Herpetic Stromal Keratitis Research Articles

Trigeminal Trophic Syndrome With Herpetic Keratitis.

The aim of this study was to report a rare observation of trigeminal trophic syndrome presenting with concurrent herpetic keratitis. This study was a case report. A 42-year-old male with a remote history of a motor vehicle accident, traumatic brain injury, extensive facial reconstructive surgery, and traumatic optic neuropathy presented with left periorbital swelling. He was found to have extensive periorbital and total hypoesthesia in the cranial nerve V1 distribution and partial hypoesthesia in the V2 distribution. Corneal findings were highly suspicious for herpes simplex keratitis or zoster ophthalmicus. The patient was diagnosed with herpetic epithelial and stromal keratitis with periorbital ulceration secondary to Trigeminal trophic syndrome. The patient was treated broad spectrum intravenous antibiotics, intravenous acyclovir, and topical antibiotics. He was treated with topical steroids upon closure of epithelial defect. Upon discharge, the patient's vision improved from hand-motion to 20/30 at near. The patient was later fit with a custom thermoplastic facial mask to minimize further selfinjurious behavior. To our knowledge, this is the first report of trigeminal trophic syndrome presenting with concurrent herpetic keratitis. Successful treatment requires a multidisciplinary approach to provide the patient insight and create protective equipment.

The immunobiology of corneal HSV-1 infection and herpetic stromal keratitis.

SUMMARYHuman alphaherpesvirus 1 (HSV-1) is a highly successful neurotropic pathogen that primarily infects the epithelial cells lining the orofacial mucosa. After primary lytic replication in the oral, ocular, and nasal mucosal epithelial cells, HSV-1 establishes life-long latency in neurons within the trigeminal ganglion. Patients with compromised immune systems experience frequent reactivation of HSV-1 from latency, leading to virus entry in the sensory neurons, followed by anterograde transport and lytic replication at the innervated mucosal epithelial surface. Although recurrent infection of the corneal mucosal surface is rare, it can result in a chronic immuno-inflammatory condition called herpetic stromal keratitis (HSK). HSK leads to gradual vision loss and can cause permanent blindness in severe untreated cases. Currently, there is no cure or successful vaccine to prevent latent or recurrent HSV-1 infections, posing a significant clinical challenge to managing HSK and preventing vision loss. The conventional clinical management of HSK primarily relies on anti-virals to suppress HSV-1 replication, anti-inflammatory drugs (such as corticosteroids) to provide symptomatic relief from pain and inflammation, and surgical interventions in more severe cases to replace damaged cornea. However, each clinical treatment strategy has limitations, such as local and systemic drug toxicities and the emergence of anti-viral-resistant HSV-1 strains. In this review, we summarize the factors and immune cells involved in HSK pathogenesis and highlight alternate therapeutic strategies for successful clinical management of HSK. We also discuss the therapeutic potential of immunoregulatory cytokines and immunometabolism modulators as promising HSK therapies against emerging anti-viral-resistant HSV-1 strains.

UVB induced reactivation leads to HSV1 in the corneas of virtually all latently infected mice and requires STING to develop corneal disease

Reactivation of latent herpes simplex type 1 results in virus returning to the cornea leading to recurrent herpetic stromal keratitis (rHSK). We compare two competing models to reactivate viruses from latency, UV-B irradiation and cyclophosphamide (CP). Results revealed that while both result in corneal recrudescence, only UV-B irradiation results in rHSK. To better understand the dynamics of reactivation, we analyzed corneas for both the presence of infectious viruses and the dynamics of exposure to multiple reactivations using UV-B. We noted that multiple reactivations result in progressively worse corneal disease. We also noted that expression of IFNα and STING, surragate markers for the presence of virus, are induced by the presence of reactivated virus. Studies to determine the importance of STING to the development of HSK revealed that in the absence of STING, mice do not develop significant HSK and the magnitude of the infiltrate of CD45+ cells in these corneas is significantly reduced. The resulting paucity of CD45+CD11b+GR-1+F4/80-neutrophils, and to a lesser extent CD45+CD11b+GR-1-F4/80+ macrophages in B6-STING KO mice following reactivation is likely the underlying cause for lack of rHSK as has been noted by ourselves and others. These results underscore the critical importance of STING’s role in developing rHSK.

