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Purpose: To compare blood pressure (BP), intraocular pressure (IOP), ophthalmic artery flow (OAF) velocity, retinal nerve fiber layer (RNFL) thickness, and visual fields in newly diagnosed hypertension (HT) patients (before treatment), chronic HT (on antihypertensive medications >5 years) and normotensives., Methods: A prospective, cross-sectional study at a tertiary care centre in India. Three groups of 45 patients each: group 1 - early HT, group 2 - chronic HT, and Group 3 - normotensives, underwent evaluation of BP, IOP by Goldmann applanation tonometry (GAT), OAF velocity by transcranial doppler (TCD), RNFL analysis by spectral-domain optical coherence tomography (SD-OCT), and visual fields., Results: The BP was highest in early HT > chronic HT > normotensives ( p  < 0.001). The IOP of early HT, chronic HT, and normotensives were 15.87 ± 2.19 mmHg, 13.47 ± 1.92 mmHg, and 15.67 ± SD 1.75 mmHg ( p  < 0.001). The OAF velocity [peak systolic velocity (PSV), end-diastolic velocity (EDV) in cm/sec] was lowest in chronic HT (30.80 ± 7.05, 8.58 ± 1.58) < early HT (35.47 ± 5.34, 10.02 ± 1.74) < normotensives (36.29 ± 4.43, 10.44 ± 2.29), ( p  < 0.001). The average RNFL thickness was significantly lower in chronic HT ( p  = 0.022). The PSV, EDV, and MFV showed significant correlation with IOP ( r  = 0.247, p  = 0.004; r  = 0.206, p  = 0.016; r  = 0.266, p  = 0.002) and average RNFL thickness ( r  = 0.309, p = <0.001; r  = 0.277, p  = 0.001; r  = 0.341, p  < 0.001)., Conclusions: Patients with chronic HT demonstrated the lowest retrobulbar flows, IOP and lower RNFL measurements. Lower ocular perfusion may be associated with lower IOP and may be a risk factor for end-organ damage (RNFL) independent of IOP.

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.)

Background: Hypertensive disorders in pregnancy are among the most serious complications of pregnancy and represent important contributors to maternal and neonatal morbidity and mortality worldwide. Preeclampsia (PE)-eclampsia syndrome is the most important hypertensive gestational condition. Maternal ophthalmic artery Doppler velocimetry enables the identification of pregnant women with increased cerebral blood flow who are at risk of developing severe PE and eclampsia. Hence the need to determine the changes in ophthalmic artery Doppler velocimetric indices in PE in Kano,Nigeria becomes paramount., Materials and Methods: Ninety-six patients with the clinical diagnosis of PE and 96 normotensive pregnant controls between 20 and 40 weeks' gestational age were recruited for this study. Ophthalmic artery Doppler velocimetric indices of the two groups were measured and documented., Results: The mean velocimetric measurements in the control group were as follows: peak systolic velocity (PSV) = 38.04 ± 13.68 cm/s, End-diastolic volume (EDV) =9.14 ± 3.65 cm/s, resistivity index (RI) = 0.75 ± 0.091, pulsatility index (PI) =1.62 ± 0.55, peak mesodiastolic velocity (PMDV) = 21.02 ± 8.83 cm/s, peak ratio (PR) = 0.56 ± 0.14. The mean velocimetric indices in the PE group were PSV = 44.59 ± 11.54 cm/s, EDV = 12.23 ± 2.66 cm/s, RI = 0.71 ± 0.069, PI = 1.67 ± 0.42, PMDV = 32.27 ± 9.12 and PR = 0.72 ± 0.10., Conclusion: There is a significant difference in the ophthalmic artery Doppler velocimetric indices between women with PE and normal pregnant women. Ophthalmic artery Doppler ultrasound is a useful tool in monitoring the hemodynamic changes in cerebral circulation in PE., Competing Interests: None

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).)

Ocular ischemic syndrome (OIS) is one of the severe ocular disorders occurring from stenosis or occlusion of the carotid arteries. As the ophthalmic artery is derived from the branch of the carotid artery, stenosis or occlusion of the carotid arteries could induce chronic ocular hypoperfusion, finally leading to the development of OIS. To date, the pathophysiology of OIS is still not clearly unraveled. To better explore the pathophysiology of OIS, several experimental models have been developed in rats and mice. Surgical occlusion or stenosis of common carotid arteries or internal carotid arteries was conducted bilaterally or unilaterally for model development. In this regard, final ischemic outcomes in the eye varied depending on the surgical procedure, even though similar findings on ocular hypoperfusion could be observed. In the current review, we provide an overview of the pathophysiology of OIS from various experimental models, as well as several clinical cases. Moreover, we cover the status of current therapies for OIS along with promising preclinical treatments with recent advances. Our review will enable more comprehensive therapeutic approaches to prevent the development and/or progression of OIS.

Objective: To analyze the blood flow in retrobulbar vessels in systemic lupus erythematosus (SLE) by color Doppler imaging (CDI) and to investigate the associations between immunological markers, retinal abnormalities, disease activity, and vascular parameters., Methods: We examined 30 patients with SLE who were aged 32.1 ± 11.6 years with a disease duration of 68.0 ± 55.6 months and 30 participants in a control group. The peak systolic velocity (PSV), end diastolic velocity (EDV), pulsatility index (PI), and resistive index (RI) of the ophthalmic artery (OA), central retinal artery (CRA), and posterior ciliary arteries (PCAs) were determined. Physical and ophthalmic examinations with assessments of immunological markers were performed. All parameters were compared between SLE patients and normal controls while the correlations among parameters were analyzed., Results: In the SLE group, CDI confirmed blood flow abnormalities in the CRA and PCAs, with significantly lower blood flow velocities and increased RI and PI ( p < 0.05). There was a significantly negative correlation between disease duration and EDV in the CRA, PCA, and OA ( p = 0.0423, 0.0453, 0.0448). There was also a significant relationship between the SLE Disease Activity Index and the PI of the OA ( p = 0.0367). The patients who had received biological agents (Rituximab) had lower EDV in the CRA and PCA ( p = 0.0026, 0.028). SLE patients with kidney or CNS involvement had a significant increase in the PI in the OA ( p = 0.0287). The PSV and EDV in the CRA were significantly related to creatinine ( p = 0.0007 and 0.0418). We also noted a significant decreased EDV in the CRA and an increased RI in the OA among participants positive for anti-dsDNA antibodies ( p = 0.0331 and 0.0228)., Conclusions: Retrobulbar circulatory disturbances were detected in SLE patients by CDI. These findings seem likely to affect smaller vessels like the CRA and PCA. However, the presence of measurable changes in the OA is generally indicative of a coexistent nephropathy or central nervous system (CNS) vasculitis. Creatinine, the disease activity index, being positive for anti-dsDNA, and receiving biological agents were associated with measurable changes on the retrobulbar blood flow.

