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Articles by Oanh Lehoang in JoVE

 JoVE Biology

Ex Vivo Assessment of Contractility, Fatigability and Alternans in Isolated Skeletal Muscles

1Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, 2Muscle Biology Research Group, University of Missouri-Kansas City, 3Pharmacology division, College of Pharmacy, DHLRI, Ohio State University


JoVE 4198

We describe a method to directly measure muscle force, muscle power, contractile kinetics and fatigability of isolated skeletal muscles in an in vitro system using field stimulation. Valuable information on Ca2+ handling properties and contractile machinery of the muscle can be obtained using different stimulating protocols.

Other articles by Oanh Lehoang on PubMed

Foscarnet in the Treatment of Cytomegalovirus Retinitis in Acquired Immune Deficiency Syndrome

Cytomegalovirus (CMV) retinitis is the major cause of visual loss in acquired immune deficiency syndrome (AIDS). Thirty-one patients with active CMV retinitis were treated with the new antiviral drug, Foscarnet (trisodium phosphonoformate). After a 3-week course of induction therapy, the retinitis improved in 29 of 31 patients (93.5%). Complete resolution of the retinitis was seen in 19 cases (61.3%). Ten patients had partial resolution (32.2%) and two (6.5%) failed to respond. After induction therapy, six patients were put on a low-dose maintenance regimen. All patients without maintenance therapy relapsed within 3 weeks after discontinuation of Foscarnet. The rate of relapse on maintenance therapy was 50% (3/6) within the first 5 weeks. The three other patients of Foscarnet maintenance did not relapse after a follow-up period of 12 weeks. In contrast to ganciclovir, Foscarnet did not induce neutropenia but it produced kidney toxicity that led to reversible renal insufficiency in three cases. Thus, Foscarnet appears to be a useful alternative to ganciclovir, particularly when combined with bone marrow toxic drugs, such as zidovudine (azidothymidine).

Susceptibility to Birdshot Chorioretinopathy is Restricted to the HLA-A29.2 Subtype

Detection of Antibodies to Human Herpesvirus-6 Using Immunofluorescence Assay

A serological study of human herpesvirus-6 (HHV-6) infection was performed by means of immunofluorescence assay on fixed HHV-6-infected cells. Comparison between indirect immunofluorescence assay (IFA) and anticomplement immunofluorescence assay (ACIF) showed that the latter test was the most appropriate for HHV-6 serology, although both methods exhibited identical sensitivity. ACIF, which was performed on HSB2 cells infected with the HBLV strain (provided by S.Z. Salahuddin), was then used to determine the titre of HHV-6 antibodies in serum by end-point dilution. The sera from 115 healthy subjects and 99 patients with presumed viral infection were tested. A similar distribution of HHV-6 titres was evidenced in both cases and the rate of individuals exhibiting a positive titre of 20 and above was about 30% of the whole population studied. No serological cross-reactivity was observed between HHV-6 and other herpesviruses, suggesting that the HHV-6 ACIF test was quite specific.

Efficacy and Tolerance of Intravitreal Ganciclovir in Cytomegalovirus Retinitis in Acquired Immune Deficiency Syndrome

Forty-four patients with acquired immune deficiency syndrome with cytomegalovirus (CMV) retinitis (64 eyes) intolerant of or refusing systemic antiviral therapy received 710 intravitreal injections of ganciclovir at the dosage of 400 micrograms per injection. The patients were followed for a mean period of 9 weeks. Induction therapy consisted of two injections a week until healing. Maintenance therapy consisted of one injection a week until relapse. All but 1 of 53 induction courses led to cicatrization, after a mean of 6.6 injections. In 54 maintenance courses, the 8-week relapse rate was 53%. During intravitreal therapy, involvement of the fellow eye occurred in 11% of the patients and CMV infection developed in a nonocular site in 16% of the patients. Five retinal detachments and two intravitreal hemorrhages occurred. No endophthalmitis or cataract was noted. Intravitreal ganciclovir appears to be a safe and effective alternative in patients intolerant of intravenous anti-CMV drugs.

[HLA-A29 Sub-types and "Birdshot" Choroido-retinopathy Susceptibility: a Possible "resistance Motif" in the HLA-A29.1 Molecule]

The Birdshot choroidoretinopathy (BSCR) is an ocular disease strongly associated with HLA-A29. The HLA-A29 specificity can be split using immunoelectrofocusing in two subtypes A29.1 and A29.2. BSCR susceptibility is exclusively linked to the HLA-A29.2 molecule. The sequence of HLA-A29.2 was established (EMBL X60108 and found to be identical between patients and healthy individuals. A single difference was found (H----D) 102) in the extra cellular domains between HLA-A29.2 and HLA-A29.1. The HLA-A29 sub-types shares the consensus HLA class I sequence (D102). The mutation exhibited by HLA-A29.1 (H102) is unique to that molecule. The ancestral type is thus HLA-A29.2 that confers the susceptibility to BSCR whereas HLA-A29.1 has arisen from a more recent mutation conferring resistance to BSCR. Another single amino-acid difference between HLA-A29.1 and HLA-A29.2 was found in the intracytoplasmic part of the molecule, HLA-A29.2 exhibiting the HLA-A consensus sequence whereas A29.1 shares with AW33.1 the mutation S----F321. In addition, the A29 specificity was assigned to L and Q amino-acids at position 62-63, which can interact with peptides into the binding groove. No specific T or B epitope of susceptibility could be considered involving the region of the mutation discriminating HLA-A29.2 from HLA-A29.1. The HLA-A29.1 mutation is unable to interact with the T cell receptor and did not seem to induce significant structural changes in the peptide-binding groove. Conversely, its position suggests that the A29.1 mutation might interfere with the binding of an accessory molecule, the CD8 molecule being the most likely candidate for that role.

In Situ Detection of Human Herpesvirus 6 in Retinitis Associated with Acquired Immunodeficiency Syndrome

Ocular Toxoplasmosis in Human Immunodeficiency Virus-infected Patients

The files of 45 human immunodeficiency virus-infected patients with ocular toxoplasmosis were reviewed, with a median follow-up of eight months. The condition was unilateral in 37 of the 45 patients (82%) and was bilateral in eight (18%). Inflammation of the anterior chamber and the vitreous was present in 32 of 53 eyes (60%) and 38 of 53 eyes (72%), respectively. Cytomegalovirus retinitis developed during the follow-up period in nine patients (20%). Cerebral toxoplasmosis was concurrently diagnosed with the ocular toxoplasmosis in 13 patients (29%). The efficacy of the combination of pyrimethamine and sulfadiazine or clindamycin was assessed in 42 patients for the induction therapy and in 38 patients for the maintenance therapy. Induction therapy was always effective within a median period of six weeks. During maintenance treatment, the 24-month relapse rates were 0.20 and 0.18 for the 50-mg/day and 25-mg/day dosage of pyrimethamine, respectively. The overall 12-month survival rate was 0.72. Our results suggested that ocular toxoplasmosis has a better ocular prognosis than cytomegalovirus retinitis, but that it requires appropriate treatment because life-threatening cerebral involvement is often associated.

HLA-A29.2 Subtype Associated with Birdshot Retinochoroidopathy

Birdshot retinochoroidopathy is strongly associated with HLA-A29. This antigen can be divided into two subtypes, A29.1 and A29.2, using an immunoprecipitation method succeeded by one-dimensional electrofocusing gel electrophoresis. We reviewed the HLA typings of 58 white French patients who had birdshot retinochoroidopathy. Of these 58 subjects, 54 (93.1%) had HLA-A29 with a relative risk of 157.30. We further analyzed the HLA-A29 subtypings of 33 patients with birdshot retinochoroidopathy. Evaluation of the results showed that HLA-A29.2 subtype was present in all patients (100%). We concluded that the absence of HLA-A29.1 subtype is statistically significant (P less than .01) in this study of HLA-A29 subtyping.

[Changes in the Fundus in Subacute Sclerosing Panencephalitis. Apropos of 23 Cases]

Subacute sclerosing panencephalitis (SSPE) is a fatal slow encephalitis. It is related to a chronic infection of the central nervous system by a defective measles virus. Among 41 patients with SSPE, 23 had ocular involvement. The ophthalmologic involvement preceded the onset of neurological signs in 4 cases, they were detected at first presentation in 9 cases, and they occurred in the course of the disease in 10 cases. The ocular involvement was bilateral in 19 cases. Various ophthalmologic features were reported: retinitis (16 eyes), macular pigment disturbances (4 eyes), optical neuritis (33 eyes), visual agnosia (1 patient). The macular lesions were typical of the disease, but at the acute stage they were liable to be confused with toxoplasmosis. This complication of measles should disappear with the systematic vaccination of 12 month old children.

