Floralozone Ameliorated Atherosclerosis in Experimental Atherosclerotic Rats Involved with Sphingosine 1-Phosphate 1 Enhancement.

Atherosclerosis (AS) is a chronical pathological process of the arterial narrows due to the AS plaque formation. The aim of this study was to explore the therapeutic effect and the underlying mechanism of Floralozone on experimental atherosclerotic model rats. Experimental atherosclerotic model rats were induced by the right carotid artery balloon injury and intraperitoneal injection of vitamin D3 in rats after 4 weeks high-fat diet. The results exhibited that Floralozone could ameliorate vascular injury and vasorelaxation of descending aortas and increase the superoxide dismutase activity and the expression of sphingosine 1-phosphate (S1P) 1 and reduce the intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, interleukin (IL)-1, IL-6 level, and the malondialdehyde activity in experimental atherosclerotic rats. However, Fingolimod, an S1P1 inhibitor, could reverse these Floralozone effects in experimental atherosclerotic rats. Our results indicated that Floralozone could inhibit the atherosclerotic plaque formation and improves arterial stenosis and reduces endothelial dysfunction in experimental atherosclerotic rats, which might be involved with S1P1 enhancement.

Inactive matrix Gla protein is a novel circulating biomarker predicting retinal arteriolar narrowing in humans.

Active matrix Gla protein (MGP), a potent inhibitor of calcification in large arteries, protects against macrovascular complications. Recent studies suggested that active MGP helps maintaining the integrity of the renal and myocardial microcirculation, but its role in preserving the retinal microcirculation remains unknown. In 935 randomly recruited Flemish participants (mean age, 40.9 years; 50.3% women), we measured plasma desphospho-uncarboxylated MGP (dp-ucMGP), a marker of poor vitamin K status using an ELISA-based assay at baseline (1996-2010) and retinal microvascular diameters using IVAN software (Vasculomatic ala Nicola, version 1.1) including the central retinal arteriolar (CRAE) and venular (CRVE) equivalent and the arteriole-to-venule ratio (AVR) at follow-up (2008-2015). CRAE (P = 0.005) and AVR (P = 0.080) at follow-up decreased across tertiles of the dp-ucMGP distribution. In unadjusted models, for a doubling of dp-ucMGP at baseline, CRAE and AVR at follow-up respectively decreased by 1.40 µm (95% confidence interval [CI], 0.32 to 2.48; P = 0.011) and 0.006 (CI, 0.001 to 0.011; P = 0.016). In multivariable-adjusted models accounting for sex, baseline characteristics and follow-up duration, these estimates were -1.03 µm (CI, -1.96 to -0.11; P = 0.028) and -0.007 (CI, -0.011 to -0.002; P = 0.007). Additional adjustment for changes from baseline to follow-up in major baseline characteristics yielded as estimates -0.91 µm (CI, -1.82 to -0.01; P = 0.048) and -0.006 (95% CI, -0.011 to -0.001; P = 0.014), respectively. Circulating inactive dp-ucMGP is a long-term predictor of smaller retinal arteriolar diameter in the general population. Our observations highlight the possibility that vitamin K supplementation might promote retinal health.

Randomized controlled trial of electro-stimulation therapies to modulate retinal blood flow and visual function in retinitis pigmentosa.

