The Topical Novel Formulations of Interferon α-2в Effectively Inhibit HSV-1 Keratitis in the Rabbit Eye Model and HSV-2 Genital Herpes in Mice.

Herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are widespread human pathogens that establish chronic latent infections leading to recurrent episodes. Current treatments are limited, necessitating the development of novel antiviral strategies. This study aimed to assess the antiviral efficacy of novel topical formulations containing interferon alpha-2b (IFN α-2b) against HSV-1 and HSV-2. The formulations, Oftalmoferon® forte (eye drops) and Interferon Vaginal Tablets, demonstrated potent antiviral effects against HSV-1 and HSV-2 in Vero cells, respectively, with concentration-dependent inhibition of viral replication. Subsequently, their efficacy was tested in animal models: HSV-1 keratitis in the rabbit eye model and HSV-2 genital herpes in mice. Oftalmoferon® forte effectively treated HSV-1 keratitis, reducing clinical symptoms and ulcerations compared to virus control. Interferon Vaginal Tablets showed promising results in controlling HSV-2 genital herpes in mice, improving survival rates, reducing clinical signs, weight loss and viral replication. The novel IFN α-2b formulations exhibited significant antiviral activity against HSV infections in cell culture and animal models. These findings suggest the potential of these formulations as alternative treatments for HSV infections, particularly in cases resistant to current therapies. Further studies are warranted to optimize treatment regimens and assess clinical efficacy in humans.

Keratic Precipitates: An Overlooked Sign of Microsporidial Stromal Keratitis?

PURPOSE: To elucidate a distinctive clinical feature in cases of microsporidial stromal keratitis (MSK). METHOD: A retrospective observational study of cases with a histopathological and/or microbiological diagnosis of MSK on corneal biopsy or host corneal button between 2016 and 2022 was conducted. RESULTS: Eighteen cases with a confirmed histopathological and/or microbiological diagnosis of MSK were detected. Careful review of slit-lamp photographs revealed the presence of pigmented keratic precipitates (KPs) beyond the area of stromal keratitis in five out of eighteen cases (27.7%). CONCLUSION: The presence of pigmented KPs beyond the area of lesion can alert the clinician to keep microsporidia as a differential cause for stromal keratitis. Management can be tailored accordingly for a better outcome.

Three-dimensional in vivo evaluation of the cornea in patients with unilateral posterior interstitial keratitis.

Purpose: The purpose of this study was to investigate the in vivo morphologic features of the cornea in patients with unilateral posterior interstitial keratitis. Methods: Seven eyes of 7 patients with unilateral posterior interstitial keratitis were examined by slit-lamp biomicroscopy, anterior segment optical coherence tomography (AS-OCT), and in vivo confocal microscopy (IVCM). The imaging features of the cornea were evaluated and analyzed. Results: By slit-lamp examination, the posterior corneal stromal opacities were observed in all 7 eyes, and deep neovascularization in 4 eyes. The posterior stromal opacities showed higher reflectivity with an intact overlying epithelium by AS-OCT and did not invade the Bowman's layer in all cases. IVCM revealed highly reflective dispersed microdots, needle-shaped bodies, and increased reflectivity of keratocytes in the lesion site in all patients. Active Langerhans cells and an attenuated subbasal nerve plexus were observed in 5 eyes. After treatment, the active Langerhans cells disappeared; however, highly reflective microdots and needle-shaped bodies remained. Conclusion: The three-dimensional evaluation of slit-lamp biomicroscopy, AS-OCT, and IVCM may help in the early diagnosis of patients with posterior interstitial keratitis.

In vivo CRISPR gene editing in patients with herpetic stromal keratitis.

In vivo CRISPR gene therapy holds large clinical potential, but the safety and efficacy remain largely unknown. Here, we injected a single dose of herpes simplex virus 1 (HSV-1)-targeting CRISPR formulation in the cornea of three patients with severe refractory herpetic stromal keratitis (HSK) during corneal transplantation. Our study is an investigator-initiated, open-label, single-arm, non-randomized interventional trial at a single center (NCT04560790). We found neither detectable CRISPR-induced off-target cleavages by GUIDE-seq nor systemic adverse events for 18 months on average in all three patients. The HSV-1 remained undetectable during the study. Our preliminary clinical results suggest that in vivo gene editing targeting the HSV-1 genome holds acceptable safety as a potential therapy for HSK.

