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- Microaneurysm turnover in mild non-proliferative diabetic retinopathy is associated with progression and development of vision-threatening complications: a 5-year longitudinal studyPublication . Santos, Ana Rita; Mendes, Luís; Madeira, Maria Helena; Marques, Inês P.; Tavares, Diana; Figueira, João; Lobo, Conceição; Cunha-Vaz, JoséAnalysis of retinal microaneurysm turnover (MAT) has been previously shown to contribute to the identification of eyes at risk of developing clinically significant complications associated with diabetic retinopathy (DR). We propose to further characterize MAT as a predictive biomarker of DR progression and development of vision-threatening complications. Methods: 212 individuals with type 2 diabetes (T2D; ETDRS grades 20 and 35) were evaluated annually in a 5-year prospective, longitudinal study, by color fundus photography and optical coherence tomography. Endpoints were diabetic macular edema (DME) or proliferative retinopathy (PDR). MAT analysis included determination of MA formation and disappearance rates, automatically assessed using the RetMarkerDR®. Retinopathy severity progression was evaluated using step increases in ETDRS severity levels. Results: Of the 212 individuals, 172 completed the 5-year follow-up study or developed an endpoint (n = 27). MAT calculated at 1 year showed a significant difference between groups of endpoint developments (p = 0.018), particularly MA disappearance rate (p = 0.007). MAT also showed a significant difference between eyes with different ETDRS severity progression in the 5-year period (p = 0.035). MAT is an indicator of the development of DME and/or PDR as well as of DR severity progression in T2D individuals with mild retinopathy.
- 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.
- 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.
- 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.