Increase In Retinal Blood Flow Research Articles

New findings on retinal microvascular changes in patients with primary COVID-19 infection: a longitudinal study.

To investigate the longitudinal alterations of retinal microvasculature in patients with primary coronavirus disease 2019 (COVID-19) infection. A cohort of participants, who had never been infected with COVID-19, was recruited between December 2022 and May 2023 at Peking Union Medical College Hospital in Beijing, China. Participants underwent comprehensive ophthalmologic examinations and fundus imaging, which included color fundus photography, autofluorescence photography, swept-source optical coherence tomography (SS-OCT) and SS-OCT angiography (SS-OCTA). If participants were infected with COVID-19 during the study, follow-ups with consistent imaging modality were conducted within one week and two months after recovery from the infection. 31 patients (61 eyes), with a mean age of 31.0 ± 7.2 years old, were eligible for this study. All participants contracted mild COVID-19 infection within one month of baseline data collection. The average period was 10.9 ± 2.0 days post-infection for the first follow-up and 61.0 ± 3.5 days for the second follow-up. No clinical retinal microvasculopathy features were observed during the follow-ups. However, SS-OCTA analysis showed a significant increase in macular vessel density (MVD) from 60.76 ± 2.88% at baseline to 61.59 ± 3.72%(p=0.015) at the first follow-up, which subsequently returned to the baseline level of 60.23 ± 3.33% (p=0.162) at the two-month follow-up. The foveal avascular zone (FAZ) remained stable during the follow-ups with areas of 0.339 ± 0.097mm2, 0.342 ± 0.093mm2, and 0.344 ± 0.098mm2 at the baseline, first follow-up (p=0.09) and second follow-up (p=0.052), respectively. Central macular thickness, cube volume and ganglion cell-inner plexiform layer showed a transient decrease at the first follow-up(p<0.001, p=0.039, p=0.002, respectively), and increased to baseline level at the two-month follow-up(p=0.401, p=0.368, p=0.438, respectively). Mild COVID-19 infection may temporarily and reversibly impact retinal microvasculature, characterized by a transient increase in retinal blood flow during the early recovery phase, which returns to the pre-infection level two months post-infection.

704 Different Therapeutic Effects on the Ipsilateral Retinal-choroidal Blood Flow and the Visual Acuity Between Carotid Endarterectomy and Carotid Artery Stentinga

INTRODUCTION: We previously reported that ipsilateral retinal-choroidal blood flow increased, and ipsilateral visual acuity improved after carotid endarterectomy (CEA) for internal carotid artery stenosis. METHODS: Twenty-eight patients who underwent CAS at participating centers were enrolled for this prospective observational study. Retinal-choroidal blood flow was evaluated by Mean Blur Ratio (MBR) with Laser Speckled Flowgraphy before and after CAS. In addition, visual acuity was measured precisely with the CSV-1000 before and after surgery. The MBR was defined as an increase in retinal blood flow above 1.14 based on the results of measurements in normal subjects. RESULTS: MBR significantly increased after CAS (MBR 34.2 vs 34.3, p = 0.02), but there was no improvement in the CSV-1000 score observed after CEA as shown in our previous CEA study (4.8 vs 4.9, p = 0.57). Furthermore, the CSV-1000 score did not improve after CAS even when the evaluation was limited to the group with a significant increase in MBR. CONCLUSIONS: The improvement in visual function after CEA that we have shown in the past was not observed after CAS. One reason for this is that postoperative MRI showed scattered microembolic infarctions after CAS in 17.9% (5 patients), whereas 7.3% after CEA in our previous study, which may have caused micro-occlusion of the retinal arteries. Although a direct comparison cannot be conducted, postoperative microembolism occurred in only 7.3% (3/41 patients) in our previous study that demonstrated improved vision after CEA. We also cannot rule out the possibility that intraoperative microemboli caused the deterioration of higher brain functions such as visual cognition, leading to the decreased score of the CSV-1000. This study might provide details on the therapeutic effects of carotid revascularization other than stroke prevention and may contribute to optimizing treatment choices for individual patients.

