Epidemiology of Pediatric Ocular Surface Inflammatory Diseases in the United States Using the Optum Labs Data Warehouse.

PURPOSE: To benchmark the epidemiologic features of pediatric ocular surface inflammatory diseases (POSID). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients 18 years of age or younger with a medical claim for a diagnosis of POSID in the Optum Labs Data Warehouse between 2007 and 2020. METHODS: Patients with claims of blepharokeratoconjunctivitis (BKC), herpes simplex keratoconjunctivitis (HSK), or vernal keratoconjunctivitis (VKC) were included. Those with less than 6 months of follow-up before the initial diagnosis of POSID were excluded. Odds ratios (ORs) were derived from multivariable logistic regression analyses evaluating the associations between epidemiologic variables and POSID development. MAIN OUTCOME MEASURES: The primary outcome was the estimated prevalence of POSID. Prevalence of POSID subtypes and changes in prevalence over time were also evaluated. RESULTS: Two thousand one hundred sixty-eight patients with POSID were identified from 2018 through 2019, yielding an estimated prevalence of 3.32 per 10 000. The prevalence of POSID was higher among children between 5 and 10 years of age, male children, those of Asian descent, and those living in the Northeast and the West census regions of the United States. The prevalence (per 10 000) of BKC, HSK, and VKC in the same period were 0.59 (95% confidence interval [CI], 0.53-0.65), 0.74 (95% CI, 0.68-0.81), and 1.99 (95% CI, 1.88-2.10), respectively, and significant differences were found in terms of age, sex, racial, ethnic, and regional distributions among the diagnoses. Between 2008 through 2009 and 2018 through 2019, a significant increase in POSID was noted among Asians (from 6.26 [95% CI, 5.28-7.36] to 11.80 [95% CI, 10.40-13.34]) driven by changes in VKC. Multivariable analysis demonstrated that age older than 5 years (OR, 2.57-3.75; 95% CI, 2.17-4.34), male sex (OR, 1.38; 95% CI, 1.26-1.50), Asian descent (OR, 3.12; 95% CI, 2.70-3.60), and Black or African American descent (OR, 1.26; 95% CI, 1.02-1.55) were associated with POSID development. CONCLUSIONS: This study provides an estimated prevalence of POSID and its 3 common subtypes in the United States, with important epidemiologic differences among them. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Harmol used for the treatment of herpes simplex virus induced keratitis.

Herpes simplex virus type 1 (HSV-1) infection of the eyes results in herpes simplex keratitis (HSK), which has led to vision loss and even blindness in patients. However, the rate of drug resistance in HSV is on the rise; therefore, new antiviral agents with sufficient safety profiles must be developed. At present, we assessed the anti-HSV-1 activity of 502 natural compounds and their ability to reduce the HSV-1-induced cytopathic effect. We chose harmol for further studies because it exhibited the highest antiviral activity. We found that harmol inhibited both HSV-1 F and HSV-1/153 (a clinical drug-resistant strain) replication, with an EC50 of 9.34 µM and 5.84 µM, respectively. Moreover, harmol reduced HSV-1 replication in corneal tissues and viral progeny production in tears, and also alleviated early corneal surface lesions related to HSK. For example, harmol treatment preserved corneal thickness and nerve density in HSK mice. Interestingly, harmol also showed a promising antiviral effect on HSV-1/153 induced HSK in mouse model. Furthermore, harmol combined with acyclovir (ACV) treatment showed a greater antiviral effect than either one alone in vitro. Therefore, harmol may be a promising therapeutic agent for managing HSK.

Emerging drugs for the treatment of herpetic keratitis.

