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MicroRNAs (miRNAs) are small regulatory molecules that control diverse biological processes that include angiogenesis. Herpes simplex virus (HSV) causes a chronic immuno-inflammatory response in the eye that may result in corneal neovascularization during blinding immunopathological lesion stromal keratitis (SK). miR-132 is a highly conserved miRNA that is induced in endothelial cells in response to growth factors, such as vascular endothelial growth factor (VEGF). In this study, we show that miR-132 expression was up-regulated (10- to 20-fold) after ocular infection with HSV, an event that involved the production of both VEGF-A and IL-17. Consequently, blockade of VEGF-A activity using soluble VEGF receptor 1 resulted in significantly lower levels of corneal miR-132 after HSV infection. In addition, low levels of corneal miR-132 were detected in IL-17 receptor knockout mice after HSV infection. In vivo silencing of miR-132 by the provision of anti-miR-132 (antagomir-132) nanoparticles to HSV-infected mice led to reduced corneal neovascularization and diminished SK lesions. The anti-angiogenic effect of antagomir-132 was reflected by a reduction in angiogenic Ras activity in corneal CD31-enriched cells (presumably blood vessel endothelial cells) during SK. To our knowledge, this is one of the first reports of miRNA involvement in an infectious ocular disease. Manipulating miRNA expression holds promise as a therapeutic approach to control an ocular lesion that is an important cause of human blindness., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

When the cornea of the eye dissolves, most commonly secondary to infection or trauma, the ventral wall of the anterior chamber of the eye is no longer supported and thus bulges forward, enlarging the anterior chamber volume. This is referred to as a corneal melt, and it has a unique CT appearance that has not been previously described.

Ocular infection with HSV causes corneal neovascularization (CV), an essential step in the pathogenesis of the blinding immunoinflammatory lesion stromal keratitis. The infection results in IL-17A production, which contributes to CV in ways that together serve to shift the balance between corneal concentrations of vascular endothelial growth factor A (VEGF-A) and the soluble vascular endothelial growth factor receptor 1 molecule, which binds to VEGF-A and blocks its function (a so-called VEGF trap). Accordingly, animals lacking responses to IL-17A signaling, either because of IL-17 receptor A knockout or wild-type animals that received neutralizing mAb to IL-17A, had diminished CV, compared with controls. The procedures reduced VEGF-A protein levels but had no effect on the levels of soluble vascular endothelial growth factor receptor 1. Hence the VEGF trap was strengthened. IL-17A also caused increased CXCL1/KC synthesis, which attracts neutrophils to the inflammatory site. Neutrophils further influenced the extent of CV by acting as an additional source of VEGF-A, as did metalloproteinase enzymes that degrade the soluble receptor, inhibiting its VEGF-blocking activity. Our results indicate that suppressing the expression of IL-17A, or increasing the activity of the VEGF trap, represents a useful approach to inhibiting CV and the control of an ocular lesion that is an important cause of human blindness.

Objective: To describe a novel surgical technique for the sealing of large corneal perforations., Method: Case report of a perforated, 3-mm, postherpetic, corneal ulcer. A single layer of amniotic membrane was sewn to the internal surface of the cornea. An absorbable fibrin sealant patch (TachoSil) was placed in the area of the perforation, and a folded double layer of amniotic membrane was finally sewn to the external face of the cornea., Result: Surgery without complications, leading to restoration of the anterior chamber and good subjective tolerance., Conclusion: The reported technique seems to represent a good alternative emergency procedure for the management of corneal perforations larger than 2 mm.