Qi-Shen-Tang alleviates retinitis pigmentosa by inhibiting ferroptotic features via the NRF2/GPX4 signaling pathway

Ferroptosis has been observed during retinal photoreceptor cell death, suggesting that it plays a role in retinitis pigmentosa (RP) pathogenesis. Qi-Shen-Tang (QST) is a combination of two traditional Chinese medicines used for the treatment of ophthalmic diseases; however, its mechanism of action in RP and ferroptosis remains unclear. Therefore, this study aimed to explore the effect and potential molecular mechanisms of QST on RP. QST significantly improved tissue morphology and function of the retina in the RP model mice. A significant increase in retinal blood flow and normalization of the fundus structure were observed in mice in the treatment group. After QST treatment, the level of iron and the production of malondialdehyde decreased significantly; the levels of superoxide dismutase and glutathione increased significantly; and the protein expression of glutathione peroxidase 4 (GPX4), glutathione synthetase, solute carrier family 7 member 11, and nuclear factor erythroid 2-related factor 2 (NRF2) increased significantly. The molecular docking results demonstrated potential interactions between the small molecules of QST and the key proteins of NRF2/GPX4 signaling pathway. Our results indicate that QST may inhibit ferroptosis by inhibiting the NRF2/GPX4 signaling pathway, thereby reducing RP-induced damage to retinal tissue.

Alterations in ocular microcirculation and oxygen metabolism in patients with lipemia retinalis

PurposeThe study aims to assess the alterations in retinal oxygen saturation and retinal and choroidal blood flow in lipemia retinalis.MethodsThis was a cross-sectional study on 10 eyes (5 patients) with history of lipemia retinalis. The study comprised 10 eyes with documented history of lipemia retinalis and 10 participants as healthy controls. Patients with a confirmed history of lipemia retinalis were grouped into two cohorts based on their most recent fundus examination: untreated lipemia retinalis (abnormal fundus) and resolved lipemia retinalis (normal fundus). Both retinal arteriolar and venular oxygen saturation were measured using the non-invasive spectrophotometric retinal oximeter (Oxymap T1). The mean blur rate (MBR) of the optic nerve and choroidal blood flow were analyzed using a laser speckle flowgraph (LSFG).ResultsPatients with untreated lipemia retinalis had a significantly higher retinal arteriolar and venular oxygen saturation than that of the other two groups (p < 0.001). Moreover, patients with untreated lipemia retinalis had significantly smaller retinal arteriolar and venular diameters (p < 0.001). On LSFG, there was a significant difference in the overall MBR (p = 0.007) and vessel MBR of the optic nerve between the groups (p = 0.011). The patients with history of lipemia retinalis (untreated and resolved) exhibited a high overall MBR and vessel MBR of the optic nerve than that of the control group. There was a significant elevation of the optic nerve (p = 0.002) and choroidal blowout score (p < 0.001), while the resistivity index of the optic nerve (p = 0.001) and choroids (p = 0.002) was significantly lower in patients with resolved and untreated lipemia retinalis.ConclusionsThere was a significant alteration in retinal oximetry, in untreated lipemia retinalis, and in retinal blood flow, in both the resolved and untreated groups. The increase in retinal blood flow and oxygen saturation may elucidate the preservation of visual acuity and function despite the fundus changes observed in lipemia retinalis.