PURPOSE: We examined changes in visual function and ocular and retinal blood flow (RBF) among retinitis pigmentosa (RP) participants in a randomized controlled trial of electro-stimulation therapies. METHODS: Twenty-one RP participants were randomized (1:1:1) to transcorneal electrical stimulation (TES) at 6 weekly half-hour sessions, electro-acupuncture or inactive laser acupuncture (sham control) at 10 half-hour sessions over 2 weeks. Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA), quick contrast sensitivity function, Goldmann visual fields, AdaptDx scotopic sensitivity, spectral flow and colour Doppler imaging of the central retinal artery (CRA), and RBF in macular capillaries were measured twice pre-treatment, after 2 TES sessions, within a week and a month after intervention completion. RESULTS: We measured a significant improvement in retrobulbar CRA mean flow velocity for both the TES (p = 0.038) and electro-acupuncture groups (p = 0.001) on average after 2 weeks of treatment when compared to sham controls. Transcorneal electrical simulation (TES) and electro-acupuncture subjects had significant 55% and 34% greater increases, respectively, in RBF in the macular vessels when compared to sham controls (p < 0.001; p = 0.008) within a week of completing six TES sessions or a month after electro-acupuncture. There was a significant difference in the proportion of eyes that had improved visual function when comparing the three intervention groups (p = 0.038): four of seven TES subjects (57%), two of seven electro-acupuncture subjects (29%) and none of the seven control subjects (0%) had a significant visual improvement outside of typical test-retest variability at two consecutive post-treatment visits. CONCLUSION: Increased blood flow following electro-stimulation therapies is an objective, physiological change that occurred in addition to visual function improvements in some RP patients.

Retinal Vascular Occlusion Secondary to Retrobulbar Injection: Case Report and Literature Review.

Retrobulbar injection has been widely practiced as a technique of ocular anesthesia for many decades. Nevertheless, the technique is not free from complications. Vascular occlusion secondary to retrobulbar injection is rare but can be vision threatening. We report a case series of two such patients who presented with poor vision following retrobulbar injection. Fundus showed pale retina with cherry red spot suggestive of central retinal artery occlusion in case 1 and pale disc with sclerosed vessels and multiple superficial hemorrhages suggestive of a combined occlusion of retinal artery and vein in case 2. Optical coherence tomography (OCT) showed thickened inner retinal layers with intact outer retinal layers in case 1 and thinning in case 2. We conclude that retrobulbar injections can rarely be associated with dreadful vision-threatening complications like in our patients. We also report the role of OCT in assessing the prognosis following vascular occlusion.

Does phacoemulsification under topical anesthesia affect retrobulbar blood flow?

PURPOSE: To investigate with color Doppler imaging the effects of phacoemulsification surgery under topical anesthesia on retrobulbar vessels hemodynamics. METHODS: In this prospective study, color Doppler imaging was used to measure the maximum (Vmax) and minimum flow velocity (Vmin) of the central retinal vein, and the Vmax and Vmin, pulsatility index and resistance index of the central retinal artery, nasal, and temporal posterior ciliary arteries, and ophthalmic artery blood flow before and 1 day after phacoemulsification surgery under topical anesthesia. RESULTS: After phacoemulsification surgery under topical anesthesia, Vmin of the central retinal artery increased (p ≤ 0.05), whereas the other variables showed no significant change. CONCLUSIONS: Phacoemulsification surgery under topical anesthesia has a minor effect on retrobulbar blood flow. Therefore topical anesthesia should be suitable for patients with ocular perfusion disorders (eg, glaucoma).

A case report of Wyburn-Mason syndrome and review of the literature.

INTRODUCTION: Wyburn-Mason syndrome is a distinct congenital neurocutaneous entity comprised of ipsilateral arteriovenous malformations (AVMs) of the midbrain, vascular abnormalities affecting the visual pathway, and facial nevi. METHODS: We report a case and review of the literature of all other reported cases of Wyburn-Mason syndrome (n = 26) in the English literature since 1973. RESULTS: In this review, we report on a 4(1/2)-year-old boy with Wyburn-Mason syndrome who presented with left retinal and orbital AVMs and a ruptured thalamic AVM. The patient did not respond to light in the left eye and demonstrated a left afferent pupillary defect. He did not have any cutaneous lesions. We also characterize other reported cases of Wyburn-Mason syndrome. CONCLUSION: The presentation of patients with Wyburn-Mason syndrome can vary greatly according to the site and the extent of vascular lesions. Intracranial AVMs occasionally hemorrhage with significant morbidity. Treatment is controversial, and patients are typically managed conservatively by observation.

Colour Doppler imaging before and after retrobulbar anaesthesia in patients undergoing cataract surgery.

