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Ozone-induced retinal vascular reactivity as assessed by optical coherence tomography angiography

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Abstract

Background: This study aimed to investigate the retinal vascular reactivity (RVR) of the macular and peripapillary capillary network in response to ozonated autohemotherapy (AHT) using optical coherence tomography angiography (OCTA). Methods: This was a single-centre prospective study. All participants that were planned to have a combination of major and minor ozone AHT underwent a complete ocular examination and OCTA imaging before and after the ozone AHT. Foveal avascular zone (FAZ) metrics and vessel density (VD) of superficial (SCP), deep capillary plexus (DCP), and radial peripapillary capillary (RPC) plexus were assessed using the built-in software. Results: A total of 40 right eyes of 40 individuals were included. No significant differences were observed for the mean values of the FAZ metrics and choriocapillaris flow area following ozone AHT compared with baseline values (p > 0.05). The mean whole VD of SCP and DCP was 47.80 ± 2.18% and 53.09 ± 3.00% before treatment, which decreased to 47.68 ± 2.7% and 52.38 ± 3.07% after treatment (p = 0.660 and p = 0.097, respectively). No significant differences were observed in the vascular densities of both SCP and DCP in any quadrant (p > 0.05). The RPC density did not show significant alterations compared with baseline values, except the inferior-hemi region. The VD in the inferior-hemi peripapillary quadrant was significantly increased after ozone AHT (p = 0.034). Conclusion: The ozone AHT did not cause evident RVR in the macular area, whereas the peripapillary area showed a partial response.

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Alterations in ocular blood flow have been implicated in mechanisms that lead to vision loss in patients with various ocular disorders such as diabetic retinopathy, glaucoma, and age-related macular degeneration. Assessment of retinal and choroidal blood flow is also a window to evaluate systemic diseases that affect microvasculature. Quantification and qualification of the blood flow in the retina and choroid help us understand pathophysiology, stratify disease risk, and monitor disease progression in these disorders. Multiple methods are employed by researchers for assessment of blood flow, but a gold standard is lacking. We review commonly used methods, both invasive and non-invasive, for evaluation of blood flow including intravital microscopy, laser Doppler velocimetry, laser Doppler flowmetry, laser interferometry, confocal scanning laser Doppler flowmetry, laser speckle flowgraphy, Doppler optical coherence tomography, blue-field entoptic simulation, retinal vessel calibre assessment, optical coherence tomography angiography, retinal function imaging, color Doppler imaging, and scanning laser ophthalmoscope angiogram. As technology evolves, better evaluation of blood flow in various ocular and systemic diseases will likely bring new perspectives into clinical practice and translate to better diagnosis and treatment.
Article
Purpose: To identify and quantify the three distinct retinal capillary plexuses and the foveal avascular zone (FAZ) in healthy subjects according to age using optical coherence tomography angiography (OCTA) with novel projection artifact removal (PAR) software and improved segmentation. Methods: All eyes in this cross-sectional study underwent OCTA imaging using RTVue XR Avanti with novel PAR AngioVue software. OCTA scans were analyzed and the three main parafoveal retinal capillary plexuses were segmented and vessel density and FAZ area were calculated. Results: A total of 152 normal eyes from 95 subjects (39 males, 56 females, mean age 42 ± 25 years) were included. The mean vessel density was 15.48 ± 2.04 mm-1 in the superficial retinal capillary plexus (SCP), 15.28 ± 1.82 mm-1 in the intermediate retinal capillary plexus (ICP), and 16.33 ± 2.32 mm-1 in the deep retinal capillary plexus (DCP) for 3 × 3-mm OCTA images. Analysis of 3 × 3-mm scans yielded a mean FAZ area of 0.270 ± 0.101 mm2. The average reduction in vessel density per year of age with 3 × 3-mm OCTA scans was 0.04 mm-1 (0.22%) in the SCP, 0.05 mm-1 (0.27%) in the ICP, and 0.06 mm-1 (0.30%) in the DCP. The average increase in FAZ area per year of age was 0.0015 mm2 (0.72%). Conclusions: Novel PAR software may provide improved visualization of all three major parafoveal retinal capillary plexuses including the ICP. Using this technology, SCP, ICP, and DCP vessel density decreased with increasing age while FAZ area increased with age.
