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- Optical coherence tomography angiography metrics Monitor severity progression of diabetic retinopathy—3-year longitudinal studyPublication . Marques, Inês P.; Kubach, Sophie; Santos, Torcato; Mendes, Luís; Madeira, Maria H.; Sisternes, Luis de; Tavares, Diana; Santos, Ana Rita; Lewis, Warren; Lobo, Conceição; Durbin, Mary K.; Cunha-Vaz, JoséTo examine retinal vessel closure metrics and neurodegenerative changes occurring in the initial stages of nonproliferative diabetic retinopathy (NPDR) and severity progression in a three-year period. Three-year prospective longitudinal observational cohort of individuals with type 2 diabetes (T2D), one eye per person, using spectral domain-optical coherence tomography (SD-OCT) and OCT-Angiography (OCTA). Eyes were examined four times with one-year intervals. OCTA vessel density maps of the retina were used to quantify vessel closure. Thickness of the ganglion cell + inner plexiform layer (GCL + IPL) was examined to identify retinal neurodegenerative changes. Diabetic retinopathy ETDRS classification was performed using the seven-field ETDRS protocol. A total of 78 eyes/patients, aged 52 to 80 years, with T2D and ETDRS grades from 10 to 47 were followed for 3 years with annual examinations. A progressive increase in retinal vessel closure was observed. Vessel density (VD) showed higher decreases with retinopathy worsening demonstrated by step-changes in ETDRS severity scale (p < 0.001). No clear correlation was observed between neurodegenerative changes and retinopathy progression. Conclusions: Retinal vessel closure in NPDR correlates with DR severity progression. Our findings provide supporting evidence that OCTA metrics of vessel closure may be used as a surrogate for DR severity progression.
- Real-world outcomes of observation and treatment in diabetic macular edema with very good visual acuity: the OBTAIN studyPublication . Busch, Catharina; Fraser-Bell, Samantha; Zur, Dinah; Rodríguez-Valdés, Patricio J.; Cebeci, Zafer; Lupidi, Marco; Fung, Adrian T.; Gabrielle, Pierre-Henry; Giancipoli, Ermete; Chaikitmongkol, Voraporn; Okada, Mali; Laíns, Inês; Santos, Ana Rita; kunavisarut, Paradee; Sala-Puigdollers, Anna; Chhablani, Jay; Ozimek, Malgorzata; Hilely, Assaf; Unterlauft, Jan Darius; Loewenstein, Anat; Iglicki, Matias; Rehak, MatusIn a real-world setting, the majority of DME patients with very good VA maintained vision at 12 months, regard- less of whether the DME was treated or not. This study supports close observation of eyes with DME and very good VA with consideration of treatment when a one line drop in vision is observed.
- Progression of Ganglion Cell-Inner Plexiform layer thickness in the initial stages of diabetic retinopathy in type 2 diabetic patients: a 5-year longitudinal studyPublication . Tavares, Diana; Madeira, Maria H.; Marques, Inês P.; Santos, Torcato; Santos, Ana Rita; Lobo, Conceição; Cunha-Vaz, JoséDiabetic Retinopathy (DR)is a frequent complication of DiabetesMellitus (DM) andthe main cause of vision loss in the working population in western countries. Diabetic Retinopathy has always been considered a microvascular disease, but it has been suggested that neurodegeneration is also associated with this complex pathology[1], although there is evidence indicating that the neurodegenerative process may progress independently[2]. To evaluate this potential association, we have examined the progression of neurodegeneration over a 5-year period of follow-up (considering thinning of ganglion cell + inner plexiform retinal layers (GCL+IPL) in individuals with type 2 diabetes (T2D) and nonproliferative DR) and explored whetheritis associated with microaneurysmturnover (MAT), diseaselevel at baseline and severity progression.
