Concomitant herpes simplex keratitis and autoimmune-associated ulcerative keratitis in rheumatoid arthritis patients.
ABSTRACT: Purpose:To describe four cases of concomitant herpes simplex keratitis (HSK) and autoimmune-associated ulcerative keratitis (UK) in patients with rheumatoid arthritis (RA). Observations:All patients developed HSK and UK while undergoing treatment for RA. The average age of onset for RA, UK and HSK was 49.3, 69.5 and 70.5 years, respectively. UK preceded HSK in three cases and followed HSK in one case. Two patients had bilateral UK and two had unilateral UK. HSK was unilateral in all cases. All the cases had been treated with immunosuppressive agents including steroid, methotrexate, calcineurin inhibitors, etanercept and tocilizumab at the onset of HSK. Every patient was treated for HSK with topical acyclovir ointment combined with oral valacyclovir. The final visual outcome was extremely poor despite intensive therapy. Conclusions and Importance:These cases raise the possibility that RA patients have an increased risk of HSK, and that HSK may tend to be severe in these patients because of their immunocompromised condition. Furthermore, the complication of HSK and UK in RA patients is difficult to treat because of the atypical clinical manifestation. Thus, the emergence of corneal ulcer, especially in patients with a long clinical history of RA, calls for careful follow-up.
Project description:PURPOSE:To evaluate the incidence, related perioperative factors, clinical characteristics, and possible etiologies of epithelial keratitis after cataract surgery. METHODS:A retrospective chart review of 666 eyes in 666 patients who underwent cataract surgery was performed to evaluate the incidence of epithelial keratitis and related factors in the postoperative period. RESULTS:Postoperative epithelial keratitis developed in 15 eyes. Eleven of the 15 eyes were diagnosed with herpes simplex keratitis (HSK); 10 of the 11 eyes were diagnosed by polymerase chain reaction, and the remaining 1 eye by clinical diagnosis. All patients diagnosed with HSK had no previous clinical history of the infection before undergoing cataract surgery. Initially, the diagnosis of all 15 eyes was toxic keratitis, but the final diagnosis of 11 of the initial 15 was found to be epithelial herpes keratitis. The incision location was shown to be related to the occurrence of HSK in our study (P < 0.05). CONCLUSIONS:HSK epithelial keratitis after cataract surgery is a relatively uncommon complication and can be misdiagnosed in its early disease course because of its relative rarity. This study explores the possibility that the temporal corneal penetrating incisional approach used in routine cataract surgery interrupts the corneal nerves and subsequently can trigger reactivation of HSK.
Project description:Herpes simplex virus (HSV) necrotizing stromal keratitis is a common type of herpetic stromal keratitis (HSK). Antiviral medication alone cannot control the disease, and corticosteroid eye drops may aggravate the ulcer and result in corneal perforation. Amniotic membrane transplantation effectively treats superficial corneal ulcer resulting from necrotizing stromal HSK. However, the efficacy of this approach seems to be limited for more serious cases. This study presented the clinical treatment of severe HSV necrotizing stromal keratitis (ulcer depth greater than half of the corneal stroma) by conjunctival flap covering surgery in 25 patients (25 eyes) combined with antivirus and corticosteroid treatment at Shandong Eye Hospital from January 2007 to December 2013. Clinical results showed that the mean best spectacle-corrected visual acuity improved from preoperative 20/333 to postoperative 20/40 (P < 0.05). All patients recovered ocular surface stabilization. There was recurrence in two eyes, which was cured with antiviral medication. Conjunctival flap covering combined with antivirus and corticosteroid treatment is effective in treating severe HSV necrotizing stromal keratitis.
Project description:Background and objectives: Recurrent herpes simplex keratitis (HSK) is the most common cause of corneal blindness in the developed world. A relationship between host gene polymorphisms and the recurrence of herpes simplex virus (HSV) infection has previously been proposed. Thus, the aim of this study was to investigate a potential association between the IL28B host genotype and recurrent HSK. Materials and Methods: Eighty patients older than 18 years of age of both genders with a history of recurrent herpes simplex labialis (HSL) were considered for inclusion. Seventy-five of these patients were found to be seropositive for HSV-1 and were subsequently enrolled in the study. Twenty-four of the enrolled patients also had a history of recurrent HSK associated with severe corneal scarring and visual acuity deterioration. Total DNA was isolated from whole blood samples. A single-nucleotide polymorphism (SNP) rs12979860 near the IL28B gene on chromosome 19 was genotyped. Results: A significant association was observed between recurrent HSK and two SNPs of the IL28B genotype (CCrs12979860 and CTrs12979860, p < 0.01). The variation CCrs12979860 showed a significantly greater association with HSK (16 out of 26 patients) compared with CTrs12979860 (8 out of 34 patients). Conclusion: Seropositive individuals with a history of recurrent HSK are likely to have the CC IL28B genotype. This genotype may be related to incomplete control of the infection and more frequent periodical viral shedding along the first nerve branch of the trigeminal ganglion, which clinically manifests as recurrent herpes keratitis. The clinical manifestation of recurrent HSV-1 infection seems to be influenced by polymorphism of the IL28B genotype.
