Long-term Ocular Outcomes in Congenital Toxoplasmosis Treated Perinatally.

BACKGROUND: Congenital toxoplasmosis (CT) can be accompanied by serious organ manifestations, particularly retinochoroiditis, and may occur throughout life. We aimed to monitor long-term ocular prognosis in a large French cohort of patients with CT and its changes over time in the context of mandatory prenatal screening (since 1992) and incidence decrease since 2008. METHODS: Patients with CT diagnosed between 1987 and 2021 were prospectively included and followed for up to 35 years. The effect of the period of conception on the risk of first retinochoroiditis has been tested using a flexible extension of the Cox model. Incidence rates of retinochoroiditis were estimated. RESULTS: A total of 646 infected live born children were followed for a median of 12 years (range, 0.5-35); 187 patients (29%) had at least 1 ocular lesion (first at a median age of 5 years; range, 0-26 years) with peaks at 7 and 12 years. Early maternal infection and the presence of nonocular signs at birth were associated with a higher risk of retinochoroiditis, whereas delayed diagnosis of CT (after birth versus before or at birth) was associated with a lower risk (13% decrease for each additional month after birth; P = .01). A period effect for the risk of developing retinochoroiditis in patients born after 2008 was not detected. CONCLUSIONS: Despite prenatal screening and prolonged perinatal treatment, retinochoroiditis is not a rare event in French patients with CT and can occur well into adulthood, with peak incidences at 7 and 12 years of age. It rarely causes severe damage but warrants regular follow-up into adulthood.

Serous macular detachment in ocular toxoplasmosis: A review.

Ocular toxoplasmosis, a disease of the eye caused by the protozoan parasite Toxoplasma gondii, represents a common cause of posterior uveitis. The Authors review the current Literature regarding the uncommon presentation of ocular toxoplasmosis as macular serous retinal detachment (SRD). It is imperative to keep in mind that inflammatory SRD is a possible presentation of toxoplasmic retinochoroiditis. Underestimation of this clinical scenario and treatment with steroids alone without appropriate antiparasitic drugs, could lead to devastating consequences.

Ocular toxoplasmosis following anti-tumour necrosis factor-α therapy combined with oral methotrexate therapy: A case report and review of literature.

Purpose: To report a case of ocular toxoplasmosis following long-term treatment with adalimumab and review the literature on ocular toxoplasmosis following anti-Tumour necrosis factor-α therapy. Method: A retrospective chart review of A 21-year-old male who developed retinochoroiditis in his left eye following adalimumab therapy combined with oral methotrexate. Result: A known patient of juvenile idiopathic arthritis (JIA) on adalimumab and oral methotrexate for the last four years presented to us with a blurring of vision for the last 15 days. Fundus examination of the left eye revealed severe vitritis and two patches of retinochoroiditis in the inferior part of the fundus. Subsequent investigations confirmed it to be a case of toxoplasma retinochoroiditis, and he responded to anti-toxoplasma treatment. A review of literature on a similar topic revealed five such cases, and the index case was the first such report in patients with JIA. Conclusion: The index case highlights the importance of early recognition and management of opportunistic infections in patients receiving biologicals.

Bacillary layer detachment as an inflammatory biomarker in toxoplasmosis retinochoroiditis: serial evolution on optical coherence tomography.

We describe the clinical course and serial evolution of bacillary layer detachment (BALAD) on optical coherence tomography (OCT) in toxoplasmosis retinochoroiditis and its importance as an inflammatory biomarker. Colour fundus photography and swept-source OCT of the BALAD were done at the time of presentation and subsequently at 1 week, 2 weeks, 4 weeks and at 11 weeks. Treatment involved oral trimethoprim (160 mg) + sulphamethoxazole (800 mg) two times per day, started at presentation for 2 months. Oral prednisolone was started after 1 week at a dose of 50 mg a day and tapered weekly over the next 5 weeks. The BALAD initially increased after starting treatment with trimethoprim-sulphamethoxazole and regressed within 1 week after initiation of oral prednisolone. Best corrected visual acuity improved to 20/40 from 20/160 at presentation (Snellen equivalent). This suggests that BALAD is an indicator of an acute inflammatory event and the accumulated fluid is secondary to retinal and choroidal inflammation.

