Comparison of Choroidal and Optic Nerve Head Blood Flow Regulation during Changes in Ocular Perfusion Pressure

Schmidl, Doreen; Boltz, Agnes; Kaya, Semira; Werkmeister, René M.; Dragostinoff, Nikolaus; Lasta, Michael; Polska, Elżbieta; Garhöfer, Gerhard; Schmetterer, Leopold

doi:10.1167/iovs.11-9055

Cited by 69 publications

(81 citation statements)

References 61 publications

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“…This is in accordance with data from a previous study performed in our laboratory, where autoregulation in the ONH started to fail at OPP values of 66% over baseline. 11 In contrast, a similar study performed by Movaffaghy et al found no cutoff point for the upper limit up ONHBF autoregulation, but their study participants only reached OPP values of 30 6 8% over baseline. 22 As in the choroid, NO is an important regulator of basal blood flow in the ONH, since administration of L-NMMA significantly decreased ONHBF.…”

Section: Discussionmentioning

confidence: 57%

“…11,22 As shown in Figure 6, ONHBF started to increase significantly when OPP was raised to values between 55% and 70% over baseline, when no drug or placebo was administered. This is in accordance with data from a previous study performed in our laboratory, where autoregulation in the ONH started to fail at OPP values of 66% over baseline.…”

Section: Discussionmentioning

confidence: 90%

“…[8][9][10] Studies done in healthy humans also indicated that choroidal blood flow is autoregulated when OPP either was increased during isometric exercise or decreased during an artificial IOP increase. [11][12][13][14][15][16] In contrast, only few data on optic nerve head (ONH) blood flow regulation during changes in OPP are available. A study performed recently in our laboratory has shown that autoregulation also is present in the ONH, but has a different regulatory range than that observed in the choroid.…”

Section: Methodsmentioning

confidence: 99%

“…A study performed recently in our laboratory has shown that autoregulation also is present in the ONH, but has a different regulatory range than that observed in the choroid. 11 ONH blood flow (ONHBF) seems to be regulated in response to an acute experimental increase and decrease in OPP. Studies supporting the autoregulatory capacity have been performed in healthy humans, nonhuman primates, cats, and rabbits.…”

Section: Methodsmentioning

confidence: 99%

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Role of Nitric Oxide in Optic Nerve Head Blood Flow Regulation during Isometric Exercise in Healthy Humans

Schmidl¹,

Boltz

Kaya³

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. We determined whether administration of a nitric oxide synthase (NOS) inhibitor alters optic nerve head blood flow (ONHBF) regulation during isometric exercise in healthy subjects. METHODS.Our study was done in a randomized, placebocontrolled, double-masked, three-way crossover design. A total of 18 healthy subjects was randomized to receive either placebo, phenylephrine, or an inhibitor of NOS (L-NMMA) on three different study days. ONHBF was measured with laser Doppler flowmetry while the study participants performed isometric exercise (squatting). This was done before drug administration and during infusion of the study drugs. Mean arterial pressure (MAP) and IOP were measured noninvasively, and ocular perfusion pressure (OPP) was calculated as 2/3 MAP À IOP.RESULTS. The response in ONHBF to isometric exercise was less pronounced than the response in OPP, indicating for some autoregulatory capacity in the ONH. Administration of L-NMMA significantly decreased ONHBF at rest (P < 0.01). In contrast, inhibition of NOS did not alter the pressure-flow relationship in the ONH during an experimental increase in OPP compared to phenylephrine and placebo (P ¼ 0.37 between groups).CONCLUSIONS. The data of our study support previous findings that ONHBF is autoregulated during an experimental increase in OPP. Nitric oxide has an important role in basal ONHBF regulation, but seems not to be involved in the autoregulatory response during an increase in OPP induced by isometric exercise. (ClinicalTrials.gov number, NCT00806741.) (Invest Ophthalmol Vis Sci.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Role of Nitric Oxide in Optic Nerve Head Blood Flow Regulation during Isometric Exercise in Healthy Humans

Schmidl¹,

Boltz

Kaya³

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…63 It would be interesting to also analyze data when OPP is decreased. We have done some experiments during a suction cup-induced increase in IOP, 33,34,53,81 but the number of subjects included in these previous studies is not sufficient to allow for the type of analysis applied in this report. Given that LDF was used in our experiments, measurements of blood flow are restricted to the subfoveal choroid.…”

Section: Discussionmentioning

confidence: 99%

Factors Associated With Choroidal Blood Flow Regulation in Healthy Young Subjects