In Situ Hybridization of HIV-1 RNA in Retinal Vascular Wall

In situ hybridization of human immunodeficiency virus-1 (HIV-1) has been performed on eight eyes from eight distinct acquired immune deficiency syndrome patients (three cases had a normal fundus examination and five presented with cytomegalovirus retinitis). The eyes were removed at autopsy and frozen immediately. Contiguous 10-mu cryostat sections were obtained and tested with a HIV probe labeled by nick-translation with [35S]-ATP. HIV-1 RNA was detected in the retina of two acquired immune deficiency syndrome patients. The first positive case presented with typical ophthalmological and histopathological cytomegalovirus retinitis, the second one was not related to cytomegalovirus, according to clinical or histopathological classical criterias. HIV-1 was localized in retinal vascular walls. This shows that there is an active replication of HIV in retina of some acquired immune deficiency syndrome patients.

Uveitis Associated with Post-transfusional Human T-lymphotropic Virus Type 1

Acute Posterior Multifocal Placoid Pigment Epitheliopathy After Hepatitis B Vaccine

To report two cases of acute posterior multifocal placoid pigment epitheliopathy after immunization with a recombinant hepatitis B virus vaccine.

A Single-center Study of 11 Patients with Intraocular Lymphoma Treated with Conventional Chemotherapy Followed by High-dose Chemotherapy and Autologous Bone Marrow Transplantation in 5 Cases

Intraocular lymphoma (IOL) is a rare form of non Hodgkin lymphoma (NHL); it has a poor prognosis and is frequently associated with central nervous system (CNS) infiltration. We report the results of a prospective study of 11 patients with IOL who received conventional chemotherapy (CT), followed by salvage high-dose (HD) CT with autologous bone marrow transplantation (ABMT) in five cases. All 11 patients had abnormal funduscopic findings and six had CNS involvement at diagnosis. The diagnosis was based on vitrectomy in 10 cases and cerebral stereotaxic biopsy in one. Pathologic studies showed large-cell NHL in all cases. These large-cell NHL were of the B-cell type in 8 cases and of the T-cell type in two. First-line therapy consisted of a combination of cisplatin 25 mg/m2 as a 24-hour IV infusion on 4 consecutive days, VP-16 40 mg/m2 for 4 days, aracytine 2 g/m2 IV on day 5, and methylprednisolone 500 mg IV daily for 5 days (ESHAP) in 5 cases; alternating courses of ESHAP and HD methotrexate (MTX) in 4 cases; and HD MTX in 2 cases. Three patients underwent ocular and whole-brain radiation therapy. Five refractory patients subsequently received intensive CT with thiotepa 750 mg/m2, busulfan 10 mg/kg and cyclophosphamide 120 mg/kg, followed by ABMT. First-line treatment failed in 10 evaluable cases. One patient died of CNS progression at 12 months. All the patients who underwent intensive CT and ABMT entered CR; two relapsed at 6 months and three are alive in CR 15, 15 and 14 months after ABMT. Six patients are alive with persistent disease at 8, 13, 14, 15, 18 and 24 months. It seems in conclusion that, high-dose thiotepa, busulfan and cyclophosphamide followed by ABMT is effective in some cases of refractory IOL.

[Retinal Manifestations of AIDS]

Cytomegalovirus (CMV) retinitis is the most common retinal opportunistic infection in AIDS patients and is the main cause of blindness. It is generally associated with a CD4+ lymphocyte count below 50/microL. CMV retinitis is often asymptomatic (54% of the cases), frequent ophtalmoscopic screening is very important. Two virostatic drugs (Cymevan and Foscavir) have been approved for the treatment of CMV retinitis. Both are effective in preventing the progression of the lesion within 3 weeks of induction therapy. Long-term use of virostatic maintenance therapy delays the onset of relapses. The differential diagnosis of CMV retinitis are: human immunodeficiency virus retinopathy, varicella-zoster virus retinitis, ocular toxoplasmosis, syphilis, candida endophthalmitis in intravenous drug users, and unfrequently, tuberculosis, choroidal pneumocystosis, intraocular lymphoma.

[Toxoplasmic Chorioretinitis Complicated by Retinal Detachment]

To describe and analyse relationship between chorioretinal toxoplasmosis and retinal detachment.

[Tyndall Automatized Photometry (PAT) in Ophthalmology]

[Technique of Implantation of A Ganciclovir-containing Intravitreal Device]

Intravenous Immune Globulin in Autoimmune Uveitis

Whipple's Syndrome (uveitis, B27-negative Spondylarthropathy, Meningitis, and Lymphadenopathy) Associated with Arthrobacter Sp. Infection

To report an unusual case of Whipple's disease, including uveitis, seronegative spondylarthropathy, meningitis, and lymphadenopathy, associated with an Arthrobacter sp. infection.

[What is Your Diagnosis and Treatment? Acute Anterior Uveitis Without Hypopyon]

[Episcleritis and Brucellosis. Apropos of a Case]

A 35-year-old man presented a case of recurrent episcleritis revealing brucellosis. No concurrent diagnosis other than brucellosis could account for the episcleritis. Moreover his status was dramatically improved by specific antibiotherapy. A review of the literature showed that uveitis and optic neuropathies are the most common ocular manifestations of brucellosis. To the best of our knowledge, this is the first case of episcleritis associated with brucellosis.

Utility of Microdissection and Polymerase Chain Reaction for the Detection of Immunoglobulin Gene Rearrangement and Translocation in Primary Intraocular Lymphoma

Primary intraocular lymphoma, a non-Hodgkin's lymphoma, is a primary central nervous system lymphoma (PCNSL). Diagnosis is usually made by identifying malignant, large B lymphocytes in the vitreous, eye, brain, and cerebral spinal fluid; however, these cells are few, friable, and difficult to recognize. Recently, clonal heavy chain immunoglobulin (IgH) gene rearrangement and bcl-2 gene translocation have been reported in systemic B-cell lymphoma and are used for the detection of malignant cells and in making a diagnosis. The authors investigated the molecular changes in three eyes and a chorioretinal biopsy specimen of four patients with PCNSL.

Retinal Pigment Epithelial Detachment: an Unusual Presentation in Ocular Sarcoidosis

Human Neutrophil Elastase in Temporal (giant Cell) Arteritis: Plasma and Immunohistochemical Studies

Few enzymes are able to attack the internal elastic lamina, which is destroyed in temporal arteritis (TA). Because human neutrophil elastase (HNE) is one of these, its role in the pathogenesis of TA was examined in patients undergoing temporal artery biopsy for suspected TA.

Schematic Interpretation of Indocyanine Green Angiography in Posterior Uveitis Using a Standard Angiographic Protocol

Indocyanine green angiography (ICGA) detects fluorescence produced by the ICG molecule in the near infrared wave lengths showing choroidal vascular structures. Indocyanine green angiography may prove useful in the workup of uveitis with choroidal involvement. The authors' purpose was to test a standardized ICGA protocol for posterior uveitis to gather systematic and comparable data and to design a schematic approach for the interpretation of angiographic signs.

Susac Syndrome

Susac syndrome is an occlusive arteriolar disease that provokes infarcts in the cochlea, retina, and brain of young subjects, mostly women. Its cause is unknown. Some infarcts may be asymptomatic and only revealed by ancillary investigation: 1) audiogram that shows bilateral sensorineural hearing loss predominating on low frequencies, 2) funduscopy and fluorescein retinal angiography demonstrating bilateral distal branch retinal artery occlusions, and 3) brain MRI T2-weighted images disclosing small multifocal hyperintensities in white and gray matter. Treatment options are not codified, ranging from antithrombotic drugs to immunomodulatory therapy. Course is self-limited after an active fluctuating phase. Dementia, blindness, and deafness are rare late sequelae, and half of patients return to normal life.

Neovascular Glaucoma After Bypass Surgery in Takayasu's Disease

Cytomegalovirus Retinitis in AIDS Patients: 1999 Update

[Ocular Manifestations of Behçet's Disease]

Ocular complications of Behçet's disease are considered one of the major criteria upon which the diagnosis is based. The ocular disease is characterized by repeated, explosive ocular inflammatory attacks which can healed spontaneously. During in-between attacks there is little or no evidence of inflammation in the eyes. The anterior segment can be involved alone presenting as a severe anterior uveitis with hypopyon. Posterior pole involvement is often sight threatening presenting as recurrent retinal vaso-occlusive disease. The fundus changes most frequently encountered are hyperhemia of the optic nerve, macular edema, retinal edema, vascular sheathing retinal exudate, and retinal hemorrhages. Complications of the inflammation include retinal and optic disc atrophy, neovascular glaucoma, vitreous hemorrhage, retinal detachment. Treatment is with topical steroids, systemic medications, including corticosteroids, colchicine, and immunosuppressive drugs. These complications are sight threatening and require a close follow up and a collaboration between ophthalmologists and Internal Medicine physicians.