Outcomes of trimethoprim/ sulfamethoxazole treatment for ocular toxoplasmosis in Congolese patients.

BACKGROUND: Ocular toxoplasmosis (OT) is the leading cause of infectious posterior uveitis in several areas worldwide. The combination of Trimethoprim/Sulfamethoxazole (TMP/SMX) has been presented as an attractive alternative to the "classic' treatment therapy (Pyrimethamine/Sulfadiazine). METHODS: A prospective study was carried out between February 2020 and September 2021 in 2 ophthalmic centers in Kinshasa. This study aimed to describe TMP/SMX treatment outcomes for OT in a cohort of immunocompetent Congolese patients. RESULTS: 54 patients were included, with a mean age at presentation of 37.5 ± 13.6 years old and a Male-Female ratio of 1.45:1. Three patients (5.6%) presented a recurrence during the follow-up period. At the end of the follow-up, improvement in VA and resolution of inflammation concerned 75.9% and 77.5% of patients, respectively. Cataracts (3.7%), macular scars (3.7%), and vitreous opacities (3.7%) were the principal causes of non-improvement in VA. Treatment-related adverse events were present in 10 patients (18.5%); gastrointestinal (14.8%) and dermatological (3.7%) adverse events were the most frequent. Dermatological adverse events led to discontinuation of treatment. CONCLUSION: TMP/SMX regimen appears to be a safe and effective treatment for OT in Congolese patients. The low cost and the accessibility of the molecules make this regimen an option for treating OT in resource-limited countries.

A new perspective in the treatment follow-up of toxoplasma retinochoroiditis: Infiltrate thickness measurement.

BACKGROUND: This study aimed to describe the spectral domain optical coherence tomography (SD-OCT) findings of active lesions in toxoplasma retinochoroiditis cases and to examine the changes in retinochoroidal infiltrate thickness after treatment. METHODS: A total of 21 newly diagnosed patients with ocular toxoplasmosis were included in this prospective study. A complete ophthalmologic examination and SD-OCT were performed at the first visit. The patients were followed up weekly, and the SD-OCT images were taken over the lesion at each visit for 6 weeks. The characteristics of the active retinochoroiditis focus at the first visit were determined, and the infiltrate thicknesses at all visits were analyzed. RESULTS: A statistically significant BCVA difference was observed at the first visit and at the last visit 6 weeks later (p < 0.01). The first week after treatment showed a significant decrease in infiltrate thickness (113.904 ± 86.001 µm). In the following weeks, this decrease continued more softly. The thickness change at 6 weeks was significantly reduced (16.095 ± 14.784 µm) compared with the previous ones. Weekly infitrate thickness changes were compared among themselves; a statistically significant difference was found between the 1st and 2nd weeks and the 5th and 6th weeks (p = 0.035 and p = 0.007, respectively). Detached posterior vitreous in 71% (15/21) and increased posterior vitreous thickness in 76% (16/21) of active lesion were detected. All patients had 100% (21/21) increased retinal reflectivity and disorganized retinal layers, and choroidal hypo-reflectivity was observed in 86% (18/21). CONCLUSION: SD-OCT is a useful imaging modality in the diagnosis and follow-up of ocular toxoplasmosis cases. Serial thickness measurements of toxoplasma retinochoroiditis lesions may help confirm our diagnosis and determine the need for treatment.

Risk factors for recurrences and visual impairment in patients with ocular toxoplasmosis: A systematic review and meta-analysis.