Dilatation of Retinal Arterioles Induced by Topical Dorzolamide for One Week Is Impaired in Patients with Type 1 Diabetes and Mild Retinopathy

Background: Diabetic retinopathy is characterised by morphological lesions in the retina secondary to disturbances in retinal blood flow. Previous studies have shown that the carbonic anhydrase inhibitor (CAI) dorzolamide can induce immediate dilatation of retinal arterioles and a sustained increase in retinal blood flow in primary open-angle glaucoma. However, the effect of sustained treatment with CAI on retinal arterioles in normal persons and in patients with diabetic retinopathy is unknown. Methods: The Dynamic Vessel Analyzer was used to assess the baseline diameter and the diameter response of retinal arterioles during an increase in arterial blood pressure induced by isometric exercise and during flicker stimulation before and 2 h, 24 h and 1 week after onset of topical treatment with dorzolamide. At each examination the diameter responses were studied before and during breathing in of a hypercapnic gas mixture. Results: Treatment with dorzolamide for 1 week significantly increased the diameter of retinal arterioles in normal persons, and breathing in of a hypercapnic gas mixture reduced this response. The pathological vasodilatation and reduced retinal autoregulation in patients with diabetic retinopathy were unaffected by dorzolamide and hypercapnia. Conclusions: The study suggests a lack of relevance of CAI for the treatment of pathological vasodilatation in early diabetic retinopathy.

Role of neuronal nitric oxide synthase in regulating retinal blood flow during flicker-induced hyperemia in cats.

To investigate how neuronal nitric oxide synthase (nNOS) contributes to regulation of the retinal circulation during rest and flicker stimulation in cats. Using laser Doppler velocimetry, we measured the vessel diameter and blood velocity simultaneously and calculated the retinal blood flow (RBF) in feline first-order retinal arterioles. After intravitreal injections of Nω-Nitro-L-arginine methyl ester (L-NAME), a nonselective NOS inhibitor, and Nω-propyl-L-arginine (L-NPA), a selective nNOS inhibitor, we continuously monitored the retinal circulation without any perturbations for 2 hours. We then examined the changes in the RBF in response to 16-Hz flicker stimuli for 3 minutes at 2 hours after intravitreal injection of phosphate-buffered saline (PBS) as a control, L-NAME, L-NPA, and thromboxane A2 (TXA2) analogue U46619 as a basal tone-adjusted control. After intravitreal injection of L-NAME and L-NPA, the baseline RBF decreased gradually in a dose-dependent manner. In the PBS group, the RBF increased gradually and reached a maximal level after 2 to 3 minutes of flicker stimuli. After 3 minutes of 16-Hz flicker stimuli, the RBF increased by 53.5% ± 3.4% compared with baseline. In the L-NAME and L-NPA groups, the increases in RBF during flicker stimulation were attenuated significantly compared with the PBS group. In the TXA2 group, the reduction in the flicker-induced increase in RBF was comparable to that in the PBS group. The current results suggested that increased RBF in response to flicker stimulation may be mediated by nitric oxide (NO) production via nNOS activation.

Retinal blood flow and vascular reactivity in chronic smokers.

The aim of this study was to investigate the impact of cigarette smoking in otherwise healthy young individuals on retinal blood flow (RBF) and vascular reactivity (RVR). An automated gas flow controller (RespirAct) was used to achieve normoxic hypercapnia in 10 nonsmokers (mean age 28.9; SD 4.6 years) and nine smokers (mean age 27.55; SD 4.7 years). Retinal blood flow measurements were obtained using a prototype Doppler spectral-domain optical coherence tomographer (SD-OCT) and bidirectional laser Doppler velocimetry and simultaneous vessel densitometry during baseline, normoxic hypercapnia, and recovery. Group mean PETCO2 (end-tidal partial pressure of CO2) was increased by 15.9% in the nonsmoking group and by 15.7% in the smoking group, with a concomitant increase in PETO2 (end-tidal partial pressure of O2) by approximately 1.5% to 2% in both groups. In nonsmokers, retinal arteriolar diameter (P < 0.0001), centerline velocity (P = 0.0004), and blood flow (P < 0.0001) significantly increased during normoxic hypercapnia. Similarly, the venous area (P = 0.0418), venous velocity (P = 0.0068), and total venous RBF (P < 0.0001), as measured by the prototype Doppler SD-OCT, significantly increased. In smokers, normoxic hypercapnia resulted in a significant increase in velocity (P = 0.0019), flow (P = 0.0029), and total venous RBF (P = 0.002). Comparing smokers and nonsmokers, the percentage change in arteriolar diameter (P = 0.0379) and blood flow (P = 0.0101) was significantly lower in the smoking group. There was no significant difference in baseline PETCO2 level between smokers and nonsmokers. Retinal vascular reactivity in response to normoxic hypercapnia is significantly reduced in young, healthy smokers compared with nonsmokers.

