Expanded Spectrum of Optical Coherence Tomography Findings in Patients with Ocular Toxoplasmosis.

PURPOSE: To describe the optical coherence tomography (OCT) findings of toxoplasmic retinochoroiditis at different stages of activity. METHODS: Observational case series. RESULTS: A total of 32 eyes of 31 patients were included; 43 sets of OCT were reviewed. A total of 14 lesions were classified as active, 13 as partially active, and 16 as inactive. All active lesions demonstrated increased retinal thickness and reflectivity with blurring of details of retinal layers. Choroidal granuloma was detected in eight (61.5%) and serous retinal detachment in nine (64%). In partially active lesions, sustained thickening and/or attachment of posterior hyaloid face with fine epiretinal membrane was the hallmark. Scarified lesions showed decreased retinal and choroidal thickness starting from the periphery. Characteristic signs for decreased activity of a lesion seen in majority of both partially active and inactive lesions were RPE changes and retina-RPE approximation. We called this unique feature 'hourglass configuration'. CONCLUSION: Features in OCT are helpful to specify and monitor the activity of toxoplasmic retinochoroiditis.

Optic nerve involvement in ocular toxoplasmosis: 12 year data from a tertiary referral center in Turkey / Acometimento de nervo óptico na toxoplasmose ocular: um relato de 12 anos de um centro de referência terciário na Turquia

ABSTRACT Purpose: To evaluate the prevalence, clinical characteristics, and types of optic nerve involvement in patients with ocular toxoplasmosis. Methods: For this retrospective cross-sectional study, we examined all patients with active ocular toxoplasmosis referred to our Uveitis Section during the last 12 years, and we included patients with optic nerve involvement in the study. The primary outcome was the prevalence of optic nerve involvement, and secondary outcomes included the types of optic nerve involvement and the final best-corrected visual acuity after treatment. Results: The prevalence of optic nerve involvement was 14.4%, with the leading cause being the activation of a juxtapapillary lesion (70.5%). We found papillitis in two eyes and neuroretinitis in two eyes (11.7% for each). We only detected one optic nerve involvement secondary to a distant active lesion (5.8%). Sixteen patients (94.1%) had unilateral ocular toxoplasmosis. The overall final best-corrected visual acuity after treatment was 10/10 (LogMAR = 0.0) excluding the three patients with a juxtapapillary scar involving the macula. Conclusions: Optic nerve involvement was common in patients with ocular toxoplasmosis. The main type of optic nerve involvement was caused by activation of an old juxtapapillary lesion. Treatment was quickly effective, but the best-corrected visual acuity was dependent on the presence of a scar in the papillomacular bundle.

RESUMO Objetivos: Avaliar a prevalência, características clínicas e tipos de acometimento do nervo óptico em pacientes com toxoplasmose ocular. Métodos: Para este estudo retrospectivo transversal, examinamos todos os pacientes com toxoplasmose ocular ativa encaminhados ao nosso Setor de Uveíte nos últimos 12 anos, e incluímos pacientes com comprometimento do nervo óptico no estudo. O resultado primário foi a prevalência do envolvimento do nervo óptico, e os resultados secundários incluíram os tipos de envolvimento do nervo óptico e a acuidade visual final melhor corrigida após o tratamento. Resultados: A prevalência de acometimento do nervo óptico foi 14,4%, sendo a principal causa a ativação de uma lesão justapapilar (70,5%). Encontramos papilite em dois olhos e neuroretinite em dois olhos (11,7% para cada um). Apenas detectamos um comprometimento do nervo óptico secundário a uma lesão ativa distante (5,8%). Dezesseis pacientes (94,1%) apresentavam toxoplasmose ocular unilateral. A acuidade visual final com melhor correção após o tratamento foi 10/10 (LogMAR= 0,0) excluindo os três pacientes com uma cicatriz justapapilar envolvendo a mácula. Conclusões: O comprometimento do nervo óptico foi comum em pacientes com toxoplasmose ocular. O principal tipo de comprometimento do nervo óptico foi causado pela ativação de uma lesão justapapilar antiga. O tratamento foi rapidamente eficaz, mas a acuidade visual final com melhor correção foi dependente da presença de uma cicatriz no feixe papilomacular.

