Peripapillary Retinoschisis in Glaucoma: A Systematic Review.

PRCIS: Peripapillary retinoschisis may bias optical coherence tomography's monitoring of glaucoma progression. Its impact on glaucoma still remains uncertain. Only two out of the ten included studies illustrated a correlation between peripapillary retinoschisis and glaucoma progression. PURPOSE: The frequent use of optical coherence tomography increased the detection of peripapillary retinoschisis, which poses challenges in the follow-up of glaucoma patients. This systematic review aims to summarize the literature regarding peripapillary retinoschisis in glaucoma, exploring its prevalence, impact on disease, and clinical management implications. METHODS: We searched PubMed, Embase, Web of Science and Scopus with tailored search queries for each platform. All studies had to report peripapillary retinoschisis in glaucoma patients. Exclusion criteria included studies with less than 10 eyes, studies focusing on schisis outside the disc area, with concomitant retinal or optic nerve lesions, with animals, reviews, studies written in non-English language and congress abstracts. RESULTS: Ten studies were included, of which 7 were case-control, one was a cohort study and two were case series.Six studies showed that peripapillary retinoschisis often overlapped pre-existing retinal nerve fiber layer defects. One study reported that the de novo development of peripapillary retinoschisis was more frequent in eyes with glaucoma progression than in eyes without progression.Visual field findings were inconsistent, with just one study (out of six) showing that glaucoma patients with peripapillary retinoschisis experienced faster visual field deterioration than those without it. Overall, solely two studies (out of seven) associated peripapillary retinoschisis with faster glaucoma progression. CONCLUSIONS: Peripapillary retinoschisis biases optical coherence tomography analysis in glaucoma. Caution is needed against overestimation of retinal nerve fiber layer thickness when peripapillary retinoschisis develops, and misinterpretation of its resolution as rapid progression. Peripapillary retinoschisis' exact impact on glaucoma progression remains unclear.

Pharmacologic Anisocoria With Azelastine: The Importance of a Good Anamnesis.

Unilateral pharmacologic mydriasis is one of the differential diagnoses of anisocoria. This is a clinical case of a 37-year-old male patient admitted to the ophthalmology emergency department with unilateral mydriasis, an infrequent side effect of the antihistaminic drug azelastine. A comprehensive medical history including ocular medication was essential to avoid the need for additional tests and to exclude life-threatening conditions responsible for a similar presentation.

Design and Development of a Web-Based Prospective Nationwide Registry for Ocular Inflammatory Diseases: UVEITE.PT - The Portuguese Ocular Inflammation Registry.

Uveitis is a heterogeneous collection of infrequent diseases, which poses significant challenges to cost-effective research in the field. Medical registries are being increasingly recognized as crucial tools to provide high-quality data, thus enabling prospective clinical research. This paper describes the design and technical structure development of an innovative countrywide electronic medical record for uveitis, Uveite.pt, and gives an overview of the cohort registered since its foundation, March 2020.Uveite.pt is an electronic medical record platform developed by the Portuguese Ocular Inflammation Group (POIG), a scientific committee of the Portuguese Ophthalmology Society. This is a nationwide customized web-based platform for uveitis patients useful for both clinical practice and real-world-based research, working as a central repository and reporting tool for uveitis. This paper describes the technical principles, the design and the development of a web-based interoperable registry for uveitis in Portugal and provides an overview of more than 400 patients registered in the first 18 months since inception.In infrequent diseases, the existence of registries enables to gather evidence and increase research possibilities to clinicians. The adoption of this platform enables standardization and improvement of clinical practice in uveitis. It is useful to apprehend the repercussion of medical and surgical treatments in uveitis and scleritis, supporting clinicians in the strict monitoring of drug adverse reactions and surgical outcomes.

Tracking Plasmacytoid Dendritic Cell Response to Physical Contact with Infected Cells.