INTRODUCTION: Herpes simplex keratitis stands as a prominent factor contributing to infectious blindness among developed nations. On a global scale, over 60% of the population tests positive for herpes simplex virus type-1 (HSV-1). Despite these statistics, there is currently no vaccine available for the virus. Moreover, the conventional nucleoside drugs prescribed to patients are proving ineffective in addressing issues related to drug resistance, recurrence, latency, and the escalating risk of vision loss. Hence, it is imperative to continually explore all potential avenues to restrict the virus. This review article centers on the present treatment methods for HSV-1 keratitis (HSK), highlighting the ongoing clinical trials. It delves into the emerging drugs, their mode-of-action and future therapeutics. AREAS COVERED: The review focuses on the significance of a variety of small molecules targeting HSV-1 lifecycle at multiple steps. Peer-reviewed articles and abstracts were searched in MEDLINE, PubMed, Embase, and clinical trial websites. EXPERT OPINION: The exploration of small molecules that target specific pathways within the herpes lifecycle holds the potential for substantial impact on the antiviral pharmaceutical market. Simultaneously, the pursuit of disease-specific biomarkers has the capacity to usher in a transformative era in diagnostics within the field.

Effect of atopic conditions on development and recurrences of infectious keratitis.

BACKGROUND: Atopic conditions are known to be associated with viral and bacterial infections. The purpose of this study was to determine the relationship between the effects of atopic conditions on the severity and recurrence of ocular infections including herpes simplex virus (HSV). METHODS: This study was performed on 474 consecutive patients with infectious keratitis caused by bacteria, fungus, acanthamoeba, HSV, or varicella-zoster virus. The relationships between the atopic condition and specific infectious pathogens and HSV were determined using real-time PCR. RESULTS: Our findings showed that atopic dermatitis (AD) was significantly associated with the incidence of HSV keratitis (odds ratio (OR), 10.2; P = 0.000). Other associations with AD were observed only with bacteria in an adverse manner. HSV proliferation in the lesions of patients with HSV keratitis whose AD was associated with non-infectious atopic blepharitis were significantly greater by 145-folds (P = 0.000). The presence of asthma or allergic rhinitis also increased the HSV DNA copy numbers. A recurrence of HSV keratitis was observed in 70 patients (43.2 %), and mean time to recurrence was 1647 days. Cox proportional hazard model indicated that the epithelial type of HSV recurrence but not the stromal type was associated with atopic conditions especially with AD. The factors significantly associated with a recurrence was AD associated with non-infectious atopic blepharitis (HR: 6.11, P = 0.000) and asthma (HR: 3.03, P = 0.025). CONCLUSIONS: Atopic conditions, especially AD with atopic blepharitis, are significantly associated with the development, increased proliferation, and shorter time to a recurrence on HSV keratitis.

Clinical and Demographic Characteristics of Herpetic Keratitis Patients-Tertiary Centre Experience.

Background and Objectives: Herpes simplex keratitis (HSK) is the leading infectious cause of corneal damage and associated loss of visual acuity. Because of its frequent recurrence, it represents a major health problem; thus, timely and accurate diagnosis is the key to successful treatment. To enable this, we aimed to determine HSK patients' demographic and clinical features. Materials and Methods: This prospective study included 55 patients diagnosed with HSK between March 2019 and August 2022 at the Department of Ophthalmology, Clinical Hospital Rijeka. Results: We found that HSK is most prevalent in the elderly, with 72.73% of patients older than 60. The most common HSK types were dendritic (HSK-D; 43.64%) and stromal with epithelial ulceration (HSK-SEU 23.64%). HSK recurrences occurred in 65.45% of patients, with most having two to five recurrences (55.56%). Visual acuity at presentation (65.5%) and after treatment (50.9%) was mostly in the 20/50 range. The longest period until the disease symptoms were resolved was in the group with stromal HSK without epithelial ulceration (HSK-SnEU), for which symptoms lasted more than 11 weeks in 87.5% of patients. The overall incidence of HSK-related complications was high (85.45%), with 76.4% of patients having corneal scarring. The average time from symptom to treatment was 15.78 days. Interestingly, we observed a strong seasonality in the incidence of HSK, which was most prevalent in the colder months, with 63.6% of cases occurring between October and March. Conclusions: To the best of our knowledge, this is the first prospective study in Croatia, and one of the few in Europe, to describe the demographic and clinical features of HSK patients. We found that HSK is most common in the elderly population, with its dendritic form as a clinical presentation. We have shown that HSK is prone to recurrence and secondary complications, with a worryingly long time between symptom and treatment, indicating the need for diagnostic testing in routine practice.

