow-Up Studies; Herpes Simplex; Humans; Infant; Infant, Newborn; Keratitis, Herpetic; Long-Term Care; Male; Recurrence

The clinical features of herpes simplex keratitis seen in 370 eyes of 356 patients (211 males and 145 females) in the outpatient clinic of the Yokohama City University hospital during the last 30 years (1963-1992) were statistically analyzed. The age of patients ranged from 1 to 75 years (mean 38.4 years). Bilateral herpetic keratitis was seen in 11 patients (10.4%) in the period of 1980-1992. Epithelial keratitis, stromal keratitis, and corneal endotheliitis were observed in 67 patients (57.3%), 46 patients (39.3%), and 4 patients (3.4%), respectively, in the period of 1980-1992. There was no significant change in the incidence of the types of corneal lesions during the last 13 years as compared with those in the previous 17 years (1963-1979). Life-table analysis revealed that 5-year recurrence rates were 17.5% in patients treated with acyclovir (ACV) and 52.9% in those treated with idoxuridine (IDU). The recurrence rate in ACV-treated patients was significantly lower than that in IDU-treated patients. Severe cases, such as those complicated by deep corneal ulcers with hypopyon, descemetoceles, or necrotizing keratitis, were decreased in number in ACV-treated patients, as compared with IDU-treated patients.

Topics: Acyclovir; Adolescent; Adult; Aged; Child; Child, Preschool; Cornea; Female; Humans; Idoxuridine; Incidence; Infant; Japan; Keratitis, Herpetic; Male; Middle Aged; Recurrence; Retrospective Studies

Ophthalmic findings are reported in 31 eyes of 28 children with herpes simplex keratitis. Twenty two had dendritic ulcers, and nine had geographic ulcers or disciform stromal keratitis. After resolution of keratitis, 80% (19/22) of children with dendritic ulcers achieved corrected visual acuity of 6/9 or better, 50% (11/22) had induced astigmatism, 45% (9/22) had one to five recurrences. In the group with geographic or disciform lesions, 89% (8/9) had reduced corrected vision, 78% (7/9) had induced astigmatism which was predominantly against the rule, and 87% (7/9) had one to six recurrences.

Topics: Acyclovir; Adolescent; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Keratitis, Dendritic; Keratitis, Herpetic; Male; Recurrence; Refractive Errors; Visual Acuity

A chronic administration of three ganciclovir gels (0.2%, 0.05%, 0.0125%) was compared with a placebo gel and a 3% acyclovir ophthalmic ointment in the treatment of HSV-1 rabbit keratitis. All the ganciclovir gels showed a clinical efficacy: a significant reduction of the corneal ulcer area, clouding and vascularization (p < 0.05) and a fast inhibition of HSV isolates into tear film with the 0.2% and 0.05% ganciclovir gels. However the efficacy was slower than using acyclovir ointment. No significant difference could be shown between the 0.2% and 0.05% ganciclovir gels or the 0.05% ganciclovir gel and the acyclovir treatment on viral isolation, when it was performed on pooled samples. The distribution of ganciclovir and acyclovir into the rabbit eyes (HPLC methods), were similar but markedly higher in solid tissues than ocular fluids. It might explain the recovery from tissue damages. The mean corneal ganciclovir concentrations were largely higher than ED 50 of ganciclovir for HSV-1. No toxicity was expected, due to very limited systemic availability. This study suggests a comparable activity on HSV-1 superficial keratitis between 0.05%, 0.2% ganciclovir gels and 3% acyclovir ointment. Higher concentration of ganciclovir gels are probably necessary in order to treat the HSV-1 kerato-uveitis.

Topics: Acyclovir; Animals; Drug Carriers; Eye; Ganciclovir; Gels; Herpesvirus 1, Human; Keratitis, Herpetic; Ointments; Ophthalmic Solutions; Rabbits; Virus Shedding

