Clinical manifestations and visual outcomes associated with ocular toxoplasmosis in a Brazilian population.

Ocular toxoplasmosis is the leading cause of posterior uveitis worldwide. We conducted an observational study of 262 consecutive individuals (n = 344 eyes) with ocular toxoplasmosis who were followed over a 34-month period. Most subjects were T. gondii IgG + /IgM- (n = 242; 92.4%; 317 eyes), and 140 eyes (40.7%) had active lesions. For eyes in which retinal lesions were active at recruitment and best-corrected visual acuity (BCVA) could be measured (n = 133), 21.0% (n = 28) remained blind (BCVA below 20/400) after inflammation resolved. In these eyes, atypical ocular toxoplasmosis (OR 4.99; 95% CI 1.14-22.85; p = 0.0330), macular lesion (OR 9.95; 95% CI 2.45-47.15; p = 0.0019) and any complication (OR 10.26; 95% CI 3.82-30.67; p < 0.0001) were associated with BCVA below 20/200. For eyes with only inactive lesions at recruitment and BCVA measured (n = 178), 28.1% (n = 50) were blind. In these eyes, having at least one lesion larger than one disc-diameter (OR 6.30; 95% CI 2.28-22.46; p = 0.0013) and macular lesion (OR 5.69; 95% CI 2.53-13.54; p < 0.0001) were associated with BCVA below 20/200. Older age (OR 1.02; 95% CI 1.00-1.05; p = 0.0493) and active disease at presentation (OR 4.74; 95% CI 1.95-12.91; p = 0.0011) were associated with recurrences. Additional clinical attention should be directed towards patients with risk factors for poor visual outcome.

Primary Ocular Toxoplasmosis Presenting to Uveitis Services in a Non-endemic Setting.

PURPOSE: This study sought to describe the different clinical features and presentations of primary ocular toxoplasmosis in a setting not demonstrating an outbreak of disease. METHODS: This was a retrospective review of patients presenting to uveitis management services in Auckland and Hamilton, New Zealand between 2003 to 2018 with uveitis and positive toxoplasmosis immunoglobulin M serology. RESULTS: We identified 16 patients with primary acquired toxoplasmosis infection and ocular involvement. The mean age was 53 years. Systemic symptoms were reported in 56% (9 / 16). Visual acuity was reduced to 20 / 30 or less in 50% of patients (8 / 16). A single focus of retinitis without a pigmented scar was the salient clinical feature in 69% (11 / 16). Optic nerve inflammation was the sole clinical finding in 19% (3 / 16). Bilateral arterial vasculitis was the sole clinical finding in 13% (2 / 16). A delay in the diagnosis of toxoplasmosis of more than two weeks occurred in 38% (6 / 16) due to an initial alternative diagnosis. Antibiotic therapy was prescribed in all cases. Vision was maintained or improved in 69% (11 / 16) at the most recent follow-up visit (15 months to 10 years). Relapse occurred in 69% (11 / 16), typically within four years from the initial presentation. CONCLUSIONS: Primary ocular toxoplasmosis presenting in adulthood is a relatively uncommon cause of posterior uveitis in New Zealand. This condition should be considered in any patient presenting with retinitis or optic nerve inflammation without a retinochoroidal scar. This disease tends to relapse; thus, close follow-up is required.

POSTERIOR UVEITIS OR WET AGE-RELATED MACULAR DEGENERATION? CASE REPORT.

We present the case of a 61-year-old patient without previous ophthalmic or general history, who developed unilateral posterior pole granuloma and was diagnosed with posterior uveitis most likely due to a systemic Toxocara canis infection. Clinical examination and ancillary investigations showed elements that were also consistent with wet ARMD, but laboratory tests and successful use of oral anti-helminthic and corticosteroid therapy in decreasing the macular lesion and improving visual acuity, confirmed the diagnosis of posterior uveitis.

Prevalence of Toxoplasma gondii and Toxocara canis among patients with uveitis.

