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ABSTRACT: Die wichtige Rolle des vaskulären endothelialen Wachstumsfaktors (VEGF) bei vielen neovaskulären und exsudativen Erkrankungen
des Auges hat sich in den letzten Jahren in zahlreichen experimentellen und klinischen Studien herausgestellt. Das therapeutische
Konzept der Anti-VEGF-Therapie zeigte sich in zahlreichen prospektiven, kontrollierten Studien mit unterschiedlichen Anti-VEGF-Präparaten
als viel versprechend. Besonders bei der neovaskulären altersbezogenen Makuladegeneration (AMD) scheint es möglich geworden
zu sein, nicht nur den Visusverlust zu verlangsamen, sondern in einem nicht unerheblichen Anteil der Patienten eine Visusverbesserung
zu erreichen. Bevacizumab (Avastin®) ist ein monoklonaler Antikörper, der alle Isoformen des VEGF bindet. Er wurde primär für die systemische Therapie in der
Onkologie entwickelt. Prospektive und retrospektive Fallserien zur systemischen und intravitrealen Anwendung von Bevacizumab
bei der neovaskulären AMD aber auch bei anderen neovaskulären und exsudativen Erkrankungen des Auges haben sehr viel versprechende
Ergebnisse bei insgesamt gutem Sicherheitsprofil gezeigt. Es ist jedoch nicht davon auszugehen, dass Bevacizumab in nächster
Zukunft eine Zulassung für die Anwendung in der Augenheilkunde erhalten wird. Wie bei vielen anderen Präparaten in der Augenheilkunde
wird die Behandlung mit Bevacizumab weiterhin nur off label oder in klinischen Studien möglich sein. Um die Rolle von Bevacizumab
bei der Behandlung verschiedener Augenerkrankungen abschließend bewerten zu können, bleiben jedoch prospektive Langzeitstudien
abzuwarten.
A number of experimental and clinical studies have show the important role of the vascular endothelial growth factor (VEGF)
in most neovascular and exudative ocular diseases. The therapeutic concept of an anti-VEGF therapy has been most promising
in a number of prospective controlled clinical trials. In the treatment of neovascular age-related macular degeneration (AMD)
intravitreal anti-VEGF therapy has shown not only to stabilize vision in most patients, but also to improve vision in a significant
number of patients. Bevacizumab (Avastin®) is a monoclonal antibody designed to bind all isoforms of VEGF. It has been primarily developed for the systemic treatment
of colon cancer in oncology. But several prospective and retrospective case series evaluating the use of systemic and intravitreal
bevacizumab in neovascular AMD and other neovascular and exudative ocular diseases have shown most promising results. Despite
the fact that results of large, prospective, long-term studies are currently unavailable, a number of studies have shown anatomic,
functional and safety results up to 6 months similar to other anti-VEGF drugs. An approval of bevacizumab in ophthalmology
by regulatory agencies cannot be expected in the near future. Similar to a number of drugs in clinical use, bevacizumab will
remain available in ophthalmology only as off label treatment or in clinical trials. To clarify the role of bevacizumab for
the treatment of a number of neovascular and exudative eye diseases, prospective long-term studies are necessary.
Spektrum der Augenheilkunde 04/2012; 21(3):154-159. · 0.26 Impact Factor
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ABSTRACT: The evaluation of OCT3 during anti-VEGF therapy.
A total of 29 patients with choroidal neovascularization secondary to AMD received 3 intravitreal injections of ranibizumab. OCT examination and visual acuity testing (ETDRS) were performed before therapy onset, after 1 week and after 1, 2 and 3 months.
The central retinal thickness (CRT) was assessed correctly by OCT in 128 out of 145 measurements. There was a distinct (84%) but not significant correlation between decrease in central retinal thickness and increase in visual acuity. Incorrect retinal layer segmentation and inadequate CRT measurements were a significant technical limitation.
During anti-VEGF therapy, OCT allows documentation and quantification of morphologic retinal changes and in most cases also for an estimation of functional improvement.
Der Ophthalmologe 08/2008; 105(7):650-5. · 0.62 Impact Factor
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ABSTRACT: HintergrundDie Evaluierung des OCT3 während einer Anti-VEGF-Therapie.
MethodikIm Rahmen einer AMD bekamen 29 Patienten mit choroidalen Neovaskularisationen insgesamt 3 intravitreale Injektionen mit Ranibizumab.
Vor Therapiebeginn, nach 1Woche sowie nach 1, 2 und 3Monaten wurden OCT3-Untersuchungen durchgeführt sowie der Visus (ETDRS)
ermittelt.