PURPOSE: To investigate the effect of retrobulbar anaesthesia on retrobulbar haemodynamics, colour Doppler imaging was performed. Furthermore, the additive effect of epinephrine was examined. METHOD: Forty-one patients (age 72.7+/-8.9; 22 f, 19 m) undergoing planned cataract surgery were included in a prospective study. Colour Doppler imaging was performed before and directly after retrobulbar anaesthesia and after cataract surgery to measure the peak systolic velocity (PSV) and end-diastolic velocity (EDV) in the ophthalmic artery, central retinal artery and central retinal vein. In 18 patients lidocaine 2% without additives (2 ml, retrobulbar transconjunctival injection) and in 23 patients lidocaine 2% with epinephrine 1:200,000 was used. RESULTS: After retrobulbar anaesthesia both groups had a significant reduction of the PSV and of the EDV. After surgery flow velocities increased again. The addition of epinephrine resulted in a significantly greater reduction and slower recovery of flow velocities. CONCLUSION: Retrobulbar anaesthesia induces a marked reduction of velocity in the retrobulbar vessels. The supplement epinephrine increases this effect, and recovery is much slower. Thus, particularly in patients with already disturbed ocular haemodynamics epinephrine should not be used in order to avoid irreversible functional damage.

Effect of retrobulbar versus subconjunctival anaesthesia on retrobulbar haemodynamics.

AIM: To investigate the effect of retrobulbar and subconjunctival anaesthesia on retrobulbar haemodynamics by colour Doppler imaging. METHOD: 39 patients (mean age 71 (SD 9) years; 19 females, 20 males) undergoing planned cataract surgery were included in the prospective study. Colour Doppler imaging (Siemens Sonoline Sienna, Germany) was performed before, directly after either subconjunctival (16 patients) or retrobulbar (23 patients) anaesthesia, and after cataract surgery to measure the peak systolic (PSV) and end diastolic velocities (EDV) in the ophthalmic artery (OA), central retinal artery (CRA), and central retinal vein (CRV). RESULTS: After retrobulbar anaesthesia there was a significant reduction of the PSV and of the EDV in all investigated vessels. After surgery the flow velocities increased again. Subconjunctival anaesthesia had no significant effects on retrobulbar haemodynamics. CONCLUSION: Retrobulbar anaesthesia induces a high reduction of velocity in the retrobulbar vessels in contrast with subconjunctival anaesthesia. Therefore subconjunctival anaesthesia should be preferred particularly in patients with problems of the ocular perfusion (for example, glaucoma).

Chorioretinal temperature monitoring during transpupillary thermotherapy for choroidal neovascularisation.

AIMS: To investigate the difference in temperature rise between normal choroid and choroidal revascularisation (CNV) during transpupillary thermotherapy (TTT) and the relation between laser spot size and power in the rat fundus. METHODS: A modified slit lamp, which was installed with two laser wavelengths (490 nm for illumination and fluorescein excitation and 810 nm for hyperthermia), was developed for TTT and temperature monitoring. Temperature rise during TTT was monitored by observing fluorescence released from thermosensitive liposomes encapsulating carboxyfluorescein. Two types of liposomes were prepared; their phase transition temperatures were 40 degrees C and 46 degrees C, respectively. Laser power settings required to observe fluorescence released from 46 degrees C liposome in normal choroid or CNV were compared. Next, the power settings with 0.5 mm and 0.25 mm spot sizes were compared following administration of 40 degrees C liposome or 46 degrees C liposome. RESULTS: The minimum power values when release from 46 degrees C liposome was observed showed a significant difference in distribution of power values between normal choroid and CNV. CNV required significantly higher power than normal choroid. With 40 degrees C liposome, the power was 9.7 (1.9) mW (mean (SD)) at a spot size of 0.25 mm, and 12.1 (1.6) mW at 0.5 mm, respectively. When using 46 degrees C liposome, the power setting was 10.2 (1.2) mW at a spot size of 0.25 mm, and 14.6 (2.2) mW at 0.5 mm, respectively. CONCLUSIONS: CNV demonstrated varying heat conduction, compared with normal choroid. Laser power required to raise the temperature should not necessarily be doubled, even when the spot size is doubled. Close attention should be given to the selection of power settings when performing TTT for CNV.

