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Purpose: The retina contains a number of vasoactive neuropeptides and corresponding receptors, but the role of these neuropeptides for tone regulation of retinal arterioles has not been studied in detail., Methods: Porcine arterioles with preserved perivascular retinal tissue were mounted in a wire myograph, and the tone was measured after the addition of increasing concentrations of bradykinin, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), substance P (SP), calcitonin gene-related peptide (CGRP) and brain natriuretic peptide (BNP). The experiments were performed during inhibition of the synthesis of nitric oxide (NO), prostaglandins and dopamine and were repeated after removal of the perivascular retinal tissue., Results: Bradykinin, VIP and CGRP induced significant concentration-dependent dilatation and NPY significant concentration-dependent contraction of the arterioles in the presence of perivascular retinal tissue (p < 0.03 for all comparisons) but not on isolated arterioles. BNP and SP had no effect on vascular tone. The NOS inhibitor L-NAME reduced bradykinin- and VIP-induced relaxation (p < 0.001 for both comparisons), whereas none of the other inhibitors influenced the vasoactive effects of the studied neuropeptides., Conclusion: The effects of neuropeptides on the tone of retinal arterioles depend on the perivascular retinal tissue and may involve effects other than those mediated by nitric oxide, prostaglandins and adrenergic compounds. Investigation of the mechanisms underlying the vasoactive effect of neuropeptides may be important for understanding and treating retinal diseases where disturbances in retinal flow regulation are involved in the disease pathogenesis., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To study the orbital perfusion parameters of ophthalmic artery (OA) and central retinal artery (CRA) in inactive TED and the changes following surgical decompression., Methods: Non-randomised clinical trial. 24 inactive moderate-to-severe TED orbits of 24 euthyroid cases underwent surgical decompression and examined again at 3 months. The peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistivity index (RI) of OA and CRA were evaluated using colour doppler imaging and normative database was established using 18 healthy controls., Results: The mean age was 39.38 ± 12.56 years and male: female ratio was 1: 1.18. Intraocular pressure was higher, and CRA-PSV, CRA-RI, OA-PSV, and OA-EDV were lower in TED in comparison to heathy orbits. The CRA-PSV, CRA-EDV, OA-PSV, and OA-EDV negatively correlated with proptosis and duration of thyroid disease. The area under curve of OA-PSV (95% CI:0.964-1.000, p < 0.001) and OA-EDV (95% CI:0.699-0.905, p < 0.001) helped in differentiating TED orbits from HC, and in predicting the severity of disease. Post decompression, CRA-PSV, CRA-EDV, OA-PSV, and OA-EDV improved, with decrease in CRA-RI and OA-RI in both lipogenic and MO., Conclusions: The orbital perfusion is reduced in inactive TED. The changes in OA flow velocities can help in differentiating inactive TED from healthy orbits and progression of TED. Sequential orbital CDI of OA and CRA can serve as an objective tool for case selection and monitoring response to surgical decompression., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: To assess changes in orbital vessels by Color Doppler Imaging (CDI) in patients with Primary Open Angle Glaucoma (POAG)., Methods: This cross-sectional study included 120 subjects - 60 patients with POAG and 60 controls, all of whom underwent full ophthalmological examinations and orbital CDI. The Ophthalmic Artery (OA), Central Retinal Artery (CRA) and Ciliary Arteries (CA) were identified, and for each of them, we measured Peak Systolic Velocity (PSV), End Diastolic velocity (EDV) and Resistivity Index (RI)., Results: The PSV of the OA and CRA were significantly lower in patients with POAG compared to normal controls (P<0.0001, < 0.009 respectively). The EDV in the OA, CRA and CA were significantly lower than in normal controls (P<0.0001). The RI of the OA, CRA and CA were significantly higher in patients with POAG compared to controls (P<0.0001). The EDV of the OA showed significant negative correlation with duration of glaucoma (r=-0.37, P<0.042). The EDV of the CA showed significant negative correlation with intraocular pressure (IOP) (r=-0.86 and P value 0.0001). The PSV and EDV of the CRA showed significant negative correlation with IOP (r=-0.45, r=-0.73, P values 0.011, and 0.0001 respectively), and the RI of the CRA showed significant positive correlation with IOP (r=0.42 and P value 0.021)., Conclusion: CDI is a feasible, noninvasive, safe tool for the assessment of hemodynamic changes in the orbital arteries of POAG patients. The orbital arteries showed significantly lower flow velocities and increased resistivity indices in patients with POAG compared to the control group, and these changes were correlated with glaucoma duration and IOP., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

We have previously reported that porcine retinal veins can be contracted by vasoactive factors such as endothelin-1, but it is still unknown which cells play the major role in such contraction responses. This study seeks to confirm whether retinal vein endothelial cells play a significant role in the endothelin-1 induced contraction of porcine retinal veins. This is a novel study which provides confirmation of the endothelial cells' ability to contract retinal veins using a live vessel preparation. Retinal veins were isolated from porcine retina and cannulated for perfusion. The vessels were exposed to extraluminal delivery of endothelin-1 (10 -8  M) and change in vessel diameter recorded automatically every 2 s. A phase contrast objective lens was also used to capture images of the endothelial cell morphometries. The length, width, area, and perimeter were assessed. In addition, vein histology and immuno-labeling for contractile proteins was performed. With 10 -8  M endothelin-1 contractions to 63.6% of baseline were seen. The polygonal shape of the endothelial cells under normal tone became spindle-like after contraction. The area, width, perimeter and length were significantly reduced by 54.8%, 48.1%, 28.5% and 10.5% respectively. Three contractile proteins, myosin, calponin and alpha-SMA were found in retinal vein endothelial cells. Retinal vein endothelial cells contain contractile proteins and can be contracted by endothelin-1 administration. Such contractile capability may be important in regulating retinal perfusion but could also be a factor in the pathogenesis of retinal vascular diseases such as retinal vein occlusion. As far as we are aware, this is the first study on living isolated veins to confirm that endothelial cells contribute to the endothelin-1 induced contraction., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: In this study, we investigated the vasodilation properties on pre-contracted retinal arteries of a restricted series of carbonic anhydrase inhibitors (CAIs) of the sulfonamide type with enhanced lipophilicity, to assess if it affects the potency of CAIs as vasodilators., Methods: Carbonic anhydrase (CA) inhibition and in vitro kinetics of the compounds designed and synthesized for testing in this study were assessed by extracting human CA isoform proteins (hCA) from human cells expressing the isoforms of interest, and then measure the affinity of the novel compound for the hCAs by stopped-flow CO 2 hydrase spectroscopy. Lipophilicity of compounds was measured by obtaining their octanol-water partition coefficient, expressed as calculated logP. Porcine eyes were obtained from a local abattoir, and the wall tension of porcine retinal arteriole segments dissected from the eyes was measured with small wire vessel myography. The effects of the CA compounds on wall tension were assessed by adding them to the myography bath, after pre-contracting the vessel by prostaglandin analog U-46619., Results: All compounds induced vasodilation but at different concentrations. Among the tested compounds the most potent vasodilators were found to be the seleno-compound 4 and sulfur-ether compound 8 with EC 50 values of 7.13 × 10 -5 and 7.93 × 10 -5 M, respectively, whereas the remaining ones induced complete vasodilation at EC 50 comprised within the sub millimolar range., Conclusions: All the data reported in this study (i.e. results from myography, in vitro kinetics and LogPs) confirm the important role played by several CA isoforms in vasodilation, although the precise mechanism of action still remains to be elucidated.