Purpose: To evaluate the severity of hemodynamic changes in the ocular vessels of patients recovered from COVID-19., Material and Methods: The study included 44 patients (88 eyes) aged 28-60 years, among them 24 (54.5%) women and 20 (45.4%) men, with SARS-CoV-2 infection confirmed by PCR no more than 2 months prior to enrollment and with no ophthalmological complaints within 2 months before the disease, as well as 20 healthy volunteers (40 eyes). At the time of the study all patients had a negative PCR result for SARS-CoV-2. The patients were divided into 2 groups. The first group comprised 24 patients who did not take any anticoagulants during the treatment. The second group consisted of 20 patients who received anticoagulants (Rivaroxaban (Xarelto)) at a dosage of 10 mg per day for 1-1.5 months. The maximum systolic (Vs), end-diastolic (Vd) blood flow velocity, as well as resistance index (RI) in the ophthalmic artery (OA), central retinal artery (CRA) and short posterior ciliary arteries (SPCA) were measured in all study patients with the ultrasound imaging system VOLUSON E8 Expert («Kretz», USA). Additionally, the flowmetry method was used to assess the volumetric ocular blood flow (VOBF) on Ocular Blood Flow Analyzer system («Paradigm Medical Industries, Inc.», USA)., Results: In the first group, a decrease in Vs and Vd was noted amid a significant increase of RI in CRA and SPCA, as well as an increase of RI in OA compared with the age-normal values ( p <0.05). In the second group, a decrease in Vs and Vd was noted amid a significant increase of RI in CRA, as well as a decrease in Vs in SPCA and an increase of RI in OA relative to the age-normal values ( p <0.05). A decrease in VOBF was noted in the first group in comparison to the second group and the age norm ( p <0.05)., Conclusion: Blood flow velocity parameters in the ocular vessels are reduced in patients recovered from COVID-19 compared to the age-normal values. There was a significant decrease in volumetric ocular blood flow parameters in COVID-19 patients who did not take any anticoagulants compared to the age-normal values. Anticoagulants intake has a positive impact on hemodynamic characteristics in the ocular vessels and volumetric ocular blood flow in patients with COVID-19.

Cytochrome P450 (CYP) signalling pathway has been shown to play a vital role in the vasoreactivity of wild type mouse ophthalmic artery. In this study, we determined the expression, vascular responses and potential mechanisms of the CYP-derived arachidonic acid metabolites. The expression of murine CYP (Cyp2c44) and soluble epoxide hydrolase (sEH) in the wild type ophthalmic artery was determined with immunofluorescence, which showed predominant expression of Cyp2c44 in the vascular smooth muscle cells (VSMC), while sEH was found mainly in the endothelium of the wild type ophthalmic artery. Artery of Cyp2c44 -/- and sEH -/- mice were used as negative controls. Targeted mass spectrometry-based lipidomics analysis of endogenous epoxide and diols of the wild type artery detected only 14, 15-EET. Vasorelaxant responses of isolated vessels in response to selective pharmacological blockers and agonist were analysed ex vivo. Direct antagonism of epoxyeicosatrienoic acids (EETs) with a selective inhibitor caused partial vasodilation, suggesting that EETs may behave as vasoconstrictors. Exogenous administration of synthetic EET regioisomers significantly constricted the vessels in a concentration-dependent manner, with the strongest responses elicited by 11, 12- and 14, 15-EETs. Our results provide the first experimental evidence that Cyp2c44-derived EETs in the VSMC mediate vasoconstriction of the ophthalmic artery., (© 2021. The Author(s).)

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.)

The ophthalmic artery (OA) is a crucial artery. Centered at the OA, there are numerous extracranial-intracranial anastomoses. The OA and its collaterals can be involved in some intracranial vascular diseases. So, it is very important to understand its specific anatomy, variation, and role in different neurovascular diseases. The OA has various anomalies both in the origin and collateral circulation. When performing endovascular treatment (EVT), the OA may suffer unexpected embolization through the numerous dangerous anastomoses. In case of a dural arteriovenous fistula or brain arteriovenous malformation mainly fed by the OA, the OA can be the passage of EVT, during which the central retinal artery could be injured. During interventional recanalization of steno-occlusive diseases of the internal carotid artery, dissection at the cavernous segment could progress to the OA segment and occlude the origin of OA. Under the circumstance of moyamoya disease, the OA can provide collateral flow to the anterior cerebral artery. When performing EVT for OA aneurysm concurrent with moyamoya disease, the parent OA should be preserved. After placement of a flow-diverting device for ophthalmic ICA aneurysm, the covered OA could experience spontaneous occlusion, leading to visual disturbance. Hence, the OA is an extremely important artery in the EVT for intracranial vascular diseases. In this article, we would extensively review the related literature to increase our understanding of the role of OA in intracranial vascular diseases. In addition, some illustrative cases would also be provided.

