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1.  Anterior and Posterior Optic Nerve Head Blood Flow in Nonhuman Primate Experimental Glaucoma Model Measured by Laser Speckle Imaging Technique and Microsphere Method 
To characterize optic nerve head (ONH) blood flow (BF) changes in nonhuman primate experimental glaucoma (EG) using laser speckle flowgraphy (LSFG) and the microsphere method and to evaluate the correlation between the two methods.
EG was induced in one eye each of 9 rhesus macaques by laser treatment to the trabecular meshwork. Prior to lasering and following onset of intraocular pressure (IOP) elevation, retinal never fiber layer thickness (RNFLT) and ONH BF were measured biweekly by spectral-domain optical coherence tomography and LSFG, respectively, until RNFLT loss was approximately 40% in the EG eye. Final BF was measured by LSFG and by the microsphere method in the anterior ONH (MS-BFANT), posterior ONH (MS-BFPOST), and peripapillary retina (MS-BFPP).
Baseline RNFLT and LSFG-BF showed no difference between the two eyes (P = 0.69 and P = 0.43, respectively, paired t-test). Mean (±SD) IOP was 30 ± 6 mm Hg in EG eyes and 13 ± 2 mm Hg in control eyes (P < 0.001). EG eye RNFLT and LSFG-BF were reduced by 42 ± 16% (P < 0.0001) and 22 ± 13% (P = 0.003), respectively, at the final time point. EG eye MS-BFANT, MS-BFPOST, and MS-BFPP were reduced by 41 ± 17% (P < 0.001), 22 ± 34% (P = 0.06), and 30 ± 12% (P = 0.001), respectively, compared with the control eyes. Interocular ONH LSFG-BF differences significantly correlated to that measured by the microsphere method (R2 = 0.87, P < 0.001).
Chronic IOP elevation causes significant ONH BF decreases in the EG model. The high correlation between the BF reduction measured by LSFG and the microsphere method provides evidence that the LSFG is capable of assaying BF for a critical deep ONH region.
The blood flow in the anterior optic nerve and retrolaminar is significantly reduced in nonhuman primate experimental glaucoma with chronic IOP elevation demonstrated independently by laser speckle flowgraphy and the microsphere method. The measurements of the two methods are significantly correlated.
PMCID: PMC3525139  PMID: 23169886
2.  Longitudinal Hemodynamic Changes Within the Optic Nerve Head in Experimental Glaucoma 
To characterize longitudinal changes in basal blood flow (BF) of the optic nerve head (ONH) during progression of structural damage in experimental glaucoma (EG).
Unilateral elevation of IOP was induced in 15 adult rhesus macaques by laser treatment to the trabecular meshwork. Prior to and after laser, retinal nerve fiber layer thickness (RNFLT) and ONH BF were measured biweekly by spectral-domain optical coherence tomography and a laser speckle flowgraphy device (LSFG), respectively.
Average postlaser IOP was 20.2 ± 5.9 mm Hg in EG eyes and 12.3 ± 2.6 mm Hg in control eyes (P < 0.0001). Longitudinal changes in basal ONH BF were strongly associated with changes in RNFLT as EG progressed from early through moderately advanced stages of damage, with Pearson correlation coefficients ranging from 0.64 to 0.97 (average = 0.81) and an average slope of 1.0. During early stage (RNFLT loss < 10%), basal ONH BF was mildly increased (9% ± 10%, P = 0.004) relative to baseline and compared with fellow controls (P = 0.02). Basal ONH BF declined continuously throughout subsequent stages in EG eyes reaching 25.0% ± 9.6% (P < 0.0001) below baseline at the final stage studied (RNFLT loss > 40%). In fellow control eyes, there was no significant change in basal ONH BF over time (P = 0.27).
In EG based on chronic mild-to-moderate IOP elevation, a two-phase pattern of ONH BF alteration was observed. ONH BF increased during the earliest stage (while RNFLT was within 10% of baseline) followed by a linear decline that was strongly correlated with loss of RNFLT.
In a nonhuman primate experimental glaucomatous model with chronic intraocular pressure elevation, a two-phase pattern of optic nerve head blood flow alteration was observed: it increased during the earliest stage followed by a linear decline that was strongly correlated with loss of retinal nerve fiber layer thickness.
PMCID: PMC3691051  PMID: 23737471
intraocular pressure; blood flow; optic nerve head; experimental glaucoma
3.  The Effect of Swimming Goggles on Intraocular Pressure and Blood Flow within the Optic Nerve Head 
Yonsei Medical Journal  2007;48(5):807-809.
Goggles are frequently worn in the sport of swimming and are designed to form a seal around the periorbital tissue orbit. The resultant pressure on the eye may have the potential to affect intraocular pressure and blood flow of the optic nerve head. This study evaluates the influence of wearing swimming goggles on intraocular pressure (IOP) and blood flow of the ocular nerve head (ONH) in normal subjects.
Materials and Methods
Thirty healthy participants took part in this study. The IOP of each participant was measured using a Goldmann tonometer. Measurements were taken immediately before putting on swimming goggles, at 5, 10, 30, and 60 minutes after putting on swimming goggles, and then immediately after taking off the goggles. Blood flow of the ONH was measured using the Heidelberg retinal flowmeter.
The average IOP before, during and after wearing the swimming goggles were 11.88 ± 2.82 mmHg, 14.20 ± 2.81mmHg and 11.78 ± 2.89 mmHg, respectively. The IOP increased immediately after putting on the goggles (p < 0.05) and then returned to normal values immediately after removal (p > 0.05). Blood flow of the ONH was 336.60 ± 89.07 Arbitrary Units (AU) before and 319.18 ± 96.02 AU after the goggles were worn (p < 0.05).
A small but significant IOP elevation was observed immediately after the swimming goggles were put on. This elevated IOP was maintained while the goggles were kept on, and then returned to normal levels as soon as they were taken off. Blood flow of the ONH did not change significantly throughout the experiment. These facts should be considered for safety concerns, especially in advanced glaucoma patients.
PMCID: PMC2628147  PMID: 17963338
Swimming goggles; intraocular pressure; blood flow of optic nerve head
4.  Optical microangiography of retina and choroid and measurement of total retinal blood flow in mice 
Biomedical Optics Express  2012;3(11):2976-2986.