Indocyanine Green Angiography in Choroidal Tuberculomas

[Retinopathy in Acute Pancreatitis]

Acute pancreatitis may involve remote organ systems, including the eye. Funduscopy may reveal in these rare cases presence of a typical ischemic retinopathy, similar to that diagnosed after severe traumas, known as the Purtscher's retinopathy. Pathogenesis of retinopathy in alcoholic retinopathy remains controversial: occurrence of fat embolism or leucothrombosis is discussed in the literature. The outcome of ischemic retinopathy in acute alcoholic pancreatitis is variable. Although there is no specific available treatment, its diagnosis may allow appropriate diagnosis of the causal disease when the general signs are not present.

CMV Retinitis in the Era of HAART

Since 1996, major advances in the treatment of AIDS have markedly changed the incidence and the prognosis of CMV retinitis. Highly active antiretroviral therapy (HAART) is a combination of nucleoside reverse transcriptase inhibitors and protease inhibitors. This new therapeutic strategy is highly efficient in reducing the HIV viral load and increasing CD(4)+ T-lymphocyte count. These biological effects are associated with an improvement of immune functions. Clinically, the completely quiescent CMV retinitis and the unusual prolonged relapse-free interval suggest a certain restoration of immune functions, making possible the discontinuation of maintenance therapy. For most authors, the decision to stop anti-CMV maintenance therapy is based on a CD4+ cell count >100 cells/microl with a low HIV viral load for at least four months. The improvement of CMV retinitis on HAART may also be associated with an intraocular inflammation called immune recovery vitritis. For some patients, this vitritis may be associated cystoid macular edema and an epiretinal membrane responsible for visual loss.

Indocyanine Green Angiography in Birdshot Chorioretinopathy

Birdshot chorioretinopathy (BC) is an ocular inflammatory disease involving both the retina and the choroid. The study goal was to evaluate indocyanine green angiographic features in BC to assess choroidal involvement.

Entry of Human Cytomegalovirus into Retinal Pigment Epithelial and Endothelial Cells by Endocytosis

Human retinal pigment epithelial (RPE) cells and endothelial cells (HUVECs) are targets of human cytomegalovirus (HCMV) infection in vivo with significantly protracted replication in vitro compared with that in fibroblasts. This study analyzes the kinetics and mechanisms of HCMV entry into both cell types.

Acute Posterior Multifocal Placoid Pigment Epitheliopathy Associated with Wegener's Granulomatosis

To report acute posterior multifocal placoid pigment epitheliopathy (APMPPE) in the course of systemic Wegener's granulomatosis.

Ultrasound Biomicroscopy in Peripheral Retinovitreal Toxocariasis

To report ultrasound biomicroscopic features in peripheral retinovitreal Toxocara uveitis.

Cystoid Macular Oedema and Cytomegalovirus Retinitis in Patients with HIV Disease Treated with Highly Active Antiretroviral Therapy

Although cystoid macular oedema (CMO) is a rare cause of visual loss in AIDS related cytomegalovirus (CMV) retinitis, nine cases are reported of CMO occurring in HIV infected patients with a prior diagnosis of CMV who were receiving highly active antiretroviral therapy (HAART).

Efficacy of Interferon Alfa-2a in Severe and Refractory Uveitis Associated with Behçet's Disease

To evaluate the efficacy of interferon alfa-2a (IFN alfa) in severe uveitis associated with Behçet's disease, that is refractory to steroids and conventional immunosuppressive agents.

Ocular and Central Nervous System Lymphoma: Clinical Features and Diagnosis

To evaluate the clinical, angiographic, and cytopathologic features of ocular and central nervous system (CNS) lymphoma.

Relapses of CMV Retinitis After 2 Years of Highly Active Antiretroviral Therapy

Ocular Tuberculosis

Despite the use of highly sensitive molecular tools, such as polymerase chain reaction, for the detection of Mycobacterium tuberculosis, ocular tuberculosis remains a subject of controversy. The diagnosis is often presumptive in the absence of ocular biopsies. Choroiditis is the most common ocular manifestation in patients with pulmonary and systemic tuberculosis. Indocyanine green angiography seems to be an interesting method to determine choroidal involvement. PCR technology is proposed to evaluate the presence of the tubercule bacillus DNA in ocular fluids and tissues when conventional microbiologic methods fail to confirm a bacterial etiology. Most of the presumed cases of ocular tuberculosis should be treated with associations of antituberculous drug, especially when a systemic steroid regimen is required.

[Current Status of Retinal Detachment in AIDS Patients]

Cytomegalovirus retinitis is the most common opportunistic ocular infection in patients with AIDS affecting 30 to 40% of the patients. It usually occurs in patients in the terminal stage of the disease presenting with low CD4+ count (<50/mm(3)). Retinal detachment (RD) is a frequent complication of this disease, with an incidence varying from 18% to 29%. Risk factors for development of rhegmatogenous RD in patients with CMV retinitis were peripheral involvement greater than 25%, the presence of active retinitis, greater patient age and lower CD4+ cell counts. Multiple or single holes, as well as micro holes, were observed in areas of retinal necrosis leading to complex retinal detachments. Strong vitreoretinal adherences in these young patients, associated with chronic inflammation, were important elements in the pathophysiology of retinal detachment in AIDS patients. For localized RD, demarcating laser photocoagulation may delayed or avoided vitreoretinal surgery. For RD with macula off, good anatomical results have been obtained by repairing CMV retinitis-related retinal detachments using primary vitrectomy and instillation of silicone oil. Despite good anatomical results, poor long term functional results are related to optic atrophy. Since the introduction of highly active antiretroviral therapy (HAART), retinal detachment incidence has nevertheless dramatically decreased. Under HAART, CMV retinitis remains quiescent for long periods of time with a reduction of retinal detachment incidence of approximately 77%. For some patients on HAART, retinal reattachment can be obtained using vitrectomy, posterior hyaloid removal, and intraocular tamponade with SF-6 gas.

[Birdshot Retinochoroidopathy]

Birdshot retinochoriodopathy is a bilateral posterior uveitis seen in adults over 45 years of age. The uveitis is associated with moderate vitreal inflammation, vasculides of large vessels, chronic papillitis and the yellow birdshot spots typical of the disease. The disease shows tight linkages with HLA A29 carried by more than 90% of the patients. The visual prognosis depends on the development of complications of the chronic ocular inflammation, particularly crystoid macular edema. These complications lead to lowered visual acuity which becomes a major handicap. Long-term local or general corticosteroid therapy is required and leads to cortico-dependence. An immunosuppressor (cyclosporinA) may be associated. As these treatments cause major morbidity, intravenous immunoglobulins offer a less toxic therapeutic approach. Intravenous immunoglobulins can reduce inflammatory phenomena, providing an interesting alternative for the treatment of birdshot retinochoroidopathy.

[Intraocular Hypotony: Use of Ultrasound Biomicroscopy (UBM) for Differential Diagnosis and Its Schematic Representation]

To determine the use of high-frequency ultrasound biomicroscopy (UBM) in the assessment of hypotony and in particular to determine the proportion of cases for which UBM contributed significant additional hitherto unaccessible information.

Intravenous Immunoglobulin (IVIg) for the Treatment of Birdshot Retinochoroidopathy

Intravenous polyclonal immunoglobulin (IVIg) treatment has been successfully used in a number of autoimmune conditions. Birdshot retinochoroidopathy (BRC) is a bilateral autoimmune posterior uveitis which, in its progressive form, frequently requires immunosuppressive therapy. We report a clinical study aimed at determining the tolerance and efficiency of IVIg treatment in patients with active BRC. The study was conducted in an open manner. Eighteen patients were included. The initial visual acuity (VA) was < or =20/30 in 26 eyes, 20/25 in five eyes, and 20/20 in five eyes. IVIg was given as sole treatment at 1.6 g/kg every four weeks for six months, followed by injections of 1.2-1.6 g/kg at six to eight-week intervals. The mean follow-up was 39 months, ranging between 12 and 53 months. The results showed that the final VA of the 26 eyes with an initial VA of < or =20/30 was increased by two lines or more in 14 eyes (53.8%) and decreased in two (7.7%). Of the five eyes with an initial VA of 20/25, four had improved to 20/20 and one remained stable. Of the five eyes with an initial VA of 20/20, four remained stable and one deteriorated to 20/25. When present, macular edema was improved in half of the eyes on fluorescein angiography. Benign side effects were observed in 12 patients: moderate transient arterial hypertension (7), headache (6), eczematous lesions (6), and hyperthermia (4). The results suggest that IVIg may represent a safe alternative therapy for patients with BRC.