Long-term Follow-up Results after Prophylactic Antiviral Administration in Patients with Herpes Simplex Keratitis

Purpose: We analyzed the effectiveness of prophylactic oral antivirals in preventing herpes simplex keratitis (HSK) and the clinical manifestations of recurrence.Methods: A retrospective analysis was conducted on 30 eyes of 30 patients diagnosed with HSK who received prophylactic oral antiviral agents for > 6 months. We analyzed the initial and recurrent clinical features of HSK, the recurrence rate, and the relationship between recurrence and the duration of oral antivirals.Results: The mean age of the patients was 64.5 ± 14.0 years, and the mean follow-up duration was 72.4 ± 40.3 months. Of the 30 eyes, 21 (70%) experienced HSK recurrence. The initial clinical features of recurrent cases included herpetic epithelial keratitis (14.3%), stromal keratitis (47.6%), and endotheliitis (38.1%). Notably, no significant associations were observed between the initial clinical features of HSK or the duration of oral antivirals and HSK recurrence. However, male patients exhibited a significantly higher recurrence rate. Epithelial keratitis (47.6%) was the most common HSK type observed during recurrence.Conclusions: A recurrence rate of 70% was observed in patients who received prophylactic oral antiviral treatment for > 6 months. Herpetic epithelial keratitis was the most common clinical phenotype after recurrence. Notably, long-term clinical monitoring could assist in predicting and preventing recurrence.

Tear lactoferrin concentration in patients with recurrent herpetic stromal keratitis and therapeutic effect of Lacto eyedrops in the multicomponent treatment for this disorder

Background: Herpetic stromal keratitis (HSK) is an immunomodulatory disease that develops as a result of herpes simplex virus (HSV)1 or HSV2 reactivation. HSK is the most common form (20-50%) of recurrent herpetic keratitis (HK) that most commonly results in significantly reduced vision. It is well known that changes in biological compound levels in tear fluid can be indicative of the state of the ocular surface and determine whether ocular surface pathology is present, and, therefore, can be used as diagnostic markers of pathological changes in the ocular surface. Lactoferrin (LF) is one of these compounds and has been proven to have innate antibacterial, antifungal, antiviral, antiparasite, anti-inflammatory, immunomodulatory, antioxidative and other properties. Purpose: To determine tear Lf concentration in patients with recurrent acute HSK, its effect on functional characteristics of the ocular surface, and the therapeutic effect of Lacto eyedrops in the comprehensive treatment for this disorder. Material and Methods: The study was conducted at the site of Corneal Pathology Department and Immunology Laboratory of the Institute in January to December 2021. Seventeen patients (17 affected eyes and 17 fellow eyes) with recurrent acute HSK were included in the study. Mean patient age plus or minus standard deviation (SD) was 48.7 ± 16.0 years. The ophthalmological examination included biomicroscopy of the bulbar conjunctiva and cornea, fluorescein test, determination of corneal sensation and basal tear production (Schirmer’s II test), and microbiological examination of the conjunctiva. Tear Lf concentration was determined by a human Lf enzyme-linked immunosorbent assay (ELISA) kit (Elabscience Biotechnology, Inc., Wuhan, China). The results were photometrically measured at 450 nm with an ELISA reader (Stat Fax 2100, Awareness Technology Inc, Palm City, FL). Lacto eyedrops were administered two times a day for 30 days. Tear Lf concentrations were determined at baseline and at day 30. Results: Mean tear LF concentration plus or minus SD in eyes of patients with recurrent HSK was 1.21 ± 0.52 g/l, with no significant difference between the affected eye and fellow eye. However, a subnormal tear LF concentration was more common in the affected eye than in the fellow eye (2 = 4.24, р = 0.04). After a 30-day anti-inflammatory treatment with Lacto eyedrops, mean tear LF concentration plus or minus SD increased by 47% to 1.78 ± 0.7 g/l in the affected eyes. A corneal sensation score of 1 to 9 was 12.4 times more common in HSK eyes than in fellow eyes (OR = 12.4; 95% CI, 2.0–76.8), which reflects neurosensory abnormalities in the affected eye. Corneal sensation loss, was, however, more common in HSK eyes with a low tear Lf concentration than in fellow eyes with a low tear Lf concentration. Median basal tear production (as assessed by Schirmer’s II test) was as low as 7-8 mm in eyes with a low tear Lf concentration and as high as 13-16 mm in eyes with a high tear Lf concentration (p less 0.05). There was a direct correlation between the basal tear production and the tear Lf concentration (r=0.45; p less 0.05). Among study patients with recurrent HSK, 24.9% showed baseline microbiological evidence of potentially pathogenic or fungal organisms in the conjunctiva. A course of multicomponent anti-inflammatory treatment with Lacto eyedrops contributed to complete removal of these organisms. Conclusion: We determined mean tear Lf concentrations in affected and fellow eyes of patients with recurrent HSK, and established certain relationships between functional characteristics of the ocular surface and tear Lf concentrations in these eyes. A disinfecting effect of Lacto eyedrops against any microorganisms present in the conjunctival sac of patients with recurrent HSK was confirmed by the absence of culture growth on completion of the multicomponent anti-inflammatory treatment.