Project description:Herpetic stromal keratitis (HSK) is a blinding ocular disease that is initiated by HSV-1 and characterized by chronic inflammation in the cornea. Although HSK immunopathology of the cornea is well documented in animal models, events preceding this abnormal inflammatory cascade are poorly understood. In this study, we have examined the activation of pathological CD4(+) T cells in the development of HSK. Dendritic cell autophagy (DC-autophagy) is an important pathway regulating major histocompatibility complex class II (MHCII)-dependent antigen presentation and proper CD4(+) T cell activation during infectious diseases. Using DC-autophagy-deficient mice, we found that DC-autophagy significantly and specifically contributes to HSK disease without impacting early innate immune infiltration, viral clearance, or host survival. Instead, the observed phenotype was attributable to the abrogated activation of CD4(+) T cells and reduced inflammation in HSK lesions. We conclude that DC-autophagy is an important contributor to primary HSK immunopathology upstream of CD4(+) T cell activation.Herpetic stromal keratitis (HSK) is the leading cause of infectious blindness in the United States and a rising cause worldwide. HSK is induced by herpes simplex virus 1 but is considered a disease of inappropriately sustained inflammation driven by CD4(+) T cells. In this study, we investigated whether pathways preceding CD4(+) T cell activation affect disease outcome. We found that autophagy in dendritic cells significantly contributed to the incidence of HSK. Dendritic cell autophagy did not alter immune control of the virus or neurological disease but specifically augmented CD4(+) T cell activation and pathological corneal inflammation. This study broadens our understanding of the immunopathology that drives HSK and implicates the autophagy pathway as a new target for therapeutic intervention against this incurable form of infectious blindness.
Project description:Eye disease due to herpes simplex virus (HSV) is a leading cause of ocular morbidity and the number one infectious cause of unilateral corneal blindness in the developed parts of the globe. Recurrent keratitis can result in progressive corneal scarring, thinning, and vascularization. Antiviral agents employed against HSV have primarily been nucleoside analogs. Early generation drugs included idoxuridine, iododesoxycytidine, vidarabine, and trifluridine. While effective, they tended to have low bioavailability and measurable local cellular toxicity due to their nonselective mode of action. Acyclovir 0.3% ointment is a more selective agent, and had become a first-line topical drug for acute HSV keratitis in Europe and other places outside of the US. Ganciclovir 0.15% gel is the most recently approved topical treatment for herpes keratitis. Compared to acyclovir 0.3% ointment, ganciclovir 0.15% gel has been shown to be better tolerated and no less effective in several Phase II and III trials. Additionally, topical ganciclovir does not cause adverse systemic side effects and is therapeutic at lower concentrations. Based on safety, efficacy, and tolerability, ganciclovir 0.15% gel should now be considered a front-line topical drug in the treatment of dendritic herpes simplex epithelial keratitis. Topics of future investigation regarding other potential uses for ganciclovir gel may include the prophylaxis of recurrent HSV epithelial keratitis, treatment of other forms of ocular disease caused by herpesviruses and adenovirus, and ganciclovir gel as an adjunct to antitumor therapy.
Project description:BACKGROUND: Dolosigranulum pigrum is a commensal inhabitant of the upper respiratory tract suspected to be responsible for ocular infections but no well-described case of D. pigrum corneal infection has been reported. Herein culture and PCR-sequencing-based investigations of corneal scraping specimens confirmed D. pigrum keratitis in three patients. CASE PRESENTATION: Three elderly patients presented with unilateral keratitis. None was a corneal-contact lens wearer, one had previous cataract surgery and another suffered rheumatoid arthritis sicca syndrome. Culturing the corneal scraping specimen was positive for two cases and PCR-sequencing of bacterial 16S rDNA in the presence of negative controls identified D. pigrum in three cases. The two D. pigrum isolates were in-vitro susceptible to penicillin G, amoxicillin, doxycycline, rifampicin and gentamicin. In all cases, surgical treatment of corneal thinning was necessary, but corneal perforation occurred in two cases despite intensive antimicrobial treatment with ticarcillin, gentamicin and vancomycin or levofloxacin eye drops leading to enucleation in one case. CONCLUSIONS: D. pigrum is the likely cause of corneal infection in three patients, with effective antibiotic treatment in two patients.
