Long-term impact of congenital toxoplasmosis on phenotypic and functional features of circulating leukocytes from infants one year after treatment onset.

Changes in immune response of children with congenital toxoplasmosis (CT) regarding infection evolution and therapeutic intervention was addressed. Infants with CT presented increased counts of monocytes, CD3-CD16-CD56High, CD3+CD56+ and CD4+ T-cells 1-year after treatment onset (TOXO1-yearAT). Smaller numbers of CD3-CD16-CD56+ and TCRγδ+ T-cells were specifically observed in infants with retinochoroidal lesions (L(+)). When infants were classified based on the baseline status, expansion of CD3-CD16-CD56High and CD4+ T-cells were observed in L(+) who had active, active/cicatricial or cicatricial lesions. Infants who had active or active/cicatricial lesions display augmented numbers of monocytes, CD3-CD16+CD56+, CD3+CD56+, CD8+DR+ and TCRγδ+ T-cells and those with active/cicatricial or cicatricial at baseline displayed increase in CD14+CD64+ monocytes. Moreover, all L(+) had increased IFN-γ+ and IL-10+ CD4+ T-cells, while L(-) had increased ratios of TNF+, IFN-γ+ and IL-4+ NK-cells upon antigen-specific stimulation. Persistent alterations in leukocytes in TOXO1-yearAT suggest long-term sequels in the immune system of infants with CT.

SARS-CoV-2 and COVID-19 for the ophthalmologist.

The COVID-19 pandemic has had an unprecedented impact on ophthalmology. This review compiles general aspects of the novel coronavirus and COVID-19, further dissects the most recent data on the role of the eye regarding disease transmission and manifestations, and summarizes preventive measures in the particular context of eye care.

Sirolimus-Loaded Intravitreal Implant for Effective Treatment of Experimental Uveitis.

Non-infectious uveitis, an ocular inflammatory condition that affects the iris, ciliary body, choroid, and adjacent tissues (retina, optic nerve, and vitreous), is an important cause of blindness worldwide. Sirolimus (SRL), a potent immunomodulatory drug, has shown promising results in the treatment of inflammatory ocular diseases. Despite this therapeutic potential, its clinical use is a major challenge due to low bioavailability and poor solubility. Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable polymer commonly used for ophthalmic drug delivery due to its suitable characteristics such as biocompatibility, good mechanical properties, and improvement of the pharmacokinetic profile of the drug. In the present study, we investigated the effects of SRL-PLGA implant on experimental autoimmune uveitis in rabbits. Clinical and histopathological examinations were performed, followed by assessment of protein levels and determination of myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) activity in the aqueous humor/vitreous. As a result, treated eyes had decreased average inflammatory scores, protein significant decreases in treated eyes, assessed after 35 days. Histopathological examination showed less severe intraocular inflammation and decreased tissue damage in treated eyes. According to these results, the SRL-PLGA implant evaluated in this study was apparently safe, reducing inflammation in treated eyes, with an extended effect possibly associated with prolonged release of SRL in the posterior segment of the eye. Therefore, intravitreal SRL-PLGA implant could be a promising alternative for treatment of non-infectious uveitis.

Clinical and Multimodal Imaging Findings and Risk Factors for Ocular Involvement in a Presumed Waterborne Toxoplasmosis Outbreak, Brazil1.

In 2015, an outbreak of presumed waterborne toxoplasmosis occurred in Gouveia, Brazil. We conducted a 3-year prospective study on a cohort of 52 patients from this outbreak, collected clinical and multimodal imaging findings, and determined risk factors for ocular involvement. At baseline examination, 12 (23%) patients had retinochoroiditis; 4 patients had bilateral and 2 had macular lesions. Multimodal imaging revealed 2 distinct retinochoroiditis patterns: necrotizing focal retinochoroiditis and punctate retinochoroiditis. Older age, worse visual acuity, self-reported recent reduction of visual acuity, and presence of floaters were associated with retinochoroiditis. Among patients, persons >40 years of age had 5 times the risk for ocular involvement. Five patients had recurrences during follow-up, a rate of 22% per person-year. Recurrences were associated with binocular involvement. Two patients had late ocular involvement that occurred >34 months after initial diagnosis. Patients with acquired toxoplasmosis should have long-term ophthalmic follow-up, regardless of initial ocular involvement.

Teleophthalmology Screening for Diabetic Retinopathy in Brazil: Applicability and Economic Assessment.

