P. Labalette

Ocular toxoplasmosis after the fifth decade

PURPOSE To describe the clinical features in patients presenting with ocular toxoplasmosis after the fifth decade and to analyze laboratory findings in comparison to uveitis history and clinical data. DESIGN Prospective consecutive observational case series. METHODS A prospective clinical analysis of 27 consecutive patients older than 50 years of age with primary or recurrent ocular toxoplasmosis was performed during a period of 8 years. These cases account for 12% of all ocular toxoplasmosis cases irrespective of age indexed in our institution during the same period. Paired serum and aqueous humor samples were tested for anti-Toxoplasma gondii IgG, IgM, and IgA antibodies. The presence of T. gondii DNA in aqueous humor was determined by polymerase chain reaction followed by DNA hydridization method. RESULTS Although similar in age, two groups were distinguished clinically: 12 patients (44%) presented with usual forms of retinochoroiditis (mean +/- SD, 1.6 +/- 0.5 disk areas [DA] in size); 15 patients (56%) presented with atypical lesions, greater than 3 DA in size (mean +/- SD, 5.0 +/- 2.0 DA). The second group showed a higher rate of complications (P =.028) and a poorer visual outcome (P =.015). Twenty-four patients (89%) had intraocular IgG production, 17 (63%) had intraocular IgA production, 3 (11%) had intraocular IgM production, and 12 (44%) had a positive T. gondii DNA detection. CONCLUSIONS After the fifth decade, ocular toxoplasmosis remains an important cause of posterior uveitis. The combination of antibody detection by immunocapture tests with T. gondii DNA detection, both in aqueous humor, allowed the diagnosis of toxoplasmic infection in the atypical cases with large ocular lesions.

Using human CD20-transfected murine lymphomatous B cells to evaluate the efficacy of intravitreal and intracerebral rituximab injections in mice.

PURPOSE The treatment of primary central nervous system lymphoma (PCNSL) and its subset, primary intraocular lymphoma (PIOL), remains of limited efficiency, and salvage therapies are often used without prior testing in adequate animal models. Most PNCSL/PIOL are aggressive B-cell malignancies. Two animal models that closely mimic the human situation were established to evaluate the efficiency of intravitreal and intracerebral anti-CD20 monoclonal antibody (rituximab) injections. METHODS Human CD20-transfected murine B-lymphoma cells (38C13 CD20(+)) were inoculated in the vitreous through the pars plana or in the caudate nucleus with the use of a stereotaxic frame in immunocompetent syngeneic mice. Animals were monitored clinically and by funduscopic and histologic examination. Rituximab was injected intravitreally or intracerebrally. Occurrences of exophthalmia, neurologic disturbance, and weight loss were monitored over 2 months. RESULTS Inoculation of 38C13 CD20(+) cells in the eye or the brain resulted in tumor occurrence after a median of 15 days or 22 days, respectively, with histologic characteristics closely resembling those of PIOL and PCNSL. Local rituximab injections eradicated tumor colonization in more than half the graft recipients and inhibited tumor progression significantly in the others compared with progression in mice that underwent grafting with the control 38C13 cell line (no human CD20 expression) and in mice that underwent grafting with 38C13 CD20(+) cells that received local injections of an irrelevant antibody (trastuzumab). CONCLUSIONS Inoculation of native or human CD20-transfected murine 38C13 cells in the vitreous or the brain of immunocompetent mice provides useful novel models for evaluating the biology and treatment of PIOL and PCNSL. Intravitreal and intracerebral rituximab injections reduced tumor occurrence and growth in each model.

Use of Fluorescence Resonance Energy Transfer Hybridization Probes To Evaluate Quantitative Real-Time PCR for Diagnosis of Ocular Toxoplasmosis

ABSTRACT Toxoplasma gondii infection is an important cause of chorioretinitis in Europe and the United States. Ophthalmological examination and a good clinical response to adequate therapy mainly support ocular toxoplasmosis diagnosis. However, clinical diagnostic may be difficult in some atypical cases. In these cases, laboratory confirmation, based on detection of local specific antibodies and parasite DNA by conventional PCR, is therefore important to confirm the disease etiology. More recently, real-time PCR has been developed to improve prenatal congenital toxoplasmosis diagnosis. We therefore examined the diagnostic value of quantitative real-time PCR for the detection of T. gondii in aqueous humor samples, associated with quantification of human β-globin to control sample quantitative quality, by using a double fluorescence resonance energy transfer hybridization probes system with a double fluorescence reading. Of the 23 the clinically toxoplasmosis suspect patients, 22 showed serological evidence of exposure to Toxoplasma; one had a serological profile indicative of active infection. The analysis of paired aqueous humor and serum samples revealed an intraocular antibody production in 9 of 23 cases (39.1%). The quantitative real-time PCR revealed positive and high parasite numbers and high Toxoplasma/human genome ratios in three cases. Furthermore, PCR was the only positive confirmatory test in two cases (11.1%). None of the patients included in the control group (n = 7) had evidence of either local specific antibody production or T. gondii DNA detection, suggesting a good relative assay specificity. On the whole, quantitative real-time PCR appears to be useful for diagnosing atypical ocular toxoplasmosis presentations.