Blindness in a Strict Vegan

Rearrangement of Immunoglobulin Gene in Metastatic Waldenström Macroglobulinemia to the Vitreous

To report metastatic Waldenström macroglobulinemia cells with immunoglobulin heavy chain gene rearrangement in the vitreous and the blood.

Chronic Severe Uveitis: Etiology and Visual Outcome in 927 Patients from a Single Center

[Indocyanine Green Angiography in Ocular Inflammatory Diseases: Principles, Schematic Interpretation, Semiology and Clinical Value]

Value of High-frequency Ultrasound Biomicroscopy in Uveitis

To determine the use of high-frequency ultrasound biomicroscopy (UBM) in the assessment of inflammatory lesions of the iris, ciliary body, pars plana and peripheral vitreous, and in particular to determine the proportion of cases for which UBM contributed significant additional, hitherto inaccessible, information.

Interleukin-10 and Intraocular-central Nervous System Lymphoma

[Vision Disorders of Central Origin]

Cortical blindness (or more generally, cerebral blindness) consists of bilateral visual loss with normal ocular examination and normal pupillary function, related to bilateral occipital lesions. Its most frequent cause in adults is hypoperfusion in the vertebral-basilar arteries, although other curable causes are described. Other syndromes, related to lesions of associative cortical areas or occipital-fugal connections may cause poorly defined visual complaints. Their recognition by the ophthalmologist is mandatory, as they may concern a potentially curable underlying disease.

[Intraocular Pressure Elevation After Subtenon Injection of Triamcinolone Acetonide During Uveitis]

New therapeutic concepts in the management of ocular inflammation have led to the development of periocular and intravitreal injections. Such treatment modalities can induce intraocular pressure elevation.

An Unusual Junctional Scotoma

A 28-year-old woman presented with painful unilateral left visual loss, impaired color vision, left afferent pupillary defect, and normal ocular fundus. Although optic neuritis was first suspected, visual fields disclosed a junctional scotoma related to chiasmal demyelination, due to a probable multiple sclerosis.

Long-term Renal Effects of Low-dose Cyclosporine in Uveitis-treated Patients: Follow-up Study

Cyclosporine (CsA), a widely used immunosuppressive drug, is an effective treatment of sight-threatening posterior idiopathic uveitis. CsA's main side effect is nephrotoxicity. The aim of this single-center prospective cohort study (conducted in a tertiary care teaching hospital in Paris, France) was to assess the long-term renal tolerance of a low-dose CsA treatment in patients with previously healthy kidneys on clinical, biologic, and pathologic criteria. Forty-one patients treated with 4.3 +/- 1.6 mg/kg body wt per day CsA for 44.9 +/- 3.6 mo were included. Mean follow-up was 55.4 +/- 0.2 mo. BP, CsA trough level, and renal function were prospectively monitored together with blood urea, creatinine clearance, GFR, and effective renal plasma flow. Eleven patients underwent serial kidney biopsies before and after 2 yr of a 4 +/- 0.9 mg/kg daily CsA treatment. Sustained low-dose CsA treatment induced a significant increase in plasma creatinine (P < 0.0001), a significant decrease in creatinine clearance (P < 0.0001), and isotopic GFR (P < 0.0001) over time. The highest dose induced more severe alterations in any of the renal parameters than the lowest dose. Prevalence of hypertension was particularly high. Histopathologic data showed significant interstitial fibrosis (P < 0.003) and tubular atrophy (P < 0.003) after 2 yr. Low-dose long-term CsA treatment induces significant renal impairment and a high incidence of hypertension. Our study suggests that lowering daily dosage may prevent CsA-induced nephrotoxicity if a daily dose of < or =3 mg/kg is used. Whether once established it is reversible is still prospective, although the occurrence of interstitial fibrosis in the kidney would argue against reversibility.

Testing Ocular Fluids in Uveitis

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.

[Herpes and Retinal Lesions: What's New?]

The viral retinitis are linked to infection by herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV). When the diagnosis is clinically suspected the antiviral treatment has to be introduced immediately after performing the ocular sampling to try to identify the infectious agent. Despite the various antiherpetic drugs available by intravenous routes and intravitreal injection, the prognostic of the herpetic retinitis remained severe because of the occurrence of retinal detachment, optic neuritis, macular necrosis. Various clinical forms are described: (1) the classical "acute necrotizing retinitis" (2) a form with a slow progression of the necrotizing retinitis (3) occlusive retinal arteritis (4) the highly severe "progressive retinal necrosis". The incidence of the CMV retinitis diminished with the highly antiretroviral therapy; however uveitis may occur with no active CMV retinitis. The various antiherpetic drugs are described with special indications.

Presumed Ocular Candidiasis in Drug Misusers After Intravenous Use of Oral High Dose Buprenorphine (Subutex)

Diagnosis of Toxoplasmic Retinochoroiditis with Atypical Clinical Features

To determine the value of aqueous humor analysis for confirming the diagnosis of ocular toxoplasmosis in patients who present with atypical clinical features and to relate the results of local antibody production and polymerase chain reaction (PCR) with the extent of active retinitis and the immune status of the patient.

[Efficacy of Intravenous Immunoglobulin in the Treatment of Birdshot Retinochoroiditis]

To evaluate the efficacy of intravenous immunoglobulin (IVIg) in the treatment of Birdshot retinochoroiditis.

Naproxen Ophthalmic Solution to Manage Inflammation After Phacoemulsification

To explore the efficacy and safety of 2 concentrations (0.1% and 0.2%) of sodium naproxen ophthalmic solution in controlling ocular inflammation in patients having phacoemulsification and intraocular lens implantation.

[Chronic Severe Uveitis: Classification, Search for Etiology and Therapeutic Approach]

PURPOSE: Severe chronic and refractory uveitis is a major diagnostic and therapeutic challenge for ophthalmologists and internists. Molecular tools, such as PCR but also new imaging techniques, 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. CURRENT KNOWLEDGE AND KEY POINTS: A retrospective study based on 927 consecutive patients presenting with severe uveitis between 1991-1996, has recently defined the epidemiological characteristics and the visual outcome of this group of patients. An associated condition was determined in 67.5% of cases, divided in 4 different subgroups: infectious uveitis; uveitis associated with a systemic disease; eye-limited, presumed immune-mediated disorder and idiopathic eye-limited disorder. The management of patients with sight-threatening forms of uveitis is efficiently performed in collaboration with internists and depends on a complete diagnostic procedure and a well-adapted treatment. FUTURE PROSPECTS AND PROJECTS: Extensive work-up is mandatory when the therapeutic response seems atypical with resistance to corticosteroids and classical immunosuppressive drugs. Infectious uveitis should be excluded in severe and intractable forms of uveitis. Thereafter, new therapeutic strategies based on type I interferon and anti-TNF molecules can be proposed in order to decrease the potential risk of blindness in this young group of patients.

Characterization of Vitreous B-cell Infiltrates in Patients with Primary Ocular Lymphoma, Using CDR3 Size Polymorphism Analysis of Antibody Transcripts

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.

[Extensive Toxoplasmic Retinochoroiditis. Diagnostic and Therapeutic Management]

To assess the diagnostic and therapeutic management of extensive toxoplasmic retinochoroiditis.

Successful Treatment with Combination of Systemic Antiviral Drugs and Intravitreal Ganciclovir Injections in the Management of Severe Necrotizing Herpetic Retinitis

To report the use of intravenous (IV) antiviral agents and intravitreal ganciclovir injections in three immunocompetent patients with severe acute retinal necrosis (ARN).

Nonnecrotizing Herpetic Retinopathies Masquerading As Severe Posterior Uveitis

Aqueous humor analysis can be performed in severe atypical forms of posterior uveitis unresponsive to conventional treatment to exclude a viral infection.

[Acute Bilateral Anterior Uveitis with Hypopyon Revealing Creeping Angle-closure Glaucoma]

We report the case of a 35-year-old Asian woman presenting with bilateral anterior uveitis with hypopyon associated with high intraocular pressure. In her past history, she described intermittent angle-closure episodes. Anterior chamber examination and ultrasound biomicroscopy revealed a creeping angle-closure glaucoma. This clinical entity can affect Asians. The angle is gradually shortened with an iris bombé that brings the peripheral iris close to the external angle wall. The acute episodes are often poorly symptomatic. An early diagnosis may prevent glaucoma damages.

