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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.
- 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.
- 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.