Innate immune deficiencies result in a spectrum of severe clinical outcomes following infection. In particular, there is a strong association between loss of the signal transducer and activator of transcription (Stat) pathway, breach of the blood-brain barrier (BBB), and virus-induced neuropathology. The gene signatures that characterize resistance, disease, and mortality in the virus-infected nervous system have not been defined. Herpes simplex virus type 1 (HSV-1) is commonly associated with encephalitis in humans, and humans and mice lacking Stat1 display increased susceptibility to HSV central nervous system (CNS) infections. In this study, two HSV-1 strains were used, KOS (wild type [WT]), and Δvhs, an avirulent recombinant lacking the virion host shutoff (vhs) function. In addition, two mouse strains were used: strain 129 (control) and a Stat1-deficient (Stat1(-/-)) strain. Using combinations of these virus and mouse strains, we established a model of infection resulting in three different outcomes: viral clearance without neurological disease (Δvhs infection of control mice), neurological disease followed by viral clearance (Δvhs infection of Stat1(-/-) mice and WT infection of control mice), or neurological disease followed by death (WT infection of Stat1(-/-) mice). Through the use of functional genomics on the infected brain stems, we determined gene signatures that were representative of the three infection outcomes. We demonstrated a pathological signature in the brain stem of Stat1-deficient mice characterized by upregulation of transcripts encoding chemokine receptors, inflammatory markers, neutrophil chemoattractants, leukocyte adhesion proteins, and matrix metalloproteases. Additionally, there was a greater than 100-fold increase in the inflammatory markers interleukin 1β (IL-1β) and IL-6. Consistent with this gene signature, we demonstrated profound CNS inflammation with a concomitant lethal breach of the BBB. Taken together, our results indicated an essential role for normal Stat1-dependent signaling in mediating a nonpathological immune response to viral CNS infection.

Purpose: According to our clinical observation, patients with quiescent herpes simplex virus (HSV) stromal keratitis often seem to present with signs of dry eye in the contralateral eye. Our goal was to compare dry eye signs and symptoms in both eyes of patients with quiescent HSV stromal keratitis with those of age- and sex-matched control subjects with healthy corneas., Methods: A case-control study with 24 subjects per group., Results: The average age of 10 men and 14 women in each group was 58 years. The HSV eye of cases was first compared with the contralateral eye with a healthy cornea. As expected, the HSV eye had a significantly lower corneal sensation threshold (P = 0.001); no significant difference was however found for Schirmer tests done with anesthesia (basal tear secretion) and without anesthesia, tear breakup time, mucus and debris in the tear film, and eyelid margin redness or swelling. Then, the HSV eye of cases was compared with the right eye of controls, whereas the healthy eye of cases was compared with the left eye of controls. Patients with unilateral quiescent HSV stromal keratitis had significantly lower bilateral Schirmer tests both with anesthesia (P = 0.001) and without anesthesia (P = 0.02). Dry eye symptoms of the healthy cornea of cases and those of controls did not differ significantly., Conclusions: Both eyes of patients with quiescent HSV stromal keratitis in our population were dry even if many patients with HSV stromal keratitis did not have symptoms in their fellow eye.

Purpose: To evaluate the success of cyanoacrylate tissue adhesive in the management of corneal perforations associated with herpetic keratitis., Methods: 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., Results: 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., Conclusion: 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.

Recurrent corneal erosion (CE) is a common anterior eye disease, which usually occurs after injury, substantially limits a patient's ability to work, and is intractable. The authors single out an individual form of CE herpetic CE (HCE) on the basis of immunofluorescence assay of a conjunctival scrape, which shows the high concentration of herpes simplex virus antigen in 53% of CE cases. Confocal microscopy revealed epithelocyte polymorphism and basement membrane defects. The treatment of patients with HCE involved 2 steps: 1) relief of acute signs of the disease via drug therapy, rapid local autocyte cinotherapy (RLACCT), or phototherapeutic keratectomy (PTK) and 2) prevention of recurrences. For this the authors developed a method based on the systemic use of a new composition of the intradermal herpes vaccine Vitaherpavac in combination with the subcutaneous interferon inducer Poludan. RLACCT was found to be the most effective medical treatment for CE and PTK was the most effective surgical one. Vaccination with the concurrent subcutaneous injection of Poludan is an effective method in preventing recurrent HCE. During a follow-up of 2 years or more, 81% of the patients achieved clinical resolution; there was a decrease in recurrence rates and severity in 15.1% and no effect in 3.8%.

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.