Atypical Presentation of Herpes Stromal Keratitis in a Contact Lens Wearer.

This article describes the case of a 21-year-old female habitual contact lens wearer who complained of left eye pain, redness, and decreased vision for one week. When a ring-shaped corneal infiltration indicative of an Acanthamoeba infection was discovered, standard anti-amoebic topical therapy with polyhexamethylene biguanide and chlorhexidine was commenced. However, her keratitis worsened. At the same time, corneal scraping revealed no pathogens. An anterior chamber examination revealed a loss of corneal sensation, and a positive herpes simplex virus (HSV) immunoglobulin G serology test indicated HSV keratitis. She was eventually treated with oral anti-viral medication and recovered completely. Her case was unusual, as she had a history of contact lens use, painful corneal ulceration, and the development of Acanthamoeba keratitis-like corneal ring infiltration. This case also reinforces the various manifestations of HSV keratitis, which lead to delayed diagnosis and treatment.

Microsporidial Stromal Keratitis in Post-Keratoplasty Eyes.

PURPOSE: The purpose of this paper is to report the clinical manifestations, diagnostic evaluation, management and outcomes of microsporidial keratitis in post-keratoplasty eyes. METHODS: This is a retrospective review of three patients diagnosed with microsporidial stromal keratitis in post-keratoplasty eyes between January 2012 and December 2021 at a tertiary referral center (Ospedali Privati Forlì "Villa Igea", Forlì, Italy). RESULTS: All patients presented with fine multifocal granular infiltrates following keratoplasty for a presumed herpetic keratitis. No microorganisms were isolated from the corneal scrapings and no clinical response was observed with broad-spectrum antimicrobial therapy. In all cases, confocal microscopy demonstrated spore-like structures. The histopathologic examination of the excised corneal buttons confirmed the diagnosis of microsporidial stromal keratitis. Following therapeutic keratoplasty and treatment with an initial high dose and extended taper of topical fumagillin, clinical resolution was achieved in all eyes. The Snellen visual acuities at the final follow-up were 20/50, 20/63 and 20/32. CONCLUSIONS: Prior to definitive surgery, confocal microscopy can be employed for the in vivo detection of pathogenic microorganisms such as Microsporidium. In post-keratoplasty eyes, therapeutic keratoplasty and an initial high dose of topical fumagillin with extended taper can allow the resolution of microsporidial stromal keratitis with a satisfactory visual prognosis.

Trachipleistophora hominis: molecular characterization of a rare pathogen causing microsporidial stromal keratitis.

The authors report the clinical and microbiological findings of a unique case of stromal keratitis caused by a rare microsporidium, Trachipleistophora hominis. This case of stromal keratitis was in a 49-year-old male with a history of COVID-19 infection and diabetes mellitus. Corneal scraping specimens revealed numerous microsporidia spores upon microscopic examination. PCR of the corneal button revealed the presence of T. hominis infection, which could be controlled by penetrating keratoplasty surgery. The graft was clear with no recurrence of infection until the last follow-up 6 weeks postsurgery. This is the first case of human stromal keratitis caused by this organism in a post-COVID infection, confirmed by molecular diagnosis.

Antiviral and Anti-Inflammatory Therapeutic Interventions for Treating Herpes Stromal Keratitis: A Systematic Review.

PURPOSE: Herpes stromal keratitis (HSK) is an immune-mediated corneal inflammation that occurs after a herpes simplex virus infection. This paper aims to systematically identify and compare interventions for treating HSK and their patient outcomes. METHODS: This systematic review followed the PRISMA methodology. Online databases were searched to obtain all relevant papers. Two independent reviewers screened through 168 records. Seven papers were included and used for data extraction. A qualitative analysis was conducted. RESULTS: HSK patients receiving prednisolone phosphate and acyclovir showed a higher treatment success rate and significantly longer time to failure compared to patients receiving only acyclovir (P < .001). No difference in resolution time was found between oral and topical acyclovir. Between groups receiving dexamethasone and flurbiprofen, resolution occurred in 93% and 67% of patients, and BCVA (LogMAR) improved from 1.0 to 0.30 and 0.48, respectively. BCVA improved in both cyclosporine-A (P < .001) and its control (prednisolone) groups (P = .002). A tacrolimus treatment group showed greater improvement in BCVA compared to its control (prednisolone) group (P < .001). CONCLUSION: Corticosteroids and antivirals managed HSK most effectively only when used concurrently. Oral acyclovir showed similar effectiveness to its ointment counterpart, a preferable alternative for easier administration. Corticosteroid use could induce greater therapeutic benefits when tapered in concentration and frequency and administrated for at least 10 weeks. Anti-inflammatory drugs including flurbiprofen, cyclosporine-A, and tacrolimus could be safe and effective for treating HSK. Future long-term follow-up and RCTs could provide insights on the therapeutic benefits of these potential alternatives.