ErgebnisseDie zentrale Netzhautdicke konnte mit dem OCT3 in 128 von 145 Messungen automatisch quantifiziert werden. Bei Monat3 fand
sich ein im Vergleich zur Baseline deutlicher Zusammenhang zwischen Abnahme der zentralen Netzhautdicke und Zunahme des Visus
(84%), jedoch keine statistisch signifikante Korrelation (Pearson=−0,18). Generelle Einschränkungen waren eine inkorrekte
Schichtensegmentierung und eine inadäquate Berechnung der zentralen Netzhautdicke bei ausgeprägten retinalen Läsionen.
SchlussfolgerungWährend einer Anti-VEGF-Therapie ermöglicht das OCT3 Dokumentation und Quantifizierung morphologischer Netzhautveränderungen
und erlaubt in der Mehrzahl der Fälle auch Rückschlüsse auf funktionelle Verbesserungen. Ein direkter Zusammenhang zwischen
Abnahme der Netzhautdicke in der OCT und Zunahme des Visus war jedoch nicht gegeben.
BackgroundThe evaluation of OCT3 during anti-VEGF therapy.
MethodsA total of 29 patients with choroidal neovascularization secondary to AMD received 3 intravitreal injections of ranibizumab.
OCT examination and visual acuity testing (ETDRS) were performed before therapy onset, after 1 week and after 1, 2 and 3 months.
ResultsThe central retinal thickness (CRT) was assessed correctly by OCT in 128 out of 145 measurements. There was a distinct (84%)
but not significant correlation between decrease in central retinal thickness and increase in visual acuity. Incorrect retinal
layer segmentation and inadequate CRT measurements were a significant technical limitation.
ConclusionDuring anti-VEGF therapy, OCT allows documentation and quantification of morphologic retinal changes and in most cases also
for an estimation of functional improvement.
Der Ophthalmologe 06/2008; 105(7):650-655. · 0.62 Impact Factor
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ABSTRACT: Recent advances in optical coherence tomography (OCT) have made it possible to increase resolution and scan velocities so that even greater central areas of the retina can be scanned. The aim of this study is to describe the possibilities offered by this new technology for age-related macular degeneration.
The study included 20 patients with confirmed active choroidal neovascularization (CNV) as well as pigment epithelial detachment (PED). Three-dimensional imaging was performed with a high-definition raster scanning OCT system (HD-OCT) with an axial resolution of 6 microm and a scan velocity of up to 20,000 A-scans/s. The scanned area measured 6 x 6 mm with a depth of 2 mm. Two-dimensional imaging was carried out with a StratusOCT (Carl Zeiss Meditec).
Comparison of the individual slices showed improved identification of intra- and subretinal structures with the HD-OCT. Demarcation of pathological changes in individual retinal layers is possible with the HD-OCT. Summation images permit accurate localization of a scan. Topographic and volumetric evaluations enable analysis of individual compartments in the entire scanned area and are suitable for monitoring treatment of CNV with anti-VEGF therapy. The raster method decreases the dependence on exploratory methods that have been necessary until now to generate retinal thickness maps.
This report presents initial experience in using a raster scanning HD-OCT system in patients with neovascular age-related macular degeneration and describes new evaluation functions that aid in obtaining more precise assessment of treatment effect and its impact on the retinal ultrastructure. The results of this study clearly show that development of high-resolution OCT systems in conjunction with development of novel treatment options for exudative diseases offers promising perspectives.
Der Ophthalmologe 04/2008; 105(3):248-54. · 0.62 Impact Factor
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ABSTRACT: HintergrundDie Weiterentwicklung der optischen Kohärenztomographie (OCT) in den letzten Jahren ermöglichte neben einer Erhöhung der Auflösung
immer höhere Scangeschwindigkeiten, mit der das Abtasten größerer zentraler Netzhautareale möglich wird. Ziel dieser Studie
war es, die Möglichkeiten dieser neuen Technologie bei altersbedingter Makuladegeneration zu beschreiben.
Material und MethodenZwanzig konsekutive Patienten, bei denen sowohl eine aktive choroidale Neovaskularisation (CNV) als auch eine Pigmentepithelabhebung
(PED) nachgewiesen wurde, wurden inkludiert. Die 3-dimensionale Bildgebung erfolgte durch ein hochauflösendes, rasterscannendes
OCT-System (HD-OCT) mit einer axialen Auflösung von 6μm und einer Scangeschwindigkeit von bis zu 20.000 A-Scans pro Sekunde.