Purpose: To assess the relative impact of elevated T-helper 2 (T(H)2)- and reduced T-Helper 1 (T(H)1)-dependent immune responses on ocular herpes simplex virus type 1 (HSV-1) infection., Methods: Signal transducer and activator of transcription protein 4 knockout mice (BALB/c-STAT4(-/-)) and wild-type BALB/c control mice were immunized with avirulent HSV-1 strain KOS or were mock-immunized. Three weeks after the third immunization, neutralizing antibody titers were determined by plaque reduction assays. Following ocular infection with virulent HSV-1 strain McKrae, viral replication in the eye, blepharitis, corneal scarring (CS), survival, and immunoglobulin (Ig) isotypes in sera were determined., Results: Vaccinated STAT4(-/-) and BALB/c mice contained significant and similar neutralizing antibody titers and were completely protected against HSV-1-induced death and CS. In contrast to vaccinated STAT4(-/-) mice, mock-vaccinated STAT4(-/-) mice had higher ocular HSV-1 titers than mock-vaccinated BALB/c mice on days 2-3 post-ocular infection. There were also significant differences in the levels of IgG2a, IgG2b, and IgG3 in the sera of STAT4(-/-) mice when compared to the control BALB/c mice., Conclusions: These results suggest that the absence of T(H)1 cytokine responses did alter protection against viral replication and IgG isotypes but not eye disease or survival.

Herpetic keratitis is an increasingly frequent pathology, especially among the adult population. Untreated, it can lead to ocular complications difficult to treat and even to visual disabilities. Also, recurrent episodes should be diagnosed and treated appropriately in order not to leave room for the complicated forms, which often lead to a slow and incomplete visual recovery.

Purpose: To evaluate the success rate of treating persistent corneal epithelial defects using 50% autologous serum eyedrops., Methods: We reviewed the medical records of all patients seen at our institution from September 2004 to May 2007 who had persistent corneal epithelial defects that were nonresponsive to conventional medical treatment and that were treated with 50% autologous serum eyedrops. We also correlated the defect duration prior to initiation of serum therapy with rate of epithelial healing., Results: A total of 25 eyes of 25 patients failed conventional medical therapy for treatment of a persistent corneal epithelial defect and were treated with 50% autologous serum eyedrops every 2 hours while awake. All corneas were neurotrophic, with the etiologies being herpetic (11 eyes), postkeratoplasty (8 eyes), postkeratorefractive surgery (1 eyes), diabetic (1 eye), post-chemical burn (1 eye), and unknown (3 eyes). The median duration of the epithelial defects prior to initiation of autologous serum eyedrops was 13.9 weeks (range 0.29-52 weeks). After institution of autologous serum therapy, 23 of the 25 eyes healed in a mean time of 22.4 days. Seventeen eyes (68.0%) healed within 4 weeks (mean 1.7 weeks) of starting therapy with 50% autologous serum eyedrops. The number of days required for healing was associated with the length of time the defect was open prior to initiation of serum drops (r = 0.68, P < 0.001)., Conclusions: The use of 50% autologous serum eyedrops appears to be an efficacious medical treatment modality for persistent corneal epithelial defects that are recalcitrant to conventional medical therapy.

Purpose: To report a case of lichen planus in a patient with a history of herpes simplex virus keratitis., Methods: Case report., Results: A 60-year-old woman with chronic conjunctivitis and a history of herpes simplex virus keratitis was evaluated for irritation and a plaque on her right upper and lower eyelid palpebral conjunctivae. A surgical excision showed acanthosis and an underlying lichenoid infiltrate with a thickened basement membrane., Conclusion: Lichen planus of the conjunctiva can be present in the absence of cicatrization in a patient with chronic irritation of the conjunctiva.

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.

Complications in urinary tract nervous routes due to herpes viruses as VZV and HSV-2 are well known. Acute urinary retention and chronic neuropathic pain are not rare when sacral dermatomes are involved by these viruses. However, an analogous condition has not yet been clearly ascribed to HSV-1 infection. We present a 32-year-old immunocompetent patient with fever, lumbar pain and acute urinary retention who had never had herpetic clinical manifestations. Urodynamic studies diagnosed a neurologic bladder with an absent filling sensation. Cystoscopic assessment revealed the presence of reddened and isolated small mucosal areas in the bladder walls. The search for herpes viruses in plasma and CSF by PCR assay were positive for HSV-1. After treatment with antiviral therapy the disease resolved. Intermittent catheterization was necessary and voiding dysfunction resolved after three weeks by its appearance. Neurological damage to the central nervous system (CNS) and/or PNS due to HSV-1 seems to be the most likely reason. The course of disease was benign and self-remitting.