Purpose: The aim of the study was to obtain the values of oxygen saturation in retinal vessels and ophthalmic blood flow parameters in a healthy Caucasian population and assess whether the oximetry parameters are affected by the flow rate or the vascular resistance., Methods: The spectrophotometric retinal oximetry and colour Doppler imaging (CDI) of retinal vessels were successfully performed with 52 healthy subjects (average age 29.7 ± 5.6 years). The retinal oximeter simultaneously measures the wavelength difference of haemoglobin oxygen saturation in retinal arterioles and venules. The arteriolar and venular saturation in both eyes was measured. The peak systolic (PSV) end diastolic (EDV) velocities, resistive (RI) and pulsatility (PI) indices were obtained for both eyes using CDI in the ophthalmic artery. A paired t-test and two sample t-tests were used for statistical analyses. The correlation was assessed using the Pearson coefficient correlation., Results: The mean oxygen saturation level was 96.9 ± 3.0% for the retinal arterioles and 65.0 ± 5.1% for the retinal venules. The A-V difference was 31.8 ± 4.6%. The mean of the measured haemodynamic parameters was PSV 46.6 ± 9.4 cm/s, EDV 12.0 ± 3.5 cm/s, PI 1.68 ± 0.38 and RI 0.74 ± 0.05. No significant difference in oxygen saturation and haemodynamic parameters was found between the left and the right eyes or the dominant and non-dominant eye. The oximetry and ultrasound values were sex independent. The Pearson correlation coefficient demonstrated a significant yet weak negative correlation between A-V difference and RI (r = -0.321, p = 0.020)., Conclusions: A negative correlation between A-V difference and resistance index was observed, suggesting that reduced oxygen consumption may reflect the increased vascular tone of the ophthalmic vessels, which is likely determined by autoregulatory mechanisms., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: Benign essential blepharospasm (EB) is a focal facial dyskinesia that occurs with the involuntary contraction of muscles around the eyes. In the literature, studies on blepharospasm focus on elucidating the pathophysiology of this condition in the brain. To the best of our knowledge, there is no research evaluating the orbital imaging findings of patients with EB. Therefore, the current study aimed to determine whether there was any change in the blood supply of muscles around the eye or ocular blood flow in patients with blepharospasm and investigate flow changes that may be caused by spasm., Methods: Thirty patients with EB and 30 controls were included in the study. Orbital Doppler ultrasound was performed in all cases to measure ophthalmic and temporal artery peak systolic velocity and end diastolic velocity and calculate resistive index values. Superior ophthalmic vein blood flow velocity (SOVBFV) was also measured., Results: There was no significant difference between the groups in terms of age and gender distribution (P = 0.345 and 0.870, respectively). SOVBFV was found to be significantly higher in the EB group (P = 0.001). No significant difference was observed in the remaining investigated parameters., Conclusions: In conclusion, our study suggested that ocular spasm in patients with EB had no effect on blood flow other than SOVBFV. When SOVBFV was compared between the EB and control groups, it was found to be increased in the EB group. We consider that this statistical difference may be clinically and pathophysiologically significant., (© 2021. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Background: To evaluate the effects of COVID-19 infection on the ocular vascular structure including choroidal thickness and retrobulbar blood flow values in comparison with healthy subjects., Methods: Ninety eyes of 90 patients were included in this study. Participants were divided into Group 1 (n = 30) with mild COVID-19 infection, Group 2 (n = 31) with moderate disease, and Group 3 with age- and sex-matched healthy subjects (n = 29). Choroidal thickness was measured at the subfoveal area and at 500-µm intervals nasal and temporal to the fovea up to a distance of 1500 µm, using the enhanced depth imaging (EDI) technique of spectral coherence tomography (SD-OCT). The peak systolic velocity (PSV), end diastolic velocity (EDV), resistive index (RI), and pulsatility index (PI) values of the central retinal artery (CRA) and ophthalmic artery (OA) were evaluated with color Doppler ultrasonography (CDU)., Results: The choroidal thickness was significantly thinner in Group 1 and Group 2 than in Group 3 at all measurement points (p <0.001). This difference was not present between Group 1 and Group 2 who had COVID-19 disease of different severity (p>0.05).Among the retrobulbar blood flow parameters, OA PSV value was significantly lower in Group 1 and Group 2 compared to Group 3 (p = 0.025, p = 0.016, respectively). However, the CRA PSV and EDV and OA EDV values, and the CRA and OA PI and RI values were not statistically different between the groups (p> 0.05)., Conclusion: COVID-19 infection may predispose patients to ocular vascular pathologies by affecting both choroidal and retrobulbar blood flow., (Copyright © 2022. Published by Elsevier B.V.)

Purpose : To assess the agreement between Line 3-5 raster scan mode and circular scan mode for measuring retinal vessel diameter, and to analyze the influence of scanning distance on retinal vessel diameter and agreement. Methods : 79 healthy participants (79 eyes) were scanned with two modes. The scanning distance was defined as the distance from the center of the optic disc to the intersection of the blood vessel and the scan line on the raster image. The large superior temporal vessel was measured, with the distance between vascular wall hyperreflectivities measured to obtain vessel diameters. The degree of agreement between the line 3-5 raster scan and circular scan modes, and the effect of scanning distance on agreement and vascular diameter were assessed. Results : There was good agreement between line 3 subgroup and the circular scan for measuring venous and arterial diameter (venous: intraclass correlation coefficients (ICCs) = 0.87, p < .001; arterial: ICCs = 0.84, p < .001). Unexpectedly, diameters from the fourth raster scan were only comparable to the circular scan in measuring venous diameter (ICCs = 0.86, p < .001), despite the same scanning distance between the fourth raster line and circular scan. Vessels with a scanning distance between 1400 μm - 1799 μm showed good agreement with the circular scan (venous and arterial: all ICCs ≥ 0.84, p < .001). In addition, venous diameter and arterial diameter decreased with increasing distance from the optic disc center, with venous and arterial diameter decreasing by 0.02 μm/μm ( p < .001) and 0.007 μm/μm ( p = .02), respectively. Conclusion : Arterial and venous diameter measured by the circular mode was comparable to only one scan line and two scan lines of the raster scan mode, respectively. Our study identified a difference between the two scan modes, with the difference not fully attributable to differences in scanning distance. Prospective studies reporting vascular diameter as a primary outcome should report the scan mode used.

Acute, painless, monocular vision loss (APMVL) usually has a vascular aetiology. We conducted a prospective observational study from 2011 to 2018 to analyse the added value of colour Doppler imaging to assess orbital vessel blood flow in the diagnosis of APMVL. The study included 67 patients (39 [58.2%] men; mean age, 65.9 years [SD 13.7]) with APMVL evaluated at the Neurosonology Laboratory within the first 5 days of symptom onset, who were classified as having either transient or persistent monocular blindness. The blood flow in the ophthalmic and central retinal arteries was assessed using colour Doppler ultrasound with a linear 7.5-MHz transducer. Thirty-three (49.3%) patients presented transient monocular blindness, with reduced blood flow in either the ophthalmic or central retinal artery. The group with persistent vision loss included 24 cases of central retinal artery occlusion (CRAO) and 10 cases of ischaemic optic neuropathy (35.8% and 14.9%, respectively, of the total sample). These patients were older and had a higher prevalence of hypertension and mild carotid atherosclerosis. Orbital colour Doppler ultrasound (OCDUS) clarified the mechanism/cause of the ischaemia in 11 (16.4%) patients and showed abnormal flow in 46 (68.7%) patients, confirming the vascular origin in 19 (57.6%) of the transient monocular blindness cases. Lower peak systolic velocity was observed in patients with CRAO ( p < 0.001), and a velocity < 10 cm/s in the central retinal artery was independently associated with the diagnosis of CRAO. OCDUS can be helpful in confirming the vascular cause and identifying the aetiology of APMVL.

Most studies of the effect of acute elevation of intraocular pressure (IOP) on ocular blood-flow have utilized optical coherence tomography (OCT) to characterize retinal and choroidal flow and vascular density. This study investigates the effect of acute IOP elevation on blood flow velocity in the retrobulbar arteries and veins supplying and draining the eye, which, unlike the retinal and choroidal vasculature, are not directly compressed as IOP is increased. By cannulation of the anterior chamber of 20 Sprague-Dawley rats, we increased IOP in 10 mmHg steps from 10 to 60 mmHg and returned to 10 mmHg. After 1 min at each IOP (and 3 min after return to 10 mmHg), we acquired 18 MHz plane-wave ultrasound data at 3000 compound images/sec for 1.5 s. We produced color-flow Doppler images by digital signal processing of the ultrasound data, identified retrobulbar arteries and veins, generated spectrograms depicting flow velocity over the cardiac cycle and characterized changes of vascular density and perfusion in the orbit overall. Systolic, diastolic and mean velocities and resistive and pulsatile indices were determined from arterial spectrograms at each IOP level. Baseline mean arterial and mean venous velocities averaged 30.9 ± 10.8 and 8.5 ± 3.3 mm/s, respectively. Arterial velocity progressively decreased and resistance indices increased at and above an IOP of 30 mmHg. Mean arterial velocity at 60 mmHg dropped by 55% with respect to baseline, while venous velocity decreased by 20%. Arterial and venous velocities and resistance returned to near baseline after IOP was restored to 10 mmHg. Both vascular density and orbital perfusion decreased with IOP, but while perfusion returned to near normal when IOP returned to 10 mmHg, density remained reduced. Our findings are consistent with OCT-based studies showing reduced perfusion of the retina at levels comparable to retrobulbar arterial flow velocity change with increased IOP. The lesser effect on venous flow is possibly attributable to partial collapse of the venous lumen as volumetric venous outflow decreased at high IOP. The continued reduction in orbital vascular density 3 min after restoration of IOP to 10 mmHg might be attributable to persisting narrowing of capillaries, but this needs to be verified in future studies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Glia and their communication via connexin 43 (Cx43) gap junctions are known to mediate neurovascular coupling, a process driven by metabolic demand. However, it is unclear whether Cx43 mediated glial communication intermediates classical autoregulation. Here we used viral transfection and a glial fibrillary acidic protein (GFAP) promoter to downregulate glial Cx43 to evaluate its role in retinal vascular autoregulation to ocular perfusion pressure (OPP) reduction., Methods: Adult rats were intravitreally injected with the viral active construct or a control. Three weeks after the injection, eyes were imaged using confocal scanning laser ophthalmoscopy before and during a period of OPP decrease induced by blood draw to lower blood pressure or by manometric IOP elevation. Vessel diameter responses to the OPP decrease were compared between Cx43-downregulated and control-injected eyes. The extent of Cx43 downregulation was evaluated by Western blot and immunohistochemistry., Results: In control eyes, the OPP decrease induced dilatation of arterioles, but not venules. In Cx43-downregulated eyes, Cx43 expression in whole retina was decreased by approximately 40%. In these eyes, the resting diameter of the venules increased significantly, but there was no effect on arterioles. In Cx43-downregulated eyes, vasoreactivity evoked by blood pressure lowering was significantly compromised in both arterioles (P = 0.005) and venules (P = 0.001). Cx43 downregulation did not affect the arteriole responses to IOP elevation, whereas the responses of the venules showed a significantly greater decrease in diameter (P < 0.001)., Conclusions: The downregulation of retinal Cx43 in GFAP-expressing cells compromises vasoreactivity of both arterioles and venules in response to an OPP decrease achieved via blood pressure lowering or IOP elevation. The results also suggest that Cx43-mediated glial communication actively regulates resting venular diameter.

