Retinal Vasoconstriction Research Articles

OCTA quantitative assessment of exercise-induced variations and recovery in retinal microvasculature of healthy subjects with or without masks

PurposeTo investigate the impact of exercise and mask-wearing on retinal microvasculature using optical coherence tomography angiography (OCTA). MethodsA total of 30 healthy volunteers were enrolled and tasked with physical exercise to reach 75–80 % maximum heart rates. Swept-source OCTA was performed on the macular region and optic nerve head (ONH) in participants with no mask, surgical mask, or N95 mask at quiescent conditions (Step 1) and 0 min, 10 min, 20 min, and 30 min post-exercise (Steps 2–5, respectively). The functional vessel density (VD), including the superficial and deep plex (SP and DP) in the macular area and the superficial plex (SP), nerve fiber plex, and small vessels in the optic nerve head, were measured. ResultsUnder quiescent conditions, the functional VD of SP and DP exhibited significant reduction with surgical and N95 masks in the foveal area (P < 0.05). In step 2 (immediately after training) with or without masks, functional VD of SP and nerve fiber both showed significant reduction in the inside disc and peripapillary area, small functional VD of nerve fiber in the ONH showed significant reduction in peripapillary area (P < 0.05). These changes had been recovered in Step 5 (30 min post-exercise) in all groups (no-mask, surgical mask and N95 mask groups) (P > 0.05). ConclusionsMask-wearing and physical exercise reduce retinal functional VD in macular and ONH areas. The retinal vasoconstriction induced by exercise tends to recover after rest for approximately 30 min. Our research provides insights into mask-wearing and physical exercise's immediate retinal microvasculature effects, hinting at systemic microvascular changes.

388 Eye towards Artificial Intelligence: Retinal Vascular Tortuosity vs. Vasoconstriction to Differentiate Preeclamptic and Normotensive Subjects

388 Eye towards Artificial Intelligence: Retinal Vascular Tortuosity vs. Vasoconstriction to Differentiate Preeclamptic and Normotensive Subjects

Effects of pupil dilation with topical 0.5% tropicamide on retinal vascular parameters assessed by VAMPIRE® software in healthy cats

Our study investigates the effects of mydriasis obtained with topical 0.5% tropicamide on retinal vascular parameters evaluated in cats using the retinal imaging software: Vascular Assessment and Measurement Platform for Images of the Retina (VAMPIRE®). Forty client-owned healthy adult cats were included in the study. Topical 0.5% tropicamide was applied to dilate only the right pupil. The left eye was used as a control. Before dilation (T0), infrared pupillometry of both pupils was performed and fundus oculi images were taken from both eyes. Right eye fundus images were then captured 30 min after topical application of tropicamide (T30), when mydriasis was achieved. The retinal vessel widths (3 arteries and 3 veins) were measured with VAMPIRE® in four standard measurement areas (SMA) identified with the letters A, B, C, D. Average value of the 3 vessel widths was used. After normality assessment, the t-test was used to analyse the mean difference in vascular parameters of the left and right eyes at T0 and T30, with p set <0.05. The two eyes showed no statistical differences in pupil and vascular parameter measurements at T0. At T30, only one artery measurement of the right eye (SMA A-peripapillary area) showed a small but statistically significant mean vasoconstriction of approximately 4%. The results indicate that local application of 0.5% tropicamide seems to be associated with a small retinal arteriolar vasoconstriction as assessed by VAMPIRE® in cats. However, this change is minimal, and should not affect the interpretation of the results when VAMPIRE® is used.

Activation of HIF-1α/VEGF-A pathway by deferoxamine ameliorates retinal hypoxia in a rat subarachnoid hemorrhage model.