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Effect of regular smoking on flicker induced retinal vasodilatation in healthy subjects

BackgroundHabitual smoking is a risk factor for a variety of vascular diseases, including ocular pathologies. In the current study, we set out to investigate whether the regulation of retinal vascular tone is impaired in habitual smokers. For this purpose, vascular reactivity was tested during flicker light induced vasodilatation in smokers and in a non-smoking control group. MethodsIn this prospective, balanced, parallel group study 24 chronic smokers (28.1±3.3years) and 24 age-matched never-smoking volunteers (28.2±4.0years) were included. Flicker induced vasodilatation was measured in major retinal arteries and veins using a retinal vessel analyzer and flicker induced changes in retinal blood velocities were assessed in retinal veins by laser Doppler velocimetry. Three flicker periods of 60s were scheduled. Blood cotinine concentration was determined and a Fagerstrom questionnaire was performed to evaluate nicotine dependency. ResultsIn non-smoking subjects, stimulation with flicker light increased retinal venous diameter by +7.7±3.1%, +6.9±2.9% and +7.1±2.8% during the three flicker periods, respectively. Flicker induced vasodilatation in veins was significantly diminished in chronic smokers (+4.9±2.4%, +6.3±3.1% and +5.7±3.4%, ANOVA between groups, p=0.032) as compared to the non-smoking control group. Calculated retinal blood flow in the measured veins increased by a maximum of +54±21%, +43±18% and +46±19% during the three stimulation periods in the non-smoking subjects, respectively. The flicker induced increase in retinal blood flow as assessed in the veins was significantly reduced in chronic smokers as compared to the non-smoking control group (+19±16%, +26±14%, +24±13%, ANOVA between groups, p=0.013). In retinal arteries, flicker stimulation increased retinal arterial diameters by 5.2±3.8%, 5.8±4.8% and 5.5±5.6% during the three flicker periods in the non-smoking group. In smokers, the flicker induced arterial vasodilatation was not significantly different compared to non-smokers (4.6±4.1%, 3.8±3.7% and 4.8±3.4%, ANOVA between groups, p=0.4). ConclusionOur data indicate that the flicker induced hemodynamic response of retinal veins is reduced in chronic smokers as compared to age matched healthy volunteers. This supports the hypothesis that chronic smoking leads to vascular dysfunction in the eye.

Regulation of retinal tissue oxygenation

Abstract Purpose To evaluate the changes in the retinal oxygen partial pressure (PO2) following physiological stimuli. Methods Evaluation of either the preretinal and intraretina partial pressure of oxygen (PO2) distribution, using oxygen sensitive microelectrodes, in various animal models. Measurements were obtained during changes of the perfusion pressure, systemic hyperoxia, hypoxia, hypercapnia, carbogen breathing and following carbonic anydrase inhibitors use. Results The oxygen tension (PO2) in the inner half of the retina remains largely unaffected by moderate changes in perfusion pressure. The increase of the systemic PaO2 through breathing of 100% O2 (hyperoxia) induces endothelin (ET) mediated marked vasoconstriction of the inner retinal arterioles in both anesthetized animals and normal human subjects. The regulatory vasoconstriction maintains the PO2 in retinal tissue constant. A decrease in PaO2 (hypoxia) induces a vasodilation of the retinal arterioles through endothelium‐derived NO release. As a result, trans‐retinal PO2 profiles made during steps of systemic hypoxia have shown that the values measured in the inner retina up to half of its thickness, remain rather stable. By contrast, the PO2 values, measured close to the choroid and in the outer retina, decrease in a linear manner with the decrease of the PaO2. An increase in the PaCO2 (hypercapnia) of arteriolar blood, produces an increase in retinal blood flow and retinal tissue PO2. Intravenous injection of acetazolamide (carbonic anhydrase inhibitor) produces an increase in preretinal PO2 due to dilation of the retinal vessels Conclusion Thanks to the autoregulatory capability of the retinal circulation, the oxygen tension (PO2) in the inner half of the retina, remains largely unaffected during physiological stimuli.

