Culture of Tropheryma whippelii from the vitreous fluid of a patient presenting with unilateral uveitis.
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Biomedical subjects
Publications and source records attributed to Bahram Bodaghi.
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PURPOSE: To report a case of papilledema and pseudotumor cerebri developed in association with Sjögren's syndrome. METHODS: Case-report of a 38-year-old woman with history, imaging and histology confirming the diagnosis of both pseudotumor cerebri and Sjögren's syndrome who presented with bilateral decrease of vision. RESULTS: Papilledema associated with pseudotumor cerebri was observed in both eyes. The patient's visual acuity improved transiently with the administration of intravenous steroids and cyclophosphamide; subsequently she needed a ventriculoperitoneal shunt. CONCLUSION: Sjögren's syndrome should be considered in the different etiologies of pseudotumor cerebri. The major improvement with corticosteroids and ventriculoperitoneal shunt makes prompt diagnosis essential.
PURPOSE: To describe the occurrence of conjunctival ulcers as a manifestation of Behçet's disease. DESIGN: Retrospective, noncomparative, interventional case series with histopathologic correlation. METHODS: Six patients who fulfilled the diagnostic criteria for Behçet's disease and presented with painful conjunctival ulcers were included in the study. Three of these ulcers were biopsied and studied histologically and immunohistochemically. The lesions were treated with topical or subconjunctival injection of corticosteroids and, in one case, with oral indomethacin. RESULTS: Although all six patients fulfilled the diagnostic criteria for Behçet's disease, two developed uveitis and other signs of Behçet's disease only months to years after the appearance of the conjunctival ulcers. The 3- to 5-mm, round to oval ulcers were located in the limbal and/or bulbar conjunctiva. Histopathology revealed disrupted epithelium, infiltration of both acute and chronic inflammatory cells, and high endothelial venules. Immunohistochemical analysis of the infiltrating lymphocytes revealed primarily T-cell populations admixed with several B cells and CD68-positive histiocytes. After treatment, the conjunctival lesions invariably healed without scarring. CONCLUSIONS: In addition to the oral and genital ulceration, ulcers can also be found in the conjunctiva of patients with Behçet's disease. Although this is a rare clinical sign, when accompanied by uveitis or orogenital ulcers, it may suggest a diagnosis of Behçet's disease.
OBJECTIVE: Aqueous humor analysis can be performed in severe atypical forms of posterior uveitis unresponsive to conventional treatment to exclude a viral infection. DESIGN: Noncomparative interventional case series. PARTICIPANTS: Thirty-seven immunocompetent patients seen with corticosteroid-resistant forms of posterior uveitis underwent extensive evaluation, including anterior chamber paracentesis, to rule out a nonnecrotizing viral retinopathy. INTERVENTION: Aqueous fluid samples were prospectively obtained. Polymerase chain reaction (PCR) and serologic evaluation of intraocular antibody production against herpesviruses were performed by molecular techniques and enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Polymerase chain reaction and local antibody production for herpes simplex virus types 1 and 2, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus were determined on aqueous fluid samples. RESULTS: Viral infection was confirmed in 5 cases (13.5%). Clinical presentation included birdshot-like retinochoroidopathy, occlusive bilateral vasculitis, and cystoid macular edema. An antiviral regimen was initiated in all cases. Inflammation was stabilized, and steroid dosage could be significantly reduced. CONCLUSIONS: Identification of a viral agent during severe posterior uveitis can dramatically change therapeutic management.
PURPOSE: To report the use of intravenous (IV) antiviral agents and intravitreal ganciclovir injections in three immunocompetent patients with severe acute retinal necrosis (ARN). METHOD: Case series. RESULTS: Three immunocompetent patients, who had lost vision in the first eye due to ARN, received intensive treatment with IV foscarnet or acyclovir or ganciclovir and intravitreal ganciclovir injections for the treatment of severe ARN involving the fellow eye. The retinitis resolved and final visual acuity of the fellow eye improved to 20/20 in all three cases after a mean follow-up of 17 months. CONCLUSIONS: Intensive treatment with a combination of two intravenous antiviral drugs and intravitreal ganciclovir injections was successful in the management of patients with acyclovir-resistant ARN and monocular status.
