Herpetic Keratitis Research Articles

Epstein-Barr viral corneal stromal keratitis occurring during rheumatoid arthritis treatment: a case report

BackgroundA case of Epstein-Barr viral (EBV) corneal stromal keratitis during rheumatoid arthritis (RA) treatment is presented.Case presentationA 74-year-old female undergoing RA treatment was previously treated for bacterial corneal ulcer and herpetic keratitis and healed with antibiotic eye drops and topical anti-herpes ointment. At the first visit to our hospital, she presented with findings of monocular posterior interstitial keratitis with neovascularization mostly located in the inferior cornea with a corneal epithelial defect. The right eye showed no thinning of the corneal periphery and anterior uveitis. Her RA had subsided with oral steroid treatment, and infectious mononucleosis (IM) had not developed. EBV DNA could be detected in her corneal sample. After an extended but ineffective period to antibiotic treatment the corneal infiltrate responded rapidly to topical corticosteroids.ConclusionEBV can cause stromal keratitis without IM during treatment for RA.

Acyclovir-Resistant Herpes Simplex Virus 1 Keratitis: A Concerning and Emerging Clinical Challenge

To describe the clinical and virological profiles of patients with herpes simplex keratitis (HSK) caused by acyclovir-resistant (ACVR) strains of herpes simplex virus 1 (HSV-1). 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. This study evaluated 18 HSK patients (13 male and 5 female, aged 66.8 ± 4.7 years) with ACVR HSV-1-positive ocular samples. Genotypic resistance testing was performed because of frequent recurrences despite adequate antiviral prophylaxis (AVP) (n=13, 72%), or poor response to suppressive antiviral therapy (n=5, 28%). Resistance mutations were found in the TK (n=15, 83%) or in the DNA pol gene (n=3, 17%). Prior to the diagnosis of resistance, the duration of disease was 29.8 ± 20.4 years, with more than 10 HSK recurrences in 15 patients (83%). The number of recurrences between the first episode and the diagnosis of resistance was significantly lower in immunocompromised patients (n=6, 33%) than in immunocompetent patients (n=12; 67%) (11.5 ± 4.9 vs 16.4 ± 1.9, P=.05). 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.

Antiviral CD19+CD27+ Memory B Cells Are Associated with Protection from Recurrent Asymptomatic Ocular Herpesvirus Infection.

Reactivation of herpes simplex virus 1 (HSV-1) from latently infected neurons of the trigeminal ganglia (TG) leads to blinding recurrent herpetic disease in symptomatic (SYMP) individuals. Although the role of T cells in herpes immunity seen in asymptomatic (ASYMP) individuals is heavily explored, the role of B cells is less investigated. In the present study, we evaluated whether B cells are associated with protective immunity against recurrent ocular herpes. The frequencies of circulating HSV-specific memory B cells and of memory follicular helper T cells (CD4+ Tfh cells), which help B cells produce antibodies, were compared between HSV-1-infected SYMP and ASYMP individuals. The levels of IgG/IgA and neutralizing antibodies were compared in SYMP and ASYMP individuals. We found that (i) the ASYMP individuals had increased frequencies of HSV-specific CD19+CD27+ memory B cells, and (ii) high frequencies of HSV-specific switched IgG+CD19+CD27+ memory B cells detected in ASYMP individuals were directly proportional to high frequencies of CD45R0+CXCR5+CD4+ memory Tfh cells. However, no differences were detected in the level of HSV-specific IgG/IgA antibodies in SYMP and ASYMP individuals. Using the UV-B-induced HSV-1 reactivation mouse model, we found increased frequencies of HSV-specific antibody-secreting plasma HSV-1 gD+CD138+ B cells within the TG and circulation of ASYMP mice compared to those of SYMP mice. In contrast, no significant differences in the frequencies of B cells were found in the cornea, spleen, and bone-marrow. Our findings suggest that circulating antibody-producing HSV-specific memory B cells recruited locally to the TG may contribute to protection from symptomatic recurrent ocular herpes. IMPORTANCE Reactivation of herpes simplex virus 1 (HSV-1) from latently infected neurons of the trigeminal ganglia (TG) leads to blinding recurrent herpetic disease in symptomatic (SYMP) individuals. Although the role of T cells in herpes immunity against blinding recurrent herpetic disease is heavily explored, the role of B cells is less investigated. In the present study, we found that in both asymptomatic (ASYMP) individuals and ASYMP mice, there were increased frequencies of HSV-specific memory B cells that were directly proportional to high frequencies of memory Tfh cells. Moreover, following UV-B-induced reactivation, we found increased frequencies of HSV-specific antibody-secreting plasma B cells within the TG and circulation of ASYMP mice compared to those of SYMP mice. Our findings suggest that circulating antibody-producing HSV-specific memory B cells recruited locally to the TG may contribute to protection from recurrent ocular herpes.