Introduction: Early diagnosis and prompt therapy of diabetic retinopathy (DR) are essential to prevent visual loss, but access of the diabetic population to regular fundus examination by an ophthalmologist remains a challenge. Methods: This prospective comparative study, including two referral health centers in the state of Minas Gerais, Southeastern Brazil, assesses applicability and economic viability of fundus photography-based teleophthalmology screening for DR. Results: A total of 2,662 eyes of 1,331 patients were examined at both health centers. Mean age was 57 years, with 836 (62.8%) females. Quality of fundus photographs was acceptable for 2,398 eyes (90.1%). The presence of DR was disclosed in 394 patients (29.6%), with 28 patients (2.1%) presenting evidence of advanced disease (severe nonproliferative or proliferative DR). Economic assessment revealed cost reduction of 28.76 US$ per patient, with a calculated break-even point of 112 exams/month or 1,344 exams/year. Conclusions: For the situation studied under the perspective of public health service, teleophthalmology was viable and cost effective when compared with ordinary ophthalmology examination. In addition, teleophthalmology allowed rapid resolution of repressed demand for fundus examination of diabetic patients locally at the two sites, with early DR diagnoses and referrals. Fundus photography-based teleophthalmology was a viable, effective, and significantly cheaper strategy for the screening of DR.

Characterisation of ocular involvement in an experimental model of neuroschistosomiasis mansoni.

The Global Burden of Disease Study 2010 listed schistosomiasis among the leading 100 causes of death in Brazil, responsible for 3.6% of the estimated total of deaths globally. Eye and adnexa are very rarely affected by schistosomiasis mansoni, with limited documentation of ocular pathology in this setting. This short communication reports ocular histolopathological findings in a murine model of neuroschistosomiasis mansoni. Lesions were found in the bulbar conjunctiva, lacrimal gland, choroid and corneoscleral limbus.

Early serum biomarker networks in infants with distinct retinochoroidal lesion status of congenital toxoplasmosis.

The present study characterized the early changes in the serum chemokines/cytokine signatures and networks in infants with congenital-toxoplasmosis/(TOXO) as compared to non-infected-controls/(NI). TOXO were subgrouped according to the retinochoroidal lesion status as no-lesion/(NL), active-lesion/(ARL), active/cicatricial-lesion/(ACRL) and cicatricial-lesion/(CRL). The results showed that TOXO display prominent chemokine production mediated by IL-8/CXCL8, MIG/CXCL9, IP-10/CXCL10 and RANTES/CCL5. Additionally, TOXO is accompanied by mixed proinflammatory/regulatory cytokine pattern mediated by IL-6, IFN-γ, IL-4, IL-5 and IL-10. While TNF appears as a putative biomarker for NL and IFN-γ/IL-5 as immunological features for ARL, IL-10 emerges as a relevant mediator in ACRL/CRL. IL-8/CXCL8 and IP-10/CXCL10 are broad-spectrum indicators of ocular disease, whereas TNF is a NL biomarker, IFN-γ and MIG/CXCL9 point out to ARL; and IL-10 is highlighted as a genuine serum biomarker of ACRL/CRL. The network analysis demonstrated a broad chemokine/cytokine crosstalk with divergences in the molecular signatures in patients with different ocular lesions during congenital toxoplasmosis.

Cytokine Signatures Associated With Early Onset, Active Lesions and Late Cicatricial Events of Retinochoroidal Commitment in Infants With Congenital Toxoplasmosis.

BACKGROUND: Ocular toxoplasmosis is a prominent and severe condition of high incidence in Brazil. The current study provides new insights into the immunological events that can be associated with retinochoroiditis in the setting of congenital toxoplasmosis in human infants. METHODS: Flow cytometry of intracytoplasmic cytokines in leukocyte subsets following in vitro short-term antigenic recall in infants with congenital T. gondii infection. RESULTS: Our data demonstrates that whereas neutrophils and monocytes from T. gondii-infected infants display a combination of proinflammatory and regulatory cytokine profiles, natural killer cells showed a predominantly proinflammatory profile upon in vitro T. gondii stimulation. The proinflammatory response of CD4(+) and CD8(+) T cells, characterized by the production of interferon γ (IFN-γ) and interleukin 17 in patients with an active retinochoroidal lesion, revealed the presence of IFN-γ and tumor necrosis factor α during early and late immunological events. This specific proinflammatory pattern is associated with early events and active retinochoroidal lesion, whereas a robust monocyte-derived interleukin 10-mediated profile is observed in children with cicatricial ocular lesions. CONCLUSIONS: These findings support the existence of a progressive immunological environment concomitant with the initial, apical, and cicatricial phases in the process of retinochoroidal lesion formation in infants with congenital toxoplasmosis that may be relevant in the establishment of stage-specific clinical management.

