The vasoactive effects of bradykinin, vasoactive intestinal peptide, calcitonin gene-related peptide and neuropeptide Y depend on the perivascular tissue in porcine retinal arterioles in vitro.

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

Downregulation of Retinal Connexin 43 in GFAP-Expressing Cells Modifies Vasoreactivity Induced by Perfusion Ocular Pressure Changes.

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

Color Doppler imaging of orbital vasculature before and after orbital decompression in thyroid eye disease.

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.

Blood Flow in Monocular Retinoblastoma Assessed by Color Doppler and Correlations With High-Risk Pathologic Features.

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

Characterization of the retina-induced relaxation in mice.

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

Association Between the Cilioretinal Artery and Choroidal Neovascularization in Age-Related Macular Degeneration: A Secondary Analysis From the Age-Related Eye Disease Study.

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

The effects of antioxidants on ocular blood flow in patients with glaucoma.

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.

Effect of intravitreal aflibercept (Eylea®) on retrobulbar hemodynamics in patients with neovascular age-related macular degeneration.

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.

Activation of Veratridine Sensitive Sodium Channels, But not Electrical Field Stimulation, Dilates Porcine Retinal Arterioles with Preserved Perivascular Tissue.

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

Retrobulbar ocular blood flow changes measured by colour Doppler imaging after intra-arterial chemotherapy in retinoblastoma.

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.

Effect of Intravitreal Aflibercept on Central Retinal Arterial Blood Flow in Type 1 Retinopathy of Prematurity.

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

The Effects of 23-Gauge Pars Plana Vitrectomy on Orbital Circulation Using Doppler Ultrasonography in Diabetic Macular Edema with Epiretinal Membrane and Taut Posterior Hyaloid.

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.

Does steep Trendelenburg positioning effect the ocular hemodynamics and intraocular pressure in patients undergoing robotic cystectomy and robotic prostatectomy?

PURPOSE: To examine the effect of steep Trendelenburg position (ST) on intraocular pressure (IOP), resistive index of the central retinal artery, and venous impedance index of the central retinal vein during robotic prostatectomy and cystectomy. METHODS: A total of fifty-three male patients were included into the study (prostatectomy: 43, cystectomy: 10). During robotic surgery, the effect of the ST on IOP, resistive index of the central retinal artery (CRA-RI), and venous impedance index of the central retinal vein (CRV-VI) was prospectively examined. The measurement times of IOP are as follows: T1: before anesthesia while supine and awake; T2: anesthetized and supine; T3: anesthetized and ST; T4: anesthetized, ST, and intraperitoneal insufflation; T5: anesthetized in ST at the end of the procedure with CO2; T6: anesthetized in ST after desufflation; and T7: anesthetized supine before awakening. RESULTS: There was no difference between the IOP values of the right and left eyes in both groups. The highest IOP values were reached at T4 and T5. CRA-RI values were different, while CRV-VI values were similar at T1 and T4. CONCLUSIONS: Despite staying in the ST for a long time provided that the ophthalmologic examination was normal, ocular complication risk is low in robotic prostatectomy and cystectomy.

Effect of smoking on retrobulbar blood flow in thyroid eye disease.

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.

Vasorelaxing Effect of Resveratrol on Bovine Retinal Arteries.

PURPOSE: Resveratrol is a red wine polyphenol that causes vasorelaxation, which could be of interest in the treatment or prevention of eye diseases with an impaired blood flow. In this study, the vasorelaxant capacity of resveratrol (cis and trans) on bovine retinal arteries, its vasorelaxing mechanism, and its influence on the relaxation induced by the retinal relaxing factor (RRF) were examined. METHODS: Isolated bovine retinal arteries were mounted into wire myographs for isometric tension measurements. Concentration-response curves of cis- and trans-resveratrol and concentration-response curves of resveratrol in the absence or presence of the endothelium or different inhibitors were constructed. Relaxations elicited by the RRF with and without resveratrol incubation were also compared. RESULTS: Both resveratrol isomers caused a similar strong concentration-dependent relaxation. Removal of the endothelium or blocking endothelium-dependent pathways did not change the relaxation. Also, K+ channel blockers did not reduce the relaxation, except the 120 mM K+ Krebs Ringer bicarbonate solution. Phorbol 12-myristate 13-acetate and phorbol 12,13-dibutyrate blocked the relaxation partially and so did the inhibition of heme oxygenase-1. Blocking adenylyl cyclase, AMP-activated protein kinase, estrogen receptors, sirtuin 1, or sarco/endoplasmic reticulum Ca2+ ATPase did not have an effect. The relaxation caused by the RRF was not altered by resveratrol incubation. CONCLUSIONS: Cis- and trans-resveratrol relax bovine retinal arteries similarly and concentration dependently. The main relaxation mechanism remains unclear, but K+ channels, carbon monoxide, and the myosin phosphatase pathway may be involved. Resveratrol does not have an influence on the RRF.