BACKGROUND: Ocular toxoplasmosis (OT) is caused by the parasite Toxoplasma gondii. OT is the leading cause of posterior uveitis globally; it is a recurrent disease that may result in visual impairment and blindness. This systematic review and meta-analysis aim to summarize and evaluate the risk factors for recurrences, visual impairment, and blindness described in the literature worldwide. METHODS AND FINDINGS: We performed a systematic literature search in PubMed, Embase, VHL, Cochrane Library, Scopus, and DANS EASY Archive. All studies reporting patients with clinically and serologically confirmed OT presenting any clinical or paraclinical factor influencing recurrences, visual impairment, and blindness were included. Studies presenting secondary data, case reports, and case series were excluded. An initial selection was made by title and abstract, and then the studies were reviewed by full text where the eligible studies were selected. Then, the risk of bias was assessed through validated tools. Data were extracted using a validated extraction format. Qualitative synthesis and quantitative analysis were done. This study was registered on PROSPERO (CRD42022327836). RESULTS: Seventy two studies met the inclusion criteria. Fifty-three were summarized in the qualitative synthesis in three sections: clinical and environmental factors, parasite and host factors, and treatment-related factors. Of the 72 articles, 39 were included in the meta-analysis, of which 14 were conducted in South America, 13 in Europe, four in Asia, three multinational, two in North America and Central America, respectively, and only one in Africa. A total of 4,200 patients with OT were analyzed, mean age ranged from 7.3 to 65.1 year of age, with similar distribution by sex. The frequency of recurrences in patients with OT was 49% (95% CI 40%-58%), being more frequent in the South American population than in Europeans. Additionally, visual impairment was presented in 35% (95% CI 25%-48%) and blindness in 20% (95% CI 13%-30%) of eyes, with a similar predominance in South Americans than in Europeans. On the other hand, having lesions near the macula or adjacent to the optic nerve had an OR of 4.83 (95% CI; 2.72-8.59) for blindness, similar to having more than one recurrence that had an OR of 3.18 (95% CI; 1.59-6.38). Finally, the prophylactic therapy with Trimethoprim/Sulfamethoxazole versus the placebo showed a protective factor of 83% during the first year and 87% in the second year after treatment. CONCLUSION: Our Systematic Review showed that clinical factors such as being older than 40 years, patients with de novo OT lesions or with less than one year after the first episode, macular area involvement, lesions greater than 1 disc diameter, congenital toxoplasmosis, and bilateral compromise had more risk of recurrences. Also, environmental and parasite factors such as precipitations, geographical region where the infection is acquired, and more virulent strains confer greater risk of recurrences. Therefore, patients with the above mentioned clinical, environmental, and parasite factors could benefit from using prophylactic therapy.

Toxoplasmic maculopathy with bacillary layer detachment in a pediatric patient.

We report the case of a 14-year-old girl with ocular toxoplasmosis presenting with severe panuveitis with anterior segment involvement, moderate vitreous haze, focal retinochoroiditis, extensive retinal periphlebitis, and macular bacillary layer detachment. Toxoplasmosis treatment was complicated by Stevens-Johnson syndrome, which developed 8 days after starting trimethoprim-sulfamethoxazole.

Current practice in the management of ocular toxoplasmosis.

