Estrogen contamination increases vulnerability of amphibians to the deadly chytrid fungus.

Aquatic contaminants and infectious diseases are among the major drivers of global amphibian declines. However, the interaction of these factors is poorly explored and could better explain the amphibian crisis. We exposed males and females of the Brazilian Cururu Toad, Rhinella icterica, to an environmentally relevant concentration of the estrogen 17-alpha-ethinylestradiol (an emerging contaminant) and to the chytrid infection (Batrachochytrium dendrobatidis), in their combined and isolated forms, and the ecotoxicity was determined by multiple biomarkers: cutaneous, hematological, cardiac, hepatic, and gonadal analysis. Our results showed that Cururu toads had many physiological alterations in response to the chytrid infection, including the appearance of cutaneous Langerhans's cells, increased blood leukocytes, increased heart contraction force and tachycardia, increased hepatic melanomacrophage cells, which in turn led to gonadal atrophy. The estrogen, in turn, increased the susceptibility of the toads to the chytrid infection (higher Bd loads) and maximized the deleterious effects of the pathogen: reducing leukocytes, decreasing the contraction force, and causing greater tachycardia, increasing hepatic melanomacrophage cells, and leading to greater gonadal atrophy, which were more extreme in females. The exposure to estrogen also revealed important toxicodynamic pathways of this toxicant, as shown by the immunosuppression of exposed animals, and the induction of the first stages of feminization in males, which corroborates that the synthetic estrogen acts as an endocrine disruptor. Such an intricate relationship is unprecedented and reinforces the importance of studying the serious consequences that multiple environmental stressors can cause to aquatic populations.

Legius Syndrome and Inflammatory Bowel Disease: A Pediatric Case Report.

Legius syndrome (LS) is a rare and underrecognized disorder that is often misdiagnosed as neurofibromatosis type 1 (NF1). It is characterized by café-au-lait macules without the tumoral manifestations of NF1. We report the case of an 11-year-old patient with multiple café-au-lait macules and intertriginous freckling who was admitted for bloody stools, joint pain, and weight loss. His clinical and endoscopic findings were consistent with inflammatory bowel disease (IBD). He also met the clinical diagnostic criteria for NF1 but not for LS. Genetic testing played a pivotal role in the differential diagnosis and revealed a loss-of-function mutation in the SPRED1 gene, confirming the diagnosis of LS. This is the first reported case of a patient with IBD and LS. The subtle manifestations of LS make it an underdiagnosed disease, which reduces the likelihood of it being diagnosed in association with other diseases, such as IBD. There are, however, 10 published case reports linking IBD and NF1, and some pathophysiological mechanisms have been proposed. Continued reporting will help clarify the relationship between IBD and RASopathies such as NF1 and LS.

Breaking Bad News in Obstetrics and Gynecology: We Must Talk About It / Más notícias em obstetrícia e ginecologia: Devemos falar sobre isso

Abstract Breaking bad news is common in obstetrics and gynecology (ob-gyn). However, it is difficult, and few doctors receive training on how to deal with this situation. This narrative review aims to gather, analyze, and synthesize part of the knowledge on the area, focused on Ob-Gyn. Among the 16 selected articles, two are randomized controlled intervention studies, and most studies refer to obstetrics. The results found by us pointed out that simulation, feedback/debriefing, lectures, and protocols could improve doctors' performance in communicating bad news. For patients, the context and how the information is transmitted seem to impact more than the content of the news. Ob-Gyn doctors could benefit from specific protocols and education, given the specialty's particularities. There is a lack of evidence about the most effective way to conduct such training. Finding validated ways to quantify and classify studies' results in the area, which would allow for the objective analysis of outcomes, is one of the biggest challenges concerning this topic.

Resumo Dar más notícias é comum em obstetrícia e ginecologia. Porém, é difícil e poucos médicos recebem treinamento sobre como lidar com essa situação. Esta revisão narrativa tem como objetivo reunir, analisar e sintetizar parte do conhecimento sobre a área, com foco na obstetrícia. Dentre os 16 artigos selecionados, dois são estudos de intervenção randomizados e controlados, e a maioria dos estudos refere-se à obstetrícia. Os resultados encontrados ressaltaram que simulação, feedback/entrevistas, palestras e protocolos podem melhorar o desempenho dos médicos na comunicação de más notícias. Para os pacientes, o contexto e como as informações são transmitidas parecem ter maior impacto do que o conteúdo das notícias. Os obstetras e ginecologistas poderiam se beneficiar de cursos e protocolos específicos, dadas as particularidades da especialidade. Faltam evidências sobre a forma mais eficaz de realizar esse treinamento. Encontrar formas validadas de quantificar e classificar os resultados dos estudos na área, permitindo uma análise objetiva dos resultados, é um dos maiores desafios neste tema.

