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Characterization of 2-year progression of different risk phenotypes in eyes with mild and moderate nonproliferative diabetic retinopathy (NPDR) in type 2 diabetes (T2D). A 2-year prospective longitudinal cohort study (CORDIS, NCT03696810) was conducted. Ophthalmological examinations were performed including best corrected visual acuity, color fundus photography and optical coherence tomography (OCT and OCTA). OCT metrics, central retinal thickness and ganglion cell layer + inner plexiform layer (GCL + IPL) thickness were analyzed. OCTA metrics, vessel density (VD), perfusion density (PD) and area of intercapillary spaces (AIS) were obtained from superficial and deep capillary plexus (SCP, DCP). Only phenotype C identified by decreased VD ≥ 2 SD of healthy controls and phenotype B identified by subclinical macular edema with decreased VD

INTRODUCTION: Age-related macular degeneration is a degenerative disease of the macula responsible for severe vision loss. It is a multifactorial and complex disease, with genet- ics, lifestyle and environmental factors contributing for its establishment and progression. The adherence to the Mediterranean diet has been suggestive of being protective for disease, but the evidence on the interaction between diet and genetics is scarce. With this work, we intend to assess the effect of the adherence to the Mediterranean diet on age-related macular degeneration stratified by the genetic risk score, in a well-characterized Por- tuguese population. METHODS: Participants performed ophthalmological exams and answered a validated food and a lifestyle questionnaire. The adherence to the Mediterranean diet was assessed with mediSCORE, a score ranging from 0 (low adherence) to 9 (high adherence). The score was de- termined individually for each participant, as the sum of the score of 9 food groups in which the food items from questionnaire were organized. A cut-off value of ≥ 6 was used as high adherence. Grading was performed using Rotterdam Classification. Participants’ genotyping was performed in collaboration with The European Eye Epidemiology Consortium. The Genetic Risk Score was calculated for each participant considering the number of alleles at each variant and their effect size. Odds ratio (OR) for the adherence to the Mediterranean diet within strata of high and low genetic risk score were calculated, adjusted for age, sex, physical exercise, and smoking. RESULTS: People at high genetic risk for age-related macular degeneration benefited from adhering to the Mediterranean diet with a 60%-risk reduction (OR=0.386, 95%CI 0.182-0.821, p=0.013). For subjects with low genetic risk (OR=0.435, 95% CI 0.177-1.072, p=0.070), a risk reduc- tion was also seen, but not significantly. In subjects with a high genetic risk, age increased the risk of having AMD in a 2- and 3 time-fold, for ages 70-75 (p=0.034) and over 75 (p, INTRODUÇÃO: A degenerescência macular da idade (DMI) é uma doença degenerativa da mácula, responsável por perda de visão grave. Factores genéticos e ambientais podem contribuir para a doença. Alguns estudos já sugeriram que a dieta mediterrância pode ser protectora da do- ença, mas o estudo da interacção entre a dieta e a genética é limitado. O nosso objetivo foi avaliar o efeito da adesão à dieta mediterrânica na DMI, estratificado por risco genético para a doença, numa população portuguesa bem caracterizada. MÉTODOS: Os participantes fizeram exames oftalmológicos e responderam a questionários de frequência alimentar e de estilo de vida. A adesão à dieta mediterrânica foi medida com o me- diSCORE, que varia entre 0 (baixa adesão) e 9 (alta adesão). O valor total do mediSCORE foi calcu- lado individualmente, como a soma dos valores dos 9 grupos alimentares nos quais os alimentos do questionário foram organizados. Um valor de cut-off ≥6 foi utilizado para determinar adesão alta. A classificação das imagens foi feita com a Classificação de Roterdão. A análise genética foi realizada em colaboração com The European Eye Epidemiology Consortium. O risco genético foi calculado com um score, individualmente, considerando o número de alelos de cada variante e o seu tamanho de efeito. Foram calculados os odds ratio (OR) para a desão à dieta mediterrância estratificados por risco genético, ajustados à idade, sexo, exercício físico e hábitos tabágicos. RESULTADOS: Os participantes com alto risco genético para a DMI beneficiaram da alta adesão à dieta mediterrânica, com uma redução de cerca de 60% no risco (OR=0,386, 95%CI 0,182- 0,821, p=0,013). Os participantes com baixo risco genético apresentaram uma redução no risco, mas não estatisticamente significativa (OR=0,435, 95% CI 0,177-1,072, p=0,070). Nos participantes com alto risco genético, a idade aumentou o risco de DMI em 2 a 3 vezes, nos intervalos 70-75 anos (p=0,034) e >75 anos (p