Article
Purpose: To investigate the impact of different gas mixtures (hyperoxia, hypoxia, and hypercapnia) on the optic nerve head (ONH) and choroidal (Ch) hemodynamics. Methods: Twenty-three healthy subjects (28 ± 6 years) took part in the study. Variations in inspired oxygen and carbon dioxide fraction were produced by a gas mixing device. Arterial oxygen saturation (SpO2) was measured continuously using a transcutaneous sensor and end-tidal carbon dioxide partial pressure by capnography. The experiment comprised three successive periods: 3-minute baseline (room air breathing), 15-minute gas mixture inhalation (normocapnic hypoxia, hypercapnia, or hyperoxia), and 15-minute recovery (room air breathing). Laser Doppler flowmeter parameters-velocity (VEL), volume (VOL), and flow (BF) of red blood cells-were measured. Two-way ANOVAs were performed for statistical analysis. Results: In response to hyperoxia, ONHBF significantly decreased by -18% ± 6% (P = 0.04) from baseline, due to significant changes in VEL (-12% ± 3% P = 0.0002). During hypoxia at 85% SpO2, ONH VEL increased by +12% ± 3% (P = 0.0009), whereas VOL and BF did not change significantly. ChBF significantly increased by +7% ± 2% (P = 0.004) in response to hypoxia, due to significant changes in VEL +5% ± 2% (P = 0.03). Both Ch and ONHBFs did not vary significantly in response to hypercapnia. Conclusions: The magnitude of the blood flow response is the most significant during hyperoxia for ONH and hypoxia for ChBF. For ONHBF, a 37% difference between hyperoxia and hypoxia can be useful when vasoreactivity to O2 will be tested in patients.
Article
Purpose: To determine the intravisit and intervisit reproducibility of optical coherence tomography angiography measurements of macular vessel density in eyes with and without retinal diseases. Methods: Fifteen healthy volunteers and 22 patients with retinal diseases underwent repeated optical coherence tomography angiography (Angiovue Imaging System, Optovue Inc) scans after pupil dilation on 2 separate visit days. For each visit day, the eyes were scanned twice. Vessel density defined as the proportion of vessel area with flowing blood over the total measurement area was calculated using Angiovue software. Intravisit and intervisit reproducibility were summarized as coefficient of variations and intraclass correlation coefficients were calculated from variance component models. Results: The coefficient of variations representing the intravisit reproducibility of the superficial macular vessel density measurements for different quadrants on 3 mm × 3-mm scans varied from 2.1% to 4.9% and 3.4% to 6.8% for healthy and diseased eyes, respectively, and for the intervisit it was 2.9% to 5.1% and 4.0% to 6.8%, respectively. The coefficient of variations were lower in healthy eyes than in diseased eyes, lower for intravisit than for intervisit, lower on 3 mm × 3-mm scans than on 6 mm × 6-mm scans, and lower for paracentral subfields than for central subfield. Conclusion: The evidence presented here demonstrates good reproducibility of optical coherence tomography angiography for measurement of superficial macula vessel density in both healthy eyes and eyes with diabetic retinopathy without diabetic macular edema.