Microphthalmia transcription factor analysis in posterior uveal melanomas.

PURPOSE The protein encoded by the Microphthalmia gene (MITF) is a transcription factor essential for the development and survival of melanocytes. It serves as a master regulator in modulating extracellular signals. Because of its central role in melanocytes survival and to assess its potential use as a histopathological marker for melanoma, MITF expression was examined in human choroidal melanomas. METHODS Fifty-seven paraffin-embedded sections of choroidal melanoma specimens and 1 choroidal melanoma cell line were analyzed using immunochemistry and RT-PCR. Normal choroids and normal choroidal melanocyte cells were used as control. RESULTS Sixty-five percent of the tumoral specimens stained positively for MITF with a predominant nuclear pattern of reactivity. MITF-M and MITF-A isoforms were detected by RT-PCR in all specimens examined. Using a chimeric protein resulting from the fusion of each Mitf protein with the GFP, Mitf-M exhibited an exclusive nuclear staining whereas Mitf-A exhibited a mixed nuclear and cytoplasmic staining. No correlation between MITF-positivity and parameters such as cell type, largest tumor diameter, sclera invasion, mitotic figures was observed. In contrast, a significant negative association was found between MITF staining and the pigmentation (p=0.02) and a positive correlation between MITF staining and the proliferative marker Ki67 was found (p=0.02). CONCLUSION MITF may be implicated in choroidal melanoma pigmentation and proliferation. Further analysis should provide new insights into the mechanisms underlying the molecular and cellular changes of choroidal melanomas.

Bilateral multifocal uveal juvenile xanthogranuloma in a young boy with systemic disease

AbstractBackground. Juvenile xanthogranuloma is a rare non-Langerhans cell histiocytosis that could occasionally produce diffuse systemic disease in young children, but associated posterior uveal lesions are very uncommon. Methods. Case report of an 8-month-old boy with macrocephaly who presented with chronic subdural haematoma and intracranial hypertension. A combination of nodular skin lesions and bilateral yellowish choroidal infiltration with limited retinal involvement suggested juvenile xanthogranuloma. Results. The diagnosis was confirmed by a skin biopsy, and oral corticosteroid therapy was introduced. Progression of the disease to involve an anterior uveitis with hypopyon and numerous other systemic lesions, including the central nervous system, lung, liver, spleen, kidney and testis, was also suggestive of Letterer-Siwe disease. Histiocytes were negative for Langerhans cell markers (S-100 and CD1a) and positive for macrophage marker (CD68). Electron microscopy failed to show Birbeck granules. Ocular lesions regressed under prolonged corticosteroid treatment, but resurgence of the other lesions required chemotherapy with vinblastine. Conclusion. In this atypical systemic variant of juvenile xanthogranuloma with bilateral uveal involvement, the immunohistochemical and ultrastructural findings were crucial in distinguishing juvenile xanthogranuloma from Langerhans cell histiocytosis.

Sarcome granulocytique orbitaire révélant l’acutisation d’un syndrome myélodysplasique: À propos d’un cas