Prosocial Tendencies Measure Validation for Portuguese Late Adolescents

O Questionário de Tendências Prossociais (MTP) de Carlo e Randall (2002) é amplamente usado para avaliar tendências prossociais. Partindo do pressuposto de que existem diferenças no comportamento pró-social entre adolescentes e adultos, o presente estudo teve como objetivo validar a versão em português do MTP com uma amostra de adolescentes. Este instrumento avalia seis tipos diferentes de tendências prossociais: altruísta, anónima, emergência, emocional, complacente e pública. Desenhado para confirmar esta estrutura fatorial do MTP com adolescentes portugueses, este estudo recolheu as perceções de um total de 1313 adolescentes a frequentar o ensino secundário. A análise fatorial confirmatória corroborou a estrutura de seis fatores da validação original. Além disso, considerando o ano escolar e o género dos alunos, a análise de invariância foi executada e atestou a invariância configural, métrica (parcialmente para género) e escalar (parcialmente para ano escolar e género) do MTP. Estes resultados demonstram ainda que a versão portuguesa MTP é confiável, aumentando a utilidade deste instrumento para avaliar comportamentos prossociais na adolescência.

The Prosocial Tendencies Measure (PTM; Carlo & Randall, 2002) is widely used for assessing prosocial tendencies. Assuming that there are differences in prosocial behavior between adolescents and adults, the current study aimed to further validate the Portuguese version of the PTM for adolescents. This instrument assesses six different types of prosocial tendencies ­ altruism, anonymous, dire, emotional, compliant and public. Designed to confirm this structure with Portuguese adolescents, this study collected a total of 1313 high school students' prosocial behaviors perceptions. Confirmatory factor analysis corroborated the six-factor structure of the original validation. Furthermore, considering the students' school year and gender, invariance analysis was executed and attested the PTM's configural, metric (partially for gender) and scalar (partially for school year and gender) invariance. These findings further demonstrate that the Portuguese version of the PTM is reliable, enhancing the utility of this instrument to assess prosocial behaviors in adolescence.

Studying the relationships between authentic leadership, structural empowerment, and civility in the palliative care sector in Portugal.

PURPOSE: This paper aims to propose a model studying the relationship of authentic leadership (AL), structural empowerment (SE) and civility in the palliative care sector. This model proposes SE as a mediator between AL and civility. DESIGN/METHODOLOGY/APPROACH: Data was collected from 213 employees working in five major public palliative care hospitals in central Portugal. The study sample was predominantly female (80.3%) and the response rate was 42.6%. Variables were measured using the Authentic Leadership Inventory, Workplace Civility Scale and Conditions of Work Effectiveness Questionnaire II scales. Hayes' PROCESS macro for mediation analysis in SPSS was used to test the hypothesized model. FINDINGS: Results suggest that AL has a significant positive direct relationship with both SE and civility. Furthermore, SE demonstrated to play a partial mediation effect between AL and civility. PRACTICAL IMPLICATIONS: This study may be of use for healthcare administration encouraging the development of AL, suggesting that the more leaders are seen as authentic, the more employees will perceive they have access to workplace empowerment structures and a civil environment. ORIGINALITY/VALUE: Considering the mainstream literature in healthcare management, to the best of the authors' knowledge, this is the first study to date to integrate the relation of AL, SE and civility in the palliative care sector. Further, the research model has not previously been introduced when considering the mediating role structural empowerment can play between AL and civility.

Using social media to educate women and healthcare providers on endometriosis: preliminary results.