Abstract: This study aimed to investigate the effects of age on the peak ratio (PR) of ophthalmic artery (OA) Doppler.The initial peak velocity (P1), second peak velocity (P2) and PR of OA were detected by color Doppler ultrasonography in 147 healthy subjects. All of the subjects were divided into 6 groups (G1-G6) according to the age. (G1, 20-29 years; G2, 30-39 years; G3, 40-49 years; G4, 50-59 years; G5, 60-69 years; and G6, 70 years or older). The blood pressure and heart rate were also examined before ultrasonography. The influences of age, blood pressure and heart rate on the P1, P2, and PR were further evaluated.There were significant differences in the P2 and PR among different age groups except for P1. There were no significant differences in the P2 and PR between the first 2 groups, neither among the latter 4 groups. Nevertheless, P2 and PR in the first 2 groups were significantly different from those in the latter 4 groups. In addition, both P2 and PR (not P1) increased significantly with age, systolic and diastolic blood pressure. P1, P2 and PR were not related to heart rate. Both P2 and PR were closely related to the age. PR also had a weak relationship with systolic blood pressure.Both P2 and PR of OA Doppler increase with age. Concern should be raised when P2 and PR are used to evaluate the hemodynamic change of OA., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Blindness following facial filler procedures, although rare, is devastating, usually acute, permanent, and attributed to an ophthalmic artery embolus. However, blindness may be delayed for up to 2 weeks, sometimes following injection at remote sites, suggesting alternative pathways and pathogenesis., Methods: Seeking solutions, fresh cadaver radiographic lead oxide injection, dissection, and histologic studies of the orbital and facial pathways of the ophthalmic angiosome, performed by the ophthalmic artery and vein, both isolated and together, and facial artery perfusions, were combined with total body archival arterial and venous investigations., Results: These revealed (1) arteriovenous connections between the ophthalmic artery and vein in the orbit and between vessels in the inner canthus, allowing passage of large globules of lead oxide; (2) the glabella, inner canthi, and nasal dorsum are the most vulnerable injection sites because ophthalmic artery branches are anchored to the orbital rim as they exit, a plexus of large-caliber avalvular veins drain into the orbits, and arteriovenous connections are present; (3) choke anastomoses between posterior and anterior ciliary vessels supplying the choroid and eye muscles may react with spasm to confine territories impacted with ophthalmic artery embolus; (4) true anastomoses exist between ophthalmic and ipsilateral or contralateral facial arteries, without reduction in caliber, permitting unobstructed embolus from remote sites; and (5) ophthalmic and facial veins are avalvular, allowing reverse flow., Conclusion: The authors' study has shown potential arterial and venous pathways for filler embolus to cause blindness or visual field defects, and is supported clinically by a review of the case literature of blindness following facial filler injection.

Our main objective was to evaluate the ophthalmic artery Doppler behavior in twin pregnancies and compare with singleton pregnancies. We studied 64 healthy twin pregnant women between 12 to 38 weeks of gestation. Resistance index (RI), pulsatility index (PI), and peak ratio (PR) were determined. The control group consisted of 289 singletons. Linear regression analysis was performed to evaluate the association between gestational age and the ophthalmic indexes. Student t test was used to compare the means and standard deviation of the Doppler indexes. There was a decrease in RI and PI and an increase in PR with advancing gestational age (ρ < 0.0001, 0.0052, and 0.0033). The means ± SDs for RI, PI, and PR were 0.77 ± 0.07, 1.79 ± 0.46, and 0.53 ± 0.12, in women with twin pregnancies and 0.75 ± 0.05, 1.88 ± 0.43, and 0.52 ± 0.10 in singletons. No significant difference was found between the PI and PR values, but significant difference was found in the RI values between the groups (P = 0.0332). We concluded that there are no significant differences in ophthalmic artery behavior in twins and the same reference values established in singleton pregnancies can be applied for PI and PR indexes in the evaluation of twin pregnancies. These indexes were the best to evaluate twin pregnancies.

Background: Injectable fillers have become an integral part of facial rejuvenation, but vascular occlusion is a dreaded complication of such injections., Objective: To determine the force required by the fingertip onto the plunger of the syringe to cause retrograde migration., Methods: In this cadaver study, twelve 2-cm arterial segments and 4 fillers were tested. Injection pressure required to force a column of filler for 1 cm was measured. Five oculoplastics specialists were subsequently recruited and asked to inject the filler at a typical injection pressure., Results: The nonhyaluronic acid filler required significantly more pressure to cause propagation of the material compared with all other fillers (p < .01). None of the other fillers differed significantly from each other. Typical injection pressures generated by experienced injectors were significantly lower than that required to cause propagation of filler at the desired velocity and significantly lower than mean arterial pressure. Measured pressure required to cause filler propagation was well within the normal range of the finger strength that can be generated by humans., Conclusion: Typical injection pressures from fingertip to plunger are lower than required to cause propagation of filler intravascularly.

Assessment and monitoring of intracranial pressure (ICP) are important in the management of traumatic brain injury and other cerebral pathologies. In the eye, ICP elevation and depression both correlate with optic neuropathies, the former because of papilledema and the latter related to glaucoma. While the relationship between ICP elevation and papilledema is well established, the relationship between low ICP and glaucoma is still poorly understood. So far, ICP monitoring is performed invasively, but this entails risks including infection, spurring the study of non-invasive alternatives. We review 11 methods of non-invasive estimation of ICP including correlation to optic nerve sheath diameter, intraocular pressure, ophthalmodynamometry and two-depth transcranial Doppler of the ophthalmic artery. While none of these methods can fully replace invasive techniques, certain measures show great potential for specific applications. Although only used in small studies to date, a MRI based method known as MR-ICP, appears to be the best non-invasive technique for estimating ICP, with two-depth transcranial ultrasound and ophthalmodynamometry showing potential as well., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Preclinical imaging, especially of rodent models, plays a major role in experimental ophthalmology. Our aim was to determine if ultrasound can be used to visualize and measure flow dynamics in the retrobulbar vessels supplying and draining the eye and the potential of contrast microbubbles to provide image and measurement enhancement. To accomplish this, we used a 128-element, 18 MHz linear array ultrasound probe and performed plane-wave imaging of the eyes of Sprague Dawley rats. Compound images were acquired by emitting unfocused wavefronts at multiple angles and combining echo data from all angles to form individual B-scans. Multiple imaging sequences were utilized, compounding up to six angles, with imaging rate of up to 3000 compound B-scans per second and sequence durations from 1.5 to 180 s. Data were acquired before and after intravenous introduction of contrast microbubbles. We found the total power of the Doppler signal in the image plane to increase approximately 20 fold after injection of contrast, followed by an exponential decay to baseline in about 90 s, The best-fit time constant of the decay averaged 41 s. While major vessels and the retinal/choroidal complex were evident pre-contrast, they were dramatically enhanced with contrast present, with details such as choroidal arterioles seen only with contrast. Ocular arteriovenous transit time determined from comparative enhancement curves in arteries and veins was approximately 0.2 s. In conclusion, plane wave ultrasound, especially with enhancement by contrast microbubbles, offers a means for the study of ocular hemodynamics using the rat eye as a model., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose : To evaluate alterations in orbital color Doppler imaging (CDI) parameters and their correlation to disease activity and severity in patients with thyroid eye disease (TED). Methods : Seventy-six orbits of 45 TED patients and 40 orbits of 40 normal controls were enrolled in this cross-sectional study. According to clinical activity score (CAS), patients were categorized to active (CAS ≥ 3) or inactive disease (CAS < 3). Patients were also classified as having mild, moderate or severe disease. Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistance index (RI) in ophthalmic artery and central retinal artery, and maximum and minimum velocity in superior ophthalmic vein and central retinal vein were determined in all subjects. Results : There was a significant difference in maximum velocity of superior ophthalmic vein and EDV and RI of ophthalmic artery between patients with TED and normal subjects. Superior ophthalmic vein maximum and minimum velocity and ophthalmic artery RI were significantly higher in patients with active disease than inactive cases. Disease severity did not affect the blood flow parameters independently. A cutoff point of 3.99 cm/s in superior ophthalmic vein maximum velocity yielded a sensitivity of 91.2% and specificity of 81.2% in detecting active disease. Conclusion : Retrobulbar blood flow is altered in TED and is related to disease activity. Superior ophthalmic vein maximum velocity could be helpful in differentiation of active and inactive cases.