We present a novel application of optical microangiography (OMAG) imaging technique for visualization of depth-resolved vascular network within retina and choroid as well as measurement of total retinal blood flow in mice. A fast speed spectral domain OCT imaging system at 820nm with a line scan rate of 140 kHz was developed to image the posterior segment of eyes in mice. By applying an OMAG algorithm to extract the moving blood flow signals out of the background tissue, we are able to provide true capillary level imaging of the retinal and choroidal vasculature. The microvascular patterns within different retinal layers are presented. An en face Doppler OCT approach [Srinivasan et al., Opt Express 18, 2477 (2010)] was adopted for retinal blood flow measurement. The flow is calculated by integrating the axial blood flow velocity over the vessel area measured in an en face plane without knowing the blood vessel angle. Total retinal blood flow can be measured from both retinal arteries and veins. The results indicate that OMAG has the potential for qualitative and quantitative evaluation of the microcirculation in posterior eye compartments in mouse models of retinopathy and neovascularization.
PMCID: PMC3493231  PMID: 23162733
(170.4500) Optical coherence tomography; (170.3880) Medical and biological imaging
5.  En face optical coherence tomography: a new method to analyse structural changes of the optic nerve head in rat glaucoma 
The British Journal of Ophthalmology  2005;89(9):1210-1216.
Aim: To investigate en face optical coherence tomography (eOCT) and its use as an effective objective technique for assessing changes in the glaucomatous rat optic nerve head (ONH) in vivo, and compare it with confocal scanning laser ophthalmoscopy (cSLO).
Methods: 18 Dark Agouti (DA) rats with surgically induced ocular hypertension were imaged with eOCT and cSLO at regular intervals. Assessment included three dimensional (3D) topographic reconstructions, intensity z-profile plots, a new method of depth analysis to define a “multilayered” structure, and scleral canal measurements, in relation to the degree of intraocular pressure (IOP) exposure.
Results: The increased depth resolution of the eOCT compared to the cSLO was apparent in all methods of analysis, with better discrimination of tissue planes. This was validated histologically. eOCT demonstrated several significant changes in imaged rat ONH which correlated with IOP exposure, including the area of ONH (p<0.01), separation between retinal vessel and scleral layers (p<0.05), and anterior scleral canal opening expansion (p<0.05).
Conclusion: eOCT appears to be effective in assessing rat ONH, allowing detailed structural analysis of the multilayered ONH structure. As far as the authors are aware, this is the first report of scleral canal expansion in a rat model. They suggest eOCT as a novel method for the detection of early changes in the ONH in glaucoma.
PMCID: PMC1772813  PMID: 16113384
image analysis; optic disc; glaucoma; intraocular pressure; animal experimentation
6.  Basal Blood Flow and Autoregulation Changes in the Optic Nerve of Rhesus Monkeys with Idiopathic Bilateral Optic Atrophy 
To characterize the hemodynamic features and the association with structural damage in the optic nerve head (ONH) of idiopathic bilateral optic atrophy (BOA) in rhesus macaque monkeys.
In five animals with BOA and nine healthy animals under general anesthesia (pentobarbital), intraocular pressure (IOP) was manometrically controlled. ONH blood flow was measured with a laser speckle flow graph device. Basal blood flow in global and quadrantal sectors was measured with IOP set at 10 mm Hg; autoregulation capacity was assessed by comparing blood flow changes before and after IOP was increased from 10 to 30 mm Hg. Spectral-domain optic coherence tomography was used to measure retinal nerve fiber layer thickness (RNFLT) by peripapillary circular scans.
Compared with control eyes, RNFLT in BOA eyes was significantly less in all sectors (P < 0.001) except the nasal (P = 0.25); the average global and sectoral blood flow in all quadrants was significantly lower (P < 0.001). These blood flow changes were significantly correlated with corresponding sectoral RNFLT (P < 0.01) except the nasal (P = 0.25). After IOP was increased to 30 mm Hg, global blood flow was significantly reduced (P < 0.001), but with no regional preferences despite prominent temporal RNFLT loss; no significant blood flow change was observed in control eyes (P = 0.24).
Basal blood flow and autoregulation capacity in the ONH of BOA were significantly compromised, with a close correlation to structural changes. The hemodynamic changes showed no regional preference across the ONH, which was consistent with postmortem histological observations.
In idiopathic bilateral optic atrophy in the rhesus monkey, basal blood flow and autoregulation capacity in the optic nerve head were compromised and closely correlated with structural damage. The finding suggests that similar changes may develop in other diseases with optic nerve atrophy, such as glaucoma.
PMCID: PMC3559073  PMID: 23287792
7.  Intraocular Pressure Elevation Induces Mitochondrial Fission and Triggers OPA1 Release in Glaucomatous Optic Nerve 
To determine whether intraocular pressure (IOP) elevation triggers mitochondrial fission and ultrastructural changes and alters optic atrophy type 1 (OPA1) expression and distribution in the optic nerve (ON) of glaucomatous DBA/2J mice.
IOP in the eyes of DBA/2J mice was measured and mitochondrial structural changes were assessed by conventional EM and EM tomography. Cytochrome c oxidase IV subunit 1 (COX), OPA1 and Dnm1, a rat homologue of dynamin-related protein-1, mRNA were measured by Taqman qPCR. COX and OPA1 protein distribution was assessed by immunocytochemistry and Western blot.
Excavation of the optic nerve head (ONH), axon loss, and COX reduction were evident in 10 month-old glaucomatous ONH of eyes with >20 mmHg IOP elevation. EM analysis showed mitochondrial fission, matrix swelling, substantially reduced cristae volume, and abnormal cristae depletion in 10 month-old glaucomatous ONH axons. The mean length of mitochondrial cross section in these axons decreased from 916.6 ± 768.4 nm in 3 month-old mice to 582.87 ± 303.3 nm in 10 month-old glaucomatous mice (P<0.001). Moderate reductions of COX mRNA were observed in the 10 month-old DBA/2J mice optic nerve heads. Larger reductions of OPA1 immunoreactivity and gene expression were coupled with larger increases of Dnm1 gene expression in 10 month-old glaucomatous ONH. Subcellular fractionation analysis indicates increased release of both OPA1 and cytochrome c from mitochondria in 10 month-old glaucomatous ONs.
IOP elevation may directly damage mitochondria in the ONH axons by promoting reduction of COX, mitochondrial fission and cristae depletion, alterations of OPA1 and Dnm1 expression, and induction of OPA1 release. Thus, interventions to preserve mitochondria may be useful for protecting ON degeneration in glaucoma.
