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

## TL;DR

This study shows that anti-VEGF therapy for diabetic macular oedema improves retinal structure and function without harming systemic blood vessels.

## Contribution

The study combines adaptive optics and Doppler ultrasonography to assess both retinal and systemic vascular changes after anti-VEGF therapy.

## Key findings

- Anti-VEGF therapy improved photoreceptor regularity and macular thickness in treated eyes.
- Arteriolar wall-to-lumen ratio increased over time, indicating retinal vascular remodelling.
- Systemic vascular metrics remained stable, suggesting no adverse effects on large arteries.

## Abstract

Objective: Evaluate the efficacy and safety following intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy in patients with diabetic macular oedema (DME). Methods: 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. Results: In the treated eye (TE), WLR showed a significant overall change (Friedman p = 0.007), with a modest V4 vs. V1 increase (Wilcoxon p = 0.045); LD also varied across visits (Friedman p = 0.034). Cone metrics improved as follows: Reg increased over time (Friedman p = 0.019), with a significant rise at V4 vs. V1 (p = 0.018), and cone number increased at V3 vs. V1 (p = 0.012). Functional/structural outcomes improved as follows: visual acuity increased at V3 (p = 0.009) and V4 (p = 0.028), while CRT decreased at V3 (p = 0.002) and V4 (p = 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 p = 0.034 and p = 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. Conclusions: 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.