- Comprehensive assessment of environmental fungus-reactive T cells response in hypersensitivity pneumonitis patientsPublication . Santos, Rita F.; Coelho, Andreia L.; Rufo, João C.; Coelho, David; Gonçalves, Melany; Gonçalves, Samuel L.; Cunha, Cristina; Carvalho, Agostinho; Delgado, Luís; Morais, António; Saraiva, Margarida; Novais-Bastos, HélderHypersensitivity pneumonitis (HP) is an interstitial lung disease that results in parenchymal and small airways inflammation and culminates in breathlessness, negatively impacting patient’s quality of life and survival. HP is initiated by an exaggerated immune response triggered by the inhalation of a variety of environmental antigens. The identification of the triggering antigen is a cornerstone of the diagnostic algorithm, and importantly, exposure avoidance ameliorates the clinical outcomes. However, the inciting antigen is not identified in a large proportion of patients. A difficult to identify, but common inciting antigen, is exposure to household fungi.
- Characterization of disease progression in the initial stages of retinopathy in type 2 diabetes: A 2-year longitudinal studyPublication . Marques, Inês P.; Alves, Dalila; Santos, Torcato; Mendes, Luís; Lobo, Conceição; Santos, Ana Rita; Durbin, Mary; Cunha-Vaz, JoséTo characterize 2-year changes occurring in neurodegeneration, edema, and capillary dropout in nonproliferative diabetic retinopathy. Two-year prospective longitudinal observational cohort of eyes/patients with type 2 diabetes using spectral domain optical coherence tomography (SD-OCT) and opti cal coherence tomography angiography (OCTA). Eyes were examined three times with intervals of 1 year. Thickness of the full retina and layer-by-layer measurements were used to identify edema or neurodegeneration. OCTA vessel density maps of the retina were used to identify capillary dropout. Early Treatment Diabetic Retinopathy Study (ETDRS) classification was performed using the seven-field ETDRS protocol. A total of 62 eyes from 62 patients with diabetes were followed for 2 years. After verification for image quality, a total of 44 eyes from 44 patients (30% women) aged 52 to 80 years were retained for data analysis. There were 18 eyes with ETDRS grades 10 to 20, 17 eyes with ETDRS grade 35, and 9 eyes with ETDRS grades 43 to 47. During the 2-year follow-up period, there was a progressive increase in capillary dropout, whereas edema and neurodegeneration remained stable. In multivariate analysis, consid ering a model adjusted for age, sex, hemoglobin A1C, visual acuity, and diabetes duration, vessel density remained significantly different between Diabetic Retinopathy Severity Scale groups (Wilks’ λ = 0.707; P = 0.015) showing association with disease progression. Capillary dropout increased in a period of 2 years in eyes with minimal, mild, and moderate diabetic retinopathy, whereas the presence of edema and neurodegeneration remained stable
- Baseline Characterization of Retinal Vascular Disease in Eyes with Mild to Moderate Non Proliferative Diabetic Retinopathy (NPDR) in Diabetes Type 2, Using Novel Non-Invasive Imaging Methods, in a Longitudinal, Prospective and Interventional 2-Year Clinical Study (Cordis)Publication . Ribeiro, M.; Marques, I.P.; Santos, Ana Rita; Coimbra, R.; Santos, T.; Figueira, J.; Cunha-Vaz, J.G.Characterization of retinal microvascular changes occurring in eyes with mild to moderate non proliferative diabetic retinopathy (NPDR), during a period of 2 years using lower than optical normal reflectivity (LOR) ratios obtained with OCT-Leakage. Capillary closure in the superficial and deep retinal vascular layers using OCTAngiography (OCTA) will be also analyzed in eyes that are at risk for developing sight threatening diabetic retinopathy (central involved macular edema (CIME) or proliferative diabetic retinopathy (PDR).