Article
Diabetes is a common cause of small vessel disease leading to stroke and vascular dementia. While the function and structure of large cerebral vessels can be easily studied, the brain's microvasculature remains difficult to assess. Previous studies have demonstrated that structural changes in the retinal vessel architecture predict stroke risk, but these changes occur at late disease stages. Our goal was to examine whether retinal vascular status can predict cerebral small vessel dysfunction during early stages of diabetes. Retinal vasoreactivity and cerebral vascular function were measured in 78 subjects (19 healthy controls, 22 subjects with prediabetes, and 37 with type-2 diabetes) using a new noninvasive retinal imaging device (Dynamic Vessel Analyzer) and transcranial Doppler studies, respectively. Cerebral blood vessel responsiveness worsened with disease progression of diabetes. Similarly, retinal vascular reactivity was significantly attenuated in subjects with prediabetes and diabetes compared to healthy controls. Subjects with prediabetes and diabetes with impaired cerebral vasoreactivity showed mainly attenuation of the retinal venous flicker response. This is the first study to explore the relationship between retinal and cerebral vascular function in diabetes. Impairment of venous retinal responsiveness may be one of the earliest markers of vascular dysfunction in diabetes possibly indicating subsequent risk of stroke and vascular dementia.
Article
Background: There is still a lack of effective treatments for acute ischemic stroke. Our pre-clinical studies suggest that ozone therapy administered by autologous blood transfusion is a convenient and safe treatment for ischemic stroke, and is popular with patients, but its therapeutic benefits are not clear. We hypothesized that ozone therapy administered by autologous blood transfusion for ischemic stroke is safe and effective, and propose a protocol for a prospective, multi-center, open-label, large-sample, parallel, randomized, non-blinded controlled trial. Methods/Design: This will be a multi-center, open-label, large-sample, parallel, randomized controlled trial. We intend to recruit 5,000 patients with acute ischemic stroke in 30 centers (including General Hospital of Shenyang Military Region, China). Patients will be randomly allocated to a control group (n = 2,500; conventional stroke therapy) or an ozone therapy group (n = 2,500; ozone therapy administered in addition to conventional therapy). The primary outcome will be a modified Rankin Scale score 0-2 at 90 days. Secondary outcomes will be National Institute of Health Stroke Scale score at 14 days, blood lipid and glucose concentrations and coagulation function at 14 days, and the incidence of post-stroke pneumonia, recurrent stroke and other vascular events in the first 90 days after stroke. Discussion: We hope that our results will illuminate the therapeutic benefits of ozone therapy administered by autologous blood transfusion for acute ischemic stroke. Trial registration: This trial was registered at Chinese Clinical Trial Registry (registration No. ChiCTR-ICR-15007093) on 18 September 2015.
Article
PURPOSE. Previous studies in humans have demonstrated that oxygen (O-2) reduces retinal vessel caliber and blood flow, whereas carbon dioxide (CO2) usually has opposite effects. The influence of O-2 and CO2 on choroidal circulation is not fully understood, however. This study was conducted to determine the effects of systemic hyperoxia and hypercapnia on global choroidal hemodynamics, as evaluated by pulsatile ocular blood flow (POBF) tonography. METHODS. In this experiment, 16 atnd 22 healthy volunteers breathed 100% O-2 and carbogen, respectively. POBF and intraocular pressure (IOP) were measured twice with a UK OBF tonograph for each of the following conditions: in ambient room air breathing, after breathing pure O-2 or carbogen through a face mask, and in ambient room air 10 minutes after mask removal, Heart rate (HR), hemoglobin oxygen saturation level (SaO(2)), and systemic arterial blood pressure (BP) were monitored throughout testing. The end-tidal CO2 (EtCO2) level and respiratory rate (RR) were also recorded during carbogen breathing. RESULTS. Results revealed that IIR was reduced (P < 0.004) and SaO(2) was increased (P = 0.0001) by both oxygen and carbogen breathing. Systemic arterial BP remained stable throughout the experiment. EtCO2 was increased during carbogen breathing (P = 0.0001), whereas RR was reduced (P = 0.0175). IOP was significantly decreased during both phases of the experiment (P = 0.0001). Finally, POBF was not altered by pure O-2 breathing, but it increased on average by 7.7% during carbogen breathing (P = 0.0222). CONCLUSIONS. The data obtained with POBF tonography indicate that the choroid reacts to increased blood CO2 concentration, bur not to systemic hyperoxia in a manner similar to that in retinal and brain vessels.