Conjunctival Ulcers in Behçet's Disease

To describe the occurrence of conjunctival ulcers as a manifestation of Behçet's disease.

Pseudotumor Cerebri Associated with Sjögren's Syndrome

To report a case of papilledema and pseudotumor cerebri developed in association with Sjögren's syndrome.

Polymerase Chain Reaction Analysis of Aqueous Humour Samples in Necrotising Retinitis

Aim: To evaluate the diagnostic value of polymerase chain reaction (PCR) performed on aqueous humour for the detection of viral DNA in patients with necrotising herpetic retinitis.

Oculo-renal Disorders in Infectious Diseases

The aim of this article is to review the potential ocular and renal disorders in infectious diseases to which humans are susceptible and to determine prevalence of these diseases.

Infliximab in Refractory Uveitis Due to Behçet's Disease

To report 4 cases of refractory panuveitis due to Behçet's disease treated with a novel therapy: infliximab.

[Bilateral Optic Neuropathy Revealing Systemic Sarcoidosis]

Although ocular involvement concerns about 25 to 60% of patients with systemic sarcoidosis, papilledema is a rare event.

Helicobacter Pylori (H. Pylori) Molecular Signature in Conjunctival Mucosa-associated Lymphoid Tissue (MALT) Lymphoma

Conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma is an extranodal marginal zone B-cell lymphoma that is characterized by an exaggerated clonal expansion of B cells, which implicate a pathological proliferative response to antigen(s) including bacteria. Helicobacter pylori (H. pylori) infection is recognized as one of the causative agents of gastric MALT lymphoma; however, it has not been reported in extra gastric MALT lymphoma. We studied 5 patients (4 adults and 1 child) with salmon-colored conjunctival lesions. One patient also had a history of abnormal bone marrow biopsy a year earlier with lymphoid aggregates involving 5% of the overall bone marrow. The conjunctival lesions of the 5 patients were biopsied. Histopathological diagnoses were consistent with conjunctival MALT lymphoma. Lymphoma and normal conjunctival cells were microdissected using laser capture microscopy or manual techniques. DNA was extracted and subjected to PCR amplification using H. pylori gene-specific primers from the urease B and vac/m2 gene. Cells from chronic conjunctivitis (normal lymphocytes), conjunctival human T-cell lymphotropic virus type-1/adult T-cell leukemia/lymphoma (HTLV-1/ATL), and orbital B-cell lymphoma were also microdissected, processed and analyzed. PCR amplification and Southern blot hybridization demonstrated H. pylori DNA in the conjunctival MALT lymphoma cells of 4/5 cases. The negative case was the one with a history of abnormal bone marrow. In contrast, H. pylori gene was not detected in normal conjunctival cells from the cases of MALT lymphoma or the lymphocytes, ATL and orbital B-lymphoma cells from the controls. These data suggest that H. pylori may play a role in conjunctival MALT lymphoma.

Clinical Characteristics of Acute HSV-2 Retinal Necrosis

To report the clinical features and evaluate the visual outcome of eleven cases of herpes simplex virus-2 (HSV-2) related acute retinal necrosis syndrome (ARN).

[Viral Cause and Management of Necrotizing Herpetic Retinopathies]

To study the viral cause and present the management of necrotizing herpetic retinopathies.

Biological Diagnosis of Primary Intraocular Lymphoma

Primary intraocular lymphoma (PIOL) is a rare presentation of lymphoma that is particularly difficult to recognize. In our institution, 36 cases of PIOL were diagnosed between March 1997 and July 2002. The recognition of lymphoma cells by cytology with or without immunophenotyping on slides generated a strong suspicion of the diagnosis in 34 of 36 cases. The diagnosis was confirmed by measurement of interleukin-10 (IL-10) in the vitreous humour or aqueous humour; high levels were observed in 35 of 36 cases, all were of B-cell origin. As expected, the only case with T-cell lymphoma had a very low level of IL-10. Furthermore, IL-10 levels excluded this diagnosis in two cases that were incorrectly suspected of PIOL after cytological examination. Finally, detection of clonality by polymerase chain reaction techniques, performed in 29 cases, represented a helpful tool in diagnosing PIOL as this approach definitively confirmed the diagnosis of B- or T-cell lymphoma in 17 cases.

[Severe Visual Loss Due to Retinal Artery Occlusion Associated with Susac's Syndrome: a Case Report]

Susac's syndrome consists of the clinical triad of cerebral microangiopathy, branch retinal artery occlusions, and hearing loss. The pathogenesis of the disease remains unknown. The severity of retinal vasculopathy remains variable.

Vogt-Koyanagi-Harada Disease in Patients with Chronic Hepatitis C

To report the cases of four patients with hepatitis C virus infection who experienced clinical features that are virtually identical to Vogt-Koyanagi-Harada disease (VKH).

Efficacy of Interferon-alpha for the Treatment of Kaposi's Sarcoma Herpesvirus-associated Uveitis

To report cases of uveitis that are associated with human herpesvirus-8 (HHV-8) and the impact of interferon-alpha therapy on their visual outcome.

Syphilitic Uveitis in Patients Infected with Human Immunodeficiency Virus

This work investigates the incidence and clinical features of syphilitic uveitis in patients infected with human immunodeficiency virus (HIV).

[Optochiasmal Cavernoma: a Rare Cause of Unilateral Visual Loss]

Optic pathways cavernomas are rare vascular hamartomas that can present either with an acute chiasmal syndrome or slowly progressive visual loss.

Therapeutic Use of Infliximab in Sight Threatening Uveitis: Retrospective Analysis of Efficacy, Safety, and Limiting Factors

Fuchs Heterochromic Cyclitis and Ocular Toxocariasis

To report the association of Fuchs heterochromic cyclitis (FHC) and ocular toxocariasis in a young adult.

[Optic Neuritis Associated with Infliximab]

Infliximab is a chimeric human-murine monoclonal antibody of the IgG1 type with a high affinity and specificity for tumor necrosis factor alpha (TNFalpha). Infliximab was used in Crohn disease, rheumatoid arthritis, spondyloarthropathy, juvenile idiopathic arthritis, Behcet's disease, Wegener's granulomatosis, HLA-B27-associated uveitis and chronic severe refractory uveitis. Reported adverse effects of this treatment were infections, development of antinuclear antibodies and anti double-stranded DNA, lymphomas, and exacerbation of demyelinating disease. We report a case of infliximab-associated optic neuritis with favorable outcome after systemic steroid treatment.

Endoretinal Biopsy in Establishing the Diagnosis of Uveitis: a Clinicopathologic Report of Three Cases

To report the value of endoretinal biopsy in establishing the diagnosis of severe posterior uveitis.

[MALT-type B-cell Lymphoma Masquerading As Scleritis or Posterior Uveitis]

Diagnostic and therapeutic management of masquerade syndromes associated with MALT-type lymphoma.

[Diagnostic and Therapeutic Management of Vogt-Koyanagi-Harada Syndrome]

To determine the most efficient diagnostic tools in Vogt-Koyanagi-Harada syndrome, taking into account the international diagnostic criteria, and to evaluate the therapeutic management of these patients.

Necrotising Retinopathies Simulating Acute Retinal Necrosis Syndrome

To determine an aetiological diagnosis in patients presenting with necrotising retinopathies that simulate acute retinal necrosis (ARN).

Detection of Helicobacter Pylori and Chlamydia Pneumoniae Genes in Primary Orbital Lymphoma

Primary orbital non-Hodgkin's lymphoma is a mucosa-associated lymphoid tissue (MALT)-type extranodal marginal zone lymphoma. Chronic antigen stimulation is implicated as a causative agent in the development of some mature B-cell proliferations; for example, there are associations involving Helicobacter pylori with gastric or conjunctival MALT lymphoma and Chlamydia psittaci with ocular adnexal lymphoma. We examined the molecular signatures of H pylori and Chlamydia in eight orbital lymphomas.

[Acute Posterior Multifocal Placoid Pigment Epitheliopathy, Serpiginous and Multifocal Choroiditis: Etiological and Therapeutic Management]

To highlight the importance of an extensive medical work-up in serpiginous and multifocal choroiditis, and acute posterior multifocal placoid pigment epitheliopathy before therapeutic management.

