Hypertension is associated with retinal arteriolar wall thickening in preclinical diabetic retinopathy while wall thickening in clinical diabetic retinopathy is likely driven by diabetes

Abstract

Purpose : Hypertension and diabetes often occur together, and both factors are known to increase the wall to lumen ratio (WLR) of retinal arterioles. However, in diabetic retinopathy (DR) the timing and impact of hypertension vs diabetes on the WLR remains unresolved. Here, we performed a prospective cross-sectional study using adaptive optics scanning laser ophthalmoscopy (AOSLO) to compare the WLR for arterioles in healthy, diabetes but no apparent DR (DMnoDR), and diabetic macular edema (DME) eyes. Our goal was to estimate the effects of hypertension, diabetes, and age on the WLR.

Methods : We examined 17 healthy controls, 15 DMnoDR subjects, and 8 patients with DME and either nonproliferative or proliferative DR. We imaged each arteriole of interest using AOSLO and measured the WLR using ImageJ. Multiple linear regression (MLR) was performed for statistical analysis.

Results : DMnoDR and DME subjects had a higher WLR than healthy subjects (0.36±0.08 and 0.42±0.08 vs 0.29±0.07, one-way ANOVA p=0.0009). MLR in healthy and DMnoDR subjects showed that hypertension had the strongest effect (regression coefficient=0.08, p=0.009), while age and diabetes were not significantly correlated with the WLR (p=0.15 for both). Analyzing all three groups together (healthy, DMnoDR, and DME), MLR showed that DR status had the strongest effect (regression coefficient=0.05, p=0.02), while age and hypertension were not significantly correlated with the WLR (p=0.46, 0.21).

Conclusions : Hypertension may be an early driver of retinal arteriolar wall thickening in preclinical DR, independent of age or diabetes, while changes specific to DR may drive wall thickening in later stages of DR as well as DME. Overall, our findings offer a new framework for understanding the pathophysiologic course of increased WLR in DR and the relative contributions of hypertension and diabetes to this process, which could potentially guide the development of future treatments to delay DR progression.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Example arterioles with annotated external and lumen diameters from a (A) healthy, (B) DMnoDR, and (C) DME eye.

 

(A) Boxplot comparing wall to lumen ratio (WLR) based on DR severity. (B) Regression coefficient plot from multiple linear regression (MLR). Red = MLR for healthy and DMnoDR subjects (excluding DME). Black = MLR for all three groups together.