BACKGROUND: Ocular toxoplasmosis is common across all regions of the world. Understanding of the epidemiology and approach to diagnosis and treatment have evolved recently. In November 2020, an international group of uveitis-specialised ophthalmologists formed the International Ocular Toxoplasmosis Study Group to define current practice. METHODS: 192 Study Group members from 48 countries completed a 36-item survey on clinical features, use of investigations, indications for treatment, systemic and intravitreal treatment with antiparasitic drugs and corticosteroids, and approach to follow-up and preventive therapy. RESULTS: For 77.1% of members, unilateral retinochoroiditis adjacent to a pigmented scar accounted for over 60% of presentations, but diverse atypical presentations were also reported. Common complications included persistent vitreous opacities, epiretinal membrane, cataract, and ocular hypertension or glaucoma. Most members used clinical examination with (56.8%) or without (35.9%) serology to diagnose typical disease but relied on intraocular fluid testing-usually PCR-in atypical cases (68.8%). 66.1% of members treated all non-pregnant patients, while 33.9% treated selected patients. Oral trimethoprim-sulfamethoxazole was first-line therapy for 66.7% of members, and 60.9% had experience using intravitreal clindamycin. Corticosteroid drugs were administered systemically by 97.4%; 24.7% also injected corticosteroid intravitreally, almost always in combination with an antimicrobial drug (72.3%). The majority of members followed up all (60.4%) or selected (35.9%) patients after resolution of acute disease, and prophylaxis against recurrence with trimethoprim-sulfamethoxazole was prescribed to selected patients by 69.8%. CONCLUSION: Our report presents a current management approach for ocular toxoplasmosis, as practised by a large international group of uveitis-specialised ophthalmologists.

Recurrence of Ocular Toxoplasmosis after Vitrectomy: Case Report and Review.

PURPOSE: The purpose of this study is to report one case of ocular toxoplasmosis (OT) recurrence after vitrectomy and review the scientific basis about it. CASE REPORT: A 58-year-old male patient with previous OT, properly treated, underwent vitrectomy due to macular hole. During follow-up, patient evolved with recurrence of the OT. After 1 year, patient presents visual acuity of 20/200 and extensive macular scar. CONCLUSION: There is no consensus on using perioperative antiparasitic therapy aiming recurrence prophylaxis. Studies with better statistical design are necessary to evaluate the recurrence risk after ocular surgeries and the possible recommendation of prophylaxis, especially in countries where the strains are more virulent and the recurrence more common.

Azithromycin concentration in rabbits' plasma and posterior segment of the eyes following oral drug administration: a dose-finding study for the application in ocular toxoplasmosis.

INTRODUCTION: Azithromycin has been used as an ocular toxoplasmosis alternative treatment due to its pharmacokinetic profiles. However, sufficient concentrations to promote toxoplasmosis eradication is still unknown. This study was aimed to evaluate azithromycin levels in rabbits after three regimens equivalent to human doses for ocular toxoplasmosis. METHODS: Three groups of New Zealand albino rabbits were given one of the following: azithromycin at 26 mg/kg BW daily (Group 1), 26 mg/kg BW every two days (Group 2), and 50 mg/kg BW once weekly (Group 3) for 14 days. Plasma and ocular azithromycin concentrations were examined. RESULTS: Following 14 days, median ratio of plasma maximum azithromycin concentration to the minimum inhibitory concentration for Toxoplasma gondii (C-max/MIC) for Group 1, and 2 were 51.29, 5.33, while Group 3 was undetected. The median azithromycin concentration in the retina-choroid was higher than the MIC in Group 1 (1356.0 ng/ml) and Group 2 (189.0 ng/ml), but not in Group 3. CONCLUSION: Azithromycin administered orally at the dose of 26 mg/kg BW daily or 26 mg/kg BW every two days resulted a sufficient criteria of C-max/MIC as well as retina-choroid concentration needed for its parasiticidal activity. However, well-conducted clinical trial is warranted to support its therapeutic potential in ocular toxoplasmosis.

Antibodies against Toxoplasma gondii positive in serum and aqueous humor to diagnose clinically suspected ocular toxoplasmosis: A case report.