Purpose : Assessment of Ocular Perfusion Pressure (OPP) requires estimation of the Mean Central Retinal Artery Pressure (MCRAP) [OPP = MCRAP-IOP]. In a seated position, MCRAP is currently estimated as 2/3 of the Mean Arterial Pressure (MAP) to account for the hydrostatic reduction of MAP at eye level. We tested a surrogate method for direct MCRAP assessment by measuring MAP with Arm-Up and cuff at eye level (AUMAP) at different postures and ages. Methods : MAP and AUMAP were assessed in a mixed population of 136 subjects (mean age 44 ± 17.39 years) including healthy participants (N = 30) and patients with optic neuropathies (Glaucoma suspects, N = 14; Open-Angle Glaucoma, N = 26, LHON, N = 19; MS, N = 47) not expected to alter systemic blood pressure. None of the subjects had history of carotid stenosis or pharmacological treatment to regulate blood pressure. AUMAP was also tested in two subgroups in supine (N = 42) and -10° Head Down body Tilt position (HDT, N = 46). Results : In the seated position, both 2/3MAP and AUMAP increased with increasing age, however with steeper (2x) slope for AUMAP ( P < .0001). With decreasing angle of body tilt, AUMAP increased while MAP decreased. The mean AUMAP/MAP ratio (posture coefficient) was, seated, 0.73 (SE 0.003); supine, 0.90 (SE 0.005); HDT, 0.97 (SE 0.005). In the seated position only, the AUMAP/MAP ratio significantly increased with age ( P < .0001). Mean posture coefficients obtained with AUMAP were in the range of those based on either direct ophthalmodynamometric measurements or hydrostatic estimations. Conclusions : Surrogate measurement of MCRAP in individual subjects is feasible using the simple AUMAP approach that provides a straightforward estimation of OPP (OPP = AUMAP - IOP) at different body postures. The standard method OPP = 2/3*MAP-IOP in the seated posture underestimates OPP at older ages. Clinical estimation of OPP would benefit from the use of AUMAP, in particular for head-down postures.

When retinal activity is increased by exposure to dynamic visual stimuli, blood vessels dilate and the flow of blood within vessels increases to meet the oxygen and glucose demands of the neurons. This relationship is termed 'neurovascular coupling' and it is critical for regulating control of the human retinal vasculature. In this study, we used a recently developed technique based on a dual-beam adaptive optics scanning laser ophthalmoscope to measure changes in red blood cell velocities, vessel diameter, and flow in interconnected small parafoveal retinal vessels (< 50 µm) of nine healthy participants. A full-field flicker stimulus was presented onto the retina to induce a vascular response to neural activity. Flicker stimulation increased blood velocity, vessel diameter, and therefore flow in arterioles, capillaries, and venules in all nine subjects. ANOVA and post hoc t-test showed significant increases in velocity and flow in arterioles and venules. These measurements indicate that the mechanism of neurovascular coupling systematically affects the vascular response in small retinal vessels in order to maintain hemodynamic regulation in the retina when exposed to visual stimulation, in our case flicker. Our findings may provide insight into future investigations on the impairments of neurovascular coupling from vascular diseases such as diabetic mellitus.

Structural and functional changes occur in the brain after vision losses. The purpose of the present study was to investigate central retinal artery (CRA) hemodynamics in the healthy eye of individuals developing late monocular blindness (LMB) using colored Doppler ultrasonography.The CRAs of 13 healthy eyes of 13 patients with LMB and of 13 healthy individuals as a control group were evaluated in this prospective study. Peak systolic velocity, end-diastolic velocity, mean flow velocity, systolic/diastolic velocity ratio, and resistivity and pulsatility index (RI, PI) values in the CRAs were determined using colored Doppler ultrasonography in both groups.The mean age of all the individuals examined was 39.3 ± 12.3 years, and loss of vision in the LMB patients had been present for a mean 22 ± 13.2 years. The PSH, DHS, and mean flow velocity values in the LMB group were 13.3 ± 2.5 cm/s, 3.1 ± 0.8 cm/s, and 6.5 ± 1.6 cm/s, respectively, significantly lower than in the control group at 18.6 ± 5 cm/s, 5.5 ± 2.8 cm/s, and 10 ± 3.2 cm/s (P < 0.05). The PI, RI, and systolic/diastolic velocity ratio values differences in the both group were not statistically significant (P > 0.05).In conclusion, the absence of a significant difference in RI and PI values between the 2 groups revealed that vascular resistance did not develop in the CRA hemodynamics of healthy eyes of individuals with LMB, although the low velocity values showed an increase in CRA width.

Background and Objectives: Fluorescein angiography (FA) is widely used in ophthalmology for examining retinal hemodynamics and vascular morphology. Artery-venous classification is an important step in FA image processing for measurement of feature parameters, such as arterio-venous passage time (AVP) and arterio-venous width ratio (AVR) that are proven useful in clinical assessment of circulation disturbance and vessel abnormalities. However, manual artery-venous classification needs expertise and is rather time consuming, and little effort has been devoted to develop automatic classification methods. In order to solve this problem, we propose a novel artery-venous classification method using region growing strategy with sequential and structural features (RGSS)., Methods: The main procedures of our proposed RGSS method include: (i) registration of FA image sequence by mutual-information method; (ii) extraction of sequential features of the dye perfusion process from the registrated FA images; (iii) extraction of vessel structural features from vascular centerline map; (iv) based on the obtained features, seeds of arteries and veins within initial growing region (here optic disk) are generated and then propagated in the entire vessel network using region growing strategy. The RGSS method was tested on our own dataset and public Duke dataset, and its performance was evaluated quantitatively., Results: Tests show that RGSS method is able to classify arteries and veins from the complicated vessel network in FA images, with high classification accuracy of 0.91 ± 0.04 on Duke dataset and 0.92 ± 0.03 on our dataset. The employed sequential and structural features are demonstrated to be effective in classifying thin arteries and veins at vessel crossings., Conclusions: Automatic artery-venous classification can be accomplished using our proposed RGSS method with high accuracy. The RGSS method not only emancipates ophthalmologists from hard work of manual marking of arteries and veins, but also helps in measuring important parameters (such as AVP and AVR) for clinical assessment of circulation disturbance and vessel abnormalities., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: To characterize ocular perfusion pressure (OPP) fluctuations with continuous telemetry over 24-hour periods across multiple days in nonhuman primates (NHPs) to test the hypotheses that OPP differs among NHPs and that the diurnal cycle of OPP is characterized by low OPP during sleep., Methods: We have developed and validated two implantable radiotelemetry systems that allow continuous measurement of intraocular pressure (IOP), arterial blood pressure (BP), and OPP up to 500 Hz. OPP was measured unilaterally in 12 male NHPs for periods of 38 to 412 days. IOP transducers were calibrated directly via anterior chamber manometry, and OPP was calculated continuously as central retinal artery BP minus IOP. OPP data were corrected for signal drift between calibrations and averaged hourly., Results: OPP varied widely among animals, with daily averages ranging from ∼47 to 65 mm Hg. In eight of 12 NHPs, OPP was significantly lower during sleep compared to waking hours. In three animals, the diurnal cycle was reversed and OPP was significantly higher during sleep (P < 0.05), and one NHP showed no diurnal cycle. Day-to-day OPP variability within NHPs was the largest source of overall OPP variability, even larger than the differences between NHPs. Average daily OPP showed an unexplained ∼32-day cyclic pattern in most NHPs., Conclusions: Average OPP varied widely and exhibited differing diurnal cycles in NHPs, a finding that matches those of prior patient studies and indicates that OPP studies in the NHP model are appropriate. Infrequent snapshot measurements of either IOP or BP are insufficient to capture true IOP, BP, and OPP and their fluctuations.

Purpose: Retinal vasomotor activity can be regulated by two major endothelial enzymes, nitric oxide synthase (NOS) and cyclooxygenase (COX). The vascular arginase also consumes a NOS substrate and thus impedes NOS-mediated vasodilation. Diabetes mellitus exhibits vascular complications in the retina with elevated oxidative stress and compromised NOS-mediated vasodilation. However, the underlying molecular mechanisms remain unclear, and the effect of diabetes on COX-mediated vasodilation is unknown. Herein, we examined the relative impact of diabetes on retinal arteriolar dilations to COX and NOS activation and the roles of arginase and superoxide in diabetes-induced vasomotor dysfunction., Methods: Retinal arterioles were isolated from streptozocin-induced diabetic pigs (2 weeks of hyperglycemia, 433 ± 27 mg/dL) or age-matched control pigs (97 ± 4 mg/dL). The vasodilations to bradykinin (NOS activator) and histamine (NOS/COX activator) were examined in vitro., Results: Retinal arteriolar dilations to histamine and bradykinin were significantly reduced after 2 weeks of diabetes. The NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) attenuated the dilations of control vessels, but not diabetic vessels, to histamine. In the presence of L-NAME and COX inhibitor indomethacin, histamine-induced dilations of control and diabetic vessels were reduced similarly. Treatment of diabetic vessels with arginase inhibitor nor-NOHA, but not superoxide dismutase mimetic TEMPOL, preserved both histamine- and bradykinin-induced dilations in an L-NAME-sensitive manner., Conclusions: Arginase, rather than superoxide, impairs endothelium-dependent NOS-mediated dilation of retinal arterioles during diabetes, whereas vasodilation mediated by COX remains intact. Blockade of vascular arginase may improve endothelial function of retinal arterioles during early onset of diabetes.