- Association between neurodegeneration and macular perfusion in the progression of diabetic retinopathy: a 3-year longitudinal studyPublication . Marques, Inês P.; Ferreira, Sónia; Santos, Torcato; Madeira, Maria H.; Santos, Ana Rita; Mendes, Luís; Lobo, Conceição; Cunha-Vaz, JoséThe aim of this study was to explore the relation between retinal neurodegenerative changes and vessel closure (VC) in individuals with nonproliferative diabetic retinopathy (NPDR) in a follow-up period of 3 years. This is a 3-year prospective longitudinal study with four annual visits. This study involved 74 individuals with type 2 diabetes, NPDR, and Early Treatment Diabetic Retinopathy Study grades from 10 to 47, one eye/person. An age-matched healthy control population of 84 eyes was used as control group. Participants were annually examined by color fundus photography, spectral domain-optical coherence tomography (SD-OCT) and OCT-angiography (OCTA). VC was assessed by OCTA vessel density maps. SD-OCT segmentations were performed to access central retinal thickness (CRT) and retinal neurodegeneration considered as thinning of the ganglion cell plus inner plexiform layer (GCL + IPL). Results: Type 2 diabetic individuals presented significantly higher CRT (p = 0.001), GCL + IPL thinning (p = 0.042), and decreased vessel density at the superficial capillary plexus (p < 0.001) and full retina (FR) (p = 0.001). When looking at changes occurring over the 3-year period of follow-up (Table 2), there were statistically significant decreases in GCL + IPL thickness (−0.438 μm/year; p = 0.038), foveal avascular zone circularity (−0.009; p = 0.047), and vessel density in superficial capillary plexus (−0.172 mm−1/year; p < 0.001), deep capillary plexus (DCP) (−0.350 mm−1/year; p < 0.001), and FR (−0.182 mm−1/year; p < 0.001). A statistically significant association was identified between GCL + IPL thinning and decrease in DCP vessel density (β = 0.196 [95% confidence interval: 0.037, 0.355], z = 2.410, p = 0.016), after controlling for age, gender, diabetes duration, hemoglobin A1c level, and CRT. Retinal neurodegenerative changes show a steady progression during a 3-year period of follow-up in eyes with NPDR and appear to be directly associated with progression in decreased vessel density including vascular closure through preferential involvement of the DCP. Our findings provide evidence that retinal neuropathy is linked with microvascular changes occurring in diabetic patients.
- Polymorphisms and haplotypes of TOLLIP and MUC5B are associated with susceptibility and survival in patients with fibrotic hypersensitivity pneumonitisPublication . Mota, P.C.; Soares, M.L.; Ferreira, A.C.; F. Santos, Rita; Cavaleiro Rufo, J; Vasconcelos, D.; Carvalho, A.; Guimarães, S.; Vasques-Novo, F.; Cardoso, C.; Melo, N.; Alexandre, A.T.; Coelho, D.; Novais-Bastos, H.; Morais, A.Hypersensitivity pneumonitis (HP) is an interstitial lung disease with diverse clinical features that can present a fibrotic phenotype similar to idiopathic pulmonary fibrosis (IPF) in genetically predisposed individuals. While several single nucleotide polymorphisms (SNPs) have been associated with IPF, the genetic factors contributing to fibrotic HP (fHP) remain poorly understood. This study investigated the association of MUC5B and TOLLIP variants with susceptibility, clinical presentation and survival in Portuguese patients with fH. A case-control study was undertaken with 97 fHP patients and 112 controls. Six SNPs residing in the MUC5B and TOLLIP genes and their haplotypes were analyzed. Associations with risk, survival, and clinical, radiographic, and pathological features of fHP were probed through comparisons among patients and controls. MUC5B rs35705950 and three neighboring TOLLIP variants (rs3750920, rs111521887, and rs5743894) were associated with increased susceptibility to fHP. Minor allele frequencies were greater among fHP patients than in controls (40.7% vs 12.1%, P<0.0001; 52.6% vs 40.2%, P = 0.011; 22.7% vs 13.4%, P = 0.013; and 23.2% vs 12.9%, P = 0.006, respectively). Haplotypes formed by these variants were also linked to fHP susceptibility. Moreover, carriers of a specific haplotype (G-T-G-C) had a significant decrease in survival (adjusted hazard ratio 6.92, 95% CI 1.73–27.64, P = 0.006). Additional associations were found between TOLLIP rs111521887 and rs5743894 variants and decreased lung function at baseline, and the MUC5B SNP and radiographic features, further highlighting the influence of genetic factors in fHP. These findings suggest that TOLLIP and MUC5B variants and haplotypes may serve as valuable tools for risk assessment and prognosis in fibrotic hypersensitivity pneumonitis, potentially contributing to its patient stratification, and offer insights into the genetic factors influencing the clinical course of the condition.
