Browsing by Author "Santos, Torcato"
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- 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.
- Characterisation of progression of macular oedema in the initial stages of diabetic retinopathy: a 3-year longitudinal studyPublication . Lobo, Conceição; Santos, Torcato; Marques, Inês P.; Madeira, Maria H.; Santos, Ana Rita; Figueira, João; Cunha-Vaz, JoséTo characterise the prevalence and three-year progression of centre-involving diabetic macular oedema (CI-DMO) in minimal to moderate non-proliferative diabetic retinopathy, using optical coherence tomography (OCT) and measurements of retinal fluid using tissue optical reflectivity ratios (OCT-Leakage). Seventy-four eyes from 74 patients were followed in a 3-year prospective longitudinal observational cohort of type 2 diabetes (T2D) patients using spectral-domain optical coherence tomography (SD-OCT), OCT-Angiography (OCT-A) and OCT-Leakage (OCT-L). Eyes were examined four times with 1-year intervals. Sixteen eyes (17.8%) were excluded from the analysis due to quality control standards. Retinal oedema was measured by central retinal thickness and retinal fluid by using optical reflectivity ratios obtained with the OCT-L algorithm. Vessel density was measured by OCT-A. Thinning of the ganglion cell and inner plexiform layers (GCL + IPL) was examined to identify retinal neurodegenerative changes. Diabetic retinopathy ETDRS classification was performed using the seven-field ETDRS protocol. CI-DMO was identified in the first visit in 9% of eyes in ETDRS groups 10–20, 10% of eyes in ETDRS group 35 and 15% of eyes in ETDRS groups 43–47. The eyes with CI-DMO and subclinical CI-DMO showed a progressive increase in retinal extracellular fluid during the 3-year period of follow-up. The eyes with CI-DMO and increased retinal extracellular fluid accumulation were associated with vision loss. The prevalence of subclinical CI-DMO and CI-DMO in the initial stages of NPDR occurs independently of severity grading of the retinopathy, showing progressive increase in retinal extracellular fluid and this increase is associated with vision loss (82% 9 out of 11 cases).
- Characterization of 2-year progression of different phenotypes of nonproliferative diabetic retinopathyPublication . Ribeiro, Luísa; Marques, Inês P.; Santos, Torcato; Carvalho, Sara; Santos, Ana Rita; Mendes, Luís; Lobo, Conceição; Cunha-Vaz, JoséThe 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.
- 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
- Characterization of initial stages of diabetic macular edemaPublication . Santos, Ana Rita; Santos, Torcato; Alves, Dalila; Marques, Inês P.; Lobo, Conceição; Cunha-Vaz, JoséThis study is aimed at characterizing the type of retinal edema in the initial stages of retinopathy in type 2 diabetes. In this retrospective cross-sectional study, spectral domain optical coherence tomography (OCT) layer by layer analysis of the retina in association with OCT-Leakage, an algorithm to detect sites of low optical reflectivity, were used to examine eyes with minimal, mild, and moderate diabetic retinopathy (DR). A total of 142 eyes from 142 patients (28% women) aged 52–88 years were imaged. Macular edema, either subclinical (SCME) or central-involved macular edema (CIME), was present in 43% of eyes in group 10–20, 41% of eyes in group 35, and 38% of eyes in group 43–47. The inner nuclear layer (INL) was the layer showing higher and most frequent increases in retinal thickness (79%). The edema was predominantly intracellular in group 10–20 (65%) and extracellular in groups 35 (77%) and 43–47 (69%). Eyes from diabetic patients in the initial stages of DR with different Early Treatment Diabetic Retinopathy Study gradings show similar prevalence of SCME and CIME, independent of the severity of the retinopathy. Retinal edema is located mainly in the INL and appears to be mostly extracellular except in the earliest stages of diabetic retinal disease where intracellular edema predominates.