PURPOSE: To investigate the prevalence of Toxoplasma gondii and Toxocara canis in patients with uveitis. METHOD: Patients with uveitis were examined. Serum antibodies to T. gondii and T. canis were tested by using enzyme-linked immunosorbent assay (ELISA). Polymerase chain reaction (PCR) was done using blood and aqueous humor (AH). RESULTS: 98 patients were enrolled. Mean age was 43.5 ± 13.2 years. Six patients were seropositive for T. gondii with the following pattern-anterior uveitis: 1; posterior uveitis with retinitis: 2; pan uveitis: 2. One patient had a positive result of PCR for T.gondii in AH, who showed pan uveitis. 23 patients were positive to serum IgG for T. canis with the following clinical manifestation-granuloma: 6; pigmented scar: 3; virtrits: 6-but none were PCR positive. CONCLUSION: T.gondii and T.canis are still one of the important causes of uveitis. Ocular toxocariasis is not an uncommon cause of uveitis even in adult.

The value of routine polymerase chain reaction analysis of intraocular fluid specimens in the diagnosis of infectious posterior uveitis.

OBJECTIVE: To assess the value of routine polymerase chain reaction (PCR) analysis on intraocular fluid from patients presenting with a first episode of suspected active infectious posterior uveitis in a population with a high prevalence of human immunodeficiency virus infection. DESIGN: Retrospective, interventional case series. Participants. 159 consecutive patients presenting at a tertiary care hospital over a five-year period. METHODS: PCR analysis was performed for cytomegalovirus, varicella zoster virus, herpes simplex virus types 1 and 2, Toxoplasma gondii, and Mycobacterium tuberculosis. RESULTS: PCR analysis confirmed the initial clinical diagnosis in 55 patients (35%) and altered the initial clinical diagnosis in 36 patients (23%). The clinical diagnosis prior to PCR testing was nonspecific (uncertain) in 51 patients (32%), with PCR providing a definitive final diagnosis in 20 of these patients (39%); necrotizing herpetic retinopathy and ocular toxoplasmosis were particularly difficult to diagnose correctly without the use of PCR analysis. CONCLUSION: The clinical phenotype alone was unreliable in diagnosing the underlying infectious cause in a quarter of patients in this study. Since the outcome of incorrectly treated infective uveitis can be blinding, PCR analysis of ocular fluids is recommended early in the disease even in resource poor settings.

Infectious causes of posterior uveitis.

The differential diagnosis of posterior infectious uveitis is broad. There are, however, a few common infectious causes of posterior uveitis that should always be considered. The more common infectious causes of posterior uveitis include syphilis, toxoplasmosis, tuberculosis, endogenous endophthalmitis, and viral causes (including herpes simplex virus, herpes zoster virus, and cytomegalovirus). The clinical features, diagnostic tools, and treatment options for each of these are reviewed in this article.

Ocular manifestations of systemic disease: toxoplasmosis.

PURPOSE OF REVIEW: To provide an overview of ocular toxoplasmosis, the leading cause of infectious posterior uveitis, focusing on recent trends of disease epidemiology, pathogenesis, diagnosis, therapy and prevention. RECENT FINDINGS: Novel aspects of epidemiology, including growing importance of water transmission are discussed. The historical controversy of congenital versus postnatally acquired toxoplasmosis is revisited. Recent insights into pathogenesis of ocular toxoplasmosis are also reviewed, tipping the delicate balance between parasite virulence and host immunity. Diagnosis of ocular toxoplasmosis is also discussed in the light of serological, molecular and imaging tools. Finally, a critical analysis of current and emerging therapies for ocular toxoplasmosis is made. Preventive aspects are also commented upon. SUMMARY: Waterborne toxoplasmosis is increasingly recognized in outbreaks and in endemic areas. The importance of postnatally acquired toxoplasmosis is now well established, but should not lead to underestimation of congenital disease. Genetic determination of parasite virulence/individual susceptibility might correlate with disease outcomes. Serological, molecular and imaging tools may improve the diagnosis and follow-up of individuals with ocular toxoplasmosis. Despite emergence of alternative therapeutic regimens, including intravitreal antibiotics, classical therapy with sulfadiazine/pyrimethamine is still standard for toxoplasmic retinochoroiditis. Adequate prophylaxis is expected to have an effect in ocular burden of toxoplasmosis.

Interleukin 17A as an effective target for anti-inflammatory and antiparasitic treatment of toxoplasmic uveitis.

