Eye involvement mimicking scleritis in a patient with chronic lymphocytic leukaemia.
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Biomedical subjects
Publications and source records attributed to C E Pavesio.
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BACKGROUND: Full field and pattern electroretinograms (ERG, PERG) are performed to assess generalised retinal function and macular function, respectively. An (electro) negative full field ERG usually describes an ISCEV standard maximal response in which the b-wave is smaller than a normal or minimally reduced a-wave and indicates dysfunction that is post-phototransduction. The most common cause of a unilateral negative ERG is central retinal artery occlusion (CRAO) or birdshot chorioretinopathy (BCR). This study examines the clinical and electrophysiological features of patients with unilateral negative ERG who do not have CRAO or BCR. METHODS: 12 patients were ascertained with a unilateral negative ERG in whom a vascular aetiology and BCR were excluded. Most presented with symptoms of central retinal dysfunction. In 11 of the 12 patients additional long duration photopic stimuli were used to test cone system ON and OFF responses. RESULTS: All 12 patients had unilateral electronegative bright flash full field ERGs indicating total or relative preservation of rod photoreceptor function, but dysfunction post-phototransduction. Seven of these patients had non-specific inflammatory changes in the eye with the negative ERG. Six patients, including five with inflammatory signs, had involvement of the cone ON response with complete preservation of cone OFF responses. A further three patients showed evidence of cone ON response abnormality with less severe OFF response involvement. CONCLUSION: The ERGs in this heterogeneous group of patients predominantly showed post-phototransduction involvement of the ON pathways. Sparing of the cone OFF response was often observed. The majority of patients had signs of previous inflammation and it is speculated that these highly unusual unilateral changes may be mediated via an autoimmune mechanism.
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Most papers on the subject of CMO associated with uveitis are retrospective, combine patients with different disease aetiologies, at different stages of evolution, and often describe patients who were previous treatment failures with other therapies besides the one under consideration. There are almost no prospective randomised double-masked controlled studies. This is perhaps in part due to the relative sparsity of uveitis patients seen by many uveitis centres. At the moment, treatment is largely empirical, based in large part on the studies, and others, quoted above. The need to regularly repeat courses of therapy, loss of efficacy of certain form of therapy after repeated use, and cumulative side-effects, all need to be taken into consideration when interpreting results and deciding upon the best approach to be adopted. The risks to the patient's well-being increase with the addition of systemic medication, and long-term steroid use can cause hypertension, induce or exacerbate diabetes, cause premature osteoporosis, cushingoid features, peptic ulceration and aseptic necrosis of the femoral head. Immunosuppressive drugs can be nephrotoxic, hepatotoxic, cause hypertension, gastric disturbances and excessive hair growth. The assessment of macular changes, both structurally and functionally, is the key aspect in understanding visual loss in CMO and also in predicting potential visualrecovery. The combined use of the various tools mentioned here, such as SLO, OCT and electrodiagnostic tests, may give us some of the necessary answers in this process. However, all these tests will need to be validated. A prospective analysis of CMO in cases of uveitis, especially if coupled with therapeutic intervention, will give us the opportunity to achieve this objective.
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Inflammation of the episclera and sclera still represents a diagnostic challenge. Many of these presentations are idiopathic and are managed empirically with the use of anti-inflammatory therapy, usually with a satisfactory response. However, some cases will have a more aggressive nature or will show resistance to conventional therapy, and those potentially are connected to an infectious or underlying disease. In such cases, there is an increased risk of visual loss and severe systemic complications requiring intensive investigations and aggressive therapy. The diseases more commonly associated with these conditions, especially with scleritis, are the connective tissue disorders and systemic vasculitis, but systemic infections and malignancies also must be excluded. Management depends on the specific diagnosis, and every year a new list of potential associations or atypical presentations is reported. For a successful outcome, it is important that these presentations are recognized.