PMCID: PMC2688012  PMID: 18469184
8.  Effects of scleral buckling and encircling procedures on human optic nerve head and retinochoroidal circulation 
AIMS—To study the effects of segmental scleral buckling and encircling procedures on tissue circulation in the human optic nerve head (ONH) and choroid and retina.
METHODS—Using the laser speckle method, the normalised blur (NB) value, a quantitative index of tissue blood velocity, was measured every 0.125 seconds and averaged over three pulses in the optic nerve head (NBONH) and choroid and retina (NBch-ret) in 10 patients with unilateral rhegmatogenous retinal detachment (mean age 52 (SD 17)). NBONH, NBch-ret, and intraocular pressure (IOP) in both eyes, and blood pressure (BP) were measured before, and 1, 4, and 12 weeks after the scleral buckling and encircling procedure.
RESULTS—NBch-ret on the buckled side was significantly reduced after surgery and smaller than that in the unoperated contralateral eye throughout the study period (ANOVA, p<0.0001). NBch-ret on the unbuckled side, in the foveal area, NBONH, IOP, and BP showed no significant change.
CONCLUSIONS—It was indicated that the segmental scleral buckling procedure with encircling elements decreased tissue blood velocity in the choroid and retina on the buckled side but caused no significant change on tissue circulation in other areas of the fundus or ONH.

PMCID: PMC1723226  PMID: 10611096
9.  Enhanced Oxygen Saturation in Optic Nerve Head of Non-Human Primate Eyes Following the Intravitreal Injection of NCX 434, an Innovative Nitric Oxide-Donating Glucocorticoid 
Hypoxia of the retina and optic nerve head (ONH) is believed to be pivotal in the development of ocular vascular disorders, including diabetic macular edema (DME). Glucocorticoids are among the most effective agents for the treatment of back of the eye diseases. However, this class of compounds is highly liable to increase intraocular pressure (IOP) and does not improve ocular perfusion or tissue oxygenation. Nitric oxide (NO) has vasodilating properties and lowers IOP in experimental models and humans, suggesting that its properties might complement those of glucocorticoids. NCX 434 is an NO-donating triamcinolone acetonide (TA) that is less likely to increase IOP while targeting both the vascular and inflammatory components of DME.
NCX 434 was studied in vitro with respect to its NO-releasing properties in isolated methoxamine-precontracted rabbit aortic rings and glucocorticoid-like activity in recombinant human glucocorticoid receptors. IOP and oxygen saturation in the ONH and overlaying arteries and veins were studied in the anesthetized cynomolgus monkey. Measurements were taken using, respectively, an applanation tonometer and a hyperspectral imaging system before and 7, 14, 21, 31 and 41 days after the intravitreal injection of NCX 434 (5.8 mg/eye) or TA equimolar doses (4.0 mg/eye).
NCX 434 inhibited 3H-dexamethasone-specific binding (IC50=34±5 nM) on human glucocorticoid receptors and elicited NO-dependent aortic ring relaxation (EC50 of 0.5±0.1 μM, Emax 98.9%). In monkey eyes, NCX 434 enhanced, whereas TA did not, oxygen saturation in various ONH areas (*P<0.05 vs. basal), decreased it in veins, and did not affect it in the overlaying arteries. Neither NCX 434 nor TA altered IOP significantly at all time points. However, at 31 days post-treatment TA appeared to start increasing IOP (ΔIOP=+3.31±0.51 mmHg, 30.8%, over baseline, NS).
NCX 434 enhances ocular tissue oxygenation. This feature appears to depend on its NO-donating properties; thus, the compound deserves to be further investigated for the treatment of DME and other ocular disorders with impaired ocular perfusion.
PMCID: PMC3078533  PMID: 21413860
10.  Blood Pressure Modifies Retinal Susceptibility to Intraocular Pressure Elevation 
PLoS ONE  2012;7(2):e31104.
Primary open angle glaucoma affects more than 67 million people. Elevated intraocular pressure (IOP) is a risk factor for glaucoma and may reduce nutrient availability by decreasing ocular perfusion pressure (OPP). An interaction between arterial blood pressure and IOP determines OPP; but the exact contribution that these factors have for retinal function is not fully understood. Here we sought to determine how acute modifications of arterial pressure will affect the susceptibility of neuronal function and blood flow to IOP challenge. Anaesthetized (ketamine:xylazine) Long-Evan rats with low (∼60 mmHg, sodium nitroprusside infusion), moderate (∼100 mmHg, saline), or high levels (∼160 mmHg, angiotensin II) of mean arterial pressure (MAP, n = 5–10 per group) were subjected to IOP challenge (10–120 mmHg, 5 mmHg steps every 3 minutes). Electroretinograms were measured at each IOP step to assess bipolar cell (b-wave) and inner retinal function (scotopic threshold response or STR). Ocular blood flow was measured using laser-Doppler flowmetry in groups with similar MAP level and the same IOP challenge protocol. Both b-wave and STR amplitudes decreased with IOP elevation. Retinal function was less susceptible to IOP challenge when MAP was high, whereas the converse was true for low MAP. Consistent with the effects on retinal function, higher IOP was needed to attenuated ocular blood flow in animals with higher MAP. The susceptibility of retinal function to IOP challenge can be ameliorated by acute high BP, and exacerbated by low BP. This is partially mediated by modifications in ocular blood flow.
PMCID: PMC3281054  PMID: 22359566
11.  An hypothesis on pressure transmission from anterior chamber to optic nerve☆ 
Medical hypotheses  2011;77(5):827-831.