Subarachnoid hemorrhage (SAH) is associated with sustained vasoconstriction in retinal vessels and vasoconstriction leads to retinal ischemia and hypoxia. Our previous finding also revealed the changes in hypoxia-related elements in the retina after SAH, further lending weight to the hypothesis that retinal vasospasm and hypoxia after SAH. Deferoxamine is a high-affinity iron chelator with reported neuroprotective effects against stroke. Here, we aimed to explore the effects of deferoxamine on retinal hypoxia after SAH. SAH was established and deferoxamine was injected intraperitoneally for 3 days in the treatment group. To detect retinal new vessels, platelet endothelial cell adhesion molecule (CD31) was labeled by immunofluorescence and immunohistochemistry. Furthermore, the effects of deferoxamine on the expression of vascular endothelial growth factor A (VEGF-A) and hypoxia-inducible factor-1α (HIF-1α) were revealed by western blot analysis. The immunofluorescence and immunohistochemical staining of CD31 revealed a marked increase in new vessels in the retinal ganglion cell layer after deferoxamine treatment. By western blot analysis, HIF-1α and VEGF-A increased gradually in the first day and then rebounded to a new level on day 7. A deferoxamine-induced increase in HIF-1α/VEGF-A expression was also confirmed by western blot. Our findings suggest that modulating the application of deferoxamine may offer therapeutic approaches to alleviate retinal complications after SAH.

Acute effects of caffeine and glucose intake on retinal vessel calibres in healthy volunteers

PurposeTo evaluate the acute effects of caffeine and glucose intake on retinal vascular calibre of healthy adults.MethodsThis prospective crossover study was conducted at the Centre for Eye Research Australia (Melbourne, Australia). Standardized doses of 300 mg caffeine (approximately 3 cups coffee), 30 g glucose or 300 ml of water, were each given to 19 healthy subjects on separate days. Retinal photographs and blood pressure measurements were taken at baseline, 30-, 60- and 120-min after ingestion of each solution. Central retinal artery and vein equivalents (CRAE, CRVE) and the arterio-venule ratio were measured using computer-assisted software. The mean retinal vascular calibre measurements were compared between pre- and post-ingestion images.ResultsAfter caffeine intake, significant reductions were observed in mean CRAE of − 9.3 μm, − 10.4 μm and − 8.5 μm and CRVE of − 16.9 μm, − 18.7 μm and − 16.1 μm at 30-, 60- and 120-min after intake when compared with baseline (p ≤ 0.002 for all; paired t test). No significant changes were observed in mean retinal vascular calibre measurements after intake of either glucose or water when compared to baseline (p ≥ 0.072 for all). When controlling for baseline characteristics and blood pressure measurements, only caffeine intake had a significant effect on reducing both CRAE and CRVE at all time points post ingestion (p ≤ 0.003 for all, multiple linear regression model).ConclusionCaffeine is associated with an acute vasoconstrictive effect on retinal arterioles and venules in healthy subjects. Factors other than blood pressure-induced autoregulation play a significant role in caffeine-associated retinal vasoconstriction.

Endothelin 1-induced retinal ganglion cell death is largely mediated by JUN activation

Glaucoma is a neurodegenerative disease characterized by loss of retinal ganglion cells (RGCs), the output neurons of the retina. Multiple lines of evidence show the endothelin (EDN, also known as ET) system is important in glaucomatous neurodegeneration. To date, the molecular mechanisms within RGCs driving EDN-induced RGC death have not been clarified. The pro-apoptotic transcription factor JUN (the canonical target of JNK signaling) and the endoplasmic reticulum stress effector and transcription factor DNA damage inducible transcript 3 (DDIT3, also known as CHOP) have been shown to act downstream of EDN receptors. Previous studies demonstrated that JUN and DDIT3 were important regulators of RGC death after glaucoma-relevant injures. Here, we characterized EDN insult in vivo and investigated the role of JUN and DDIT3 in EDN-induced RGC death. To accomplish this, EDN1 ligand was intravitreally injected into the eyes of wildtype, Six3-cre+Junfl/fl (Jun−/−), Ddit3 null (Ddit3−/−), and Ddit3−/−Jun−/− mice. Intravitreal EDN1 was sufficient to drive RGC death in vivo. EDN1 insult caused JUN activation in RGCs, and deletion of Jun from the neural retina attenuated RGC death after EDN insult. However, deletion of Ddit3 did not confer significant protection to RGCs after EDN1 insult. These results indicate that EDN caused RGC death via a JUN-dependent mechanism. In addition, EDN signaling is known to elicit potent vasoconstriction. JUN signaling was shown to drive neuronal death after ischemic insult. Therefore, the effects of intravitreal EDN1 on retinal vessel diameter and hypoxia were explored. Intravitreal EDN1 caused transient retinal vasoconstriction and regions of RGC and Müller glia hypoxia. Thus, it remains a possibility that EDN elicits a hypoxic insult to RGCs, causing apoptosis via JNK-JUN signaling. The importance of EDN-induced vasoconstriction and hypoxia in causing RGC death after EDN insult and in models of glaucoma requires further investigation.