Deep learning-based classification of infectious keratitis on slit-lamp images.

Infectious keratitis (IK) is an ocular emergency caused by a variety of microorganisms, including bacteria, fungi, viruses, and parasites. Culture-based methods were the gold standard for diagnosing IK, but difficult biopsy, delaying report, and low positive rate limited their clinical application. This study aims to construct a deep-learning-based auxiliary diagnostic model for early IK diagnosis. A retrospective study. IK patients with pathological diagnosis were enrolled and their slit-lamp photos were collected. Image augmentation, normalization, and histogram equalization were applied, and five image classification networks were implemented and compared. Model blending technique was used to combine the advantages of single model. The performance of combined model was validated by 10-fold cross-validation, receiver operating characteristic curves (ROC), confusion matrix, Gradient-wright class activation mapping (Grad-CAM) visualization, and t-distributed Stochastic Neighbor Embedding (t-SNE). Three experienced cornea specialists were invited and competed with the combined model on making clinical decisions. Overall, 4830 slit-lamp images were collected from patients diagnosed with IK between June 2010 and May 2021, including 1490 (30.8%) bacterial keratitis (BK), 1670 (34.6%) fungal keratitis (FK), 600 (12.4%) herpes simplex keratitis (HSK), and 1070 (22.2%) Acanthamoeba keratitis (AK). KeratitisNet, the combination of ResNext101_32x16d and DenseNet169, reached the highest accuracy 77.08%. The accuracy of KeratitisNet for diagnosing BK, FK, AK, and HSK was 70.27%, 77.71%, 83.81%, and 79.31%, and AUC was 0.86, 0.91, 0.96, and 0.98, respectively. KeratitisNet was mainly confused in distinguishing BK and FK. There were 20% of BK cases mispredicted into FK and 16% of FK cases mispredicted into BK. In diagnosing each type of IK, the accuracy of model was significantly higher than that of human ophthalmologists (p < 0.001). KeratitisNet demonstrates a good performance on clinical IK diagnosis and classification. Deep learning could provide an auxiliary diagnostic method to help clinicians suspect IK using different corneal manifestations.

Epithelial hypertrophy - an unusual representation of herpes simplex keratitis

Herpes simplex virus (HSV) keratitis is believed to be an important cause of infectious blindness, mainly resulting from stromal opacification. It has multiple manifestations with involvement of the individual layers of the cornea (epithelium, stroma, and endothelium). We report a rare presentation of HSV keratitis, a clinical representation that includes epithelial hypertrophy and subepithelial activity with the appearance of multiple fronds of vessels arising from superficial vascularization with infiltration, which reduced on administration of topical corticosteroids and systemic antivirals. Epithelial hypertrophy also regressed over time.

Superior orbital fissure syndrome secondary to ophthalmic herpes zoster: Case Report

Objective: The objective of this study is to report a case of superior orbital fissure syndrome (SOFS), secondary to ocular herpes zoster, with a favorable evolution.Materials and Methods: Herpes zoster ophthalmicus (HZO) usually presents with ocular manifestations, being infrequent with the ophthalmoplegia. SOFS secondary to HZO is rare. We present the case of a 72-year-old man with dermatome involvement of the first left trigeminal branch, secondary to herpes zoster infection, who also developed herpetic keratitis in the left eye. After 8 days of antiviral treatment, he developed total left eye ophthalmoplegia that required steroid treatment. The evolution of the ophthalmoplegia was favorable with resolution at 3 months of follow-up.Conclusions: It is essential to make known one of the complications of HZO infection, although not as frequent, just as important, is to recognize this pathology when it occurs for prompt management and recovery.