- Characterization of one-year progression of risk phenotypes of diabetic retinopathyPublication . Ribeiro, Luísa; Marques, Inês P.; Coimbra, Rita; Santos, Torcato; Madeira, Maria H.; Santos, Ana Rita; Barreto, Patrícia; Lobo, Conceição; Cunha-Vaz, JoséWe characterized the progression of different diabetic retinopathy (DR) phenotypes in type 2 diabetes (T2D). A prospective longitudinal cohort study (CORDIS, NCT03696810) was conducted with three visits (baseline, 6 months, and 1 year). Demographic and systemic data included age, sex, diabetes duration, lipid profile, and hemoglobin A1c (HbA1c). Ophthalmological examinations included best-corrected visual acuity (BCVA), color fundus photography (CFP), and optical coherence tomography (OCT and OCTA). Phenotype classification was performed at the 6-month visit based on microaneurysm turnover (MAT, on CFP) and central retinal thickness (CRT, on OCT). Only risk phenotypes B (MAT < 6 and increased CRT) and C (MAT ≥ 6 with or without increased CRT) were included. ETDRS grading was performed at the baseline visit based on seven-field CFP.A total of 133 T2D individuals were included in the study; 81 (60%) eyes were classified as phenotype B and 52 (40%) eyes as phenotype C. Of these, 128 completed the 1-year follow-up. At baseline, eyes with phenotype C showed greater capillary closure (superior capillary plexus, deep capillary plexus, and full retina, p < 0.001) and increased foveal avascular zone (FAZ) area (p < 0.001), indicating more advanced microvascular disease. Neurodegeneration represented by thinning of the ganglion cell layer + inner plexiform layer (GCL + IPL) was present in both phenotypes. When analyzing the 1-year progression of each phenotype, only phenotype C revealed a significant decrease in BCVA (p = 0.02) and enlargement of the FAZ (p = 0.03). A significant progressive decrease in the vessel density of the deep capillary layer and in MAT occurred in both phenotypes, but these changes were particularly relevant in phenotype C and ETDRS grades 43–47. During the 1-year period, both phenotypes B and C showed progression in GCL + IPL thinning (p < 0.001). In the 1-year period of follow-up, both phenotypes B and C showed progression in retinal neurodegeneration, whereas phenotype C showed more marked disease progression at the microvascular level.
- A conversion model for OCTA vessel density metrics in diabetic eyes: AngioVue vs AngioplexPublication . Santos, Ana Rita; Santos, Torcato; Coimbra, Rita; Pais, Inês; Marques, Inês P.; Cunha-Vaz, JoséG.To understand measurements variability between 2 different OCTA devices and to develop a conversion model that translate vascular metrics into a standardized and comparable value in patients with different stages of DR.
- ETDRS grading with CLARUS ultra-widefield images shows agreement with 7-fields colour fundus photographyPublication . Santos, Ana Rita; Ghate, Sejal; Lopes, Marta; Rocha, Ana Cláudia; Santos, Torcato; Reste-Ferreira, Débora; Manivannan, Niranchana; Foote, Katharina; Cunha-Vaz, José; Santos, Ana RitaTo analyse and compare the grading of diabetic retinopathy (DR) severity level using standard 35° ETDRS 7-fields photography and CLARUS™ 500 ultra-widefield imaging system. A cross-sectional analysis of retinal images of patients with type 2 diabetes (n=160 eyes) was performed for this study. All patients underwent 7-fields colour fundus photography (CFP) at 35° on a standard Topcon TRC50DX® camera, and ultra-widefield (UWF) imaging at 200° on a CLARUS™ 500 (ZEISS, Dublin, CA, USA) by an automatic montage of two 133° images (nasal and temporal). 35° 7-fields photographs were graded by two graders, according to the Early Treatment Diabetic Retinopathy Study (ETDRS). For CLARUS UWF images, a prototype 7-fields grid was applied using the CLARUS review software, and the same ETDRS grading procedures were performed inside that area only. Grading of DR severity level was compared between these two methods to evaluate the agreement between both imaging techniques. Images of 160 eyes from 83 diabetic patients were considered for analysis. According to the 35° ETDRS 7-fields images, 22 eyes were evaluated as DR severity level 10–20, 64 eyes were evaluated as DR level 35, 41 eyes level 43, 21 eyes level 47, 7 eyes level 53, and 5 eyes level 61. The same DR severity level was achieved with CLARUS 500 UWF images in 92 eyes (57%), showing a perfect agreement (k>0.80) with the 7-fields 35° technique. Fifty-seven eyes (36%) showed a higher DR level with CLARUS UWF images, mostly due to a better visualization of haemorrhages and a higher detection rate of intraretinal microvascular abnormalities (IRMA). Only 11 eyes (7%) showed a lower severity level with the CLARUS UWF system, due to the presence of artifacts or media opacities that precluded the correct evaluation of DR lesions. UWF CLARUS 500 device showed nearly perfect agreement with standard 35° 7-fields images in all ETDRS severity levels. Moreover, CLARUS images showed an increased ability to detect haemorrhages and IRMA helping with finer evaluation of lesions, thus demonstrating that a UWF photograph can be used to grade ETDRS severity level with a better visualization than the standard 7-fields images.
