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

Objective: 1) 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. Design: Cross-sectional, case-control. Subjects: We 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. Methods: Inner 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 measures: Structural: macular GCIPL and RNFL (mRNFL), peripapillary RNFL (pRNFL) thickness. Vascular: RBF, retinal vascular resistance (RVR), autoregulatory reserve (AR). 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). 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). Conclusions: We 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.