Biomarker analysis revealed distinct profiles of innate and adaptive immunity in infants with ocular lesions of congenital toxoplasmosis.

Toxoplasma gondii is the main infectious cause of human posterior retinochoroiditis, the most frequent clinical manifestation of congenital toxoplasmosis. This investigation was performed after neonatal screening to identify biomarkers of immunity associated with immunopathological features of the disease by flow cytometry. The study included infected infants without NRL and with retinochoroidal lesions (ARL, ACRL, and CRL) as well as noninfected individuals (NI). Our data demonstrated that leukocytosis, with increased monocytes and lymphocytes, was a relevant hematological biomarker of ARL. Immunophenotypic analysis also revealed expansion of CD14(+)CD16(+)HLA-DR(high) monocytes and CD56(dim) cytotoxic NK-cells in ARL. Moreover, augmented TCRγ δ (+) and CD8(+) T-cell counts were apparently good biomarkers of morbidity. Biomarker network analysis revealed that complex and intricated networks underscored the negative correlation of monocytes with NK- and B-cells in NRL. The remarkable lack of connections involving B-cells and a relevant shift of NK-cell connections from B-cells toward T-cells observed in ARL were outstanding. A tightly connected biomarker network was observed in CRL, with relevant connections of NK- and CD8(+) T-cells with a broad range of cell subsets. Our findings add novel elements to the current knowledge on the innate and adaptive immune responses in congenital toxoplasmosis.

Bilateral acute iris transillumination (BAIT) syndrome: Differential diagnosis based on clinical, OCT and UBM findings.

INTRODUCTION: Bilateral acute iris transillumination (BAIT) is a relatively new syndrome whose etiopathogenesis is still not fully understood. It is characterized by acute bilateral onset of intense pigment dispersion in the anterior chamber, iris depigmentation with severe transillumination defects, accentuated pigment deposition in the angle, and elevated intraocular pressure (IOP). In literature, the first case was of bilateral acute iris depigmentation (BADI) reported in 2004 in a 77-year-old woman. In 2019, Perone et al. published a review about BAIT syndrome. They reported a total of 79 cases have been published up that date, mainly in Europe and especially in Turkey and Belgium. The majority of reported cases were of bilateral acute iris depigmentation (BADI). BAIT syndrome might be mainly confused with acute iridocyclitis, acute primary angle-closure (APAC) and pigment dispersion syndrome (PDS). In relation to BAIT, controversies still exist regarding the etiology being the differential diagnosis of paramount importance for adequate treatment. PURPOSE: To report a case of BAIT syndrome associated to refractory glaucoma and to discuss the differential diagnosis based on clinical, OCT and UBM findings. METHODS: We present a case of BAIT syndrome in which clinical, OCT and UBM findings have pointed out the similarities and, mainly the diagnosis differences with other ocular diseases. CONCLUSIONS: BAIT syndrome with accentuated IOP rise must be differentiated of other ocular diseases. It requires urgent clinical therapy and/or surgical management as occurred in the present case for avoiding structural damage in OCT and visual field loss. OCT and UBM are critical for early recognition, differential diagnosis and management.

Genetic characterization of Toxoplasma gondii revealed highly diverse genotypes for isolates from newborns with congenital toxoplasmosis in southeastern Brazil.

Recent studies of Toxoplasma gondii isolates from animals in Brazil have revealed high genetic diversity. Many of these isolates are virulent to mice. It is speculated that these isolates may also be virulent to humans. However, there is very limited data regarding T. gondii strains from human infection. Therefore, it is not clear whether there is any association between parasite genotypes and disease phenotypes. In this study, a total of 27 T. gondii strains were isolated from humans with congenital toxoplasmosis in Minas Gerais state, Brazil. The genetic variability was assessed by restricted fragment length polymorphism in 11 loci (SAG1, 5' plus 3' SAG2, alternative [alt.] SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico). Genetic analysis of 24 strains revealed 14 different genotypes, including 7 previously identified from animals and 7 new types. The widespread genotype BrII accounted for 29% (7/24) of the isolates and was the dominant genotype involved in this study. This is the first report of genotyping of T. gondii isolates obtained from blood samples from newborns with congenital toxoplasmosis. Genotypic characterization of these isolates suggests high genetic diversity of T. gondii in this human population in Brazil. Future studies are needed to determine the source of contamination of this human population.

Real-time PCR as a prognostic tool for human congenital toxoplasmosis.