Der gescannte Bereich maß 6×6mm bei 2mm Tiefe. Die 2-dimensionale Bildgebung wurde mit einem Stratus®-OCT (Carl Zeiss Meditec)
durchgeführt.
ErgebnisseDer Vergleich der Einzelschnitte zeigt eine bessere Identifizierung intra- und subretinaler Strukturen durch das HD-OCT. Eine
Eingrenzung der Pathologie auf einzelne Netzhautschichten wird im HD-OCT möglich. Summationsbilder erlauben die genaue Lokalisation
eines Scans. Topographische und volumetrische Auswertungen ermöglichen die Analyse einzelner Kompartimente im gescannten Areal
und eignen sich zur Therapiekontrolle bei CNV unter Anti-VEGF-Therapie. Die Rastermethode reduziert die Abhängigkeit von den
bisher zur Erstellung von Netzhautdickenkarten benötigten Extrapolationsmethoden.
SchlussfolgerungenDie vorliegende Arbeit präsentiert erste Ergebnisse des Einsatzes eines rasterscannenden, hochauflösenden OCT-Systems bei
Patienten mit neovaskulärer altersbedingter Makuladegeneration und stellt neue Auswertungsfunktionen vor, mit deren Hilfe
exaktere Aussagen zu Therapieeffekt und dessen Auswirkungen auf die retinale Ultrastruktur gemacht werden können. Die Ergebnisse
der vorliegenden Studie verdeutlichen, dass die Entwicklung hochauflösender OCT-Systeme begleitend zur Entwicklung neuartiger
Behandlungsoptionen exsudativer Erkrankungen vielversprechende Perspektiven bietet.
BackgroundRecent advances in optical coherence tomography (OCT) have made it possible to increase resolution and scan velocities so
that even greater central areas of the retina can be scanned. The aim of this study is to describe the possibilities offered
by this new technology for age-related macular degeneration.
Material and methodsThe study included 20 patients with confirmed active choroidal neovascularization (CNV) as well as pigment epithelial detachment
(PED). Three-dimensional imaging was performed with a high-definition raster scanning OCT system (HD-OCT) with an axial resolution
of 6 µm and a scan velocity of up to 20,000 A-scans/s. The scanned area measured 6×6 mm with a depth of 2 mm. Two-dimensional
imaging was carried out with a Stratus®OCT (Carl Zeiss Meditec).
ResultsComparison of the individual slices showed improved identification of intra- and subretinal structures with the HD-OCT. Demarcation
of pathological changes in individual retinal layers is possible with the HD-OCT. Summation images permit accurate localization
of a scan. Topographic and volumetric evaluations enable analysis of individual compartments in the entire scanned area and
are suitable for monitoring treatment of CNV with anti-VEGF therapy. The raster method decreases the dependence on exploratory
methods that have been necessary until now to generate retinal thickness maps.
ConclusionsThis report presents initial experience in using a raster scanning HD-OCT system in patients with neovascular age-related
macular degeneration and describes new evaluation functions that aid in obtaining more precise assessment of treatment effect
and its impact on the retinal ultrastructure. The results of this study clearly show that development of high-resolution OCT
systems in conjunction with development of novel treatment options for exudative diseases offers promising perspectives.
Der Ophthalmologe 02/2008; 105(3):248-254. · 0.62 Impact Factor
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ABSTRACT: To investigate a potential difference in ocular vascular reactivity during carbogen breathing in optic nerve head, choroid, and retina between healthy smokers and non-smokers.
25 (13 smokers and 12 non-smokers) healthy male volunteers participated in this observer masked, two cohort study. During inhalation of carbogen (5% CO(2) and 95% O(2)) over 10 minutes measurements were taken using laser Doppler flowmetry to assess submacular choroidal and optic nerve head blood flow, laser interferometry to assess fundus pulsation amplitudes, and retinal vessel analyser (RVA) to assess retinal vessel diameters.
At baseline choroidal blood flow was higher (p = 0.018, ANOVA) in smokers than in non-smokers. During administration of carbogen the response in choroidal blood flow was significantly different between the two groups: there was an increase in non-smokers after carbogen breathing (p = 0.048) compared with relatively stable blood flow in smokers (p = 0.049 between groups, ANOVA). A similar response pattern was seen for fundus pulsation amplitude, which increased notably after carbogen breathing in non-smokers but not in smokers (p<0.001 between groups, ANOVA). Optic nerve head blood flow and retinal vessel diameters were reduced in both groups to a comparable degree during carbogen breathing.
