We describe and test a new approach to quantify retinal blood flow, based on standard clinical examinations and imaging techniques, linked together with a physiological model. We use these findings to generate individualized estimates of the autoregulation range. We provide evidence that healthy subjects are closer to the lower autoregulation limit than thought before. This suggests that some retinas are less prepared to withstand hypoperfusion, even after small intraocular pressure rises or blood pressure drops.

Purpose: To determine the intrasession repeatability (test-retest variability) of parafoveal and peripapillary perfused capillary density (PCD) and normalized flux index (NFI) as assessed with Canon OCT-HS100 angiography. Methods: Pairs of optical coherence tomography angiography (OCT-A) images were obtained from the parafoveal and peripapillary region of 30 eyes of 30 healthy subjects. PCD and NFI were calculated using generic image-processing software. Macular ganglion-cell complex thickness (GCC) and peripapillary retinal nerve fiber layer thickness (RNFLT) were also recorded. Bland-Altman analysis was performed and the coefficient of repeatability (CoR) and intraclass correlation coefficient (ICC) were calculated. Correlations of parafoveal PCD/NFI with GCC and of peripapillary PCD/NFI with RNFLT were also computed. Results: Mean (standard deviation) parafoveal and peripapillary PCD were 40.0% (1.8%) and 44.5% (1.3%), respectively. Corresponding values for NFI were 151.2 (6.8) and 164.2 (3.9). For PCD, ICC was 0.76 for parafoveal and 0.79 for peripapillary measurements; corresponding CoRs were 2.7% and 1.8%. Corresponding values for NFI were 0.62 and 0.67 for ICC and 13.3 and 7.0 for CoR. Average measures ICC was 0.87/0.88 and 0.76/0.80 for the parafoveal/peripapillary PCD and NFI, respectively. PCD and NFI were weakly correlated with GCC (r = 0.39, P = 0.035; r = 0.33, P = 0.077) and moderately correlated with RNFLT (r = 0.43, P = 0.017; r = 0.55, P = 0.002). Conclusions: Repeatability of a commercially available OCT-A with generic image-processing software was good (NFI) to excellent (PCD). Our results indicate that changes surpassing the variability in healthy subjects should be easily detectable in a clinical setting. Translational Relevance: Repeatability estimates provide information regarding the relevance of changes in retinal perfusion.

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.

Purpose: To investigate the agreement between a fundus camera and a scanning laser ophthalmoscope in retinal vessel caliber measurements and to identify whether the presence of the central light reflex (CLR) explains potential discrepancies. Methods: For this cross-sectional study, we obtained fundus camera and scanning laser ophthalmoscope images from 85 eyes of 85 healthy individuals (aged 50–65 years) with different blood pressure status. We measured the central retinal artery equivalent (CRAE) and central retinal artery vein equivalent (CRVE) with the Knudtson–Parr–Hubbard algorithm and assessed the CLR using a semiautomatic grading method. We used Bland–Altman plots, 95% limits of agreement, and the two-way mixed effects intraclass correlation coefficient for consistency [ICC(3,1)] to describe interdevice agreement. We used multivariable regression to identify factors associated with differences in between-device measurements. Results: The between-device difference in CRAE (9.5 µm; 95% confidence interval, 8.0–11.1 µm) was larger than the between-device difference in CRVE (2.9 µm; 95% confidence interval, 1.3–4.5 µm), with the fundus camera yielding higher measurements (both P < 0.001). The 95% fundus camera–scanning laser ophthalmoscope limits of agreement were –4.8 to 23.9 µm for CRAE and –12.0 to 17.8 µm for CRVE. The corresponding ICCs(3,1) were 0.89 (95% confidence interval, 0.83–0.92) and 0.91 (95% confidence interval, 0.86–0.94). The between-device CRAE difference was positively associated with the presence of a CLR (P = 0.002). Conclusions: Fundus cameras and scanning laser ophthalmoscopes yield correlated but not interchangeable caliber measurements. The CLR induces bias in arteriolar caliber in fundus camera images, compared with scanning laser ophthalmoscope images. Translational Relevance: Refined measurements could yield better estimates of the association between retinal vessel caliber and ophthalmic or systemic disease.

Background/Objectives: To investigate the potential association between the endothelial dysfunction and arterial stiffness with retinal changes observed through optical coherence tomography (OCT) and OCT-angiography (OCT-A) in patients with retinal vein occlusion (RVO). Methods: Participants in this cross-sectional study were 28 patients with RVO. The demographic and clinical characteristics of all participants were recorded. Comprehensive ophthalmologic examinations were performed, including fundus photography, OCT and OCT-A. Endothelial dysfunction was assessed by measuring the endothelial glycocalyx thickness via the perfused boundary region (PBR5-25). Arterial stiffness was evaluated by measuring the carotid-femoral pulse wave velocity (PWV), the central systolic and diastolic blood pressures (cSBP and cDBP) and the augmentation index (Aix). For each ophthalmological outcome, we generated a saturated linear regression model with demographic and systemic vascular parameters serving as independent variables. Regression coefficients with the corresponding 95% confidence intervals (CIs) were reported. A p value < 0.05 was considered as statistically significant. Results: A 1 m/s increase in PWV was associated with a 0.6% reduction in inferior macular vessel density (VD) (p = 0.050). A 10 mmHg increase in cSBP was associated with a 0.03 mm² increase in foveal avascular zone (FAZ) area (p = 0.033). A 1% increase in Aix was associated with a 0.005 mm² increase in FAZ area (p = 0.008). A 1 μm increase in PBR5-25 was associated, on average, with a 4.4% decrease in superior peripapillary VD (p = 0.027). Conclusions: In patients with RVO, structural and microvascular retinal parameters were significantly associated with markers of endothelial dysfunction and arterial stiffness.

Background/Objectives: The ankle-brachial index (ABI) is a non-invasive diagnostic tool for peripheral artery disease (PAD) and a marker of systemic atherosclerosis, predictive of cardiovascular (CV) events. The ambulatory arterial stiffness index (AASI), derived from 24-h blood pressure monitoring, also predicts CV morbidity and mortality, particularly stroke. However, their combined prognostic utility in acute myocardial infarction (AMI) remains underexplored. This study aimed to assess the predictive value of ABI and AASI in patients with AMI. Methods: We conducted a single-center observational cohort study including 441 consecutive patients with AMI (79% male; mean age 62 years). ABI was measured using an automated device, with ≤0.9 defined as abnormal. AASI was calculated from 24-h blood pressure recordings. The primary endpoint was a composite of all-cause and CV death and major CV events, assessed in-hospital and over a 3-year follow-up. Results: Median ABI was 1.10 (IQR 1.00–1.18); 10.4% had abnormal ABI. Abnormal ABI was associated with a threefold higher risk of in-hospital adverse events (OR 2.93, 95% CI: 1.48–5.81, p = 0.002). In Cox regression, abnormal ABI predicted long-term all-cause mortality (HR 2.88, 95% CI: 1.53–5.42, p = 0.001), independent of traditional risk factors. Each 0.1 increase in AASI was linked to a 21% higher risk of the composite outcome (p = 0.001) and 25% increased risk of recurrent AMI or urgent revascularization (p = 0.001). Conclusions: In this prospective cohort of patients with AMI, ABI and AASI were associated with adverse outcomes, suggesting their potential role in risk stratification. These exploratory findings require validation in larger, multicenter cohorts to assess their incremental prognostic value and generalizability.