Blockade of IL-27 signaling ameliorates herpes stromal keratitis with upregulated CD4+ Foxp3+ regulatory T cells influx in mice

Purpose: The purpose of this study was to investigate the production of IL-27 p28 and EBI3 in the ocular inflammatory sites, and the role of IL-27 signaling in a model of HSV-1 induced herpetic stromal keratitis (HSK). Methods: The BALB/c mice were injected intraperitoneally (24 h before infection) with anti-IL-27 antibody or IgG antibody as control, infected with HSV-1 via corneal scarification, and then injected intraperitoneally with anti-IL-27 antibody or IgG antibody at 1, 3, and 5 days postinfection. Slit lamp and histopathology were used to assess disease outcome. The levels of IL-27 p28 and EBI3 in corneas were determined by western blotting and immunofluorescence. Furthermore, viral titers were determined, and immune cell infiltrates were collected and analyzed by flow cytometry. Results: We found that the levels of IL-27 p28 and EBI3 in corneas were elevated significantly at the peak of HSK, and both of them were expressed simultaneously in the epithelium, stroma, and endothelium of corneas. In the group of anti-IL-27 treatment, the severity of the corneal lesion and CD4+ T cells infiltration were significantly decreased, and the percentage of CD4+ Foxp3+ Tregs was upregulated markedly in the spleen, DLNs and cornea of HSK mice compared to IgG treatment. Conclusion: These results provided evidence that IL-27 as a pathogenic pro-inflammatory cytokine controlled CD4+ Foxp3+ Tregs production in HSK, which ultimately resulted in promoting the progression of HSK and poor prognosis.

An unusual occurrence of stromal keratitis in dengue fever

Dengue is a mosquito-borne infection endemic in the tropical and subtropical regions of the world. Classic dengue fever is a self-limiting, influenza-like illness transmitted by Aedes aegypti mosquito. Ophthalmic manifestations though rare can involve both the anterior and posterior segments and are usually associated with the thrombocytopenic state. However, ophthalmic complications such as anterior uveitis and vasculitis suggest immune-mediated pathogenesis. Herein, we report a rare case of stromal keratitis and an unusual occurrence of simultaneous bilateral blindness following dengue fever in a young girl.

Role of CD160/BTLA-HVEM-LIGHT/LT-α signaling pathway related to herpetic stromal keratitis / 中华实验眼科杂志

Ocular infection of herpes simplex virus-1 (HSV1) can result in herpetic stromal keratitis (HSK),which impairs vision and is a common cause of human blindness.Studies indicated that HSK lesions are mainly orchestrated by CD4+ T cells.Herpesvirus entry mediator (HVEM),a tumor necrosis factor receptor superfamily member,facilitates virus entry through interactions with viral glycoprotein D (gD).HVEM,a widely expressed tumor necrosis factor (TNF) receptor superfamily member with diverse roles in immune signaling.Intriguingly,HVEM has five receptors:two costimulatory molecules (LIGHT and LT-α),two coinhibitory molecules (BTLA and CD160),and the HSV-gD.HVEM is referred to as a molecular switch because of its capacity to deliver costimulatory signals when bound to LIGHT/LT-α and to produce inhibitory signals when bound to BTLA/CD160.In this paper,the researching progress of the five receptors functions of HVEM and CD160/BTLA-HVEM-LIGHT/LT-α signaling pathway in the HSK were reviewed.We have to provide an insight into the pathogenesis of HSK and clinical ideas for the effective treatment of HSK.Through effective clinical intervention,the inflammatory immune response is reduced,thereby achieving therapeutic effects on recurrence of autoimmune diseases and chronic immune diseases.

Clinical efficacy of oral and topical acyclovir in herpes simplex virus stromal necrotizing keratitis.

Purpose: To evaluate the efficacy of systemic and topical antiviral therapy in the treatment of active herpes simplex virus (HSV) necrotizing stromal keratitis (NSK). Design: Prospective interventional case series. Methodology: Patients with a diagnosis of HSV NSK based on history and clinical findings were enrolled in the study. A standard protocol was used for microbiologic investigations. Ten weeks regime of systemic acyclovir and 2 weeks of topical acyclovir was given. Complete ophthalmic examination was performed at every visit. Outcome measures were a reduction in the area of infiltration and improvement in visual acuity. Results: Fifteen patients were enrolled in the study. The mean age of presentation was 51.53 years. The duration of symptoms at presentation ranged from 2 to 8 weeks. HSV1 DNA polymerase chain reaction was positive in 70% cases of those tested. Area of infiltration at trial entry and at the end of 2 weeks of antiviral treatment reduced significantly (P = 0.007). All patients showed a complete resolution of keratitis at the end of study. Conclusion: Topical and systemic acyclovir for treatment of NSK facilitates healing of ulceration. Topical steroids after initial antiviral therapy are safe and decreases inflammation and improve visual recovery. Early initiation of therapy has better outcomes as compared to late presentations.