Effects of hachimi-jio-gan (ba-wei-di-huang-wan) on blood flow in the human central retinal artery.

Hachimi-jio-gan (HJG), a Chinese herbal formula, and a placebo were given to 12 healthy adults, and the changes in blood flow in the central retinal artery were observed with the latest ultrasonic diagnosis device before and after administration. After administration of HJG, the systolic flow velocity, diastolic flow velocity and mean flow velocity in the central retinal artery showed significant increases. No change was observed in vascular resistance. The subjects deemed suitable for use of HJG showed remarkable increases in blood flow. No changes in blood flow velocities and vascular resistance were observed after administration of the placebo. HJG is frequently used in the aged, often with eye diseases such as cataract. It has been reported that a decrease of blood flow in the central retinal artery becomes more marked in proportion to the progress of various eye diseases. As increases in blood flow were obvious in the cases that were treated with HJG, it is suggested that increases in blood flow in the central retinal artery due to HJG give direct evidence supporting the positive effects of HJG on eye diseases.

Relationship between the effect of carbon dioxide inhalation or nilvadipine on orbital blood flow in normal-tension glaucoma.

PURPOSE: To investigate the relationship between the effect of carbon dioxide (CO2) inhalation or oral nilvadipine, a calcium-channel blocker, on orbital blood flow in patients with normal-tension glaucoma, as determined by color Doppler imaging. PATIENTS AND METHODS: Sixteen patients with normal-tension glaucoma (mean age, 55.6+/-9.8 years; male:female ratio, 3:13) underwent color Doppler imaging to measure the resistance index, and peak systolic and end-diastolic blood flow velocities of the ophthalmic artery, central retinal artery, and nasal and temporal short posterior ciliary arteries. Measurements were taken before and during CO2 supplementation sufficient to increase the end-tidal CO2 partial pressure by 10%. The color Doppler imaging measurements were repeated after 2 to 4 weeks of treatment with 2 mg oral nilvadipine, and comparisons were made between the effects of the two treatments. RESULTS: Both CO2 inhalation and nilvadipine treatment significantly reduced the resistance index in the central retinal artery, nasal short posterior ciliary artery, and temporal short posterior ciliary artery. There was a significant correlation between the effects of the two treatments on the difference in the resistance indexes of the ophthalmic artery and central retinal artery, but not on those of the nasal or temporal short posterior ciliary artery. CONCLUSIONS: Both CO2 inhalation and oral nilvadipine significantly reduce the resistance index measured by color Doppler imaging in orbital vessels. The effect of oral nilvadipine might be predicted by CO2 inhalation in patients with normal-tension glaucoma.

Effects of peribulbar anesthesia on ocular blood flow in patients undergoing cataract surgery.

PURPOSE: The effects of extraconal, peribulbar anesthesia on ocular blood flow may be caused by concomitant elevations in intraocular pressure or direct pharmacologic alteration of vascular tone. We quantified the effect on ocular circulation with a new technique for assessment of ocular hemodynamics. METHODS: In a prospective study, ocular hemodynamics were measured before and 1 and 5 minutes after peribulbar anesthesia in 22 eyes with age-related cataract. Measurements included fundus pulsation amplitude with a laser interferometric method assessing the pulsatile choroidal blood flow and mean blood flow velocity as well as resistive index in the ophthalmic and central retinal artery with Doppler sonography. Systemic blood pressure and pulse were monitored throughout the period of ocular hemodynamic measurements. RESULTS: Fundus pulsation amplitude decreased significantly after peribulbar anesthesia (after 1 minute and 5 minutes: -13% and -8%; P < .001). In the central retinal artery, mean blood flow velocity dropped (-15%; P < .001) and resistive index increased (+3%; P = .02) 1 minute after peribulbar anesthesia compared with baseline. There were no changes in ophthalmic artery hemodynamics. Intraocular pressure was elevated 1 minute after peribulbar anesthesia (+29%; P = .003) but reached baseline values after 5 minutes. CONCLUSION: Pulsatile choroidal blood flow and retinal blood flow velocities were reduced after peribulbar anesthesia. These reductions were still present 5 minutes after peribulbar anesthesia, when intraocular pressure had returned to baseline values. This supports the theory of drug-induced vasoconstriction after peribulbar anesthesia. A loss of vision may be a risk of peribulbar anesthesia in patients who have compromised ocular blood flow before surgery.

