Relentless placoid chorioretinitis (RPC) is a rare, vision-threatening posterior uveitis that predominantly affects young adults. The hallmark clinical findings are numerous scattered placoid chorioretinal lesions involving the midperipheral and far peripheral fundus as well as the posterior pole and a persistent or recurrent course resulting in lesions at different chronological stages, with fresh creamy placoid lesions and healing pigmented lesions being present at the same time. Although RPC is frequently described as a disease that is intermediate between acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and serpiginous choroiditis, it more closely resembles APMPPE. It is important to identify those patients with RPC who present with an APMPPE phenotype so that appropriate immunomodulatory therapy is instituted without delay, as most cases of RPC are refractory to corticosteroid monotherapy. Examination findings may help differentiate RPC and APMPPE. Multimodal imaging, including ultra-widefield imaging, and selective investigations aid in distinguishing RPC from other placoid diseases and types of posterior uveitis.

Ocular syphilis is a re-emerging inflammatory eye disease with a clear gender imbalance, disproportionately affecting men. We investigated the impact of gender on the presentation, management practices and clinical outcomes of this condition. Data generated from a study of patients consecutively diagnosed with ocular syphilis who attended a subspecialist uveitis service at one of four hospitals in Brazil over a 30-month period were disaggregated for analysis by gender. Two-hundred and fourteen eyes (161 men and 53 women) of 127 patients (96 men and 31 women) were included. Posterior uveitis was the most common presentation in both men and women (80.1% vs. 66.7%, p > 0.05), but men were significantly more likely to have vitritis as a feature of their disease (49.4% versus 28.8%, p = 0.019). Three eyes of women had nodular anterior scleritis (p = 0.015). Men were more likely to undergo a lumbar puncture to assess for neurosyphilis (71.9% vs. 51.6%, p = 0.048), but men and women undergoing a lumbar puncture were equally likely to have a cerebrospinal fluid abnormality (36.2% vs. 25.0%, p = 0.393). All patients were treated with aqueous penicillin G or ceftriaxone, and there was a trend towards more men receiving adjunctive systemic corticosteroid treatment as part of their management (65.2% vs. 46.7%, p = 0.071). There were no significant differences in the age of presentation, bilaterality of disease, anatomical classification of uveitis, initial or final visual acuity, and rates of ocular complications between men and women. Our findings indicate that ocular syphilis has comparable outcomes in men and women, but that there are differences in the type of ocular inflammation and management practices between the genders.

We report three cases of refractory chronic endophthalmitis after cataract surgery presenting to a referral center, and with repeated negative cultures. Initial treatment consisted of intravitreal and systemic antibiotics, with partial improvement. After subsequent worsening, pars plana vitrectomy, intraocular lens explantation and en bloc capsulectomy were performed. Histopathological examination revealed multiple filamentous fungal structures, sequestered between anterior/posterior lens capsule in all cases. Chronic postoperative fungal endophthalmitis may manifest with negative cultures possibly associated with sequestration of the microorganism into the capsular bag. Careful histopathological examination of lens capsule in these cases may be essential for a definite diagnosis.

Prenatal systematic screening for congenital toxoplasmosis has been performed in Austria and France since 1975 and neonatal screening for congenital toxoplasmosis has been part of the New England Newborn screening program since 1986.In this narrative review we review the data leading up to the systematic screening programs in Austria and France, highlighting the main finding of the European Union funded research in the 1990s and early 2000s. Different descriptive studies of the effect of pre- or postnatal treatment are discussed. Toxoplasma gondii has different genetic lineages with different pathogenicity in humans. This means that results in areas with a low pathogenic lineage cannot be extrapolated to an area with highly pathogenic lineages. The importance of meat as a source of infection is discussed in the light of an increased prevalence of T.gondii in organic livestock production .