OBJECTIVE: This study aimed to evaluate the performance of our Facebook fan page and compare it to similar pages. METHODS: The authors reviewed page-specific metrics provided by Facebook, including number of fans, their age and sex, and country of origin; number of views, likes, and shares tied to our posts. A search for similar fan pages using keyword "endometriosis" found pages in Portuguese, English, and Spanish. They were analyzed for country of origin, authors, number of fans and posts, and were compared to our page. RESULTS: Our fan page went online on April 2016 and 127 posts have been published up to December 2017. Most of its 1746 fans (89% women; 11% men) were Brazilians (n=1677). Our audience comprised primarily women aged 25-34 (39%) and 35-44 (30%) years. The most viewed posts discussed thrombosis and oral contraceptives (n =11078); continuous use of oral contraceptives (n=6448); deep endometriosis (n=4425); intrauterine levonorgestrel system (n=4045); IVF and endometriosis (n=2885); and endometriosis and cancer (n=2431). Our search found 399 Facebook pages from 44 different countries. The United States (n=81), Brazil (n=49), and the United Kingdom (n=46) topped the list of countries hosting pages, while most of the fan pages were written in English. The majority of the pages were active and 20% claimed they were based on science. Physicians administered four of the 10 most popular pages. Page heterogeneity prevented comparisons between them. CONCLUSION: Men and women have visited our Facebook fan page to obtain information on endometriosis. The pages found in our search were exceedingly heterogeneous and were not compared. Developing pages with sound information is an important step toward educating individuals about endometriosis and helping them make informed choices on available treatments.

O que facilita e dificulta a aprendizagem? a perspetiva de adolescentes / ¿qué facilita y dificulta el aprendizaje? la perspectiva de los adolescentes / What makes learning easier and more difficult? the perspective of teenagers

RESUMO Este estudo qualitativo teve como objetivo analisar as perceções de alunos adolescentes acerca dos aspetos que facilitam e dificultam a sua aprendizagem. O conhecimento das perceções dos alunos sobre a sua aprendizagem permite melhorar a qualidade dos processos de ensino-aprendizagem. A partir de um guião semiestruturado, foram realizados cinco grupos focais, em cinco escolas privadas do Norte de Portugal, tendo participado 32 alunos selecionados aleatoriamente. Os participantes eram alunos do 3º ciclo do Ensino Básico (7º, 8º e 9º anos), com idades compreendidas entre os 12 e os 15 anos. A análise dos dados seguiu um processo semi-indutivo de codificação descritiva. Os resultados realçam o papel fundamental do professor na aprendizagem; a importância da ação vs passividade dos alunos na sala de aula; a relevância da dimensão emocional e relacional para o envolvimento do aluno; e a relevância das estratégias de autorregulação da aprendizagem. Como implicações sugere-se a concretização de ações junto de professores e alunos assente nos dados recolhidos e analisados, que sejam promotoras da metacognição de ambos.

RESUMEN Este estudio cualitativo tuvo como objetivo analizar las percepciones de alumnos adolescentes acerca de los aspectos que facilitan y dificultan su aprendizaje. El conocimiento de las percepciones de los alumnos sobre su aprendizaje permite mejorar la calidad de los procesos de enseñanza-aprendizaje. A partir de un guión semiestructurado, cinco discusiones en grupos focales se llevaron a cabo en cinco escuelas privadas en el Norte de Portugal, que han participado 32 estudiantes seleccionados aleatoriamente. Los participantes eran alumnos del 3º ciclo de la Enseñanza Básica (7º, 8º y 9º años), con edades comprendidas entre los 12 y los 15 años. El análisis de los datos siguió un proceso semi-inductivo de codificación descriptiva. Los resultados subrayan el papel fundamental del profesor para el aprendizaje; la importancia de la acción de los alumnos en el aula versus pasividad; la relevancia de la dimensión emocional y relacional para la participación del alumno y de las estrategias de autorregulación del aprendizaje. Como implicaciones se sugiere la concreción de acciones junto a profesores y alumnos acerca de los datos recogidos y analizados, que sean promotores de la metacognición de ambos.

ABSTRACT This qualitative study aimed to understand the perceptions of adolescent students about what facilitates and hinders their learning. The knowledge of students' perceptions about their learning allows to improve the quality of the learning processes quality. Five focus groups were conducted, with a semi-structured script, in five different private schools from the North of Portugal, having participated in 32 students randomly selected. Participants were students from 7th, 8th and 9th grades, with ages between 12 and 15 years old. The data analysis followed a semi-inductive process and descriptive coding of data. The results highlighted the key role of teachers in students' learning; the importance of students action versus passivity in the classroom; the relevance of emotional and relational dimension to enhance students' engagement, and the relevance of learning self-regulation strategies. As for implications, it is suggested that actions be carried out with teachers and students based on the data collected and analyzed, in order to promote metacognition of both.

Serological study on toxoplasmosis in the Haliti-Paresí community of the Utiariti indigenous territory, Campo Novo do Parecis, Mato Grosso, Brazil.

