Browsing by Author "Madeira, Maria H."
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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 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.
- 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.
- 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.
- Retinal neurodegeneration in different risk phenotypes of diabetic retinal diseasePublication . Madeira, Maria H.; Marques, Inês P.; Ferreira, Sónia; Tavares, Diana; Santos, Torcato; Santos, Ana Rita; Figueira, João; Lobo, Conceição; Cunha-Vaz, JoséDiabetic retinopathy (DR) has been considered a microvascular disease, but it has become evident that neurodegeneration also plays a key role in this complex pathology. Indeed, this complexity is reflected in its progression which occurs at different rates in different type 2 diabetic (T2D) individuals. Based on this concept, our group has identified three DR progression phenotypes that might reflect the interindividual differences: phenotype A, characterized by low microaneurysm turnover (MAT <6), phenotype B, low MAT (<6) and increased central retinal thickness (CRT); and phenotype C, with high MAT (≥6). In this study, we evaluated the progression of DR neurodegeneration, considering ganglion cell+inner plexiform layers (GCL+IPL) thinning, in 170 T2D individuals followed for a period of 5 years, to explore associations with disease progression or risk phenotypes. Ophthalmological examinations were performed at baseline, first 6 months, and annually. GCL+IPL average thickness was evaluated by optical coherence tomography (OCT). Microaneurysm turnover (MAT) was evaluated using the RetMarkerDR. ETDRS level and severity progression were assessed in seven-field color fundus photography. In the overall population there was a significant loss in GCL+IPL (−0.147 μm/year), independently of glycated hemoglobin, age, sex, and duration of diabetes. Interestingly, this progressive thinning in GCL + IPL reached higher values in phenotypes B and C (−0.249 and −0.238 μm/year, respectively), whereas phenotype A remained relatively stable. The presence of neurodegeneration in all phenotypes suggests that it is the retinal vascular response to the early neurodegenerative changes that determines the course of the retinopathy in each individual. Therefore, classification of different DR phenotypes appears to offer relevant clarification of DR disease progression and an opportunity for improved management of each T2D individual with DR, thus playing a valuable role for the implementation of personalized medicine in DR.
- Standardization of optical coherence tomography angiography imaging biomarkers in diabetic retinal diseasePublication . Vujosevica, Stela; Cunha-Vaz, José; Figueira, João; Löwensteind, Anat; Midena, Edoardo; Parravano, Mariacristina; Scanlon, Peter Henry; Simó, Rafael; Hernández, Cristina; Madeira, Maria H.; Marques, Inês P.; Martinho, António C.-V.; Santos, Ana Rita; Simó-Servat, Olga; Salongcayk, Recivall P.; Zurd, Dinah; Peto, TundeOptical coherence tomography Angiography (OCT-A) represents a revolution in the noninvasive evaluation of retinal and choroidal circulation especially in detecting early clinical signs of diabetic retinal disease (DRD). With appropriate use, OCT-A characteristics and measurements have the potential to become new imaging biomarkers in managing and treating DRD. Major challenges include (a) provision of standardized outputs from different OCT-A instruments providing standardized terminology to correctly interpret data; (b) the presence of artifacts; (c) the absence of standardized grading or interpretation method in the evaluation of DRD, similar to that already established in fundus photography; and (d) establishing how OCT-A might be able to provide surrogate markers to demonstrate blood retinal barrier breakdown and vascular leakage, commonly associated with DRD. In fact, OCT-A guidelines for DRD are still evolving. The outputs of quantitative OCT-A data offer a unique opportunity to develop tools based on artificial intelligence to assist the clinicians in diagnosing, monitoring, and managing patients with diabetes. In addition, OCT-A has the potential to become a useful tool for the evaluation of cardiovascular diseases and different neurological diseases including cognitive impairment. This article written by the members of Diabetic Retinopathy expert committee of the European Vision Clinical Research network will review the available evidence on the use of OCT-A as an imaging biomarker in DRD and discuss the limits and the current application as well as future developments for its use in both clinical practice and research trials of DRD.
- Swept-source OCTA quantification of capillary closure predicts ETDRS severity staging of NPDRPublication . Santos, Torcato; Warren, Lewis H.; Santos, Ana Rita B. M.; Marques, Inês Pereira; Kubach, Sophie; Mendes, Luís G.; Sisternes, Luís de; Madeira, Maria H.; Durbin, Mary; Cunha-Vaz, José G.To test whether a single or composite set of parameters evaluated with optical coherence tomography angiography (OCTA), representing retinal capillary closure, can predict non-proliferative diabetic retinopathy (NPDR) staging according to the gold standard ETDRS grading scheme. 105 patients with diabetes, either without retinopathy or with different degrees of retinopathy (NPDR up to ETDRS grade 53), were prospectively evaluated using swept-source OCTA (SS-OCTA, PlexElite, Carl Zeiss Meditec) with 15×9 mm and 3×3 mm angiography protocols. Seven-field photographs of the fundus were obtained for ETDRS staging. Eyes from age-matched healthy subjects were also imaged as control. In eyes of patients with type 2 diabetes without retinopathy or ETDRS levels 20 and 35, retinal capillary closure was in the macular area, with predominant alterations in the parafoveal retinal circulation (inner ring). Retinal capillary closure in ETDRS stages 43-53 becomes predominant in the retinal midperiphery with vessel density average values of 25.2±7.9 (p=0.001) in ETDRS 43 and 23.5±3.4 (p=0.001) in ETDRS 47-53, when evaluating extended areas of 15×9 protocol. Combination of acquisition protocols 3×3 mm and 15×9 mm, using SS-OCTA, allows discrimination between eyes with mild NPDR (ETDRS 10, 20, 35) and eyes with moderate-to-severe NPDR (ETDRS grades 43-53). Retinal capillary closure, quantified by SS-OCTA, can identify NPDR severity progression. It is located mainly in the perifoveal retinal capillary circulation in the initial stages of NPDR, whereas the retinal midperiphery is predominantly affected in moderate-to-severe NPDR.