Dendritic cells (DCs) are key regulators of both innate and adaptive immunity via varied functions, including cytokine production and antigen presentation. Plasmacytoid DC (pDC) is a DC subset specialized in the production of type I and III interferons (IFNs). They are thus pivotal players of the host antiviral response during the acute phase of infection by genetically distant viruses. The pDC response is primarily triggered by the endolysosomal sensors Toll-like receptors, which recognize nucleic acids from pathogens. In some pathologic contexts, pDC response can also be triggered by host nucleic acids, hereby contributing to the pathogenesis of autoimmune diseases, such as, e.g., systemic lupus erythematosus. Importantly, recent in vitro studies from our laboratory and others uncovered that pDCs sense viral infections when a physical contact is established with infected cells. This specialized synapse-like feature enables a robust type I and III IFN secretion at the infected site. Therefore, this concentrated and confined response likely limits the correlated deleterious impacts of excessive cytokine production to the host, notably due to tissue damages. Here we provide a pipeline of methods for ex vivo studies of pDC antiviral functions, designed to address how pDC activation is regulated by cell-cell contact with virally infected cells and the current approaches enabling to decipher the underlying molecular events leading to an efficient antiviral response.

[Evaluation of the Manchester Triage System in Patients with Acute Primary Angle Closure Attack: A Retrospective Study]. / Avaliação do Sistema de Triagem de Manchester em Doentes com Crise de Encerramento Agudo Primário do Ângulo Iridocorneano: Um Estudo Retrospetivo.

INTRODUCTION: Acute primary angle closure attack is an ophthalmological emergency. The aim of this study was to describe the cases diagnosed in the Emergency Department, by correlating the initial complaint with the Manchester triage level and ultimately the time needed until ophthalmological evaluation and iridotomy. MATERIAL AND METHODS: Retrospective analysis of the electronic medical records of patients with acute primary angle closure attack that attended the Ophthalmology Emergency Department of our tertiary center between January 2010 and December 2020. Overall, 2228 Emergency Department episodes coded with the diagnoses glaucoma or ocular hypertension were retrieved, followed by screening of each episode for correct identification of true acute primary angle closure attacks. Clinical data was gathered, including Manchester triage level, presenting complaint, intraocular pressure at presentation, first medical specialty that observed the patient, time until observation by Ophthalmology and time until laser iridotomy. RESULTS: Among the 120 patients identified, 84 (70%) were female and the mean age was 68 ± 12 years. Mean intraocular pressure at admission was 53.4 ± 12.4 mmHg, and 9.2% of patients presented only non-ocular complaints, while 9.2% presented mixed complaints (ocular and non-ocular). Most patients (68.1%) with only non-ocular or mixed complaints were triaged to a non-ophthalmologist (p < 0.001). Concerning the triage system, at admission, most patients (66.7%) were labelled yellow (urgent), while 9.2% and none were labelled as orange (very urgent) or red (emergent), respectively. Most patients (83.3%) were directly sent to Ophthalmology (properly triaged), while the remaining were incorrectly assigned to a non-ophthalmologist. Median time until observation by Ophthalmology was 49 minutes in the properly triaged group (min. 15, max. 404), while it was 288 minutes (min. 45, max. 871) in those who were incorrectly triaged (p < 0.001). Likewise, median time until treatment with laser iridotomy was 203 minutes in the properly triaged group (min. 22, max. 1440) and 353 minutes in the incorrectly triaged group (min.112, max. 947) (p < 0.001). CONCLUSION: Most patients with acute primary angle closure attack were not properly triaged according to the level of the Manchester triage system. There was a significant delay in the diagnosis and treatment of those patients who were first assigned to non-ophthalmologists. There is a need to raise awareness regarding the presenting signs and symptoms of an acute primary angle closure attack in order to avoid preventable vision loss.