Toxoplasma gondii is the etiological agent of toxoplasmosis, a widespread zoonosis that affects several homeothermic animals, including humans. This disease causes serious health problems, such that 10% of infected individuals develop clinical manifestations. Some studies on indigenous human populations have indicated variations in seroprevalence from 10.6% to 80.4% in such populations in different regions of Brazil and in other countries like Venezuela and Malaysia. To date, there have been no studies regarding the prevalence of anti-T. gondii antibodies in Haliti-Paresí Indians living in Campo Novo do Parecis, Mato Grosso, Brazil. Our objective here was to determine the frequency of occurrence of antibodies against this protozoon in nine Haliti-Paresí villages by correlating seroprevalence with locations and variables. Serodiagnoses were made using the indirect immunofluorescence antibody test (IFAT) and enzyme-linked immunosorbent assay (ELISA) in the Laboratory for Toxoplasmosis and Other Protozoan Diseases of IOC/Fiocruz. It was considered that samples tested positive for T. gondii infection if IgG/IgM antibodies against this protozoon were detected through serodiagnosis using either IFAT or ELISA. Among the 293 samples analyzed, 66.9% presented anti-T. gondii IgG and 3.4% presented anti-T. gondii IgM. It was observed that there were no statistically significant differences in frequency of antibody occurrence among infected individuals, based on sex, schooling or occupation/activities. However, there were statistical differences based on age and villages. The prevalence observed in this study is in agreement with values found in other studies on indigenous populations in Latin America. Like among other such populations, the Haliti-Paresí villages are located close to forests and the individuals have domestic cats as pets, are involved in hunting and farming and consume water directly from water accumulation sources. These factors might cause exposure to T. gondii tissue cysts and oocysts.

Microaneurysm turnover is a predictor of diabetic retinopathy progression.

AIM: To analyse retinopathy phenotypes and microaneurysm (MA) turnover in mild non-proliferative diabetic retinopathy (NPDR) as predictors of progression to diabetic central-involved macular oedema (CIMO) in patients with type 2 diabetes mellitus (DM) in two different ethnic populations. METHODS: 205 patients with type 2 DM and mild NPDR were followed in a prospective observational study for 2 years or until development of CIMO, in two centres from different regions of the world. Ophthalmological examinations, including best-corrected visual acuity (BCVA), fundus photography with RetmarkerDR analysis, and optical coherence tomography (OCT), were performed at baseline and 6 12 and 24 months. RESULTS: 158 eyes/patients reached either the study endpoint, CIMO (24) or performed the last study visit (24-month visit) without developing CIMO (134). From the eyes/patients in analysis, 27 eyes (17.1%) progressed to more advanced ETDRS (Early Treatment Diabetic Retinopathy Study) levels: 6 progressed to mild NPDR (level 35), 15 progressed to moderate NPDR (level 43), 5 progressed to moderately severe NPDR (level 47) and 1 progressed to high risk PDR (level 71). Worsening in ETDRS level is associated with phenotype C (p=0.005). From the 130 eyes/patients with a low MA turnover, 18 (13.8%) eyes/patients had an increase in ETDRS level, and from the 19 eyes/patients with a high MA turnover, 9 (47.4%) had an increase in ETDRS level (p<0.001). CONCLUSION: Eyes in the initial stages of diabetic retinopathy show different phenotypes with different risks for progression to CIMO. In phenotype C, MA turnover correlates with ETDRS grading worsening and development of CIMO.

Adherence to a Mediterranean diet, lifestyle and age-related macular degeneration: the Coimbra Eye Study - report 3.

PURPOSE: To characterize the lifestyle and nutritional risk profile associated with the Mediterranean diet in a Portuguese population with and without age-related macular degeneration (AMD). METHODS: Nested case-control study (n = 883) within the Coimbra Eye Study, including 434 subjects with AMD and 449 age- and sex-matched subjects without AMD. All enrolled subjects underwent a full risk assessment, including lifestyle-related risk factors and a thorough food frequency questionnaire. This allowed us to build an adherence score to the Mediterranean diet (mediSCORE, range 0-9) constructed from individual food intakes. Food intake was also further analysed by conversion to micronutrient consumption. RESULTS: Our results suggest that physical activity has a protective role in AMD [p = 0.018 after multivariate adjustment, OR: 0.69 (0.51-0.93)]. High (mediSCORE ≥6) was also found to be protective [p = 0.041, OR: 0.62 (95% CI: 0.38-0.97)]. Food group analysis unveiled a specific protective role for increased fruits consumption (p = 0.029). Finally, micronutrient analysis revealed a protective role associated with increased consumption of caffeine, fibres, beta-carotene, vitamin C and vitamin E (p < 0.05). CONCLUSION: High mediSCORE appears to confer protection against the development of AMD in a Mediterranean population. This effect is driven by increased consumption of fruits and some antioxidant micronutrients, which emerged as statistically significant protective factors. Further studies are required to establish dietary recommendations with clinical application.