BACKGROUND: Toxoplasmosis is the most common cause of posterior uveitis in immunocompetent subjects. The requirement of limiting both parasite multiplication and tissue destruction suggests that the balance between T-helper (Th) 17 and T-regulatory cells is an important factor in toxoplasmosis-induced retinal damage. METHODS: In a prospective clinical study of acute ocular toxoplasmosis, we assessed the cytokine pattern in aqueous humors of 10 affected patients. To determine the immunological mechanisms, we evaluated intraocular inflammation, parasite load, and immunological responses using messenger RNA and protein levels in a mouse model. Anti-interleukin 17A (IL-17A) monoclonal antibodies (mAbs) were administered with the parasite to evaluate the role of IL-17A. RESULTS: Severe ocular inflammation and cytokine patterns comparable to human cases were observed, including IL-17A production. Neutralizing IL-17A decreased intraocular inflammation and parasite load in mice. Detailed studies revealed up-regulation of T-regulatory and Th1 pathways. When interferon γ (IFN-γ) was neutralized concomitantly, the parasite multiplication rate was partially restored. CONCLUSIONS: Local IL-17A production by resident cells plays a central role in the pathology of ocular toxoplasmosis. The balance between Th17 and Th1 responses (especially IFN-γ) is crucial for the outcome of infection. This data reveals new in vivo therapeutic approaches by repressing inflammatory pathways using intravitreal injection of IL-17A mAbs.

Infectious causes of posterior uveitis and panuveitis in Thailand.

PURPOSE: To determine the infectious causes of posterior uveitis (PU) and panuveitis (panU) in Thailand. METHODS: We investigated the infectious causes of uveitis involving the posterior segment of the eye by using real-time polymerase chain reaction (PCR) for cytomegalovirus (CMV), herpes simplex virus (HSV-1, HSV-2), varicella zoster virus and Toxoplasma gondii (T. gondii) DNA in intraocular samples of 80 human immunodeficiency virus (HIV)-negative patients. Additionally, in 61 patients, we performed Goldmann-Witmer coefficient (GWC) analysis for T. gondii. RESULTS: Twenty-four (30 %) patients with PU and/or panU had a positive PCR result. Overall, CMV was the most frequently identified organism. While CMV was the most common cause of uveitis in the patients on immunosuppressive medications for nonocular disorders, HSV was the most common cause of posterior and panuveitis in the patients not receiving such medication. In 38 PU patients, CMV was the most common detected pathogen. In 42 panU patients, CMV and HSV-2 were the most frequently identified pathogens. Out of 61 paired samples analyzed for T. gondii by GWC analysis, only 1 revealed a positive result. There was no difference in PCR results between aqueous humor and vitreous samples. CONCLUSIONS: CMV was the most frequently identified infectious organism in posterior and panuveitis of HIV-1-negative Thai patients. Aqueous humor and vitreous samples showed similar diagnostic values in PCR analysis.

Real-time polymerase chain reaction and intraocular antibody production for the diagnosis of viral versus toxoplasmic infectious posterior uveitis.

PURPOSE: The aim of this work was to determine the diagnostic performance of real-time polymerase chain reaction (RT-PCR) and to assess intraocular specific antibody secretion (Goldmann-Witmer coefficient) on samples from patients with signs of posterior uveitis presumably of infectious origin and to target the use of these two biologic tests in the diagnostic of Toxoplasma/viral Herpesviridae posterior uveitis by the consideration of clinical behavior and delay of intraocular sampling. METHODS: Aqueous humour and/or vitreous fluid were collected from patients suspected of having posterior uveitis of infectious origin at presentation (140 samples). The diagnosis was confirmed by quantification of antibodies with the Goldmann-Witmer coefficient (GWC) and for detection of Herpesviridae and Toxoplasma gondii genomes with RT-PCR. Forty-one patients had final diagnosis of uveitis of non-Toxoplasma/non-viral origin and 35 among them constituted the control group. The main outcome measures were sensitivity, specificity, and positive and negative predictive values (PPV and NPV). RESULTS: When pre-intraocular testing indication was compared with final diagnosis, GWC was a more sensitive and specific method than RT-PCR, and was successful in detecting T. gondii, especially if the patient is immunocompetent and the testing is carried out later in the disease course, up to 15 months. For viral Herpesviridae uveitis, the sensitivity and PPV of PCR evaluation was higher than detected with GWC with respectively 46% compared with 20% for sensitivity and 85% versus 60% for PPV. In either viral retinitis or toxoplasmosis infection, RT-PCR results were positive from 24 h, although GWC was not significant until 1 week after the onset of signs. In toxoplasmosis patients, positive RT-PCR results were statistically correlated with the chorioretinitis area (more than three disc areas; p = 0.002), with the age older than 50 (p = 0.0034) and with a clinical anterior inflammation (Tyndall ≥1/2+) and panuveitis; (p = 0.0001). CONCLUSIONS: For the diagnosis of viral or toxoplasmosis-associated intraocular inflammation, the usefulness of laboratory diagnosis tools (RT-PCR and GWC) depends on parameters other than the sensitivity of the tests. Certain patient characteristics such as the age of the patients, immune status, duration since the onset of symptoms, retinitis area, predominant site and extent of inflammation within the eye should orientate the rational for the choice of laboratory testing in analysis of intraocular fluids.