Purpose: Maternal ocular sonography offers a window into cerebrovascular and intracranial pressure changes in pregnancy. This study aimed to determine the Doppler velocimetric variables of the ophthalmic artery, and the mean diameter of the optic nerve sheath (ONSD), in an Australian cohort of healthy pregnant women., Methods: A prospective observational cohort study of healthy women with uncomplicated singleton pregnancies in the third trimester was undertaken in a tertiary maternity service. A single prenatal ultrasonographic examination was performed on all participants, with a postnatal examination performed on a subgroup with uncomplicated deliveries., Results: Fifty women were examined at a mean gestation of 35 weeks. The mean ± SD Doppler variables in the ophthalmic artery were peak systolic velocity (PSV) 41.89 ± 13.13 cm/s, second peak velocity 20.63 ± 8.97 cm/s, end diastolic velocity 9.29 ± 5.13 cm/s, pulsatility index 1.97 ± 0.53, resistive index 0.78 ± 0.07, peak ratio (second peak velocity/PSV) 0.49 ± 0.12, while the mean ONSD was 4.34 ± 0.4 mm. None of these variables had a demonstrable relationship with gestation or mean arterial pressure (MAP), nor did the sheath diameter have a relationship with any of the Doppler variables., Conclusions: The ocular sonographic variables observed in this population are similar to those reported in other cohorts. No clear relationship could be identified in this cohort between ophthalmic artery Doppler variables and the ONSD, and between each of these variables and gestation or MAP., (© 2019 Wiley Periodicals, Inc.)

Purpose : To characterise variations in the location of the optic canal and its entry into the orbit in relation to the sphenoid sinus. Methods : In this observational study, patients with high-resolution computed tomography (CT) scans seen by 2 specialists (RG and DR) over a period of 12 years were reviewed for study entry. The primary outcome measure was characterisation of the optic canal route in relation to the sphenoid sinus and the location of its opening within the orbit. Three-dimensional reconstructions of the bony orbits were created using the Mimics imaging software. Optic canals were classified according to the location of their entry into the orbit. Type 1 was defined as a canalicular course along the lateral wall of the sphenoid sinus and entry into the orbit through the medial wall. Type 2 was defined as a canalicular course in the superior wall of the sphenoid sinus with entry into the orbit through the roof. The angle of entry of each nerve into the orbit was calculated. Results : One-hundred patients (52 females and 48 males) contributed 100 orbits to the study. Type 1 configuration was noted in 90 orbits, whereas Type 2 was noted in 10 orbits. The mean angle (SD) of entry of Type 1 optic nerves into the orbit was 61° (10.7), whereas the angle of entry of Type 2 nerves was 32.35° (6.8). The difference was significant ( p  < 0.01). Conclusions : This study demonstrates variability of the path and outlet of the optic canal and presents a relatively common (10%) configuration in which the optic canal travels in the roof of the sphenoid sinus rather than the expected position in the lateral wall.

Background/aims: Takayasu arteritis (TAK) is a chronic granulomatous vasculitis that can lead to ischaemic ocular complications. We aimed to document ocular complications, ocular blood flow and the association of them with systemic clinical findings in TAK., Material and Methods: We included 65 patients with TAK (60 female, 5 male, mean age: 41.8±12.9 years) and 30 healthy subjects (30 female, mean age: 39.0±7.5 years) in this study. All of the patients had a detailed rheumatological and ophthalmological evaluation. Ocular blood flow in ophthalmic artery (OA) and central retinal artery (CRA) was evaluated with colour Doppler ultrasonography., Results: Hypertensive retinopathy was observed in 33.9%, and Takayasu retinopathy was observed in 6.2% of patients. Posterior subcapsular cataracts or a history of cataract surgery was seen in 15.4% of the cases. None of the patients experienced visual loss due to ischaemic or neovascular complications. Patients with TAK had increased resistivity index (RI) in ophthalmic artery (0.75 vs 0.66, p=0.002) and CRA (0.75 vs 0.67, p=0.001). Patients with hypertensive retinopathy had significantly longer disease duration (p=0.016). Ophthalmic artery RI was significantly higher in patients with ipsilateral radial artery pulselessness compared with patients without (0.77 vs 0.68, p=0.031)., Conclusion: This study reported the lowest prevalence of Takayasu retinopathy and is the only series without permanent visual loss. We documented for the first time that radial artery pulselessness can predict reduction of ipsilateral ocular perfusion. We believe that better management of TAK with current medications reduced ocular complication rates., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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.

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.)

