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To investigate longitudinal changes in peripapillary choroidal thickness (pCT) and retinal nerve fiber thickness (pRNFLT) in patients with Type 2 diabetes mellitus.This was a prospective observational cohort study. Patients with Type 2 diabetes mellitus without diabetic retinopathy (DR) at baseline were recruited, followed up for three years, and further divided into an incident DR group and a non-DR group according to the outcome. The pCT and pRNFLT were measured through swept-source optical coherence tomography at 1-year interval, and the mean rates of pCT and pRNFLT thinning were compared between the DR groups.A total of 682 patients (682 eyes) were included in the final analysis. After 3-years follow-up, 122 (17.89%) developed DR. Both pCT and pRNFLT progressively thinned (-2.37 [-2.80 to -1.95] µm/year; -0.40 [-0.55 to -0.25] µm/year, respectively, P0.05) and accelerated thinning was observed in the incident DR group. The rates of pCT thinning (-3.92 [-4.96 to -2.88] µm/year, -2.03 [-2.49 to -1.57] µm/year, respectively) and pRNFLT loss (-1.03 [-1.31 to -0.76] µm/year, -0.26 [-0.43 to -0.09] µm/year, respectively) in the incident DR group were 1.93 and 3.96 times faster than those in the non-DR group, respectively. In addition, pCT and pRNFLT thinning were negatively related in Type 2 diabetes mellitus population, and faster pCT thinning indicated slower pRNFLT loss.Patients with Type 2 diabetes mellitus were at a higher risk of developing DR when accelerated pCT and pRNFLT thinning were present, indicating that heavier choroidal damage and retinal neurodegeneration precede clinical DR. The pCT and pRNFLT have the potential to serve as novel sensitive biomarkers of preclinical and early DR.

Background Aberrant epigenetic modifications such as DNA methylation may contribute to the pathogenesis of DR. We aimed at elucidating the role of novel DNA methylation modifications in diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) using an extreme phenotypic design. Methods/results Two consecutive studies were conducted. A cross-sectional study using an extreme phenotypic design was conducted to identify rare methylation modifications that might contribute to DR pathogenesis. A 2-year longitudinal nested case–control study was conducted to validate the results and assess whether these novel methylation modifications could be used as biomarkers for predicting DR onset. A large number of differentially methylated CpG sites were identified in the cross-sectional study, and two (cg12869254 and cg04026387) corresponding to known genes were replicated in the longitudinal study. Higher methylation of cg12869254 significantly correlated with macular RNFL thinning in the superior and nasal subregions, and that of cg04026387 correlated with reduced deep capillary plexus VD in the superior and inferior subregions after adjusting for covariates. Conclusions Cg12869254 and cg04026387 hypermethylation may complement the known risk factors that contribute to the pathogenesis of DR and as novel biomarkers for disease prediction.

To determine the predictive value of the microcirculation of the optic nerve head by swept-source optical coherence tomography angiography for identifying individuals with high risk of diabetic retinopathy (DR) progression and diabetic macular edema (DME) development.Prospective observational cohort study.A total of 946 patients (1879 eyes) with type 2 diabetes mellitus were recruited who had no DR or mild nonproliferative DR at baseline, and no DME. All subjects underwent 3 × 3 mm swept-source optical coherence tomography angiography centered on the optic nerve head to generate angiograms in 4 layers: radial peripapillary plexus, superficial retinal capillary plexus (SCP), deep retinal capillary plexus, and choriocapillaris (CC). The CC flow deficit percentage (CC FD%), vessel density (VD), and perfusion density (PD) were quantified.During the 3 consecutive years of follow-up, 312 eyes (16.60%) experienced DR progression and 115 eyes (6.12%) developed DME. The DR progression was related to a lower VD of the SCP (relative risk per standard deviation decrease, 95% confidence interval): 1.30, 1.14-1.48; P.001), a lower PD of the SCP (1.41, 1.24-1.60; P.001), a lower VD of the radial peripapillary plexus (1.23, 1.08-1.40; P = .002), and an elevated CC FD% (1.62, 1.40-1.88; P.001). The DME occurrence was associated with a lower VD of SCP (1.35, 1.09-1.66; P = .005), a lower PD of SCP (1.29, 1.05-1.59; P = .016), and a higher CC FD% (1.29, 1.03-1.61; P.001). The CC FD% significantly improved the predictive power, with the increase of the C-statistic for DR progression and DME occurrence by 3.83% (P = .002) and 5.24% (P.001), respectively.This study provides the first longitudinal evidence suggesting that peripapillary CC FD% can improve the prediction of DR progression and DME development beyond traditional risk factors.