[Choroidal Metastasis Revealing Pulmonary Adenocarcinoma]

Lung cancer is the first cause of choroidal metastasis in man. Generally, its discovery is made at end-stage of the disease. It can be uncommonly the presenting sign as in our case. We report a case of a 28-year-old patient with no prior medical history. He presented with visual decrease and metamorphopsia that lead to the diagnosis of a metastatic adenocarcinoma of the lung (bone, liver, choroid, nodles). Chemotherapy permitted to improve visual acuity, in parallel with disappearance of choroidal metatasis. Discovery of choroidal tumor should evoke in first line metastasis. Chemotherapy can improve visual acuity and the quality of life.

Evaluation of the Effect on Outcomes of the Route of Administration of Corticosteroids in Acute Vogt-Koyanagi-Harada Disease

To compare the effect on outcomes of the route of administration of corticosteroids in acute Vogt-Koyanagi-Harada disease.

Regulatory T Cells Control Uveoretinitis Induced by Pathogenic Th1 Cells Reacting to a Specific Retinal Neoantigen

In many clinical cases, uveitis develops secondary to an infection. This could result from peripheral activation followed by ocular penetration and reactivation of T cells specific for microbial Ags expressed in the retina. To gain insights into the pathophysiology of uveitis, we developed a new mouse model based on stable retinal expression of influenza virus hemagglutinin (HA) neoantigen by adeno-associated virus-mediated gene transfer. One month thereafter, we adoptively transferred HA-specific T cells, which were activated in vitro or in vivo. Intraocular inflammation was clinically and histologically observed in all animals within 15 days. The ocular infiltrate was composed mostly of macrophages and HA-specific T cells with a proinflammatory cytokine profile. Depletion of CD4(+)CD25(+) regulatory T cells exacerbated the disease, whereas HA-specific CD4(+)CD25(+) T cells given i.v. controlled the disease. This novel model should allow to better study the pathophysiology and therapeutic of uveitis.

Diagnosis and Treatment of Cytomegalovirus Iridocyclitis Without Retinal Necrosis

To describe the diagnostic and therapeutic management of cytomegalovirus (CMV) anterior uveitis unassociated with retinal necrosis in immunocompetent patients.

First a Third, then a Fourth Nerve Palsy in Multiple Intracranial Aneurysms

Intracranial aneurysms may be a cause of ocular motor dysfunction, the third nerve being more often involved than the two other cranial ocular motor nerves.

Acute Retrobulbar Optic Neuropathy Due to Rupture of an Anterior Communicating Artery Aneurysm

The vast majority of ruptured aneurysms of the anterior communicating artery typically present with subarachnoid haemorrhage. Isolated visual complaints are very uncommon in this setting. We present an unusual case of a patient with an acute retrobulbar optic neuropathy, secondary to a ruptured anterior communicating artery aneurysm.

Ocular Adnexal Marginal Zone B Cell Lymphoma: a Clinical and Pathologic Study of 23 Cases

To better characterize ocular adnexal marginal zone lymphoma of mucosa-associated lymphoid tissue (MZL-MALT), we analyzed the clinical and pathologic features of 23 patients (11 men, 12 women, median age 66 years). The tumor was confined to one ocular structure in 18 cases (conjunctiva, n=8; orbit, n=8; or lacrimal gland, n=2). Concurrent extraorbital disease was detected by the staging procedure in five patients, and preferentially involved other MALT sites. Histogenetic B cell marker studies, available in 13 cases, showed an early post-germinal center (GC) phenotype (BCL-6(-)/IRF4(+)/CD138(-)) (n=5) or a late post-GC phenotype (BCL-6(-)/IRF4(+)/CD138(+)) (n=8), which could be helpful for discrimination from other types of small-B cell lymphoma. BCL10 was positive in 12 of 13 patients tested, with nuclear (n=4) or cytoplasmic (n=8) immunoreactivity. These staining patterns ruled out t(1;14)(p22;q32) translocation. T(11;18)(q21;q21), another MZL-MALT-specific translocation, was detected by reverse transcriptase polymerase chain reaction in four of 15 patients tested. Clinical outcome was excellent but the overall relapse rate was 26.1% with a median follow-up of 39 months (range 6-132 months). Regardless of the disease stage at diagnosis, combined chemotherapy and radiotherapy seemed to be more effective than chemotherapy alone in ocular adnexal MZL-MALT, as persistent complete remission was achieved in nine patients receiving combination therapy, while six of 14 patients treated with chemotherapy alone relapsed.

Acute Choroidal Closure Caused by Hemodialysis Accident in an Amyloidosic Patient

We report the case of a 43-year-old man haemodialysed for 20 years for systemic amyloidosis who underwent an acute choroidal occlusion after a haemodialysis accident.

Fluorescein and Indocyanine Green Angiographies in Susac Syndrome

Susac syndrome is a rare microangiopathy of the brain, retina, and cochlea that mainly affects young women. We studied the management of this disease using retinal fluorescein and indocyanine green angiographies.

Th1 and Th2 Responses on the Ocular Surface in Uveitis Identified by CCR4 and CCR5 Conjunctival Expression

To investigate CC chemokine receptor 4 (CCR4) and CC chemokine receptor 5 (CCR5) expression, known to be related to the Th2 and Th1 inflammatory pathways, respectively, and human leukocyte antigen-D related (HLA-DR) antigens as hallmarks for ocular surface inflammation in patients with uveitis using conjunctival impression cytologic specimens.

IL-10 Measurement in Aqueous Humor for Screening Patients with Suspicion of Primary Intraocular Lymphoma

To determine the value of IL-10 measurement in aqueous humor (AH) for screening in primary intraocular lymphoma (PIOL).

Impaired Th1/tc1 Cytokine Production of Tumor-infiltrating Lymphocytes in a Model of Primary Intraocular B-cell Lymphoma

Primary intraocular lymphoma is a high-grade non-Hodgkin lymphoma with a pathogenesis that is still unclear. Microenvironment is known to be crucial in controlling tumor growth and maintenance. To study the immune microenvironment in intraocular lymphomas and to characterize the cytokine polarization of infiltrating T-lymphocytes, a new murine model of intraocular B-cell lymphoma was developed.

Interferon-alpha2a and Vogt-Koyanagi-Harada Disease: a Double-edged Sword?

Successful therapy based on the use of interferon-alpha has been reported in different types of severe chronic uveitis. The immunomodulatory effects of this drug, combined with its antiviral properties seem to contribute to its efficacy in the treatment of different forms of severe and refractory uveitis such as Vogt-Koyanagi-Harada disease, Behçet-associated uveitis, or even human herpes virus 8 (HHV-8) associated uveitis. At the same time, severe ocular complications have been reported in patients treated with interferon-alpha for chronic viral hepatitis C. Among these complications, six cases of Vogt-Koyanagi-Harada-like disease have been described.We report a small case series of two patients with refractory Vogt-Koyanagi-Harada disease, treated with interferon-alpha and discuss the potential benefits or detrimental role of interferon therapy in these patients.

[Therapy of Chronic Non Infectious Uveitis]

PURPOSE: Chronic non infectious uveitis represents two-thirds of the causes of chronic uveitis referred in tertiary referral ophthalmology centre. One case out of 5 may evolve towards blindness. Therapy should be discussed on the basis of the uveitis severity and the diagnosis; it uses topics or systemic drugs, mainly corticosteroids and immunosuppressors. CURRENT KNOWLEDGE AND KEY POINTS: Besides corticosteroids and ciclosporin, use of immunosuppressors and biotherapy in chronic non infectious uveitis is not an indication of the Autorisation de Mise sur le Marché. However, immunosuppressors and biotherapy were the subjects of several studies, although controlled studies are scarce. Controlled studies concerned cyclosporine, azathioprine and intravenous cyclophosphamide in Behçet's disease, ciclosporine and tacrolimus in uveitis of various causes. Therapy of chronic non infectious uveitis was recently enriched by new drugs: mycophenolate mofetil, initially used in transplantation, has its indications extended to systemic diseases; TNF inhibitors initially used in therapy of systemic diseases; interferon efficacy revealed in Behçet's disease is now used in uveitis due to other causes. FUTURE PROSPECTS AND PROJECTS: Controlled studies are suitable in order to determinate the respective part of immunosuppressors and biotherapies in the treatment of chronic non infectious uveitis.

Retinal Fluorescein and Indocyanine Green Angiography and Optical Coherence Tomography in Successive Stages of Vogt-Koyanagi-Harada Disease

To report features of retinal fluorescein (FA) and indocyanine green (ICGA) angiography and optical coherence tomography (OCT) at successive stages of Vogt-Koyanagi-Harada (VKH) disease.