Ultrasonographic characteristics of active ocular toxoplasmosis / Achados ultrassonográficos em toxoplasmose ocular ativa

ABSTRACT Purpose: To evaluate ophthalmic ultrasonographic findings associated with active ocular toxoplasmosis. Methods: Forty-seven eyes with active ocular toxoplasmosis in 47 patients were subjected to ocular ultrasonography using the transpalpebral technique (10-MHz transducer) and fundus photography. Patient medical records were retrospectively reviewed. Results: Ocular ultrasonography revealed vitritis, posterior vitreous detachment, retinal wall thickening, and non-rhegmatogenous retinal detachment in 47 (100%), 36 [76.6%; partial in 12 (25.5%) and total in 23 (48.9%)], 12 (25.5%), and 5 eyes (10.6%). Thirty-five of the 36 eyes with posterior vitreous detachment (97.2%) exhibited posterior hyaloid thickening; moreover, adhesion to the exudative lesion and vitreoschisis were observed in 4 (11.1%) and 12 eyes (25.5%), respectively. Ultrasonography detected the location of the exudative focus in 12 eyes (25.5%). Conclusion: Ultrasonography is helpful for detecting important intraocular findings of acute ocular toxoplasmosis that can be hindered by medial opacity or posterior synechiae.

RESUMO Objetivo: Avaliar os achados da ultrassonografia na toxoplasmose ocular ativa. Métodos: Quarenta e sete olhos com toxoplasmose ocular ativa em 47 pacientes foram submetidos à ultrassonografia ocular pela técnica transpalpebral (transdutor de 10 MHz) e fundo de olho. Os prontuários médicos foram revistos retrospectivamente. Resultados: A ultrassonografia ocular revelou vitreíte, descolamento vítreo posterior, espessamento da parede da retina e descolamento de retina não regmatogênico em 47 (100%), 36 [76,6%; parcial em 12 (25,5%) e total em 23 (48,9%)], 12 (25,5%) e 5 olhos (10,6%). Trinta e cinco dos 36 olhos com descolamento vítreo posterior (97,2%) exibiram espessamento hialoide posterior; além disso, a adesão à lesão exsudativa e vitreosquise foi observada em 4 (11,1%) e 12 (25,5%), respectivamente. A ultrassonografia detectou a localização do foco exsudativo em 12 olhos (25,5%). Conclusão: A ultrassonografia é útil na detecção de importantes achados intra-oculares de toxoplasmose ocular aguda que podem ser prejudicados pela opacidade medial ou sinéquia posterior.

Increased IL-27/IL-27R expression in association with the immunopathology of murine ocular toxoplasmosis.

Interleukin 27 (IL-27) is a member of the IL-6/IL-12 family, and IL-27 receptor (IL-27R) consists of WSX-1 (the IL-27Rα subunit) and the signal-transducing subunit gp130. Human and mouse mast cells (MCs) express the IL-27R. To explore the expressions of IL-27/IL-27R subunits (WSX-1 and gp130) during acute ocular toxoplasmosis (OT), we established mouse model by intraocular injection of 500 Toxoplasma gondii RH strain tachyzoites. Histopathological changes were analyzed, MCs were counted by toluidine blue staining, and tryptase+/IL-27+ MCs were examined by immunofluorescence double-staining in the eyes and cervical lymph nodes (CLNs) of T. gondii-infected mice. The mRNA expressions of IL-27p28, WSX-1, gp130, and tachyzoite specific surface antigen 1 (SAG1) in the eyes and CLNs of T. gondii-infected mice, and the expressions of WSX-1 and gp130 in the murine mastocytoma cell line P815 infected with T. gondii tachyzoites in vitro were examined by using quantitative real-time reverse transcription-polymerase chain reaction. Our results showed that, after T. gondii infection, severe histopathological changes, increased numbers of total MCs and degranulated MCs, elevated expressions of IL-27p28, WSX-1, and gp130 were found in the eyes and CLNs, and significant correlations between the levels of IL-27 and SAG1 existed in the eyes and CLNs of T. gondii-infected mice. In addition, increased levels of WSX-1 and gp130 were examined in T. gondii-infected P815 cells. Our data suggested that IL-27/IL-27R expression induced by T. gondii infection may regulate MC-mediated immune response during acute OT in mouse model.