Adherence to a Mediterranean diet and its association with age-related macular degeneration. The Coimbra Eye Study-Report 4.

OBJECTIVES: This study aimed to characterize the association of lifestyle and nutritional risk profiles with age-related macular degeneration (AMD) in two subpopulations with differing AMD prevalence. METHODS: This case-control study (n = 1992) included 768 patients with AMD and 1224 age- and sex-matched participants without AMD with a single visit at a primary health care unit. Enrolled participants completed a validated lifestyle and food frequency questionnaire. A score to measure adherence to the Mediterranean diet (mediSCORE; Range, 0-9) was constructed from individual food intakes, which were further analyzed by conversion to nutrient consumption. RESULTS: Higher adherence to the Mediterranean diet (mediSCORE ≥6) was significantly associated with no AMD (odds ratio [OR] = 0.73; P = 0.009). The subpopulation with lower AMD prevalence presented significantly higher adherence to the Mediterranean diet in relation to all individual food groups that comprised the mediSCORE (P < 0.014) with the exception of cereals. Food group analysis showed significant associations between the increased consumption of vegetables (OR = 0.63; P < 0.001) and fruit and nuts (OR = 0.78; P = 0.010) with no AMD. Nutrient analysis revealed that an increased ingestion of water, fibers, total fat, monounsaturated and polyunsaturated fatty acids, linoleic acid, vitamins A and C, carotene, alpha-tocopherol, folate, magnesium, iron, and zinc were significantly associated with no AMD (P < 0.0013). Finally, regular physical activity was associated with no AMD (P = 0.003). CONCLUSIONS: High adherence to a Mediterranean diet and regular physical activity seem to be protective factors for AMD in a Portuguese population. The effect of the diet is likely driven by the increased consumption of vegetables, fruits, and nuts.

Subclinical Macular Edema as a Predictor of Progression to Central-Involved Macular Edema in Type 2 Diabetes.

PURPOSE: The aim of this study was to examine the relationship between subclinical diabetic macular edema (SCME) and the development of central-involved macular edema (CIME) in patients with diabetes mellitus type-2 and mild nonproliferative diabetic retinopathy (NPDR), from 2 populations of different ethnicities. METHODS: Two hundred and five patients with diabetes mellitus type-2 and mild NPDR with no prior laser or intravitreal treatment were followed for 2 years or until the development of CIME. Ophthalmological examinations, including BCVA, fundus photography with RetmarkerDR analysis, and optical coherence tomography were performed at baseline and months 6, 12, and 24. RESULTS: One hundred and fifty eight eyes/patients reached either the study endpoint, CIME (n = 24), or performed the 24-month visit without developing CIME (n = 134). Fifty eyes/patients had SCME at baseline (31.6%). Of these 50 eyes, 16 (32.0%) developed CIME, whereas of the 108 eyes with normal retinal thickness (RT) at baseline, only 8 (7.4%) developed CIME (p < 0.001). Patients with increased RT in the central subfield at baseline showed a 12-fold risk of progression to CIME compared with patients without SCME. CONCLUSIONS: In patients with mild NPDR, the presence of SCME is a good predictor of progression to CIME.

Características clínicas, funcionais e sobrevida dos pacientes com pneumonia de hipersensibilidade do Ambulatório de Doenças Pulmonares Intersticiais do Hospital das Clinicas da Universidade Federal de Minas Gerais (HC-UFMG) / Clinical, functional and survival in patients with hypersensitivity pneumonia Center of Pulmonary Interstitial Disease of Hospital das Clínicas da Universidade Federal de Minas Gerais (HC- UFMG)