Anesthetic management of a patient with erythema multiforme for emergency appendectomy

Erythema multiforme (EM) is an acute, immune-mediated, mucocutaneous disease, caused by several factors such as infections, drugs, malignancy, autoimmune disease, radiation, and immunization. The anesthetic concerns in these patients include possibility of difficult airway, intraoperative steroid supplementation, avoidance of precipitating drugs, intraoperative arrhythmias, perioperative skin, and eye care. A 13-year-old boy, a known case of EM with a history of recurrent ocular herpes and impaired vision along with fibrosis at the bilateral angle of the mouth underwent emergency open appendectomy under spinal anesthesia. Spinal anesthesia with injection hyperbaric bupivacaine (0.5%) is a safe and suitable alternative in a patient with EM with recurrent herpes simplex virus.

Herpes simplex virus conjunctival dendritic ulcer as a primary infection in an immunocompetent patient

AbstractPurposeTo describe an atypical case of conjunctival herpetic dendritic ulceration in an immunocompetent patient with no history of herpetic primary infection.MethodsThis is a single observational case report and a review of the literature. The patient was followed in successive appointments.ResultsOcular involvement by the herpes simplex virus (HSV) in its recurrent form is characteristic for dendritic ulcers in the corneal epithelium, which are postulated to obtain this form due to the corneal nerve plexus. We describe the first case to date of an immunocompetent patient, age &gt; 70 years and without prior immunosuppressive treatment, with a primary herpetic infection clinically diagnosed by presenting a dendritic ulcer in the bulbar conjunctiva. The patient had nonspecific corneal involvement, and the case was subsequently confirmed with polymerase chain reaction for HSV‐1.ConclusionsThe presentation of a dendritic ulcer in the bulbar conjunctiva in a case of ocular herpes infection is a rare finding, and the physiopathology is unknown. It casts doubt on the theory that corneal dendritic ulcer morphology is only formed because of the corneal sub‐basal nerve plexus involvement. This suggests that conjunctiva examination is of vital importance in herpetic ocular infection, and that it can used a diagnostic methodology if no other eye conditions are found.

Adenovirus-mediated RNA interference against herpes simplex virus infection in vitro.

Herpetic keratitis caused by the herpes simplex virus (HSV) is the most common form of ocular herpes that causes corneal blindness. Although treatments for herpes keratitis have improved in recent years. there is still considerable room for new treatments against viral infection that shows great promise. The aim of the study was to evaluate the effect of RNA interference on HSV Type 1 (HSV1) infection in vitro, first prophylactically then therapeutically. The highly conserved glycoproteins D (gD) and E (gE) were chosen as targets for this study. Different small interfering RNA (siRNA) duplexes that target gD and gE were designed and chemically synthesized. The recombinant adenovirus type 5 was developed and used as the vehicle with which we delivered the siRNA into the Vero cells infected with the HSV1 KOS strain. Evaluation of the efficacy of siRNA-mediated inhibition was performed either before virus inoculation (prophylactically) or after virus inoculation at the first appearance of lesions (therapeutically). The expression of messenger RNA encoding gD and gE was detected using a real-time polymerase chain reaction (qPCR). We analyzed HSV replication in Vero cells, cytotoxicity of HSV, and cell viability. When used prophylactically, the siRNA-targeting gD and gE created a more marked decrease in viral titer than when used therapeutically. The transfection of cells with recombinant adenovirus containing the siRNA expression cassette was associated with very low cytotoxicity. Adenovirus-mediated siRNA-targeting gD and gE genes effectively inhibit the replication of the HSV in Vero cells. In addition, these findings indicate that the prophylactic use of siRNA is far more effective at inhibiting HSV replication than the therapeutic use.