The primary objective of this study was to optimize the process of remedial treatment at health reports of Sochi, Gelendzhik, and Anapa by introducing sun, air, and sea water baths in the system of sanatorium-and-spa treatment of the children with various nosologic forms of psoriasis and concomitant ophthalmoherpes that necessitated keratoplastic surgery. The study included children at the age of 7-13 years with plaque and nummular psoriasis vulgaris who received rehabilitative treatment after keratoplasty for ophthalmoherpes. The children were randomly allocated to two groups. One comprised patients based at the specialized children's sanatoria "Yunost", "Vulan", and "Bimlyuk" (Roszdrav) (group 1, n = 278). Patients of the control group were given conventional treatment in municipal outpatient settings in compliance with the existing standards (group 2, n = 278). The study showed a 2.39-fold decrease of the psoriasis area and severity index (PASI) in the children of group 1 compared with its 1.38-fold decrease in group 2. It is concluded that a combination of natural physical factors of the Kuban' Black Sea coastal area has highly beneficial effect on the outcome of postoperative treatment of children with plaque and nummular psoriasis vulgaris and concomitant ophthalmoherpes responsible for corneal ulceration that requires corrective keratoplastic surgery.

Purpose: To study the microbiological and clinical profile of cases of microbial keratitis in patients with Down syndrome., Methods: A retrospective chart review of all patients with Down syndrome and microbial keratitis admitted to the Royal Victorian Eye and Ear Hospital, Melbourne, Australia, between January 1997 and January 2007 was undertaken. Main parameters evaluated were clinical and microbiological profile and final outcome., Results: Of 18 patients included in this study, 11 were men and 7 were women, with mean age of 50 +/- 29 years (range 20-61 years). The most common associated ocular abnormality was eyelid diseases (94%) followed by atopic keratoconjunctivitis (44%). Positive microbiological cultures were obtained in 5 (28%) cases with Streptococcus pneumoniae being the most prevalent isolate. Ocular herpes was detected in 2 patients with polymerase chain reaction. Surgical intervention was required in 13 (72%) patients in the form of keratoplasty (n = 3) corneal gluing (n = 2), tarsorrhaphy (n = 5), botox injection (n = 1), and enucleation (n = 2)., Conclusions: Microbial keratitis in Down syndrome is associated with eyelid problems and ocular atopy, and due to failure of medical therapy alone, surgical intervention is required in majority of cases.

Angiogenesis and inflammatory mediators are critical pathogenic factors in herpetic stromal keratitis (HSK). Since disease progresses without infectious virus, HSV-DNA and HSV-IgG complexes (HSV-IC) may contribute to HSK by triggering these factors. Production of VEGF and MMP-9 was studied in vitro using corneal epithelial cells (HCE), fibroblasts (HCRF) and macrophages (THP-1). VEGF was elevated in HCRF and THP-1 following treatment with HSV-DNA and HSV-IC. MMP-9 was elevated in THP-1 but not in corneal cells. When anti-HSV-IgG(Fab')2 complexes stimulated THP-1, MMP-9 was reduced to control levels. Pretreatment of THP-1 with anti-TLR-2 and -3 inhibited MMP-9 production. Thus, HSV-IC may stimulate THP-1 through the Fc receptor and TLRs. Proinflammatory cytokines (IL-1b, IL-6, and TNF-alpha) increased VEGF and MMP-9 in corneal cells and macrophages. These studies indicate that the continued presence of HSV-DNA and HSV-IC contribute to angiogenesis and inflammation in HSK. Thus, cytokines and TLRs may be potential targets for intervention.

Purpose: 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., Methods: Case report., Results: 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., Conclusions: 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.

Purpose: To repair corneal perforation using human fibrin glue and determine its efficacy., Methods: A case series study was performed on corneal perforations up to 3 mm in diameter who were admitted in Farabi Eye Hospital. Age, visual acuity, presence and size of corneal thinning, corneal epithelial defect, size and depth of corneal infiltration, site and size of corneal perforation, corneal vascularization, anterior chamber depth, and reaction and the etiology of corneal perforation were recorded. Then, corneal perforation was sealed using FG and soft contact lens, and the patients were followed up for at least 3 months. Healing of the corneal perforation with adhesive was considered as a success (the primary outcome) and reported., Results: Of 18 patients, 8 were women and 10 men. The mean age of the patients was 52 +/- 25.7 years. The size of corneal perforations was 0.6-3 mm (mean = 1.88 mm). The etiologies of corneal perforation were postinfectious in 11 and noninfectious in 7. Fifteen (83.3%) eyes had successful healing of corneal perforation after 3 months. All the patients who were failed had corneal perforation larger than 2 mm in diameter. The success rate was higher in corneal perforation

Purpose: 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., Methods: Case report and review of medical literature., Results: 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., Conclusions: Bevacizumab may be a valid complementary treatment in patients with corneal neovascularization caused by herpetic stromal keratitis.