Anti-Toxoplasma gondii secretory IgA in tears of patients with ocular toxoplasmosis: immunodiagnostic validation by ELISA.

Toxoplasma gondii causes posterior uveitis and the specific diagnosis is based on clinical criteria. The presence of anti-T. gondii secretory IgA (sIgA) antibodies in patients' tears has been reported and an association was found between ocular toxoplasmosis and the anti-T. gondii sIgA isotype in Brazilian patients. The purpose of this study was to provide an objective validation of the published ELISA test for determining the presence of anti-T. gondii sIgA in the tears of individuals with ocular toxoplasmosis. Tears from 156 patients with active posterior uveitis were analysed; 82 of them presented characteristics of ocular toxoplasmosis (standard lesion) and 74 patients presented uveitis due to other aetiologies. Cases of active posterior uveitis were considered standard when a new inflammatory focus satellite to old retinochoroidal scars was observed. The determination of anti-T. gondii sIgA was made using an ELISA test with crude tachyzoite antigenic extracts. Tears were collected without previous stimulation. Detection of sIgA showed 65.9% sensitivity (95% CI = 54.5-74.4), 71.6% specificity (95% CI = 59.8-81.2), a positive predictive value of 72% (95% CI = 60.3-81.5) and a negative predictive value of 65.4% (95% CI = 54.0-75.4). sIgA reactivity was higher in the tears of patients with active posterior uveitis due to T. gondii (p < 0.05). The test is useful for differentiating active posterior uveitis due to toxoplasmosis from uveitis caused by other diseases.

Anti-Toxoplasma gondii secretory IgA in tears of patients with ocular toxoplasmosis: immunodiagnostic validation by ELISA

Toxoplasma gondii causes posterior uveitis and the specific diagnosis is based on clinical criteria. The presence of anti-T. gondii secretory IgA (sIgA) antibodies in patients' tears has been reported and an association was found between ocular toxoplasmosis and the anti-T. gondii sIgA isotype in Brazilian patients. The purpose of this study was to provide an objective validation of the published ELISA test for determining the presence of anti-T. gondii sIgA in the tears of individuals with ocular toxoplasmosis. Tears from 156 patients with active posterior uveitis were analysed; 82 of them presented characteristics of ocular toxoplasmosis (standard lesion) and 74 patients presented uveitis due to other aetiologies. Cases of active posterior uveitis were considered standard when a new inflammatory focus satellite to old retinochoroidal scars was observed. The determination of anti-T. gondii sIgA was made using an ELISA test with crude tachyzoite antigenic extracts. Tears were collected without previous stimulation. Detection of sIgA showed 65.9 percent sensitivity (95 percent CI = 54.5-74.4), 71.6 percent specificity (95 percent CI = 59.8-81.2), a positive predictive value of 72 percent (95 percent CI = 60.3-81.5) and a negative predictive value of 65.4 percent (95 percent CI = 54.0-75.4). sIgA reactivity was higher in the tears of patients with active posterior uveitis due to T. gondii (p < 0.05). The test is useful for differentiating active posterior uveitis due to toxoplasmosis from uveitis caused by other diseases.