Changes in optic nerve head blood flow and retrobular hemodynamics following calcium-channel blocker treatment of normal-tension glaucoma.

BACKGROUND: Because calcium channel blockers reduce vascular resistance, they may have a clinical application in the treatment of normal-tension glaucoma (NTG). This study investigates changes in both the optic disc blood flow and the hemodynamics of retrobulbar vessels in NTG patients after the systemic administration of a calcium channel blocker. METHODS: Twelve eyes of 12 NTG patients (mean age 57.6 +/- 15.3 years) were examined before and after a 4-week treatment with 2 mg b.i.d. oral nilvadipine, an L-typc calcium channel blocker. By scanning laser-Doppler flowmetry (SLDF), we obtained the velocity, flow, and volume from within a 10 x 10 pixel window placed on the temporal rim region of the optic disc perfusion map. By ultrasound color Doppler imaging (CDI), we measured the peak systolic velocity (PSV) and the end diastolic velocity (EDV) of the ophthalmic artery (OA), central retinal artery (CRA), nasal posterior ciliary artery (NPCA), and temporal posterior ciliary artery (TPCA). We then calculated a resistance index (RI) for each vessel. RESULTS: After treatment, the flow and velocity of the optic disc blood flow significantly increased (P < 0.05). Nilvadipine also significantly reduced RIs of the CRA, NPCA, and TPCA (P < 0.05), and increased both the PSV of the NPCA and the EDVs of the CRA, NPCA, and TPCA. The percent change in velocity correlated significantly with the percent changes of the CRA RI and NPCA RI. CONCLUSIONS: Oral nilvadipine appears to reduce orbital vascular resistance, which consequently increases the optic disc blood flow.

The effect of nilvadipine, a calcium-channel blocker, on the hemodynamics of retrobulbar vessels in normal-tension glaucoma.

PURPOSE: To investigate the effect of nilvadipine, a calcium-channel blocker, on the hemodynamics of retrobulbar vessels in normal-tension glaucoma. METHODS: Twenty-five patients who prospectively met the enrollment criteria underwent color Doppler imaging of the retrobulbar vessels before and after receiving 4 weeks of treatment with 2 mg oral nilvadipine twice daily. RESULTS: Nilvadipine significantly increased the end-diastolic velocity in the central retinal artery and a short posterior ciliary artery. It significantly reduced the resistance index in the central retinal artery and posterior ciliary arteries, but not in the ophthalmic artery. The calculated ocular perfusion pressure was not affected. CONCLUSION: Oral nilvadipine reduces vascular resistance in distal retrobulbar arteries in normal-tension glaucoma without affecting more proximal blood vessels. Therefore, nilvadipine may have a beneficial effect on the hemodynamics of retrobulbar vessels in normal-tension glaucoma.

A color Doppler analysis of nifedipine-induced posterior ocular blood flow changes in open-angle glaucoma.

PURPOSE: This pilot study used color Doppler imaging to investigate the effects of nifedipine on the posterior ocular blood flow of patients with glaucoma progression at normal intraocular pressures. PATIENTS AND METHODS: Eighteen patients, 11 men and seven women with a median age of 61.7 years, were imaged before and 6 weeks after the initiation of 30 mg of sustained-release nifedipine (Procardia XL; produced by either Pfizer or Pratt) daily. RESULTS: There was no statistically significant change in the blood velocity of the ophthalmic artery, central retinal artery, and main nasal and temporal short posterior ciliary arteries after treatment with nifedipine. CONCLUSION: The routine use of nifedipine in patients with normal tension glaucoma progression is not supported by this study.