Combined branch retinal vein and artery occlusion in toxoplasmosis / Oclusão combinada de ramo arterial e venoso retinianos em toxoplasmose

ABSTRACT A 22-year-old man complained of low visual acuity and pain in his left eye for five days. His ophthalmological examination revealed 2+ anterior chamber reaction and a white, poorly defined retinal lesion at the proximal portion of the inferotemporal vascular arcade. There were retinal hemorrhages in the inferotemporal region extending to the retinal periphery. In addition, venous dilation, increased tortuosity, and ischemic retinal whitening along the inferotemporal vascular arcade were also observed. A proper systemic work-up was performed, and the patient was diagnosed with ocular toxoplasmosis. He was treated with an anti-toxoplasma medication, and his condition slowly improved. Inferior macular inner and middle retinal atrophy could be observed on optical coherence tomography as a sequela of ischemic injury. To our knowledge, this is the first report of combined retinal branch vein and artery occlusion in toxoplasmosis resulting in a striking and unusual macular appearance.

RESUMO Um paciente do sexo masculino, com 22 anos de idade, queixou-se de redução da acuidade visual no olho esquerdo por 5 dias. O exame oftalmológico mostrou reação de câmara anterior 2+ e uma lesão retiniana esbranquiçada, pouco definida, na porção proximal da arcada vascular temporal inferior. Foram observadas hemorragias retinianas na região temporal inferior estendendo-se à periferia, assim como ingurgitamento venoso, aumento da tortuosidade e palidez isquêmica da retina no mesmo quadrante. Exames laboratoriais corroboraram o diagnóstico de toxoplasmose ocular. O paciente melhorou lentamente após tratamento apropriado. Foi evidenciada atrofia da retina macular inferior interna e média à tomografia de coerência óptica, como sequela da isquemia retiniana. Para nosso conhecimento, este é o primeiro relato de oclusão retiniana combinada de ramo arterial e venoso em toxoplasmose ocular, levando a um aspecto fundoscópico atípico e peculiar.

Visual function and macular architecture in patients with inactive zone 2 and 3 toxoplasmic retinochoroiditis / Função visual e arquitetura macular em pacientes com retinocoroidite toxoplásmica inativa nas zonas 2 e 3

ABSTRACTPurpose:To evaluate the visual function and architecture of the central and peripapillary retina in patients with inactive toxoplasmic retinochoroiditis outside the macular and peripapillary regions (zones 2 and 3).Methods:Cross-sectional study of 20 eyes (18 patients) with zone 2 and 3 toxoplasmic scars and visual acuity ≥20/25. Patients underwent Humphrey 10-2 perimetry, contrast sensitivity (Mars test), and color vision testing (L'Anthony desaturated D-15). The retinal nerve fiber layer (RNFL) and macular thicknesses were determined by optical coherence tomography.Results:The patients' mean age was 27.4 ± 10.3 years, and the mean duration of remission was 6.15 ± 5.19 months. Abnormal contrast sensitivity and color vision were observed in three (15.0%) and four eyes (20.0%), respectively. Mean deviation (MD) and pattern standard deviation (PSD) fell outside the 95% normal confidence limits of the perimeter's database in 14 (70.0%) and seven eyes (35.0%), respectively. Foveal and mean RNFL thicknesses were within the normal limits in all eyes. Eyes with zone 2 retinochoroiditis had lower foveal sensitivity than eyes with zone 3 lesions (p=0.041). Eyes with a longer duration of remission had a higher MD (r=0.575; p=0.013) and a lower PSD (r=-0.593; p=0.010).Conclusions:Despite normal central and peripapillary retinal architecture, eyes with inactive zone 2 and 3 toxoplasmic retinochoroiditis can present with abnormal color, contrast, and macular perimetric sensitivity. Zone 2 retinochoroiditis was associated with lower foveal sensitivity, and a longer duration of retinochoroiditis remission was associated with better perimetric parameters (MD and PSD).