Article
Purpose: To evaluate the ability of optical coherence tomography angiography to detect early microvascular changes in eyes of diabetic individuals without clinical retinopathy. Methods: Prospective observational study of 61 eyes of 39 patients with diabetes mellitus and 28 control eyes of 22 age-matched healthy subjects that received imaging using optical coherence tomography angiography between August 2014 and March 2015. Eyes with concomitant retinal, optic nerve, and vitreoretinal interface diseases and/or poor-quality images were excluded. Foveal avascular zone size and irregularity, vessel beading and tortuosity, capillary nonperfusion, and microaneurysm were evaluated. Results: Foveal avascular zone size measured 0.348 mm (0.1085-0.671) in diabetic eyes and 0.288 mm (0.07-0.434) in control eyes (P = 0.04). Foveal avascular zone remodeling was seen more often in diabetic than control eyes (36% and 11%, respectively; P = 0.01). Capillary nonperfusion was noted in 21% of diabetic eyes and 4% of control eyes (P = 0.03). Microaneurysms and venous beading were noted in less than 10% of both diabetic and control eyes. Both diabetic and healthy control eyes demonstrated tortuous vessels in 21% and 25% of eyes, respectively. Conclusion: Optical coherence tomography angiography was able to image foveal microvascular changes that were not detected by clinical examination in diabetic eyes. Changes to the foveal avascular zone and capillary nonperfusion were more prevalent in diabetic eyes, whereas vessel tortuosity was observed with a similar frequency in normal and diabetic eyes. Optical coherence tomography angiography may be able to detect diabetic eyes at risk of developing retinopathy and to screen for diabetes quickly and noninvasively before the systemic diagnosis is made.
Article
It is now well established that hyperglycemia, present in both type 1 and type 2 diabetes, causes a variety of biochemical derangements leading to a diffused vascular damage responsible for several pathologic manifestations. Although preclinical and clinical studies have been performed by an unreliable administration route, the correct approach of oxygen-ozonetherapy may break a vicious circle. Messengers, released by a precise interaction ex vivo of the patient's blood with an equivalent calculated dose of ozone (0.42-0.84 mM), react with a variety of cells after blood infusion and restore a number of functions went astray. This paper aims to open a debate on this new therapy for improving the prognosis of diabetes.
Article
`Ozone (O 3 ) gas discovered in the mid-nineteenth century is a molecule consisting of three atoms of oxygen in a dynamically unstable structure due to the presence of mesomeric states. Although O 3 has dangerous effects, yet researchers believe it has many therapeutic effects. Ozone therapy has been utilized and heavily studied for more than a century. Its effects are proven, consistent, safe and with minimal and preventable side effects. Medical O 3 is used to disinfect and treat disease. Mechanism of actions is by inactivation of bacteria, viruses, fungi, yeast and protozoa, stimulation of oxygen metabolism, activation of the immune system. Medication forms in a gaseous state are somewhat unusual, and it is for this reason that special application techniques have had to be developed for the safe use of O 3 . In local applications as in the treatment of external wounds, its application in the form of a transcutaneous O 3 gas bath has established itself as being the most practical and useful method, for example at low (sub-atmospheric) pressure in a closed system guaranteeing no escape of O 3 into the surrounding air. Ozonized water, whose use is particularly known in dental medicine, is optimally applied as a spray or compress. Diseases treated are infected wounds, circulatory disorders, geriatric conditions, macular degeneration, viral diseases, rheumatism/arthritis, cancer, SARS and AIDS.