The Effect of Phosphodiesterase Type 5 Inhibitors on the Development of Retinopathy of Prematurity in Imam Khomeini Hospital's, Ahvaz, Iran Preterm Infants: A Randomized Clinical Trial

Background: Retinopathy of prematurity (ROP) affects premature infants, and it is characterized by the development of vascular proliferation due to hyperoxia, down regulation of Vascular endothelial growth factor(VEGF) and death of endothelial cells. We hypothesized that inhibition of Phosphodiesterase 5 enzyme suppresses retinal vasoconstriction and prevent ROP.&#x0D; Study Design: 109 newborns with respiratory distress syndrome treated with oxygen with early gestational age (GA) ≤30 weeks and birth weight (BW) ≤1500 g were randomized into two groups, 52 patients in sildenafil and 50 patients in placebo group were studied, Group sildenafil (as case group) and placebo Group (as control group), sildenafil was administered via nasogastric tube. Occurrence of ROP phase 1 as primary outcome and stage 2-5 ROP, duration of mechanical ventilation, oxygen therapy and duration of hospitalization as secondary outcomes were assessed.&#x0D; Results: There was no differences between the two group in demographic characteristics. ROP phase 1 was seen in 11(22%) and 7(14%) of placebo and interventional group, respectively. Stage 3 ROP was not seen in any of the patients.&#x0D; Conclusion: Sildenafil therapy did not affect ROP development in premature infants treated with oxygen. May be due to our exclusion criteria (BW less than 1000g) and this fact that there is a high incidence of ROP in extremely low birth weight neonates, we didn’t find any significant difference. More studies with larger population and expanded criteria are needed to find the effect of sildenafil on ROP.

The short-term effects of intravitreal aflibercept injections and dexamethasone implant on ocular hemodynamics in retinal vein occlusions.

PurposeTo determine the early effects of intravitreal anti-VEGF and dexamethasone application on blood flow velocities in patients with retinal vein occlusions.MethodsThe ophthalmic (OA) and the central retinal arteries (CRAs) of the affected and unaffected eyes of 21 patients with central retinal vein occlusion (CRVO), and 26 patients with branch retinal vein occlusion (BRVO) were investigated by Color Doppler imaging (CDI). Peak systolic volume (PSV), end diastolic volume (EDV), and average blood velocity (Vmean) of the CRA and OA were measured and resistive indexes (RI) were calculated at pre-injection and the 1st week and 1st month post-injection.ResultsThere was no statistically significant difference between the OA values for affected and unaffected eyes in the CRVO group before treatment. The CRA, EDV, and Vmean values were significantly lower in affected eyes. Blood flow velocities of both CRA and OA were not significantly different than in the fellow unaffected eyes in the BRVO group. The differences between PSV, EDV, and Vmean measurements of OA and CRA at different times pre- and post-injection in response to anti-VEGF and dexamethasone treatment in the CRVO group were significant; but there was no difference in RI value. OA blood flow velocity measurements were not statistically different post-injection in the BRVO group; however, the values of PSV and EDV of CRA decreased post-injection.ConclusionIntravitreal anti-VEGF and dexamethasone implant may induce retinal arteriolar vasoconstriction in patients with retinal vein occlusion.

Neuropeptide Y treatment induces retinal vasoconstriction and causes functional and histological retinal damage in a porcine ischaemia model.

To investigate the effects of intravitreal neuropeptide Y (NPY) treatment following acute retinal ischaemia in an invivo porcine model. In addition, we evaluated the vasoconstrictive potential of NPY on porcine retinal arteries exvivo. Twelve pigs underwent induced retinal ischaemia by elevated intraocular pressure clamping the ocular perfusion pressure at 5mmHg for 2hr followed by intravitreal injection of NPY or vehicle. After 4weeks, retinas were evaluated functionally by standard and global-flash multifocal electroretinogram (mfERG) and histologically by thickness of retinal layers and number of ganglion cells. Additionally, the vasoconstrictive effects of NPY and its involved receptors were tested using wire myographs and NPY receptor antagonists on porcine retinal arteries. Intravitreal injection of NPY after induced ischaemia caused a significant reduction in the mean induced component (IC) amplitude ratio (treated/normal eye) compared to vehicle-treated eyes. This reduction was accompanied by histological damage, where NPY treatment reduced the mean thickness of inner retinal layers and number of ganglion cells. In retinal arteries, NPY-induced vasoconstriction to a plateau of approximately 65% of potassium-induced constriction. This effect appeared to be mediated via Y1 and Y2, but not Y5. In seeming contrast to previous invitro studies, intravitreal NPY treatment caused functional and histological damage compared to vehicle after a retinal ischaemic insult. Furthermore, we showed for the first time that NPY induces Y1- and Y2- but not Y5-mediated vasoconstriction in retinal arteries. This constriction could explain the worsening invivo effect induced by NPY treatment following an ischaemic insult and suggests that future studies on exploring the neuroprotective effects of NPY might focus on other receptors than Y1 and Y2.