Project description:PURPOSE:To report the isolation of Pestalotiopsis clavispora from the cornea of a patient with recurrent keratitis. CASE REPORT:A 73-year-old male gardener presented with conjunctival injection and an oval infiltrate with feathery margins in the temporal half of the cornea in the right eye. His ocular history in the right eye included cataract surgery, five episodes of herpes simplex keratitis, three glaucoma surgeries, and bullous keratopathy. He had been treated with corticosteroids for years. Light microscopy of corneal scrapings revealed a filamentous fungus, and fungal keratitis was diagnosed. Treatment with topical voriconazole and pimaricin ointment was commenced. One month later, the infiltrate resolved. The antifungal agents were discontinued 7 months later, and keratitis relapsed 4 days after the discontinuation. The fungus was isolated and identified by molecular techniques as P. clavispora. Based on the results of antifungal susceptibility testing, treatment with topical and intravenous micafungin was initiated. The corneal infiltrate resolved 1 month after the relapse. CONCLUSION:Molecular identification of the pathogen, and antifungal susceptibility testing, are useful in treating patients with fungal keratitis caused by a rare human pathogen.
Project description:Chronic inflammation in tissues often causes the development of hypoxia. Herpes stromal keratitis (HSK) is a corneal chronic inflammatory condition that develops in response to recurrent HSV-1 infection. In this study, we investigated the development of hypoxia, the expression of hypoxia-associated glycolytic genes in HSV-1 infected corneas, and the outcome of blocking hypoxia-inducible factor (HIF) dimerization on the severity of HSK. Our results showed the development of hypoxia, an elevated expression of hypoxia-associated glycolytic genes, and an increased level of lactate in corneas with progressing HSK lesions. The magnitude of hypoxia correlated with the extent of neutrophils infiltrating the infected corneas, and the depletion of neutrophils reduced the development of hypoxia in infected corneas. Additionally, in progressing HSK lesions, nuclear localization of HIF-2? protein was detected in corneal epithelial cells, whereas HIF-1? protein stabilization was observed in infiltrating immune cells. Administration of acriflavine drug to HSV-1-infected mice inhibited nuclear accumulation of HIF-1? and HIF-2? protein in immune cell types and epithelial cells, respectively, in infected corneas. As a result, a decreased influx of CD4 T cells and nongranulocytic myeloid cells, but an increased influx of neutrophils, was noted in developing HSK lesions. Interestingly, acriflavine treatment given during the clinical disease period decreased neovascularization but increased the opacity in HSV-1-infected corneas. Taken together, the results of our study lay the foundation to dissect the role of inflammatory hypoxia and hypoxia-associated genes in the pathogenesis of HSK.
Project description:We report the first known case of fungal keratitis caused by Aspergillus nomius. Ocular injury was known as a predisposing factor. The patient was treated with natamycin and econazole eye drops, itraconazole eye ointment, and oral ketoconazole. A therapeutic penetrating keratoplasty was performed 16 days after presentation. A sequence-based approach was used to assign the isolate to a species.
Project description:Herpes simplex virus type 1 (HSV-1) is a neurotrophic virus that can cause herpes stromal keratitis (HSK), a severe corneal inflammation that can lead to corneal scarring and blindness. This study identified neurologic changes that occur in HSV-1-infected corneas and related them to HSV-1-induced immunopathology.Corneas of BALB/c and C57BL/6 mice were infected with HSV-1 strains that induce HSK. Changes in sensory nerves were identified by immunofluorescence staining of sensory and sympathetic nerves for substance P (SP) and tyrosine hydroxylase (TH), respectively, and confocal microscopic examination. Some mice received superior cervical ganglionectomy (SCGx) to eliminate sympathetic nerves from the cornea.Normal corneas exclusively expressed sensory nerves that entered the stroma as large nerve stalks, branched to form a plexus at the epithelial/stromal interface, and extended termini into the epithelium. These nerves completely retracted from the infected cornea and were replaced by sympathetic nerves that sprouted extensively to hyperinnervate the corneal stroma but failed to form a plexus or extend termini into the epithelium. The hyperinnervating nerves expressed the sympathetic nerve marker TH and their invasion was blocked by performing SCGx. Moreover, the corneal opacity and neovascularization that normally characterizes HSK in this mouse model were largely abrogated by SCGx. Sensory nerves reinnervated infected corneas following SCGx, reformed a nerve plexus, and extended termini into the epithelium resulting in recovery of corneal sensitivity.Sympathetic nerves have a central role in HSK in mice, preventing reinnervation by sensory nerves and promoting severe and persistent corneal inflammation.