RESUMOObjetivo:Avaliar a função visual e arquitetura da retina central e peripapilar em pacientes com retinocoroidite toxoplásmica inativa fora da região macular e peripapilar (zonas 2 e 3).Métodos:Estudo transversal de 20 olhos (18 pacientes) com cicatrizes toxoplásmicas nas zonas 2 e 3 com acuidade visual ≥20/25. Os pacientes foram submetidos à perimetria Humphrey 10-2, teste de sensibilidade ao contraste (Teste Mars) e teste de visão de cores (L'Anthony D-15 dessaturado). As espessuras da camada de fibras nervosas da retina (CFNR) e da mácula foram determinadas pela tomografia de coerência óptica.Resultados:A média de idade dos pacientes foi 27,4 ± 10,3 anos, e a duração média da remissão da retinocoroidite foi de 6,15 ± 5,19 meses. Alterações na sensibilidade ao contraste e cores foram observada em, respectivamente, 3 olhos (15,0%) e 4 olhos (20,0%). Os índices perimétricos mean deviation (MD) e pattern standard deviation (PSD) estiveram fora do intervalo de confiança de 95% do perímetro em 14 olhos (70,0%) e 7 olhos (35,0%), respectivamente. A espessura foveal e da CFNR média estiveram dentro do limite da normalidade em todos os olhos. Olhos com retinocoroidite na zona 2 tiveram menor sensibilidade foveal que olhos com lesões na zona 3 (p=0,041). Olhos com remissão de longa duração tiveram um MD mais alto (r=0,575; p=0,013) e um PSD mais baixo (r=-0,593; p=0,010).Conclusão:Apesar da arquitetura normal da retina central e peripapilar, olhos com retinocoroidite inativa nas zonas 2 e 3 podem apresentar anormalidades da visão de cores, sensibilidade ao contras e perimetria macular. A retinocoroidite na zona 2 está associada a uma menor sensibilidade foveal. Longos intervalos de remissão da retinocoroidite estiveram associados a melhores parâmetros perimétricos (MD e PSD).

Subretinal fluid in eyes with active ocular toxoplasmosis observed using spectral domain optical coherence tomography.

PURPOSE: To describe the clinical finding of subretinal fluid (SRF) in the posterior pole by spectral domain optical coherence tomography (SD-OCT) in eyes with active ocular toxoplasmosis (OT). DESIGN: Retrospective case series. PARTICIPANTS: Thirty-nine eyes from 38 patients with active OT [corrected].. METHODS: Eyes with active OT which underwent SD-OCT were reviewed. SRFs in the posterior pole were further analyzed. MAIN OUTCOME MEASURES: Presence of SRF; its accompanying features, e.g. retinal necrosis, cystoid macular edema (CME), choroidal neovascularization (CNV); and longitudinal changes of SRF, including maximum height and total volume before and after treatment. RESULTS: SRF presented in 45.5% (or 15/33) of eyes with typical active OT and in 51.3% (or 20/39) of eyes with active OT. The mean maximum height and total volume of SRF were 161.0 (range: 23-478) µm and 0.47 (range: 0.005-4.12) mm3, respectively. For 12 eyes with SRF related to active retinal necrosis, SRF was observed with complete absorption after conventional anti-toxoplasmosis treatment. The mean duration for observation of SRF clearance was 33.8 (range: 7-84) days. The mean rate of SRF clearance was 0.0128 (range: 0.0002-0.0665) mm3/day. CONCLUSIONS: SRF (i.e., serous retinal detachment) is a common feature in patients with active OT when SD-OCT is performed. The majority of SRF was associated with retinal necrosis and reacted well to conventional therapy, regardless of total fluid volume. However, SRF accompanying with CME or CNV responded less favorably or remained refractory to conventional or combined intravitreal treatment, even when the SRF was small in size.

Interleukin-6-driven inflammatory response induces retinal pathology in a model of ocular toxoplasmosis reactivation.

Ocular inflammation is one of the consequences of infection with the protozoan parasite Toxoplasma gondii. Even if lesions are self-healing in immunocompetent persons, they pose a lifetime risk of reactivation and are a serious threat to vision. As there are virtually no immunological data on reactivating ocular toxoplasmosis, we established a model of direct intravitreal injection of parasites in previously infected mice with a homologous type II strain. Two different mouse strains with variable ability to control retinal infection were studied in order to describe protective and deleterious reaction patterns. In Swiss-Webster mice, which are already relatively resistant to primary infection, no peak of parasite load was observed upon reinfection. In contrast, the susceptible inbred strain C57BL/6 showed high parasite loads after 7 days, as well as marked deterioration of retinal architecture. Both parameters were back to normal on day 21. C57BL/6 mice also reacted with a strong local production of inflammatory and Th1-type cytokines, like interleukin-6 (IL-6), IL-17A, and gamma interferon (IFN-γ), while Swiss-Webster mice showed only moderate expression of the Th2 cytokine IL-31. Interestingly, rapid intraocular production of anti-Toxoplasma antibodies was observed in Swiss-Webster but not in C57BL/6 mice. We then localized the cellular source of different immune mediators within the retina by immunofluorescence. Finally, neutralization experiments of IFN-γ or IL-6 demonstrated the respective protective and deleterious roles of these cytokines for parasite control and retinal integrity during reinfection. In conclusion, we developed and immunologically characterized a promising mouse model of reactivating ocular toxoplasmosis.