A Rare Microsporidial Infection in Lamellar Corneal Tissue, following Transepithelial Photorefractive Keratectomy.

The aim of this study was to report a unique case of microsporidial keratitis over deep anterior lamellar keratoplasty after transepithelial photorefractive keratectomy surgery that was successfully treated with therapeutic lamellar keratoplasty without recurrence at King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia. The patient presented with recurrent attacks of eye pain, redness, photophobia, and decreased vision. The patient was initially treated as a case of presumed herpetic keratouveitis using antiviral medication and topical steroids with partial improvement. During the last episode, the condition deteriorated and patient underwent therapeutic lamellar keratoplasty. Histopathology indicated an infected graft with evidence of microsporidial infection. The patient was discharged with complete corneal epithelial healing and no signs of recurrence during follow-up. Microsporidial infection is a rare cause of stromal keratitis that affects both immunocompetent and immunosuppressed patients. Microsporidia should be suspected after surface ablation refractive surgery if the patient presents with recurrent symptoms of keratoconjunctivitis or stromal keratitis that are partially responsive to topical steroid therapy.

Delayed-onset pressure-induced interlamellar stromal keratitis (PISK) and interface epithelial ingrowth 10 years after laser-assisted in situ keratomileusis.

Purpose: To report a case of pressure-induced interlamellar stromal keratitis (PISK) 10 years after laser assisted in situ keratomileusis (LASIK). Observations: A case of a 36-year-old man who underwent LASIK and presented with PISK 10 years later. Before presenting to our department he consulted elsewhere for red eye, decreased visual acuity, foreign body sensation, and pain on the RE for 1 week. He was then prescribed topical prednisolone six times per day and was lost to follow-up. On examination and after 1 month of continuous use of steroids uncorrected distance visual acuity (UCDV) was 20/400 in the right eye (RE) and 20/20 in the left eye (LE). Best corrected visual acuity was 20/80 on the RE. The Goldmann intraocular pressure (IOP) was 26 and 17 mmHg in the RE and LE, respectively. Slit lamp biomicroscopy revealed fluid in the interface and epithelial ingrowth. Fundoscopic examination results were normal in both eyes. Treatment was initiated with topical brimonidine tartrate 0.2%, timolol 0.5%, and dorzolamide 2.0% BID. Once the pressure was controlled the patient was scheduled for mechanical debridement of the epithelial ingrowth with significant improvement of UCVA (20/25). Conclusions: Refractive surgeons should be aware of PISK as a potential complication of LASIK even years after the procedure. Intraocular pressure can be misleading, and diligent and careful examination are key to diagnosis and treatment of this potentially blinding complication.

The atypical chemokine receptor-2 fine-tunes the immune response in herpes stromal keratitis.

Herpes stromal keratitis (HSK) is a blinding corneal disease caused by herpes simplex virus-1 (HSV-1), a common pathogen infecting most of the world's population. Inflammation in HSK is chemokine-dependent, particularly CXCL10 and less so the CC chemokines. The atypical chemokine receptor-2 (ACKR2) is a decoy receptor predominantly for pro-inflammatory CC chemokines, which regulates the inflammatory response by scavenging inflammatory chemokines thereby modulating leukocyte infiltration. Deletion of ACKR2 exacerbates and delays the resolution of the inflammatory response in most models. ACKR2 also regulates lymphangiogenesis and mammary duct development through the recruitment of tissue-remodeling macrophages. Here, we demonstrate a dose-dependent upregulation of ACKR2 during corneal HSV-1 infection. At an HSV inoculum dose of 5.4 x 105 pfu, but not at higher dose, ACKR2 deficient mice showed prolonged clinical signs of HSK, increased infiltration of leukocytes and persistent corneal neovascularization. Viral clearance and T cell activation were similar in ACKR2-/- and wild type mice, despite a transient diminished expression of CD40 and CD86 in dendritic cells. The data suggest that ACKR2 fine-tunes the inflammatory response and the level of neovascularization in the HSK.