Pulse wave attenuation characteristics reflect compliance and resistance properties of the vessel wall as well as initial pulse generation factors. Recently, it has become possible to measure and map the retinal vessel wall pulse wave amplitudes. Predictable pulse wave amplitude distribution may allow inferences to be made concerning vascular compliance and resistance. Twenty-eight eyes from sixteen subjects (8 male and 8 female) were examined using modified retinal photoplethysmography with simultaneous ophthalmodynamometry. This allowed the assessment of vessel wall pulsation amplitudes under a dynamic range of intraocular pressures. Pulse amplitudes were calculated using harmonic regression analysis. The pulse wave attenuation was measured under different ranges of ophthalmodynamometric force (ODF) as a function of distance along the vessel (VDist), which in turn was calculated in disc diameters (DD) from the center of the optic disc. A linear mixed-effects model with randomized slopes and intercepts was used to estimate the correlations between the logarithmically transformed harmonic regression wave amplitude (HRWa) and the Fourier trigonometric coefficients with the predictors (VDist and ODF). The retinal venous harmonic regression wave attenuation (coefficient value±standard error) -0.40±0.065/DD, (p-value < 0.00001, 95% confidence interval (CI) -0.53 to -0.27), which was approximately twice that of the arterial -0.17±0.048/DD, (p-value < 0.0004, 95% CI = -0.27 to -0.08). There was a positive correlation between attenuation of the harmonic regression wave and ophthalmodynamometric force in both vascular systems. The attenuation of all but the sine coefficient of the second Fourier harmonic (bn2) achieved statistical significance in the correlation with VDist. The cosine coefficient of the first Fourier harmonic an1 was the only coefficient to achieve statistical significance in the correlation with the predictors VDist and ODF in both vascular systems. The an1 coefficient value in the correlation with VDist was -3.79±0.78 and -1.269±0.37 (p < 0.0006), while this coefficient value in the correlation with ODF was 0.026±0.0099 and 0.009±0.04 (p < 0.01) in both the retinal veins and arteries respectively. The predictable attenuation characteristics in normal subjects suggest that this technique may allow the non-invasive quantification of retinal vascular compliance and other hemodynamic parameters., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Globally, a detrimental shift in cardiovascular disease risk factors and a higher mortality level are reported in some black populations. The retinal microvasculature provides early insight into the pathogenesis of systemic vascular diseases, but it is unclear whether retinal vessel calibers and acute retinal vessel functional responses differ between young healthy black and white adults., Methods: We included 112 black and 143 white healthy normotensive adults (20-30 years). Retinal vessel calibers (central retinal artery and vein equivalent (CRAE and CRVE)) were calculated from retinal images and vessel caliber responses to flicker light induced provocation (FLIP) were determined. Additionally, ambulatory blood pressure (BP), anthropometry and blood samples were collected., Results: The groups displayed similar 24 h BP profiles and anthropometry (all p > .24). Black participants demonstrated a smaller CRAE (158 ± 11 vs. 164 ± 11 MU, p < .001) compared to the white group, whereas CRVE was similar (p = .57). In response to FLIP, artery maximal dilation was greater in the black vs. white group (5.6 ± 2.1 vs. 3.3 ± 1.8%; p < .001)., Conclusions: Already at a young age, healthy black adults showed narrower retinal arteries relative to the white population. Follow-up studies are underway to show if this will be related to increased risk for hypertension development. The reason for the larger vessel dilation responses to FLIP in the black population is unclear and warrants further investigation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Diabetic retinopathy is characterized by disturbances in retinal blood flow mediated by capillary occlusion, intraretinal microvascular abnormalities (IRMAs), neovascularizations, and omega loops and reduplications. It is likely that the study of oxygen saturation in these abnormalities can provide knowledge about their role in the development of diabetic retinopathy., Methods: The oxygen saturation in IRMA vessels and venous loops and reduplications were studied in 40 diabetic patients with severe nonproliferative or proliferative diabetic retinopathy. The saturation values in the studied vascular abnormalities were compared to those of the larger retinal arterioles and venules., Results: There was a similar oxygen saturation (mean ± SD) in IRMAs observed to connect arterioles with venules (78.6% ± 11.8%, n = 22) and IRMAs connecting venules with venules (79.2% ± 9.0%, n = 12; P > 0.999). The saturation in IRMAs was significantly lower (P < 0.0002) than in arterioles (97.4% ± 5.2%, n = 40) and significantly higher (P < 0.0001) than the saturation in omega loops and reduplications (54.2% ± 19.3%, n = 6), which in turn showed no significant difference from the saturation in the venules (61.8% ± 6.8%, n = 40, P = 0.4)., Conclusions: The findings suggest that the oxygen saturation in vascular abnormalities in diabetic retinopathy depends on the extent of arteriovenous (A-V) shunting, with venous saturation due to no A-V shunting in venous loops and reduplications, and intermediate oxygen saturation due to moderate shunting in IRMAs. This may precede the development of neovascularizations with arterial oxygen saturation due to high A-V shunting.

Acute respiratory distress syndrome (ARDS) is a clinical syndrome of acute lung failure in critically sick patients, which severely compromises the function of multiple organs, including the brain. Although, the optic nerve and the retina are a part of the central nervous system, the effects of ARDS on these ocular structures are completely unknown. Thus, the major goal of this study was to test the hypothesis that ARDS affects vascular function in the eye. ARDS was induced in anesthetized pigs by intratracheal injection of lipopolysaccharide (LPS). Sham-treated animals served as controls. Pigs were monitored for 8 h and then sacrificed. Subsequently, retinal arterioles and short posterior ciliary arteries were isolated and cannulated with micropipettes to measure vascular responses by videomicroscopy. Levels of reactive oxygen species (ROS) were quantified in isolated vessels using dihydroethidium (DHE). Messenger RNA expression of hypoxic, inflammatory, prooxidative, and antioxidative genes was assessed by real-time PCR. When group-dependent differences in mRNA expression levels were found for a particular gene, immunostainings were conducted. Strikingly, responses to the endothelium-dependent vasodilator, bradykinin, were markedly impaired in retinal arterioles of LPS-treated pigs, but no differences were seen between ciliary arteries of LPS- and sham-treated animals. ROS levels were increased in retinal arterioles but not in ciliary arteries of LPS-treated pigs. Messenger RNA levels for HIF-1α, VEGF-A and NOX2 were markedly increased in retinal arterioles of LPS-treated pigs, whereas ciliary arteries had only negligible mRNA level changes. Pronounced immunoreactivity for HIF-1α, VEGF-A and NOX2 was seen in the endothelium of retinal arterioles from LPS-treated pigs. Histologically, massive edema was seen especially in the retinal nerve fiber layer of pigs treated with LPS. Our study provides the first evidence that ARDS induced by intratracheal LPS application evokes endothelial dysfunction in porcine retinal arterioles together with retinal edema, indicative of vascular leakage. In contrast, ciliary arteries appear to be resistant to intratracheal LPS application., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose : To measure alterations in orbital blood flow parameters using color Doppler imaging (CDI) before and after orbital decompression in patients with moderate to severe thyroid eye disease (TED). Methods : Resistance index (RI) and maximum and minimum velocity of ophthalmic artery (OA), superior ophthalmic vein (SOV), and central retinal artery (CRA) of 24 eyes (14 patients) with TED were measured before and at least 3 months after cosmetic orbital decompression procedure (single or double walls) using CDI. Complete eye examination was performed to define the severity (EUGOGO classification) and activity (clinical activity score) of TED. Results : Median OA ( p  = 0.003) and CRA ( p  = 0.001) resistance indices were significantly reduced postoperatively. Significant differences were found in maximum ( p  = 0.001) and minimum ( p  = 0.014) velocity of SOV before and after surgery. While a significant decrease in exophthalmometry was observed after the orbital decompression ( p  = 0.031), intraocular pressure changes were not significant ( p  = 0.182). Conclusion : Orbital decompression procedure led to a significant reduction of RI in both CRA and OA in patients with TED.

Aging is a major risk factor for vascular cognitive impairment and dementia (VCID). Recent studies demonstrate that cerebromicrovascular dysfunction plays a causal role in the development of age-related cognitive impairment, in part via disruption of neurovascular coupling (NVC) responses. NVC (functional hyperemia) is responsible for adjusting cerebral blood flow to the increased energetic demands of activated neurons, and in preclinical animal models of aging, pharmacological restoration of NVC is associated with improved cognitive performance. To translate these findings, there is an increasing need to develop novel and sensitive tools to assess cerebromicrovascular function and NVC to assess risk for VCID and evaluate treatment efficacy. Due to shared developmental origins, anatomical features, and physiology, assessment of retinal vessel function may serve as an important surrogate outcome measure to study neurovascular dysfunction. The present study was designed to compare NVC responses in young (< 45 years of age; n = 18) and aged (> 65 years of age; n = 11) healthy human subjects by assessing flicker light-induced changes in the diameter of retinal arterioles using a dynamic vessel analyzer (DVA)-based approach. We found that NVC responses in retinal arterioles were significantly decreased in older adults as compared with younger subjects. We propose that the DVA-based approach can be used to assess NVC, as a surrogate cerebromicrovascular outcome measure, to evaluate the effects of therapeutic interventions in older individuals.