Evaluation of cystoid change phenotypes in ocular toxoplasmosis using optical coherence tomography.

PURPOSE: To present unique cystoid changes occurring in patients with ocular toxoplasmosis observed in spectral domain optical coherence tomography (OCT). METHODS: Forty-six patients (80 eyes) with a diagnosis of ocular toxoplasmosis, who underwent volume OCT examination between January 2005 and October 2012, were retrospectively collected. Review of clinical examination findings, fundus photographs, fluorescein angiograms (FA) and OCT image sets obtained at initial visits and follow-up. Qualitative and quantitative analyses of cystoid space phenotypes visualized using OCT. RESULTS: Of the 80 eyes included, 17 eyes (15 patients) demonstrated cystoid changes in the macula on OCT. Six eyes (7.5%) had cystoid macular edema (CME), 2 eyes (2.5%) had huge outer retinal cystoid space (HORC), 12 eyes (15%) had cystoid degeneration and additional 3 eyes (3.75%) had outer retinal tubulation due to age related macular degeneration. In one eye with HORC, the lesion was seen in the photoreceptor outer segment, accompanied by photoreceptor elongation and splitting. Three eyes presented with paravascular cystoid degeneration in the inner retina without other macular OCT abnormality. CONCLUSIONS: In this study, different phenotypes of cystoid spaces seen in eyes with ocular toxoplasmosis using spectral domain OCT (SD-OCT) were demonstrated. CME presented as an uncommon feature, consistently with previous findings. Identification of rare morphological cystoid features (HORC with/without photoreceptor enlongation or splitting) on clinical examination had provided evidence to previous experimental models, which may also expand the clinical spectrum of the disease. Cystoid degeneration in the inner retina next to the retinal vessels in otherwise "normal" looking macula was observed, which may suggest more often clinical evaluation for those patients. Further studies are needed to verify the relevance of cystoid features seen on SD-OCT in assisting with the diagnosis and management of ocular toxoplasmosis.

Morphometric changes in C57BL/6 mice retina infected by Toxoplasma gondii ME 49 strain.

This study evaluated the morphometric implications in C57BL/6 mouse retina infected by Toxoplasma gondii, ME 49 strain. Twenty C57BL/6 female mice were divided into group 1 (n=8, intraperitoneally infected with 30 cysts of T. gondii ME 49 strain) and group 2 (n=12 non-infected controls). The eyes were enucleated on the 60th day after infection, fixed and processed for light microscopy. Changes in retinal thickness and in the perimeter/area ratio (P/A) of the retinal layers were analyzed by digital morphometry. We considered that P/A was the measurement of retinal architecture distortion induced by toxoplasmosis. This study considered the ganglion cells and nerve fiber layers as a monolayer, thus six layers of retina were evaluated: photoreceptors (PRL), outer nuclear (ONL), outer plexiform (OPL), inner nuclear (INL), inner plexiform (IPL) and ganglion cells/nerve fiber monolayer (GNL). Histological analysis of infected mouse retina showed inflammatory infiltrate, necrosis, glial reaction and distortion of the retina architecture. It also presented increased thickness (167.8±24.9µm versus 121.1±15.4µm, in controls) and increased retinal thickness within the retinitis foci (187.7±16.6µm versus 147.9±12.2µm out of the retinitis foci). A statistically significant difference in P/A was observed between infected and uninfected mouse retinas. The same was observed in PRL, OPL, INL and GNL. Retinal morphometry may be used to demonstrate differences between infected and uninfected mouse retinas.

Severe South American ocular toxoplasmosis is associated with decreased Ifn-γ/Il-17a and increased Il-6/Il-13 intraocular levels.

In a cross sectional study, 19 French and 23 Colombian cases of confirmed active ocular toxoplasmosis (OT) were evaluated. The objective was to compare clinical, parasitological and immunological responses and relate them to the infecting strains. A complete ocular examination was performed in each patient. The infecting strain was characterized by genotyping when intraocular Toxoplasma DNA was detectable, as well as by peptide-specific serotyping for each patient. To characterize the immune response, we assessed Toxoplasma protein recognition patterns by intraocular antibodies and the intraocular profile of cytokines, chemokines and growth factors. Significant differences were found for size of active lesions, unilateral macular involvement, unilateral visual impairment, vitreous inflammation, synechiae, and vasculitis, with higher values observed throughout for Colombian patients. Multilocus PCR-DNA sequence genotyping was only successful in three Colombian patients revealing one type I and two atypical strains. The Colombian OT patients possessed heterogeneous atypical serotypes whereas the French were uniformly reactive to type II strain peptides. The protein patterns recognized by intraocular antibodies and the cytokine patterns were strikingly different between the two populations. Intraocular IFN-γ and IL-17 expression was lower, while higher levels of IL-13 and IL-6 were detected in aqueous humor of Colombian patients. Our results are consistent with the hypothesis that South American strains may cause more severe OT due to an inhibition of the protective effect of IFN-γ.

