Retinal Organisation and Systemic Vascular Changes Assessed by Adaptive Optics and Doppler Ultrasonography Following Anti-VEGF Therapy in Patients with Diabetic Macular Oedema

<b>Objective:</b> Evaluate the efficacy and safety following intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy in patients with diabetic macular oedema (DME). <b>Methods:</b> To evaluate retinal microvascular remodelling and photoreceptor metrics using adaptive optics (AO) alongside systemic vascular status assessed by brachial/aortic hemodynamic and carotid ultrasound. We conducted a single-centre longitudinal study including twenty-one patients with DME. The following four diagnostic visits were performed: baseline (V1, no anti-VEGF treatment), 2-3 months (V2), 6-8 months (V3), and 12-14 months (V4). Adaptive optics (rtx1) measured foveal cone number (N) and regularity (Reg) within a standardised 80 × 80 µm window, and superior temporal retinal arteriole morphology after the first bifurcation (vessel diameter [VD], lumen diameter [LD], wall thickness [WT], wall-to-lumen ratio [WLR], and wall cross-sectional area [WCSA]). SphygmoCor provided peripheral (brachial) and central (aortic) pressures, augmentation pressure (AP), augmentation index (AIx), and carotid-femoral pulse wave velocity (PWV and PWVHR heart rate adjusted). Carotid ultrasound assessed intima-media thickness (IMT), carotid lumen diameter (CLD), and IMT/CLD ratio (IMTLR) 2 mm proximal to the bifurcation in diastole. Visual acuity (Visus), intraocular pressure (IOP), and central retinal thickness (CRT) were obtained at each visit. <b>Results:</b> In the treated eye (TE), WLR showed a significant overall change (Friedman <i>p</i> = 0.007), with a modest V4 vs. V1 increase (Wilcoxon <i>p</i> = 0.045); LD also varied across visits (Friedman <i>p</i> = 0.034). Cone metrics improved as follows: Reg increased over time (Friedman <i>p</i> = 0.019), with a significant rise at V4 vs. V1 (<i>p</i> = 0.018), and cone number increased at V3 vs. V1 (<i>p</i> = 0.012). Functional/structural outcomes improved as follows: visual acuity increased at V3 (<i>p</i> = 0.009) and V4 (<i>p</i> = 0.028), while CRT decreased at V3 (<i>p</i> = 0.002) and V4 (<i>p</i> = 0.030); IOP remained stable compared to V1. Systemic hemodynamics was largely unchanged; small fluctuations in DBP and cDBP across V1-V4 were observed (Friedman <i>p</i> = 0.034 and <i>p</i> = 0.022, respectively), whereas AIx, AP, PWV, and PWVHR showed no significant trends. Carotid IMT, CLD, and IMTLR did not change significantly across visits, supporting systemic vascular safety. <b>Conclusions:</b> Intravitreal anti-VEGF therapy in DME was associated with improvements in photoreceptor organisation and macular structure/function, with AO-derived arteriolar remodelling detectable over time, and no adverse changes in large-artery structure. These findings support ocular efficacy and systemic vascular safety; confirmation in larger cohorts is warranted.