Purpose: The purpose of this study was to evaluate ocular hemodynamics in patients with a disease believed to be related to a chronic vascular damage [ie, normal tension glaucoma (NTG)] in comparison with an entity with an acute ischemic impact on the optic nerve [ie, acute nonarteritic anterior ischemic optic neuropathy (NAION)]., Materials and Methods: Blood-flow velocities [peak systolic velocity (PSV), enddiastolic velocity (EDV)] of the ophthalmic artery (OA), central retinal artery (CRA), and nasal and temporal posterior ciliary arteries were measured using color Doppler imaging. Resistive index (RI) of all vessels was calculated (PSV-EDV/PSV). A total of 41 patients suffering from acute NAION (onset of symptoms <10 d) and 64 age-matched patients suffering from NTG were included in this prospective study., Results: No significant differences were recorded for either age or intraocular pressure inbetween the 2 groups. Systolic blood pressure was significantly higher in the NAION group, whereas no significant differences were recorded for the diastolic blood pressure. Only 3 color Doppler imaging parameters were found to differ significantly. The PSV (P<0.005) and EDV (P<0.02) in the CRA were significantly higher in NTG patients. Furthermore, the RI in the OA was significantly higher in the NAION patients (P<0.005)., Conclusions: Decreased blood-flow velocities in the CRA and a higher RI in the OA can be recorded in NAION patients as compared with NTG. No differences with regard to the posterior ciliary arteries' velocities were recorded. Ocular hemodynamics are suspected to play a critical role in NAION and NTG, whereas the blood-flow disturbances seem to be more severe in NAION than in NTG.

Diabetic retinopathy is characterized by retinal lesions related to disturbances in retinal blood flow. The metabolic dysregulation in diabetes involves hyperglycemia which in both clinical and experimental studies has been shown to induce dilatation of larger retinal vessels, which has been suggested to be mediated by nitric oxide (NO). However, the effects of glucose on the diameter of smaller retinal vessels that are the site of development of diabetic retinopathy are unknown. Diameter changes in porcine retinal arterioles, pre-capillary arterioles and capillaries were studied ex vivo during acute changes in intraluminal glucose concentrations that mimicked changes in plasma glucose in diabetic patients. The experiments were repeated during blocking of NO-synthesis. Intravascular application of 2 mM glucose dilated arterioles and capillaries significantly, while 20 mM glucose dilated precapillary arterioles significantly. Intravascular application of 20 mM glucose dilated precapillary arterioles previously exposed to 2 mM glucose, while no significant diameter changes were observed after application of 2 mM glucose in vessels previously exposed to 20 mM glucose. No diameter changes were observed after application of 5.5 mM glucose in vessels previously exposed to both 2 mM and 20 mM glucose in either order. There was no significant difference between the diameter responses in the absence and presence of NO-synthesis blocker. Glucose induced dilatation of porcine precapillary arterioles ex vivo differs from the response in larger arterioles and capillaries, and the response is unaffected by the blocking of NO-synthesis. This may have implications for understanding the pathophysiology of diseases in the retinal microcirculation, such as diabetic retinopathy., (Copyright © 2018. Published by Elsevier Ltd.)

Purpose: Thrombin, a serine protease, causes organ-specific responses to vessels. However, the mechanism by which thrombin affects the retinal microcirculation remains unclear. We examined the effects of thrombin on the retinal microvasculature and signaling mechanisms., Methods: Porcine retinal arterioles were isolated, cannulated, and pressurized (55 cmH 2 O) without flow in this in vitro study. Videomicroscopy techniques recorded changes in diameter in the retinal arterioles in response to thrombin at concentrations ranging from 0.001 to 20 mU/ml., Results: Extraluminal administration of thrombin induced concentration-dependent vascular responses, that is, vasoconstriction at low concentrations less than 5 mU/ml and vasorelaxation with high concentrations greater than 5 mU/ml. However, intraluminal administration of thrombin (5 mU/m) did not constrict the retinal arterioles; in denuded vessels, intraluminal administration constricted the retinal arterioles. Thrombin-induced vasoconstriction was significantly (p < 0.01) suppressed by pretreatment with a protein kinase C (PKC) inhibitor and a protease-activated receptor (PAR)-1 inhibitor but not by PAR-2 and PAR-4 inhibitors or denudation. A rho kinase (ROCK) inhibitor also suppressed thrombin-induced vasoconstriction (5 mU/ml) compared with sodium nitroprusside. Endothelial denudation and pretreatment with an endothelial nitric oxide (NO) synthase inhibitor suppressed vasorelaxation caused by a high concentration of thrombin., Conclusions: A low concentration of thrombin causes vasoconstriction of smooth muscles via PAR-1, PKC, and ROCK, and a high concentration of thrombin possibly causes vasorelaxation of the retinal arterioles via nitric oxide synthase activation in the endothelium. The vascular endothelium might block signaling of thrombin-induced vasoconstriction in the retinal arterioles when administered intraluminally.

Purpose: To use color Doppler to analyze blood flow in the retrobulbar central retinal artery (CRA) and central retinal vein (CRV) in monocular retinoblastoma., Methods: This prospective study included patients with group D and E retinoblastomas managed with only enucleation. Peak blood velocities were assessed in the CRA and CRV of tumor-containing eyes (CRAv and CRVv, respectively). The resistivity index in the CRA (RIa) and pulse index in the CRV (PIv) were calculated and related to optic nerve invasion (ONi), choroid invasion (mCHi), and tumor volume. RIa and PIv were also calculated for healthy eyes., Results: In total, 25 patients with a mean age of 30.8-months old were included. The means (SD) for CRAv, CRVv, RIa, and PIv were 26.94 (12.32) cm/s, 16.2 (9.56) cm/s, 0.88 (0.12) and 0.79 (0.29), respectively. Tumor volume was significantly correlated with CRAv (P = 0.025) and RIa (P = 0.032). ONi was present in 19 eyes and correlated with a smaller PIv (P < 0.001). A PIv less than 0.935 had a sensitivity of 89.5% and specificity of 83.3% for predicting ONi. mCHi was not correlated with flow values. Healthy eyes had a significantly lower RIa (P < 0.001) and lower PIv than eyes with (P = 0.009) and without (P < 0.001) ONi., Conclusions: In advanced-stage monocular retinoblastoma, tumor volume was directly correlated with CRAv and RIa, and lower PIv was correlated with optic nerve invasion when a predictive cut-off value of less than 0.935 was applied. Comparisons with healthy eyes showed that tumor-containing eyes were associated with higher RIa and PIv values.

Cerebral microcirculation is critical for the preservation of brain health, and vascular impairment is associated with age-related neurodegenerative diseases. Because the retina is a component of the central nervous system, cellular changes that occur in the aging retina are likely relevant to the aging brain, and the retina provides the advantage that the entire vascular bed is visible, en face. In this study, we tested the hypothesis that normal, healthy aging alters the contractile vascular smooth muscle cell (VSMC) coverage of retinal arterioles. We found that aging results in a significant reduction of contractile VSMCs in focal patches along arterioles. Focal loss of contractile VSMCs occurs at a younger age in mice deficient in the senescence-associated protein, caveolin-1. Age-related contractile VSMC loss is not exacerbated by genetic depletion of insulin-like growth factor-1. The patchy loss of contractile VSMCs provides a cellular explanation for previous clinical studies showing focal microirregularities in retinal arteriolar responsiveness in healthy aged human subjects and is likely to contribute to age-related retinal vascular complications., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The retinal relaxing factor (RRF) is a continuously released factor from the retina that causes vasorelaxation, the identity and potential role in physiology of which remain largely unknown. Experiments were performed to find out whether the RRF-induced relaxation is influenced by serotonin, glutamate, L-cysteine, the cytochrome P450 pathway, the cyclooxygenase pathway, or oxidative stress. In addition, the sensitivity of retinal and non-retinal arteries towards the RRF was compared., Methods: In vitro tension measurements were performed on isolated mouse femoral or bovine retinal arteries to study the vasorelaxing effect of the RRF, induced by mouse or bovine retinas., Results: The presence of serotonin, glutamate, or L-cysteine did not alter the RRF-induced relaxation. Increasing oxidative stress by hydroquinone and diethyldithiocarbamic acid sodium salt enhanced the RRF response. Inhibition of the cytochrome P450 or the cyclooxygenase pathway did not cause any alteration. Surprisingly, the RRF-induced relaxation was enhanced by the presence of flufenamic acid or carbenoxolone. Furthermore, bringing retinal tissue in close contact with retinal or non-retinal arteries induced comparable relaxations., Conclusions: Serotonin, glutamate, L-cysteine, the cytochrome P450, and the cyclooxygenase pathway do not influence the RRF-induced relaxation and the RRF-induced relaxation seems to be resistant to oxidative stress. The mechanism responsible for the enhanced RRF-induced relaxation in the presence of flufenamic acid or carbenoxolone remains elusive and the RRF does not show more effectivity on retinal arteries.