Uveitis and Other Ocular Complications Following COVID-19 Vaccination.

Coronavirus disease 2019 (COVID-19) vaccines can cause transient local and systemic post-vaccination reactions. The aim of this study was to report uveitis and other ocular complications following COVID-19 vaccination. The study included 42 eyes of 34 patients (20 females, 14 males), with a mean age of 49.8 years (range 18–83 years). The cases reported were three herpetic keratitis, two anterior scleritis, five anterior uveitis (AU), three toxoplasma retinochoroiditis, two Vogt-Koyanagi-Harada (VKH) disease reactivations, two pars planitis, two retinal vasculitis, one bilateral panuveitis in new-onset Behçet’s disease, three multiple evanescent white dot syndromes (MEWDS), one acute macular neuroretinopathy (AMN), five retinal vein occlusions (RVO), one non-arteritic ischemic optic neuropathy (NAION), three activations of quiescent choroidal neovascularization (CNV) secondary to myopia or uveitis, and one central serous chorioretinopathy (CSCR). Mean time between vaccination and ocular complication onset was 9.4 days (range 1–30 days). Twenty-three cases occurred after Pfizer-BioNTech vaccination (BNT162b2 mRNA), 7 after Oxford-AstraZeneca vaccine (ChAdOx1 nCoV-19), 3 after ModernaTX vaccination (mRNA-1273), and 1 after Janssen Johnson & Johnson vaccine (Ad26.COV2). Uveitis and other ocular complications may develop after the administration of COVID-19 vaccine.

Ocular and Facial Herpes Zoster and Meningitis in an Adult after Zoster Vaccination

Purpose: To report a case of ocular and facial herpes zoster and meningitis after herpes zoster vaccination.Case summary: A 60-year-old man was administered Zostavax® on his left arm; he developed a vesicular rash over his left eye and forehead 4 days afterwards. He started antiviral drugs for the rash, and visited the hospital for severe headache and spread of the rash to involve the tip of his nose, face, and palate by day 7. He was taking Synthyroid® (Bukwang Pharmaceuticals, Seoul, Korea) since his thyroidectomy for thyroid cancer 6 years ago. He had never been diagnosed with chickenpox, but had an episode of red facial rash in childhood. Slit-lamp examination revealed conjunctival chemosis, hyperemia, and a pseudodendrite in the peripheral cornea. The anterior chamber was quiet, and there were no significant findings on his brain magnetic resonance imaging. Varicella zoster virus was detected in the cerebrospinal fluid by polymerase chain reaction. The patient was treated with oral acyclovir drugs and topical ganciclovir, levofloxacin, and bromfenac. One week later, the pseudodendrite disappeared and conjunctival chemosis improved. There was no recurrence during 6 months follow-up.Conclusions: Reactivation of ocular or facial herpes zoster or meningitis after zoster vaccination may occur, rarely. Immediate antiviral treatment is required in these cases.

Офтальмологические проявления герпесвирусной инфекции у собак

This article describes the main aspects of the epizootology and pathogenesis of Cahv-1 (canine herpesvirus), also, the clinical forms of manifestations of pathology in dogs of different ages and physiological status are described. Particular attention is paid to ocular pathologies developing at Cahv-1, such as herpetic conjunctivitis, blepharitis, ulcerative and stromal keratitis. The features of the diagnosis and differentiation of these pathologies are described. The systematic and local medicines used by us in the practice of treating dogs with herpetic eye, the principles and algorithms of their prescription are presented. The difficulties of diagnostics Cahv-1 are described, and the reasons for frequent false-negative results during PCR explained in the article. Besides additional laboratory verification methods for Cahv-1 as well as methods of prevention of herpetic infection of dogs are indicated.

Herpetic Keratitis Recurred after the Use of a Thermal Medical Device: A Case Report

Herpetic Keratitis Recurred after the Use of a Thermal Medical Device: A Case Report

Outcome of Lamellar Graft Patching for the Treatment of Noninfectious Corneal Perforations.