[Scientific legacy of Professor A.A. Kasparov. Inductor of endogenous interferon Poludan in the treatment of ocular herpes and other corneal diseases]. / Nauchnoe nasledie professora A.A. Kasparova. Induktor endogennogo interferona Poludan v lechenii oftal'mogerpesa i drugikh zabolevanii rogovitsy.

This article presents a retrospective analysis of the research findings by professor A.A. Kasparov, who developed and implemented a novel approach to treating ocular herpes. The treatment system is fundamentally different from the conventional chemotherapeutic approach and revolves around non-specific immunotherapy using an endogenous interferon inducer - a biosynthetic complex of polyriboadenylic and polyribouridylic acids, known as Poludan. This approach also incorporates personalized cell therapy based on Poludan, along with herpes vaccine aimed at preventing recurrence. The regenerative and antiviral properties of this approach have proven successful in treating other corneal conditions such as adenovirus infections, early postoperative bullous keratopathy, as well as in stimulation of epithelialization after refractive surgeries (photorefractive keratectomy, phototherapeutic keratectomy).

Herpes simplex keratitis following Smart Pulse Technology assisted transepithelial photorefractive keratectomy: a case report.

BACKGROUND: Herpes simplex keratitis (HSK) is a rare and sight-threatening complication following refractive surgery. SmartSurfACE surgery is the result of combining transepithelial photorefractive keratectomy (trans-PRK) with Smart Pulse Technology (SPT) to diminish surface irregularities of the residual stromal bed after surgery with less pain, faster re-epithelialization, and better postoperative visual acuity. In this article, we report the first case of HSK following SmartSurf ACE without history of herpetic eye disease. CASE PRESENTATION: A 21-year-old woman underwent bilateral SmartSurfACE without history of clinical herpetic infection, active eye disease, or systemic disease. Mild superficial punctate keratitis occurred on the tenth postoperative day. The condition was not improved by ophthalmic drugs of anti-inflammation or epithelial healings. Dendritic corneal ulcer appeared within one month, which is the commonly recognized clinical manifestation of herpes simplex keratitis. The patient was managed with topical and systemic antiviral agents. After nine days of antiviral therapy, the lesion healed up, remaining mild stromal scarring in both eyes ultimately. CONCLUSION: Herpes simplex keratitis is a rare but sight-threatening complication following refractive surgery. For the ocular irritation symptoms of postoperative patients, we should consider the possibility of HSK and give timely treatment.

Herpes Simplex Keratitis in Patients with SARS-CoV-2 Infection: A Series of Five Cases.

Herpes simplex virus type 1 (HSV-1) is a leading cause of infectious blindness worldwide. Most of the initial infection cases manifest as acute epithelial keratitis. Reactivation of herpesviruses is common in critically ill patients, including patients with severe Coronavirus disease (COVID-19). However, the data on COVID-19-related ocular infections is sparse, despite recent observations that more than 30% of COVID-19-infected patients had ocular manifestations. We report five cases of HSV-1 keratitis in COVID-19 patients. In total, five COVID-19 patients underwent ophthalmic examination, showing similar symptoms, including photophobia, tearing, decreased vision, eye redness, and pain. After initial assessment, tests of visual acuity and corneal sensitivity, a fluorescein staining test, and complete anterior and posterior segment examinations were performed. A diagnosis of HSV-1 keratitis was confirmed in all cases. Therapy was initiated using a local and systemic antiviral approach together with local antibiotic and mydriatic therapy. The complete reduction of keratitis symptoms and a clear cornea was achieved in all patients within 2 weeks. SARS-CoV-2 infection may be a risk factor for developing HSV-1 keratitis, or it may act as a potential activator of this ocular disease.