Article
The relative magnitude of vascular reactivity to inhaled gas stimuli in the major retinal arterioles has not been systematically investigated. The purpose of this study was to compare the magnitude of retinal vascular reactivity in response to inhaled gas provocation at equivalent measurement sites in the superior-, and inferior-, temporal retinal arterioles (STA, ITA). One randomly selected eye of each of 17 healthy volunteers (age 24.4 ± 4.7) was prospectively enrolled. Volunteers were connected to a sequential gas delivery circuit and a computer-controlled gas blender (RespirAct™, Thornhill Research Inc., Canada) and underwent an isocapnic hyperoxic challenge i.e. P(ET)O(2) of 500 mm Hg with P(ET)CO(2) maintained at 38 mm Hg during baseline and hyperoxia. Four retinal hemodynamic measurements were acquired using bi-directional laser Doppler velocimetry and simultaneous vessel densitometry (Canon Laser Blood Flowmeter, CLBF-100, Japan) at equivalent positions on the STA and ITA. Statistical analysis was performed using linear mixed-effect models. During the hyperoxic phase, the vessel diameter (STA p=0.004; ITA p=0.003), blood velocity (STA p<0.001; ITA p<0.001) and flow (STA p<0.001; ITA p<0.001) decreased in both the STA and the ITA relative to baseline. The diameter, velocity and flow were equivalent between STA and ITA at baseline and during hyperoxia; and their magnitude of change remained comparable with hyperoxia (p>0.05). The magnitude of retinal arteriolar vascular reactivity in response to isocapnic hyperoxic inhaled gas challenge was not significantly different between the STA and ITA. However, the correlation analysis did not reveal a significant relationship between the percentage changes in diameter, velocity and flow of the STA and ITA and did not demonstrate equal responses from the STA and ITA to gas provocation.
Article
Please cite this paper as: Venkataraman, Flanagan and Hudson (2010). Vascular Reactivity of Optic Nerve Head and Retinal Blood Vessels in Glaucoma—A Review. Microcirculation17(7), 568–581. Glaucoma is characterized by loss of retinal nerve fibers, structural changes to the optic nerve, and an associated change in visual function. The major risk factor for glaucoma is an increase in intraocular pressure (IOP). However, it has been demonstrated that a subset of glaucoma patients exhibit optic neuropathy despite a normal range of IOP. It has been proposed that primary open angle glaucoma could be associated with structural abnormalities and/or functional dysregulation of the vasculature supplying the optic nerve and surrounding retinal tissue. Under normal conditions, blood flow is autoregulated, i.e., maintained at a relatively constant level, in the retina and ONH, irrespective of variation in ocular perfusion pressure. A number of factors released by the vascular endothelium, including endothelin-1 and nitric oxide, are suggested to play an important role in the regulation of local perfusion in the retina and ONH. Most work to-date has investigated homeostatic hemodynamic parameters in glaucoma, rather than the measurement of the hemodynamic response to a provocation. Future work should comprehensively assess blood flow in all the ocular vascular beds and blood vessels supplying the eye in response to standardized stimuli in order to better understand the pathophysiology of glaucomatous optic neuropathy.
Article
To compare the magnitude of vascular reactivity in response to metabolic provocation in retinal arterioles of varying diameter in healthy young subjects. Ten healthy young subjects (26.2 +/- 3.5 years [mean +/- SD]) attended for three sessions. Session 1 was used to select two discrete hemodynamic measurement sites along the superior temporal arteriole. Retinal arteriolar blood flow was assessed at relatively narrow and wide sites. At sessions 2 and 3, CO(2) and O(2) were sequentially administered (and alternated across sessions) using manual gas flow control via a modified sequential rebreathing circuit to achieve target hypercapnia and hyperoxia. Blood flow was assessed for each gas phase. Total vascular reactivity capacity (TVRC) was taken as the difference in flow between hypercapnia and hyperoxia. The baseline diameter for the narrow and wide measurement sites was 92.4 microm (+/-13.6) and 116.7 microm (+/-12.7), respectively (ReANOVA; P < 0.0001). Hyperoxia induced a decrease in blood flow, whereas hypercapnia increased flow (P < 0.0001). TVRC was greater for the wide than for the narrow measurement sites (Delta flow narrow = 3.0 microL/min versus Delta flow wide = 6.6 microL/min; P < 0.0001). In terms of percentage change in flow relative to baseline, TVRC was the same between the wide and narrow sites (Delta narrow = 67% versus Delta wide = 61%; P > 0.05). In response to metabolic provocation, absolute TVRC was greater for retinal arteriolar measurement sites with wider baseline vessel diameters. However, percentage change in retinal blood flow was the same irrespective of initial arteriolar diameter.