Introduction Vitreoretinal lymphoma is a rare ocular cancer with high morbidity and mortality despite treatment. Diagnosis by cytopathology is often delayed, and various molecular and image-based investigations have been developed. Diverse treatments are used, but there is a limited medical evidence to differentiate their effectiveness. We designed an international registry that would collect diagnostic, treatment and outcomes data, to establish new evidence for the management of this cancer.Methods and analysis The International Vitreoretinal B-Cell Lymphoma Registry will accrue data retrospectively for individuals aged 18 years or older, diagnosed with new or recurrent vitreoretinal B-cell lymphoma on or after 1 January 2020. A steering committee of subspecialised ophthalmologists identified 20 key clinical data items that describe patient demographics, tissue involvements, diagnostic testing, ocular and systemic treatments and treatment complications, and visual acuity and survival outcomes. Customised software was designed to permit collection of these data across a single baseline and multiple follow-up forms. The platform collects data without identifiers and at 3 month reporting intervals. Outcomes of the project will include: (1) descriptions of clinical presentations, and diagnostic and therapeutic preferences; (2) associations between clinical presentations, and diagnostics and treatments, and between diagnostics and treatments (assessed by ORs with 95% CIs); and (3) estimations of rates of vision loss, and progression-free and overall survival (assessed by Kaplan-Meier estimates).Ethics and dissemination The registry has received Australia-wide approval by a national human research ethics committee. Sites located outside Australia are required to seek local human research ethics review. Results generated through the registry will be disseminated primarily by peer-reviewed publications that are expected to inform clinical practice, as well as educational materials.

Background Birdshot retinochoroiditis (BRC) is a rare and chronic bilateral uveitis mostly found in Caucasians. As few data are available about the clinical course of BRC in Hispanic patients, we aimed to report the clinical findings and the evolution of BRC in Brazilian patients. Methods This retrospective cohort multicenter nationwide study was performed by analyzing the records of patients with BRC diagnoses from Brazilian ophthalmological centers from April 1995 to May 2020. Results Forty patients (80 eyes) with a diagnosis of BRC were evaluated. The mean age was 53 years, and there was no sex predominance. All tested patients (34/40) were positive for HLA-A29. The diagnosis of BRC was made following the Levinson et al. criteria, and all ancillary tests were performed to exclude differential diagnoses. Clinical signs and symptoms, such as complications and treatment, were described. Conclusions BRC evolution in Brazilian patients seems to have some peculiarities that diverge from the published literature available about Caucasians, as AS inflammation is higher in this population.

Multiple studies around the world suggest that syphilis is re-emerging. Ocular syphilis - with a wide range of presentations, most of which are subtypes of uveitis - has become an increasingly common cause of ocular inflammation over the past 20 years. Its rising incidence, diagnostic complexity, and manifestations that have only recently been characterized make ocular syphilis relevant from the public health, clinical, and scientific perspectives. We review the demographics, epidemiology, clinical features, ocular imaging findings, diagnosis, and medical management of this condition.

Proliferative sickle cell retinopathy (PSCR) is the most important ocular manifestation of sickle cell disease (SCD), but understanding of its pathophysiology remains incomplete. Red blood cell (RBC) deformability has been identified as a critical factor in SCD and is intrinsically related with cell sphericity index (SI). The aim of this study was to develop an algorithm that automatically analyzes defocusing microscopy (DM) images, providing biomechanical parameters of individual RBCs, including cellular SI. Furthermore, association of RBC SI with severity of PSCR in individuals with HbSC-SCD was also investigated. We determined the SI of 255 RBCs from 17 individuals using DM. Nine individuals (53 HbSC-SCD. Mean SI was significantly lower in SCD than in control group (0.69 versus 0.73), and also in severe than in mild PSCR (0.67 versus 0.70). Lower SI was also associated with more severe retinopathy (ROC AUC = 0.85) and the proportion of participants with SI <= 0.69 was significantly greater in severe than in mild PSCR (100 DM was associated not only with the presence of SCD, but also with more severe PSCR, possibly being a surrogate biomarker of disease severity.

Purpose: To provide recommendations for diagnosis of vitreoretinal lymphoma (VRL). Methods: Literature was reviewed for reports supporting the diagnosis of VRL. A questionnaire (Delphi 1 round) was distributed to 28 participants. In the second round (Delphi 2), items of the questionnaire not reaching consensus (75% agreement) were discussed to finalize the recommendations. Results: Presenting symptoms include floaters and painless loss of vision, vitreous cells organized into sheets or clumps. Retinal lesions are usually multifocal creamy/white in the outer retina. Other findings include retinal lesions with "leopard-skin" appearance and retinal pigment epithelium atrophy. Severe vitreous infiltration without macular edema is the most likely presentation. Diagnostic vitrectomy should be performed. Systemic corticosteroid should be discontinued at least 2 weeks before surgery. An interleukin (IL)-10:IL-6 ratio > 1, positive mutation for the myeloid differentiation primary response 88 gene and monoclonality are indicators of VRL. Multi-modal imaging (optical coherence tomography, fundus autofluorescence) are recommended. Conclusions: A consensus meeting allowed the establishment of recommendations important for the diagnosis of VRL.