Short-term results of acellular porcine corneal stroma keratoplasty for herpes simplex keratitis.

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

Corneal perforation after noncontact tonometry in patients with active recurrent herpes simplex keratitis: case report.

PURPOSE: To report iatrogenic complications and to review the potential complications caused by noncontact tonometry (NCT) in related literature. METHODS: This case report describes two cases of active recurrent herpes simplex keratitis (HSK) on top of a thin corneal scar. The cornea was perforated by the air pulse from the NCT, resulting in an air bubble in the anterior chamber. RESULTS: Both patients were diagnosed with active recurrent necrotizing stromal HSK on top of a thinned corneal scar after previous therapeutic treatment involving tissue adhesive glue with a bandage contact lens (BCL) to treat a perforated cornea. During a follow-up visit, both patients reported similar symptoms of acute pain and fluid exuding from their eyes immediately after undergoing NCT. Slit-lamp examination revealed a perforated cornea with an intracameral air bubble. Treatment involved use of tissue adhesive glue and BCL in both cases. CONCLUSION: NCT may not be sufficiently safe in patients with active infectious keratitis, particularly in cases where the cornea is relatively thin and necrotic.

Double bubble with the big-bubble technique during deep anterior lamellar keratoplasty.

PURPOSE: To report a case of intraoperative double bubble that formed during big-bubble DALK surgery in a patient with corneal scarring secondary to herpetic stromal keratitis. METHODS: Case report. RESULTS: A 22 year old woman presented with a large corneal scar, likely secondary to previous herpetic stromal keratitis. She underwent big-bubble DALK surgery for visual rehabilitation. Intraoperatively, a mixed bubble with persistent type 2 bubble postoperatively was noted. The second bubble resorbed with clearance of the graft and good visual outcome after 6 weeks. CONCLUSIONS: This case report describes the unusual development of a mixed bubble during big-bubble DALK surgery. This graft cleared with resolution of the second bubble postoperatively without further surgical intervention.

Indications and graft survival analysis in optical penetrating keratoplasty in a tertiary care center in North India: a 5-year study.

PURPOSE: To study the indications and variables correlating with graft survival in optical penetrating keratoplasty in a tertiary care hospital in north India. PARTICIPANTS: All patients who underwent optical keratoplasty, except those undergoing lamellar grafts, tectonic grafts transplants and penetrating keratoplasty done for therapeutic purposes were included in the study. Patients with follow-up less than 2 years were excluded from the study. MATERIALS AND METHODS: Data were obtained by reviewing the records of 101 patients who underwent optical penetrating keratoplasty from 2008 to 2013 for various indications. RESULTS: Out of 101 patients who underwent optical penetrating keratoplasty, 71 were males and 30 were females. The mean age of the recipient was 48.53 years with range 1-82 years. The main indications were previous failed graft (29.7%), healed keratitis except HSV (15.8%), pseudophakic or aphakic bullous keratopathy (14.8%), corneal dystrophies/degenerations (12.9%), adherent leucoma (9.9%), post-HSV scars (8.9%), and others like anterior staphyloma, congenital corneal opacities, buphthalmos and keratoconus (7.9%). The graft survival rate was 67.33% at 1-year follow-up and 59.4% at 2-year follow-up. The mean survival time of the grafts was 22.42 months. The mean time for graft failure was 7.12 (±0.9) months. CONCLUSION: One- and 2-year survival of grafts at our center is lower as compared to western studies, probably due to higher percentage of poor prognosis indications for surgery and a relative scarcity of excellent-quality donor corneas.