Polymerase chain reaction analysis of aqueous and vitreous specimens in the diagnosis of posterior segment infectious uveitis.

PURPOSE: To assess polymerase chain reaction (PCR) analysis of intraocular fluid as a test for infectious uveitis of the posterior segment in a representative patient population. DESIGN: Retrospective, interventional case series. METHODS: One hundred and thirty-three patients with possible infectious chorioretinitis underwent PCR testing of aqueous or vitreous in a university setting. Baseline characteristics predictive of test positivity were identified. Positive and negative predictive values were calculated. RESULTS: Four hundred and thirty-three PCR tests of 105 aqueous and 38 vitreous specimens (mean, 3.3 tests per patient) identified 77 of the 95 patients with a final clinical diagnosis of infectious uveitis (81%). Herpes simplex virus, varicella zoster virus, and cytomegalovirus PCR analysis were performed in almost all cases, with fewer tests for toxoplasmosis or Epstein-Barr virus. Clinical features associated with positive PCR results were retinal vascular inflammation (P < .001), optic nerve involvement (P = .008), immunocompromised state (P = .039), and extensive retinitis (P = .002). Cases sampled within one week of presentation were more likely to have positive PCR results than those sampled later (P = .071). The predictive value of positive and negative tests was 98.7% and 67.9%, respectively, in this patient group. Alteration in treatment based on PCR and syphilis serologic results led to resolution in 25 of 26 patients after treatment was changed. CONCLUSIONS: PCR testing is a useful adjunct in the diagnosis of infectious causes of posterior uveitis. Cases with vascular or optic nerve inflammation, extensive retinitis, or immunocompromise are more likely to have positive PCR results and may benefit from PCR testing of aqueous humor.

[Clinical characteristics of 64 individuals carrying active posterior presumptively toxoplasmic uveitis, in Pernambuco]. / Características clínicas de 64 indivíduos portadores de uveítis posterior activa presumiblemente toxoplásmica en Pernambuco.

PURPOSE: To describe clinical characteristics of posterior active uveitis presumptively by Toxoplasma gondii (PAUPT) in patients with typical lesion. Tranversal study. METHODS: Sixty-four patients with retinochoroiditis scatter and active satellite lesions examined in Pernambuco, Brazil. All were older than 10 years and immunocompetent. Gender, age, skin color, and residence were recorded. Previous uveitis, visual accuracy, intraocular pressure (IOP), and ocular examination were analyzed. RESULTS: 52% were males, most of them with white skin (68.8%). Mean age 29 years (+/-10.87). Eighty-four percent of the patients lived in the metropolitan area. 56.2% were having the first episode of uveitis. In the damaged eye, visual accuracy mean was 20/200, IOP mean 14.5 mmHg (+/-64). Hyperemia of the conjunctiva was observed in 29.7% of the patients and alterations of the cornea in 51.6%. There were cells in the aqueous humor in 62.7%. 6.2% had posterior synechiae. All had vitreous damage and 45.3% retinal vasculitis. In 42.2% of the patients, lesions were located in zone I of Holland and 90.6% had the size of one discus diameter or greater. Neuritis was observed in 28.2%. Uveitis was more frequent in the right eye (54.7%). CONCLUSION: PAUPT affects young people and the main symptom was reduction of visual acuity. IOP mean was normal. Alterations of the vitreous were observed in all cases. Injuries were equal to one discus diameter or greater and located in zone I of Holland.

Características clínicas de 64 indivíduos portadores de uveítis posterior activa presumiblemente toxoplásmica en Pernambuco / Clinical characteristics of 64 individuals carrying active posterior presumptively toxoplasmic uveitis, in Pernambuco