Few studies have characterized how pressure in the anterior chamber (AC) of the eye is transmitted via the vitreous to the vitreous–ganglion cell interface. We are aware of only one study that simultaneously measured the pressures in the AC and vitreous humor; and of only one study that simultaneously measured the pressures in the AC and the suprachoroidal space (SCS). The pressure in the AC is defined as the intraocular pressure (IOP), which when elevated beyond statistically normal limits is a recognized risk factor for glaucoma, a malady best described as an optic neuropathy with degeneration and eventual death of the retinal ganglion cells (GC’s) and highly characteristic changes in the optic nerve head (ONH). Most investigators currently believe that the prevalent risk factor for GC apoptosis is ocular hypertension, but no one has demonstrated how an increase in IOP in the AC is transmitted to the GC’s. In patients with primary open angle glaucoma, the pressure in the AC increases due to an increase in the resistance of the trabecular meshwork (TM) outflow pathway. We questioned how such increased pressure in the AC would be transmitted to the GC to produce the changes in the ONH seen in glaucoma. Based on our preliminary data and purview of the literature, we hypothesize that a pressure increase originating in the AC is likely transmitted via both the SCS and the vitreous, with transmission via the former pathway probably most efficient in affecting the GC. Independently of the mechanism that produces GC apoptosis, the ones that are first affected, as repeatedly shown by visual field tests, are the most peripheral ones; i.e., those whose axons are the most external as they form the ONH and enter the lamina cribrosa. There are no published reports explaining this peculiarity. The dogma is that the pressure transmitted via the vitreous is higher at the periphery because it is transmitted across a shorter distance, since the vitreous acts as a buffer that absorbs part of the pressure being transmitted. We propose that IOP is not only transmitted via the vitreous but also via the SCS. Increases in IOP could be efficiently applied via the SCS to the most external axons of the ONH as they leave the eye. Our hypothesis can also explain low-tension glaucoma in which the most peripheral GC’s are also affected first, because pressure is transmitted without decay due to a reduced uveoscleral (UVS) flow.
PMCID: PMC3713462  PMID: 21855227
12.  The Effect of Ageing on Ocular Blood Flow, Oxygen Tension and Retinal Function during and after Intraocular Pressure Elevation 
PLoS ONE  2014;9(5):e98393.
To investigate the effect of ageing on the recovery of ocular blood flow, intravitreal oxygen tension and retinal function during and after intraocular pressure (IOP) elevation.
Long Evans rats (3- and 14-month-old) underwent acute stepwise IOP elevation from 10 to 120 mmHg (5 mmHg steps each 3 minutes). IOP was then returned to baseline and recovery was monitored for 2 hours. Photopic electroretinograms (ERG) were recorded at each IOP step during stress and at each minute during recovery. Ocular blood flow and vitreal oxygen tension (pO2) were assayed continuously and simultaneously using a combined laser Doppler flow meter (LDF) and an oxygen sensitive fibre-optic probe, respectively. The combined sensor was placed in the vitreous chamber, proximal to the retina. Data were binned into 3 minute intervals during stress and 1 min intervals during recovery. Recovery data was described using a bi-logistic function.
Rats of both ages showed similar susceptibility to IOP elevation, with pO2 showing a closer relationship to ERG than LDF. During recovery, both ages showed a distinctive two-phased recovery for all three measures with the exception of the LDF in 3-month-old rats, which showed only 1 phase. In all animals, LDF recovered fastest (<1 minute), followed by pO2 (<10 minute) and ERG (>1 hour). 14-month-old rats showed surprisingly faster and greater LDF recovery compared to the younger group, with similar levels of pO2 recovery. However, the ERG in these middle-aged animals did not fully recover after two hours, despite showing no difference in susceptibility to IOP during stress compared to the young group.
Young and middle-aged eyes showed similar susceptibility to IOP elevation in terms of pO2, LDF and ERG. Despite this lack of difference during stress, older eyes did not completely recover function, suggesting a more subtle age-related susceptibility to IOP.
PMCID: PMC4035318  PMID: 24866182
13.  The effect of trabeculectomy on ocular hemodynamics. 
PURPOSE: To evaluate the effects of chronic reduction of intraocular pressure (IOP) on ocular hemodynamics. METHODS: Multisite, prospective evaluation of patients requiring trabeculectomy for treatment of glaucoma. Patients were recruited from the glaucoma service of 2 university hospitals. Patients were evaluated prior to surgery and at 3, 6, and 12 months after trabeculectomy. Color Doppler imaging was used to measure blood flow in the ophthalmic artery, central retinal artery, and short posterior ciliary arteries. Heidelberg retinal flowmetry was used to evaluate perfusion in the peripapillary and optic disc capillary beds. IOP was measured at baseline and at each study visit. RESULTS: There were highly significant reductions in IOP from presurgical baseline measures. At 3 months, mean IOP reduction was 17.1 mm Hg (62.3%; P < .001). At the 6- and 12-month evaluations, the mean IOP reductions were 15.7 mm Hg (57.3%) and 15.5 mm Hg (56.5%), respectively, P < .001. Despite the significant reduction in IOP, there were no significant differences in any ocular blood flow parameters before and after trabeculectomy. CONCLUSIONS: The findings of this study suggest that chronic reduction of IOP does not alter ocular blood flow and that IOP may be an independent risk factor for progression of glaucoma. These findings also suggest that the eye has the ability to autoregulate to chronically increased IOP over time and that additional studies evaluating the long-term effects of IOP changes are needed to further define this relationship.
PMCID: PMC1359016  PMID: 11797313
14.  Diurnal Tension Curves for Assessing the Development or Progression of Glaucoma 
Executive Summary
Clinical Need: Condition and Target Population
There are two main types of glaucoma, primary open angle (POAG) and angle closure glaucoma, of which POAG is the more common type. POAG is diagnosed by assessing degenerative changes in the optic disc and loss of visual field (VF). Risk factors for glaucoma include an increase in intraocular pressure (IOP), a family history of glaucoma, older age and being of African descent. The prevalence of POAG ranges from 1.1% to 3.0% in Western populations and from 4.2% to 8.8% in populations of African descent.
Usually the IOP associated with POAG is elevated above the normal distribution (10-20 mmHg), but when IOP is not elevated it is often referred to as normal-tension glaucoma (NTG). In population based studies, approximately one-third to half of the patients with glaucomatous VF loss have normal IOP on initial examination.
People with elevated IOP (>21 mmHg), but with no evidence of optic disc or VF damage have ocular hypertension. It has been estimated that 3 to 6 million people in the United States including 4% to 7% of those older than 40 years have elevated IOP without detectable glaucomatous damage on standard clinical tests. An Italian study found the overall prevalence of ocular hypertension, POAG, and NTG in 4,297 people over 40 years of age to be 2.1%, 1.4% and 0.6% respectively.
Diurnal Curves for Intraocular Pressure Measurement
Diurnal Curve
In normal individuals, IOP fluctuates 2 to 6 mmHg over a 24 hour period. IOP is influenced by body position with higher readings found in the supine relative to the upright position. As most individuals sleep in the supine position and are upright during the day, IOP is higher on average in people, both with and without glaucoma, in the nocturnal period. IOP is generally higher in the morning compared to the afternoon.