A novel rare sugar inhibitor of murine herpes simplex keratitis.

PURPOSE: To determine the therapeutic efficacy of a novel rare sugar, l-psicose, for the treatment of HSV-1 induced herpetic stromal keratitis (HSK) in a mouse eye model. METHODS: One rare sugar l-psicose was assayed for HSV-1 inhibition of in vitro virus adsorption. The IC50 and IC90 values of l-psicose were determined using plaque reduction assay (PRA) in CV-1 cell. Female Balb/c mice were corneally infected with HSV-1, strain KOS-GFP; A topical eye drop treatment of l-psicose was started 24 h after infection and continued four times daily for ten consecutive days. The severity of HSK was monitored by slit lamp examination in a masked fashion and Infectious HSV-1 shedding was determined by PRA. RESULTS: l-psicose was found to have anti-viral activity in vitro at an IC50 dose of 99.5 mM and an IC90 dose of 160 mM. Topical eye drop treatment with 200 mM l-psicose in PBS solution significantly reduced the severity of HSK compared to the mock treatment group. The in vivo mouse ocular model results of l-psicose therapy correlated with accelerated clearance of virus from eye swabs. CONCLUSION: The results suggest that topical treatment with rare sugar l-psicose has efficacy against HSK through inhibition of HSV-1.

Herpes simplex virus keratitis: an update of the pathogenesis and current treatment with oral and topical antiviral agents.

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

Herpes simplex keratitis: A brief clinical overview.

The aim of our minireview is to provide a brief overview of the diagnosis, clinical aspects, treatment options, management, and current literature available regarding herpes simplex keratitis (HSK). This type of corneal viral infection is caused by the herpes simplex virus (HSV), which can affect several tissues, including the cornea. One significant aspect of HSK is its potential to cause recurrent episodes of inflammation and damage to the cornea. After the initial infection, the HSV can establish a latent infection in the trigeminal ganglion, a nerve cluster near the eye. The virus may remain dormant for extended periods. Periodic reactivation of the virus can occur, leading to recurrent episodes of HSK. Factors triggering reactivation include stress, illness, immunosuppression, or trauma. Recurrent episodes can manifest in different clinical patterns, ranging from mild epithelial involvement to more severe stromal or endothelial disease. The severity and frequency of recurrences vary among individuals. Severe cases of HSK, especially those involving the stroma and leading to scarring, can result in vision impairment or even blindness in extreme cases. The cornea's clarity is crucial for good vision, and scarring can compromise this, potentially leading to visual impairment. The management of HSK involves not only treating acute episodes but also implementing long-term strategies to prevent recurrences and attempt repairs of corneal nerve endings via neurotization. Antiviral medications, such as oral Acyclovir or topical Ganciclovir, may be prescribed for prophylaxis. The immune response to the virus can contribute to corneal damage. Inflammation, caused by the body's attempt to control the infection, may inadvertently harm the corneal tissues. Clinicians should be informed about triggers and advised on measures to minimize the risk of reactivation. In summary, the recurrent nature of HSK underscores the importance of both acute and long-term management strategies to preserve corneal health and maintain optimal visual function.

Metabolic signatures of tear extracellular vesicles caused by herpes simplex keratitis.

