U-Shaped Effect of Blood Pressure on Structural OCT Metrics and Retinal Perfusion in Ophthalmologically Healthy Subjects

Abstract

Purpose: We wanted to investigate the association of blood pressure (BP) status with the ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) thickness of nonglaucomatous eyes and to elucidate whether this effect is related to vascular metrics proxying retinal perfusion.

Methods: For this case-control study, we prospectively included 96 eyes of 96 healthy subjects (age 50-65) from a large-scale population-based cohort in the northern Netherlands (n = 167,000) and allocated them to four groups (low BP, normal BP [controls], treated arterial hypertension [AHT], untreated AHT). We measured macular GCIPL and RNFL (mRNFL) and peripapillary RNFL (pRNFL) thicknesses with optical coherence tomography (OCT). We estimated retinal blood flow (RBF), retinal vascular resistance (RVR), and autoregulatory reserve (AR) from quantitative OCT-angiography, fundus imaging, BP, and intraocular pressure. We compared structural and vascular metrics across groups and performed mediation analysis.

Results: Compared to controls, GCIPL was thinner in the low BP group (P = 0.013), treated hypertensives (P = 0.007), and untreated hypertensives (P = 0.007). Treated hypertensives exhibited the thinnest mRNFL (P = 0.001), temporal pRNFL (P = 0.045), and inferior pRNFL (P = 0.034). The association of GCIPL thickness with BP was mediated by RBF within the combined low BP group and controls (P = 0.003), by RVR and AR within the combined treated hypertensives and controls (P = 0.001, P = 0.032), and by RVR within the combined untreated antihypertensives and controls (P = 0.022).

Conclusions: Inner retinal thinning was associated with both tails of the BP distribution and with ineffective autoregulation. Longitudinal studies could clarify whether these defects can explain the reported glaucomatous predisposition of these population groups.

Figure 1.

Structural (A, B) and vascular (C, D) regions of interest. (A) The mRNFL and GCIPL thicknesses measured within the larger (10 mm diameter) circle centered at the fovea, excluding the innermost 1 mm diameter circle and the nasal sector of the outer ring. (B) The pRNFL measured at a circle of 3.45 mm diameter centered at the ONH. (C) OCT-A scan of 6 × 6 mm centered at the fovea. Signal intensity inside the innermost 3-mm diameter circle is binarized in flow (black) and non-flow (white). (D) A 45° fundus image centered at the ONH. The six largest arterioles and six largest venules between rings of two and three optic disc diameters are marked in blue.

Figure 2.

Theoretical autoregulation curve (axes in arbitrary units). RBF is displayed as a function of RPP. Within the autoregulation range, blood flow is maintained constant. The distance of the actual (measured) RPP from the LARL is the AR.

Figure 3.

GCIPL, mRNFL, and pRNFL as a function of BP status. Significant differences after post hoc comparisons (adjusted for multiple testing) are marked. The thicker layers observed in the control group (normal BP) than in the low BP or AHT groups create a characteristic (inverse) U shape.

Figure 4.

Absolute total RBF, RVR, and AR as a function of BP status. Significant differences after post hoc comparisons (adjusted for multiple testing) are marked. With increasing BP, RBF increases less than RVR, resulting in an autoregulation effect visible in the first panel. A statistically significant larger variability is observed for the AR of treated hypertensives (third panel), suggesting that subjects in this group can be very close or very far from the lower autoregulation limit.

Figure 5.

Quantile regression models for AR at each BP status. Parameter estimates (y-axis) represent the relative AR (compared to controls) for every AR decile (x-axis). Low BP individuals (left panel) have a smaller AR than controls (y < 0), whereas individuals with untreated AHT (right panel) have a larger AR than controls (y > 0). Individuals with treated AHT (middle panel) have a smaller AR only when intensively treated (leftmost deciles).