INTRODUCTION: Previously, diagnosis of ocular toxoplasmosis is based on clinical symptoms and Toxoplasma serology. Checking serological indicators often cannot reflect the real intraocular situation, and may even mislead clinicians to make wrong judgments. PATIENT CONCERNS: A 38-year-old male patient visited our ophthalmology clinic with a chief complaint of decreased vision for about 5 days in his right eye. DIAGNOSIS: Aqueous humor sample analysis found Toxoplasma DNA detectable, and Toxoplasma immunoglobulin G (IgG) and immunoglobulin M (IgM) to be positive. His serum Toxoplasma IgG was also positive (10.04 IU/mL; reference range: 0 to 7.2 IU/mL). Therefore, the final diagnose was ocular toxoplasmosis involving his right eye. INTERVENTIONS: Oral prednisone 60 mg/day and azithromycin 0.25 g/day were started. Oral antibiotic treatment for toxoplasma was continued for 4 weeks, and prednisone followed by weekly stepwise tapering in steps of 10 mg/day. OUTCOMES: The BCVA and fundus of right eye remained stable after treatment at follow-up. CONCLUSIONS: This article reported a case of ocular Toxoplasma gondii infection diagnosis by serum and aqueous humor antibody tests. We provide some additional information on the T gondii infection diagnosis.

In vitro and in vivo anti-Toxoplasma activities of HDAC inhibitor Panobinostat on experimental acute ocular toxoplasmosis.

Ocular toxoplasmosis (OT) is retinochoroiditis caused by Toxoplasma gondii infection, which poses a huge threat to vision. However, most traditional oral drugs for this disease have multiple side effects and have difficulty crossing the blood-retinal barrier, so the new alternative strategy is required to be developed urgently. Histone deacetylases (HDAC) inhibitors, initially applied to cancer, have attracted considerable attention as potential anti-Toxoplasma gondii drugs. Here, the efficacy of a novel HDAC inhibitor, Panobinostat (LBH589), against T. gondii has been investigated. In vitro, LBH589 inhibited the proliferation and activity of T. gondii in a dose-dependent manner with low toxicity to retinal pigment epithelial (RPE) cells. In vivo, optical coherence tomography (OCT) examination and histopathological studies showed that the inflammatory cell infiltration and the damage to retinal architecture were drastically reduced in C57BL/6 mice upon treatment with intravitreal injection of LBH589. Furthermore, we have found the mRNA expression levels of inflammatory cytokines were significantly decreased in LBH589-treated group. Collectively, our study demonstrates that LBH589 holds great promise as a preclinical candidate for control and cure of ocular toxoplasmosis.

Rate of recurrence of toxoplasmosis retinochoroiditis at a tertiary eye centre in Auckland.

AIM: Our aim was to examine rate of recurrence of toxoplasmosis retinochoroiditis and risk factors for recurrence. No New Zealand epidemiological data on recurrence rates of toxoplasmosis retinochoroiditis have been previously published. METHODS: Retrospective chart review of all patients with toxoplasmosis retinochoroiditis presented to Auckland District Health Board Department of Ophthalmology between 2006-2019. RESULTS: One hundred and twenty-six eyes of 115 patients were included with a median age at initial diagnosis of 36.7 years (IQR 23.7-53.8). Fifty-nine patients were female (51.3%), and 16 patients (13.9%) were immunosuppressed. Twenty-six of the 86 patients tested (30.2%) were IgM positive at presentation. Mean follow-up was 6.1 years and 73 recurrences occurred during the follow-up period in 36 patients (31.3%). Treatment was initiated in 87.4% of cases, with oral cotrimoxazole or clindamycin the most common options. Recurrence occurred in 14.8% in the first year (95% CI 10.3%-21.0%), and the risk of recurrence was increased 2x for every previously documented recurrence (HR 2.00; p<0.001). There was no statistically significant increased risk of recurrence with age, IgM positivity, immunosuppression or macular involvement. CONCLUSIONS: Toxoplasmosis retinochoroiditis had a 14.8% risk of recurrence in the first year, with each previous recurrence increasing the risk by two-times.

Posterior segment findings by spectral-domain optical coherence tomography and clinical associations in active toxoplasmic retinochoroiditis.