PURPOSE: Herpes simplex keratitis (HSK), caused by type 1 herpes simplex virus (HSV) reactivation, is a severe infectious disease that leads to vision loss. HSV can trigger metabolic reprogramming in the host cell and change the extracellular vesicles (EV) cargos; however, little is known about the EV metabolic signatures during ocular HSV infection. Here, we aimed to depict the EV-associated metabolic landscape in HSK patients' tears. METHODS: We collected 82 samples from 41 participants with unilateral HSK (contralateral unaffected tears were set as negative control), including subtype cohorts of 13 epithelial, 20 stromal, and 8 endothelial HSK. We isolated tear EVs via our previously established platform and conducted metabolic analysis using LC-MS/MS. The metabolic signatures for recognizing HSK and subtypes were assessed through differential analysis and machine learning algorithms. RESULTS: Hypopsia and increased extracellular CD63 levels were observed in affected eyes. We identified 339 metabolites based on sEVs isolated from tears. Differential analysis revealed alterations in energy and amino acid metabolism, as well as the infectious microenvironment. Furthermore, we observed dysregulated metabolite such as methyldopa, which is associated with inappropriate neovascularization and corneal sensation loss, contributing to the HSK severity particularly in the stromal subtype. Moreover, machine learning classification also suggested a set of EV metabolic signatures that have potential for pan-keratitis detection. CONCLUSIONS: Our findings demonstrate that tear EV metabolites can serve as valuable indicators for comprehending the underlying pathological mechanisms. This knowledge is expected to facilitate the development of liquid biopsy means and therapeutic target discovery.

Overexpression of NLRP12 enhances antiviral immunity and alleviates herpes simplex keratitis via pyroptosis/IL-18/IFN-γ signaling.

Herpes simplex keratitis (HSK) is a blinding disease caused by herpes simplex virus type 1 (HSV-1) infection, and rapid eradication of the virus from the affected cornea is imperative. Nod-like receptors (NLRs) are intracellular innate immune sensors closely associated with cell death, inflammation and immune responses. In this study, we investigated the role of NLRP12 in the antiviral immunology in HSK and the underlying mechanisms. We found that NLRP12 expression was significantly decreased in HSV-1-infected human corneal epithelial cells (HCE-Ts) and HSK mouse corneas. Overexpression of NLRP12 significantly reduced viral replication in infected HCE-Ts and functioned through inflammasome-mediated pyroptosis and downstream IL-18-IFN-γ axis. In HSK mouse models, overexpression of NLRP12 reduced viral replication in the cornea and alleviated HSK symptoms. This resulted from enhanced antiviral immune responses including the activation of specific immune cells in both the cornea and the draining lymph nodes. Specifically, the NLRP12-IL-18-IFN-γ axis regulated the interaction between infected corneal epithelial cells and macrophages. In conclusion, our study identified a role of NLRP12 in mediating pyroptosis and regulating antiviral immune responses. This novel finding opens the possibilities of NLRP12 as a viable target in the therapeutic strategies for HSV-1 infection.

Targeted delivery of herpes simplex virus glycoprotein D to CD169+ macrophages using ganglioside liposomes alleviates herpes simplex keratitis in mice.

Herpes simplex keratitis (HSK) is a common blinding corneal disease caused by herpes simplex virus type 1 (HSV-1) infection. Antiviral drugs and corticosteroids haven't shown adequate therapeutic efficacy. During the early stage of HSV-1 infection, macrophages serve as the first line of defense. In particular, CD169+ macrophages play an important role in phagocytosis and antigen presentation. Therefore, we constructed GM-gD-lip, a ganglioside GM1 liposome vaccine encapsulating HSV-1 glycoprotein D and targeting CD169+ macrophages. After subconjunctival injection of the vaccine, we evaluated the survival rate and ocular surface lesions of the HSK mice, as well as the virus levels in the tear fluid, corneas, and trigeminal ganglia. We discovered that GM-gD-lip reduced HSV-1 viral load and alleviated the clinical severity of HSK. The GM-gD-lip also increased the number of corneal infiltrating macrophages, especially CD169+ macrophages, and polarized them toward M1. Furthermore, the number of dendritic cells (DCs) and CD8+ T cells in the ocular draining lymph nodes was significantly increased. These findings demonstrated that GM-gD-lip polarized CD169+ macrophages toward M1 to eliminate the virus while cross-presenting antigens to CD8+ T cells via DCs to activate adaptive immunity, ultimately attenuating the severity of HSK. The use of GM-gD-lip as an immunotherapeutic method for the treatment of HSK has significant implications.