Cilindros retrocorneanos: un hallazgo poco usual de la queratitis por sífilis / Retrocorneal cylinders: an unusual fi nding of syphilitic keratitis

Objetivo: Describir el caso de una paciente con una presentación inusual de queratitis intersticial por sífilis. Diseño: Estudio descriptivo, retrospectivo, reporte de caso. Metodología: Se realizó una revisión de la historia clínica del paciente y de la literatura con referencia al diagnóstico. Resultados: Paciente femenina de 67 años quien consulta por cuadro de 4 días de evolución de disminución progresiva y dolorosa de agudeza visual en ojo derecho. En el examen oftalmológico se evidenció una lesión cilíndrica, ramificada en cámara anterior, con adherencias al endotelio corneano, edema y leucoma corneano por lo cual se diagnosticó queratitis intersticial por sífilis; se confirmó por serología y se realizó el manejo correspondiente. Conclusiones: Aunque la queratitis intersticial por sífilis tiene baja incidencia y prevalencia en la actualidad, debe tenerse en cuenta dentro de los diagnósticos diferenciales en pacientes que presenten queratitis estromal no ulcerativa y así mismo, debe hacerse estudio serológico en todos los casos de queratitis estromal bilateral cuya causa no esté definida ya que puede ser la única manifestación de la enfermedad. Un hallazgo clínico raro es la aparición de cilindros, rollos o membranas retrocorneales. El conocimiento de todas las formas de presentación, aún las más infrecuentes, como en nuestro caso es importante en el diagnóstico y manejo de esta patología.

Objective: Describe the case of a patient with an unusual presentation of syphilitic interstitial keratitis. Design: A descriptive, retrospective study and case report. Methodology: A literature review was made about the pathology and specific diagnosis. Results: A 67-year-old female patient was seen for a 4-day course of progressive and painful decrease of visual acuity in the right eye. During the ophthalmologic examination, a cylindrical and branching lesion with adhesions to the corneal endothelium was noted, corneal edema and leukoma was also founded. Diagnosis of interstitial syphilitic keratitis was made; the clinical picture was confi rmed by serology and the patient was managed accordingly. Conclusions: Although syphilitic interstitial keratitis has low incidence and prevalence, this disease must be considered into the differential diagnosis of patients with non-ulcerative stromal keratitis and a serology study must be done in all cases of bilateral stromal keratitis, as it may be the only manifestation of the disease. An unusual finding is the appearance of cylinders, rolls or retrocorneal membranes. Knowledge of all forms of presentation, even the most infrequent, as in this case, is important in the diagnosis and management of this condition.

A Case of Multiple Complications in Herpes Zoster Ophthalmicus

PURPOSE: We report a case of stromal keratitis, corneal infiltration, anterior uveitis, central retinal artery occlusion and optic neuropathy in a patient with herpes zoster ophthalmicus. CASE SUMMARY: A 73-year-old man who was hospitalized for pain and vesicles on his left face was referred to our clinic with sudden onset visual disturbance in his left eye. His best corrected visual acuity in the right eye was 0.8 and light-perception in his left eye. Relative afferent pupillary defect was found in his left eye. Slit-lamp examination showed anterior uveitis secondary to herpes zoster ophthalmicus presented with stromal keratitis. Fundus examination showed retinal hemorrhage, vitreous opacity, cherry-red spot in the fovea and optic disc swelling. Delayed arterial filling and arteriovenous transit time were observed on fluorescence angiography. He was treated with topical antiviral and steroid eye drops for stromal keratitis and anterior uveitis. He was also treated systemically with an intravenous antiviral agent and oral steroid, but visual acuity did not improve. CONCLUSIONS: Stromal keratitis, corneal opacity, anterior uveitis, central retinal artery occlusion and optic neuropathy can be complications of herpes zoster ophthalmicus.