Article
In this study we have investigated the effects of ozone on human blood, as well as on resuspended buffy coats and Ficoll-purified mononuclear cells. Samples were exposed at different ozone concentrations (from 2.2 micrograms to 108 micrograms/ml) for 30 sec and then incubated for different times at 37 degrees C in a 95% air-5% CO2 humidified atmosphere. Supernatants were collected and frozen at-20 degrees C until tested for interferon (IFN) activity. We have determined that the ozone concentration is critical for lymphokine induction. In fact, while low concentrations (2.2 micrograms/ml) are effective in lymphocytes, they do not induce IFN in either whole or diluted (1:1) human blood, or resuspended buffy coats. In such cases levels as high as 42 micrograms/ml are required. On the other hand, a very high ozone concentration (108 micrograms/ml) is not effective and probably toxic. Maximal IFN production occurs 72-96 h after ozone exposure, and the kinetics of IFN release is similar to that after Staphylococcal Enterotoxin B addition. Because ozonization of blood is a medical procedure followed in several countries for treatment of viral diseases, this study can open a new field of investigation that may yield useful results both in biological and practical terms.
Article
The retinal blood vessels serve for nutrition of the retinal ganglion cells and their axons. This study was undertaken to evaluate the vessel diameter in normal and glaucoma eyes. The calibers of the superior temporal and inferior temporal retinal artery and vein were measured at the optic disc border and at a distance of 2 mm from the optic disc center; 473 eyes of 281 patients suffering from chronic primary open-angle glaucoma and 275 eyes of 173 normal subjects were examined. Fifteen-degree, color stereo optic disc photographs were used. In the normal eyes the inferior temporal vessels were significantly larger than the superior temporal vessels. This corresponds with: (1) the configuration of the normal neuroretinal rim, which is significantly broader in the inferior disc region than in the superior disc area; (2) the visibility of the retinal nerve fibers, which are better detectable in the inferior temporal area than in the superior temporal one; and (3) the foveola location 0.53 +/- 0.34 mm inferior to the optic disc center. The retinal vessel diameter was independent of the patients' age and optic disc and parapapillary chorioretinal atrophy size. In the glaucoma group the vessel caliber was significantly smaller than in the normal eyes. The differences were more marked for the arteries and the inferior temporal vessels, respectively. The vessel diameters decreased significantly with increasing glaucoma stage independently of the patients' age. The parapapillary retinal vessel diameter may reflect the need of vascular supply in the corresponding superficial retinal area. It may be correlated with the local ganglion cell density and retinal nerve fiber layer thickness.
Article
Autoregulation of blood flow in response to changes in perfusion pressure is known to occur in a number of tissues including the human retina. Defective autoregulation may play a part in the pathophysiology of several retinal diseases. Laser Doppler velocimetry has been used to study retinal blood flow. Technically superior measurements are obtained from veins by this method but arterial measurements might provide additional information. The response of the normal human retina to an acute elevation of systemic blood pressure induced by isometric exercise was investigated in nine normal volunteers using laser Doppler velocimetry and computer-assisted image analysis. Measurements were taken from retinal veins and arteries. Autoregulation was demonstrated by an 8.4% rise in flow in response to a 34% rise in perfusion pressure (P = 0.0007) using data derived from veins and a 4.8% rise in flow in response to a 33% rise in perfusion pressure (P = 0.01) using data derived from arteries. Arteries constricted by 3.4% (P = 0.002) and veins dilated by 1.6% (P = 0.02). Red cell velocity rose in veins by 5.0% (P = 0.008) and in arteries by 12.2% (P = 0.02). The variability in velocity change derived from veins (SD 3.4%) was lower than that from arteries (SD 12.1%). A similar pattern of flow change was found in both sets of data. This makes venous measurements more useful for obtaining statistically reliable results from these techniques.