Acute Hyperglycemia-Induced Endothelial Dysfunction in Retinal Arterioles in Cats

To investigate the effects of acute hyperglycemia on retinal microcirculation and endothelial function in cats and removal of superoxide to prevent retinal endothelial dysfunction from hyperglycemia. Hyperglycemia was induced by intravenous injection of 25% glucose to maintain the plasma glucose concentration at 30 mM. Laser Doppler velocimetry was used to measure the vessel diameter (D) and blood velocity (V) simultaneously and calculated retinal blood flow (RBF) in second-order retinal arterioles in cats. Intravitreous, endothelial-dependent vasodilator bradykinin (BK) and endothelium-independent vasodilator sodium nitroprusside (SNP) were administered into the vitreous cavity to evaluate endothelial function in the retinal arterioles. To control osmolality, 25% mannitol was administered the same way. Systemic hyperoxia was induced to noninvasively examine endothelial function during hyperglycemia. To determine the effect of the superoxide on the hyperglycemia-induced changes in the retinal circulation, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) was administered in drinking water for 14 days before the experiment. The D, V, and RBF increased with acute hyperglycemia and mannitol compared with baseline. BK-induced increases in D, V, and RBF significantly declined, whereas SNP-induced increases were unattenuated during acute hyperglycemia. Return of the decreased RBF to baseline after cessation of systemic hyperoxia was significantly (P < 0.05) inhibited by acute hyperglycemia. TEMPOL significantly (P < 0.05) prevented a decrease in the BK-induced increase in RBF during hyperglycemia. The results suggest that acute hyperglycemia increases RBF via increased osmolality and may cause retinal endothelial dysfunction partially via increased oxidative stress. Systemic hyperoxia can be used to noninvasively evaluate retinal endothelial function during hyperglycemia.

A comparative study of the effects of brinzolamide and dorzolamide on retinal oxygen saturation and ocular microcirculation in patients with primary open-angle glaucoma

Aims:To assess the effects of brinzolamide and dorzolamide on ocular haemodynamics and retinal oxygen saturation in patients with primary open-angle glaucoma (OAG).Methods:Fifteen patients with OAG were evaluated in a randomised,...

Retinal Circulatory Changes Associated with Interferon-Induced Retinopathy in Patients with Hepatitis C

To evaluate the effect of interferon (IFN) therapy on retinal microcirculation. Thirty-six patients with chronic hepatitis C who were treated with high-dose IFN were included in this prospective study. The changes in vessel diameter and blood velocity were measured, and the retinal blood flow (RBF) and wall shear rate (WSR) were calculated in the retinal arteries before and 2, 4, 8, 16, and 24 weeks after IFN therapy by using laser Doppler velocimetry. Retinal blood velocity, RBF, and WSR significantly (P < 0.0001) increased in all patients, as early as 2 weeks after IFN therapy. The increase in RBF was independently correlated with a decrease in the red blood cell count. In 22 (61%) of the 36 patients asymptomatic retinopathy developed during treatment. In patients with retinopathy, the blood velocity and WSR increased, but the vessel diameter did not change, whereas the vessel diameter increased but the blood velocity and WSR did not change in patients without retinopathy 2 weeks after IFN therapy. Multiple logistic regression analysis showed that patient age and the change in WSR at week 2 were risk factors for the development of IFN-induced retinopathy. RBF increases in association with IFN therapy in patients with chronic hepatitis C. In addition, the increased WSR in patients with retinopathy indicates that retinal vascular endothelial dysfunction may be associated with IFN-induced retinopathy, because wall shear stress should be constant under physiologic conditions.