Hemodynamic and visual function effects of oral nifedipine in patients with normal-tension glaucoma.

PURPOSE: To investigate ocular hemodynamic and visual function changes in patients with normal-tension glaucoma after treatment with a calcium channel blocker (nifedipine). METHODS: In 21 patients with normal-tension glaucoma, color Doppler imaging of the ophthalmic, central retinal, and short posterior ciliary arteries was carried out after a 4-week washout of prior drug treatment and again after 6 months of treatment with nifedipine (30 mg per day). Visual field sensitivity, spatial contrast sensitivity, and intraocular pressure were also recorded. RESULTS: Three subjects experienced intolerable side effects from the drug and were removed from the study. In two other patients, visual function was substantially reduced after 4 months of treatment; nifedipine was discontinued. In the remaining 16 subjects, mean intraocular pressure, retrobulbar hemodynamics, visual field mean sensitivity, and contrast sensitivity at 3, 12, and 18 cycles per degree (cpd), respectively, were unchanged after nifedipine treatment. Contrast sensitivity at 6 cpd, however, improved after drug treatment (P = .004). Individuals with the greatest improvements in contrast sensitivity at 6 cpd showed the largest increases in ophthalmic arterial peak systolic velocity (r = .57; P = .02) and end-diastolic velocity (r = .65; P = .001). CONCLUSION: Nifedipine fails to provide uniform visual function or retrobulbar hemodynamic responses in patients with normal-tension glaucoma. Those patients who do show improved visual function also show improved indices of retrobulbar perfusion.

[Perfusion time of the central retinal artery in normal pressure glaucoma. Initial results]. / Perfusionszeit der A. centralis retinae bei Normaldruckglaukom. Erste Ergebnisse.

UNLABELLED: A possible explanation for the progressive visual field defects in normal tension glaucoma is reduced ocular blood flow. We have tried to answer this question using fluorescence perfusion scintigraphy that measures the circulation times between the subclavian vein, carotid artery, central retinal artery and central retinal vein. PATIENTS: Eight normal subjects and eight age- and sex-matched normal tension glaucoma patients were compared. Inclusion criteria for NTG patients were an IOP below 23 mmHg, glaucomatous visual field defects, glaucomatous disk cupping, normal chamber angle and no neurologic deficits. The subclavian carotid time, the carotid retina time and the mean retinal perfusion time of the intravenously injected radioactive fluorescein bolus were measured using digitized scanning laser angiography and technetium scintigraphy. RESULTS: Subclavian carotid time and mean retinal perfusion time were not significantly different between groups, whereas the carotid retina time was 1.6 s (min = 0.8, max = 2.6) in normals and 3.3 (min = 2.6, max = 4.2) in normal tension glaucoma. This difference was highly significant (P < 0.001). CONCLUSIONS: The delay of the carotid retina circulation time in normal tension glaucoma patients may reflect a reduced blood flow velocity in the internal carotid artery, the ophthalmic artery and the central retinal artery. The subclavia carotid time and ultrasound investigation of the carotid artery were normal. This suggests that the delayed carotid retina time is an indicator of reduced blood flow velocity in ophthalmic and mainly central retinal artery. The good discrimination between normal subjects and NTG patients must be confirmed in a larger group of patients.

The use of nimodipine in a patient with eclampsia: color flow Doppler demonstration of retinal artery relaxation.

Color flow Doppler ultrasonography was used to demonstrate a significant and sustained reduction in the central retinal artery pulsatility index after administration of the calcium antagonist nimodipine to a patient with eclampsia. Nimodipine is an effective cerebral vasodilator and may be useful in the management of eclamptic patients with severe vasospasm.