To assess the efficacy of prophylactic topical antiviral therapy after penetrating keratoplasty for herpes simplex keratitis in the postoperative period and during the treatment of allograft rejection episodes with topical steroids. We used these data to make predictions of the sample size required to perform a prospective study of prophylactic oral acyclovir in the postoperative period.. Retrospective review.. A university referral cornea service.. One hundred thirty-two consecutive penetrating keratoplasties for herpes simplex keratitis in 119 eyes of 118 patients. Only four grafts were performed in actively inflamed eyes.. Sixty-six (52%) of the grafts performed in quiescent eyes received prophylactic postoperative topical antiviral treatment, three (2%) received oral acyclovir, and 59 (46%) received no antiviral therapy. The mean (+/- SD) duration of antiviral therapy was 12.8 +/- 22.5 months.. Herpetic recurrence, allograft rejection episodes, and graft failure.. Multivariate analysis showed that early antiviral use was associated with a decreased risk of herpes simplex keratitis recurrence (relative risk [RR] = 0.44; 95% confidence interval [CI], 0.21 to 0.94; P = .007) and allograft rejection (RR = 0.43; 95% CI, 0.25 to 0.75; P = .002). Graft failure was associated with herpetic recurrence within the first year (RR = 2.25; 95% CI, 1.09 to 4.64; P = .001) and allograft rejection episodes (RR = 2.56; 95% CI, 1.20 to 5.26; P = .003). Using these data, a prospective trial of postoperative oral acyclovir would require between 59 and 112 patients per group.. Postoperative prophylactic antiviral treatment is associated with decreased rates of herpes simplex viral keratitis recurrence and allograft rejection. Early recurrence is associated with an increased risk of graft failure. A prospective study of postoperative oral acyclovir would require a multicentered approach.

Topics: Acyclovir; Administration, Oral; Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Child; Combined Modality Therapy; Female; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Middle Aged; Multivariate Analysis; Recurrence; Retrospective Studies; Treatment Outcome

Topics: Acyclovir; Administration, Oral; Cornea; Female; Fever; Humans; Keratitis, Herpetic; Recurrence

In vitro permeability studies were conducted on isolated rabbit corneal membranes using aliphatic acyl esters of acyclovir to determine the effect of lipophilicity on the transcorneal diffusion. Corneal membrane permeability coefficients increased with increasing lipophilicity of the straight chain aliphatic esters. The branch chain ester, acyclovir isobutyrate, displayed an anomalously low corneal permeability when compared to acyclovir esters having similar molecular size and 1-octanol/water partition coefficient. In vivo corneal penetration studies were conducted on unanesthetized rabbits. The aqueous humor concentrations of acyclovir and the ester prodrugs were measured at twenty five minutes after the topical instillation of an aqueous solution of the appropriate compound. The concentration of acyclovir in the aqueous humor increased with increasing 1-octanol/water partition coefficient. The lipophilic modification was shown to have a greater effect on increasing productive corneal absorption than the precorneal loss pathways. The effectiveness of acyclovir butyrate as a treatment for primary herpetic keratitis was evaluated in the McKrae strain infected rabbit model. The compound did not lose activity due to the esterification of the 2' hydroxyl group.

Topics: Absorption; Acyclovir; Acylation; Animals; Aqueous Humor; Biological Transport; Cell Membrane Permeability; Cornea; Disease Models, Animal; Drug Evaluation; Esters; Herpesvirus 1, Human; Keratitis, Herpetic; Male; Prodrugs; Rabbits

Seventeen patients with presumed chronic herpetic uveitis of all anatomic types underwent systemic treatment with oral and/or intravenous, acyclovir. The diagnosis of herpes had been established on data from serological tests of the aqueous humor. Results were judged according to corticodependance and visual acuity. Results were all the more positive as treatment was more prolonged and also correlated with the dose of acyclovir injected intravenously or taken orally every day. Follow-up ranged from 6 months to several years.

Topics: Acyclovir; Administration, Oral; Adult; Aged; Dose-Response Relationship, Drug; Female; Humans; Injections, Intravenous; Keratitis, Herpetic; Male; Middle Aged; Time Factors; Uveitis

To determine the potential efficacy and anatomic sites of action of prophylactic oral acyclovir using a murine model of ultraviolet-B-induced reactivation of herpes simplex 1 keratitis.. Latent infection with herpes simplex 1 (McKrae) was established in 80 National Institutes of Health inbred strain of mice. Forty of the mice were given acyclovir orally and the other 40 latently infected mice served as controls. Mice were exposed to 250 mJ/cm2 of ultraviolet-B radiation and killed on days 1, 2, 3, and 4 after ultraviolet-B radiation. Trigeminal ganglia and eyes from these mice were homogenized and incubated on Vero cell monolayers for recovery of reactivated virus.. Based on the recovery of infectious virus after ultraviolet-B in treated versus control groups, acyclovir effectively reduced detectable viral reactivation at both the ocular level (P = 0.003) and the ganglionic level (P = 0.025). The numbers of viral culture-positive eye and trigeminal ganglia homogenates in the control group were 11 and 6 out of 40, respectively, compared to 1 and 0 out of 40 culture-positive eye and trigeminal ganglia homogenates in the acyclovir treated mice. Therapeutic serum levels of acyclovir were confirmed by high performance liquid chromatography. In the acyclovir-tested group, the single case of viral break-through at the ocular surface was not an acyclovir-resistant mutant.. Prophylactic acyclovir effectively reduces the incidence of herpes simplex virus-1 reactivation after ultraviolet-B-induced reactivation in National Institutes of Health inbred strain of mice.