Purpose: To report a case of Alport syndrome with recurrent herpes simplex virus (HSV) keratitis., Methods: Case report and review of the literature., Results: 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., Conclusions: 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.

Purpose: To report the outcomes of laser in situ keratomileusis (LASIK) in patients with a history of ocular herpes simplex virus (HSV) or herpes zoster ophthalmicus (HZO)., Setting: Clínica Baviera, Instituto Oftalmológico Europeo, Madrid, Spain., Methods: In this retrospective case series, the records of eyes with a history of ocular herpes that had LASIK from 2003 through 2005 were reviewed. The main outcome measure was postoperative recurrence of ocular herpes., Results: Forty-nine eyes (48 patients) with a history of ocular herpes (HSV keratitis, 28 eyes; HSV eyelid lesions, 17 eyes; HZO, 4 eyes) were identified. All LASIK procedures were uneventful. Herpetic disease was inactive at the time of surgery in all eyes and for more than 1 year in 31 eyes. Perioperative antiviral systemic prophylaxis was used in 13 patients with a history of HSV keratitis. No eye developed reactivation of herpetic keratitis during the follow-up (range 1 to 28 months)., Conclusions: Laser in situ keratomileusis was safe in patients with a history of ocular herpes; no recurrences occurred during the follow-up period. However, candidates should be selected with caution and surgery performed only in eyes in which the herpes has been inactive for 1 year before surgery, without stromal disease, and with regular topography and pachymetry maps and normal corneal sensitivity. The most reasonable clinical strategy is perioperative systemic antiviral prophylaxis.

Aim: To determine the incidence, methods of diagnosis, treatment strategies and outcomes for acute retinal necrosis (ARN) in the UK., Methods: A 12-month active case ascertainment study was carried out between March 2001 and March 2002 to record cases of ARN presenting to ophthalmologists via the British Ophthalmological Surveillance Unit (BOSU) reporting system. Questionnaires were sent to the reporting consultants, requesting data on patient characteristics, presentation, clinical findings, investigations and treatment. Diagnosis was made using the American Uveitis Society diagnostic criteria. Further questionnaires were sent at 2 weeks and 6 months to assess outcome and therapies., Results: 74 cases of ARN were reported by 58 consultants between March 2001 and March 2002. Questionnaires were returned for 49 cases (66.2%), of which 18 (36.7%) were excluded. Of the 31 cases included, 22 (71.0%) were male and 9 (29.0%) were female. The age range was 13 to 85 years (mean 54.3 years). 28 cases (90.3%) were unilateral, with 3 patients (9.7%) presenting with bilateral ARN. An aqueous or vitreous biopsy was performed in only 18 patients, with one patient having both. Herpes viral DNA analysis was performed on all 19 biopsies, with identification of the viral DNA in 16; results from 3 biopsies were not documented. Varicella zoster virus (VZV) was the commonest cause identified in 10 patients (56%). Of the 31 subjects, 27 (87.1%) were treated for ARN with systemic antiviral treatment: with intravenous antiviral in 23 cases (85.2%) and oral antiviral in 4 cases (14.8%). 21 of these patients went on to receive oral antiviral maintenance therapy. In addition to antiviral treatment, systemic steroids were given to 16 subjects (51.6%). Surgical intervention for retinal detachment was performed on 5 patients., Conclusions: During the 12-month study period, 31 cases of ARN met the diagnostic criteria set by the American Uveitis Society. The incidence in the UK based on this study is approximately 1 case per 1.6 to 2.0 million population per year. We have ascertained that the management of ARN throughout the UK is variable, suggesting that national guidelines would be of benefit.

Purpose: To present two patients with prior unilateral, herpetic keratitis who developed acute retinal necrosis (ARN) in the contralateral eye. These cases have noticeable similarities to the von Szily reaction. This describes the development of a contralateral retinitis subsequent to an anterior chamber injection of herpes simplex virus (HSV)., Design: Interventional case series., Methods: Retrospective chart and literature review., Results: The first patient had neonatally acquired herpetic keratitis and developed ARN at age 21. Polymerase chain reaction of a vitreous biopsy detected HSV type-2 (HSV-2). The second patient was clinically diagnosed with ARN contralateral to varicella zoster keratitis. A detailed literature search located seven prior case reports with a von Szily reaction. These resembled our two cases except none had HSV-2 or years of latency from keratitis to retinitis., Conclusions: Clinicians need to be cognizant of the von Szily reaction.

