Different Risk Profiles for Progression of Nonproliferative Diabetic Retinopathy: A 2-Year Study

INTRODUCTION: Characterization of 2-year progression of different risk phenotypes in eyes with mild and moderate nonproliferative diabetic retinopathy (NPDR) in type 2 diabetes (T2D). METHODS: A 2-year prospective longitudinal cohort study (CORDIS, NCT03696810) was conducted. Ophthalmological examinations were performed including best corrected visual acuity, color fundus photography and optical coherence tomography (OCT and OCTA). OCT metrics, central retinal thickness and ganglion cell layer + inner plexiform layer (GCL + IPL) thickness were analyzed. OCTA metrics, vessel density (VD), perfusion density (PD) and area of intercapillary spaces (AIS) were obtained from superficial and deep capillary plexus (SCP, DCP). Only phenotype C identified by decreased VD ≥ 2 SD of healthy controls and phenotype B identified by subclinical macular edema with decreased VD < 2 SD of healthy controls were included. RESULTS: One hundred twenty-two eyes from T2D individuals were included in study; 65 eyes (53%) were classified as phenotype B and 57 eyes (47%) as phenotype C. For phenotype B, progression was associated with thinning of the GCL + IPL (ETDRS 35, 1 year p = 0.013, 2 year p < 0.001; ETDRS 43–47, 2 year p = 0.003) and vessel closure involving mainly the DCP for both ETDRS grades (ETDRS 35, 1 year p = 0.025, 2 year p = 0.034; ETDRS 43–47, 1 year p = 0.011). For phenotype C there was also progressive thinning of the GCL + IPL (ETDRS 35, in both years p ≤ 0.001; ETDRS 43–47, 1 year p = 0.002, 2 year p = 0.001), with vessel closure involving mainly SCP (ETDRS 35, 1 year p = 0.012, 2 year p = 0.023 in full-retina), which appeared to stabilize at maximal values in ETDRS grade 43–47 at the end of 2 years. ETDRS severity changes at the end of the 2-year period showed that worsening was associated with phenotype C with changes involving predominantly the SCP (VD, p = 0.005; PD, p = 0.008; AIS, p = 0.005). CONCLUSIONS: Association between ETDRS classification of NPDR severity and identification of different risk phenotypes offers new perspective to predict disease progression in T2D individuals with NPDR.