The aims of this study were to evaluate the clinical outcome of lamellar graft patching used for treating noninfectious corneal perforations and to determine the clinical factors affecting tectonic integrity. This retrospective study includes a total of 71 eyes of 67 patients who underwent lamellar graft patching for the treatment of corneal perforations due to persistent epithelial defects secondary to limbal stem cell deficiency (LSCD, 21 eyes; 29.6%), peripheral ulcerative keratitis (17 eyes; 23.9%), neurotrophic keratitis due to herpes simplex keratitis (HSK, 14 eyes; 19.7%), and other causes (19 eyes; 26.8%). We evaluated the tectonic integrity of the globe, visual outcomes, and postoperative complications. Tectonic integrity was achieved in 53 eyes (74.6%). The survival proportions of eyes that achieved clear grafts were 77.8% and 65.2% at 12 and 24 months, respectively. Graft failure was observed in 19 eyes (26.8%). The survival rate of tectonic integrity and eyes that finally achieved a clear graft was significantly worse in eyes with LSCD compared with those without ( P < 0.001). The logarithm of minimal angle resolution improved significantly from 1.79 ± 0.98 to 1.22 ± 0.87 at 12 months and 1.08 ± 0.81 at 24 months. Postoperative complications included cataract formation (32 eyes, 45.1%), intraocular pressure rise (23 eyes, 32.4%), recurrent perforations (15 eyes, 21.1%), infectious keratitis (14 eyes, 19.7%), recurrence of herpes simplex keratitis (7 eyes, 9.9%), and traumatic graft dehiscence (1 eye, 1.4%). Lamellar graft patching is an effective and safe surgical treatment for noninfectious corneal perforations; however, careful attention to severe complications is necessary, especially in eyes with LSCD.

Intramuscular Vaccination With the HSV-1(VC2) Live-Attenuated Vaccine Strain Confers Protection Against Viral Ocular Immunopathogenesis Associated With γδT Cell Intracorneal Infiltration.

Herpes simplex virus type-1 (HSV-1) ocular infection is one of the leading causes of infectious blindness in developed countries. The resultant herpetic keratitis (HK) is caused by an exacerbated reaction of the adaptive immune response that persists beyond virus clearance causing substantial damage to the cornea. Intramuscular immunization of mice with the HSV-1(VC2) live-attenuated vaccine strain has been shown to protect mice against lethal ocular challenge. Herein, we show that following ocular challenge, VC2 vaccinated animals control ocular immunopathogenesis in the absence of neutralizing antibodies on ocular surfaces. Ocular protection is associated with enhanced intracorneal infiltration of γδ T cells compared to mock-vaccinated animals. The observed γδ T cellular infiltration was inversely proportional to the infiltration of neutrophils, the latter associated with exacerbated tissue damage. Inhibition of T cell migration into ocular tissues by the S1P receptors agonist FTY720 produced significant ocular disease in vaccinated mice and marked increase in neutrophil infiltration. These results indicate that ocular challenge of mice immunized with the VC2 vaccine induce a unique ocular mucosal response that leads into the infiltration of γδ T cells resulting in the amelioration of infection-associated immunopathogenesis.

The Durability of Vaccine Efficacy against Ocular HSV-1 Infection Using ICP0 Mutants 0∆NLS and 0∆RING Is Lost over Time.