- Real-world outcomes of non-responding diabetic macular edema treated with continued anti-VEGF therapy versus early switch to dexamethasone implant: 2-year resultsPublication . Busch, Catharina; Fraser-Bell, Samantha; Iglicki, Matias; Lupidi, Marco; Couturier, Aude; Chaikitmongkol, Voraporn; Giancipoli, Ermete; Rodríguez-Valdés, Patricio J.; Gabrielle, Pierre-Henri; Laíns, Inês; Santos, Ana Rita; Cebeci, Zafer; Amphornphruet, Atchara; Degenhardt, Valentin; Unterlauft, Jan-Darius; Cagini, Carlo; Mané-Tauty, Valérie; Ricci, D'Amico Giuseppe; Hindi, Isaac; Agrawal, Kushal; Chhablani, Jay; Loewenstein, Anat; Zur, Dinah; Regak, MatusThe beneficial effect of an early switch to DEX implant in DME non-responders seen at month 12 was main- tained during the second year. A later switch from anti-VEGF to steroids still provided significant improvement. Eyes continued on anti-VEGF over a period of 24 months maintained vision. A quarter of eyes, which had not improved vision at 12 months, exhibited a delayed response to treatment.
- Retinal capillary nonperfusion in preclinical diabetic retinopathyPublication . Santos, Torcato; Santos, Ana Rita; Almeida, Ana Catarina; Rocha, Ana Cláudia; Reste-Ferreira, Débora; Marques, Inês Pereira; Martinho, António Cunha-Vaz; Mendes, Luís; Foote, Katharina; Cunha-Vaz, JoséThe aim of the study was to identify retinal microvascular changes using optical coherence tomography angiography (OCTA) in type 2 diabetes (T2D) patients with preclinical retinopathy identified by ultra-widefield fundus photography (UWF-FP). This is a cross-sectional observational study. All patients underwent UWF-FP 200° examinations with OPTOS California (Optos, Dunfermline, UK) and Cirrus AngioPlex® spectral-domain (SD)-OCTA 3 × 3 mm acquisitions (ZEISS, Dublin, CA, USA). The absence of visible lesions was identified using UWF-FP. One hundred and ninety three eyes of individuals with T2D with no visible lesions in the fundus and identified in a screening setting were included in the study. Skeletonized vessel density (SVD), perfusion density (PD), and areas of capillary nonperfusion (CNP) values on SD-OCTA were significantly decreased when compared with healthy population (p < 0.001). SVD and CNP values of the superficial capillary plexus (SCP) were more frequently decreased (35% and 45%, respectively) than SVD values of the deep capillary plexus (DCP) (9% and 15%, respectively), demonstrating that diabetic microvascular changes occur earlier in the SCP than in the DCP. The ischemic phenotype, identified by a definite decrease in SVD or CNP in the SCP may, therefore, be identified in the preclinical stage of diabetic retinal disease. Retinal capillary nonperfusion detected by OCTA metrics of SVD and CNP can be identified in the central retina in eyes with T2D before development of visible lesions in the retina. Our findings confirm the relevance of OCTA to identify macular microvascular changes in the initial stages of diabetic retinopathy, allowing the identification of its ischemic phenotype very early in the disease process.
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