Multiple IOP measurements over the course of a day can be used to generate a diurnal curve and may have clinical importance in terms of diagnosis and management of patients with IOP related conditions since a solitary reading in the office may not reveal the peak IOP and fluctuation that a patient experiences. Furthermore, because of diurnal and nocturnal variation in IOP, 24-hour monitoring may reveal higher peaks and wider fluctuations than those found during office-hours and may better determine risk of glaucoma progression than single or office-hour diurnal curve measurements.
There is discrepancy in the literature regarding which parameter of IOP measurement (e.g., mean IOP or fluctuation/range of IOP) is most important as an independent risk factor for progression or development of glaucoma. The potential for increased rates or likelihood of worsening glaucoma among those with larger IOP swings within defined time periods has received increasing attention in the literature.
According to an expert consultant:
The role of a diurnal tension curves is to assess IOP in relationship to either a risk factor for the development or progression of glaucoma or achievement of a target pressure which may direct a therapeutic change.
Candidates for a diurnal curve are usually limited to glaucoma suspects (based on optic disc changes or less commonly visual field changes) to assess the risk for development of glaucoma or in patients with progressive glaucoma despite normal single office IOP measurements.
Clinically diurnal tension curves are used to determine the peak IOP and range.
Single IOP Measurements
Intraocular pressure fluctuation as a risk factor for progression of glaucoma has also been examined without the use of diurnal curves. In these cases, single IOP measurements were made every 3-6 months over several months/years. The standard deviation (SD) of the mean IOP was used as a surrogate for fluctuation since no diurnal tension curves were obtained.
To determine whether the use of a diurnal tension curve (multiple IOP measurements over a minimum 8 hour duration) is more effective than not using a diurnal tension curve (single IOP measurements) to assess IOP fluctuation as a risk factor for the development or progression of glaucoma.
To determine whether the use of a diurnal tension curve is beneficial for glaucoma suspects or patients with progressive glaucoma despite normal single office IOP measurements and leads to a more effective disease management strategy.
Research Methods
Literature Search
Search Strategy
A literature search was performed on July 22, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2006 until July 14, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist, then a group of epidemiologists until consensus was established. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology.
Inclusion Criteria
Open angle glaucoma (established or OHT high risk) in an adult population
IOP measurement by Goldmann applanation tonometry (the gold standard)
Number and timing of IOP measurements explicitly reported (e.g., 5 measurements a day for 5 visits to generate a diurnal curve or 1 measurement a day [no diurnal curve] every 3 months for 2 years)
IOP parameters include fluctuation (range [peak minus trough] or standard deviation) and mean
Outcome measure = progression or development of glaucoma
Study reports results for ≥ 20 eyes
Most recent publication if there are multiple publications based on the same study
Exclusion Criteria
Angle closure glaucoma or pediatric glaucoma
Case reports
IOP measured by a technique other than GAT (the gold standard)
Number and timing of IOP measurements not explicitly reported
Outcomes of Interest
Progression or development of glaucoma
There is very low quality evidence (retrospective studies, patients on different treatments) for the use of a diurnal tension curve or single measurements to assess short or long-term IOP fluctuation or mean as a risk factor for the development or progression of glaucoma.
There is very low quality evidence (expert opinion) whether the use of a diurnal tension curve is beneficial for glaucoma suspects or patients with progressive glaucoma, despite normal single office IOP measurements, and leads to a more effective disease management strategy.
PMCID: PMC3377558  PMID: 23074414
15.  Factors associated with topographic changes of the optic nerve head induced by acute intraocular pressure reduction in glaucoma patients 
Eye  2010;25(2):201-207.
To investigate factors associated with changes in optic nerve head (ONH) topography after acute intraocular pressure (IOP) reduction in patients with primary open-angle glaucoma (POAG).
Untreated POAG patients (IOP >21 mm Hg) were prospectively enrolled. Systemic and ocular information were collected, including central corneal thickness (CCT) and corneal hysteresis (CH). All patients underwent confocal scanning laser ophthalmoscopy and tonometry (Goldmann) before and 1 h after pharmacological IOP reduction. The mean of three measurements was considered for analysis. Changes in each ONH topographic parameter were assessed (one eye was randomly selected), and those that changed significantly were correlated with patient's systemic and ocular characteristics.
A total of 42 patients were included (mean age, 66.7±11.8 years). After a mean IOP reduction of 47.3±11.9%, significant changes were observed in cup area and volume, and in rim area and volume (P<0.01), but not in mean cup depth (P=0.80). Multiple regression analysis (controlling for baseline IOP and magnitude of IOP reduction) showed that CH (r2=0.17, P<0.01) and diabetes diagnosis (r2⩾0.21, P<0.01) were negatively correlated with the magnitude of changes in ONH parameters, whereas the cup-to-disc ratio was positively correlated (r2=0.30, P<0.01). Age, race, disc area, and CCT were not significant (P⩾0.12). Including all significant factors in a multivariable model, only the presence of diabetes remained significantly associated with all ONH parameters evaluated (P<0.01).
Different systemic and ocular factors, such as diabetes, CH, and the relative size of the cup, seem to be associated with the magnitude of changes in ONH topography after acute IOP reduction in POAG patients. These associations partially explain the ONH changes observed in these patients and suggest that other factors are possibly implicated in an individual susceptibility to IOP.
PMCID: PMC3169223  PMID: 21127505
glaucoma; intraocular pressure; optic nerve head; corneal biomechanics
16.  Effects of 0.5% apraclonidine on optic nerve head and peripapillary retinal blood flow 
The British Journal of Ophthalmology  1997;81(12):1070-1072.
AIMS—To examine the effects of 0.5% apraclonidine on optic nerve head (ONH) and peripapillary retinal blood flow by scanning laser Doppler flowmetry (SLDF).
METHODS—ONH and peripapillary retinal blood flow of 17 healthy subjects were measured by SLDF before and 1 hour and 3 hours after unilateral administration of 0.5% apraclonidine. The fellow eyes were treated with balanced salt solution and the examiners were masked as to which eye was treated with apraclonidine. On each occasion, three scans were obtained and haemodynamic variables (volume, flow, and velocity) were analysed at eight locations, four in the neural rim and four in the peripapillary retina, avoiding ophthalmoscopically visible vessels. The statistical significance of changes from the baseline value of variables and the differences in the measured quantities between apraclonidine treated eyes and fellow eyes at each time point were evaluated using Wilcoxon signed rank test.