Toxoplasmic retinochoroiditis is a common, potentially blinding parasitic infection. We sought to define the spectrum and frequency of signs of active toxoplasmic retinochoroiditis by spectral domain optical coherence tomography (SD-OCT), and to identify clinical associations. Ninety eyes of 90 individuals presenting consecutively to a tertiary referral uveitis service with active toxoplasmic retinochoroiditis and gradable SD-OCT scans were evaluated prospectively. SD-OCT features were collated, and associations with lesion location, primary versus recurrent episode, serological status, human immunodeficiency virus infection and best-corrected Snellen visual acuity were explored. Active toxoplasmic retinochoroiditis presented with thickened (65%) and hyperreflective (61%) retina, choroidal thickening (55%) and hyporeflectivity (61%), hyperreflective vitreous dots (80%) and deposits (36%), and posterior hyaloid thickening (35%) on SD-OCT. Most signs occurred with similar frequency across clinical groups. Retinal hyporeflectivity (17%) was significantly associated with a visual acuity of 20/200 or worse at resolution. Our observations demonstrate that active toxoplasmic retinochoroiditis has diverse SD-OCT signs and that none are universally present. Retinal hyporeflectivity-suggesting liquefactive necrosis-predicts poor visual outcome.

[Multimodal imaging in toxoplasmic external punctate retinitis: about a case]. / Imagerie multimodale dans la rétinite ponctuée externe toxoplasmique: à propos d'un cas.

Punctuate Outer Retinal Toxoplasmosis (PORT) is a rare variant of toxoplasma chorioretinitis. We report the case of a 21-year-old patient presenting with visual blur of the left eye (LE). The examination found a corrected visual acuity (VA) at 3/10th, a quit anterior segment and a 1+ vitreous haze. Fundus examination showed a suprafoveolar yellowish-white lesions associated to multiple peripheral atrophic and pigmented ones. Visual acuity of the right eye was 10/10th with a calm anterior segment. Fundus examination depicted an upper temporal cicatricial pigmented lesion. Multimodal imaging of LE objectified a PORT. The patient received antibiotic and corticosteroids with favorable clinical and functional outcome. Final VA reached 10/10 at day ten. This case illustrates the importance of multimodal imaging in the differentiation of PORT from the white dots syndrome and other unilateral retinitis.

Ocular toxoplasmosis, an overview focusing on clinical aspects.

Toxoplasma gondii is a widespread protozoan parasite infecting approximately one third of the world population. After proliferation of tachyzoites during the acute stage, the parasite forms tissue cysts in various anatomical sites and establishes chronic infection. Nowadays the nature of the interplay between the protozoan and its human host remains elusive. This is clearly evident in ocular toxoplasmosis, in which the parasite establishes an ambivalent relationship with the eye, manipulating the immune response and inducing variable initial lesions and further relapses. This review will focus on epidemiology and environmental, parasite and host related risk factors, clinical manifestations and laboratory findings, treatment and prophylaxis approaches in ocular toxoplasmosis. An image collection of patients referred to the Unit of Ophthalmology of Pisa's Hospital will be presented, too.

Ocular Co-infection with Mycobacterium Tuberculosis and Toxoplasma Gondii in an Immunocompetent Patient - A Case Report.

PURPOSE: To report a case of ocular co-infection with Mycobacterium tuberculosis and Toxoplasma gondii in an immunocompetent woman. METHOD: Retrospective observational case report. RESULT: A 61-year-old woman presented with decreased vision and floaters in the right eye of 1-month duration. Ocular examination revealed panuveitis with a large yellowish-white retinochoroiditis lesion adjacent to a chorioretinal scar. Investigations showed positive Mantoux test, QuantiFERON TB test, and HRCT chest suggestive of active pulmonary tuberculosis. Serology revealed raised IgG anti T. gondii antibody. Vitreous aspirate was positive for M. tuberculosis and T. gondii genome by polymerase chain reaction and showed high IgG and IgM T. gondii antibodies. She was treated with anti toxoplasmic and antitubercular therapy along with oral corticosteroid and therapeutic vitrectomy. CONCLUSION: Ocular tuberculosis and toxoplasmosis can not only mimic each other but also present as co-infection in rare cases.