Correlation Between Choroidal Thickness and Ciliary Artery Blood Flow Velocity in Normal Subjects.

BACKGROUND AND OBJECTIVE: To study the correlation between the choroidal thickness (CT) measured by spectral-domain optical coherence tomography (SD-OCT) and retrobulbar blood flow measured by color Doppler flowmetry (CD) in normal subjects. PATIENTS AND METHODS: Healthy subjects underwent enhanced-depth imaging SD-OCT and CD using a linear 6 MHz to 18 MHz transducer. The maximal peak systolic velocity and resistance index (RI) were obtained for the ophthalmic artery (OA), short posterior ciliary artery (SPCA), and central retinal artery (CRA) and correlated with the subfoveal CT measured by SD-OCT. RESULTS: Twenty-seven eyes of 27 healthy patients were enrolled (mean age: 40.6 ± 12.4 years; range: 27-68 years). An inverse proportional relationship (P = .0496) was identified between the RI of the SPCA (mean, 0.6117 ± 0.07911) and the subfoveal CT (319.9 µm ± 83.79 µm) but not between the RI and the OA (mean: 0.7019 µm ± 0.07317 µm) or the CRA (mean: 0.68843 µm ± 0.08994 µm). CONCLUSION: The results of this study suggested there is an inverse proportional relationship between the RI of the SPCA and the subfoveal CT. The data also suggested a correlation between a decrease in the CT and increased RI in the retrobulbar arteries. Therefore, lower choroidal blood flow may explain the thinner CT in normal subjects.

Purinergic mechanisms and prostaglandin E receptors involved in ATP-induced relaxation of porcine retinal arterioles in vitro.

PURPOSE: Adenosine triphosphate (ATP) is involved in the tone regulation of retinal arterioles, and the effect may be direct, through ATP degradation or mediated by cyclo-oxygenase products. However, the relative contribution of these mechanisms and the extent to which the mechanisms are active in the retinal vascular wall or depend on the perivascular retinal tissue are unknown. METHODS: Porcine retinal arterioles with perivascular retinal tissue were mounted in a wire myograph for isometric tone recordings. The relaxing effects of ATP and the non-degradable analogue ATP-x03B3;S were studied in the presence of antagonists to ATP, adenosine and prostaglandin E (EP) receptors. The experiments were repeated after removal of the perivascular retinal tissue. RESULTS: ATP induced a significant concentration-dependent relaxation of retinal arterioles (p < 0.05) which was reduced after removal of perivascular retinal tissue. The effect was due to non-degraded ATP and a degradation product of ATP acting via adenosine receptors. Relaxation was reduced by ibuprofen and blocking of EP1 receptors. CONCLUSION: ATP-induced relaxation of retinal arterioles is mediated by ATP, ATP degradation products and by stimulation of EP1 receptors, involving both the perivascular retina and the vascular wall. The findings emphasize the complexity of purinergic effects in the regulation of retinal vascular tone.

Effect of intravitreal bevacizumab on retrobulbar blood flow of patients with diabetic macular edema.

PURPOSE: To determine the effect of intravitreal bevacizumab on retrobulbar blood flow of patients with diabetic macular edema. METHODS: Peak systolic velocity, end-diastolic velocity, resistance, and pulsatility indices of central retinal artery (CRA), nasal posterior ciliary artery (NPCA), temporal posterior ciliary artery (TPCA), and ophthalmic artery (OA) were assessed by color Doppler ultrasonography in injected and uninjected eyes of 37 patients at baseline and at day 1 and day 7 after the injection. RESULTS: At day 1 after the injection, peak systolic and end diastolic velocities of the CRA and NPCA in the injected eyes and peak systolic velocity of NPCA in the uninjected eyes decreased significantly (p<0.05, p = 0.025, respectively). Peak systolic and end diastolic velocities were not significantly different in the injected and uninjected eyes at day 7 after the injection (p>0.05). In the injected eyes, there was no significant change in resistance and pulsatility indices (p>0.05), but a decrease in resistance index of NPCA and resistance and pulsatility indices of TPCA occurred in uninjected eyes at day 7 after the injection (p = 0.016, p = 0.023, and p = 0.025, respectively). CONCLUSIONS: Intravitreal bevacizumab affects retrobulbar blood flow in injected and uninjected eyes of patients with diabetic macular edema.