RESULTS—The intraocular pressure was reduced significantly in apraclonidine treated eyes by 15.0% (p=0.001) at 1 hour and 30.0% (p=0.000) at 3 hours after administration. In the volume, flow, or velocity of ONH and peripapillary retinal blood flow, there were no significant changes from the baseline values at 1 hour and 3 hours after apraclonidine administration in either apraclonidine treated eyes (p >0.4) or fellow eyes (p >0.2). Also, no significant differences were found in the measured quantities between apraclonidine treated eyes and fellow eyes at each time point (p >0.1).
CONCLUSION—A single dose of topical apraclonidine 0.5% in healthy subjects does not have adverse effects on the ONH and peripapillary retinal blood flow.

PMCID: PMC1722079  PMID: 9497467
17.  Comparison of Intraocular Pressure, Blood Pressure, Ocular Perfusion Pressure and Blood Flow Fluctuations During Dorzolamide Versus Timolol Add-On Therapy in Prostaglandin Analogue Treated Glaucoma Subjects 
Pharmaceuticals  2012;5(3):325-338.
Objective: To compare the effects of dorzolamide and timolol add-on therapy in open-angle glaucoma (OAG) patients previously treated with prostaglandin analogue (Pg), by evaluating fluctuations in the intraocular (IOP), blood (BP), ocular perfusion pressures (OPP) and retrobulbar blood flow (RBF) parameters. Methods: 35 OAG patients (35 eyes), 31 women (88.6%) age 63.3 (8.9) years were evaluated in a 3 month randomized, cross-over, single-masked study. During the experiments BP, heart rate, IOP and OPP were assessed 4 times per day (8–12–16–20 h). RBF was measured twice per day (8–20 h) using Color Doppler imaging in the ophthalmic (OA), central retinal (CRA), nasal (nSPCA) and temporal (tSPCA) posterior ciliary arteries. In each vessel, peak systolic velocity (PSV) and end-diastolic velocity (EDV) were assessed and vascular resistance (RI) calculated. Results: Both add-on therapies lowered IOP in a statistically significant manner from 15.7 ± 2.4 mmHg at latanoprost baseline to 14.9 ± 2.2 mmHg using dorzolamide (p < 0.001) and 14.2 ± 1.9 mmHg using timolol (p < 0.001). The IOP lowering effect was statistically significant at 20 h, favoring timolol as compared to dorzolamide (1.4 ± 2.4 vs. 0.2 ± 2.1 mmHg), (p < 0.05). Dorzolamide add-on therapy showed smaller IOP (2.0 ± 1.4), SPP (13.3 ± 7.9), systolic BP (13.5 ± 8.7) and diastolic BP (8.4 ± 5.4) fluctuations as compared to both latanoprost baseline or timolol add-on therapies. Higher difference between morning and evening BP was correlated to decreased evening CRA EDV in the timolol group (c = −0.41; p = 0.01). With increased MAP in the morning or evening hours, we found increased evening OA RI in timolol add-on group (c = 0.400, p = 0.02; c = 0.513, p = 0.002 accordingly). Higher MAP fluctuations were related to impaired RBF parameters during evening hours-decreased CRA EDV (c = −0.408; p = 0.01), increased CRA RI (c = 0.576; p < 0.001) and tSPCA RI (c = 0.356; p = 0.04) in the dorzolamide group and increased nSPCA RI (c = 0.351; p = 0.04) in the timolol add-on group. OPP fluctuations correlated with increased nSPCA RI (c = 0.453; p = 0.006) in the timolol group. OPP fluctuations were not related to IOP fluctuations in both add-on therapies (p < 0.05). Conclusions: Both dorzolamide and timolol add-on therapies lowered IOP in a statistically significant fashion dorzolamide add-on therapy showed lower fluctuations in IOP, SPP and BP. Higher variability of daytime OPP led to impaired RBF parameters in the evening.
PMCID: PMC3763637  PMID: 24281382
retrobulbar blood flow; intraocular pressure; ocular perfussion pressure; color dopler imaging; open-angle glaucoma
18.  Clinical characteristics of retinal venous occlusions occurring at different sites 
Aims: To identify the contributory factors associated with different sites of occlusion and the presence or absence of optic nerve head swelling (ONHS).
Methods: 874 cases of retinal venous occlusion (RVO) were prospectively examined at a tertiary referral centre and classified according to three defined sites of occlusion: arteriovenous crossing RVO (AV-RVO); optic cup RVO (OC-RVO); and optic nerve sited RVO. Optic nerve sited RVOs were further divided on the basis of presence (ONHS-RVO) and absence (NONHS-RVO) of ONHS. RVOs not occurring at any of the defined sites were grouped as no-site RVO (NS-RVO). Important clinical parameters were compared among four of the five subgroups by multivariate analysis of variance and χ2 test (NS-RVO excluded).
Results: The overall multivariate analysis of variance for differences in the mean age, systolic and diastolic blood pressure, body mass index, and intraocular pressure (IOP) among the four subgroups were highly significant (p <0.0001). The F ratios indicated that the differences in the mean age and IOP accounted for this statistical trend. The mean age was statistically significantly lower in the ONHS-RVO group compared to the rest of the groups (p <0.0001). The mean age was significantly higher in OC-RVO compared to the AV-RVO group (p <0.05). The mean IOP was significantly higher in OC-RVO than in the rest of the groups (p <0.01 to 0.0001), while it was also higher in the NONHS-RVO group compared to the ONHS-RVO and AV-RVO groups (p <0.0001). The prevalence of primary open angle glaucoma (POAG), sex, laterality, involvement of the fellow eye, smoking and hypertension were compared by χ2 tests. POAG was significantly more prevalent in the OC-RVO group than in the rest of the groups (p <0.0083), while it was also significantly more prevalent in the NONHS-RVO group compared to AV-RVO or ONHS-RVO (p <0.0083) groups. Smoking was significantly more prevalent in AV-RVO than in the rest of the groups (p <0.05). The proportion of male sex was significantly higher in ONHS-RVO compared to the AV-RVO group (p <0.05). Hypertension was significantly more prevalent in the AV-RVO than in the ONHS-RVO or NONHS-RVO groups (p <0.05).
Conclusion: A new classification of RVO based on the site of occlusion and ONHS has been evaluated. The higher prevalence of hypertension and smoking in AV-RVO suggests a particular importance of cardiovascular risk factors in this group. The association of POAG with CRVO has been confirmed, but only for those cases without ONHS. A distinctive relation between raised IOP and OC-RVO has been demonstrated, suggesting a causal association. RVOs with ONHS tend to occur in younger people, with a higher proportion of males, and a lower prevalence of hypertension and POAG, suggesting that other causal factors may be important in this group. The new scheme resolves the confusion in the literature regarding classification of RVO, and has diagnostic, causal, prognostic, and therapeutic implications.
