U-shaped effect of blood pressure on structural OCT metrics and retinal blood flow autoregulation in ophthalmologically healthy subjects

Abstract

Objective1) To investigate the effect of low blood pressure (BP), treated arterial hypertension (AHT), and untreated AHT on the ganglion cell-inner plexiform layer (GCIPL) and the retinal nerve fiber layer (RNFL) thickness of non-glaucomatous eyes and 2) to elucidate whether this effect is related to crossing the lower limit of retinal blood flow (RBF) autoregulation.DesignCross-sectional, case-control.SubjectsWe included 96 eyes of 96 ophthalmologically healthy subjects (age 50-65). Participants were prospectively recruited from a large-scale cohort study in the northern Netherlands (n=167,000; Lifelines Biobank). They were allocated to four groups (low BP, normal BP [controls], treated AHT, untreated AHT), based on information from previous visits and strict distribution criteria.MethodsInner retinal layer thicknesses were obtained with optical coherence tomography (OCT). Fractal dimension of the superficial microvasculature was quantified with OCT-angiography and customized software. Central retinal vessel diameters were obtained from fundus images. BP and intraocular pressure measurements were also acquired. Measurements were combined with a validated physiological model to estimate vascular outcome measures. Structural and vascular metrics were compared across groups and mediation analysis was performed.Main outcome measuresStructural: macular GCIPL and RNFL (mRNFL), peripapillary RNFL (pRNFL) thickness. Vascular: RBF, retinal vascular resistance (RVR), autoregulatory reserve (AR).ResultsCompared 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). In multivariable analysis, RBF was mediating the association of GCIPL thickness with BP within the combined low BP group and controls (P=0.003), RVR together with AR were mediating the same association within the combined treated hypertensives and controls (P=0.001 and P=0.032), and RVR was mediating the association within the combined untreated antihypertensives and controls (P=0.022).ConclusionsWe uncovered GCIPL and RNFL thinning related to both tails of the BP distribution. GCIPL thinning was associated with reduced RBF autoregulatory capacity. This predisposition to glaucomatous damage could explain the frequent epidemiological finding of increased glaucoma risk in certain subgroups, such as subjects with nocturnal BP dipping or aggressively treated AHT. Longitudinal studies could confirm this postulation.

Evaluation of retinal nerve fibre layer thickness as a possible measure of diabetic retinal neurodegeneration in the EPIC-Norfolk Eye Study

“…An inverse U-shaped effect exists between BP status and structural OCT metrics, with both low and high BP associated with inner retinal layer thinning. 48 ACEIs and diuretics have been proposed to have differential effects on the ocular microvasculature structurally and functionally in terms of diurnal BP regulation compared to other classes of antihypertensive medications. 47 Moreover, only a small autoregulatory reserve is present in individuals with low BP, or in those with intensively treated arterial hypertension.…”

“…47 Moreover, only a small autoregulatory reserve is present in individuals with low BP, or in those with intensively treated arterial hypertension. 48 Low or unstable BP can subsequently result in low ocular perfusion pressure, 49 thereby increasing the risk of flow-mediated damage to RGCs. Considering that up to 40-60% of participants with DM may have concomitant hypertension, 50 51 the results of our study have important implications for the use of anti-hypertensive medications and retinal health, and highlight an area where further research is needed.…”

Parallelism and non-parallelism in diabetic nephropathy and diabetic retinopathy

“…Studies have shown that diabetic patients have elevated blood and serum viscosity and elevated red blood cell aggregation and adhesion, which increase the resistance to blood flow and reduce its stability in the flow process, leading to slow blood flow and decreased blood flow rate and triggering circulatory disorders ( 117 ). From a hemodynamic perspective, ocular blood flow is determined by the balance between ocular perfusion pressure and vascular resistance ( 118 ). Prolonged hyperglycemia leads to endothelial dysfunction, increased vascular resistance, abnormal retinal perfusion, and exacerbation of retinal ischemia and hypoxia ( 119 ).…”