Real-time PCR (qPCR) was positive in 72/150 (48%) blood samples of newborns with congenital toxoplasmosis. Among infants with active retinochoroiditis, 68% had positive qPCR results, while positivity was 29% (P=0.009) in the absence of ocular involvement. Positive qPCR was associated with the presence of retinochoroidal lesions, with an odds ratio of 2.8.

Efficacy and Safety Evaluation of Mometasone Furoate in Treating Ocular Inflammation.

Mometasone furoate (MF) is a medium-potency synthetic glucocorticosteroid with anti-inflammatory, antipruritic, and vasoconstrictive properties. However, its role in the treatment of ocular inflammation has not yet been explored. This work investigated the anti-inflammatory activity of MF in ocular tissues. First, the in vivo safety of the intravitreal (IVT) injection of MF (80, 160, and 240 µg) was evaluated via clinical examination (including the assessment of intraocular pressure), electroretinography (ERG), and histopathology. Second, MF was tested in an experimental model of bacillus Calmette-Guérin (BCG)-induced uveitis in Wistar rats. Intraocular inflammation was then evaluated via a slit-lamp and fundus examination, ERG, histopathology, and the quantification of pro-inflammatory markers. Intravitreal MF showed no toxicity in all the investigated doses, with 160 µg leading to attenuated disease progression and improvement in clinical, morphological, and functional parameters. There was a significant reduction in the levels of inflammatory markers (myeloperoxidase, interleukins 6 and 1ß, CXCL-1, and tumor necrosis factor-alpha) when compared to the levels in untreated animals. Therefore, MF should be further investigated as a promising drug for the treatment of ocular inflammation.

Glaucoma and Telemedicine.

PRCIS: Teleglaucoma is the future, but there is a need for clearer regulation by government agencies and medical entities, as well as for studies to further demonstrate the cost-effectiveness and safety of teleglaucoma strategies at a global scale. ABSTRACT: The coronavirus disease 2019 pandemic drastically impacted global health, forcing institutions to provide alternative models of safe and reliable health care. In this context, telemedicine has been successfully used to overcome distance barriers and improve access to medical services. Teleglaucoma is the application of telemedicine to screen and monitor glaucoma, a chronic and progressive optic neuropathy. Teleglaucoma screening aims to detect the disease at an earlier stage, especially in high-risk populations and underserved areas, also identifying patients who require more urgent treatment. Teleglaucoma monitoring seeks to provide remote management through virtual clinics, where classic in-person visits are replaced by synchronous data collection (clinical measurements) performed by non-ophthalmologists and asynchronous review (decision-making) by ophthalmologists. This may be employed for low-risk patients with early disease, improving health care logistics, reducing the number of face-to-face consultations, and saving time and costs. New technologies may also allow home monitoring of patients in teleglaucoma programs, with the addition of artificial intelligence methods, which are expected to increase the accuracy of remote glaucoma screening/monitoring and support clinical decision-making. However, for the incorporation of teleglaucoma into clinical practice, a complex system for collection, transfer, flow, and interpretation of data is still necessary, in addition to clearer regulatory markers by government agencies and medical entities.

Trends in the epidemiological and microbiological profiles of infectious keratitis in southeastern Brazil.

PURPOSE: To investigate the antibiotic susceptibility as well as the clinical, epidemiological, and microbiological profiles of microbial keratitis. METHODS: This was a longitudinal retrospective study, and we retrospectively reviewed medical and laboratory records from 2015 to 2019. RESULTS: In total, 380 pathogens (321 bacteria and 59 fungi) were isolated from the corneas of 352 patients. Staphylococcus species (45%) were most abundant within the organisms that were isolated, followed by Pseudomonas (18.4%), fungi (15.5%), Streptococcus (7.9%), and Serratia species (3.2%). The isolated gram-positive bacteria were not resistant to amikacin or vancomycin, although 14.8% of the gram-positive isolates were resistant to ciprofloxacin (p<0.05). All the gram-negative isolates were susceptible to amikacin. Male patients represented 62.8% of the 129 cases with accessible clinical data. The mean age of the patients was 53.17 ± 21 years. The time to presentation (from onset of symptoms) was 14.9 ± 19.4 days (median: 7 days). Large ulcers (>5 mm in any dimension) were present in 49.6% (64 eyes) of the cases. The duration of treatment was 49 ± 45.9 days (median: 38 days). Direct ocular trauma was reported by 48 (37.2%) patients, and 15 patients (11.6%) reported using contact lenses. For 72 (55.8%) patients, topical treatment had been previously prescribed, and 16 (12.4%) patients reported using other classes of drugs. Hospitalizations were required for 79 (61.2%) patients, and in terms of major complications, 53 (41.1%) patients had corneal perforations. A total of 40 patients (31%) underwent tectonic penetrating keratoplasty, and 28 (21.7%) developed secondary glaucoma. A progression to endophthalmitis occurred in 8 (6.2%) patients, with 50% of those patients' (3.1% of the total) endophthalmitis evolving to evisceration. The patients' microbial keratitis was largely treated empirically, with 94 (72.9%) patients prescribed moxifloxacin and 56 (43.4%) prescribed ciprofloxacin before receiving their culture results. CONCLUSIONS: For the most part, our hospital treated patients with severe microbial keratitis. Despite identifying gram-positive bacteria in most of the isolates, we also frequently identified gram-negative rods and fungi. Our susceptibility results support prescribing a combination of vancomycin and amikacin as an effective empirical therapeutic regimen to treat microbial keratitis.