Overexpression of NLRP12 enhances macrophage immune response and alleviates herpes simplex keratitis.

Introduction: Herpes simplex keratitis (HSK) is a blinding disease caused by corneal infection of Herpes simplex virus type 1 (HSV-1). Effective clearance of HSV-1 from the infected cornea is crucial for HSK management. Macrophages play an important part in the innate immune defense against viral infections. This study investigates the immunomodulatory role of NLRP12 in macrophage immune response during HSV-1 infection. Methods: NLRP12 expression post-infection was assessed in various macrophage cell lines. Overexpression of NLRP12 was achieved by lentiviral transfection, and its effect on HSV-1 replication and immune responses were examined. Mechanistic insights into the role of NLRP12 were explored using immunofluorescence and Western Blot. For in vivo studies, ocular adoptive transfer of NLRP12-overexpressing bone marrow derived macrophages (BMDMs) was performed. HSV-1 viral loads, HSK symptoms, and macrophage-mediated immune responses were investigated. Results: A significant decrease in NLRP12 expression post-infection was observed in various macrophage cell lines. Overexpression of NLRP12 in macrophages reduced HSV-1 replication. Mechanistically, overexpression of NLRP12 triggered early and robust pyroptosis in response to HSV-1 infection, inducing interleukin (IL)-18 production and activating downstream antiviral responses through the JAK-STAT signaling pathway. In vivo, ocular adoptive transfer of NLRP12-overexpressing BMDMs to mouse corneas alleviated HSK damage and reduced HSV-1 viral loads. NLRP12-overexpressing BMDMs improved antiviral responses in the cornea and promoted the maturation of corneal-infiltrating macrophages and dendritic cells. Additionally, NLRP12-overexpressing BMDMs amplified the adaptive immune response in the submandibular draining lymph nodes. Discussion: These findings highlight the role of NLRP12 in macrophage-mediated immune response against HSV-1 infection and suggest its potential for possible immunotherapy for HSK.

[Postoperative therapy after penetrating keratoplasty in herpes simplex keratitis]. / Herpes simplex keratitisekben végzett perforáló keratoplasztika posztoperatív terápiája.

INTRODUCTION: Keratitis due to herpes simplex infection is a common cause of corneal damage resulting in impaired vision. AIM: The aim of this study was to assess the outcome of penetrating keratoplasties in patients treated with systemic antiviral and immunosuppressive drugs. METHOD: The authors retrospectively analysed data of 12 patients who underwent penetrating keratoplasty. The average age at onset of the first keratitis preceding surgery was 18 years (between 5 and 40 years). The indication for surgery in 9 cases was to improve vision and in 3 patient to prevent corneal perforation. Nine patients were given both acyclovir and mycophenolate mofetil, as anti-viral agent and immunosuppressive treatment, respectively. Two patients were treated with anti-viral agent only while one patient received no systemic therapy. The average follow-up time was 53.1 months (between 16 and 84 months). RESULTS: Of the 9 patients who underwent surgery for improving vision, 8 patients had transparent grafts during follow up without vascularization. All eight patients had been treated with acyclovir and mycophenolate mofetil. In one patient who had no systemic treatment recurrence and graft rejection was observed. Only one of the surgeries performed in acute stage of inflammation resulted in a properly healed transparent graft without recurrence and rejection. In this patient acyclivir and mycophenolate mofetil therapy had been given previously. In two cases the preventive - full or partial - systemic treatment had no effect. The visual acuity improved in all cases. In three patients visual acuity was influenced by some other factors as well. CONCLUSIONS: The systemic acyclovir and mycophenolat mofetil therapy is fairly successful in perforating keratoplasty due to herpes simplex infection. Acyclovir decreases the risk of recurrence, while mycophenolate mofetil may prevent graft rejection. The timing of surgery is decisive; it leads to better results when performed in a scarred, noninflammatory state.