Herpes simplex virus infection is a frequent cause of intraocular inflammation or anterior uveitis. Ocular hypertension is a common feature in herpetic keratouveitis. We describe a fluid accumulation and flap displacement in late postoperative period (28 months) of LASIK associated with ocular hypertension caused by herpetic keratouveitis. This finding supports the theory that flap attachment after LASIK is only partial and the virtual space remains indefinitely. The presence of ocular hypertension may lead to corneal edema and fluid accumulation in the interface.

Purpose: To compare the efficacy of oral antiviral prophylactic treatment for herpes simplex virus (HSV) recurrences in patients with and without self-reported atopy., Design: Retrospective cohort comparative study., Methods: 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., Results: 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., Conclusion: Antiviral prophylaxis for HSV recurrences was more effective in reducing infections in atopics and less effective in reducing inflammatory episodes in atopics versus nonatopics.

Purpose: To compare the characteristics of ocular herpes simplex virus (HSV) in patients with and without atopy., Design: Retrospective cohort comparative study., Methods: Patients who presented at the Cornea Service, Wills Eye Hospital, between March 2003 and March 2004 who had been previously diagnosed in the same institution as having ocular HSV diagnosis or were just diagnosed as having the disease were asked to complete a study questionnaire that enabled categorization into atopic and nonatopic. In April 2005, 223 patients who agreed to be in the study had their charts reviewed, and 125 patients were excluded according to exclusion criteria: immunosuppression, follow-up less than one year, previous history of penetrating keratoplasty (PK) out of the Cornea Service, and no active HSV episode during follow-up., Main Outcome Measures: Incidence of all types of HSV recurrences., Secondary Outcome Measures: Bilaterality, visual loss, need for PK , and secondary bacterial infection in both groups. HSV episodes were classified into infectious, inflammatory, and mixed for analysis., Results: Ninety eight patients (110 eyes) were included in the study. Atopic/nonatopic (P value): the mean follow-up was 11.6 (+/- 10.6)/8.8 years (+/- 8.4) (P = .14); the mean incidence of HSV episodes per year of follow-up was: total episodes 0.32 (+/- 0.36)/0.28 (+/- 0.33) (P = .14), infectious 0.16 (+/- 0.22)/0.10 (+/- 0.14) (P < .01), inflammatory 0.11 (+/- 0.19)/0.11 (+/- 0.19) (P < .01), and mixed 0.09 (+/- 0.20)/0.07 (+/- 0.16) (P = .06); bilateral HSV was present in 9/3 patients (P = .22); the mean loss of vision was four lines of Snellen in both groups; PK was performed in 14 of 16 eyes (P = .45); secondary bacterial infection was present in two of four eyes (P = .26)., Conclusions: Atopic patients had considerably more infectious and fewer inflammatory episodes when compared with nonatopics.

Purpose: 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., Methods: 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., Results: None of the eyes developed reactivation of herpetic keratitis during follow-up., Conclusions: This study suggests that perioperative antiviral prophylaxis may protect the cornea from herpes simplex virus reactivation after LASIK.

A 76-year-old man presented with features of bilateral herpes simplex virus (HSV) keratitis. It was found to be recurrence of bilateral HSV keratitis following the use of Bimatoprost eye drops for uncontrolled intraocular pressure in a case of bilateral primary open-angle glaucoma.

Purpose: To record the natural history of herpes simplex keratitis and estimate visual impairment in eyes of patients diagnosed with herpes simplex keratitis., Materials: This was a retrospective, descriptive case study for five years of the eyes of patients with clinically diagnosed herpes simplex keratitis. These patients had presented to the cornea services and a cornea specialist carried out the ocular examination under slit-lamp magnification. The medical records were reviewed by the authors. Visual acuity at presentation and clinical details on examination were recorded and, diagnosis of the stage of disease given in the case record was noted. Statistical analysis was done using chi-square-test and Fisher exact test., Results: Of a total of 212 patients (220 eyes), there were 144 males and 68 females; 118 eyes presented with stromal lesions, 44 eyes with epithelial lesions, 39 eyes with epithelial and stromal lesions and 19 eyes with endothelitis. The improvement in visual acuity to more than 20/40 in the four clinical groups was 23 out of 44 eyes with epithelial lesion (52.27%), 83 out of the 118 eyes with stromal lesions (70.33%), 23 out of 39 eyes with epithelial and stromal lesions (58.97%) and 8 out of the 19 eyes with endothelitis (42.10%). The mean improvement in visual acuity was 3.44 lines (SD +/- 4.06)., Conclusion: Most patients had mild disease. The majority of the patients attained the final visual acuity of 6/12 or better in the affected eye. Thus, there was only a temporary visual morbidity with fairly good functional visual outcome in majority of the patients.