Introdução: A crise de encerramento agudo primário do ângulo iridocorneano é uma emergência oftalmológica. O objetivo deste estudo foi descrever os casos admitidos no Serviço de Urgência do Centro Hospitalar Universitário São João, correlacionando a queixa inicial com o nível de triagem de Manchester atribuído e o tempo até observação por Oftalmologia e realização de iridotomia. Material e Métodos: Análise retrospetiva dos registos clínicos dos doentes com encerramento agudo primário do ângulo, admitidos no Serviço de Urgência entre janeiro de 2010 e dezembro de 2020. Foram revistos 2228 episódios com diagnóstico de glaucoma ou hipertensão ocular para identificação correta dos casos de crise de encerramento do ângulo. Foram extraídas variáveis, nomeadamente o nível de triagem de Manchester atribuído, queixa principal, pressão intraocular à admissão, especialidade responsável pelo primeiro contacto médico e tempos até observação por Oftalmologia e até iridotomia. Resultados: Foram identificados 120 doentes, 84 (70%) do sexo feminino, com idade média de 68 ± 12 (desvio padrão) anos. A pressão intraocular média à admissão foi de 53,4 ± 12,4 mmHg. Em 9,2% dos doentes a queixa principal foi não-ocular, enquanto 9,2% apresentavam queixas não-oculares e oculares associadas. A maioria (68,1%) dos doentes com queixas não-oculares ou mistas foi triada para um não-oftalmologista. Segundo o sistema de triagem, a maioria (66,7%) dos doentes foi triada com nível amarelo (urgente), 9,2% foram triados com laranja (muito urgente) e nenhum vermelho (emergente). O primeiro especialista a observar os doentes após a triagem foi um oftalmologista em 83,3% dos casos (corretamente triados), enquanto os restantes foram inicialmente observados por outra especialidade. O tempo mediano até observação por Oftalmologia foi de 288 minutos (min. 45, máx. 871) num doente incorretamente triado e 49 minutos (min. 15, máx. 404) (p < 0,001) em doentes corretamente triados. O tempo mediano até realização de iridotomia laser foi de 353 minutos (min. 112, máx. 947) nos doentes incorretamente triados e 203 minutos (min. 22, máx. 1440) nos corretamente triados (p < 0,001). Conclusão: A maioria dos doentes com crise de encerramento agudo primário do ângulo iridocorneano não foi triada de acordo com o grau de prioridade apropriado segundo o sistema de triagem de Manchester. Nos doentes que não foram imediatamente seguidos por Oftalmologia verificou-se um atraso significativo no diagnóstico e início do tratamento. Torna-se premente a consciencialização dos profissionais de saúde sobre esta condição clínica e a otimização do processo de triagem para minimizar a perda de visão.

Severe COVID-19 patients have impaired plasmacytoid dendritic cell-mediated control of SARS-CoV-2.

Type I and III interferons (IFN-I/λ) are important antiviral mediators against SARS-CoV-2 infection. Here, we demonstrate that plasmacytoid dendritic cells (pDC) are the predominant IFN-I/λ source following their sensing of SARS-CoV-2-infected cells. Mechanistically, this short-range sensing by pDCs requires sustained integrin-mediated cell adhesion with infected cells. In turn, pDCs restrict viral spread by an IFN-I/λ response directed toward SARS-CoV-2-infected cells. This specialized function enables pDCs to efficiently turn-off viral replication, likely via a local response at the contact site with infected cells. By exploring the pDC response in SARS-CoV-2 patients, we further demonstrate that pDC responsiveness inversely correlates with the severity of the disease. The pDC response is particularly impaired in severe COVID-19 patients. Overall, we propose that pDC activation is essential to control SARS-CoV-2-infection. Failure to develop this response could be important to understand severe cases of COVID-19.

Morphometry of cryopreserved organs from the gastrointestinal system of squirrel monkeys (Saimiri sciureus, Linnaeus, 1758) for improvement of management.

