Macular perfusion alterations in people with recent-onset diabetes and novel diabetes subtypes

Our aim was to detect early structural and functional changes in the macular capillaries using optical coherence tomography angiography during the course of type 1 or 2 diabetes mellitus.

In this cross-sectional study, individuals with type 1 diabetes (n=143) or type 2 diabetes (n=197) from the German Diabetes Study (ClinicalTrials.gov registration no. NCT01055093) underwent clinical examination and cluster analysis to identify phenotype-based diabetes subtypes, using BMI, age, HbA_1c, homoeostasis model estimates and islet autoantibodies. Colour fundus photography, optical coherence tomography and optical coherence tomography angiography were performed within the first year of diabetes diagnosis (baseline) and at 5 year intervals up to year 10. Age- and sex-adjusted participants served as control participants (n=105). Perfusion density, vessel density, presence of retinal microaneurysms in superficial, intermediate and deep capillary plexus (SCP, ICP, DCP), choriocapillaris flow deficit density (CC FD) and the foveal avascular zone (FAZ) of the macula as well as retinal layer thickness, visual acuity and contrast sensitivity were analysed.

Perfusion density and vessel density of SCP were already reduced at baseline in type 2 diabetes (expected difference compared with control participants: -0.0071, p=0.0276, expected difference: -0.0034, p=0.0184, respectively), especially in participants with severe insulin-deficient and mild obesity-related diabetes. At year 10 only perfusion density of the SCP and DCP was reduced in both type 1 and 2 diabetes (p=0.0365, p=0.0062, respectively). The FAZ was enlarged and the CC FD within the first year increased in type 1 (p=0.0327, p=0.0474, respectively) and more markedly in type 2 diabetes (p=0.0006, p<0.0001). The occurrence of microaneurysms in SCP and DCP was significant at year 5 (p=0.0209, p=0.0279, respectively) and year 10 (p=0.0220, p=0.0007). Presence of microaneurysms in SCP and DCP was associated with decreases in perfusion density and vessel density in both SCP and ICP. Furthermore, microaneurysms were associated with decreased ganglion cell layer and inner plexiform layer thickness.

Type 2 diabetes already reduces macular perfusion SCP at time of clinical diagnosis, while long-standing diabetes affects both SCP and DCP. The FAZ of the SCP and the CC FD are early indicators of diabetic alterations, with more pronounced changes observed in type 2 diabetes. Microaneurysms in the macular plexus are associated with a decrease of ganglion cell layer and inner plexiform layer. Subclinical microangiopathy occurs prior to manifestation of diabetic retinopathy, disease-related visual acuity impairment or inner retinal layer thinning.