- Intraretinal microvascular abnormalities in eyes with advanced stages of nonproliferative diabetic Retinopathy: Comparison between UWF-FFA, CFP, and OCTA-The RICHARD studyPublication . Santos, Ana Rita; Lopes, Marta; Santos, Torcato; Reste‑Ferreira, Débora; Marques, Inês P.; Yamaguchi, Taffeta C. N.; Miranda, Telmo; Mendes, Luís; Martinho, António C. V.; Pearce, Liz; Cunha‑Vaz, JoséThis study aimed to evaluate intraretinal microvascular abnormalities (IRMA) in eyes with advanced nonproliferative diabetic retinopathy (NPDR) using multimodal approach in co-located areas focusing on central retina (up to 50°) and to look at possible correlations between IRMA and other structural changes, like ischemia and presence of microaneurysms. The RICHARD study (NCT05112445) included 60 eyes from 60 patients with type 2 diabetes with moderate-severe NPDR, diabetic retinopathy severity levels 43, 47, and 53 (DRSS). IRMA were defined as capillary tortuosity covering a minimum circular area of 300 µm (calculated to correspond to the Early Treatment Diabetic Retinopathy Study standard photo 8A) and were identified using multimodal imaging with distinct fields of view (FoV): color fundus photography (CFP) using a Topcon TRC-50DX camera (Topcon Medical Systems, Japan), Optos California ultra wide field fundus fluorescein angiography (UWF-FFA) (Optos plc, UK), and swept-source optical coherence tomography angiography (SS-OCTA) (PLEX® Elite 9000, ZEISS, USA). Different areas of the retina were examined: central macula (up to 20°) and posterior pole (between 20° and 50°). Multimodal imaging was used to identify IRMA in co-located areas (FoV < 50°) including UWF-FFA, CFP, and SS-OCTA. In eyes with DRSS levels 47 and 53, IRMA were identified in both areas of the retina, while in eyes with DRSS level 43, IRMA were detected only outside of the central macula (FoV > 20°). Our results show that when evaluating the presence of IRMA (FoV < 50°), UWF-FFA detected 203 IRMA, SS-OCTA detected 133 IRMA, and CFP detected 104 IRMA. Our results also show that the presence of IRMA was positively associated with presence of microaneurysms. dentification of IRMA in eyes with advanced NPDR is better achieved by UWF-FFA than CFP and SS-OCTA. A statistically significant correlation was found between the presence of IRMA and the increase in number of microaneurysms.
- Measurements of retinal fluid by oct leakage in diabetic macular edema: A biomarker of visual acuity response to treatmentPublication . Santos, Ana Rita; Alves, Dalila; Santos, Torcato; Figueira, João; Rufino, Silva; Cunha-Vaz, José G.Optical coherence tomography leakage changes after anti-vascular endothelial growth factor treatment of diabetic macular edema, identifying the degree of decrease in retinal fluid in the outer layers of the retina is a more robust biomarker of BCVA recovery than central retinal thickness, disorganization of the inner retinal layer, or ellipsoid zone disruption changes.