Morphometric analysis of small arteries in the human retina using adaptive optics imaging: relationship with blood pressure and focal vascular changes

Abstract

Objectives: The wall-to-lumen ratio (WLR) of retinal arteries is a recognized surrogate of end-organ damage due to aging and/or arterial hypertension. However, parietal morphometry remains difficult to assess in vivo. Recently, it was shown that adaptive optics retinal imaging can resolve parietal structures of retinal arterioles in humans in vivo. Here, using adaptive optics retinal imaging, we investigated the variations of parietal thickness of small retinal arteries with blood pressure and focal vascular damage.

Methods: Adaptive optics imaging of the superotemporal retinal artery was done in 49 treatment-naive individuals [mean age (±SD) 44.9 years (±14); mean systolic pressure 132 mmHg (±22)]. Semi-automated segmentation allowed extracting parietal thickness and lumen diameter. In a distinct cohort, adaptive optics images of arteriovenous nicking (AVN; n = 12) and focal arteriolar narrowing (FAN; n = 10) were also analyzed qualitatively and quantitatively.

Results: In the cohort of treatment-naive individuals, by multiple regression taking into account age, body mass index, mean, systolic, diastolic and pulse blood pressure, the WLR was found positively correlated to mean blood pressure and age which in combination accounted for 43% of the variability of WLR. In the cohort of patients with focal vascular damage, neither FANs or AVNs showed evidence of parietal growth; instead, at sites of FANs, decreased outer diameter suggestive of vasoconstriction was consistently found, while at sites of AVNs venous narrowing could be seen in the absence of arteriovenous contact.

Conclusion: High resolution imaging of retinal vessels by adaptive optics allows quantitative microvascular phenotyping, which may contribute to a better understanding and management of hypertensive retinopathy.

Trial registration: ClinicalTrials.gov NCT01546181.

FIGURE 1

Adaptive optics (AO) imaging and segmentation of a retinal arteriole (same patient as in supplementary video 1). (a) Single videoframe (right panel: magnification). Note that parietal structures (between arrowheads in magnification) can be seen (A: arteriole, V: venule; bar, 250 μm). (b) Image averaging and segmentation. (c) Morphogram of the segmented vessel (D: diameter; L: length).

FIGURE 2

Mean blood pressure plotted against parietal (P), diameter (D) and wall-to-lumen ratio (WLR). Pearson's correlation coefficients are inserted. All regressions lines are statistically significant (P < 0.01).

FIGURE 3

Representative adaptive optics (AO) imaging of arteriovenous crossings. Arrowheads bracket the arteriolar wall. (a) Normal arteriovenous crossing (right panel: magnification). (b) Representative cases of arteriovenous nicking (AVN). Note the focal venous narrowings (asterisks) upstream and downstream of the arteriovenous overlap. (c) Case of venous nicking occurring in the immediate vicinity of an arteriole in the absence of arteriovenous overlapping, allowing the direct observation of the arteriovenous interface; note the gap between the arteriolar wall and the vein, suggesting that there is not direct contact (bars, 125 μm; additional cases are shown in supplementary Figure 1).

FIGURE 4

(a) Adaptive optics (AO) NIR imaging of two representative cases of focal arteriolar narrowings (FANs) with their corresponding morphograms (arrowheads in AO images and in morphograms show lumen narrowing). In both cases, the parallelism of the inner and outer vascular limits was maintained. There was no detectable increase of WCSA at the site of FAN (bar, 100 μm; see also supplementary Figure 2). (b): comparison of wall-to-lumen ratio (WLR) between the superotemporal artery (STA), AVN (n = 12) and FANs (n = 10). The difference between groups is statistically significant (P < 0.01).