Purpose: To evaluate the effects of carotid artery angioplasty and stenting (CAAS) on patients who were diagnosed with ocular ischemic syndrome (OIS)., Methods: Sixty-four eyes of 64 OIS patients with ipsilateral internal carotid artery stenosis ≥70% were included in the study. The study eyes were divided into two groups according to the presence of iris neovascularization: NVI-absent group and NVI-present group, with 32 eyes, respectively. All patients received ocular treatment modality according to the presence of non-perfusion area (pan-retinal photocoagulation) and intraocular pressure (medical treatment included timolol maleate eye drops combined with brinzolamide eye drop; trabeculectomy and cyclophotocoagulation). All patients went through CAAS surgery for treatment of internal carotid artery stenosis. Best-corrected visual acuity (BCVA); intraocular pressure (IOP), slit lamp examination, iris fluorescence angiography, fundus fluorescein angiography and color Doppler ultrasound of the internal carotid artery (ICA), ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (PCA) were performed pre-operatively and 1 month, 3 months, 6 months, and 12 months post-operatively., Results: There was no significant BCVA change postoperatively in the NVI-absent group, while postoperative BCVA in the INV-present group decreased significantly. There was no significant BCVA difference at pre-operative and 1month post-operative follow-up between the two groups. However, post-operative BCVA of NVI-present group starting from 3-months follow-up was significantly worse than NVI-absent group. Arm-retinal artery circulation time and arteriovenous circulation time decreased significantly in NVI-absent group, while showed no statistical difference in NVI-present group during the 12-months follow-up. Postoperative peak systolic velocity (PSV) of the ophthalmic artery, the central retinal artery, and short posterior ciliary artery showed significant increases at 1 month, 3 months, 6 months and 12 months follow-up in both groups., Conclusion: CAAS can greatly improve ocular blood in OIS patients with and without iris neovascularization. However, CAAS improved BCVA only in patients without iris neovascularization.

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.)

Objectives: Physiopathological mechanisms that trigger clinical manifestations in pre-eclampsia (PE) remain unclear, and management is still a challenge. The identification of tools to predict the onset of the disease and prevent its complications is of great interest in medical practice. The present study aims to evaluate uterine perfusion, endothelial function and central nervous system blood flow in pregnant women with high-risk factors for PE, for comparison of the results between the group of patients who developed early onset PE and those who remained normotensive throughout pregnancy., Study Design: Sixty-two patients were recruited from our high-risk prenatal service, and followed throughout gestation. Patients were submitted to flow-mediated dilation, Dopplervelocimetry of uterine arteries and Dopplervelocimetry of ophthalmic arteries at three distinct moments of pregnancy: between 16+0 and 19+6weeks, between 24+0 and 27+6weeks and at hospital admission to delivery., Main Outcome Measures: Pulsatility index of uterine arteries, flow-mediated dilation and ophthalmic arteries resistance index were evaluated and compared between the two groups of patients., Results: Ten pregnancies were complicated by early onset PE, and these patients presented a significantly higher pulsatility index of uterine arteries between 16+0 and 19+6weeks of gestation, compared with the normotensive group (p=0,016). Both flow-mediated dilation and ophthalmic arteries resistance index values were lower in affected patients at 24+0 to 27+6weeks (p=0,001), and by the time of delivery (p<0,002)., Conclusions: Those findings suggest that impaired placental perfusion, endothelial dysfunction and central hyperperfusion temporarily precede the clinical manifestations of early onset pre-eclampsia., (Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objective: To examine the association of ophthalmic artery (OA) Doppler measure - the ratio of velocity peaks (PR) - to adverse pregnancy outcomes in preeclampsia., Study Design and Main Outcomes: Prospective cohort study of 56 women with preeclampsia that underwent Doppler measurements of OA flow, medial to optic nerve. PR results were classified as normal (PR < 0.78), abnormal (PR 0.78-0.98), or highly abnormal (PR ≥ 0.99). Attending clinicians were blinded to OA Doppler results. The primary endpoints were (1) a composite of adverse maternal outcomes-central nervous system injury (eclampsia or posterior reversible encephalopathy syndrome), HELLP syndrome, hypertensive crisis, maternal admission to the intensive care unit, and maternal death-and (2) a composite of adverse perinatal outcomes-birth weight <10th percentile for gestational age, neonatal acidemia, 5-min Apgar score <7, admission of infants weighing >2500 g to the neonatal intensive care, preterm birth <32 weeks, fetal or neonatal death., Results: Adverse maternal outcomes became more frequent as the PR values increased (p=.005). The occurrence of hypertensive crisis after hospital admission (secondary endpoint) was also positively associated with PR values (p=.001). Adverse perinatal outcomes were not associated with PR values (p=.551), but women in the highly abnormal PR group (PR ≥ 0.99) had the earliest deliveries (p=.001) and the smallest newborns (p=.004). All women in the highly abnormal PR group (n=16) had an adverse outcome., Conclusions: Maternal OA Doppler PR ≥ 0.99 in preeclampsia may identify women at increased risk of adverse maternal outcomes and pregnancies at the greatest risk of preterm birth., (Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

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/.)

Laser speckle flowgraphy (LSFG) is an ophthalmologic equipment that qualitatively detects the blood flow of the optic nerve head, which is known to be related with cerebral microcirculation. LSFG can also measure the mean blur rate, which quantitatively calculates the blood flow. We aimed to assess the utility of LSFG in the evaluation of cerebral perfusion during aortic surgery under hypothermic circulatory arrest with retrograde and antegrade cerebral perfusion. Two patients underwent total arch replacement for aneurysm. The blood flow of the optic nerve head was monitored with LSFG and the mean blur rate value was measured during the surgery. The LSFG could detect the blood flow quantitatively in the optic nerve head during both retrograde and antegrade cerebral perfusion; and the value was correlated with rSO2 value.

Nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) plays an important role in the maintenance of ocular vascular homeostasis. Therefore, perturbations in vascular NO synthesis have been implicated in the pathogenesis of several ocular diseases. We recently reported that eNOS contributes significantly to vasodilation of the mouse ophthalmic artery. Interestingly, dilatory responses were also retained in eNOS gene-deficient mice (eNOS-/-), indicating inherent endothelial adaptive mechanism(s) that act as back-up systems in chronic absence of eNOS to preserve vasorelaxation. Thus, this study endeavoured to identify the compensatory mechanism(s) in the ophthalmic artery of eNOS-/- mice employing isolated arterial segments and pharmacological inhibitors in vitro. Endothelium removal virtually abolished acetylcholine (ACh)-induced vasodilation, suggesting an obligatory involvement of the endothelium in cholinergic control of vascular tone. However, non-NOS and non-cyclooxygenase components compensate for eNOS deficiency via endothelium-derived hyperpolarizing factors (EDHFs). Notably, arachidonic acid-derived metabolites of the 12-lipoxygenase pathway were key mediators in activating the inwardly rectifying potassium channels to compensate for chronic lack of eNOS. Conclusively, endothelium-dependent cholinergic responses of the ophthalmic artery in the eNOS-/- mice are largely preserved and, this vascular bed has the ability to compensate for the loss of normal vasodilator responses solely via EDHFs.

Accurate and clinically safe measurements of intracranial pressure (ICP) are crucial for secondary brain damage prevention. There are two methods of ICP measurement: invasive and noninvasive. Invasive methods are clinically unsafe; therefore, safer noninvasive methods are being developed. One of the noninvasive ICP measurement methods implements the balance principle, which assumes that if the velocity of blood flow in both ophthalmic artery segments - the intracranial (IOA) and extracranial (EOA) - is equal, then the acting ICP on the IOA and the external pressure (Pe) on the EOA are also equal. To investigate the assumption of the balance principle, a generalized computational model incorporating a fluid-structure interaction (FSI) module was created and used to simulate noninvasive ICP measurement by accounting for the time-dependent behavior of the elastic internal carotid (ICA) and ophthalmic (OA) arteries and their interaction with pulsatile blood flow. It was found that the extra balance pressure term, which incorporates the hydrodynamic pressure drop between measurement points, must be added into the balance equation, and the corrections on a difference between the velocity of blood flow in the IOA and EOA must be made, due to a difference in the blood flow rate., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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 evaluate using Doppler ultrasonography (DUS) how pars plana vitrectomy (PPV) affects orbital circulation in diffuse diabetic macular edema (DME) associated with either the epiretinal membrane (ERM) or taut posterior hyaloid (TPH)., Methods: The sample included 46 eyes of 42 patients with DME associated with the ERM (n = 22, Group 1) or TPH (n = 24, Group 2). All participants received panretinal laser photocoagulation and antivascular endothelial growth factor injections preoperatively and underwent 23-gauge PPV combined with ERM or TPH removal and internal limiting membrane (ILM) peeling. Pre- and postoperative peak systolic velocity (PSV), end-diastolic velocity (EDV), and the resistivity index (RI) of the ophthalmic artery (OA), central retinal artery (CRA), posterior ciliary artery (PCA), and central retinal vein were measured with DUS., Results: Statistically significant decreases in the PSV and EDV of the OA, CRA, and PCA were detected in all groups. In Group 1, the PSV of the OA and CRA as well as the EDV and PSV of the PCA declined significantly. In Group 2, the EDV of the OA and both the PSV and EDV of the CRA and PCA decreased. Postoperatively, the CRA's PSV and EDV were lower in Group 2, while the preoperative and postoperative RI of the CRA and preoperative RI of the PCA were greater in Group 2 than in Group 1. Changes in the CRA's RI, PSV, and EDV were greater in Group 2 after surgery., Conclusions: 23-Gauge PPV combined with ERM or TPH removal and ILM peeling in DME reduces blood flow rates of both choroidal and retinal vessels. In eyes with TPH, the RIs of the CRA and PCA were significantly greater preoperatively and the changes in the CRA's RI, PSV, and EDV were greater postoperatively. The removal of the TPH may play a role in regulating blood flow.

PurposeTo evaluate the effect of smoking on retrobulbar blood flow parameters by color Doppler imaging in patients with thyroid eye disease.Patients and methodsIn this observational case series, blood flow parameters in the ophthalmic artery, superior ophthalmic vein, central retinal artery, and vein were determined by color Doppler imaging in patients with thyroid eye disease. Patients were grouped as smokers and non-smokers. Never smokers and those who had stopped smoking for at least 1 year before onset of ophthalmopathy were considered as non-smokers. A thorough ophthalmic examination including Hertel exophthalmometry was performed. Orbital CT scan was also carried out in all patients.ResultsFifty-one orbits from 30 patients between 21 and 62 years old (mean±SD: 40.8±12.0) were enrolled in this study. Smokers had greater proptosis and more active and sever disease. (P<0.05) Muscle involvement based on CT scan did not vary in smokers and non-smokers. Maximum velocity (3.78±1.74 vs 5.27±2.14, P<0.001; t-test) and minimum velocity (1.74±0.78 vs 3.26±1.36, P =0.014; t-test) in superior ophthalmic vein were significantly lower in smokers than non-smokers. Even after adjusting for age, sex, and clinical activity score and severity, smokers had a lower minimum velocity in superior ophthalmic vein (P =0.01; ANCOVA analysis).ConclusionCigarette smoking may correlate with increase in orbital venous congestion in thyroid eye disease.

Purpose: To evaluate the relationship between retrobulbar hemodynamic parameters in the ophthalmic artery (OA), central retinal artery, and short posterior ciliary artery and 24-hour blood pressure (BP) measurements in dipper and nondipper patients with primary open-angle glaucoma (POAG)., Methods: A prospective, cross-sectional, and observational study was conducted on consecutive patients, referred or recruited, attending the outpatient service of our ophthalmology department. Ambulatory BP monitoring, Doppler imaging, and ocular pulse amplitude measurements were performed on the same day. Patients with nocturnal BP decrease up to 10% of the diurnal BP were defined as dippers and those with BP decrease less than 10% were defined as nondippers., Results: A total of 114 patients (36 nondippers and 78 dippers) were included in the study. The end-diastolic velocity was significantly lower and the resistivity index (RI) was significantly higher in the dippers than in the nondippers (p&lt;0.0001 and p&lt;0.0001, respectively). The RI in the OA was significantly correlated with daytime and nighttime systolic BP and with the daytime mean arterial pressure in the dippers., Conclusions: The RI in the OA significantly correlates with BP in patients with POAG with nocturnal BP dips. Additionally, retrobulbar blood flow parameters are reduced in dippers as compared with nondippers with POAG.