A pneumonia de hipersensibilidade (PH) constitui síndrome inflamatória causada pela resposta imune exagerada a partículas antigênicas inaladas. Objetivo: descrever características clínicas, radiológicas, funcionais esobrevida de pacientes com PH. Metodologia: estudo retrospectivo, envolvendo pacientes em acompanhamento no ambulatório de doenças pulmonares intersticiais do HC-UFMG no período de 2011 a 2015. Analisados dados clínicos, radiológicos, funcionais e morfológicos coletados através de um protocolo padronizado. Resultados: Dentre 139 pacientes com doenças intersticiais pulmonares, 34 (24%) tinham PH, com idade de 60,7 ± 18,1 anos. Exposição a mofo foi a etiologia mais frequente (19;55%). A forma crônica foi predominante (100% doas casos), assim como a presença de padrão reticular na tomografia de tórax (100%), com ou sem faveolamento. Observou-se distúrbio restritivo leve (CVF=69,00 ± 17,62L) associado a redução moderada da difusão de monóxido de carbono (59,20 ± 16,99%). O lavado broncoalveolar não auxiliou no diagnóstico e a biópsia transbrônquica foi diagnóstica em 5 (55%) casos e a biópsia cirúrgica foi conclusiva em 6 (85,7%). A sobrevida mediana foi de 75 meses. Conclusão: Nesta amostra de um ambulatório de referência, a PH respondeu por cerca de um quarto dos pacientes com doença intersticial pulmonar. A exposição a mofo foi a principal etiologia e a mortalidade significativa, o que reforça a importância da adoção de medidas preventivas através do reconhecimento precoce da exposição aos fatores de risco. (AU)

Hypersensitivity pneumonitis (HP) inflammatory is a syndrome caused by an excessive immune response to inhaled antigen particles. Objective:To describe clinical, radiological and functional characteristics and survival in patients with HP. Methodology: Retrospective study involving patients followed up at the pulmonary interstitial diseases clinic of the HC-UFMG from 2011 to 2015. Clinical, radiological, functional and morphological data were analysed from a standardized protocol. Results: Among 139 patients with interstitial lung disease, 34 (24%) had HP, aged 60.7 ± 18.1 years. Mold exposure was the most frequent cause (19; 55%). The chronic form predominated (100% donate cases), as well as the presence of reticular pattern on the chest tomography (100%), with or without honeycombing. There was mild restrictive lung disease (FVC = 69.00 ± 17,62L) associated with moderate reduction in carbon monoxide diffusion (59.20 ± 16.99%). Bronchoalveolar lavage did not help in the diagnosis and transbronchial biopsy was diagnostic in 5 (55%) cases; surgical biopsy was conclusive in 6 (85.7%). Median survival was 60 months. Conclusion: In this sample of a reference clinic, HP accounted for about a quarter of the patients with interstitial lung disease. The mold exposure was the main etiology and the mortality rate was significant, what reinforces the importance of adopting preventive measures through early recognition of exposure to risk factors. (AU)

Different Phenotypes of Mild Nonproliferative Diabetic Retinopathy with Different Risks for Development of Macular Edema (C-TRACER Study).

PURPOSE: To evaluate diabetic retinopathy (DR) progression in patients with diabetes mellitus type 2 in 2 populations of different ethnicity. METHODS: A prospective observational study was designed to follow eyes/patients with mild nonproliferative DR, for 2 years or until the development of central-involved macular edema (CIME), in 2 centers from different regions of the world. A total of 205 eyes/patients fulfilled the inclusion/exclusion criteria and were included in this study. Ophthalmological examinations, fundus photography with RetmarkerDR analysis, and optical coherence tomography were performed at baseline and at 6, 12 and 24 months. RESULTS: Of the 158 eyes/patients that completed this study, 24 eyes developed CIME and 134 eyes were present at the last study visit. Eighty-eight eyes (56.4%) were classified as phenotype A, 49 (31.4%) as phenotype B, and 19 (12.2%) as phenotype C. Phenotype A is associated with a very low risk for development of CIME in comparison with phenotypes B and C. The OR for development of CIME was 19.0 for phenotype B and 25.1 for phenotype C. CONCLUSION: Eyes in the initial stages of DR show different phenotypes with different risks of progression to ME. The phenotypes associated with increased risks of progression show different distributions in patients of different ethnicities.

Diabetic Retinopathy Phenotypes of Progression to Macular Edema: Pooled Analysis From Independent Longitudinal Studies of up to 2 Years' Duration.