BACKGROUND: Nonhuman primates (NHPs) are fundamental for countless types of research and their phylogenetic similarities with humans make them valuable biomodels. Saimiri (squirrel monkeys) is the New World simian genus that is most widely used in research; however, little is known about the morphology of the gastrointestinal tract (GIT) of these animals. METHODS: The morphological and topographical aspects of GIT organs from 14 previously frozen carcasses of captive squirrel monkeys (Saimiri sciureus) were described as a means for refining clinical and laboratory diagnoses, with the aim of providing a basis for clinical assessments and animal management. The carcasses were gradually thawed, macroscopically evaluated for their appearance, measured, weighed, photographed, and necropsied. The characteristics of all the GIT organs (main and accessories) were evaluated, with measurement of the dimensions and description of the shape, consistency, and color of each one. RESULTS: The stomach of squirrel monkeys is simple and of non-compartmentalized type and the cecum does not have numerous folds, compared with other species. These characteristics are compatible with omnivorous simian species with no adaptive digestive specialization for the food fermentation process. Significant correlations were found between the weights of the carcass and GIT (p < .05); carcass and tongue (0.83; p < .01); and liver and right salivary gland (0.83; p < .01). It was also observed that the animals showed good body score conformation and GIT organs in good condition, which indicated that their nutritional management had been adequate. Regarding the correlations found among the organs: (i) squirrel monkeys with heavier carcasses had better-developed GIT with greater food storage capacity; (ii) the bigger the animal was, the greater its overall muscle development was, including that of the tongue, which would enable intensification of its feeding activity; and (iii) the measurements of the esophagus, small and large intestines, pancreas, and salivary glands were not sex-dependent in Saimiri sciureus. CONCLUSIONS: Previously cryopreserved carcasses of squirrel monkeys can be used for gastrointestinal system studies, with the potential to make clinical, zootechnical, management, and scientific contributions.

Best Fit Sphere Back and Adjusted Maximum Elevation of Corneal Back Surface as Novel Predictors of Keratoconus Progression.

Purpose: We evaluated the Maximum Elevation of Corneal Back Surface adjusted to the same Best Fit Sphere Back (BFSB) between timeline measurements (AdjEleBmax) and the BFSB radius (BFSBR) itself as new tomographic parameters for documentation of ectasia progression and compare them with the most recent and reliable parameters used on keratoconus (KC) progression. Results: We evaluated the performance and the ideal cutoff point of Kmax, D-index, posterior radius of curvature from the 3.0 mm centered on the thinnest point (PRC), EleBmax, BFSBR, and AdjEleBmax as isolated parameters to document KC progression (defined as a significant change in two or more variables), we found a sensitivity of 70%, 82%, 79%, 65%, 51%, and 63% and a specificity of 91%, 98%, 80%, 73%, 80%, and 84% to detect KC progression. The area under the curve (AUC) for each variable was 0.822, 0.927, 0.844, 0.690, 0.695, 0.754, respectively. Conclusion: AdjEleBmax presented a greater specificity, larger AUC, and better performance compared to EleBmax without any adjustment, with similar sensitivity. Although AdjEleBmax and BFSB demonstrated smaller AUC and specificities comparing with Kmax and D-Index, AdjEleBmax still presented a good performance with a reasonable AUC. Since the shape of the posterior surface, more aspheric and curved than the anterior, may facilitate detection of change, we suggest the inclusion of AdjEleBmax in the evaluation of KC progression in conjunction with other variables to increase the reliability of our clinical evaluation and early detection of progression.

Predicting retinal pigment epithelium remodelling and its functional impact.

PURPOSE: To identify predictive factors for RPE tear remodelling and its correlation with functional and morphological outcomes. METHODS: Retrospective longitudinal study of patients with retinal pigment epithelium (RPE) tears secondary to age-related macular degeneration (AMD). Imaging was performed using spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF). RPE layer integrity in the RPE-denuded area was examined with SD-OCT, and variation in the RPE-denuded homogeneous hypofluorescent area was examined with FAF over time for each case (eye). Patients were divided in two groups, according to the presence (Rem) or absence (No Rem) of evidence of RPE tear remodelling. Data were collected at three different time points: at baseline (at diagnosis of exudative AMD), at RPE tear diagnosis, and at the last available follow-up. Using SD-OCT, the following parameters were evaluated: type of CNV, type of PED and its dimensions, presence of subretinal (SRF) or intraretinal (IRF) fluid, central retinal thickness (CRT), presence and location of hyperreflective dots, and dimension and location of RPE tear. RESULTS: This study included 32 eyes from 31 patients (19 female and 12 male), with RPE tears secondary to AMD. RPE remodelling after tear development was evident in 17 (53.1%) eyes after 7 [1-59] months. Anatomical recovery was associated with a younger age at RPE tear diagnosis (73 ± 7 vs. 81 ± 7 years old, p=0.01), smaller and narrower retinal pigment epithelial detachment (PED) at tear diagnosis (height 369 vs. 602 µm, p=0.02; width 2379 vs. 3378 µm, p=0.04), and the presence of SRF at tear diagnosis (94% vs. 53%, p=0.02). After adjusting for other covariates, a younger age at RPE tear diagnosis maintained significant association with RPE tear remodelling. RPE tear remodelling did not correlate with a better visual outcome at last follow-up (43 ± 22.8 vs. 34 ± 23.8 ETDRS letters, p=0.30). Final VA was directly proportional to VA at tear diagnosis (r= 0.654; p<0.001) and correlated negatively with PED width at tear diagnosis (r = -0.388; p=0.03). CONCLUSION: RPE remodelling was evident in half of our sample and was associated with a younger age, smaller and narrower PED at RPE tear diagnosis, and presence of SRF also at tear diagnosis. Nevertheless, this structural recovery did not result in a better functional outcome.