Topics: Acyclovir; Administration, Oral; Animals; Cornea; Disease Models, Animal; Female; Herpesvirus 1, Human; Keratitis, Herpetic; Mice; Mice, Inbred Strains; Premedication; Ultraviolet Rays; Vero Cells; Virus Activation

The combination of acyclovir and ribavirin has been established to be more effective on experimental herpes simplex keratoconjunctivitis in rabbits than the treatment with individual drugs. The better therapeutic effect of the combination is proved by the decreased severity of the ocular infection and the reduction of the virus shedding in tear film, as well as by the diminished duration of the infection.

Topics: Acyclovir; Animals; Drug Evaluation, Preclinical; Drug Therapy, Combination; Keratitis, Herpetic; Keratoconjunctivitis; Rabbits; Ribavirin; Simplexvirus; Tears; Time Factors

We studied the alteration in the clinical features of herpes simplex virus-induced keratitis (HSK) after the introduction of acyclovir (ACV) (in 1986). Over a nine-year period, this study investigated 101 patients (52 men and 49 women) whose conditions were diagnosed clinically as HSK. In addition, HSK recurred in 48 (47.5%) of the 101 patients. The distribution of clinical types of primary HSK before 1985 did not differ from that after 1986. Recurrent HSK was significantly more frequent in patients aged 26 to 40 years (75.0%). Although the five-year recurrence rates in primary HSK treated with ACV were significantly lower than those in patients treated with idoxuridine, the recurrence frequency before 1985 was equal to that after 1986. The discordance of the decreased recurrence rate in ACV-treated patients and the high recurrence frequency in patients with recurrent disease after the introduction of ACV were considered to be the result of the incomplete inhibitory effect of this drug.

Topics: Acyclovir; Adolescent; Adult; Aged; Child; Child, Preschool; Cornea; Female; Humans; Idoxuridine; Infant; Keratitis, Herpetic; Male; Middle Aged; Recurrence; Simplexvirus; Virus Activation

Although several drugs are available to treat superficial herpes simplex keratitis, viral latency and recurrences represent clinical challenges that have been inadequately addressed by current topical antiviral agents. One hundred and ninety patients with previous herpes simplex keratitis were entered in an open study to evaluate the efficacy of the prophylactic therapy of recurrence with Acyclovir (200 mg) four times daily for 1 month to 24 months. Forty patients were treated because of frequently recurring herpetic keratitis; 36 were treated during a short period because of known risk factors; 23 were treated after ocular surgery which needed topical corticosteroid therapy in the postoperative period and 91 patients were treated after penetrating keratoplasty for herpetic keratitis. The results of this study indicate that oral Acyclovir significantly lowered the incidence of recurrences of herpetic keratitis in selected patients.

Topics: Acyclovir; Administration, Oral; Drug Evaluation; Humans; Keratitis, Herpetic; Recurrence; Tablets; Time Factors

Keratoplasties are performed relatively frequently in herpes-afflicted eyes. However, intraocular lenses (IOLs), for eyes with intraocular recurrent herpes simplex virus (HSV) disease remain a verdict in most surgical centers. As most herpetic disease is uniocular and cataract is a frequent complication in the long run, a real need exists for triple procedures in such eyes so as to achieve their full visual rehabilitation. Taking full advantage of systemic aciclovir therapy and prophylaxis, we started with triple procedures in herpes-afflicted eyes in 1987. Up to July 1991, we operated on 29 eyes, and 28 could be optically rehabilitated. One eye was given up and received a conjunctival cover for sociomedical reasons. Three repeat keratoplasties (10%) were necessary, and a considerable number of complications had to be overcome; ten eyes suffered from sustained fibrinous exsudations (35%), ten were threatened by one or more endothelial immune therapy reactions (35%), and ten experienced one or more herpes recurrences (35%), mostly intraocular recurrences. As this study was not performed as a randomized, placebo-controlled, double-blind study, no absolute scientific proof of aciclovir's value in these patients can be presented. Nonetheless, we would conclude from the exceedingly good rehabilitation rate of 96% observed during an average follow-up period of 19 months that in all probability, systemic aciclovir was in the first rank responsible for this success rate. Thus, there is good clinical evidence that systemic aciclovir prophylaxis and therapy is indeed the most important key for successful triple procedures in eyes afflicted with herpetic disease.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Cataract Extraction; Female; Follow-Up Studies; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating; Lenses, Intraocular; Male; Middle Aged; Postoperative Complications; Recurrence; Reoperation; Treatment Outcome