Case report: Visual acuity loss as a warning sign of ocular syphilis: A retrospective analysis of 17 cases.

Objectives: To define the clinical features of ocular syphilis and analyze the cerebrospinal fluid (CSF) of ocular syphilis patients to determine the co-occurrence of neurosyphilis. Methods: This was a retrospective study of 17 patients (23 eyes) with ocular syphilis admitted to the Fifth People's Hospital, Suzhou, China from September 2017 to December 2021. Clinical manifestations, laboratory tests, treatment, and clinical outcomes were analyzed, and a review was conducted. Results: Eight males (12 eyes) and nine females (11 eyes) were enrolled. Mean patient age was 49.06 ± 3.47 years. The total manifestation time for ocular symptoms ranged from 10 days to 6 years. The cohort was comprised of three cases of early syphilis, four cases of late syphilis, and ten cases of unknown stage. The primary complaints were decreased visual acuity in 15 cases (21 eyes), ptosis in 1 case (1 eye), and loss of light perception in 1 case (1 eye). Cases were diagnosed as chorioretinitis in 7 cases (8 eyes), optic nerve retinitis in 4 cases (6 eyes), optic neuritis in 4 cases (7 eyes), and oculomotor nerve palsy in 1 case (1 eye), syphilitic stromal keratitis in 1 case (1 eye). Serum HIV antibody was positive in one case(Nos.2). All patients had reactive serum Treponema Pallidum Particle Agglutination (TPPA) and Toluidine Red Unheated Serum Test (TRUST). All patients underwent CSF examination. CSF white blood cell count was ≥5 × 106/L in 13 cases, CSF protein was >500 mg/L in 6 cases, TPPA was reactive in 15 cases, and TRUST was reactive in 5 cases. Eleven cases were also diagnosed with neurosyphilis. Patients were treated with either penicillin G sodium or ceftriaxone sodium. At time of discharge, 12 patients reported improved visual acuity. Abnormal serum or CSF examination improved in ten patients during the 6-12 month follow-up. Conclusion: Visual acuity loss is a warning indicator of ocular syphilis. Ocular syphilis primarily manifests as posterior uveitis, involving the choroid, retina, and optic nerve, and often co-occurs with neurosyphilis. Effective treatment should be administered immediately to avoid irreversible visual impairment and other serious adverse outcomes.

A Case of Candida parapsilosis Stromal Keratitis after Descemet's Membrane Endothelial Keratoplasty: A Case Report and Review of the Literature.

A 68-year-old diabetic male with Fuchs endothelial corneal dystrophy cataract underwent combined DMEK and cataract surgery of the left eye. Post-operative course was complicated by a partial graft detachment on POD 3, treated with a re-bubbling procedure. The patient subsequently developed a corneal infiltrate, cultured by aqueous sample, that was found to be C. parapsilosis. Oral fluconazole and voriconazole, topical voriconazole 1%, and amphotericin B as well as intracameral and intrastromal voriconazole and amphotericin B were employed. By post-operative day 45, symptoms and signs of DMEK stromal C. parapsilosis keratitis had resolved, and a corneal scar remained. Best corrected visual acuity, at post-operative month 4, was 20/25-2 without correction. Post-DMEK fungal stromal keratitis is a rare post-operative complication. We present a case of C. parapsilosis DMEK stromal keratitis and describe diagnostic and therapeutic modalities that allowed for resolution of the infection, without explantation of the patient's graft, and preservation of visual acuity.

Clinical Management of Herpes Simplex Virus Keratitis.

Herpes simplex virus (HSV) keratitis is one of the leading causes of blindness worldwide. Additionally, up to 90% of the population in some countries is seropositive for HSV. HSV can cause a wide spectrum of ocular disease ranging from blepharitis to retinitis. Although the initial clinical expressions of HSV-1 and HSV-2 are similar, HSV-2 has been reported more frequently in association with recurrent HSV disease. Besides irreversible vision loss from keratitis, HSV also causes encephalitis and genital forms of the disease. Despite these statistics, there remains no vaccine against HSV. Current treatment therapies for related ocular diseases include the use of oral and topical antivirals and topical corticosteroids. While effective in many cases, they fail to address the latency and elimination of the virus, making it ineffective in addressing recurrences, a factor which increases the risk of vision loss. As such, there is a need for continued research of other potential therapeutic targets. This review utilized several published articles regarding the manifestations of HSV keratitis, antiviral immune responses to HSV infection, and clinical management of HSV keratitis. This review will summarize the current knowledge on the host-virus interaction in HSV infections, as well as highlighting the current and potential antiviral therapeutics.