This issue of ACTA

This issue of <i>ACTA</i>

Vasoconstriction and Impairment of Neurovascular Coupling after Subarachnoid Hemorrhage: a Descriptive Analysis of Retinal Changes.

Impaired cerebral autoregulation and neurovascular coupling (NVC) contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Retinal vessel analysis (RVA) allows non-invasive assessment of vessel dimension and NVC hereby demonstrating a predictive value in the context of various neurovascular diseases. Using RVA as a translational approach, we aimed to assess the retinal vessels in patients with SAH. RVA was performed prospectively in 24 patients with acute SAH (group A: day 5-14), in 11 patients 3months after ictus (group B: day 90±35), and in 35 age-matched healthy controls (group C). Data was acquired using a Retinal Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and NVC using flicker-light excitation. Diameter of retinal vessels-central retinal arteriolar and venular equivalent-was significantly reduced in the acute phase (p<0.001) with gradual improvement in group B (p<0.05). Arterial NVC of group A was significantly impaired with diminished dilatation (p<0.001) and reduced area under the curve (p<0.01) when compared to group C. Group B showed persistent prolonged latency of arterial dilation (p<0.05). Venous NVC was significantly delayed after SAH compared to group C (A p<0.001; B p<0.05). To our knowledge, this is the first clinical study to document retinal vasoconstriction and impairment of NVC in patients with SAH. Using non-invasive RVA as a translational approach, characteristic patterns of compromise were detected for the arterial and venous compartment of the neurovascular unit in a time-dependent fashion. Recruitment will continue to facilitate a correlation analysis with clinical course and outcome.

The S1P1 receptor-selective agonist CYM-5442 protects retinal ganglion cells in endothelin-1 induced retinal ganglion cell loss

We investigated the feasibility and efficacy of using a specific sphingosine 1–phosphate (S1P1) receptor agonist, CYM-5442, to slow or block retinal ganglion cell (RGC) loss in endothelin-1 (ET-1) induced RGC loss. A single intravitreal injection of ET-1 (20pmol/ul), a potent vasoactive peptide that produces retinal vessels vasoconstriction, was used to induce and characterize RGC-specific cell death. CYM-5442 (1 mgr/kg) or vehicle was administered intraperitoneally for five consecutive days after ET-1-induced RGC loss. The functional extent of RGC loss injury was evaluated with pattern visual evoked potentials (VEP) and electroretinography. RGCs and retinal nerve fiber layer (RNFL) thickness were assessed in vivo using optical coherence tomography and ex vivo using Brn3a immunohistochemistry in flat-mounted retinas.ET-1 caused significant RGC loss and function loss one week after intravitreal injection. VEP showed preserved visual function after CYM-5442 administration compared to vehicle-treated animals (11.95 ± 0.86 μV vs 3.47 ± 1.20 μV, n = 12) (p < 0.05). RNFL was significantly thicker in the CYM treated-animals compared to the vehicle (93.62 ± 3.22 μm vs 77.72 ± 0.35 μm, n = 12) (p < 0.05). Furthermore, Brn3a immunohistochemistry validated this observation, showing significantly higher RGCs numbers in CYM treated rats than in the vehicle group (76,540 ± 303 vs 52,426 ± 1,932 cells/retina, n = 9) (p = 0.05). CYM-5442 administration was associated with significant retinal cleaved caspase-3 deactivation, indicating reduced apoptotic levels. The results of the present study further demonstrate the important role of S1P1 receptor agonists to lessen intravitreal ET-1 induced RGC loss.