Expression of interleukin-9 in murine cornea with herpetic stromal keratitis / 中华实验眼科杂志

Background Herpetic stromal keratitis (HSK) is an immunopathologic eye disorder mediated by CD4+ T lymphocytes.Interleukin-9 (IL-9) is a cytokine linked to the process of many immune inflammatory diseases,but whether IL-9 is involved in the immunopathology of HSK remains unclear.Objective This study was to investigate the expression of IL-9 in murine cornea during the development of HSK and its relationship with the degree of HSK.Methods One hundred and eighty clean BALB/c mice were divided into the normal control group (20 mice) and experimental group (160 mice).HSK models were established by scratching on the surface of the cornea followed by inoculation of 1 × 106 plague forming unit(PFU) herpes simplex virus type 1 (HSV-1) KOS strain.Change of ocular surface was examined under the slit lamp biomicroscopy before and I day,3,5,7,8,10,14,21 days after inoculation of HSV-1.The corneas of mice were collected on the time points mentioned above.The relative expression level of IL-9 mRNA in the cornea of mice was detected by real-time PCR.Immunocytochemical localization of IL-9 protein in murine cornea was viewed by a confocal microscope after preparation of the corneal cryostat sections.All experimental manipulations were undertaken in accordance with the institutional guidelines for the care and use of laboratory animals.Results Punctiform,dendriform or geographic defect in corneal epithelium were seen 3 days and healing 6 days after inoculation of HSV-1.However,edema and opacity of the corneal stroma appeared 7 days and peaked 14 days following the inoculation.Real-time PCR assay showed that very little of IL-9 mRNA (A260/A280) was expressed in the cornea in the mice of the control group.But in 1 day,3,5,7,8,10 and 14 days,the relative level of IL-9 mRNA was 6.37±0.45,5.66±0.53,3.93±0.35,3.62±0.34,3.23±0.18,2.57±0.14,2.19±0.20,with a significant difference among the various time points (F=92.764,P=0.000),and IL-9 mRNA in 1 day,3,5,7,8,10 and 14 days after inoculation was significantly higher than before inoculation (P＜0.05);while no markedly difference was found in IL-9 mRNA expression between the 21-day group after inoculation and the normal control group (P =0.340).IL-9 protein was expressed in the epithelial layer,stromal layer and endothelial cell layer of the corneas,with a stronger green fluorescence in the HSK mice,but no expression of IL-9 protein was seen in the control mice.Conclusions HSK model can be successfully created by corneal scratching and inoculation of HSV-1 KOS strain in BALB/c mouse.IL-9 is involved in the pathogenesis and development of HSK mediated by immunoresponse.

Clinical Analysis of Herpetic Keratitis in Korea

PURPOSE: To investigate the clinical characteristics of herpetic keratitis in Korea. METHODS: A retrospective analysis was performed on 90 eyes of 84 patients who were clinically diagnosed with herpetic keratitis and were followed for at least 4 months or more. Information on prior herpetic keratitis, type of keratitis, time to remission, recurrence rate, administration of oral acyclovir, final visual acuity was reviewed. Remission time and recurrence rate were compared according to types of herpetic keratitis and the application of oral acyclovir in epithelial, stromal or endothelial keratitis; and the relation of history of previous herpetic keratitis, recurrence and final vision, was analyzed. RESULTS: Sex ratio (M:F) was 1.31 and the mean age was 54.6 years. Of 90 eyes, the proportion of infectious epithelial keratitis, stromal keratitis, endothelitis and neurotrophic ulcer was 51.1, 17.8, 25.6 and 5.6%, respectively. The mean remission time was 1.92+/-1.01, 4.13+/-5.05, 5.52+/-5.08, 4.00+/-1.00, respectively (p=0.001, one-way Anova). Recurrence occurred in 21 (42.9%) eyes of 49, which were followed up for more than 12 months, in a year after the previous attack. The rates of recurrence of infectious epithelial keratitis, stromal keratitis and endothelitis were 25.0%, 63.6% and 53.8%, respectively. Oral acyclovir neither shortens the remission nor prevents the recurrence. The percentage of final vision over 20/40 in infectious epithelial keratitis, stromal keratitis and endothelitis was 81.1, 57.1 and 60.0%, respectively. The final vision was worse in the group with a history of herpetic keratitis. CONCLUSIONS: Stromal keratitis and endothelitis showed a higher recurrence rate and longer remission time than infectious epithelial keratitis. Because recurrent and severe keratitis may result in corneal opacity and vision loss, aggressive and proper treatment is needed. However, these cases are often resistant to therapy.