Purpose: To test the risk of progression to macular edema (ME) of different phenotypes of mild nonproliferative diabetic retinopathy (NPDR). Methods: Data from 882 patients with mild NPDR, Early Treatment Diabetic Retinopathy Study grades 20 and 35, with no prior laser treatment, enrolled in four separate longitudinal studies during 2007-2015 using the same reading center and with the same inclusion criteria and were pooled for analysis. One eye per patient was followed for up to 2 years until development of ME. Ophthalmological examinations included best corrected visual acuity, color fundus photography (CFP), and optical coherence tomography (OCT). They were performed at baseline and 6 months, with the last visit at 12 or 24 months, depending on the study. The eyes/patients were classified as belonging to phenotypes A, B, and C on the basis of OCT central subfield thickness and microaneurysm activity. Results: A total of 882 eyes/patients performed the 12- or 24-month visit or developed ME. Of these 882 eyes/patients that completed the studies, 103 developed ME, 14 from phenotype A (14 of 466: 3.0%), 48 from phenotype B (48 of 164: 18.6%), and 41 from phenotype C (41 of 252: 16.3%). Eyes/patients from phenotypes B and C showed much higher risks for ME development compared with phenotype A: odds ratio (OR) 95% confidence interval (CI): 13.30 (7.09-24.97) P < 0.001; OR (CI): 6.32 (3.36-11.90) P < 0.001, respectively. Conclusions: NPDR phenotypes based on microaneurysm turnover and central macular thickness OCT at the 6-month visit using CFP and OCT, both noninvasive examinations, identified the eyes at increased risk of developing ME.

OCT-Leakage: A New Method to Identify and Locate Abnormal Fluid Accumulation in Diabetic Retinal Edema.

Purpose: To identify retinal extracellular fluid changes and their correlation with increased retinal thickness (RT) in eyes with subclinical and clinical macular edema in diabetes type 2. Methods: A cohort of 48 eyes from 48 type 2 diabetic patients with mild or moderate nonproliferative diabetic retinopathy (Early Treatment Diabetic Retinopathy Study levels 20/35) were classified as having normal RT (10), subclinical macular edema (30), or clinical macular edema (8). They were examined with Cirrus spectral-domain optical coherence tomography (OCT) at baseline visits (ClinicalTrials.gov number, NCT01145599) in the Coimbra center. Results from automated analysis of the retinal extracellular space, using our OCT-Leakage algorithm to identify sites of low optical reflectivity, were compared with those from a control group of 25 healthy eyes. Results: The highest increases in RT in the eyes with subclinical and clinical macular edema were found in the inner nuclear layer (INL). These increases were, on average, 49.9% in subclinical macular edema and 104.7% in clinical macular edema. Extracellular space increases in the INL that were identified with the OCT-Leakage algorithm showed a strong positive correlation with the increases in RT in the central subfield (r = 0.71, P < 0.001). Conclusions: Increases in number of sites with lower optical reflectivity positively correlate with the increase in RT in the initial stages of macular edema in diabetes type 2. Diabetic macular edema is represented mainly by extracellular fluid accumulation that preferentially involves the INL of the retina.

Age-related macular degeneration in Portugal: prevalence and risk factors in a coastal and an inland town. The Coimbra Eye Study - Report 2.

PURPOSE: To determine the age- and sex-specific prevalence of early and late age-related macular degeneration (AMD) in two Portuguese population-based samples and to identify its risk factors. POPULATION: A population of 6023 adults aged ≥55 years was recruited from two Portuguese primary healthcare units in the central region of Portugal - one from a coastal (n = 3000) and another from an inland town (n = 3023). METHODS: Cross-sectional population-based study. Participants were enrolled in the two locations between August 2009 and October 2013. Responders underwent standardized interviews and ophthalmologic examination, including digital fundus imaging. All fundus photographs were graded according to an International Classification and Grading System. The main outcome measures consisted of age- and sex-adjusted prevalence of early and late AMD. Potential epidemiologic risk factors were also evaluated using logistic regression analysis. RESULTS: Of the 6023 subjects enrolled, 5996 had gradable fundus images and were included in the analysis. The crude prevalence of early and late AMD was 6.99 and 0.67%, respectively, for the coastal town and 15.39 and 1.29% for the inland town. Age- and sex-adjusted prevalence of any AMD for the Portuguese population was 12.48% (95% CI: 11.61-13.33) with late AMD accounting for 1.16% (95% CI: 0.85-1.46). Neovascular AMD (NV-AMD) and geographic atrophy (GA) accounted for 0.55% (95% CI: 0.36-0.75) and 0.61% (95% CI: 0.37-0.84) of individuals, respectively. After adjusting for possible confounding factors, prevalence of early and late AMD increased with increasing age (OR = 1.35; 95% CI: 1.23-1.49 for early and OR = 3.01; 95% CI: 2.22-4.08 for late AMD, per each decade of age increase, p < 0.001). After adjustment for age, sex, family history, smoking history, hypertension, diabetes and BMI, subjects from the inland town presented a significantly higher OR of early and late AMD than subjects from the coastal town (OR = 2.57, 95% CI: 2.12-3.12, p < 0.001 for early and OR = 2.06, 95% CI: 1.07-3.95, p = 0.029 for late AMD). CONCLUSIONS: The prevalence of early and late AMD in this Portuguese population was similar to other large-scale population-based cohorts. After controlling for confounders, age and study site of inclusion were significant independent predictors for both early and late forms of the disease. Further analysis will be needed to completely unravel the underlying reasons for this difference regarding geographic location.