Upper aerodigestive tract carcinoma: Development of a (epi)genomic predictive model for recurrence and metastasis.

Despite the increased molecular knowledge and the diagnostic and therapeutic improvements, the survival of patients with upper aerodigestive tract carcinoma remains poor. The identification of early diagnostic and prognostic biomarkers and the development of molecular models to distinguish patients that will recur and/or develop metastasis after treatment as well as to benefit with target therapies can be important to decrease mortality, improve survival rates and improve the quality of life of these patients. The current study analyzed 21 upper aerodigestive tract carcinomas through array comparative genomic hybridization and methylation-specific multiplex ligation-dependent probe amplification techniques. A number of chromosomal regions and genes were observed with copy number alterations and methylation. A predictive (epi)genomic model that comprises the 3p chromosomal region and WT1, VHL and THBS1 genes was built, highlighting a molecular signature with possible clinical use. The current study may aid in the development of a more individualized patient management and targeted drug design. The power of this genomic and epigenetic model to predict the recurrence and metastasis development should be evaluated and validated in future larger cohort study.

Role of real-time myocardial contrast echocardiography in the assessment of viability after acute myocardial infarction and angioplasty.

OBJECTIVE: To assess the role of myocardial contrast echocardiography (MCE) in early identification of myocardial viability in patients with residual segmental dysfunction after myocardial infarction and primary angioplasty (PA), in comparison with dobutamine stress echocardiography (DSE), using late functional recovery as gold standard. DESIGN: Prospective study for comparison of the two methods. SETTING: Hospital. PATIENTS: 17 patients (11 male, 53 +/- 11 years old) were consecutively included, with a first myocardial infarction and PA, with residual segmental akinesis or dyskinesis and good echocardiographic window. METHODS: All patients underwent: a) baseline echocardiographic study, MCE, and DSE obtained at 4.0 +/- 1.2 days after PA; b) late echocardiographic study performed at 4.4 +/- 0.8 months after PA. MCE was performed with Optison, administered as a slow infusion via a peripheral vein and a modality of real-time perfusion imaging with power pulse inversion and flash and subsequent data acquisition of triggered end-systolic images. Segmental contractility and perfusion were assessed using a 16-segment model. Perfusion assessment was qualitative (three perfusion patterns) and quantitative (ratio of maximal intensity between dysfunctional segments and contralateral normal segments). The viability criterion for MCE was defined as homogenous enhancement in 50% of wall thickness in each segment. The standard criterion for myocardial viability was defined as late functional recovery. 6. RESULTS: Viability was present in 56 (63.6%, Group 1) of dysfunctional segments and was absent in the remaining 32 (36.4%, Group 2). The sensitivity of DSE for viability was 80.0%, while specificity was 86.5%. The positive and negative predictive values were, respectively, 91.8% and 69.6%. MCE yielded a sensitivity of 96.5% and specificity of 78.1%, while positive and negative predictive values were respectively 86.2% and 94.1%. With the two methods together, the positive predictive value was 90.3% and negative was 80.0%. The intensity ratio was higher for viable segments (Group 1) in comparison with non-viable ones (Group 2; p<0.005). 7. CONCLUSIONS: This study showed a potentially valuable role for MCE in assessing viability in patients with myocardial infarction and PA. In comparison with DSE, MCE yielded a higher negative predictive value as well as a high positive predictive value. The use of both methods together is promising as a useful tool for early assessment of viability after primary angioplasty.