Importance: A hemodynamic role in the pathogenesis of age-related macular degeneration (AMD) has been proposed, but to our knowledge, an association between retinal vasculature and late AMD has not been investigated., Objective: To determine whether the presence and location of a cilioretinal artery may be associated with the risk of late AMD in the Age-Related Eye Disease Study (AREDS)., Design, Setting, and Participants: Retrospective analysis of prospective, randomized clinical trial data from 3647 AREDS participants. Fundus photographs of AREDS participants were reviewed by 2 masked graders for the presence or absence of a cilioretinal artery and whether any branch extended within 500 μm of the central macula. Multivariate regressions were used to determine the association of the cilioretinal artery and vessel location, adjusted for age, sex, and smoking status, with the prevalence of choroidal neovascularization (CNV) or central geographic atrophy (CGA) and AMD severity score for eyes at randomization and progression at 5 years., Main Outcomes and Measures: Association of cilioretinal artery with prevalence and 5-year incidence of CNV or CGA., Results: Among AREDS participants analyzed, mean (SD) age was 69.0 (5.0) years, with 56.3% female, 46.6% former smokers, and 6.9% current smokers. A total of 26.9% of patients had a cilioretinal artery in 1 eye, and 8.4% had the vessel bilaterally. At randomization, eyes with a cilioretinal artery had a lower prevalence of CNV (5.0% vs 7.6%; OR, 0.66; 95% CI, 0.51-0.85; P = .001) but no difference in CGA (1.1% vs 0.8%; OR, 1.33; 95% CI, 0.76-2.32; P = .31). In eyes without late AMD, those with a cilioretinal artery also had a lower mean (SD) AMD severity score (3.00 [2.35] vs 3.19 [2.40]; P = .02). At 5 years, eyes at risk with a cilioretinal artery had lower rates of progression to CNV (4.1% vs 5.5%; OR, 0.75; 95% CI, 0.56-1.00; P = .05) but no difference in developing CGA (2.2% vs 2.7%; OR, 0.83; 95% CI, 0.56-1.23; P = .35) or change in AMD severity score (0.65 [1.55] vs 0.73 [1.70]; P = .11). In patients with a unilateral cilioretinal artery, eyes with the vessel showed a lower prevalence of CNV than fellow eyes (4.7% vs 7.2%; P = .01)., Conclusions and Relevance: The presence of a cilioretinal artery is associated with a lower risk of developing CNV, but not CGA, suggesting a possible retinal hemodynamic contribution to the pathogenesis of neovascular AMD., Trial Registration: ClinicalTrials.gov Identifier: NCT00000145.

Purpose: To evaluate the impact of dynamic exercise on retinal vessel oxygen saturation in healthy individuals., Methods: Twenty-six healthy participants underwent moderate dynamic exercise (modified Master's two-step exercise). In all subjects, intraocular pressures (IOP), systolic and diastolic blood pressures (SBP and DBP), retinal vessel calibres and retinal arterial and venous oxygen saturation were measured at baseline, immediately following exercise and 15 min postexercise., Results: Moderate dynamic exercise increased SBP and DBP immediately postexercise (SBP: 116 (±13) mmHg to 150 (±21) mmHg; p < 0.001 and DBP: 69 (±10) mmHg to 74 (±10); p < 0.001), while IOP decreased by an average of 2 mmHg (baseline: 13 (±3) mmHg)) immediately postexercise (11 (±2) mmHg). Oxygen saturation in retinal arteries remained unchanged (baseline = 93 ± 8%; immediately postexercise = 94 ± 9% and 15 min postexercise = 96 ± 8%; p = 0.069), but increased in retinal veins immediately postexercise and did not return to baseline values within 15 min postexercise (baseline = 54 ± 12%; immediately postexercise = 56 ± 15%; 15 min postexercise=57 ± 12%; p = 0.036)., Conclusion: There is a mild increase in retinal venous oxygen saturation and there is a trend towards an increase in arterial saturation in otherwise healthy individuals following dynamic exercise., (© 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Incident myocardial infarction (MI) is a leading cause of adult mortality in the United States. However, because MI has a relatively low incidence in the young population, little information exists on the disease in younger adults. Because the retina has the unique quality that its vasculature is readily and noninvasively visible, the retina is frequently studied to evaluate correlations between vessels and cardiovascular diseases. In the current study, we evaluated the retinal microvasculature of patients who had experienced an MI before 50 years of age (n = 53 subjects) and age- and sex-matched patients who had not experienced an MI (n = 53 patients). We used circular optical coherence tomography (OCT) scans to image peripapillary venules and arterioles. The diameter of each vessel was measured and the respective arterial-venous ratio (AVR) was calculated. We did not detect any significant differences between MI and control subjects in retinal vessel calibre or AVR.

Purpose: To investigate the short-term effect of single intravitreal aflibercept injection on retrobulbar blood flow in patients with neovascular age-related macular degeneration (nAMD)., Methods: Twenty eyes of 20 patients with nAMD scheduled for single intravitreal aflibercept (Eylea ® ) injection and 20 fellow eyes (uninjected) were enrolled in this prospective interventional study. The hemodynamic parameters of the ophthalmic artery (OA), central retinal artery (CRA) and posterior ciliary artery (PCA) comprising peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) were measured by using color Doppler ultrasonography (CDU) in both injected and uninjected fellow eyes at baseline and 1 week after the injection., Results: The measured first-week values of PSV and EDV in the CRA, OA and PCA showed a statistically significant reduction when comparing baseline values in both injected and uninjected fellow eyes (p = 0.0001). Also, it was found a significant increase in the post-injection RI values of all the CRA, OA, PCA in injected eye and OA in the uninjected eye (p = 0.0001). There was any significant difference between pre- and post-injection RI values of the CRA and PCA in the fellow eyes (p = 0.137, p = 0.736, respectively)., Conclusion: Single intravitreal administration of aflibercept alters retrobulbar blood flow velocities (BFVs) in both injected and uninjected fellow eyes in the short-term period.

Purpose: To investigate the effects of an antioxidant dietary supplement that includes Ginkgo biloba, on retinal and retrobulbar blood flow in patients with open-angle glaucoma (OAG)., Methods: Forty-five patients with confirmed OAG were enroled in a randomized, double blinded, placebo-controlled cross-over study. Baseline and postadministration measurements of intraocular pressure (IOP), ocular perfusion pressure (OPP), retrobulbar blood flow, and retinal capillary blood flow were non-invasively measured (ultrasound and laser Doppler modalities, respectively) before and one month after antioxidant nutraceuticals and placebo administration. Changes in measurements between the active supplement and placebo arms were evaluated using paired t-tests, with p < 0.05 considered statistically significant., Results: Antioxidant supplementation produced a statistically significant increase in peak systolic and/or end diastolic blood flow velocities in all retrobulbar blood vessels compared to placebo. Vascular resistance was also reduced in central retinal and nasal short posterior ciliary arteries following antioxidant administration. Additionally, antioxidant supplementation increased superior and inferior temporal retinal capillary mean blood flow and the ratio of active to non-active retina capillaries compared to placebo., Conclusion: One-month oral administration of antioxidants produced increases in biomarkers of ocular blood flow within retinal and retrobulbar vascular beds in patients with OAG., (© 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

The human eyes provide a natural window for noninvasive measurement of the pulse wave velocity (PWV) of small arteries. By measuring the retinal PWV, the stiffness of small arteries can be assessed, which may better detect early vascular diseases. Therefore, retinal PWV measurement has attracted increasing attention. In this study, a jump-scanning method was proposed for noninvasive measurement of retinal PWV using spectral-domain optical coherence tomography (SD-OCT). The jump-scanning method uses the phase-resolved Doppler OCT to obtain the pulse shapes. To realize PWV measurement, the jump-scanning method extracts the transit time of the pulse wave from an original OCT scanning site to another through a transient jump. The measured retinal arterial PWV of a young human subject with normal blood pressure was in the order of 20 to 30 mm/s, which was consistent with previous studies. As a comparison, PWV of 50 mm/s was measured for a young human subject with prehypertension, which was in accordance with the finding of strong association between retinal PWV and blood pressure. In summary, it is believed the proposed jump-scanning method could benefit the research and diagnosis of vascular diseases through the window of human eyes., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: To investigate the effects of Valsalva maneuver (VM) on retrobulbar blood flow parameters in healthy subjects., Methods: Participants without any ophthalmologic or systemic pathology were examined in supine position with color and pulsed Doppler imaging for blood flow measurement, via a paraocular approach, in the ophthalmic artery (OA), central retinal artery (CRA), central retinal vein (CRV), nasal posterior ciliary artery (NPCA), and temporal posterior ciliary artery (TPCA), 10 seconds after a 35- to 40-mm Hg expiratory pressure was reached. Peak systolic velocity (PSV), end-diastolic velocity (EDV), pulsatility index (PI), and resistivity index (RI) values were recorded for each artery. PSV and EDV values were recorded for CRV., Results: There were significant differences between resting and VM values of PSV and EDV of CRA, RI of NPCA, and PI, RI, and EDV of TPCA. Resting CRA-EDV, CRV-PSV, and CRV-EDV were positively correlated whereas resting OA-PSV and CRA-PI, and OA-PSV, CRA-PSV, and CRA-EDV during VM, were negatively correlated with age., Conclusions: VM induces a short-term increase in CRA blood flow and a decrease in NPCA and TPCA RI. Additional studies with a longer Doppler recording during VM, in a larger population sample, are required to allow definitive interpretation. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:551-555, 2017., (© 2017 Wiley Periodicals, Inc.)