The aim of this study was to analyze the possible differences between retrobulbar blood flows in normotensive glaucomatous optic neuropathy patients versus patients with hypertensive glaucomatous optic neuropathy, with intraocular pressure controlled treatment. All the patients in the study group were subjected to a color Doppler echography of retrobulbar vessels. Afterwards, systolic and diastolic blood velocities were measured in both eyes in ophthalmic artery (OA), central retinal artery (CRA) and posterior ciliary arteries (PCA). The device calculated the Resistivity index Pourcelot (RI) automatically.

It is known that elevated intraocular pressure (IOP) is the primary risk factor for glaucoma. Recently, more and more evidences have shown that the vascular deficit also plays an important role in the pathogenesis and progressions of glaucomatous optic neuropathy. This issue is backed up by glaucomatous optic neuropathy (GON) cases drug compensated in which the progression of the disease in one or both eyes is ascertained despite a normal and relatively constant IOP. The present study evaluated the hemodynamic parameters in the retrobulbar circulation in patients with progressive glaucomatous optic neuropathy in one eye, who received compensated medication. The hemodynamic parameters (PSV, EDV, IR) were measured by using color Doppler ultrasound and progression was evaluated by a repeated automated perimetry. The obtained values were statistically analyzed and compared with those obtained for the stable eye.

Purpose: Elevated intra-ocular pressure (IOP) has been identified as a major risk factor for glaucoma. Additionally, extensive literature depicts a vascular dysfunction to exist in these patients. However, a large ocular blood flow-oriented trial to integrate these findings in the clinical setting is lacking. This study would likely help to identify which of these vascular data can be used as a clinical tool for screening and disease stratification., Method: Prospective, cross-sectional, case-control hospital-based study. Patients with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), ocular hypertension (OHT), glaucoma suspects and healthy volunteers were recruited. In addition to a comprehensive ophthalmological examination, a vascular-oriented questionnaire was completed and ocular blood flow assessment (colour Doppler imaging of retrobulbar vessels, retinal oximetry, dynamic contour tonometry, optical coherent tomography enhanced-depth imaging of the choroid) were performed. Statistical analysis was based on multiple imputation to account for missingness., Results: A total of 614 subjects (291 males) were recruited between March and December 2013 (POAG: 214, NTG: 192; OHT: 27; glaucoma suspect: 41; healthy controls: 140). Glaucoma groups (NTG and POAG) were age and gender matched with the control group (p > 0.05). Glaucoma groups were paired in terms of functional and structural parameters (p > 0.08). Mean ocular perfusion pressure was higher in the glaucoma groups than in controls (p < 0.001). Glaucoma groups had lower retrobulbar velocities, higher retinal venous saturation and choroidal thickness asymmetries when compared to the healthy group, in line with the current literature., Conclusions: The Leuven Eye Study stands as one of the largest clinical trials on ocular blood flow in glaucoma. The creation of this vast database may help integrate the vascular aspects of glaucoma into the clinical practice of glaucoma., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To investigate differences in ocular blood flow between people of African descent (AD) and European descent (ED) with healthy eyes., Materials and Methods: Retrobulbar and retinal capillary blood flow was assessed in 1 eye of 58 participants (24 AD, 34 ED) with healthy eyes with systemic blood pressure lower than 140/90. Retrobulbar blood flow was measured in the ophthalmic artery (OA), central retinal artery (CRA), nasal posterior ciliary artery (NPCA) and temporal posterior ciliary artery (TPCA). Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index (RI) were assessed. Retinal capillary blood flow was assessed using mean retinal flow and avascular space defined as the percent of area measured with no blood flow. Groups were compared using t tests and Pearson correlations were compared using Fisher r-to-z transformation., Results: Compared with people of ED, people of AD had significantly lower EDV in the NPCA (P=0.01), and higher RI in the CRA (P=0.04) and TPCA (P=0.01). No significant differences were observed in mean retinal capillary flow or avascular area. In the CRA, a significant negative correlation was observed between pattern standard deviation and peak systolic velocity (P=0.02) in the AD group and this correlation was significantly different from that observed in the ED group (P=0.01). A significant correlation was also observed between pattern standard deviation and EDV (0.04) in the AD group., Conclusions: This study suggests that retrobulbar blood flow is lower in healthy eyes in persons of AD compared with ED. This may provide a mechanism through which people of AD are at increased risk for ophthalmic diseases such as glaucoma.

Background: It has been proposed that sildenafil citrate can increase ocular blood flow, and that this property can be used to treat ocular disorders that involve reflex vasoconstriction. This study therefore proposes to ascertain the vasodilator effect of the drug on retrobulbar circulation in healthy rabbits. For this matter rabbits treated with sildenafil citrate or saline solution had their intraocular pressure (IOP), mean arterial pressure (MAP), ocular perfusion pressure (OPP) and color Doppler imaging of the external ophthalmic artery measured prior to treatment and on days one (moment M1), seven (when M2), fourteen (moment M3), twenty-one (moment M4), and thirty (moment M5) of treatment., Results: The MAP and OPP values of treated group were lower than those of control group at all times, and the mean values differed statistically at moments M1 (S = 71.52 mmHg, C = 84.76 mmHg, p = 0.0356) and M5 (S = 71.38 mmHg, C = 85.52 mmHg, p = 0.0252). The IOP and color Doppler values of the external ophthalmic artery did not differ between tested groups., Conclusions: The dose of 10 mg of sildenafil citrate administered to healthy rabbits causes systemic vasodilation and consequently lower values of MAP and OPP. However, it does not induce changes in IOP and retrobulbar hemodynamics identifiable by color Doppler assessment of the external ophthalmic artery.