OBJETIVO: Describir características clínicas de uveítis posterior activa, presumiblemente por Toxoplasma gondii (UPAPT) en portadores de lesión típica. Estudio tranversal. MÉTODOS: 64 portadores de UPAPT con retinocorroiditis cicatrizada y lesión satélite activa, mayores de 10 años, inmunocompetentes, examinados en Permambuco, Brazil. Se analizó: sexo, edad, color de la piel, procedencia, uveítis anteriores, agudeza visual, presión ocular y exámen ocular. RESULTADOS: Masculino en 52 por ciento. Edad media 29 años (±10,87). Piel blanca en 68,8 por ciento. Domicilio en la área metropolitana en 80,4 por ciento. Primer episodio de uveítis en 56,2 por ciento. Media de visión en ojo afectado 20/200. Presión ocular media 14,5 mmHg (±7,64) en ojo afectado. Conjuntiva hiperemiada en 29,7 por ciento. Alteraciones corneales en 51,6 por ciento. Células en el humor acuoso en 67,2 por ciento. Sinéquias posteriores en 6,2 por ciento. Compromiso vítreo en 100 por ciento. Vasculitis retiniana en 45,3 por ciento. Lesiones localizads en la zona I de Holland en 42,2 por ciento, siendo de tamaño igual o mayor de un diámetro de disco en 90,6 por ciento. Neuritis en 28,2 por ciento. CONCLUSIÓN: UPAPT afecta adultos jóvenes, siendo el síntoma principal la disminución de la visión. Presión ocular media normal. Compromiso vítreo en todos los casos. Com mayor frequencia las lesiones fueron mayores de un diámetro de disco localizadas en la zona I de Holland.

PURPOSE: To describe clinical characteristics of posterior active uveitis presumptively by Toxoplasma gondii (PAUPT) in patients with typical lesion. Tranversal study. METHODS: Sixty-four patients with retinochoroiditis scatter and active satellite lesions examined in Pernambuco, Brazil. All were older than 10 years and immunocompetent. Gender, age, skin color, and residence were recorded. Previous uveitis, visual accuracy, intraocular pressure (IOP), and ocular examination were analyzed. RESULTS: 52 percent were males, most of them with white skin (68.8 percent). Mean age 29 years (±10.87). Eighty-four percent of the patients lived in the metropolitan area. 56.2 percent were having the first episode of uveitis. In the damaged eye, visual accuracy mean was 20/200, IOP mean 14.5 mmHg (±64). Hyperemia of the conjunctiva was observed in 29.7 percent of the patients and alterations of the cornea in 51.6 percent. There were cells in the aqueous humor in 62.7 percent. 6.2 percent had posterior synechiae. All had vitreous damage and 45.3 percent retinal vasculitis. In 42.2 percent of the patients, lesions were located in zone I of Holland and 90.6 percent had the size of one discus diameter or greater. Neuritis was observed in 28.2 percent. Uveitis was more frequent in the right eye (54.7 percent). CONCLUSION: PAUPT affects young people and the main symptom was reduction of visual acuity. IOP mean was normal. Alterations of the vitreous were observed in all cases. Injuries were equal to one discus diameter or greater and located in zone I of Holland.

Diagnosis of ocular toxocariasis by establishing intraocular antibody production.

PURPOSE: To investigate the role of Toxocara canis in posterior uveitis of undetermined origin. DESIGN: Retrospective case-study. METHODS: Paired ocular fluid (47 aqueous humor [AH] and two vitreous fluids) and serum samples of 37 adults and 12 children with undetermined posterior uveitis were retrospectively analyzed for intraocular IgG antibody production against Toxocara canis by enzyme-linked immunosorbent assay and Goldmann-Witmer coefficient (GWC) determination. Previous diagnostic investigation by polymerase chain reaction and GWC for Herpes simplex virus, Varicella zoster virus, and Toxoplasma gondii had not provided a cause of the posterior uveitis. RESULTS: Three of 12 (25%) children showed intraocular IgG production against Toxocara canis. One child had vitritis, one presented with a low-grade uveitis and a peripheral retinal lesion, and the third had posterior uveitis and a chorioretinal scar. All three children had AH IgG titers exceeding those of the corresponding serum. In fact, two children had low Toxocara serum IgG titers (<1:32) and would have been considered seronegative upon routine serology screening. Intraocular antibody production against Toxocara canis was absent in all 37 adults, including five seropositive patients. CONCLUSIONS: Our results indicate that ocular toxocariasis is mainly a pediatric disease. Serological screening is not informative for the diagnosis of intraocular Toxocara infection. Toxocara GWC analysis, however, can be of value when diagnosing patients with posterior focal lesions or vitritis of unknown etiology.