Purpose: This study investigated the safety and therapeutic efficacy of licarin A (LCA) in the treatment of intraocular inflammation. Methods:In vitro safety of LCA in retinal pigmented epithelial cells (ARPE-19) and human embryonic stem cell derived-retinal pigmented epithelial cells (hES-RPE) was evaluated using CellTiter-Blue® kit. The chorioallantoic membrane (CAM) assay was used to investigate LCA safety and antiangiogenic activity. In vivo safety of intravitreal LCA was accomplished by clinical examination (including assessment of intraocular pressure), electroretinography (ERG), and histopathology. Uveitis was induced in rats by subcutaneous and intravitreal injection of bacillus Calmette-Guérin (BCG) antigen of Mycobacterium bovis. Intraocular inflammation was graded by slit-lamp and fundus examination, ERG, and histopathology. Results: LCA was safe to cells and to the CAM at concentration below 12.0 μM. LCA significantly reduced the percentage of blood vessels in the CAM. Retinal safety and anti-inflammatory efficacy of intravitreal injection of LCA 6.0 μM were confirmed through clinical, functional, and histopathological evaluation. Significant reduction of inflammatory cytokines (tumor necrosis factor-α and interleukin-6) was also found, when compared to untreated animals. Conclusion: The results suggest that LCA is a potential new drug for the treatment of inflammatory eye disease.

Toxoplasmosis affects one-third of the human population worldwide. Humans are accidental hosts and are infected after consumption of undercooked meat and water contaminated with Toxoplasma gondii cysts and oocysts, respectively. Neutrophils have been shown to participate in the control of T. gondii infection in mice through a variety of effector mechanisms, such as reactive oxygen species (ROS) and neutrophil extracellular trap (NET) formation. However, few studies have demonstrated the role of neutrophils in individuals naturally infected with T. gondii. In the current study, we evaluated the activation status of neutrophils in individuals with acute or chronic toxoplasmosis and determined the role of T. gondii-induced NET formation in the amplification of the innate and adaptive immune responses. We observed that neutrophils are highly activated during acute infection through increased expression of CD66b. Moreover, neutrophils from healthy donors (HDs) cocultured with tachyzoites produced ROS and formed NETs, with the latter being dependent on glycolysis, succinate dehydrogenase, gasdermin D, and neutrophil elastase. Furthermore, we observed elevated levels of the chemokines (CXC motif) CXCL8 and (CC motif) CCL4 ligands in plasma from patients with acute toxoplasmosis and production by neutrophils from HDs exposed to T. gondii. Finally, we showed that T. gondii-induced NETs activate neutrophils and promote the recruitment of autologous CD4+ T cells and the production of interferon gamma (IFN-γ), tumor necrosis factor (TNF), interleukin 6 (IL-6), IL-17, and IL-10 by peripheral blood mononuclear cells. In conclusion, we demonstrated that T. gondii activates neutrophils and promotes the release of NETs, which amplify human innate and adaptive immune responses. IMPORTANCE Approximately one-third of the human population is estimated to be chronically infected with the obligate intracellular parasite Toxoplasma gondii. Humans are accidental hosts that are infected with T. gondii after consumption of undercooked meat or contaminated water. Neutrophils have been shown to control T. gondii growth by different mechanisms, including neutrophil extracellular traps (NETs). In the current study, we observed that neutrophils are highly activated during acute toxoplasmosis. We also determined that T. gondii-induced NETs are dependent on the energetic profile of neutrophils as well as the production of ROS and gasdermin D (GSDMD) cleavage. In addition, we showed that T. gondii-induced NETs activate neutrophils, promote the recruitment of autologous CD4+ T cells, and induce the production of cytokines by peripheral blood mononuclear cells, amplifying the innate and adaptive immune responses.