Background and Purpose: Intra-arterial chemotherapy for retinoblastoma is not always a straightforward procedure, and it may require an adaptable approach. This study illustrates strategies used when the ophthalmic artery is difficult to catheterize or not visible, and it ascertains the effectiveness and safety of these strategies., Materials and Methods: A retrospective study was performed on a series of 108 eyes affected by intraocular retinoblastoma and selected for intra-arterial chemotherapy (follow-up range, 6-82 months). We recognized 3 different patterns of drug delivery: a fixed pattern through the ophthalmic artery, a fixed pattern through branches of the external carotid artery, and a variable pattern through either the ophthalmic or the external carotid artery., Results: We performed 448 sessions of intra-arterial chemotherapy, 83.70% of them through the ophthalmic artery and 16.29% via the external carotid artery. In 24.52% of eyes, the procedure was performed at least once through branches of the external carotid artery. In 73 eyes, the pattern of drug delivery was fixed through the ophthalmic artery; for 9 eyes, it was fixed through branches of the external carotid artery; and for 17 eyes, the pattern was variable. Statistical analysis did not show any significant difference in the clinical outcome of the eyes (remission versus enucleation) treated with different patterns of drug delivery. Adverse events could not be correlated with any particular pattern., Conclusions: Alternative routes of intra-arterial chemotherapy for intraocular retinoblastoma appear in the short term as effective and safe as the traditional drug infusion through the ophthalmic artery., (© 2016 by American Journal of Neuroradiology.)

Cerebral vasculature is often the target of stroke studies. However, the vasculature supplying the eye might also be affected by ischemia. The aim of the present study was to investigate if the transient global cerebral ischemia (GCI) enhances vascular effect of endothelin-1 (ET-1) and 5-hydroxytryptamine/serotonin (5-HT) on the ophthalmic artery in rats, leading to delayed retinal damage. This was preformed using myography on the ophthalmic artery, coupled with immunohistochemistry and electroretinogram (ERG) to assess the ischemic consequences on the retina. Results showed a significant increase of ET-1 mediated vasoconstriction at 48 hours post ischemia. The retina did not exhibit any morphological changes throughout the study. However, we found an increase of GFAP and vimentin expression at 72 hours and 7 days after ischemia, indicating Müller cell mediated gliosis. ERG revealed significantly decreased function at 72 hours, but recovered almost completely after 7 days. In conclusion, we propose that the increased contractile response via ET-1 receptors in the ophthalmic artery after 48 hours may elicit negative retinal consequences due to a second ischemic period. This may exacerbate retinal damage after ischemia as illustrated by the decreased retinal function and Müller cell activation. The ophthalmic artery and ET-1 mediated vasoconstriction may be a valid and novel therapeutic target after longer periods of ischemic insults.

Purpose: To study the retrobulbar haemodynamics in patients with Coats' disease., Methods: The clinical study included 43 patients with Coats' disease. Using colour Doppler imaging, we measured the blood flow velocity in the ophthalmic artery (OA), central retinal artery (CRA) and posterior ciliary arteries (PCA), and recorded the peak systolic velocity (PSV), end diastolic velocity (EDV), time averaged maximum velocity (TAMX), pulsatility index (PI) and resistance indexes (RI). The unaffected contralateral eyes served as control group. The disease was graded into four stages., Results: Compared to the contralateral eyes, the Coats' disease affected eyes showed for the CRA a significant decrease in PSV (7.08 ± 1.38 cm/s versus 8.64 ± 1.45 cm/s; p < 0.001), EDV (2.03 ± 0.41 cm/s versus 2.52 ± 0.62 cm/s; p < 0.001) and TAMX (3.67 ± 0.96 cm/s versus 4.40 ± 1.22 cm/s; p = 0.003) and for the PCA a significant decrease in PSV (9.15 ± 1.87 cm/s versus 10.14 ± 1.61 cm/s; p = 0.01). Subgroup analysis revealed that the decrease in haemodynamic parameters existed mainly in patients with stage 3A2 and stage 3B of Coats' disease., Conclusions: As measured by colour Doppler imaging, the retrobulbar blood vessels showed decreased haemodynamic parameters in patients with Coats' disease on the affected side as compared to the contralateral unaffected side, in particular in advanced stages of the disease. Future studies may address the causes and effects of these haemodynamic changes., (© 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Vascular insufficiency has been reported to be a cause of normal tension glaucoma (NTG). The aim of this study was to compare ocular perfusion pressure (OPP) and ophthalmic artery flow (OAF) between patients with NTG and those without glaucoma., Methods: We considered one eye each from 31 NTG and 15 non-glaucoma control patients. Blood pressure and intraocular pressure (IOP) were measured in the sitting position, for calculation of OPP. Humphrey visual field (HVF) assessment was then carried out on NTG patients. All patients then underwent Transcranial Doppler ultrasound measurements of OAF parameters, including mean flow velocity (MFV), end diastolic velocity (EDV), peak systolic velocity (PSV) and resistive index (RI). We looked at differences in OPP and OAF parameters between the two groups, and their correlations in NTG patients. T-tests, χ (2), ANOVA and Pearson Correlation tests were performed, with p < 0.05 considered statistically significant., Results: There were no statistically significant differences in OPP between the NTG and control groups (60.5+/-8.7 mmHg and 62.9+/-10.2 mmHg respectively, p = 0.393), and also no statistically significant differences in MFV, EDV, PSV and RI (all p > 0.05). In the NTG group, there were positive correlations between OPP and both MFV (r = 0.416, p = 0.020) and EDV (r = 0.369, p = 0.041). There were no statistically significant correlations between HVF mean deviation and OPP or OAF parameters (all p > 0.05)., Conclusion: There is no difference in OPP and OAF parameters between patients with NTG and non-glaucoma controls, suggesting that vascular insufficiency or dysregulation by themselves may not account for the pathogenesis of NTG.

Purpose: To investigate orbital flow parameters of ophthalmic artery (OA) in patients with pseudoexfoliation glaucoma (XFG) by ultrasonography., Methods: This case-control study included 38 patients with XFG and 32 healthy control subjects. Color Doppler imaging was performed to evaluate orbital flow parameters of OA. Receiver operating characteristic analyses were performed to define the best cutoff value., Results: In the XFG group, decreased peak systolic velocity (p = 0.114), end diastolic velocity (p = 0.002), and increased resistivity index (RI) (p&lt;0.001) at OA compared to healthy controls were observed. A cutoff value 0.72 for OA RI was found to have a sensitivity of 66% and specificity of 94%., Conclusions: The results support the findings of increased vascular resistance in OA XFG. High sensitivity and specificity obtained for OA RI may be useful in evaluation of future therapeutic vascular agents.