Influence of exercise induced hyperlactatemia on retinal blood flow during normo- and hyperglycemia

Purpose. Short term hyperglycemia has previously been shown to induce a blood flow increase in the retina. The mechanism behind this effect is poorly understood. We set out to investigate whether exercise-induced hyperlactatemia may alter the response of retinal blood flow to hyperglycemia. Methods. We performed a randomized, controlled two-way cross over study comprising 12 healthy subjects, performed a 6-minutes period of dynamic exercise during an euglcaemic or hyperglycaemic insulin clamp. Retinal blood flow was assessed by combined vessel size measurement with the Zeiss retinal vessel analyzer and measurement of red blood cell velocities using bi-directional laser Doppler velocimetry. Retinal and systemic hemodynamic parameters were measured before, immediately after and 10 and 20 minutes after isometric exercise. Results. On the euglycemic study day retinal blood flow increased after dynamic exercise. The maximum increase in retinal blood flow was observed 10 minutes after the end of exercise when lactate plasma concentration peaked. Hyperglycemia increased retinal blood flow under basal conditions, but had no incremental effect during exercise induced hyperlactatemia. Conclusions. Our results indicate that both lactate and glucose induce an increase in retinal blood flow in healthy humans. This may indicate a common pathway between glucose and lactate induced blood flow changes in the human retina.

Role of nitric oxide in regulation of retinal blood flow during hypercapnia in cats.

To investigate whether nitric oxide (NO) contributes to the regulation of retinal circulation during hypercapnia in cats. NG-nitro-L-arginine-methylester (L-NAME; n=8), a NOS inhibitor; NG-nitro-D-arginine-methylester (D-NAME; n=6), the inactive isomer; or phosphate-buffered saline (PBS; n=8) was injected intravitreously into the cat's eye. A selective neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7-NI; n=6), was injected intraperitoneally. Hypercapnia was induced for 10 minutes by inhalation of 5% carbon dioxide with 21% oxygen and 74% nitrogen. The vessel diameter and blood velocity were measured simultaneously in large retinal arterioles in cats by laser Doppler velocimetry and the retinal blood flow (RBF) calculated. Retinal vascular resistance (RVR) was also estimated. In the PBS group, the vessel diameter (9.5% +/- 2.7%, P<0.05), blood velocity (15.6% +/- 4.4%, P<0.05), and RBF (37.2% +/- 3.7%, P<0.05) increased, and the RVR decreased (-26.0% +/- 2.7%, P<0.05) during hypercapnia. In the L-NAME group, those changes were greatly suppressed in response to hypercapnia. D-NAME was inactive with regard to RBF during hypercapnia. The RBF responses to hypercapnia after the 7-NI injection were significantly attenuated compared with those before 7-NI injection (P<0.05). These results indicate that NO contributes to the increase in RBF during hypercapnia. Furthermore, the NO synthesized by the action of nNOS may participate in regulation of RBF during hypercapnia.