The aim of the study was to characterize the 2-year progression of risk phenotypes of nonproliferative diabetic retinopathy (NPDR) in type 2 diabetes (T2D) phenotype C, or ischemic phenotype, identified by decreased skeletonized retinal vessel density (VD), ≥2 SD over normal values, and phenotype B, or edema phenotype, identified by increased retinal thickness, i.e., subclinical macular edema, and no significant decrease in VD. A prospective longitudinal cohort study (CORDIS, NCT03696810) was conducted with 4 visits (baseline, 6 months, 1 year, and 2 years). Ophthalmological examinations included best-corrected visual acuity, color fundus photography (CFP), and optical coherence tomography (OCT) and OCT angiography. Early Treatment Diabetic Retinopathy Study grading was performed at the baseline and last visits based on 7-field CFP. Results: One hundred and twenty-two eyes from T2D individuals with NPDR fitted in the categories of phenotypes B and C and completed the 2-year follow-up. Sixty-five (53%) of the eyes were classified as phenotype B and 57 (47%) eyes as phenotype C. Neurodegeneration represented by thinning of the ganglion cell layer and inner plexiform layer was present in both phenotypes and showed significant progression over the 2-year period (p < 0.001). In phenotype C, significant progression in the 2-year period was identified in decreased skeletonized VD (p = 0.01), whereas in phenotype B microvascular changes involved preferentially decrease in perfusion density (PD, p = 0.012). Phenotype B with changes in VD and PD (flow) and preferential involvement of the deep capillary plexus (p < 0.001) is associated with development of center-involved macular edema. In the 2-year period of follow-up, both phenotypes B and C showed progression in retinal neurodegeneration, with changes at the microvascular level characterized by decreases in PD in phenotype B and decreases in VD in phenotype C.

Introduction: To date several genetic variants are known to play an important role in age-related macular degeneration(AMD). Variations in the genetic pool of different populations impact the disease prevalence, incidence and risk of progression. This report aims to determine the genetic contribution in the development of AMD in a Portuguese population from the Coimbra Eye Study (CES,NCT01298674,NCT02748824), and to determine the genetic risk score(GRS). Methods: Participants in the CES underwent ophthalmologic examination and imaging in baseline and 6.5-year follow-up visits. AMD staging was performed in a centralized reading center. Two genetic analyses were performed, a case-control analysis and a progression to AMD analysis. Genomic DNA was isolated from blood samples collected in the follow-up visit. Genetic sequencing was performed using the EYERISK assay under the European Eye Epidemiology Consortium (E3). Sixty-nine single nucleotide polymorphisms (SNPs) were genotyped and tested for association under an additive model with presence/absence of AMD in the follow-up visit, and with progression/no progression in the longitudinal analysis. Logistic regression analysis was performed to assess allelic odds ratio at 95% CI for each variant, adjusted for age and sex. GRS were calculated for AMD cases/controls and progressors/non-progressors. Results: In case-control analysis samples from 237 patients and 640 controls were included. The SNPs associated to increased risk of AMD were: ARMS2 rs10490924, ARMS2/HTRA1 rs3750846,CFH rs35292876,SLC16A8 rs8135665,TGFBR1 rs1626340. The SNPs with protective effect were: CFH rs10922109, CFH rs1410996,C2/CFB/SKIV2L rs429608,CETP rs5817082,CNN2 rs10422209,CFB rs641153 and RDBP_CFB rs760070. In progression to AMD analysis (630 non-progressors and 137 progressors), identified risk-variants for progression were: ARMS2 rs10490924, ARMS2/HTRA1 rs3750846,CFH rs35292876; and protective variants were C2_CFB_SKIV2L rs429608,CFH rs10922109,CFH rs1410996,CNN2 rs10422209,CFHR5 rs10922153,SYN3/TIMP3 rs5754227,COL10A1 rs3812111. The GRS for AMD cases and controls was 1.12±1.19 and 0.65±1.12 (p, Introdução: Vários single nucleotide polymorphisms (SNPs) foram já identificados em associação à degenerescência macular da idade (DMI). Variações no pool genético afetam a prevalência, incidência e risco de progressão da doença em diferentes populações. Este estudo tem como objetivo caracterizar as associações genéticas na DMI numa população portuguesa do estudo epidemiológico Coimbra Eye Study (CES,NCT01298674,NCT02748824) e determinar o genetic risk score (GRS). Métodos: Os participantes foram submetidos a exame oftalmológico e imagiologia na visita inicial do CES e na dos 6,5 anos de seguimento. O estadiamento da DMI foi realizado num centro de leitura centralizado. Procedemos a duas análises genéticas: uma de caso-controlo e uma longitudinal de progressão para DMI. O DNA genómico foi isolado de amostras de sangue e o sequenciamento genético foi realizado usando o EYERISK-assay do European Eye Epidemiology Consortium (E3). Sessenta e nove SNPs foram genotipados e testados para associação com presença/ausência de DMI na coorte da visita final, e com progressores/não-progressores na análise longitudinal. Usámos regressão logística para avaliar a odds ratio alélica com IC a 95% para cada variante, ajustada ao sexo e idade. Os GRS foram calculados para casos/controlos e progressores/não-progressores. Resultados: Na análise caso-controlo foram incluídas amostras de 237 doentes e 640 controlos. Os SNPs associados a risco aumentado de DMI foram: ARMS2 rs10490924,ARMS2/HTRA1 rs3750846,CFH rs35292876,SLC16A8 rs8135665,TGFBR1 rs1626340. Os SNPs com efeito protetor foram: CFH rs10922109,CFH rs1410996,C2 / CFB / SKIV2L rs429608,CETP rs5817082,CNN2 rs10422209,CFB rs641153 e RDBP_CFB rs760070. Na análise de progressão para DMI (630 não-progressores e 137 progressores), as variantes de risco identificadas foram: ARMS2 rs10490924,ARMS2/HTRA1 rs3750846,CFH rs35292876; e as variantes protetoras foram C2_CFB_SKIV2L rs429608,CFH rs10922109,CFH rs1410996,CNN2 rs10422209,CFHR5 rs10922153,SYN3/TIMP3 rs5754227, COL10A1 rs3812111. O GRS de casos e controlos foi 1,12±1,19 e 0,65±1,12 (p