Efficacy of Interferon Alpha in the Treatment of Refractory and Sight Threatening Uveitis: a Retrospective Monocentric Study of 45 Patients

Severe uveitis is potentially associated with visual impairment or blindness in young patients. Therapeutic strategies remain controversial. The efficacy of interferon alpha-2a (IFN-alpha2a) in severe uveitis, refractory to steroids and conventional immunosuppressive agents, was evaluated.

Long-term Efficacy and Safety of Low-dose Interferon Alpha2a Therapy in Severe Uveitis Associated with Behçet Disease

To investigate long-term responsiveness of patients with severe uveitis associated with Behçet disease to interferon alpha2a (IFN-alpha2a).

Intravitreal Bevacizumab for Refractory Choroidal Neovascularization (CNV) Secondary to Uveitis

To assess the short-term efficacy and safety of intravitreal bevacizumab injections (IVB) for refractory choroidal neovascularization (CNV) secondary to uveitis.

Cataract Surgery in Childhood Uveitis

Uveitic Macular Oedema: Correlation Between Optical Coherence Tomography Patterns with Visual Acuity and Fluorescein Angiography

(1) To associate optical coherence tomography (OCT) patterns with particular fluorescein angiography (FA) findings in uveitis patients with macular oedema. (2) To investigate the correlation between tomographic features and visual acuity (VA). (3) To determine the impact of OCT patterns on visual improvement over time.

High Prevalence of Fastidious Bacteria in 1520 Cases of Uveitis of Unknown Etiology

The etiologic evaluation of uveitis is frequently unsuccessful when noninvasive methods are used. We conducted a prospective study to evaluate systematic screening for pathogens of uveitis. All patients with uveitis referred to the participating tertiary ophthalmology departments from January 2001 to September 2007 underwent intraocular and serum specimen collection. The standardized protocol for laboratory investigations included universal polymerase chain reaction (PCR)-based detection of any bacteria and mycoses, specific PCR-based detection of fastidious (difficult-to-grow) bacteria and herpes viruses, and culture of vitreous fluid. Sera were tested for fastidious bacteria. Among the 1321 included patients (1520 specimens), infection was diagnosed in 147 (11.1%) patients: 78 (53%) were caused by fastidious bacteria that included spirochetes, Bartonella species, intracellular bacteria (Chlamydia species, Rickettsia species, Coxiella burnetii), and Tropheryma whipplei; 18 by herpes viruses; and 9 by fungi. Bartonella quintana, Coxiella burnetii, Paracoccus yeei, Aspergillus oryzae, and Cryptococcus albidus were found to be associated with uveitis for the first time, to our knowledge. We recommend applying a 1-step diagnostic procedure that incorporates intraocular, specific microbial PCR with serum analyses in tertiary centers to determine the etiology of uveitis.

Animal Models of Intraocular Lymphomas

Primary intraocular lymphoma is a high-grade non-Hodgkin lymphoma whose pathogenesis is still unclear. Few animal models exist in order to study this condition. Although intraocular lymphomas in humans are usually B cell lymphomas, most of these models are T cell lymphomas. Recently, a major step forward has been realized with the development of new models of intraocular B cell lymphoma. New therapeutic tools are being evaluated in these models of B cell lymphoma. We evaluate the contribution of the different animal models available to study intraocular lymphomas, and we discuss the new therapeutic strategies and their various targets in the tumor as well as in the environment, which are currently investigated through the development of these models.

Primate Model of Uveoretinitis and Vasculitis/experimental Autoimmune Uveoretinitis Induced in Cynomolgus Monkeys by Retinal S Antigen

We aimed to describe the clinical and angiographic changes in an experimental model of autoimmune uveoretinitis and vasculitis in primates.

Editorial

[Multiple Evanescent White Dot Syndrome and Acute Idiopathic Blind Spot Enlargement: Angiographic and Electrophysiologic Findings]

Multiple white evanescent white dot syndrome (MEWDS) and acute idiopathic blind spot syndrome enlargement (AIBSE) are two acute retinopathies occurring in young patients: improvement is the rule. The present review describes two cases: one case of MEWDS and one of AIBSE. We observed these patients from the acute phase until absolute recovery. Comparing these two reports, we noted differences in ophthalmoscopic, fluorescein angiographics, and multifocal electroretinographic (mERG) analysis, but common findings were observed in clinical presentation and indocyanine green imagery. The first and recent description of these two disorders dates from less than 25 years ago. Although the pathophysiology is still unknown, some authors suggest that these two syndromes could be two different expressions of the same disease, depending on the patient's sensitivity. In our two case reports, multifocal ERG anomalies were directly related to visual impairment and visual field alterations. MEWDS and AIBSE are two acute retinopathies that must be recognized, because of the spontaneous visual recovery that the patient needs to understand for a good follow-up.

[Neoretinal Antigen Expression: a Comparison of Anatomical and Clinical Features of a Murine Uveoretinitis Model]

Uveitis is an inflammation involving the retina. The antigens targeted by the experimental models are located in the pigmentary epithelium-photoreceptor complex. To gain insights into the variations in topographic expression of the antigen in the retina, we studied a new mouse model.

Maculopathy in Uveitis of Juvenile Idiopathic Arthritis: an Optical Coherence Tomography Study

The aim of this study was to examine the frequency and characteristics of macular lesions observed in juvenile idiopathic arthritis (JIA) uveitis, using optical coherence tomography (OCT).

[Diagnostic Management of Childhood Uveitis]

Long-term Visual Outcomes of Intravitreal Bevacizumab in Inflammatory Ocular Neovascularization

To assess the long-term role of bevacizumab (Avastin; Genentech Inc, South San Francisco, California, USA) in inflammatory ocular neovascularization.

Clinical Features, Treatment Methods, and Evolution of Birdshot Chorioretinopathy in 5 Different Families

To report familial cases of birdshot chorioretinopathy (BSCR).

Retinal Fluorescein, Indocyanine Green Angiography, and Optic Coherence Tomography in Non-Hodgkin Primary Intraocular Lymphoma

To determine the presence of clinicopathological correlations for primary intraocular non-Hodgkin lymphoma (NHL)in fluorescein angiographies (FA), indocyanine green (ICGA) angiographies, and optical coherence tomography (OCT) images.

Painful Ophthalmoplegia As Ocular Manifestation in Cytophagic Histiocytic Panniculitis Associated with Churg Strauss Syndrome

Laser Flare Photometry in the Therapeutic Management of Bacterial Chronic Pseudophakic Endophthalmitis

To evaluate laser flare photometry in measuring aqueous humor inflammation in chronic pseudophakic endophthalmitis.

Uveitis Related to Juvenile Idiopathic Arthritis: Familial Cases and Possible Genetic Implication in the Pathogenesis

To describe four cases of familial Juvenile Idiopathic Arthritis (JIA) associated uveitis.

[Ocular Manifestations of Behçet's Disease]

Eye involvement in Behçet's disease (BD) is frequent and an important cause of morbidity. The mean age at onset of uveitis is between 20 and 30 years in male and 30 years in female patients. Ocular involvement includes anterior, posterior or panuveitis. Uveitis may be the presenting manifestation of the disease in 20% of cases or may appear 2 or 3 years after the disease onset. The estimated risk of blindness at 5 years ranges from 15 to 25%. The main goals in the management of patients with BD uveitis are the rapid control of intraocular inflammation, the prevention of recurrent attacks, the achievement of complete remission, and preservation of vision. The medical treatment of patients with severe uveitis relies on the use of systemically administered drugs, including corticosteroids and cytotoxic agents. Anti-TNF agents and interferon-alpha seem to be efficient and well-tolerated alternative therapeutic options. Controlled clinical trials are mandatory to define the place of these new immunomodulatory agents in the therapeutic strategy, and especially their use as first-line therapy.

Conservative Surgical Treatment of Medulloepithelioma of the Ciliary Body

Frequency of Distinguishing Clinical Features in Vogt-Koyanagi-Harada Disease

To determine the frequency of occurrence of limited clinical features which distinguish patients with Vogt-Koyanagi-Harada (VKH) disease from those with non-VKH uveitis.

Deep Sclerectomy and Trabeculectomy in Uveitic Glaucoma

To compare the results of deep sclerectomy (DS) and trabeculectomy (TRAB) in the management of uveitic glaucoma.

Usefulness of Gallium Scintigraphy Patterns in a Case of Idiopathic Retinal Vasculitis, Aneurysms and Neuroretinitis

Acute Posterior Multifocal Placoid Pigment Epitheliopathy As the Initial Manifestation of Sarcoidosis

To report an undiagnosed case of systemic sarcoidosis manifesting with bilateral acute posterior multifocal placoid pigment epitheliopathy (APMPPE).