Short-term effect of ß-adrenoreceptor blocking agents on ocular blood flow

Purpose. In this study the acute effect of the topically-delivered non-selective ß-blockers timolol and carteolol, and the selective ß-blocker betaxolol, were evaluated with respect to ocular blood flow, intraocular pressure (IOP) and vessel resistance in rabbits’ eyes. Methods. In a double masked randomized design, one eye of each subject (n = 9) received two drops of 0.5 % timolol or 2 % cartelol or 0.5 % betaxolol ophthalmic solution and a separate group of nine rabbits received two drops of placebo consisting of physiological saline in both eyes to serve as control. Using hydrogen clearance method, ciliary body blood flow (CiBF), choroidal blood flow (CBF), and retinal blood flow (RBF) were measured. IOP and systemic mean arterial pressure (MAP) of each subject were measured under same condition before and after the administration of respective drugs to calculate the ocular perfusion pressure (OPP) and vessel resistance. Results. In timolol- and carteolol-treated eyes significant reduction was observed in IOP (p < 0.01), CiBF (p < 0.01), CBF (p < 0.01) and RBF (p < 0.01) compared to control eyes. However, in betaxolol-treated eyes a marginal reduction in IOP was observed accompanied by significant increase in CiBF (p < 0.01) and RBF (p < 0.05). The non-selective ß-blocker-treated eyes tended to have increased vessel resistance, whereas, selective ß-blocker-treated eyes tended to have decreased vessel resistance. Conclusions. Our current results comparing non-selective and selective ß-blockers suggest that the selective ß-blocker betaxolol may be more appropriate for maintenance of retinal blood flow in situations with low perfusion. Currently the mechanism for regulation of IOP is unclear; however, the findings from this study indicate that decreased CiBF may contribute to reduction in IOP.

High-altitude retinopathy and retinal vascular dysregulation.

(a) To show that high-altitude retinopathy (HAR) is common at high altitudes even in well-acclimatised climbers and that it should not be regarded as part of the spectrum of benign mountain sickness but rather as a clinical sign with a separate aetiology. (b) To test the hypothesis that HAR could be interpreted as a clinical expression of 'ocular vascular dysregulation'. Both eyes of the 8 mountaineers of the First Vienna Himalayan Expedition in May/June 1996 were examined 2 weeks before departure to and 2 weeks after descent from a high altitude. Retinal blood flow was measured in the right eyes of 7 climbers, using the Heidelberg Retina Flowmeter (HRF). Two of the 8 climbers had bilateral retinal haemorrhage after the expedition. In 5 climbers chronic hypoxic exposure caused an increase in retinal blood flow between +18% and +96%, and in 2 climbers a decrease in retinal blood flow between -21% and -31%. The 2 climbers (climbers 1 and 2) with bilateral retinal haemorrhage showed a significant increase in HRF parameters. HAR may be a clinical sign of mountaineers with a tendency towards ocular vascular dysregulation. The pronounced increase in all haemodynamic parameters in the 2 climbers with retinal haemorrhage combined with a dilated epipapillary network 2 weeks after the exposure reflects a retinal vessel configuration, as might be expected at high altitudes under acute hypoxic stress. An inadequate autoregulatory response of the retinal circulation under conditions of chronic hypoxia may play an important part in the pathogenesis of HAR.

Retinal expression, regulation, and functional bioactivity of prostacyclin-stimulating factor.

Prostacyclin-stimulating factor (PSF) acts on vascular endothelial cells to stimulate the synthesis of the vasodilatory molecule prostacyclin (PGI2). We have examined the expression, regulation, and hemodynamic bioactivity of PSF both in whole retina and in cultured cells derived from this tissue. PSF was expressed in all retinal cell types examined in vitro, but immunohistochemical analysis revealed PSF mainly associated with retinal vessels. PSF expression was constitutive in retinal pericytes (RPCs) but could be modulated in bovine retinal capillary endothelial cells (RECs) by cell confluency, hypoxia, serum starvation, high glucose concentrations, or inversely by soluble factors present in early vs. late retinopathy, such as TGF-beta, VEGF, or bFGF. In addition, RPC-conditioned media dramatically increased REC PGI2 production, a response inhibited by blocking PSF with a specific antisense oligodeoxynucleotide (ODN). In vivo, PGI2 increased retinal blood flow (RBF) in control and diabetic animals. Furthermore, the early drop in RBF during the initial weeks after inducing diabetes in rats, as well as the later increase in RBF, both correlated with levels of retinal PSF. RBF also responded to treatment with RPC-conditioned media, and this effect could be partially blocked using the antisense PSF ODN. We conclude that PSF expressed by ocular cells can induce PGI2, retinal vascular dilation, and increased retinal blood flow, and that alterations in retinal PSF expression may explain the biphasic changes in RBF observed in diabetes.

