Caracterização imagiológica do estadio pré-proliferativo da retinopatia diabética para identificar risco de progressão e instituir tratamento atempado

We aim to conduct a longitudinal prospective clinical study in DMT2 patients with moderate to severe NPDR/ mild PDR (at risk for progression) to explore imaging, functional and systemic biomarkers of DR progression, using state of the art methodologies, commonly applied in clinical practice. Primary objective: 1. To characterize the progression of retinal microvascular changes occurring in patients with moderate to severe NPDR and mild PDR over 2 years of follow up. The vascular occlusion will be well characterized using OCTA methodologies (spectral domain and swept source) as well as UWF-FA. The presence of vascular abnormalities such as microaneurysms and intraretinal microvascular abnormalities (IRMAs), will be analysed to assess disease progression to neovascularization, focusing on non-invasive OCT, WF-OCTA and UWF-CP. UWF-FA, an invasive method, will be also used for comparison; 2. To characterize macular edema occurring in patients with moderate to severe NPDR and mild PDR using OCT measurements of central retinal thickness (CRT); 3. To characterize the neurodegenerative changes occurring in these patients using OCT examination of GCL + IPL thickness. Secondary Objectives: 1. To investigate the relationship between the previous ocular structural characteristics, namely microvascular changes, development of macular edema and neurodegeneration; 2. To correlate the degree of capillary closure by OCTA and DRSS severity level changes during a period of 2 years; 3. To investigate the association between vascular occlusion and neurodegeneration (thickness of GCL+IPL retinal layers) with visual function changes (BCVA); 4. To understand whether these structural/ functional measurements have the potential to be validated as clinical endpoints; 5. To investigate the influence of systemic risk factors in structural/ functional measurements during the 2 years of follow up. At the end of the study we will be able to establish risk profiles of progression and determine which patients are prone to develop complications and could benefit from early treatment. The primary endpoints of the study will be: 1. Capillary non perfusion, measured with OCTA (skeletonized VD, binarized VD (PD)) on the superficial and deep retinal vascular layers on OCTA (SD-OCTA AngioPlex, and SS-OCTA PLEX Elite, Zeiss) in macular region and midperiphery (3x3 mm, 6x6 mm and wide-field 15x15 mm); FAZ area, perimeter and circularity; 2. Ischemic Index measured on UWF FFA (Optos 200Tx system); 3. CRT and GCL + IPL thickness evaluated by SD-OCT; 4. DRSS severity level, assessed in Wide-field imaging (UWF CP) using 100° Clarus 500TM (Zeiss) or 200° Optos 200Tx system camera with ETDRS mask; 5. MA counting and turnover assessment in fundus colour photograph; 6. IRMA and NVs assessment using UWF CP, UWF FFA and OCTA. Secondary endpoints will be: 7. OCTA metrics changes over 2 years of follow up 8. Changes in CRT and GCL + IPL thickness over the 2 years of follow up 9. One and 2-steps change on DRSS changes 10. BCVA changes in number of letters along the 2 years period. Outcomes to determine disease progression to VTC: 1. Development of PDR demonstrated by the presence of new vessels in the vitreous needing treatment, neovascularization in the iris/angle during the follow up period, vitreous/pre-retinal haemorrhage; 2. Development of clinically significant DME (CSME) during the follow up period, needing treatment.