PMCID: PMC1771127  PMID: 11973257
retinal venous occlusion; cardiovascular risk factors
19.  Reflectance Decreases before Thickness Changes in the Retinal Nerve Fiber Layer in Glaucomatous Retinas 
In this study, a decrease in RNFL reflectance was found near the ONH in glaucomatous eyes. The change preceded thinning of the RNFL, suggesting that a decrease in RNFL reflectance near the ONH is an early sign of glaucomatous damage.
Glaucoma damages the retinal never fiber layer (RNFL). RNFL thickness, measured with optical coherence tomography (OCT), is often used in clinical assessment of the damage. In this study the relation between the RNFL reflectance and thickness at early stages of glaucoma was investigated.
A rat model of glaucoma was used that involved laser photocoagulation of the trabecular meshwork. The reflectance of the RNFL in an isolated retina was measured, followed by immunohistochemical staining of the axonal cytoskeleton. RNFL thickness was measured by confocal fluorescence imaging. RNFL reflectance was calculated for bundle areas located at radii of 0.22, 0.33, and 0.44 mm from the optic nerve head (ONH) center. Linear regression was used to study the relation between reflectance and thickness. For glaucomatous eyes, only those bundles with no apparent structural damage were used.
Bundles in 11 control retinas and 10 treated retinas were examined. Bundle thickness of both groups at each radius was similar (P = 0.89). The reflectance of the bundles at radii of 0.33 and 0.44 mm was found to be similar in both control and treated retinas (P > 0.5). However, the reflectance of the bundles at the 0.22-mm radius decreased significantly in the treated group (P = 0.005).
Elevation of intraocular pressure causes decrease in RNFL reflectance for bundles near the ONH. Change in RNFL reflectance precedes thinning of the RNFL. The results suggest that a decrease in RNFL reflectance near the ONH is an early sign of glaucomatous damage.
PMCID: PMC3175984  PMID: 21730345
20.  Comparison of Intraocular Pressure Fluctuations Measured by Goldmann Applanation Tonometer and Pulsatile Ocular Blood Flow Analyser 
Intraocular pressure (IOP) is the major known risk factor in glaucoma and the primer mover of the functional damage in glaucomatous patients but it is not a unique determinant of glaucomatous damage. Clinical assessment of glaucoma patients may not be a true reflection of overall IOP control. Evaluation of the effect of glaucoma medication is restricted by measurement of IOP as a dynamic physiological parameter.
To compare IOP fluctuations over time using Goldmann applanation tonometry (IOPGAT) and pulsatile ocular blood flow analyzer (IOP-POBFA) under the Dorzolamide/timolol or latanoprost treatment regimes.
Prospective 1 year follow-up study.
30 randomly chosen controlled open angle glaucoma patients (60 eyes): 16 patients (32 eyes) receiving Dorzolamide/timolol fixed combination (D/T) and 14 (28 eyes) latanoprost 0.005% treatment. Main outcome measures: Changes in IOP and perfusion pressure dynamics.
There was no statistically significant difference in baseline IOP parameters between study groups: 15.69 ± 2.02 mmHg with D/T and 16.71 ± 2.84 mmHg with latanoprost (p=0.314). Both treatment regimes were tolerated and patients were adherent to treatment. Determined a strong positive correlation between IOP-GAT and IOP-POBFA; verified over time period under particular treatment regime. After 1 year follow-up D/T and latanoprost results referred to statistically significant tachyphylaxis effect, i.e. IOP-GAT increased in 2.31mmHg with D/T (p=0.007) and 2.72 mmHg (p=0.004) with latanoprost and IOP-POBFA increased in 1.74 mmHg (p=0.026) and 3.13 mmHg (p=0.007) respectively. Multiple regression analysis revealed no important blood flow factors as predictors in the increase of IOP.
Strong positive correlation was revealed between IOP-POBFA and IOP-GAT over a time period. Observed tachyphylaxis effects after 1 year under both treatment regimes should be assessed with respect to patient compliance and persistence to treatment.
PMCID: PMC3614641  PMID: 23675012
glaucoma; intraocular pressure; Goldmann applanation tonometry; pulsatile ocular blood flow analyser
21.  Effect of acute intraocular pressure changes on short posterior ciliary artery haemodynamics 
BACKGROUND/AIMS—Vascular insufficiency due to abnormal autoregulation has been proposed as a major factor in the development of glaucoma. The anterior optic nerve is primarily perfused by the short posterior ciliary arteries. The autoregulatory capacity of these vessels in response to acutely elevated intraocular pressure (IOP) was examined in normal human subjects.
METHODS—Colour Doppler imaging was performed on the short posterior ciliary arteries of 10 normal subjects at baseline and during four incremental IOP elevations. Using a scleral suction cup placed temporally, IOP was elevated to approximately 25, 30, 40, and 50 mm Hg. Additional measurements were performed immediately after pressure release. Systolic and diastolic flow velocities were measured and Pourcelot's resistivity index was calculated.
RESULTS—Systolic and diastolic flow velocities decreased linearly with each incremental increase in IOP (p<0.001). Pourcelot's resistivity index increased linearly with each incremental increase in IOP (p<0.001). Changes in end diastolic velocity, peak systolic velocity, and Pourcelot's resistivity index were linearly related to changes in IOP.
CONCLUSION—The normal healthy eye is not able to autoregulate to maintain PCA blood flow velocities in response to acute large elevations in IOP.

 Keywords: blood flow; colour Doppler imaging; posterior ciliary artery; retrobulbar haemodynamics
PMCID: PMC1722788  PMID: 10209431
22.  Global Changes in Optic Nerve Head Gene Expression after Exposure to Elevated Intraocular Pressure in a Rat Glaucoma Model 
In glaucoma, the optic nerve head (ONH) is the likely site of initial injury and elevated intraocular pressure (IOP) is the best-known risk factor. This study determines global gene expression changes in the pressure-injured ONH.
Unilateral sustained IOP elevation (glaucoma, n = 46) or optic nerve transection (n = 10) was produced in rats. ONHs were removed, and the retrobulbar optic nerves were graded for degeneration. Gene expression in the glaucomatous ONH with extensive injury was compared with that in the fellow ONH (n = 6/group), by using cDNA microarrays. Data from 12 arrays were normalized, significant differences in gene expression determined, and significantly affected gene classes identified. For the remaining ONH, grouped by experimental condition and degree of injury, quantitative reverse transcriptase-PCR (qPCR) and ANOVA were used to compare selected message levels.