Retrospective analysis of the effect of aflibercept loading dose on the retinal vessel diameters in patients with treatment-naive neovascular AMD

Background: To evaluate the effects of intravitreal aflibercept (IVA) on retinal vessel diameters in patients with neovascular age-related macular degeneration (AMD).Design, setting, and participants: A retrospective study conducted at the Kutahya Dumlupinar University Faculty of Medicine included 15 eyes of 15 patients with treatment naive neovascular AMD.Methods: All eyes received IVA injections once per month for 3 months; untreated contralateral eyes were used as controls. The central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and artery-vein ratio (AVR) values were measured using a computer-based program before the first IVA injection and 30 days after the first, second, and third injections. The main outcome measurements were the central macular thickness (CMT), best-corrected visual acuity (BCVA), choroidal thickness, CRAE, CRVE, and AVR.Results: Significant vasoconstriction of the retinal arterioles was observed in all eyes treated with IVA when compared to baseline (p = 0.009). However, no significant differences were found for CRVE or AVR throughout the study period in treated eyes. In the control group, all parameters measured during each visit were similar to baseline measurements (p > 0.05). The mean BCVA significantly improved at the end of the loading dose of IVA, when compared to baseline (p = 0.006). After the IVA injections, the mean CMT and choroidal thickness were significantly reduced at all visits, compared to baseline (p < 0.001).Conclusions: The current study showed that IVA led to significant retinal arteriolar vasoconstriction and choroidal thinning, which may cause reduced retinal blood flow.

Comparative Retinal Vessel Size Study of Intravitreal Ranibizumab and Bevacizumab in Eyes with Neovascular Age-Related Macular Degeneration

Purpose: The aim of this paper was to assess and compare the effects of intravitreal ranibizumab and bevacizumab on retinal vessel diameter in eyes with neovascular age-related macular degeneration (AMD). Methods: Patients with neovascular AMD who underwent intravitreal injection of either ranibizumab or bevacizumab were included. Noninjected fellow eyes served as a control. The main outcome measures were central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and the artery-vein ratio (AVR). Results: In the ranibizumab group, the mean CRAE value decreased significantly at 1 week and 1 month (p = 0.002). The AVR value decreased significantly at 1 month (p = 0.028). CRVE values did not change at 1 week and 1 month (p = 0.083). In the bevacizumab group, the preinjection CRAE, CRVE, and AVR values did not change through the study period (p = 0.128, p = 0.600, and p = 0.734, respectively). Conclusion: These results suggest that intravitreal ranibizumab led to significant retinal arteriolar vasoconstriction in eyes with neovascular AMD.

Effects of Ophthalmic Formulations Containing Cilostazol Nanoparticles on Retinal Vasoconstriction in Rats Injected with Endothelin-1

bstract Cilostazol (CLZ) is useful for the management of diabetic retinal vascular dysfunction and neuronal degeneration. However, drugdelivery in a posterior segment, such as retina,is not possible using eye drops with traditional formulations.In this study, we designed new ophthalmic formulations containing CLZ solid nanoparticles, and investigated whether these ophthalmic formulations provide noninvasive delivery systems targeting the posterior segment of the eye. The new ophthalmic formulations containing 1% CLZ solid nanoparticles were prepared byadding various additives [0.005% benzalkonium chloride (BAC), 0.5% d-mannitol, 2-hydroxypropyl-β-cyclodextrin (HPβCD) and 1% methylcellulose] and subjecting the mixtures to mill methods(CLZnano ophthalmic formulations; particle size 61 ± 43 nm, mean ± S.D.). The addition of HPβCD and mannitol enhanced the stability of the CLZ dispersion (CLZnano), and no precipitation from the CLZnano ophthalmic formulations was observed until 21 days after preparation. In addition, in the measurement of the antimicrobial activity against Escherichia coli (ATCC 8739),the CLZ nanoparticles in ophthalmic formulations didn’t affect the antimicrobial activityby preservative, such as BAC. In this study, retinal vasoconstriction was produced in rats by intravitreal injection of 1×10-5 M endotheline-1 (15 µL, ET-1); retinal vasoconstriction in ET-1-injected ratsreturned to normal by 48 h after injection. On the other hand, the instillation of CLZnano ophthalmic formulations suppressed the retinal vasoconstriction in ET-1-injected rats, and theretinal vascular caliber in rats instilled with CLZnano was similar than that in non-treated rats 3 h after intravitreal injection. It is possible that dispersions containing CLZ nanoparticles provide new possibilities for an effective, noninvasive method to deliver therapeutic agents to intraocular tissues such as the retina, and that an ocular drug delivery system using drug nanoparticles may expand their usage as therapy in the ophthalmologic field.