Schmidl

Schmetterer

Witkowska

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To analyze regulation of subfoveal choroidal blood flow (FLOW) during isometric exercise in healthy subjects in dependence of intraocular pressure (IOP), mean arterial pressure (MAP), ocular perfusion pressure (OPP), age, sex, fasting glucose, cholesterol, triglycerides, creatinine, and C-reactive protein levels and hematocrit. METHODS.We retrospectively analyzed results obtained in 261 healthy subjects who underwent a period of 6 minutes of isometric exercise during which FLOW was measured continuously and MAP was measured every minute. From these data, OPP and choroidal pressure/flow curves were calculated. Subjects were grouped into tertiles with regard to the dependent variables, and pressure/flow relationships were compared. RESULTS.Choroidal blood flow started to increase at OPP values of approximately 65% dependent on the MAP/IOP tertile. A significant increase of FLOW from baseline was noted at 67.7 6 2.1% in the lowest MAP tertile, at 67.7 6 2.0% in the second MAP tertile, and at 61.8 6 2.0% in the highest MAP tertile (P ¼ 0.01). At the three IOP levels, FLOW started to increase at an OPP increase of 69.8 6 2.1%, 70.1 6 2.2%, and 65.4 6 1.9% above baseline, respectively (P ¼ 0.03). Choroidal pressure/flow curves were independent of the other variables.CONCLUSIONS. The present analysis indicates that FLOW regulation during isometric exercise is dependent on absolute MAP as well as IOP levels. This indicates that regulation depends on pressure levels at both the arterial and the venous side of the choroidal circulation and highlights the complexity of FLOW regulation during changes in OPP that cannot be simply characterized by classical autoregulation models.Keywords: choroidal blood flow, blood pressure, autoregulation T he choroid is a richly vascularized tissue that oxygenizes the outer retina including the photoreceptors.1,2 Regulation of blood flow in the choroid in response to changes in ocular perfusion pressure (OPP) is complex.3 For decades the choroidal vasculature was considered a passive vascular bed showing a linear pressure/flow relationship. In the early 1990s, however, a landmark paper proved that the pressure/flow relationship is nonlinear in the rabbit. 4 This result was later verified in a wide variety of rabbit experiments. [5][6][7][8][9][10][11][12][13][14][15] In humans, evidence for active choroidal blood flow (FLOW) regulation was obtained during an increase in OPP as well as during a decrease in OPP. [16][17][18][19][20][21] Alterations of FLOW regulation during changes in perfusion pressure were observed in patients with age-related macular degeneration, 22 We set out to analyze factors associated with the regulatory capacity of the choroid during isometric exercise-induced changes in OPP. For this purpose, we analyzed data that were previously collected in clinical studies in our department. Tested parameters included arterial blood pressure, intraocular pressure (IOP), OPP, heart rate, age, and sex as well as several factors measured in blood plasma and serum. METHOD...

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The Effect of Orally Administered Dronabinol on Optic Nerve Head Blood Flow in Healthy Subjects—A Randomized Clinical Trial

Hommer

Kallab

Szegedi

et al. 2020

Clin Pharma and Therapeutics

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It has been hypothesized that besides its intraocular pressure (IOP) lowering potential, tetrahydrocannabinol (THC) may also improve ocular hemodynamics. The aim of the present study was to investigate whether single oral administration of dronabinol, a synthetic THC, alters optic nerve head blood flow (ONHBF) and its regulation in healthy subjects. The study was carried out in a randomized, placebo‐controlled, double‐masked, two‐way crossover design in 24 healthy subjects. For each study participant, 2 study days were scheduled, on which they either received capsules containing 5 mg dronabinol or placebo. ONHBF was measured with laser Doppler flowmetry at rest and while the study participants performed isometric exercise for 6 minutes to increase mean arterial blood pressure (MAP). This was repeated 1 hour after drug intake. Ocular perfusion pressure (OPP) was calculated as 2/3MAP–IOP. Dronabinol was well tolerated and no cannabinoid‐related psychoactive effects were reported. Neither administration of dronabinol nor placebo had an effect on IOP, MAP, or OPP. In contrast, dronabinol significantly increased ONHBF at rest by 9.5 ± 8.1%, whereas placebo did not show a change in ONHBF (0.3 ± 7.4% vs. baseline, P < 0.001 between study days). Dronabinol did not alter the autoregulatory response of ONHBF to isometric exercise. In conclusion, the present data indicate that low‐dose dronabinol increases ONHBF in healthy subjects without affecting IOP, OPP, or inducing psychoactive side effects. In addition, dronabinol does not alter the autoregulatory response of ONHBF to an experimental increase in OPP. Further studies are needed to investigate whether this effect can also be observed in patients with glaucoma.

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Comparison of Choroidal and Optic Nerve Head Blood Flow Regulation during Changes in Ocular Perfusion Pressure

Cited by 69 publications

References 61 publications

Role of Nitric Oxide in Optic Nerve Head Blood Flow Regulation during Isometric Exercise in Healthy Humans

Role of Nitric Oxide in Optic Nerve Head Blood Flow Regulation during Isometric Exercise in Healthy Humans

Factors Associated With Choroidal Blood Flow Regulation in Healthy Young Subjects

The Effect of Orally Administered Dronabinol on Optic Nerve Head Blood Flow in Healthy Subjects—A Randomized Clinical Trial

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