Purpose: To evaluate the blood flow changes of the central retinal artery measured with color Doppler imaging (CDI) in infants receiving intravitreal aflibercept (IVA) for treatment of type 1 retinopathy of prematurity (ROP)., Methods: Patients with type 1 ROP were assessed prospectively by CDI following IVA. Color Doppler imaging was used to measure the peak systolic velocity, end diastolic velocity (EDV), pulsatility index (PI), and resistivity index (RI) of the central retinal artery (CRA) before IVA injection and 1 hour, 1 week, and 1 month after injection., Results: A total of 29 eyes of 15 infants were included in this study. The mean gestational age at birth was 28.62 ± 2.48 weeks and the mean birthweight was 1,198.62 ± 348.99 g. All treated eyes showed complete regression of ROP and peripheral retinal vascularization continued. Measurements of EDV-CRA, RI-CRA, and PI-CRA showed significant changes after IVA treatment., Conclusions: This study showed that IVA is an effective treatment for type 1 ROP. After IVA treatment, vascular resistance increases, ocular blood flow decreases, and changes in hemodynamic parameters of CRA may remain for a month. Further studies are needed to evaluate the effect of anti-vascular endothelial growth factor agents on ocular hemodynamics in infants with ROP.

Purpose: Disturbances in retinal blood flow are a prominent feature of vision threatening retinal diseases. The regulation of tone in retinal resistance vessels involves the perivascular retinal tissue, but it is unknown to what extent neurons or glial cells contribute to the effect. Therefore, the purpose of the present study was to study the contribution of neurons in the perivascular retina to vascular tone during activation of voltage-gated sodium channels with veratridine and electrical field stimulation (EFS)., Methods: Porcine retinal arterioles with and without perivascular tissue were mounted in an isometric myograph system for studying the effects of the voltage-gated sodium channel opener veratridine and EFS on retinal vascular tone., Results: Veratridine induced concentration-dependent relaxation of retinal arterioles which was more pronounced in arterioles with preserved perivascular retinal tissue than in isolated vessels. In the presence of this tissue, veratridine-induced relaxation was inhibited by the voltage-gated sodium channel blocker tetrodotoxin and the nitric oxide synthase inhibitor, N ω -Nitro-L-arginine methyl ester (L-NAME), but was unaffected by the inhibition of the cyclo-oxygenase inbitior ibuprofen and by blocking of adenosine receptors with 8-(p-Sulfophenyl)theophylline hydrate (8-PSPT). Electrical field stimulation induced no changes in retinal vascular tone., Conclusions: Sodium channels of neuronal origin are likely to be involved in the regulation of retinal vascular tone. The lack of effect of EFS on retinal vascular tone may be due to the lack of autonomic nerves in the retina.

Purpose: To establish a model of the retinal capillary circulation in pigs, which in many aspects is close to the human retina., Methods: Using high density confocal microscopy image stacks of immunolabeled porcine retinal whole mounts, microvessels close to the optic nerve head were traced in three dimensions. The direction of flow of individual capillaries was deduced from their arteriolar and/or venous connections., Results: From major arteries, second-order arteries traversed the nerve fiber layer and resolved exclusively into the superficial vascular plexus (SVP), which dichotomized the blood flow between radial peripapillary capillaries (RPCs) on one side and the intermediate (IVP) and deep vascular plexus (DVP) on the other. Each RPC was supplied by one or several capillaries from the SVP and drained to the IVP or DVP. The DVP was a mosaic of approximately 300 to 600 μm wide anastomotic watersheds, each drained by one or two venules connected to major veins. A presumptive direction of flow could be determined for >90% of capillaries. These results suggest a model of the capillary circulation in which the three microvessel layers are serially organized with RPCs are in parallel between the SVP and IVP or DVP., Conclusions: In the peripapillary retina of pigs, microvascular layers have a serial arrangement, with RPCs emerging from the SVP and draining to the IVP or DVP; hence, connected in parallel of this scheme. The bulk of flow, therefore, traverses the SVP and DVP successively. This organization contributes to the higher oxygen saturation in the SVP and RPCs than in the DVP. Physiopathologic implications of this model regarding retinal diseases are discussed.

Purpose: To evaluate the effects of intra-arterial chemotherapy on retrobulbar blood flow parameters in patients with retinoblastoma., Methods: 20 eyes of 10 patients with unilateral retinoblastoma that were treated with intra-arterial chemotherapy were evaluated using colour Doppler imaging. The peak systolic and end-diastolic velocities of the ophthalmic, central retinal and posterior ciliary arteries were determined. The pulsatility and resistance indices were calculated automatically. The treated eye was compared with the untreated (control) eye and with itself before and after intra-arterial chemotherapy., Results: When comparing the retinoblastoma-containing eyes with the contralateral normal eyes, the peak systolic and end-diastolic velocities of the central retinal artery were significantly higher in the tumorous eyes than in the normal eyes before intra-arterial chemotherapy. Moreover, the peak systolic and end-diastolic velocities in the posterior ciliary and central retinal arteries were significantly decreased after intra-arterial chemotherapy in the tumorous eyes (p<0.05). There were no statistically significant differences in the other parameters., Conclusions: Our results suggest that intra-arterial chemotherapy has a measurable effect on the retrobulbar blood flow, which can cause a decrease in the peak systolic and end-diastolic velocities in the posterior ciliary and central retinal arteries., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: To explore the potential relationship between optic disc haemorrhage, venous pulsation pressure (VPP), ocular perfusion pressures and visual field change in glaucomatous and glaucoma suspect eyes., Materials and Methods: This prospective observational study examined 155 open angle glaucoma or glaucoma suspect eyes from 78 patients over 5 years. Patients were followed with 3 monthly non-mydriatic disc photographs, 6 monthly standard automated perimetry and annual ophthalmodynamometry. The number of disc haemorrhages in each hemidisc was counted across the study period. Visual field rate of change was calculated using linear regression on the sensitivity of each location over time, then averaged for the matching hemifield. VPP and central retinal artery diastolic pressure (CRADP) were calculated from the measured ophthalmodynanometric forces (ODF). The difference between brachial artery diastolic pressure (DiastBP) and CRADP was calculated as an index of possible flow pathology along the carotid and ophthalmic arteries., Results: Mean age of the cohort was 71.9 ± 7.3 Years. 76 out of 155 eyes (49%) followed for a mean period of 64.2 months had at least 1 disc haemorrhage. 62 (81.6%) of these 76 eyes had recurrent haemorrhages, with a mean of 5.94 recurrences over 64.2 months. Using univariate analysis, rate of visual field change (P<0.0001), VPP (P = 0.0069), alternative ocular perfusion pressure (CRADP-VPP, P = 0.0036), carotid resistance index (DiastBP-CRADP, P = 0.0108) and mean brachial blood pressure (P = 0.0203) were significantly associated with the number of disc haemorrhages. Using multivariate analysis, increased baseline visual field sensitivity (P = 0.0243, coefficient = 0.0275) was significantly associated with disc haemorrhage, in conjunction with higher VPP (P = 0.0029, coefficient = 0.0631), higher mean blood pressure (P = 0.0113, coefficient = 0.0190), higher carotid resistance index (P = 0.0172, coefficient = 0.0566), and rate of visual field loss (P<0.0001, coefficient = -2.0695)., Conclusions: Higher VPP was associated with disc haemorrhage and implicates the involvement of venous pathology, but the effect size is small. Additionally, a greater carotid resistance index suggests that flow pathology in the ophthalmic or carotid arteries may be associated with disc haemorrhage.

Purpose: To compare the retinal blood flow velocity using laser speckle flowgraphy (LSFG) and a retinal function imager (RFI) in healthy Japanese subjects., Methods: This study included a total of 15 eyes of 15 healthy Japanese subjects (mean age, 41.7 ± 17.0 years). The retinal blood flow velocities were separately measured in arteries and veins around the optic disc using LSFG and an RFI. Linear regression analyses were used to analyze possible correlations of retinal blood flow velocities between the devices., Results: The average blood flow velocities using LSFG as the mean blur rate were 18.6 ± 4.8 in arteries and 18.3 ± 5.5 in veins. The average blood flow velocities using the RFI were 3.4 ± 1.1 mm/second in arteries and 2.9 ± 0.9 mm/second in veins. Although retinal blood flow velocities in arteries and veins using LSFG were nearly the same, there were statistical differences in retinal blood flow velocities between arteries and veins using the RFI (P = 0.701 using LSFG, P = 0.041 using the RFI). Significant correlations were found between LSFG and the RFI in arteries and veins (all, P < 0.001)., Conclusion: There were strong positive correlations in retinal blood flow velocities between LSFG and the RFI in healthy subjects.

Purpose: The prevailing view is that the human retina is supplied by the central retinal artery (CRA), the short posterior ciliary arteries (SPCAs) support the choroid, and both the CRA and the SPCAs are so-called "end artery" systems. In this study, we investigate whether vascular connections among the retina, choroid, and the optic nerve head (ONH) exist, using selective cannulation and microperfusion-labeling techniques., Methods: The CRA and/or one or more of the SPCAs were selected for cannulation in 18 human donor eyes. Fluorescent probes with different excitation wavelengths were perfused through different arteries on the same eye to distinguish the supply sources of different vascular beds. After labeling and fixation, the ONH region was dissected either longitudinally or transversely as thick sections for confocal microscopy. Retina, choroid, and ONH were imaged from whole-mount specimens., Results: Probes perfused through the CRA or the SPCA alone labeled the microvessels in the retina, choroid, and ONH regions, as well as the optic nerve trunk. The vessels of the lamina cribrosa and the optic nerve trunk were labeled when probes were perfused through the SPCA. Perfusion through both the CRA and SPCA produced double labeling of vessels in the retina, the choroid, and the ONH., Conclusions: The results indicate an inter-relationship of arterial supply to the retina, choroid, and ONH in the human eye. This has important implications in understanding clinical observations and disease mechanisms such as that of glaucoma and ischemic optic nerve disease.