In vivo CRISPR gene editing in patients with herpetic stromal keratitis

Invivo 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 18months on average in all three patients. The HSV-1 remained undetectable during the study. Our preliminary clinical results suggest that invivo gene editing targeting the HSV-1 genome holds acceptable safety as a potential therapy for HSK.

Role of IL-27 in HSV-1-Induced Herpetic Stromal Keratitis.

Herpetic stromal keratitis (HSK) is a painful and vision-impairing disease caused by recurrent HSV-1 infection of the cornea. The virus replication in the corneal epithelium and associated inflammation play a dominant role in HSK progression. Current HSK treatments targeting inflammation or virus replication are partially effective and promote HSV-1 latency, and long-term use can cause side effects. Thus, understanding molecular and cellular events that control HSV-1 replication and inflammation is crucial for developing novel HSK therapies. In this study, we report that ocular HSV-1 infection induces the expression of IL-27, a pleiotropic immunoregulatory cytokine. Our data indicate that HSV-1 infection stimulates IL-27 production by macrophages. Using a primary corneal HSV-1 infection mouse model and IL-27 receptor knockout mice, we show that IL-27 plays a critical role in controlling HSV-1 shedding from the cornea, the optimum induction of effector CD4+ T cell responses, and limiting HSK progression. Using invitro bone marrow-derived macrophages, we show that IL-27 plays an antiviral role by regulating macrophage-mediated HSV-1 killing, IFN-β production, and IFN-stimulated gene expression after HSV-1 infection. Furthermore, we report that IL-27 is critical for macrophage survival, Ag uptake, and the expression of costimulatory molecules involved in the optimum induction of effector T cell responses. Our results indicate that IL-27 promotes endogenous antiviral and anti-inflammatory responses and represents a promising target for suppressing HSK progression.

Topical cyclosporine: A versus prednisolone in the treatment of herpetic stromal keratitis

Topical cyclosporine: A versus prednisolone in the treatment of herpetic stromal keratitis

Role of Innate Interferon Responses at the Ocular Surface in Herpes Simplex Virus-1-Induced Herpetic Stromal Keratitis.

Herpes simplex virus type 1 (HSV-1) is a highly successful pathogen that primarily infects epithelial cells of the orofacial mucosa. After initial lytic replication, HSV-1 enters sensory neurons and undergoes lifelong latency in the trigeminal ganglion (TG). Reactivation from latency occurs throughout the host's life and is more common in people with a compromised immune system. HSV-1 causes various diseases depending on the site of lytic HSV-1 replication. These include herpes labialis, herpetic stromal keratitis (HSK), meningitis, and herpes simplex encephalitis (HSE). HSK is an immunopathological condition and is usually the consequence of HSV-1 reactivation, anterograde transport to the corneal surface, lytic replication in the epithelial cells, and activation of the host's innate and adaptive immune responses in the cornea. HSV-1 is recognized by cell surface, endosomal, and cytoplasmic pattern recognition receptors (PRRs) and activates innate immune responses that include interferons (IFNs), chemokine and cytokine production, as well as the recruitment of inflammatory cells to the site of replication. In the cornea, HSV-1 replication promotes type I (IFN-α/β) and type III (IFN-λ) IFN production. This review summarizes our current understanding of HSV-1 recognition by PRRs and innate IFN-mediated antiviral immunity during HSV-1 infection of the cornea. We also discuss the immunopathogenesis of HSK, current HSK therapeutics and challenges, proposed experimental approaches, and benefits of promoting local IFN-λ responses.

Overweight and Obesity as Risk Factors for Recurrent Herpetic Stromal Keratitis during Long-Term Antiviral Prophylaxis.