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Administration of Toxoplasma cysts by intraperitoneal innoculation in the Syrian Golden Hamster provides a reproducible animal model of acquired Toxoplasmic retinochoroiditis and cysts are observed in the brain. However, toxoplasmosis is frequently acquired by oral ingestion of contaminated foodstuffs and it is recognised that the route by which disease is acquired may influence its pathogenesis and clinical expression. This study aimed to determine whether retinochorioiditis and cysts in the brain develop after oral ingestion in the Syrian Golden Hamster model as this is the route of induction akin to that in man and may therefore be more relevant in the study of disease pathogenesis. All animals developed disease by 4 weeks. Ocular and cerebral inflammation was confirmed by histology at 16 weeks and this was milder than in the original model.
Ocular disease is the commonest disabling consequence of toxoplasma infection. Incidence and lifetime risk of ocular symptoms were determined by ascertaining affected patients in a population-based, active reporting study involving ophthalmologists serving a population of 7.4 million. Eighty-seven symptomatic episodes were attributed to toxoplasma infection. Bilateral visual acuity of 6/12 or less was found in seven episodes (8%) and was likely to have been transient in most cases. Black people born in West Africa had a 100-fold higher incidence of symptoms than white people born in Britain. Only two patients reported symptoms before 10 years of age. The estimated lifetime risk of symptoms in British born individuals (52% of all episodes) was 18/100000 (95% confidence interval: 10.8-25.2). The low risk and mild symptoms in an unscreened British population indicate limited potential benefits of prenatal or postnatal screening. The late age at presentation suggests a mixed aetiology of postnatally acquired and congenital infection for which primary prevention may be appropriate, particularly among West Africans.
PURPOSE: To evaluate the effects of drug therapy on the clinical course of acute acquired Toxoplasma retinochoroiditis and on the number of Toxoplasma cysts present in the brain and ocular tissues in the hamster animal model. METHODS: The Syrian golden hamster animal model of Toxoplasma retinochoroiditis was used. In acute disease, systemically administered atovaquone was compared with conventional therapies (pyrimethamine combined with sulfadiazine; clindamycin; and spiramycin). The clinical course of the ocular disease was determined with retinal examination and photography of the fundus. The number of Toxoplasma cysts remaining after treatment was evaluated in aliquots of brain homogenate and in retinal tissue. The effect of atovaquone on cerebral Toxoplasma cyst count was also studied in chronic disease. RESULTS: None of the drugs administered altered the course of the acute disease, judged by clinical examination. Atovaquone alone significantly reduced the number of cerebral Toxoplasma cysts after acute disease. Atovaquone also significantly reduced the cerebral Toxoplasma cyst count in chronic disease. CONCLUSIONS: Tissue cysts are believed to be responsible for reactivation of Toxoplasma retinochoroiditis. Atovaquone has the potential to reduce the risk of recurrent disease.
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Retinal infections caused by the varicella-zoster virus (VZV) have been reported in immunocompetent and immunocompromised individuals. Two cases of a VZV-related retinitis are described with the characteristic features of the recently described progressive outer retinal necrosis (PORN) syndrome. Both patients suffered from the acquired immunodeficiency syndrome (AIDS) with greatly reduced peripheral blood CD4+ T lymphocyte counts, and presented with macular retinitis without vitritis. The disease was bilateral in one case and unilateral in the other. The clinical course was rapidly progressive with widespread retinal involvement and the development of rhegmatogenous retinal detachment with complete loss of vision in the affected eyes despite intensive intravenous antiviral therapy. VZV DNA was identified in vitreous biopsies, by molecular techniques based on the polymerase chain reaction (PCR), in both patients. At present, the use of very high-dose intravenous acyclovir may be the best therapeutic option in these patients for whom the visual prognosis is poor. Intravitreal antiviral drugs could also contribute to the management of these cases.