The involvement of anti-inflammatory protein, annexin A1, in ocular toxoplasmosis.

PURPOSE: The aim of this study was to evaluate the expression of the protein annexin A1 (ANXA1), a potent endogenous regulator of the inflammatory process, in ocular toxoplasmosis. METHODS: C57BL/6 female mice were infected using intravitreal injections of either 10(6) tachyzoites of Toxoplasma gondii (RH strain; T. gondii) or PBS only (control groups). After 24, 48, and 72 h, animals were sacrificed and their eyes were harvested for histopathological, immunohistochemical, and ultrastructural immunocytochemical analysis of ANXA1. Human retinal pigment epithelial (RPE) cells (ARPE-19) were infected in vitro with T. gondii and collected after 60, 120, 240 min, and 24 h. RESULTS: Compared with non-infected eyes, an intense inflammatory response was observed in the anterior (24 h after infection) and posterior segments (72 h after infection) of the infected eye, characterized by neutrophil infiltration and by the presence of tachyzoites and their consequent destruction along with disorganization of normal retina architecture and RPE vacuolization. T. gondii infection was associated with a significant increase of ANXA1 expression in the neutrophils at 24, 48, and 72 h, and in the RPE at 48 and 72 h. In vitro studies confirmed an upregulation of ANXA1 levels in RPE cells, after 60 and 120 min of infection with T. gondii. CONCLUSIONS: The positive modulation of endogenous ANXA1 in the inflammatory and RPE cells during T. gondii infection suggests that this protein may serve as a therapeutic target in ocular toxoplasmosis.

Use of CD25 as an immunohistochemical marker for acquired ocular toxoplasmosis / Uso do CD25 como um marcador imuno-histoquímico de toxoplasmose ocular adquirida

PURPOSE: Toxoplasmosis is the most common cause of posterior infectious uveitis worldwide. It is often impossible to determine its congenital or acquired nature. Interleukin-2 (IL-2) in peripheral blood has been described as a possible marker for acquired toxoplasmosis. The purpose of this study is to evaluate the histopathological characteristics of ocular toxoplasmosis cases using CD25 as a marker for the expression of interleukin-2. METHODS: Ten formalin-fixed, paraffin-embedded enucleated globes from ten immunocompetent patients with clinical diagnosis of toxoplasmosis were evaluated. Four patients had the acquired form of ocular toxoplasmosis (positive IgM) while six were IgM negative and IgG positive for toxoplasmosis. Histopathological slides were reviewed for the extension of the retinal necrosis, number of toxo cysts, the granulomatous inflammatory reaction, the presence of T and B cells within the choroid and the IL-2 expression. Immunohistochemistry using monoclonal antibodies was performed to observe the expression of CD4, CD8, CD20, CD25, and CD68. RESULTS: The histopathological evaluation disclosed no differences between acquired and the other ocular toxoplasmosis cases regarding the characteristics studied. However, CD25 showed a higher expression of IL-2 on the 4 acquired cases of ocular toxoplasmosis compared to the remainders. CONCLUSIONS: To the best of our knowledge, this is the first report showing that the use of CD25 as a marker for interleukin-2 could differentiate acquired ocular toxoplasmosis.