Article
Although glaucomatous visual field defects are more common in the superior field than in the inferior field, microaneurysms are more frequent in the superior than in the inferior retina in diabetic retinopathy. The authors hypothesized that differences in vascular hemodynamics in the two areas might contribute to these phenomena. The blood flow response to hyperoxia and hypercapnia was evaluated in peripapillary retinal tissue superior and inferior to the optic nerve head using confocal scanning laser Doppler flowmetry. In 14 young, healthy persons, blood flow was measured while breathing room air and during isocapnic hyperoxia (100% O2 breathing) and isoxic hypercapnia (PCO2 increased 15% above baseline). Histograms were generated from pixel-by-pixel analysis of retinal portions of superior and inferior temporal quadrants of the entire image. Baseline blood flow in the inferior temporal quadrant was significantly greater than in the superior temporal quadrant (P < 0.05). However, the inferior region failed to increase in perfusion during hypercapnia and experienced significant mean blood flow reduction; flow reduction in the pixels at the 25th, 50th, 75th, and 90th percentile of flow; and an increased percentage of pixels without measurable flow, during hyperoxia (each P < 0.05). In contrast, in the superior temporal region, hyperoxia failed to reduce blood volume, velocity, or flow, whereas hypercapnia significantly increased mean flow; increased flow in the pixels at the 25th, 50th, 75th, and 90th percentile of flow; and reduced the percentage of pixels without measurable flow (each P < 0.05). The inferior temporal quadrant of the peripapillary retina is, in comparison with the superior temporas region, less responsive to vasodilation and more responsive to vasoconstriction. These differences could contribute to different susceptibility to visual field defect or vascular dysfunction in the superior and inferior retina.
Article
Several studies have investigated the changes in retinal vessel diameter during physiological stress or pathologic conditions. These studies were principally based on individual fundus photographs and as such did not allow the evaluation of vessel dynamics over time. The research objective was to detail the time course and amplitude changes in the diameter of arteries and veins across all retinal quadrants, during and after hyperoxic vascular stress. The dynamics of changes in retinal vessel diameter were quantified with a retinal vessel analyzer, which digitizes fundus images in real time and simultaneously quantifies vessel diameter. The arterial and venous diameters within one disc diameter of the optic nerve head in each quadrant were studied. Twenty young adults participated in this study in which the vessel diameters were measured during successive phases of breathing either room air or pure oxygen. The oxygen saturation level (SaO(2)), end-tidal carbon dioxide (EtCO(2)), pulse rate (PR), respiratory rate (RR), and blood pressure (BP) were also monitored throughout testing. Breathing 100% O(2) caused an increase in SaO(2) and a decrease in the EtCO(2). All other systemic parameters measured (PR, RR, BP, and ocular perfusion pressure [OPP]) remained unchanged. However, the retinal veins and arteries constricted by approximately 14% and approximately 9% respectively, in all retinal quadrants. After experimental hyperoxia, inhalation of room air was associated with a progressive increase in the caliber of vessels toward their pretest size. The amplitude and overall profile of vessel reactivity to and recovery from hyperoxia was the same across retinal quadrants. These data indicate that, during systemic hyperoxic stress, the retinal vessels change in caliber uniformly across retinal quadrants in healthy young adults. This type of physiological vascular provocation could be used to investigate the quality of vascular regulation during aging and in vascular diseases of the eye.