Vaccines to viral pathogens in experimental animal models are often deemed successful if immunization enhances resistance of the host to virus challenge as measured by cumulative survival, reduction in virus replication and spread and/or lessen or eliminate overt tissue pathology. Furthermore, the duration of the protective response against challenge is another important consideration that drives a vaccination regimen. In the current study, we assessed the durability of two related vaccines, 0∆NLS and 0∆RING, against ocular herpes simplex virus type 1 (HSV-1) challenge in mice thirty days (short-term) and one year (long-term) following the vaccine boost. The short-term vaccine efficacy study found the 0∆RING vaccine to be nearly equivalent to the 0∆NLS vaccine in comparison to vehicle-vaccinated mice in terms of controlling virus replication and preserving the visual axis. By comparison, the long-term assessment of the two vaccines found notable differences and less efficacy overall as noted below. Specifically, the results show that in comparison to vehicle-vaccinated mice, the 0∆NLS and 0∆RING vaccinated groups were more resistant in terms of survival and virus shedding following ocular challenge. Moreover, 0∆NLS vaccinated mice also possessed significantly less infectious virus in the peripheral and central nervous systems but not the cornea compared to mice vaccinated with vehicle or 0∆RING which had similar levels. However, all vaccinated groups showed similar levels of blood and lymphatic vessel genesis into the central cornea 30 days post infection. Likewise, corneal opacity was also similar among all groups of vaccinated mice following infection. Functionally, the blink response and visual acuity were 25–50% lower in vaccinated mice 30 days post infection compared to measurements taken prior to infection. The results demonstrate a dichotomy between resistance to infection and functional performance of the visual axis that collectively show an overall loss in vaccine efficacy long-term in comparison to short-term studies in a conventional prime-boost protocol.

BX795-Organic Acid Coevaporates: Evaluation of Solid-State Characteristics, In Vitro Cytocompatibility and In Vitro Activity against HSV-1 and HSV-2.

BX795 is a TANK binding kinase-1 inhibitor that has shown excellent therapeutic activity in murine models of genital and ocular herpes infections on topical delivery. Currently, only the BX795 free base and its hydrochloride salt are available commercially. Here, we evaluate the ability of various organic acids suitable for vaginal and/or ocular delivery to form BX795 salts/cocrystals/co-amorphous systems with the aim of facilitating pharmaceutical development of BX795. We characterized BX795-organic acid coevaporates using powder X-ray diffractometry, Fourier-transform infrared spectroscopy (FT-IR), Raman spectroscopy, 1H-nuclear magnetic resonance spectroscopy, thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) to elucidate the interaction between BX795 and various organic acids such as taurine, maleic acid, fumaric acid, tartaric acid, and citric acid. Furthermore, using human corneal epithelial cells and HeLa cells, we evaluated BX795-organic acid coevaporates for in vitro cytocompatibility and in vitro antiviral activity against herpes simplex virus-type 1 (HSV-1) and type-2 (HSV-2). Our studies indicate that BX795 forms co-amorphous systems with tartaric acid and citric acid. Interestingly, the association of organic acids with BX795 improved its thermal stability. Our in vitro cytocompatibility and in vitro antiviral studies to screen suitable BX795-organic acid coevaporates for further development show that all BX795-organic acid systems, at a concentration equivalent to 10 µM BX795, retained antiviral activity against HSV-1 and HSV-2 but showed differential cytocompatibility. Further, dose-dependent in vitro cytocompatibility and antiviral activity studies on the BX795-fumaric acid system, BX795-tartaric acid co-amorphous system, and BX795-citric acid co-amorphous system show similar antiviral activity against HSV-1 and HSV-2 compared to BX795, whereas only the BX795-citric acid co-amorphous system showed higher in vitro cytocompatibility compared to BX795.

Anti-glaucoma agents-induced pseudodendritic keratitis presumed to be herpetic simplex keratitis: a clinical case series

Anti-glaucoma agents-induced corneal toxicity may be misdiagnosed as herpetic simplex keratitis (HSK). In our study, nineteen glaucoma patients were presumed to have HSK before referral. Corneal lesions were classified into (I) linear pseudodendritic lesions formed by elevated opacified cells, (II) linear pseudodendritic lesions formed by grouped superficial punctate keratitis (SPK), (III) satellite full-thickness epithelial defects, (IV) satellite lesions formed by elevated opacified cells, and (V) geographic lesions formed by grouped SPK. We observed thirty-one events, with 15 in the lower and 16 in the central corneas. There were 21 (67.7%) type II, five (16.1%) type V, two (6.5%) of each for types III and IV, and one (3.2%) type I events. Among linear lesions (types I and II), 17 (77.3%) had horizontal and 5 (22.7%) had curvilinear orientations. Exposure duration to the last-added anti-glaucoma agent was three days to 14.5 years. About half of the events (16/31, 51.6%) used prostaglandin analogues, and 30/31 (96.8%) applied benzalkonium chloride (BAK)-containing agents. All lesions resolved within two months after decreasing offending medications or enhancing protection of ocular surface. In conclusion, anti-glaucoma agents-induced pseudodendritic keratitis presents majorly in central-lower cornea as horizontally linear lesions, and BAK-containing agents are observed in the most events.