Diffuse unilateral subacute neuroretinitis (DUSN) is a rare ocular infectious disease caused by migrating larvae of a nematode. DUSN is often a diagnostic challenge as it is difficult to identify the pathogenic nematode on funduscopic examination because it moves frequently and often resides within the subretinal space. Herein, the authors present a patient with unilateral, chronic visual loss who was noted to have a live, motile worm within the vitreous cavity. Initial attempts to treat with laser photocoagulation were unsuccessful. In the accompanying video, the authors report the first case of a live intraocular parasite successfully removed with pars plana vitrectomy.

An international, expert led consensus initiative was set up by the Collaborative Ocular Tuberculosis Study (COTS) group to develop systematic, evidence, and experience-based recommendations for the treatment of ocular TB using a modified Delphi technique process. In the first round of Delphi, the group identified clinical scenarios pertinent to ocular TB based on five clinical phenotypes (anterior uveitis, intermediate uveitis, choroiditis, retinal vasculitis, and panuveitis). Using an interactive online questionnaires, guided by background knowledge from published literature, 486 consensus statements for initiating ATT were generated and deliberated amongst 81 global uveitis experts. The median score of five was considered reaching consensus for initiating ATT. The median score of four was tabled for deliberation through Delphi round 2 in a face-to-face meeting. This report describes the methodology adopted and followed through the consensus process, which help elucidate the guidelines for initiating ATT in patients with choroidal TB.

Toxoplasmosis is highly endemic worldwide. In Brazil, depending on the geographical region and socioeconomic status, 40-70% of individuals become seropositive at some point in their lives. A significant proportion of Toxoplasma gondii-chronically infected individuals who are otherwise immunocompetent develop recurrent ocular lesions. The inflammatory/immune mechanisms involved in development of ocular lesion are still unknown and, despite previous investigation, there are no reliable immune biomarkers to predict/follow disease outcome. To better understand the impact of the immune response on parasite control and immunopathology of ocular toxoplasmosis, and to provide insights on putative biomarkers for disease monitoring, we assessed the production of a large panel of circulating immune mediators in a longitudinal study of patients with postnatally acquired toxoplasmosis stratified by the presence of ocular involvement, both at the early acute stage and 6 months later during chronic infection, correlating them with presence of ocular involvement. We found that T. gondii-infected patients, especially during the acute stage of the disease, display high levels of chemokines, cytokines, and growth factors involved in the activation, proliferation, and migration of inflammatory cells to injured tissues. In particular, major increases were found in the IFN-induced chemokines CXCL9 and CXCL10 in T. gondii-infected patients regardless of disease stage or clinical manifestations. Moreover, a specific subgroup of circulating cytokines and chemokines including GM-CSF, CCL25, CCL11, CXCL12, CXCL13, and CCL2 was identified as potential biomarkers that accurately distinguish different stages of infection and predict the occurrence of ocular toxoplasmosis. In addition to serving as predictors of disease development, these host inflammatory molecules may offer promise as candidate targets for therapeutic intervention.

Multimodal imaging relies on combination of multiple imaging modalities to precisely delineate pathological changes in the posterior segment of the eye associated with a wide range of conditions. This combined application of fundus photography, optical coherence tomography, fundus reflectance/autofluorescence and fundus angiography (with fluorescein, indocyanine green and/or optical coherence tomography) is of great utility for assessment of patients with ocular toxoplasmosis. Multimodal imaging is helpful to characterize the typical pattern of toxoplasmic retinochoroiditis, with primary focal inflammatory involvement of the neurosensory retina, and secondary changes at the level of underlying choroid, retinal blood vessels, vitreous and even optic disc. It may also be valuable to document and follow local complications, including macular edema, vascular occlusions, and choroidal neovascularization, among others.

Apresentacao Em boa hora, decidiu a Sociedade Brasileira de Cardiologia (SBC) fazer uma diretriz em telemedicina aplicada a cardiologia, tambem designada telecardiologia. A Organizacao Pan-americana de Saude (OPAS) e a Organizacao Mundial de Saude (OMS) definem Telemedicina como “a prestacao de servicos de saude remotos na promocao, prevencao, diagnostico, tratamento e reabilitacao pelos profissionais de saude que utilizam as tecnologias de informacao e comunicacao, que lhes permitem trocar dados, com o objetivo de facilitar o acesso e a oportunidade na [...]