Le sarcome granulocytique est une complication orbitaire rare des leucemies aigues et concerne essentiellement les enfants de moins de 10 ans presentant une leucemie aigue myeloide de novo . Ce type d’atteinte se rencontre exceptionnellement chez le sujet âge lors de l’acutisation d’un syndrome myelodysplasique, cela pose un probleme de diagnostic et par voie de consequence de prise en charge therapeutique. Nous rapportons le cas d’une patiente de 77 ans ayant presente une exophtalmie brutale au decours d’une ethmoidite droite en voie de resolution. Le diagnostic evoque par l’imagerie qui montre une tumeur intra-orbitaire extraconique a point de depart sinusien est confirme lors du bilan hematologique. Une exophtalmie brutale evoluant dans un contexte de leucemie aigue myeloblastique oriente fortement vers le diagnostic de sarcome granulocytique. Une chimiotherapie par cytarabine et hydroxycarbamide associee a une corticotherapie intraveineuse permet d’observer une disparition complete de l’exophtalmie en une dizaine de jours. Le but de ce cas clinique est de rappeler ce mode d’expression du syndrome tumoral au cours des leucemies aigues myeloides. Nous abordons aussi les differentes methodes de diagnostic, les differents abords therapeutiques, l’evolution et la surveillance des patients.Granulocytic sarcoma is a rare orbital complication of acute leukemia. It concerns primarily children under 10 years of age suffering from primitive acute myeloid leukemia. As this type of symptom can sometimes affect the elderly during the acute phase of myelodysplastic syndrome, it raises a problem with diagnosis and consequently with therapeutic treatments. We report the case of a 77-year-old female patient who had acute inflammatory proptosis during regressive right ethmoiditis. The diagnosis was reached by computed tomography showing an extraconical intraorbital tumor sprouting from the sinus, and by clinical examination and confirmed by the hematological investigation. Acute proptosis developing in an acute myeloblastic leukemia context heavily swayed diagnosis towards orbital granulocytic sarcoma. Chemotherapy by cytarabine and hydroxycarbamide associated with intravenous corticoid therapy resulted in complete disappearance of the proptosis within 10 days. This case report is a reminder of this peculiar sign of tumoral syndrome in acute myeloid leukemia. We also discuss different diagnostic methods and various therapeutic approaches, and analyze the disease course and patient follow-up.

Hémorragie intra-vitréenne du nouveau-né et galactosémie : À propos d'un cas

Galactosemia is an inherited metabolic disorder due to a defect in one of the three enzymes required to fully metabolize the galactose in glucose: the galactose 1-phosphate uridyltransferase. Because this enzyme is present in the normal foetal liver since the tenth week of gestation, its defect cause congenital abnormality due to galactose accumulation, when the mother had taken milk during the pregnancy. It is mainly a liver pathology whereas the foetal cataract is rare. This latter is usually considered as the sole ophthalmic consequence of this disorder but exceptional ocular haemorrhages have also been described. We report the case of a neonate with galactosemia free from foetal cataract but presenting an unilateral vitreous haemorrhage. Retinal anomalies seen after vitrectomy are probably the source of the vitreous blood favoured by the coagulopathy associated with the neonatal disease. The causes of infant vitreous haemorrhages are often debated and their complications, especially severe amblyopia, require vitrectomy within the month following their discovery. In galactosemia, vitreous haemorrhage can be prevented by an early diagnosis and an appropriate treatment of the liver pathology.La galactosemie est une affection hereditaire due a un deficit de l’une des trois enzymes du metabolisme du lactose en glucose : la galactose 1 phosphate uridyltransferase. Presente dans le foie normal des la dixieme semaine de gestation, son deficit peut entrainer des manifestations congenitales par accumulation de galactose des lors que la mere a une alimentation lactee pendant la grossesse. Il s’agit principalement de la survenue d’une insuffisance hepatique neonatale alors que la cataracte fœtale est rare. Celle-ci est habituellement consideree comme la seule manifestation ophtalmologique, mais d’exceptionnelles complications hemorragiques intra-oculaires ont ete decrites. Nous rapportons le cas d’un nouveau-ne atteint de galactosemie ne presentant pas de cataracte fœtale, mais une hemorragie intra-vitreenne unilaterale. Les anomalies retiniennes mises en evidence apres la vitrectomie expliqueraient la survenue d’hemorragies dont la diffusion intra-vitreenne serait favorisee par les troubles de la coagulation de la maladie neonatale. Chez l’enfant, les causes des hemorragies intra-vitreennes sont sujet a controverse et leurs complications, dont l’installation rapide d’une amblyopie, justifient une vitrectomie dans le mois qui suit leur apparition. La prevention du risque d’hemorragie intra-oculaire compliquant une galactosemie depend de la precocite du diagnostic etiologique de l’insuffisance hepatique et de sa prise en charge therapeutique.