Diphenyleneiodonium Treatment Inhibits the Development of Severe Herpes Stromal Keratitis Lesions.

Reactive oxygen species (ROS) play an important role in tissue inflammation. In this study, we measured the intracellular level of ROS in herpes stromal keratitis (HSK) corneas and determined the outcome of manipulating ROS level on HSK severity. Our results showed the predominance of ROS generation in neutrophils but not CD4 T cells in HSK corneas. NADPH oxidase 2 (NOX2) enzyme is known to generate ROS in myeloid cells. Our results showed baseline expression of different NOX2 subunits in uninfected corneas. After corneal herpes simplex virus-1 (HSV-1) infection, an enhanced expression of NOX2 subunits was detected in infected corneas. Furthermore, flow cytometry results showed a higher level of gp91 (Nox2 subunit) protein in neutrophils from HSK corneas, suggesting the involvement of NOX2 in generating ROS. However, no significant decrease in ROS level was noticed in neutrophils from HSV-1-infected gp91-/- mice than in C57BL/6J (B6) mice, suggesting NOX2 is not the major contributor in generating ROS in neutrophils. Next, we used diphenyleneiodonium (DPI), a flavoenzyme inhibitor, to pharmacologically manipulate the ROS levels in HSV-1-infected mice. Surprisingly, the neutrophils from peripheral blood and corneas of the DPI-treated group exhibited an increased level of ROS than the vehicle-treated group of infected B6 mice. Excessive ROS is known to cause cell death. Accordingly, DPI treatment resulted in a significant decrease in neutrophil frequency in peripheral blood and corneas of infected mice and was associated with reduced corneal pathology. Together, our results suggest that regulating ROS levels in neutrophils can ameliorate HSK severity. IMPORTANCE Neutrophils are one of the primary immune cell types involved in causing tissue damage after corneal HSV-1 infection. This study demonstrates that intracellular ROS production in the neutrophils in HSK lesions is not NOX2 dependent. Furthermore, manipulating ROS levels in neutrophils ameliorates the severity of HSK lesions. Our findings suggest that excessive intracellular ROS in neutrophils disrupt redox homeostasis and affect their survival, resulting in a decrease in HSK lesion severity.

Controlling Herpes Simplex Virus-Induced Immunoinflammatory Lesions Using Metabolic Therapy: a Comparison of 2-Deoxy-d-Glucose with Metformin.

Herpes simplex virus (HSV) infection of the eye can result in a blinding immunoinflammatory lesion in the cornea called herpetic stromal keratitis (HSK). This lesion is orchestrated by T cells and can be reduced in magnitude by anti-inflammatory drugs and procedures that change the balance of cellular participants in lesions. This report evaluates the effect of drugs that cause metabolic reprogramming on lesion expression using two drugs that affect glucose metabolism: 2-deoxy-d-glucose (2DG) and metformin. Both drugs could limit HSK severity, but 2DG therapy could result in herpes encephalitis if used when replicating virus was still present. The reason metformin was a safer therapy was its lack of marked inhibitory effects on inflammatory cells particularly interferon-γ (IFN-γ)-producing Th1 and CD8 T cells in the trigeminal ganglion (TG), in which HSV latency is established and sustained. Additionally, whereas 2DG in TG cultures with established latency accelerated the termination of latency, this did not occur in the presence of metformin, likely because the inflammatory cells remained functional. Our results support the value of metabolic reprogramming to control viral immunoinflammatory lesions, but the approach used should be chosen with caution. IMPORTANCE Herpes simplex virus (HSV) infection of the eye is an example where damaging lesions are in part the consequence of a host response to the infection. Moreover, it was shown that changing the representation of cellular participants in the inflammatory reaction can minimize lesion severity. This report explores the value of metabolic reprogramming using two drugs that affect glucose metabolism to achieve cellular rebalancing. It showed that two drugs, 2-deoxy-d-glucose (2DG) and metformin, effectively diminished ocular lesion expression, but only metformin avoided the complication of HSV spreading to the central nervous system (CNS) and causing herpetic encephalitis. The report provides some mechanistic explanations for the findings.