Microarray analysis identified more than 2000 significantly regulated genes. For 225 of these genes, the changes were greater than twofold. The most significantly affected gene classes were cell proliferation, immune response, lysosome, cytoskeleton, extracellular matrix, and ribosome. A 2.7-fold increase in ONH cellularity confirmed glaucoma model cell proliferation. By qPCR, increases in levels of periostin, collagen VI, and transforming growth factor β1 were linearly correlated to the degree of IOP-induced injury. For cyclinD1, fibulin 2, tenascin C, TIMP1, and aquaporin-4, correlations were significantly nonlinear, displaying maximum change with focal injury.
In the ONH, pressure-induced injury results in cell proliferation and dramatically altered gene expression. For specific genes, expression levels were most altered by focal injury, suggesting that further array studies may identify initial, and potentially injurious, altered processes.
PMCID: PMC1950563  PMID: 17591886
23.  Wavelength-Dependent Change of Retinal Nerve Fiber Layer Reflectance in Glaucomatous Retinas 
Retinal nerve fiber layer (RNFL) reflectance is often used in optical methods for RNFL assessment in clinical diagnosis of glaucoma, yet little is known about the reflectance property of the RNFL under the development of glaucoma. This study measured the changes in RNFL reflectance spectra that occurred in retinal nerve fiber bundles with different degrees of glaucomatous damage.
A rat model of glaucoma with laser photocoagulation of trabecular meshwork was used. Reflectance of the RNFL in an isolated retina was measured at wavelengths of 400–830 nm. Cytostructural distribution of the bundles measured optically was evaluated by confocal imaging of immunohistochemistry staining of cytoskeletal components, F-actin, microtubules, and neurofilaments. RNFL reflectance spectra were studied in bundles with normal-looking appearance, early F-actin distortion, and apparent damage of all cytoskeletal components. Changes of RNFL reflectance spectra were studied at different radii (0.22, 0.33, and 0.44 mm) from the optic nerve head (ONH).
Bundles in 30 control retinas and 41 glaucomatous retinas were examined. In normal retinas, reflectance spectra were similar along the same bundles. In glaucomatous retinas, reflectance spectra changed along bundles with the spectra becoming flatter as bundle areas approached the ONH.
Elevation of intraocular pressure (IOP) causes nonuniform changes in RNFL reflectance across wavelengths. Changes of reflectance spectra occur early in bundles near the ONH and prior to apparent cytoskeletal distortion. Using the ratio of RNFL reflectance measured at different wavelengths can provide early and sensitive detection of glaucomatous damage.
Reflectance spectrum of the RNFL was changed in glaucomatous retina. The change preceded apparent distortion of axonal ultrastructure, indicating that measuring the RNFL reflectance ratio can provide early detection of axonal degeneration.
PMCID: PMC3428115  PMID: 22836775
24.  Effects of body mass index on intraocular pressure and ocular pulse amplitude 
To investigate the effects of body mass index (BMI) on intraocular pressure (IOP) and ocular pulse amplitude (OPA).
Totally 140 healthy individuals without any systemic diseases were included in the study. BMI (kg/m2) was calculated for every individual. IOP and OPA were measured with Pascal Dynamic contour tonometer (DCT). Blood pressure was also measured along with the DCT. The patients were divided into three groups according to BMI as: Group1, BMI<25; Group2, 25≤BMI<30; Group3, BMI≥30. Mean values of IOP, OPA, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were used in statistical analysis.
In Group1, the means of IOP, OPA, were 16.8±2.3mmHg, 2.7±0.7mmHg respectively; and SBP, DBP were 120.0±6.1mmHg, and 77.4±5.6mmHg respectively. In group2, the mean IOP, OPA, SBP, and DBP were found to be 16.6±2.1mmHg, 2.4±0.7mmHg, 121.7±5.3mmHg, and 79.5±4.9mmHg respectively. In group3, the mean IOP, OPA, SBP, and DBP were found to be 17.3±1.7mmHg, 2.1±0.7mmHg, 122.4±5.7mmHg, and 79.7±5.2mmHg respectively. There were no statistically significant difference between groups in terms of IOP, SBP and DBP, while OPA values were significantly lower in group3 (P=0.001).
Decreased OPA values in individuals with higher BMI may indicate that subjects with higher BMI have lower choroidal perfusion and lower ocular blood flow.
PMCID: PMC3484700  PMID: 23166873
body mass index; choroidal perfusion; intraocular pressure; ocular pulse amplitude; obesity
25.  The Effect of Vasopressin on Choroidal Blood Flow, Intraocular Pressure, and Orbital Venous Pressure in Rabbits 
Choroidal blood flow is influenced by vasoactive substances of local and systemic origin. Vasopressin is a potent choroidal blood flow modulator and is involved in homeostatic regulation of choroidal hemodynamics and ocular hydrodynamics.
To investigate the effects of arginine-vasopressin (AVP) on intraocular pressure (IOP), orbital venous pressure (OVP), and choroidal blood flow (ChorBF) regulation in anesthetized rabbits.
Mean arterial pressure (MAP), IOP, and OVP were measured by direct cannulation of the central ear artery, the vitreous, and the orbital venous sinus, respectively. Laser Doppler flowmetry was used to record ChorBF. To change the perfusion pressure (PP), MAP was manipulated mechanically with occluders around the aorta and vena cava. In the first group of animals (n = 11) the dose-response relationship was measured. In the second group of animals (n = 8) pressure-flow relationships were determined at baseline and in response to intravenous application of a low (0.08 ng/kg/min) and a high (1.33 ng/kg/min) infusion rate of AVP.
AVP caused a dose-dependent increase of MAP and choroidal vascular resistance (ChorR), whereas IOP, OVP, ChorBF, and heart rate (HR) were decreased. In contrast to the high infusion rate, the low infusion rate of AVP had no effect on baseline ChorBF. However, the pressure-flow relationship was shifted downward significantly by both infusion rates at PP below baseline.
AVP reduces IOP and OVP significantly and is a potent vasoconstrictor in the choroidal vascular bed. In the choroid, the effect of AVP is not only dose-dependent, but also PP-dependent, which is indicated by the reduced perfusion relative to control with low-dosed AVP at low PP.
PMCID: PMC3207716  PMID: 21791588

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