Key PointsQuestionIs retinopathy observed in patients with yellow fever? FindingsIn this cross-sectional study of 64 patients who had received a confirmed diagnosis of yellow fever during 2 recent outbreaks in Southeastern Brazil, 13 patients (20%) had retinopathy, with the most common retinal findings being retinal nerve fiber layer infarct, superficial hemorrhage, and grayish outer retinal lesions. Elevated serum aspartate aminotransferase, total bilirubin, arterial lactate, and serum creatinine levels as well as disease severity and low platelet counts were associated with retinopathy in these patients. MeaningRetinopathy can be observed among patients with yellow fever but may be overlooked, especially if more severe disease precludes careful ophthalmoscopic examinations. ImportanceYellow fever still threatens people in endemic areas, and besides conjunctival icterus, little is known about the ocular changes that occur in these patients. ObjectiveTo characterize retinal changes in patients with confirmed yellow fever during 2 recent outbreaks of the disease in Minas Gerais, Southeastern Brazil. Design, Setting, and ParticipantsThis cross-sectional, observational study conducted at a single referral center for infectious diseases in Southeastern Brazil collected data between January 2017 and February 2018 from 94 consecutive patients with suspicion of yellow fever who were eligible for the study. Main Outcomes and MeasuresPatients underwent ophthalmic examination. Clinical findings, laboratory results, and occurrence of retinopathy and death during hospitalization were reported, including age, sex, comorbidities, disease severity, serum aspartate aminotransferase level, total bilirubin level, serum creatinine level, arterial lactate level, international normalized ratio, and platelet count at hospital admission. ResultsIn total, 64 patients were included who had received a confirmed diagnosis of yellow fever, with a median (interquartile range) age of 47 (38-56) years, and 12 patients (19%) were women. Twenty eyes (16%) of 13 patients (20%) had retinopathy at the same time as yellow fever. The most common fundus changes among the 20 eyes were retinal nerve fiber layer infarcts (11 [55%]), superficial hemorrhages (7 [35%]) and grayish deep lesions (6 [30%]), possibly at the level of the outer retina or choroid. Aspartate aminotransferase levels higher than 3000 U/L (odds ratio [OR], 14.2; 95% CI, 3.5-77.8; P<.001), total bilirubin levels higher than 2.3 mg/dL (OR, 20.0; 95% CI, 4.4-159.7; P<.001), serum creatinine levels higher than 2.0 mg/dL (OR, 8.2; 95% CI, 2.1-36.0; P=.003), arterial lactate levels higher than 17.1/mg/dL (OR, 4.6; 95% CI, 1.1-19.0; P=.03), platelet count lower than 94x10(3)/mu L (OR, 7.8; 95% CI, 1.8-59.9; P=.004), and classification of disease as severe (OR, 11.7; 95% CI, 2.0-301.0; P=.003) were associated with retinopathy. Arterial hypertension, diabetes, international normalized ratio, and death were not associated with retinopathy. Conclusions and RelevanceRetinopathy was present in 20% of patients with yellow fever and appeared to be associated with more severe systemic disease. Retinal nerve fiber layer infarcts and superficial hemorrhages, but not the grayish deep lesions, resembled those associated with other flavivirus (eg, dengue virus) infections. The clinical relevance of these findings may warrant further investigation. This cross-sectional single-center study conducted in Southeastern Brazil evaluates clinical findings and biomarkers associated with retinopathy and characterizes retinal changes among patients with confirmed yellow fever during 2 recent outbreaks of the disease.

Purpose: To report the manifestation of Vogt?Koyanagi?Harada-like disease (VKH) following yellow fever vaccination. Methods: Case report. Results: A 34-year-old immunocompetent male had tinnitus, headache, and decreased vision after a booster dose of yellow fever vaccine. Visual acuity was 20/100 in the right eye and 20/80 in the left, with serous retinal detachment (SRD) and choroidal thickening identified on clinical examination and multimodal imaging. Lumbar puncture revealed pleocytosis and an increased protein content, but extensive investigations ruled out infectious/neurological diseases. Pulse intravenous methylprednisolone was given, followed by a tapering regimen of high-dose oral prednisone. Azathioprine was started early, 3 weeks after initiation of oral steroids. Intraocular inflammation and SRD rapidly resolved, with visual acuity reaching 20/20 in both eyes, after 3 weeks. No recurrence of intraocular inflammation or sign of depigmentation was so far noticed, at 2 years of follow-up. Conclusion: Yellow fever vaccine may be a possible trigger for VKH.