The location of the peaks of the circumpapillary retinal nerve fiber layer (cpRNFL) thickness is affected by several ocular parameters. In this study, we have generated equations that can determine the peaks of the cpRNFL. This study was a prospective, observational, cross sectional study of 118 healthy right eyes. The axial length, optic disc tilt, superiortemporal (ST)- and inferiortemporal (IT)-peaks of the cpRNFL thickness, and angles of the ST and IT retinal arteries (RA) and veins (RV) were determined. The correlations between the location of the ST- and IT-peaks and ocular structural parameters and the sex, body height and weight were calculated. The best fit equations to generate the location of the ST/IT-peaks were determined using corrected-Akaike Information Criteria. The location of the ST-peak was 0.72+(0.40 x ST-RA)+(0.27 x ST-RV)+(0.14 x height)-(0.47 x papillo-macular-position)-(0.11 x disc tilt) with a coefficient of correlation of 0.61 (P<0.0001). The location of the IT-peak was 21.88+(0.53 x IT-RA)+(0.15 x IT-RV)+(0.041 x corneal thickness)-(1.00 x axial length) with a coefficient of correlation of 0.59 (P<0.0001). The location of ST/IT peaks is determined by different parameters of the ocular structure. These equations allow clinicians to obtain an accurate location of the peaks for a more accurate diagnosis of glaucoma.

Ocular vasculature consists of the central retinal and ciliary vascular systems, which are essential to maintaining visual function. Many researchers have attempted to determine their origins and development; however, the detailed, stepwise process of ocular vasculature formation has not been established. In zebrafish, two angioblast clusters, the rostral and midbrain organizing centers, form almost all of the cranial vasculature, including the ocular vasculature, and these are from where the cerebral arterial and venous angioblast clusters, respectively, differentiate. In this study, we first determined the anatomical architecture of the primary ocular vasculature and then followed its path from the two cerebral angioblast clusters using a time-lapse analysis of living Tg(flk1:EGFP)k7 zebrafish embryos, in which the endothelial cells specifically expressed enhanced green fluorescent protein. We succeeded in capturing images of the primary ocular vasculature formation and were able to determine the origin of each ocular vessel. In zebrafish, the hyaloid and ciliary arterial systems first organized independently, and then anastomosed via the inner optic circle on the surface of the lens by the lateral transfer of the optic vein. Finally, the choroidal vascular plexus formed around the eyeball to complete the primary ocular vasculature formation. To our knowledge, this study is the first to report successful capture of circular integration of the optic artery and vein, lateral transfer of the optic vein to integrate the hyaloidal and superficial ocular vasculatures, and formation of the choroidal vascular plexus. Furthermore, this new morphological information enables us to assess the entire process of the primary ocular vasculature formation, which will be useful for its precise understanding.

Objective: To investigate the influence of long-time video operation on hemodynamics of the retrobulbar arteries in operators. Methods: From March to October, 2015, a total of 120 soldiers for office work engaged in video surveillance were enrolled as study group, and 155 fire fighters were enrolled as control group. The incidence of eye discomfort was compared between the two groups. Color Doppler ultrasound was used to measure and compare the peak systolic velocity (PSV) , end-diastolic velocity (EDV) , and resistance index (RI) of the central retinal artery (CRA) and the short posterior ciliary artery (SPCA) , and the correlation of video operation time with the hemodynamic parameters of the retrobulbar arteries was analyzed. Results: The study group had a significantly higher incidence rate of eye discomfort than the control group ( P <0.05) . Compared with the control group, the study group had significant reductions in the PSV and EDV of the CRA and the SPCA and a significant increase in the RI of the CRA ( P <0.05) . Video operation time was negatively correlated with the PSV and EDV of the CRA and the SPCA ( r =-0.61, -0.54, -0.65, and-0.68, all P <0.05) and positively correlated with the RI of the CRA and the SPCA ( r =0.56 and 0.63, P <0.05) . Conclusion: Long-time video operation can increase the incidence of eye discomfort and lead to increased blood resistance of the CRA and the SPCA and reduced retinal perfusion.

Background/aims: Previous studies suggest that vascular abnormalities are involved in the pathogenesis of open-angle glaucoma. This study aims to examine the relationship of baseline retrobulbar blood flow measurements with functional and structural glaucomatous progression in patients with open-angle glaucoma over 4 years., Methods: In this study, 112 patients with open-angle glaucoma were examined at baseline and 78 with retrobulbar blood flow assessments were followed to 4 years. Colour Doppler imaging was used to evaluate retrobulbar blood flow. Structural disease progression was examined with optical coherence tomography and Heidelberg Retinal Tomography III. Functional disease progression was monitored with automated perimetry using Humphrey visual fields. Mixed-model analysis of covariance was used to test for significance of changes from baseline to 4-year follow-up. Two-sample t tests and χ 2 tests were used to test for baseline blood flow differences between patients who progressed and those who did not progress., Results: Patients who progressed structurally had a statistically significant lower baseline mean ophthalmic artery peak systolic velocity (PSV) (p=0.024) and ophthalmic artery end diastolic velocity (EDV) (p=0.012) compared with those who did not progress. Similarly, a lower baseline mean ophthalmic artery PSV (p=0.031) and ophthalmic artery EDV (p=0.005) were associated with patients who progressed functionally compared with those who did not progress after 4 years., Conclusions: In this study population, lower baseline ophthalmic artery blood flow velocities were associated with simultaneous structural and functional glaucoma progression after 4 years., Competing Interests: Competing interests: AH would like to disclose that he receives remuneration from Stemnion, Biolight, Nano Retina, AdOM, Science Based Health, Isarna Therapeutics, and Ono Pharmaceuticals for serving as a consultant. He also holds an ownership interest in AdOM, Nano Retina and Oxymap. All relationships listed above are pursuant to Indiana University's policy on outside activities., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: To observe the efficacy and explore the effect mechanism on visual display terminal syndrome treated with jingjin therapy of Zhuang medicine., Methods: Sixty-five patients of visual fatigue induced by the visual display terminal operation were treated with jingjin trigeminy therapy of Zhuang medicine, e.g. massage manipulation, acupuncture and cupping; acting on the specific stimulating areas in Zhuang medicine, relevant with orbit, temple, forehead, ear and Baihui (GV 20). Each treatment lasted 40 min, once every two or three days. Totally, 10 to 14 treatments were required. The scores of visual symptoms and the ocular hemodynamics before and after treatment were observed, and clinical effect were evaluated in the two groups., Results: After treatment, the scores of visual symptoms were reduced apparently as compared with those before treatment (all P <0.05). The total effective rate was 84.6% (55/65). The peak systolic velocity (PSV), the end diastolic velocity (EDV) in anterior ciliary artery (ACA) and the central retinal artery (CRA) were improved obviously, indicating the significant differences before and after treatment (all P <0.05)., Conclusions: The jingjin therapy of Zhuang medicine alleviates the visual symptoms in patients of visual fatigue and improves visual quality. The effects are related to the improvement of ocular microcirculation.

Purpose: To study the retinal oxygen saturation in normal eyes of Chinese adolescents., Methods: Performing retinal oximetry with the Oxymap T1 Retinal Oximeter in healthy children and adolescents (aged 5-18 years old), we measured the arterial (SaO 2 ) and venular (SvO 2 ) oxygen saturation and the arteriovenous difference in oxygen saturation (Sa-vO 2 )., Results: The study included 122 individuals with a mean age of 13.0 ± 2.9 years (range: 5-18 years) and a mean refractive error of -3.25 ± 2.49 dioptres (range:-8.88 to +3.13 dioptres). Mean SaO 2 , SvO 2 and Sa-vO 2 was 85.5 ± 7.1%, 48.2 ± 5.5% and 37.3 ± 6.5%, respectively. Mean SaO 2 was significantly (p < 0.001) the lowest in the inferotemporal quadrant (79.1 ± 9.0%), followed by the superotemporal quadrant (83.4 ± 9.7%), the inferonasal quadrant (90.4 ± 10.6%) and the superonasal quadrant (93.4 ± 10.8%). In a similar manner, the values of the SvO 2 were the lowest (p < 0.001) in the inferotemporal quadrant (42.1 ± 8.3%), followed by the superotemporal quadrant (47.8 ± 7.2%), the inferonasal quadrant (52.3 ± 8.4%) and the superonasal quadrant (55.1 ± 7.6%). Arteriovenous difference in oxygen saturation (Sa-vO 2 ) did not differ significantly (all p > 0.05) between the fundus quadrants. In multiple linear regression analysis, SaO 2 increased (regression coefficient r 2  = 0.28) with older age (standardized regression coefficient β: 0.23; p = 0.01) and more myopic refractive error (β: -0.39; p < 0.001). Higher SvO 2 was significantly correlated with more myopic refractive error (β: -0.46; p < 0.001; r 2  = 0.20), while Sa-vO 2 increased significantly only with older age in the multivariate analysis (β: 0.26; p = 0.01; r 2  = 0.07)., Conclusions: Our study provides normative data for Chinese children and adolescents who showed lower values than adults for SaO 2 and SvO 2 . SaO 2 increased with older age and higher myopic refractive error, SvO 2 increased with higher myopic refractive error, and Sa-vO 2 increased with older age., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)