Although past research has shown an association between obesity and herpes simplex virus infection, the relationship between body mass index (BMI) and herpetic stromal keratitis (HSK) recurrence has never been investigated. In this study, we included HSK patients who received oral valacyclovir as prophylactic treatment between January 2016 and January 2021. Recurrence, possible risk factors, and the time to recurrence were recorded during follow-ups. Among the 56 patients included in this study, recurrence was reported in 21 (37.5%) patients. The age at disease onset and mean follow-up time were not significantly different in the recurrence and non-recurrence groups. However, in the Cox regression analysis, BMI ≥ 24 kg/m2 was noted as the variable having significant correlation with recurrence (p = 0.01 in univariate analysis and p = 0.001 in multivariate analysis). In conclusion, overweight and obesity were revealed as risk factors for HSK recurrence in patients receiving long-term antiviral prophylaxis. Further studies are needed to determine the appropriate acyclovir concentrations in the blood or aqueous humour in order to achieve desirable prophylactic effects, especially in the overweight and obese patients.

Stromal Herpetic Keratitis with Ulceration Associated with Reactivation of Epstein–Barr Virus and Human Herpes Virus Type 6: Experience of Diagnosis and Therapy

Objective: to study the clinical manifestations of herpetic stromal keratitis with ulceration associated with EBV and HHV-6 reactivation.Patients and methods. 172 patients with anterior ophthalmic herpes were under observation, of which 43 patients had herpetic stromal keratitis with ulceration with an average duration of complaints of more than 60 days. Tear, saliva, blood and urine samples were used as a material for PCR (qualitative and quantitative) for the presence of HSV, VZV, CMV, EBV, HHV-6, HHV-7 DNA. Local therapy of the acute period included instillation of antiviral, anti-inflammatory agents and lubricants. Systemic antiherpetic therapy included oral use of selective nucleoside analogues: valacyclovir and famciclovir in increased daily dosages.Results. 87 cumulative positive results were obtained, of which the proportion of EBV and HHV-6 DNA detection was 23 % and 28 %. Complex local therapy with the inclusion of heparin-containing lubricant and a drug containing 5 % dexpanthenol (“Corneregel”) combined with systemic therapy with nucleoside analogues in increased daily dosages led to complete relief of objective symptoms within 14 to 28 days.Conclusions. EBV and HHV-6 were detected in more than 50 % of cases, which determines systemic antiviral therapy in increased daily dosages and a prolonged course. The pathogenesis of ulcerative defects may be associated with the direct reactivation of HHV-6 and EBV, which requires the use of active reparative therapy from the first days of curation. The phenomenon of a transient viral “surge” detected by PCR during disease course can be observed by adequate systemic therapy and is a normal laboratory pattern indicating the correct tactics.

Unilateral Herpetik Keratitli Hastalarda Kuru Göz Parametrelerinin Değerlendirilmesi

Objective: Our aim in this study was to examine the tear parameters between affected and unaffected eyes of unilateral herpes simplex virus (HSV) keratitis patients, especially the meibomian glands status. Methods: The examinations and tear parameters including; tear film meniscus height (TMH) and area (TMA), non-invazive break up time (NIBUT), schirmer test, meibomian gland’s ekspressibility grade, drop out grade and microstructure of patients who were treated in our clinic with the diagnosis of unilateral herpetic endothelitis or herpetic stromal keratitis, and who had a quiescent period of about 3 months, were evaluated retrospectively. Results: The median age of our patients was 58.0 (55.25-72.25) years. The median NIBUT was 6.85 (4.62-17.0) sec. in affected eye and 15.85 (10.47-17.15) sec. in unaffected eye. NIBUT values were observed to be remarkable lower in the affected eye, although the change between groups was not statistically significant. Schirmer test values, TMH and TMA were similar between affected and unaffected eyes. Meibomian gland evaluations of affected and unaffected eyes were shown similar distribution across meibomian expressibility and drop out grades. Conclusion: We observed similar effects in both morphological and microstructural features of meibomian glands in both eyes. This condition makes us think that the developing dry eye disease in both eyes may be caused not only by neurosensorial anomalies but also by changes in the meibomian glands.

E3 ligase RNF5 inhibits type I interferon response in herpes simplex virus keratitis through the STING/IRF3 signaling pathway.