The C-Terminal Penta-Peptide Repeats of Major Royal Jelly Protein 3 Ameliorate the Progression of Inflammation in Vivo and in Vitro.

Royal jelly (RJ) has been used as a functional foodstuff and in cosmetics for many years. RJ contains various molecules, including major royal jelly proteins (MRJPs), and affords a number of health benefits such as anti-inflammatory activity. As MRJP3 has been reported to possess anti-inflammatory properties by the in vitro analysis, we investigated the anti-inflammatory effects of MRJP3 and its derived peptides both in vitro and in vivo. Expression of both tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) mRNAs in lipopolysaccharides (LPS)-stimulated THP-1 cells was reduced by the addition of MRJP3 or its C-terminal tandem penta-peptide repeats (TPRs) sequence. In the herpes simplex virus type 1 (HSV-1)-induced herpes stromal keratitis (HSK) model mice, the instillation of TPRs reduced the disease scores and the expression levels of TNF-α and IL-6 in HSV-1-infected eyes. In addition, synthetic penta-peptides derived from TPRs reduced the expression of TNF-α and IL-6 both in the THP-1 cell cultures and in the HSK model mice. Our results indicated that MRJP3 TPRs would be useful in controlling inflammation.

Evidence in the prevention of the recurrence of herpes simplex and herpes zoster keratitis after eye surgery.

OBJECTIVE: Herpetic keratitis, either due to herpes simplex keratitis (HSK) or herpes zoster ophthalmicus (HZO), can recur after eye surgery.º Prophylaxis is postulated as necessary to avoid it. The objective of this study was to review the scientific evidence on the preventive methods used in the perioperative period in patients previously affected by HSK/HZO. METHODS: An exhaustive search was carried out in the PubMed and Web of Science databases to identify relevant articles on prophylaxis and risk of recurrence of HSK/HZO in patients undergoing eye surgery up to 31 December 2019. RESULTS: There is strong evidence that oral prophylaxis should be recommended after penetrating keratoplasty in patients who have previously had HSK/HZO. For other types of surgery, the evidence is less compelling. However, a latent period of inactivity should be considered between disease and oral prophylaxis. CONCLUSIONS: Penetrating and lamellar keratoplasty, corneal crosslinking, cataract surgery, and photorefractive and phototherapeutic surgery cause an alteration of the subbasal nerve plexus of the cornea. Due to surgical trauma, as well as the modulation of the ocular immune response caused by steroids applied in the postoperative period, it is possible to induce the reactivation of HSK/HZO, which is common in some cases. Within this article, we discuss the available evidence for HSK/HZO prophylaxis in eye surgery. Further studies are necessary to define the real risk of HSK/HZO recurrence after ocular surgeries, particularly in cataract surgery, and to confirm the efficacy of perioperative prophylaxis with anti-HSK/HZO antivirals.

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

BACKGROUND: A case of Epstein-Barr viral (EBV) corneal stromal keratitis during rheumatoid arthritis (RA) treatment is presented. CASE PRESENTATION: A 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. CONCLUSION: EBV can cause stromal keratitis without IM during treatment for RA.

Pathogenesis and virulence of herpes simplex virus.

Two of the most prevalent human viruses worldwide, herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2, respectively), cause a variety of diseases, including cold sores, genital herpes, herpes stromal keratitis, meningitis and encephalitis. The intrinsic, innate and adaptive immune responses are key to control HSV, and the virus has developed mechanisms to evade them. The immune response can also contribute to pathogenesis, as observed in stromal keratitis and encephalitis. The fact that certain individuals are more prone than others to suffer severe disease upon HSV infection can be partially explained by the existence of genetic polymorphisms in humans. Like all herpesviruses, HSV has two replication cycles: lytic and latent. During lytic replication HSV produces infectious viral particles to infect other cells and organisms, while during latency there is limited gene expression and lack of infectious virus particles. HSV establishes latency in neurons and can cause disease both during primary infection and upon reactivation. The mechanisms leading to latency and reactivation and which are the viral and host factors controlling these processes are not completely understood. Here we review the HSV life cycle, the interaction of HSV with the immune system and three of the best-studied pathologies: Herpes stromal keratitis, herpes simplex encephalitis and genital herpes. We also discuss the potential association between HSV-1 infection and Alzheimer's disease.