In vivo confocal microscopic features of naturally acquired canine herpesvirus-1 and feline herpesvirus-1 dendritic and punctate ulcerative keratitis.

To describe the in vivo confocal microscopy (IVCM) features of the corneal epithelium and stroma in dogs and cats with herpetic dendritic ulcerative keratitis. 6 client-owned dogs and 10 client-owned cats with herpetic dendritic ulcerative keratitis (affected group) and 10 dogs and 10 cats from specific-pathogen-free laboratory colonies (nonaffected group). After complete ophthalmic examination, IVCM corneal examination was performed on the clinically diseased eyes of animals in the affected group and on both eyes of animals in the nonaffected group. Results by species were compared between groups. In the affected group, all 6 dogs had unilateral ocular lesions (total, 6 eyes examined), whereas 7 cats had unilateral lesions and 3 cats had bilateral lesions (total, 13 eyes examined). For the nonaffected group, 20 cat eyes and 20 dog eyes were examined. Corneal epithelial morphological abnormalities were identified in all examined eyes of animals in the affected group and in no examined eyes of the nonaffected group. Hyperreflective punctate opacities and inflammatory cells were present in all epithelial layers in examined eyes of affected animals but were absent in nonaffected animals. Similarly, Langerhans cells and anterior stromal dendritic cells were identified in corneas of eyes examined for animals in the affected group but not in any eye of animals in the nonaffected group. Stromal changes were less consistent in the affected group, but absent in the nonaffected group. Results indicated that herpetic dendritic ulcerative keratitis in dogs and cats is associated with microanatomic corneal abnormalities that can be detected by IVCM.

Anti-viral activity of Staphylococcus aureus lysates against herpes simplex virus type-I infection: an in vitro and in vivo study.

To investigate the effect of Staphylococcus aureus (S. aures) lysates (SALs) on herpes simplex virus type-I (HSV1) infection in human corneal epithelial (HCE) cells and in a mouse model of HSV1 keratitis. HCE, Vero, HeLa, and BV2 cells were infected with HSV1 [HSV1 f strain, HSV1f; HSV-1-H129 with green fluorescent protein (GFP) knock-in, HSV1g]. Pre- or post-infection, SAL at various concentrations was added to the culture medium for 24h. GFP fluorescence in HSV1g or plaque formation by HSV1f were examined. The effects of heat-treated SAL, precooled acetone-precipitated SAL, and SAL subjected to ultrafiltration (100 kDa) were evaluated. The effects of other bacterial components and lysates on HSV1 infection were also tested, including lipoteichoic acid (LTA), peptidoglycan (PGN), staphylococcal protein A (SPA), and α-hemolysin from S. aureus (α-toxin) as well as lysates from a wild-type S. aureus strain, S. epidermidis, and Escherichia coli (W-SAL, SEL, and ECL, respectively). In addition, SAL eye drops were applied topically to BALB/c mice with HSV1 keratitis, followed by in vivo observations. The cytopathic effect, plaque formation (HSV1f), and GFP expression (HSV1g) in infected cells were inhibited by SAL in a dose-dependent manner. The active component of SAL (≥100 kDa) was heat-sensitive and retained activity after acetone precipitation. In HSV1g-infected cells, treatment with LTA-sa, α-toxin, PGN-sa, or SPA did not inhibit GFP expression. SAL, W-SAL, and SEL (but not ECL) decreased GFP expression. In mice with HSV1 keratitis, SAL reduced corneal lesions by 71%. The results of this study demonstrate that SAL can be used to inhibit HSV1 infection, particularly keratitis. Further studies are needed to determine the active components and mechanism underlying the effects of SAL.