Effect of a single intravitreal injection of anti‐VEGF agents on retinal arteriolar caliber in mini pig eyes

AbstractPurpose The aim is to investigate the short‐term effect of a single intravitreal bevacizumab, ranibizumab or pegaptanib sodium injection on the retinal arteriolar caliber in minipigs.Methods 15 eyes received an intravitreal injection: bevacizumab 1,25mg (n=5), ranibizumab 0,5mg (n=5) and pegaptanib sodium 0,3mg (n=5). The diameter of the retinal arterioles was measured in vivo with a Retinal Vessel Analyzer (RVA) every 15 minutes for 2 hours.Results After the injection of bevacizumab statistical significant vasoconstriction was reached 1h after injection (p&lt; 0.01) and persisted until the end of the measurements (2h). Although there appears to be a trend towards vasoconstriction after ranibizumab injection, analysis of measurements indicate that statistical significance (p&lt;0.05) is reached only 1h 30min following injection. After the injection of pegaptanib sodium injection revealed no vasomotor effect of the substance. (p&gt;0.05)Conclusion The results suggest that intravitreal injection of anti‐VEGF that blocks all isoforms of VEGF, induces retinal vasoconstriction. Further studies with a larger number of subjects would be helpful in establishing more clearly the effect of intravitreal anti‐vascular endothelial growth factor treatment on retinal vessel diameters.

Retinal Hemodynamic Effects of Antioxidant Supplementation in an Endotoxin-Induced Model of Oxidative Stress in Humans

The Age-Related Eye Disease Study 1 (AREDS 1) has shown that nutritional supplementation with antioxidants and zinc modifies the natural course of AMD. It is presumed that the supplements exert their beneficial effects by ameliorating oxidative stress due to the scavenging of reactive oxygen species (ROS). We have shown in a human model that under oxidative stress induced by administration of lipopolysaccharide (LPS) the vasoconstrictor response of retinal vessels to oxygen breathing is diminished. This reduced vascular response to hyperoxia was previously shown to be normalized by the AREDS 1 supplements. In the present study, we tested the hypothesis that the response can also be restored by a different antioxidant formulation. This randomized, double-masked, placebo-controlled parallel group study included 40 healthy volunteers. On each study day, retinal red blood cell (RBC) flow and the reactivity of retinal RBC flow to hyperoxia were investigated in the absence and presence of 2 ng/kg LPS. Between the two study days, subjects received either the supplement or placebo for 14 days. Before supplementation LPS reduced retinal arterial vasoconstriction (P < 0.001) and reactivity of retinal RBC flow (P = 0.03) in response to 100% oxygen breathing. Two weeks of supplementation did not affect baseline retinal RBC flow, but normalized the LPS-induced change in the response to hyperoxia. The arterial vasoconstrictor response during LPS and 100% oxygen breathing was 4.1 ± 1.0% after administration of placebo and 10.6 ± 0.9% after supplementation (P = 0.005). The response of RBC flow to 100% oxygen breathing during LPS was 52.2 ± 2.1% after administration of placebo and 59.5 ± 2.0% after supplementation (P = 0.033). Our data show that the supplement used in the present study can normalize the response of retinal RBC flow to hyperoxia under LPS administration. This indicates that supplementation can prevent endothelial dysfunction induced by oxidative stress, which is assumed to play a role in the pathophysiology of AMD. (ClinicalTrials.gov number, NCT00914576.).

Long‐term results of the effect of intravitreal ranibizumab on the retinal arteriolar diameter in patients with neovascular age‐related macular degeneration