Cataract Surgery with Primary Intraocular Lens Implantation in Children with Uveitis: Long-term Outcomes

To report long-term outcomes of cataract surgery with primary posterior chamber intraocular lens (IOL) implantation in children with chronic uveitis.

Understanding Uveitis: the Impact of Research on Visual Outcomes

The term uveitis encompasses a very diverse group of inflammatory ocular diseases that cause a significant burden of legal and economic blindness. Indeed, the socioeconomic impact of uveitis is at least as significant as that of diabetic retinopathy and, in the majority of cases, those affected are young individuals of working age. Significant progress has been made in our understanding of the mechanisms underlying the inflammatory process through the use of animal models, but correlation with human disease has proved elusive and many scientific approaches which appear highly effective in animal models prove to be less effective in patients. Nevertheless, effective, targeted treatments are needed in uveitis as current treatment is based on corticosteroids and immunosuppressive drugs whose usefulness is limited by their many side-effects. The aims of this review are to summarize the state of clinical research in uveitis, to identify gaps in our knowledge, and to propose new opportunities and methodologies for future developments in all aspects of uveitis research, including epidemiology, economic impact analysis, diagnosis, therapeutics, and clinical study design. Optimal patient management and efficient drug development depend on validated structured tools, such as those that have helped to drive a rapid acceleration in the means and methods available to assess and treat patients with rheumatoid arthritis and cancer. Uveitis care should witness a similar boom as the issues discussed are resolved.

QuantiFERON-TB Gold Cut-off Value: Implications for the Management of Tuberculosis-related Ocular Inflammation

To evaluate the accuracy of QuantiFERON-TB Gold testing in patients with presumptive tuberculosis-ocular inflammation.

Ocular Modifications in a Young Girl with Cryopyrin-associated Periodic Syndromes Responding to Interleukin-1 Receptor Antagonist Anakinra

An 8-year-old patient with genetically confirmed chronic infantile neurological cutaneous and articular syndrome was treated with interleukin-1 receptor antagonist, anakinra. She initially presented with recurrent episodes of fever, rash, chronic fatigue, frequent headaches, ocular involvement (corneal infiltrate and papillary edema), and permanent increased biologic inflammatory markers. Following treatment with anakinra, all symptoms and inflammation resolved. Ophthalmologic signs normalized. This ophthalmologic description (optic nerve and cornea) has never been illustrated, even if ocular affections are classic in the cryopyrin-associated periodic syndromes.

Intravascular Lymphoma Mimicking a Vogt-Koyanagi-Harada Disease

To report a case of intravascular lymphoma (IVL) mimicking a Vogt-Koyanagi-Harada disease (VKH).

Intravitreal Bevacizumab As First Local Treatment for Uveitis-related Choroidal Neovascularization: Long-term Results

To report long-term results of intravitreal (IVT) bevacizumab as first local treatment for choroidal neovascularization (CNV) secondary to uveitis.

Effect of the Duration of Immunomodulatory Therapy on the Clinical Features of Recurrent Episodes in Vogt--Koyanagi--Harada Disease

To evaluate the duration of immunomodulatory therapy (corticosteroids, immunosuppressive drugs) with regard to the rate of relapses and clinical features (exudative retinal detachment or anterior uveitis) in inflammatory episodes of Vogt--Koyanagi--Harada disease.

Spontaneous Branch Artery Occlusion in Idiopathic Retinitis, Vasculitis, Aneurysms, and Neuroretinitis Syndrome Despite Panretinal Laser Photocoagulation of Widespread Retina Nonperfusion

Diagnostic Approach in Optic Neuropathy

The diagnostic of optic neuropathy (ON) is a clinical diagnostic, relying on a detailed medical history, and a thorough clinical examination. In some cases, the attribution of the vision loss to a lesion of the optic nerve can be challenging, and further work-up is required to confirm the optic neuropathy. Once the diagnostic of optic neuropathy is stated, the pathophysiological mechanism of the ON has to be determined so that the appropriate therapeutic strategy can be initiated as promptly as possible. The diagnostic work-up must be as targeted as possible, oriented by the clinical examination. The different steps leading to the positive diagnostic of ON, and the etiologic work-up are detailed hereafter in order to achieve the most targeted work-up as possible. Differentials and current pitfalls are being reviewed.

Use of Fluorescein Angiography in the Diagnosis and Management of Uveitis

Three-year Visual and Anatomic Results of Administrating Intravitreal Bevacizumab in Inflammatory Ocular Neovascularization

To assess the 3-year visual outcome of intravitreal bevacizumab in inflammatory ocular neovascularization.

Sympathetic Ophthalmia After Proton Beam Irradiation for Choroïdal Melanoma

To determine the incidence and to discuss pathogenic mechanisms of sympathetic ophthalmia in patients treated for choroïdal melanoma.

Ocular Sarcoidosis

Sarcoidosis, a chronic multisystem disease, is a common cause of ocular inflammation. Even though clinical features are well-established, diagnosis requires histological confirmation, which remains difficult in patients with uveitis. Thus, the frequency of ocular sarcoidosis is overestimated. A set of criteria has been recently established in order to improve the diagnostic procedure. New imaging tools will enable the ophthalmologist to evaluate the level of ocular inflammation and to monitor its resolution after treatment initiation. Indocyanine green angiography and optical coherence tomography have dramatically improved our understanding of choroidal granulomas and macular edema. Treatment is based on topical and systemic corticosteroids in most of the cases, but immuno-suppressive agents may be necessary. The visual outcome remains favorable but severe complications, including glaucoma, cystoid macular edema and choroidal neovascularization, may need a prompt and aggressive management.

Anti-tumor Necrosis Factor-α Agents in Noninfectious Uveitis

Anti-tumor necrosis factor-α (anti-TNF-α) agents represent a major breakthrough for the therapeutic management of different autoimmune conditions. Noninfectious uveitis may lead to various sight threatening complications. Hence, from extrapolation of the benefit observed in autoimmune systemic diseases, anti-TNF-α agents are widely used in the treatment of noninfectious uveitis. However, their use remains mostly 'off-label' in this indication, and the lack of evidence from randomized controlled studies limits a rationale choice. This review gives an update on the management of uveitis with TNF-α inhibitors, highlighting important issues, including initiation time, type of molecule, duration of therapy but also major adverse events.

The Gold Standard of Noninfectious Uveitis: Corticosteroids

Corticosteroids (CS) are considered to be the mainstay of therapy in noninfectious uveitis. They can be administered only after excluding an infectious origin or a possible masquerade syndrome. Different CS preparations can be used with various modes of administration: topical, periocular, intraocular, systemic or a combination of the above routes. Their indications depend upon numerous factors, among them the type (involving or not the posterior segment), the severity, the uni-/bilaterality, the chronicity of the intraocular inflammation. The induction treatment must be aggressive in order to overcome the intraocular inflammation as rapidly as possible avoiding permanent tissue damage. The dosage regimen is then tapered according to the clinical response and after a minimum period of quiescence. The maintenance CS treatment should not exceed 6-12 months under the threat of severe adverse effects. In chronic cases, high-dosage CS monotherapy cannot be used; it is important to add an immunomodulatory treatment on time when a long-term therapy is needed to control the disease. Although CS represent the first line of treatment, the type of clinical response to CS is not a reliable indicator of the effectiveness of immunomodulation: a noninfectious uveitis unresponsive to CS may respond to immunomodulation alone or combined with CS.

Ocular Whipple's Disease: Therapeutic Strategy and Long-term Follow-up

To characterize the clinical features of ocular Whipple's disease (WD) and determine the long-term prognosis after antibiotic treatment.

Toxoplasmosis: New Challenges for an Old Disease

More than a century after the identification of Toxoplasma gondii, major issues need to be addressed for the optimal management of ocular disease. Toxoplasmic retinochoroiditis is the main cause of posterior uveitis in several geographical areas. The parasite establishes a love-hate relationship with the eye, manipulating the immune response and inducing variable initial lesions and further relapses. It is now well established that most cases are acquired after birth and not congenital. The severity of the disease is mainly due to the parasite genotype and the host immune status. Diagnosis is based on clinical features, but may be confirmed by biological tools applied to ocular fluids. Combining several techniques improves the diagnostic yield in equivocal cases. Therapeutic management is the most important challenge. Even though evidence-based data on the efficacy of anti-parasitic drugs are still missing, new strategies with a good safety profile are available and may be proposed earlier during the course of the disease, but also in selected cases, to reduce sight-threatening relapses. Revisiting the therapeutic options and indications may be an important step towards long-term maintenance of the visual function and avoidance of major complications.

[Choroidal Tuberculoma]

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