Importance de la rééducation de l'amblyopie dans les cataractes congénitales unilatérales partielles de découverte tardive

Objectif Le but de cette etude est de rappeler l’importance de la reeducation de l’amblyopie chez les patients porteurs d’une cataracte congenitale unilaterale partielle de decouverte tardive (apres l’âge de 2 ans). Materiel et methodes Une etude retrospective a ete realisee chez 11 patients atteints d’une cataracte congenitale unilaterale partielle non operes. Chaque patient a beneficie d’un examen ophtalmologique complet avec une refraction objective sous atropine. L’âge moyen de decouverte de la cataracte est de 35 mois. L’acuite visuelle initiale moyenne est de 1,5/10 en vision de loin et de Rossano-Weiss 1/8 en vision de pres. Apres correction optique, une reeducation de l’amblyopie par occlusion a ete realisee. L’observance de la reeducation a ete mauvaise dans 2 cas. Le suivi moyen a ete de 28 mois (5 a 60 mois). Resultats Une ametropie est retrouvee chez tous les patients avec anisometropie dans 9 cas (α Conclusion L’amblyopie est en rapport avec les opacites cristalliniennes mais egalement avec l’anisometropie frequemment associee. L’amelioration fonctionnelle est plus importante en vision de pres qu’en vision de loin. La reeducation de l’amblyopie chez ces patients non operes permet de conserver l’accommodation, facteur essentiel chez le jeune enfant ou la vision de pres est preferentielle. Cette etude permet de rappeler l’importance de la refraction et de la reeducation de l’amblyopie qui doit etre realisee de facon systematique avant d’envisager un eventuel geste chirurgical dans ces cataractes congenitales unilaterales partielles.

Hémangiopéricytome des fosses nasales révélé par un épisode de dacryocystite aiguë

Nous rapportons un cas de tumeur vasculaire de type hemangiopericytome des fosses nasales, chez une patiente de 42 ans. Cette lesion a ete decouverte au decours d’un episode de dacryocystite aigue. Un bilan clinique rhinoscopique et une tomodensitometrie orbito-faciale ont mis en evidence une tumefaction situee en regard du sac lacrymal et du canal lacrymonasal. Une exerese de la lesion par voie endonasale avec examen anatomopathologique a permis d’etablir le diagnostic d’hemangiopericytome. Une irradiation complementaire adjuvante a ete mise en œuvre au niveau de la region du canthus interne et du toit du sinus maxillaire.

Sarcome granulocytique orbitaire révélant l’acutisation d’un syndrome myélodysplasique

Le sarcome granulocytique est une complication orbitaire rare des leucemies aigues et concerne essentiellement les enfants de moins de 10 ans presentant une leucemie aigue myeloide de novo . Ce type d’atteinte se rencontre exceptionnellement chez le sujet âge lors de l’acutisation d’un syndrome myelodysplasique, cela pose un probleme de diagnostic et par voie de consequence de prise en charge therapeutique. Nous rapportons le cas d’une patiente de 77 ans ayant presente une exophtalmie brutale au decours d’une ethmoidite droite en voie de resolution. Le diagnostic evoque par l’imagerie qui montre une tumeur intra-orbitaire extraconique a point de depart sinusien est confirme lors du bilan hematologique. Une exophtalmie brutale evoluant dans un contexte de leucemie aigue myeloblastique oriente fortement vers le diagnostic de sarcome granulocytique. Une chimiotherapie par cytarabine et hydroxycarbamide associee a une corticotherapie intraveineuse permet d’observer une disparition complete de l’exophtalmie en une dizaine de jours. Le but de ce cas clinique est de rappeler ce mode d’expression du syndrome tumoral au cours des leucemies aigues myeloides. Nous abordons aussi les differentes methodes de diagnostic, les differents abords therapeutiques, l’evolution et la surveillance des patients.Granulocytic sarcoma is a rare orbital complication of acute leukemia. It concerns primarily children under 10 years of age suffering from primitive acute myeloid leukemia. As this type of symptom can sometimes affect the elderly during the acute phase of myelodysplastic syndrome, it raises a problem with diagnosis and consequently with therapeutic treatments. We report the case of a 77-year-old female patient who had acute inflammatory proptosis during regressive right ethmoiditis. The diagnosis was reached by computed tomography showing an extraconical intraorbital tumor sprouting from the sinus, and by clinical examination and confirmed by the hematological investigation. Acute proptosis developing in an acute myeloblastic leukemia context heavily swayed diagnosis towards orbital granulocytic sarcoma. Chemotherapy by cytarabine and hydroxycarbamide associated with intravenous corticoid therapy resulted in complete disappearance of the proptosis within 10 days. This case report is a reminder of this peculiar sign of tumoral syndrome in acute myeloid leukemia. We also discuss different diagnostic methods and various therapeutic approaches, and analyze the disease course and patient follow-up.