Objective: To evaluate the efficacy of multilayer amniotic membrane transplantation (AMT) combined with antivirus and corticosteroid drug to treat necrotizing herpes simplex stromal keratitis., Methods: 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)., Results: 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., Conclusion: Multilayer AMT combined with antivirus and corticosteroid treatment is an effective method to treat necrotizing herpes simplex stromal keratitis.

The last decade has seen herpes simplex virus (HSV)-induced stromal keratitis (SK) research shift from being a topic only of interest to vision researchers to one that fascinates the general field of inflammatory disease. Studies on experimental mouse lesions have uncovered several fundamental processes that explain lesion development. In this model, the chronic immuno-inflammatory lesions are mainly orchestrated by CD4+ T cells, but multiple early events occur that set the stage for the subsequent pathology. These include virus replication, the production of key cytokines and chemokines, neovascularization of the avascular cornea and the influx of certain inflammatory cell types. Many of these early events are subject to modulation, providing an approach to controlling this important cause of human blindness. We also comment on events ongoing during chronic SK, debating whether or not these represent virus-induced or autoimmune lesions.

Purpose: To evaluate anatomical and functional prognosis of urgent penetrating keratoplasty in perforated infectious corneal ulcers., Methods: Seven eyes of seven patients had an urgent penetrating keratoplasty for perforated infectious corneal ulcers. Anatomical success was defined by eradication of infection and preservation of eye from enucleation and phthisis bulbi. Corneal graft survival was defined by the presence of a clear graft., Results: The patients'mean age was 40.5 years. Four eyes had bacterial corneal ulcer and three eyes had herpetic corneal ulcer. Anatomical success was obtained in six eyes. The graft remained clear in two eyes. Graft rejection was noted in four eyes after a mean period of 4.5 months. Postoperative complications were ocular inflammation (one eye), ocular hypertension (three eyes), cataract (one eye), peripheral anterior synechiae (one1 eye), graft ectasia (one eye), bacterial infection (one eye) and recurrent herpetic keratitis (one eye). The mean follow-up period was 22 months, ranging from 9 to 32 months., Conclusion: Urgent penetrating keratoplasty can preserve eye integrity and eradication of the infectious process in a large part of perforated bacterial and herpetic corneal ulcers. Visual rehabilitation is often a secondary objective. Adapted antimicrobial treatment reduces graft reinfection and steroid treatment reduces the frequency of some complications, especially graft rejection.

Neurotrophic keratitis is a degenerative disease of the cornea caused by reduced corneal innervation. Trauma, tumors, inflammatory lesions and surgical procedures can damage the first branch of the trigeminal nerve on its entire course from brainstem to and within the cornea. Loss or reduction of corneal innervation leads to a reduced aqueous phase of the tear film and due to reduced supply with neurotransmitters/trophic factors also to reduced epithelial healing capacity (impaired mitosis and migration). Combined existence of tear film deficiency and impaired epithelial healing capacity predispose to persistent epithelial defects, corneal ulcers and perforation. Early diagnosis and adequate treatment may prevent this catastrophic chain of events.

In this study a novel flow cytometry based quantitative assay for measuring corneal angiogenesis is demonstrated. Corneas of Balb/c mice were lightly scarified and infected with 5 x 10(5), 5 x 10(4) and 5 x 10(3) pfu Herpes simplex virus 1 (HSV-1) RE virus. Development of corneal angiogenesis was studied on day 15 post infection by direct visualisation of infected cornea with a slit-lamp biomicroscope. Endothelial cells constituting the newly developed blood vessels in cornea were stained with murine anti CD31 antibody on frozen corneal sections and corneal whole mounts at day 15 post infection. Total number of endothelial cells was quantified at day 15 post infection by flow cytometry. Mice infected with different doses of HSV-1 RE developed severe to mild corneal angiogenesis at day 15 post infection. Endothelial cells constituting the newly formed blood vessels expressed CD31 at day 15 post infection. Flow cytometry revealed that, the number of CD31 positive cells isolated from diseased corneas increased with the increase in Neovascularisation index. The flow cytometry analysis used in this present study is a useful, accurate and cost effective method for quantifying corneal angiogenesis.