PURPOSE: These studies were undertaken to establish an animal model for use in studies of ocular toxoplasmosis. An animal model is needed to examine the development, progression, and resolution of ocular Toxoplasma infections and to study the effects on the disease of currently used and experimental therapies. METHODS: Cysts of the ME 49 strain of Toxoplasma gondii were injected intraperitoneally into each of 60 golden hamsters. The hamsters' eyes were examined before inoculation and at intervals after inoculation, and fundus photographs were taken. Histologic sections were analyzed and photographed to document the ocular effects of the infection. RESULTS: Retinochoroiditis was found in both eyes of all hamsters within 2 to 3 weeks of inoculation. The disease resolved spontaneously without treatment and was quiescent in most cases at 12 weeks after inoculation. The animals remained in good general health, and those tested had high antibody titers to Toxoplasma (1:256 to 1:32,000) at 6 months after the infection. The discovery of cysts and lesions in the retina confirmed the diagnosis. CONCLUSIONS: Although the lesions were not identical to those of human disease, this animal model of ocular toxoplasmosis offers several advantages: reproducibility, short incubation time, spontaneous resolution without treatment, consistent production of cysts, and ease of inoculation intraperitoneally without intraocular injection.
Ultrastructural studies were undertaken to reexamine the structure and function of the micropore of Toxoplasma gondii. By incubating tachyzoites with the tracer horseradish peroxidase (HRP), we showed for the first time cytochemically that an extracellular tracer was internalized into vacuoles at the micropore. Our morphological observations also demonstrated that the base of the micropore in both tachyzoites and bradyzoites was sometimes covered by a clathrin-like bristle coat. A coated vesicle was observed in continuity with a bradyzoite micropore, and large (150-nm) coated vesicles were occasionally present just beneath the micropore. These results suggest that receptor-mediated endocytosis occurs at the micropore. In other micrographs, however, the micropore appeared uncoated. In some bradyzoites, the uncoated micropore was greatly dilated, and it contained vesicles like those found in the cyst matrix associated with debris from disintegrated parasites. We had previously observed such debris from fragmented organisms in cysts prepared in vivo. These results indicate that residues from dead bradyzoites may provide nutrients for younger, developing parasites in the same cysts. Our observations also suggest that either receptor-mediated or bulk endocytosis can occur at the micropore, perhaps depending upon the availability of specific ligands. Investigation of a receptor-mediated pathway may reveal a means for targeting therapy selectively to the parasites to benefit patients with disseminated toxoplasmosis.
Seventy-one consecutive patients presenting with their first episode of uveitis at the age of 60 or more years, were studied retrospectively. The majority were found to have idiopathic uveitides on investigation. In those who did have associated systemic disease, the commonest finding was non-insulin-dependent diabetes mellitus or an autoimmune disease. There were no cases of ocular lymphoma in this series. We conclude that, contrary to some previous reports, idiopathic uveitis may occur in the elderly, and that the relative frequencies of acute anterior, chronic anterior, intermediate and posterior uveitides are similar to those seen in young patients.
The living parasites in Toxoplasma cysts cannot be eradicated by current therapy and maintain latent infections for many years. Relatively little is known about encysted Toxoplasma. We therefore undertook studies using mice infected with the avirulent ME 49 strain of Toxoplasma. The bradyzoites in young (12- to 17-day-old) cysts contained the same organelles as did tachyzoites. The bradyzoites of older cysts (4 weeks postinoculation) had differentiated, losing certain organelles and acquiring others. Our major new finding was that in animals inoculated greater than or equal to 4 weeks previously, some bradyzoites were totally disrupted, spilling their contents (perhaps including lytic substances) into the cyst matrix. Many older bradyzoites in the same cysts lacked internal membranes and their viability was questionable, but there were also occasional parasites resembling viable tachyzoites and mature bradyzoites, organisms that might possibly initiate daughter cyst formation after cyst rupture. The life span of an individual bradyzoite may be shorter than formerly appreciated despite the prolonged course of latent infections.
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