Article
The aim of this review is to dispel misconceptions and skepticism regarding ozone therapy and to clarify the biochemical and pharmacological mechanisms of action of ozone dissolved in biological fluids. The work performed in the last decade in our laboratory allows drawing a comprehensive framework for understanding and recommending ozone therapy in some diseases. It is hoped that this report will open a dialogue among clinical scientists and will inform physicians about the beneficial effects of ozone therapy.
Article
Study of retinal autoregulation is important because vascular dysfunction is a precursor of many retinal diseases. Previous research has focused on venular blood flow because the minimal venular pulsatility was thought to provide more reproducible results. This study compared the variability of arteriolar and venular blood flow measurements in response to isocapnic hyperoxia, a provocation known to constrict blood vessels and reduce blood velocity. Data was collected using a non-invasive laser Doppler instrument that permitted the simultaneous measurement of retinal blood velocity and vessel diameter, allowing the derivation of blood flow. Measurements were collected from 20 young subjects before, during and after exposure to hyperoxia. Isocapnia was maintained throughout hyperoxia using a previously validated sequential re-breathing circuit. Arteriolar and venular diameters decreased during hyperoxia by 8.7% (p=0.0001) and 14.2% (p=0.0001), respectively. Hyperoxia caused significant decreases in arteriolar and venular blood velocity (31.2%, p=0.0001 and 18.0%, p=0.0001, respectively) and flow (43.2%, p=0.0001 and 40.0%, p=0.0002, respectively). The coefficients of variation for intra-individual measurements of diameter, velocity and flow were comparable in magnitude between the two vessel types. Measures of arteriolar pulsatility, such as Pulsatility ratio, Resistivity ratio and Pulsatility index, increased significantly during hyperoxia, indicating increased downstream vascular resistance. We conclude that retinal arterioles and venules provide equally reproducible results for autoregulation studies and that arteriolar pulsatility profiles provide additional useful information regarding vascular resistance.
Article
Optimal retinal neuronal cell function requires an appropriate, tightly regulated environment, provided by cellular barriers, which separate functional compartments, maintain their homeostasis, and control metabolic substrate transport. Correctly regulated hemodynamics and delivery of oxygen and metabolic substrates, as well as intact blood-retinal barriers are necessary requirements for the maintenance of retinal structure and function. Retinal blood flow is autoregulated by the interaction of myogenic and metabolic mechanisms through the release of vasoactive substances by the vascular endothelium and retinal tissue surrounding the arteriolar wall. Autoregulation is achieved by adaptation of the vascular tone of the resistance vessels (arterioles, capillaries) to changes in the perfusion pressure or metabolic needs of the tissue. This adaptation occurs through the interaction of multiple mechanisms affecting the arteriolar smooth muscle cells and capillary pericytes. Mechanical stretch and increases in arteriolar transmural pressure induce the endothelial cells to release contracting factors affecting the tone of arteriolar smooth muscle cells and pericytes. Close interaction between nitric oxide (NO), lactate, arachidonic acid metabolites, released by the neuronal and glial cells during neural activity and energy-generating reactions of the retina strive to optimize blood flow according to the metabolic needs of the tissue. NO, which plays a central role in neurovascular coupling, may exert its effect, by modulating glial cell function involved in such vasomotor responses. During the evolution of ischemic microangiopathies, impairment of structure and function of the retinal neural tissue and endothelium affect the interaction of these metabolic pathways, leading to a disturbed blood flow regulation. The resulting ischemia, tissue hypoxia and alterations in the blood barrier trigger the formation of macular edema and neovascularization. Hypoxia-related VEGF expression correlates with the formation of neovessels. The relief from hypoxia results in arteriolar constriction, decreases the hydrostatic pressure in the capillaries and venules, and relieves endothelial stretching. The reestablished oxygenation of the inner retina downregulates VEGF expression and thus inhibits neovascularization and macular edema. Correct control of the multiple pathways, such as retinal blood flow, tissue oxygenation and metabolic substrate support, aiming at restoring retinal cell metabolic interactions, may be effective in preventing damage occurring during the evolution of ischemic microangiopathies.