To study the effect of intravitreal (IVT) ranibizumab on the retinal arteriolar diameter in patients with neovascular age-related macular degeneration (AMD). Ten eyes of 10 patients with previously untreated neovascular AMD were included. All eyes had three monthly IVT injections of ranibizumab and then were retreated as needed, based on visual acuity and optical coherence tomography (OCT) criteria. The diameter of the retinal arterioles was measured in vivo with a retinal vessel analyser (RVA) before the first IVT injection, 7 and 30 days after the first, the second and the third injection, and at month 12 of follow-up. A significant vasoconstriction of the retinal arterioles was observed following each one of the first three IVT injections of ranibizumab. Thirty days following the first, second and third injection, there was a mean decrease of 8.4 ± 3.2%, 11.9 ± 4.5% and 18.5 ± 7.2%, respectively, of the retinal arteriolar diameter compared with baseline (p < 0.01). At month 12, the vasoconstriction was still present with a mean decrease of 19.1 ± 8.3% of the retinal arteriolar diameter compared with baseline (p < 0.01). Median number of ranibizumab injections was 4 (range 3-10). There was no correlation between the number of injections and percentage diameter decrease at month 12 (r = -0.54, p > 0.1). There was no significant change in mean arterial pressure (MAP) during the period of follow-up (p > 0.05). These results suggest that IVT ranibizumab induces sustained retinal arteriolar vasoconstriction in eyes with neovascular AMD.

Retinal arteriolar responses to acute severe elevation in systemic blood pressure in cats: Role of endothelium-derived factors

The purpose of this study was to investigate the roles of endothelium-derived factors in the retinal arteriolar responses to acute severe elevation in systemic blood pressure (BP) in cats. Acute elevation of mean arterial BP by 60% for 5 min was achieved by inflating a balloon-tipped catheter in the descending aorta. The retinal arteriolar diameter, flow velocity, wall shear rate (WSR) and blood flow (RBF) changes during BP elevation were assessed with laser Doppler velocimetry 2 h after intravitreal injections of nitric oxide (NO) synthase inhibitor l-NAME, cyclooxygenase inhibitor indomethacin, endothelin-1 receptor antagonists (BQ-123 for type A and BQ-788 for type B), or Rho kinase inhibitor fasudil. BP elevation caused a marked increase in retinal arteriolar flow velocity and WSR with slight vasoconstriction, resulting in an increase in RBF. The increases in velocity, WSR and RBF, but not diameter, were correlated with the increase in ocular perfusion pressure. With l-NAME or indomethacin, the increase in RBF upon BP elevation was significantly attenuated due to enhanced retinal arteriolar vasoconstriction. In contrast, BQ-123 and fasudil potentiated the increased RBF. BQ-788 had no effect on arteriolar diameter and hemodynamics. Our data suggest that acute elevation of BP by 60% leads to an increase in RBF due to the release of NO and prostanoids probably through a shear stress-induced vasodilation mechanism. The release of endothelin-1 and Rho kinase activation help to limit RBF augmentation by counteracting the vasodilation. It appears that the retinal endothelium, by releasing vasoactive substances, contributes to RBF regulation during acute severe elevation of systemic blood pressure.

Comparison of retinal vasodilator and constrictor responses in type 2 diabetes

The retinal blood vessels provide a unique way to directly examine the human microvasculature, which is frequently damaged in individuals with diabetes. Previous studies have demonstrated that retinal flickering light-induced vasodilation and hyperoxia-induced vasoconstriction may operate by enhancing or reducing similar vasoregulatory factor(s), but a comparison between these two provocative stimuli in individuals with diabetes has not been studied. The purpose of the study was to examine the association between retinal flickering light-induced vasodilation and retinal hyperoxia-induced vasoconstriction in type 2 diabetic subjects and in healthy controls. Twenty men and women with type 2 diabetes and 10 men and women without diabetes between 21 and 75 years of age were recruited. Changes in retinal artery and vein diameters to flickering light and during hyperoxia (100% oxygen) stimuli were measured on the same visit using a noninvasive retinal imaging device (Dynamic Vessel Analyzer, Imedos Inc., Germany). Compared with controls, diabetic subjects had impaired arterial vasodilator and vasoconstrictor responses to both flickering light and hyperoxia, respectively (both p<0.001). Merging both groups, an inverse correlation (r=-0.56; p=0.003) between the retinal artery's responses to flickering light-induced vasodilation and hyperoxia-induced vasoconstriction was demonstrated independent of glucose or insulin levels. This suggests that both responses are attenuated to a similar degree in diabetic subjects and that the attenuation to both stimuli can be observed in retinal arteries and veins. This would suggest that similar vasoregulatory factor(s) might in part help to explain the retinal diameter responses between the two stimuli. One suggested common vasoregulator of vascular tone is nitric oxide; however, other factor(s) may be involved, which contribute to this association and require further research.