OBJETIVO: Toxoplasmose é a causa mais comum de uveíte posterior no mundo. Em grande parte dos casos, não é possível determinar se a doença ocular é devida a um quadro congênito ou adquirido. Interleucina-2 (IL-2) no sangue periférico foi descrita como um possível marcador de toxoplasmose adquirida. O objetivo deste estudo foi avaliar as características de casos de toxoplasmose usando CD25 como um marcador da expressão de interleucina-2. MÉTODOS: Dez olhos enucleados fixados com formalina e embebidos em parafina de dez pacientes imunocompetentes com diagnóstico clínico de toxoplasmose ocular foram examinados. Quatro pacientes tinham a forma adquirida (IgM positivo) enquanto 6 eram IgM negativo e IgG positivo para toxoplasmose. Cortes histopatológicos foram avaliados quanto a extensão de necrose retiniana, número de cistos de T. gondii, reação granulomatosa e presença de células B e T na coróide, bem como a expressão de interleucina-2. Estudo imuno-histoquímico utilizando anticorpos monoclonais foi realizado para determinar a expressão de CD4, CD8, CD20, CD25 e CD68. RESULTADOS: A avaliação histopatológica não mostrou diferenças entre os casos de toxoplasmose ocular com relação às características avaliadas mencionadas anteriormente. Entretanto, CD25 revelou maior expressão de interleucina-2 nos 4 casos adquiridos comparado com os demais. CONCLUSÕES: Expressão elevada de CD25 foi encontrada em todos os casos de toxoplasmose ocular adquirida. Assim, o uso de CD25 como marcador da interleucina-2 pode ser uma ferramenta útil para diferenciar toxoplasmose ocular congênita de adquirida.

[Toxoplasmic retinochoroiditis: relapse vs choroidal neovascular membrane]. / Retinocoroiditis toxoplásmica: ¿recidiva o membrana neovascular coroidea?

CLINICAL CASE: We report four patients with both decreased visual acuity and retinochoroidal lesions compatible with ocular toxoplasmosis in which a diagnosis of active toxoplasmic retinochoroiditis or choroidal neovascular membrane was made based on a specifically designed diagnostic screening. DISCUSSION: In the context of a compatible clinical picture, with retinochoroidal scars and low grade or absence of inflammation, choroidal neovascular membranes may mimic active toxoplasmic retinochoroiditis and vice-versa. A thorough ophthalmic, serological, and immunological examination (in ocular fluids) may help in the differential diagnosis allowing for proper therapeutic decision-making.

Use of CD25 as an immunohistochemical marker for acquired ocular toxoplasmosis.

PURPOSE: Toxoplasmosis is the most common cause of posterior infectious uveitis worldwide. It is often impossible to determine its congenital or acquired nature. Interleukin-2 (IL-2) in peripheral blood has been described as a possible marker for acquired toxoplasmosis. The purpose of this study is to evaluate the histopathological characteristics of ocular toxoplasmosis cases using CD25 as a marker for the expression of interleukin-2. METHODS: Ten formalin-fixed, paraffin-embedded enucleated globes from ten immunocompetent patients with clinical diagnosis of toxoplasmosis were evaluated. Four patients had the acquired form of ocular toxoplasmosis (positive IgM) while six were IgM negative and IgG positive for toxoplasmosis. Histopathological slides were reviewed for the extension of the retinal necrosis, number of toxo cysts, the granulomatous inflammatory reaction, the presence of T and B cells within the choroid and the IL-2 expression. Immunohistochemistry using monoclonal antibodies was performed to observe the expression of CD4, CD8, CD20, CD25, and CD68. RESULTS: The histopathological evaluation disclosed no differences between acquired and the other ocular toxoplasmosis cases regarding the characteristics studied. However, CD25 showed a higher expression of IL-2 on the 4 acquired cases of ocular toxoplasmosis compared to the remainders. CONCLUSIONS: To the best of our knowledge, this is the first report showing that the use of CD25 as a marker for interleukin-2 could differentiate acquired ocular toxoplasmosis.

Immunopathology in ocular toxoplasmosis: facts and clues

Although parasite-mediated host cell lysis is deemed to be an important cause of tissue destruction in ocular toxoplasmosis (OT), the severity of the disease is probably correlated with hypersensitivity and inflammation. Notwithstanding, the mechanisms that regulate the inflammatory process in recurrent OT are poorly understood. Recent evidence has identified interleukin (IL) 17 as a marker for disease severity. The ocular and cerebral presence of this cytokine is generally associated with the induction of autoimmune responses in the brain and the eye. Indeed, there are indications that autoimmunity may contribute to clinical variability in the activity of OT. IL-23, which induces the proliferation of IL-17-producing cells and IL-27, which is a counterplayer to IL-17, may regulate T(H)-1-cell-mediated responses in OT. The importance of these cytokines in experimental models of uveitis and encephalitis has been recently reported. CD25(+) regulatory T-cells may control the local inflammatory response and protect the host against collateral inflammatory tissue damage. The responses of these cells to OT may be suitably tailored to cope with either an acquired or a congenital aetiology. Knowledge relating to immunoreactivity in OT has grown impressively during the past few years. Its characteristic and variable features have been identified and the potential relevance of autoimmunity has been assessed. In light of this knowledge, potential future treatment options have been considered.

