Early retinal neurovascular impairment in patients with diabetes without clinically detectable retinopathy

Aims To investigate the function and the corresponding neurovascular structures in patients with diabetes without clinically detectable retinopathy. Methods Sixty-six patients with type 2 diabetes without retinopathy (NDR) and 62 healthy controls were recruited. The 16 and 32 Tds flicker electroretinography (ERG) was performed using a mydriasis-free, full-field flicker ERG recording device (RETeval). The vessel density (VD) of superficial capillary plexus (SCP) and deep capillary plexus (DCP), FD300 and ganglion cell complex (GCC) thickness in the macula were quantified using optical coherence tomography angiography (OCTA). The retinal nerve fibre layer (RNFL) thickness and the radial peripapillary capillary (RPC) density in the peripapillary area were also measured with OCTA. Results Parafoveal and perifoveal VD in both SCP and DCP decreased in NDR group in comparison to control group (all p<0.01). However, macular GCC thickness was comparable between the two groups (p=0.661). Peripapillary RNFL thickness and RPC density were significantly lower in NDR group (p<0.001 and p=0.009, respectively). With regard to ERG parameters, delayed implicit time and decreased amplitude were found in NDR group in comparison to the control group (all p<0.01). In the multiple linear regression analyses, delayed implicit time for 16 and 32 Tds stimuli was significantly correlated with increased HbA1c (beta=0.350, p<0.001; beta=0.328, p<0.001, respectively) and decreased VD of SCP in the parafoveal region (beta=-0.266, p=0.013; beta=-0.253, p=0.005, respectively). However, delayed implicit time for 16 and 32 Tds stimuli was not correlated with the thickness of GCC (beta=-0.008, p=0.818) in multiple linear regression analyses. Conclusion Functional and structural impairments have already started in diabetic retina even in the absence of visible retinal lesions. Subtle microvascular abnormalities rather than ganglion cell loss might be associated with early functional changes in NDR patients. Poor control of blood glucose was associated with delayed implicit time of flicker ERG in preclinical diabetic retinopathy.