The nucleoside analog 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5- ethyluracil (FEAU) was tested in a rabbit model of acute herpetic keratitis and its effectiveness compared with that of acyclovir (ACV). FEAU or ACV was applied topically 3 times daily, beginning 3 days post-HSV-1 inoculation and continued for a period of 7 days. FEAU at a concentration of 1% (w/v) or 3% ACV resulted in significant lessening of the severity of corneal lesions, conjunctivitis, iritis, and corneal clouding at 24 to 48 h after beginning chemotherapy. No toxic reaction was observed in any rabbit eyes treated with either FEAU or ACV. The duration of virus shedding into tear film and colonization of the trigeminal ganglia, however, were not reduced by either FEAU or ACV treatment begun 3 days post-inoculation. Fifty percent effective dose (ED50) of FEAU determinations performed on isolates from tear film and on the virus inoculum in secondary rabbit kidney cultures yielded a range of 4.6-7 microM, with two in vitro resistant isolates having ED50S of greater than or equal to 1500 microM of FEAU. Fifty percent cell growth inhibition for FEAU was 3000 microM at 72 h.

Topics: Acyclovir; Animals; Antiviral Agents; Arabinofuranosyluracil; Cells, Cultured; Cornea; Disease Models, Animal; Drug Evaluation, Preclinical; Keratitis, Herpetic; Male; Ophthalmic Solutions; Rabbits; Simplexvirus

A case of acyclovir-resistant herpes simplex virus keratouveitis after penetrating keratoplasty is reported.. Resistance to acyclovir was evident clinically and was confirmed by in vitro susceptibility testing. The susceptibility of the herpes simplex isolates to acyclovir and foscarnet was determined by a dye uptake assay that measured cytopathic effect, and thymidine kinase activity was measured by a plaque autoradiography technique.. The viral isolate from postoperative day 22 was susceptible to acyclovir and foscarnet, and showed normal thymidine kinase activity. Isolates from postoperative days 29 and 32 (coinciding with deterioration in clinical appearance) were resistant to acyclovir, susceptible to foscarnet, and deficient in thymidine kinase activity.. Practitioners should be aware of the potential for the emergence of resistance in this setting; prophylaxis and rational alternate therapies are discussed.

Topics: Acyclovir; Administration, Oral; Animals; Drug Resistance, Microbial; Foscarnet; Humans; Keratitis, Herpetic; Keratoplasty, Penetrating; Male; Microbial Sensitivity Tests; Middle Aged; Ophthalmic Solutions; Postoperative Complications; Simplexvirus; Uveitis; Vero Cells; Visual Acuity

Twenty-two cases 23 eyes with obstinate stromal keratitis treated by combination of traditional Chinese and Western medicines are reported in this paper. According to clinical manifestations, they are consistent with the clinical diagnosis of stromal herpes simplex keratitis. Since no specific Western medicine is known to be effective in treating this disorder, it is proposed to apply systemic and topical TCM and, if necessary, add beta-ray irradiation to shorten the clinical course of disease, decrease or prevent recurrence and maintain useful visual acuity, avoiding frequent relapses leading to blindness.

Topics: Acyclovir; Adolescent; Adult; Ascorbic Acid; Beta Particles; Combined Modality Therapy; Drugs, Chinese Herbal; Female; Humans; Keratitis, Herpetic; Male; Middle Aged

The combined antiviral effects of acyclovir (ACV) and ribavirin (Rbv) on herpes simplex virus type 1 (HSV-1) and pseudorabies virus (PRV) in cell cultures and on experimental HSV-1 keratitis in rabbits were studied. The antiviral activity in vitro was based on cytopathogenicity inhibition and yield reduction. The combination of the two drugs exhibited synergy as evaluated graphically (isobolograms). Rbv also potentiated the antiviral effect of ACV in vivo, in the experimental HSV-1 keratitis model in rabbits. This was evident from both the severity of corneal lesions and virus shedding in the tear film. The potentiating effect of Rbv on the anti-HSV-1 activity of ACV in vitro was reversed by guanosine.

Topics: Acyclovir; Animals; Cells, Cultured; Drug Interactions; Drug Synergism; Drug Therapy, Combination; Guanosine; Herpesvirus 1, Suid; Keratitis, Herpetic; Rabbits; Ribavirin; Simplexvirus