Effect of angiotensin-converting enzyme inhibition with perindopril and β-blockade with atenolol on retinal blood flow in hypertensive diabetic subjects

The effect of angiotensin-converting enzyme (ACE) inhibitors on the diabetic retinal circulation has not been studied previously. The aim of this study was to evaluate the effect of ACE inhibition and beta-blockade on retinal blood flow (RBF) in a group of 45 hypertensive diabetic subjects using a randomized double-blind trial over a period of 12 months. Laser Doppler velocimetry and computed image analysis were used to measure RBF. The changes in blood pressure over 12 months were comparable (perindopril [PE]: systolic [SBP] 152.1 ± 3.3 and diastolic [DBP] 97.2 ± 1.7 mm Hg to SBP 136.8 ± 3.4 and DBP 85.8 ± 2.1; atenolol: SBP 158.9 ± 5.1 and DBP 97.5 ± 1.6 mm Hg to SBP 137.9 ± 3.4 and DBP 85.1 ± 1.6; P = .607, mean ± SEM). RBF decreased from 17.19 ± 2.21 μL · min −1 to 14.18 ± 1.50 μL · min −1 in the PE group (n = 15, P = .208) while it increased with atenolol from 15.80 ± 1.24 μL · min −1 to 16.99 ± 1.18 μL · min −1 (n = 17, P = .399). The comparison of percentage changes in RBF (PE −7.16% ± 11.49%; atenolol, +15.31% ± 9.51%) reached statistical significance ( P < .05). There was an increase in RBF in 33.3% of subjects receiving PE and in 70.6% of those receiving atenolol. Similar trends were found for retinal conductance. There were no significant changes in the parameters of retinal vascular permeability. Albuminuria decreased to a greater degree with PE, but did not reach significance (PE, 112.1 ± 39.5 mg/24 h to 88.6 ± 30.5 mg/24 h; atenolol, 87.3 ± 51.7 mg/24 h to 82.1 ± 47.7 mg/24 h). This suggests that ACE inhibition therapy may promote a hemodynamic milieu in the hypertensive diabetic retinal circulation that serves to protect against the progression of diabetic retinopathy, whereas beta-blockade has the opposite effect.

Vascular Endothelial Growth Factor and Severity of Nonproliferative Diabetic Retinopathy Mediate Retinal Hemodynamics In Vivo: A Potential Role for Vascular Endothelial Growth Factor in the Progression of Nonproliferative Diabetic Retinopathy

To determine the effect of vascular endothelial growth factor and retinopathy level on retinal hemodynamics in nondiabetic and diabetic rats and to evaluate retinal hemodynamics in nondiabetic and diabetic patients. Forty-eight diabetic and 22 nondiabetic patients had their diabetic retinopathy levels determined from fundus photographs according to Early Treatment Diabetic Retinopathy Study (ETDRS). Fluorescein angiograms were recorded from the left eye by video fluorescein angiography. Retinal blood flow was calculated from the digitized angiograms. Human recombinant vascular endothelial growth factor or vehicle alone was injected intravitreally into 13 nondiabetic and 11 diabetic rats. Retinal blood flow decreased 33% in patients with ETDRS retinopathy level 10 compared with control patients (P = .001) and increased sequentially in more advanced stages of retinopathy, with a strong correlation between retinal blood flow and retinopathy level (r2 = 0.434, P = .001). In the diabetic rats, retinal blood flow was decreased 35.6% (P = .01). Vascular endothelial growth factor maximally increased retinal blood flow by 36.1% in nondiabetic rats after 25 minutes (P = .001) and by 73.7% in diabetic rats after only 5 minutes (P = .01) and caused a greater response in diabetic than in nondiabetic rats. Retinal blood flow increases with advancing nonproliferative diabetic retinopathy in humans, and diabetes accentuates the vascular endothelial growth factor-induced increase in retinal blood flow and venous dilation in rats. Vascular endothelial growth factor may contribute to the changes in retinal hemodynamics and morphology observed in early diabetic retinopathy.