Relevance of Retinal Thickness Changes in the OCT Inner and Outer Rings to Predict Progression to Clinical Macular Edema: An Attempt of Composite Grading of Macular Edema.

PURPOSE: To characterize the relevance of macular thickness changes in the inner and outer rings in the progression of macular edema in eyes/patients with diabetes type 2. METHODS: A total of 374 type 2 diabetic patients with mild nonproliferative diabetic retinopathy (ETDRS levels 20-35) were included in a 12-month prospective observational study to identify retinopathy progression. Retinal thickness analyses were performed in 194 eyes/patients using Cirrus SD- OCT and 166 eyes/patients using Spectralis SD-OCT. The DRCR.net classification of subclinical and clinical macular edema was used. A composite grading of macular edema is proposed in this study. RESULTS: A total of 317 eyes/patients completed the study. SD-OCT identified clinical macular edema in 24 eyes/patients (6.7%) and subclinical macular edema in 104 eyes/patients (28.9%) at baseline. Increased thickness of the central subfield is the best predictor for the development of clinical macular edema, with 85.7% sensitivity and 71.9% specificity (OR: 2.57, 95% CI: 0.82-7.99). However, the involvement of the inner and outer rings is a cumulative predictor of progression to clinical macular edema (OR: 8.69, 95% CI: 2.85-26.52). CONCLUSIONS: A composite OCT grading of macular edema taking into account the retinal thickness changes in the inner and outer macular rings offers a simple way to characterize macular edema, with added clinical value.

Retinal layer location of increased retinal thickness in eyes with subclinical and clinical macular edema in diabetes type 2.

PURPOSE: To identify the retinal layer predominantly affected in eyes with subclinical and clinical macular edema in diabetes type 2. METHODS: A cohort of 194 type 2 diabetic eyes/patients with mild nonproliferative diabetic retinopathy (ETDRS levels 20/35) were examined with Cirrus spectral-domain optical coherence tomography (OCT) at the baseline visit (ClinicalTrials.gov identifier: NCT01145599). Automated segmentation of the retinal layers of the eyes with subclinical and clinical macular edema was compared with a sample of 31 eyes from diabetic patients with normal OCT and an age-matched control group of 58 healthy eyes. RESULTS: From the 194 eyes in the study, 62 had subclinical macular edema and 12 had clinical macular edema. The highest increases in retinal thickness (RT) were found in the inner nuclear layer (INL; 33.6% in subclinical macular edema and 81.8% in clinical macular edema). Increases were also found in the neighboring layers. Thinning of the retina was registered in the retinal nerve fiber, ganglion cells and inner plexiform layers in the diabetic eyes without macular edema. CONCLUSIONS: The increase in RT occurring in diabetic eyes with macular edema is predominantly located in the INL but extends to neighboring retinal layers indicating that it may be due to extracellular fluid accumulation.

One-year progression of diabetic subclinical macular edema in eyes with mild nonproliferative diabetic retinopathy: location of the increase in retinal thickness.

PURPOSE: To characterize the 1-year progression of retinal thickness (RT) increase occurring in eyes with subclinical macular edema in type 2 diabetes. METHODS: Forty-eight type 2 diabetic eyes/patients with mild nonproliferative diabetic retinopathy (NPDR; levels 20 and 35 in the Early Treatment Diabetic Retinopathy Study) classified as presenting subclinical macular edema at baseline completed the 1-year follow-up period, from a sample of 194 followed in a 12-month observational and prospective study (ClinicalTrials.gov identifier: NCT01145599). Automated segmentation of the retinal layers in these eyes was performed, followed by verification and correction by a human grader. RESULTS: The highest increase in RT over the 1-year follow-up period for the 48 eyes/patients with subclinical macular edema was found in the inner nuclear layer (INL). Progression to clinical macular edema was also associated with increased thickening of other retinal layers aside from the INL. The microvascular disease activity shown by microaneurysm (MA) turnover ≥6 was associated with progression from subclinical to clinical macular edema. CONCLUSIONS: Increases in RT occurring over a period of 1 year in diabetic eyes with mild NPDR and subclinical macular edema occur mainly in the INL. The development of clinical macular edema appears to be associated with increased thickening of other retinal layers and microvascular disease activity.