Herpes simplex keratitis (HSK), caused by the herpes simplex virus 1 (HSV-1), is a major blinding disease in developed countries. HSV-1 can remain latent in the host for life and cannot be eradicated. The infection causes the secretion of various cytokines and aggregation of inflammatory cells. In the early stage of inflammation, mainly neutrophils infiltrate the cornea, and CD4+ T cells mediate the immunopathological changes in herpetic stromal keratitis in the subsequent progression. The STING/IRF3-mediated type I interferon (IFN) response can effectively inhibit viral replication and control infection, but the activity of STING is affected by various ubiquitination modifications. In this study, we found that the expression of RNF5 was elevated in corneal tissues and corneal epithelial cells after infection with HSV-1. Immunofluorescence staining confirmed that RNF5 was mainly expressed in the corneal epithelial layer. We silenced and overexpressed RNF5 expression in corneal epithelial cells and then inoculated them with HSV-1. We found that the expressions of STING, p-IRF3, p-TBK1, and IFN-β mRNA increased after RNF5 silencing. The opposite results were obtained after RNF5 overexpression. We also used siRNA to silence RNF5 in the mouse cornea and then established the HSK model. Compared with the siRNA-control group, the siRNA-RNF5 group showed significantly improved corneal inflammation, reduced clinical scores and tear virus titers, and significantly increased corneal IFN-β expression. In addition, the expressions of the proinflammatory cytokines IL-6 and TNF-α in the corneal tissue were significantly decreased, indicating that RNF5 silencing could effectively promote IFN-I expression, inhibit virus replication, alleviate inflammation, and reduce corneal inflammatory damage. In summary, our results suggest that RNF5 limits the type I IFN antiviral response in HSV corneal epithelitis by inhibiting STING/IRF3 signaling.

CD137 costimulation is associated with reduced herpetic stromal keratitis and with developing normal CD8+ T cells in trigeminal ganglia.

Costimulatory interactions can be critical in developing immune responses to infectious agents. We recently reported that herpes simplex type 1 (HSV-1) infections of the cornea require a functional CD28-CD80/86 interaction to not only reduce the likelihood of encephalitis, but also to mediate herpetic stromal keratitis (HSK) following viral reactivation. In this same spirit we decided to determine the role that CD137 costimulation plays during HSK. Using both B6-CD137L-/- mice, as well as antagonistic and agonistic antibodies to CD137 we characterize the immune response and to what extent CD137 plays an important role during this disease. Immune responses were measured in both the cornea and in the trigeminal ganglia where the virus forms a latent infection. We demonstrate that CD137 costimulation leads to reduced corneal disease. Interestingly, we observed that lack of CD137 costimulation resulted in significantly reduced CD8+ T expansion and function in the trigeminal ganglia. Finally, we showed that viruses that have been genetically altered to express CD137 display significantly reduced corneal disease, though they did present similar levels of trigeminal infection and peripheral virus production following reactivation of a latent infection. CD137 interactions lead to reduced HSK and are necessary to develop robust trigeminal CD8+ T cell responses.

Antibody response to herpes simplex virus-1 is increased in autoimmune encephalitis.

Antibody response to herpes simplex virus-1 is increased in autoimmune encephalitis.

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.

Modulating glutamine metabolism to control viral immuno-inflammatory lesions

Infection of the cornea with HSV results in an immune-inflammatory reaction orchestrated by proinflammatory T cells that is a major cause of human vision impairment. The severity of lesions can be reduced if the representation of inflammatory T cells is changed to increase the presence of T cells with regulatory function. This report shows that inhibiting glutamine metabolism using 6-Diazo-5-oxo-l-norleucine (DON) administered via intraperitoneal (IP) starting 6 days after ocular infection and continued until day 15 significantly reduced the severity of herpetic stromal keratitis lesions. The therapy resulted in reduced neutrophils, macrophages as well proinflammatory CD4 Th1 and Th17 T cells in the cornea, but had no effect on levels of regulatory T cells. A similar change in the representation of inflammatory and regulatory T cells occurred in the trigeminal ganglion (TG) the site where HSV infection establishes latency. Glutamine metabolism was shown to be required for the in-vitro optimal induction of both Th1 and Th17 T cells but not for the induction of Treg that were increased when glutamine metabolism was inhibited. Inhibiting glutamine metabolism also changed the ability of latently infected TG cells from animals previously infected with HSV to reactivate and produce infectious virus.

Fermented pomegranate extracts protect against oxidative stress and aging of skin.

