Aim To prospectively monitor subclinical changes in capillary perfusion and retinal layer thickness in patients with type 2 diabetes and early diabetic retinal disease over 2 years.

Methods In this longitudinal study we performed biannual retinal vascular imaging using optical coherence tomography angiography (RTVue) to analyse the foveal avascular zone (FAZ) area, perimeter, acircularity index (AI) and parafoveal superficial/deep vessel density (VD). Spectral-domain optical coherence tomography (Spectralis) was used to measure the thickness of nine macular layers and the peripapillary nerve fibre layer.

Results Among 117 eyes (58 left) of 59 patients (21 female), 105 had no diabetic retinopathy (DR), 6 mild and 6 moderate non-proliferative DR at baseline. We found DR progression in 13 eyes at year 2. The FAZ area (+0.008±0.002 mm²/year, p<0.0001), perimeter (+0.036±0.010 mm/year, p=0.006) and AI (+0.005±0.002/year, p=0.0280) increased significantly. A pronounced decrease was found in the superficial (−1.425±0.290%/year, p<0.0001) but not the deep VD. Inner neuroretinal loss was confined to the ganglion cell (−0.539±0.150 µm/year, p=0.0004) and the inner plexiform layer (−0.361±0.127 µm/year, p=0.0045). In the outer retina, we observed a statistically significant decrease in thickness in the outer plexiform, photoreceptor layer and pigment epithelium of −0.921±0.161 µm/year, −0.325±0.139 µm/year and −0.385±0.084 µm/year, respectively.

Conclusion Subclinical signs of microangiopathy and neurodegeneration appear in parallel and are highly progressive even in the earliest stages of diabetic retinal disease.

Trial registration number EudraCT20156000239634.