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PURPOSE: Histopathology usually cannot be performed and cytology is unfortunately frequently insufficient to confirm a suspicion of primary intraocular lymphoma (PIOL). The purpose of this study was to evaluate the Immunoscope technique for the identification of ocular B-cell monoclonal infiltrates in patients with malignant or immune conditions. METHODS: Polymorphism analysis of the size of the third complementarity-determining region (CDR3) of heavy chain antibody transcripts was used to differentiate between a polyclonal infiltrate and a monoclonal infiltrate within a clinical vitreous sample of two groups of patients. PIOL was confirmed in all patients of the first group (n = 6). Five patients with autoimmune uveitis or immune-recovery uveitis associated with AIDS were included in the control group. The level of IL-10 in the vitreous was determined in all patients. RESULTS: In five cases of severe PIOL, CDR3 polymorphism analysis confirmed the presence of a dominant B-cell clone within the eye. In one case of confirmed PIOL presenting with mild vitritis, CDR3 polymorphism analysis was consistent with the existence of a polyclonal profile in the ocular sample studied. Conversely, it was shown that the detection of an intraocular monoclonal B-cell population does not necessarily imply ocular lymphoma. A clonal expansion was detected in a control patient who exhibited merely a nonmalignant response associated with immune-recovery uveitis. CONCLUSIONS: This PCR-based technique can make an important contribution to the characterization of intraocular B cells, but it alone cannot confirm or exclude the existence of a malignant lymphocyte proliferation. In the evaluation of a patient with intraocular inflammation in whom PIOL is suspected, CDR3 polymorphism analysis is recommended to confirm clonality. In general, the information about lymphocyte diversity provided by this technology opens up new possibilities for the analysis of ocular infiltrates.
Human cytomegalovirus (HCMV) remains one of the major pathogens in immunocompromised patients (AIDS and transplants) and the main cause for congenital infections leading from slight cognitive defects up to severe mental retardation. The drugs that are currently available for the treatment of HCMV infections, i.e. ganciclovir, foscarnet and cidofovir, are all acting at the level of the viral DNA polymerase. Here we describe an entirely new molecule, the 2-chloro-3-pyridin-3-yl-5,6,7,8-tetrahydroindolizine-1-carboxamide (CMV423), that shows very potent in vitro activity against HCMV. CMV423 is highly active against HCMV reference strains and clinical isolates, but also against those strains, isolated from patients or emerging after in vitro selection, that are resistant to either ganciclovir, foscarnet or cidofovir. CMV423 also showed activity in two ex vivo models, that are both highly relevant for the pathophysiology of HCMV, the retinal pigment epithelial and the bone marrow stromal cell assays. Viral antigen expression analysis by flow cytometry, as well as time of addition experiments, confirmed that CMV423 acts on a step of the viral replicative cycle that precedes the DNA polymerase step and, most likely, coincides with the immediate early (IE) antigen synthesis. Finally, CMV423 combined with either ganciclovir, foscarnet or cidofovir in checkerboard experiments demonstrated a highly synergistic activity.
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Infectious uveitis is a serious condition requiring rapid diagnosis and therapeutic management. Molecular tools, such as PCR and its variants, have significantly changed the diagnostic approach during the last 10 years. Presumed and empirical diagnosis should be excluded in the face of atypical clinical presentations, but also inadequate response to anti-inflammatory drugs. It is of particular importance to note that most of these tests need to be processed in specialized central laboratories to ensure the best sensitivity and specificity. Molecular techniques have their own limits, sometimes caused by inadequate primers or PCR-inhibitors and contaminants. PCR positivity means detection of pathogen DNA, but does not confirm a productive infection. Cultures from ocular fluids should be improved to obtain complementary data about pathogen life cycles and resistance to antibiotics or antivirals. Furthermore, diagnostic yield is significantly increased when PCR and local antibody production are associated, especially in viral infections. This step is of particular importance to identify new infectious entities in cases that are presently considered to be idiopathic or autoimmune disorders.