Ocular Toxoplasmosis.

INTRODUCTION: Ocular toxoplasmosis is the leading cause of posterior uveitis worldwide, affecting individuals acrossdifferent age groups. The key to reducing vision loss includes prompt diagnosis and treatment. However, despite the prevalence of ocular toxoplasmosis, there has been little consensus regarding its pathophysiology,clinical features, diagnosis, and especially management. METHODS: The data sources were literature reviews, including Pub Med and Medline databases. Search terms included toxoplasmosis, retinitis, vasculitis, vitritis, uveitis alone or in combination with, serum, aqueous, vitreous eye, ocular and review. RESULTS: In this review paper, we have sought to provide an overview of the pathophysiology, epidemiology, and clinical features of the disease, both based on current literature and our own clinical experience. We have also discussed the use of serology, ocular fluid, and ophthalmic investigations that could further facilitate the diagnosis of ocular toxoplasmosis.Different management strategies have been reported worldwide, including newer approaches such as local therapy. CONCLUSION: A better understanding of critical aspects of ocular toxoplasmosis will hopefully lead to reduced morbidity, including blindness associated with this condition.

Early diagnosis of congenital toxoplasmosis in newborn infants using IgG subclasses against two Toxoplasma gondii recombinant proteins.

The aim of this work was to evaluate the utility of ELISA-based testing of total IgG (IgGt) antibodies and its subclasses (IgG1, IgG2, IgG3 and IgG4) against soluble (STAg) and recombinant (rSAG1 and rMIC3) antigens of Toxoplasma gondii for diagnosing congenital toxoplasmosis. Sera from 217 newborns initially testing positive for specific IgM in filter paper dried blood spots were tested for specific IgM and IgG by ELFA-VIDAS. Congenital toxoplasmosis was confirmed in 175 and ruled out in 42 infants. The validity of the ELISA tests was determined using the persistence of IgG antibodies (ELFA-VIDAS kit) at the end of 12 months, which is considered the reference test for the diagnosis of congenital toxoplasmosis. The frequency of positivity with IgGt against STAg, rSAG1 and rMIC3 was found in 97.2%, 96.3% and 80.2%, respectively, of the newborns with confirmed congenital toxoplasmosis. IgG1 reacted with all three antigens, while IgG3 and IgG4 reacted preferentially with rMIC3. Higher mean values of reactivity (sample optical density/cut-off) were found for all subclasses when using rMIC3. All of the antigens showed high sensitivity and low specificity in detecting anti-T. gondii IgGt and IgG1 and low sensitivity and high specificity in detecting IgG3 and IgG4. In conclusion, the combined detection of IgG antibody subclasses against recombinant toxoplasmic antigens may be useful for the early diagnosis of congenital toxoplasmosis.

Optical Coherence Tomography Findings in Infectious Posterior Uveitis.

PURPOSE: To describe and illustrate the main optical coherence tomography (OCT) findings of infectious uveitis. METHODS: Narrative review. RESULTS: Posterior segment OCT in patients with infectious uveitis reveals posterior hyaloid face precipitates, superficial retinal precipitates and infiltrates, foveolitis, retinitis, neuro-retinitis, choroidal granulomas, and choroiditis as main imaging biomarkers. Some of these features are specific to the underlying causing etiology and may support the diagnosis and the initiation of treatment. Some OCT features disappear completely with resolution; some others are associated with irreversible retinal damage. CONCLUSIONS: OCT identifies different features of infectious uveitis into the vitreous, the retina, and the choroid. OCT characteristics, combined with other multimodal imaging features, are helpful in the differential diagnosis of infectious uveitis, the early detection of complications, and the assessment of the response to therapy.