Punica granatum (pomegranate) potentially ameliorates skin inflammation and pain, including herpetic stromal keratitis. Fermentation is a biotechnological technique that may naturally induce health benefits by producing antioxidants. However, the anti-aging effect of fermented pomegranate extracts (FPE) on the skin is still unclear. This investigation evaluates the effects of fermented pomegranate as a functional supplement (FPE drink, FPE-D) and a cosmetic ingredient (FPE serum, FPE-S) in vitro and in vivo. The effects of FPE products for anti-oxidation, anti-tyrosinase, anti-inflammation, and anti-aging were examined. Forty subjects were randomly allocated to FPE-D or placebo drink groups (50ml of a FPE-D /placebo drink daily for 8weeks for each subject), and another 40subjects were recruited to FPE-S or placebo serum groups (about 3ml of a FPE-S /placebo serum daily and nightly/daily for 4weeks for each subject) in a double-blind study. The effects of FPE products on the DPPH, ABTS+ , and NO· free radical scavenging activities, their inhibiting of tyrosinase activity and their enhancement of the skin health of healthy subjects, were investigated. FPE-D improved the moisture, brightness, elasticity, and collagen density of the skin of most subjects at 8weeks relative to the baseline without treatment (p<0.05). After 4weeks of FPE-S serum consumption, the moisture, brightness, elasticity, spots, UV spots, and collagen density of skin were slightly better than those at week 0 (p<0.05). The daily consumption of fermented pomegranate extracts can protect the skin against oxidative stress and slow skin aging.

IFN-λ Regulates Neutrophil Biology to Suppress Inflammation in Herpes Simplex Virus-1-Induced Corneal Immunopathology.

HSV-1 infection of the cornea causes a severe immunoinflammatory and vision-impairing condition called herpetic stromal keratitis (SK). The virus replication in corneal epithelium followed by neutrophil- and CD4+ T cell-mediated inflammation plays a dominant role in SK. Although previous studies demonstrate critical functions of type I IFNs (IFN-α/β) in HSV-1 infection, the role of recently discovered IFN-λ (type III IFN), specifically at the corneal mucosa, is poorly defined. Our study using a mouse model of SK pathogenesis shows that HSV-1 infection induces a robust IFN-λ response compared with type I IFN production at the corneal mucosal surface. However, the normal progression of SK indicates that the endogenous IFN responses are insufficient to suppress HSV-1-induced corneal pathology. Therefore, we examined the therapeutic efficacy of exogenous rIFN-λ during SK progression. Our results show that rIFN-λ therapy suppressed inflammatory cell infiltration in the cornea and significantly reduced the SK pathologic condition. Early rIFN-λ treatment significantly reduced neutrophil and macrophage infiltration, and IL-6, IL-1β, and CXCL-1 production in the cornea. Notably, the virucidal capacity of neutrophils and macrophages measured by reactive oxygen species generation was not affected. Similarly, ex vivo rIFN-λ treatment of HSV-1-stimulated bone marrow-derived neutrophils significantly promoted IFN-stimulated genes without affecting reactive oxygen species production. Collectively, our data demonstrate that exogenous topical rIFN-λ treatment during the development and progression of SK could represent a novel therapeutic approach to control HSV-1-induced inflammation and associated vision impairment.

Topical Corticosteroids for Infectious Keratitis Before Culture-Proven Diagnosis.

PurposeIn clinical practice we sometimes encounter patients with severe corneal ulcers who have been treated with topical corticosteroids. This study reviewed the clinical features and visual outcomes of these patients and investigated the background of the prescription of topical corticosteroids.Patients and MethodsThe medical records of patients who visited the Cornea Service at Fujita Health University Bantane Hospital and were treated for infectious keratitis from April 2016 to March 2020 were retrospectively reviewed. Patients treated with topical corticosteroids before a culture-proven diagnosis were studied in terms of demographics, best-corrected visual acuity at arrival and at last visit, the clinical course after visit, ocular history, and combination therapy by the previous ophthalmologist.ResultsOut of the 200 eyes of 197 patients with infectious keratitis, 14 eyes of 14 patients were treated with topical corticosteroids before a culture-proven diagnosis. All 14 patients were referred, as they had severe keratitis that could not be cured with topical antibiotics and corticosteroids. Based on the culture results, we diagnosed Acanthamoeba keratitis (AK) in six patients, fungal keratitis (FK) in two patients, bacterial keratitis (including a suspected case) in two patients, and unknown cause in four patients. Two patients with AK, FK, and unknown keratitis had unfortunate clinical courses and poor visual outcomes. From the information in the referral letters, at least six of the 14 patients were treated with either acyclovir ocular ointment or valaciclovir tablets, along with topical corticosteroids.ConclusionApplication of topical corticosteroids for keratitis that does not respond to empirical antibiotic therapy is harmful since AK or FK is likely involved in these topical antibiotic-resistant cases. Microbiological evidence, as well as a differential diagnosis of herpetic stromal keratitis, is needed when prescribing topical corticosteroid for the treatment of suspected infectious keratitis.