Ocular neovascularization often results in vision impairment. Frequently vascular endothelial cell growth factors (VEGFs) are mainly responsible for the pathological neovascularization as in the case in neovascularization induced by CpG oligodeoxynucleotides and herpes simplex virus infection in this report. siRNAs targeting either VEGFA, VEGFR1, VEGFR2, or a mix of the three were shown to significantly inhibit neovascularization induced by CpG when given locally or systemically. The efficacy of systemic administration was facilitated by the use of a polymer delivery vehicle. Additional experiments showed a significant inhibitory effect of the siRNAs mix when given either locally or systemically in vehicle against herpes simplex virus-induced angiogenesis as well as against lesions of stromal keratitis. These results indicate that the use of VEGF pathway-specific siRNAs represents a useful therapy against neovascularization-related eye diseases.

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.

Purpose: To evaluate whether use of particular topical hypotensive therapies is associated with ocular herpes simplex virus (OHSV)., Materials and Methods: This population-based, retrospective, cohort study used claims records from the Protocare Sciences managed care database (United States). Data were extracted from September 1, 1996 through June 30, 2002. An OHSV event was either a medical claim from the utilization database coded with an International Classification of Diseases Ninth Revision (ICD-9) code for OHSV (ICD-9 = 054.4, 054.40-054.44, 054.49) or a pharmacy claim for vidarabine or trifluridine ophthalmic solution., Results: A total of 93,869 eligible glaucoma patients, 21 different ocular hypotensive agents, and 192,840 agent-utilizing patient combinations were identified. In all, 411 patients had an OHSV event; 272 of 411 patients had at least 1 ocular hypotensive agent dispensed prior to the OHSV event but not preceding the event by less than 7 days. Of these, 219 had only 1 ocular hypotensive agent dispensed on the last fill date prior to the OHSV event, yielding an overall OHSV event rate of 0.11%. There was no significant association between OHSV event rates and agent use for either the set of 21 agents (P = 0.260; chi2) or when 14 products having < 5% usage were combined (P = 0.058). Prevalence rates were estimated as 161 per 100,000 population for 2000 to 2001 and 165 per 100,000 for 1999 to 2001., Conclusions: Ocular herpes simplex virus is extremely rare in patients treated with ocular hypotensive therapies, and its prevalence is similar to that found in the general population. The current analysis revealed no association between the use of particular topical ocular hypotensive therapies and OHSV.

Purpose: To describe the spectrum and recurrence of herpes simplex virus (HSV) keratitis in children and adolescents., Design: Retrospective cohort study., Methods: Twenty-three patients younger than age 16 years were diagnosed with HSV keratitis at one institution., Results: 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., Conclusion: Children with herpetic keratitis may have bilateral ocular involvement and are at risk for recurrent keratitis and amblyopia.

Purpose: To determine the specific immune responses involved in the exacerbation of corneal scarring induced by HSV-1 in gK vaccinated mice., Materials and Methods: BALB/c mice were vaccinated with HSV-1 glycoprotein K (gK) and ocularly challenged with HSV-1. Infiltration into the cornea of T cells and macrophages was monitored by immunocytochemistry, and the effect of depletion of CD4+ T-cells, CD8+ T-cells, or macrophages on corneal scarring was determined., Results: Following ocular challenge, CD4+ and CD8+ T-cells and macrophages were more abundant in the corneas of gK-vaccinated mice than in the corneas of mock vaccinated mice. Depletion of CD8+ T-cells, but not of CD4+ T-cells or macrophages, reduced the severity of corneal scarring in gK-vaccinated mice., Conclusions: We have shown that gK vaccination causes an overall increase in T cells and macrophages in the cornea after ocular HSV-1 challenge. The immunopathology induced by gK vaccination appears to be related to CD8+ T-cell activity, as depletion of these cells, but not other immune cells, reduced corneal scarring.