Serum and aqueous humour cytokine response and histopathological alterations during ocular Toxoplasma gondii infection in C57BL/6 mice.

Toxoplasma gondii, an obligate intracellular protozoan parasite, infects most species of warm-blooded animals, and in humans it causes toxoplasmosis. Healthy people that become infected rarely present clinical symptoms because the immune system prevents the parasite from causing illness. Congenital toxoplasmosis may result in abortion, hydrocephalus, as well as neurological and ocular disease (most frequently retinochoroiditis) of the newborn. In immunocompromised patients, reactivation of latent disease can cause encephalitis. Cell-mediated immunity to T. gondii antigens involves innate acute inflammatory responses and antigen-specific adaptive immunity. Considering the complexity of the immunological events triggered during toxoplasmosis, systemic and local responses were evaluated by cytokine measurements. Aqueous humour and serum were obtained from non-infected and T. gondii Me-49 strain infected C57BL/6 mice for cytokine quantification. Histopathological analyses were made with eyes enucleated from mice after 30 days of infection. ELISA assays showed an increase of IFN-gamma levels both in serum and aqueous humour of infected mice in opposition to a decrease in IL-10 levels. On the other hand, TGF-beta was high, whereas IL-12 and TNF-alpha were present in small levels in both groups. We also detected higher levels of IL-4 and IL-6 in aqueous humour than in serum of infected mice when compared to the control group. MIP-2 presented no significant differences between the two groups. Fas and Fas-L were also present in similar levels in serum of non-infected and infected mice, but both chemokines were increased in the aqueous humour of infected mice. Histopathological analysis of infected mice showed inflammatory infiltrates around blood vessels and alteration of the outer photoreceptor segments, on the external and inner nuclear layer. Parasites were observed in 82% of eyes, inside the blood vessels associated with inflammatory infiltrate. Edema, characterized by the increase of interstitial spaces between the FTR, forming lacunae was also noted. These alterations take the form of projections (retino-vitreal), characteristic of retinochoroiditis. In conclusion, T. gondii infection of C57BL/6 mice revealed that cytokine patterns alone do not assure susceptibility or resistance against infection, thus reinforcing the notion that it is necessary more than cytokine dosage to determine Th1 or Th2 profile in this model.

Coroidite toxoplásmica unilateral: apoptose retiniana com migração de células pigmentares / Unilateral toxoplasmic choroiditis: retinal apoptosis with pigment-containing cells migration

No relato de um caso de toxoplasmose, com as lesões secundárias, os autores mostram como devem ser entendidos os achados anatomopatológicos. Em face do avanço da tecnologia e do infindável número de trabalhos correlatos, é importante detalhar o significado de cada alteração nos diversos segmentos das membranas oculares. Essa é a razão da valorização das técnicas clássicas de rotina e do destaque dado às seguintes partes: 1 – A clínica – 2 – a macroscopia, mostrando a gravidade da inflamação ocular. 3 – A microscopia com as etapas para o diagnóstico etiológico, nas quais se procuram correlacionar os achados dos corantes de rotina – HE, azul de toluidina e tricrômico – com as reações específicas imunohistoquímicas para toxoplasma. 4 – Imagens que visam a separar a inflamação da coróide, do processo degenerativo secundário da retina, a apoptose. 5 – Degeneração cistóide da retina e evidência, anatomopatológica, de apoptose retiniana e migração de células do epitélio pigmentar para a retina. 6 – Comentários sobre os significados da retinopatia pigmentar, da retinite pigmentosa e da apoptose

In a report of a toxoplasmosis case with secondary lesions, the authors show how the anatomopathologic findings should be understood. In face of the technological improvements and the great number of related works it is important to specify the meaning of eachchange in ocular membranes. This is the reason for valorization of the classical laboratory practice and the distinction given to the following parts: 1 – The clinic. 2 – Macroscopy showing the graveness of the ocular inflammation. 3 – Microscopy with the stages for etiological diagnosis, in which the authors try to correlate the findings of the routine procedure stains – HE, toluidine blue and trichromic – with the specific immunohistochemical reactions for toxoplasm. 4 – Images that aim at separating clearly the inflammation of the choroid, from the secondary degenerative process of retina, the apoptosis. 5 – Retinal cystoid degeneration and anatomopathologic evidence of retinal apoptosis, and migration of pigment epithelial cells to retina. 6 – Comments on the meaning of pigmentary retinopathy, retinitis pigmentosa and apoptosis