The study indicated abnormal choroidal vascular reactivity in chronic smokers. These early haemodynamic changes may be related to the increased risk to smokers of developing ocular vascular diseases. The specific mechanisms underlying abnormal choroidal vascular reactivity in chronic smokers remain to be characterised.
British Journal of Ophthalmology 07/2004; 88(6):776-81. · 2.90 Impact Factor
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ABSTRACT: Aims/background: To investigate the reproducibility and potential diurnal variation of choroidal blood flow parameters in healthy subjects over a period of 12 hours.
The choroidal blood flow parameters of 16 healthy non-smoking subjects were measured at five time points during the day (8:00, 11:00, 14:00, 17:00, and 20:00). Outcome parameters were pulsatile ocular blood flow as assessed by pneumotonometry, fundus pulsation amplitude as assessed by laser interferometry, blood velocities in the opthalmic and posterior ciliary arteries as assessed by colour Doppler imaging, and choroidal blood flow, volume, and velocity as assessed by fundus camera based laser Doppler flowmetry. The coefficient of variation and the maximum change from baseline in an individual were calculated for each outcome parameter.
None of the techniques used found a diurnal variation in choroidal blood flow. Coefficients of variation were within 2.9% and 13.6% for all outcome parameters. The maximum change from baseline in an individual was much higher, ranging from 11.2% to 58.8%.
These data indicate that in healthy subjects the selected techniques provide adequate reproducibility to be used in clinical studies. Variability may, however, be considerably higher in older subjects or subjects with ocular disease. The higher individual differences in flow parameter readings limit the use of the techniques in clinical practice. To overcome problems with measurement validity, a clinical trial should include as many choroidal blood flow outcome parameters as possible to check for consistency.
British Journal of Ophthalmology 05/2004; 88(4):533-7. · 2.90 Impact Factor
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ABSTRACT: Untreated hypertension is associated with ocular complications and is a risk factor for the development and progression of vascular ocular pathologies. We set out to investigate the association between systemic blood pressure and choroidal blood flow.
All subjects were male non-smokers, who did not receive any medication and had normal or slightly elevated blood pressure (systolic blood pressure < or = 160 mmHg; diastolic blood pressure < or = 100 mmHg). The association between systemic blood pressure and fundus pulsation amplitude, a measure of pulsatile choroidal blood flow, was investigated in 318 volunteers. In addition, the association between systemic blood pressure and blood flow velocities in the posterior ciliary arteries supplying the choroid was investigated in these subjects.
Ocular fundus pulsation amplitude (r = 0.252; P < 0.001) and mean flow velocity in the posterior ciliary arteries (r = 0.346, P < 0.001) were significantly associated with mean arterial pressure. The correlation of ocular haemodynamic variables with systolic and diastolic blood pressure was in the same range.
Our data indicate a small, but significant increase in choroidal blood flow with increasing blood pressure.
Eye 01/2003; 17(1):84-8. · 1.85 Impact Factor
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ABSTRACT: Purpose Untreated hypertension is associated with ocular complications and is a risk factor for the development and progression of vascular ocular pathologies. We set out to investigate the association between systemic blood pressure and choroidal blood flow.Methods All subjects were male non-smokers, who did not receive any medication and had normal or slightly elevated blood pressure (systolic blood pressure 160 mmHg; diastolic blood pressure 100 mmHg). The association between systemic blood pressure and fundus pulsation amplitude, a measure of pulsatile choroidal blood flow, was investigated in 318 volunteers. In addition, the association between systemic blood pressure and blood flow velocities in the posterior ciliary arteries supplying the choroid was investigated in these subjects.Results Ocular fundus pulsation amplitude (r=0.252; P<0.001) and mean flow velocity in the posterior ciliary arteries (r=0.346, P<0.001) were significantly associated with mean arterial pressure. The correlation of ocular haemodynamic variables with systolic and diastolic blood pressure was in the same range.Conclusions Our data indicate a small, but significant increase in choroidal blood flow with increasing blood pressure.Keywords: choroidal blood flow, fundus pulsation, Doppler sonography, hypertensive retinopathy
Eye 12/2002; 17(1):84-88. · 1.85 Impact Factor
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ABSTRACT: To determine the effects of various mixtures of O(2) and CO(2) on retinal blood flow in healthy subjects.
A randomised, double masked, four way crossover trial was carried out in 12 healthy male non-smoking subjects. Gas mixtures (100% O(2), 97.5% O(2) + 2.5% CO(2), 95% O(2) + 5% CO(2), and 92% O(2) + 8% CO(2)) were administered for 10 minutes each. Two non-invasive methods were used: laser Doppler velocimetry (LDV) for measurement of retinal blood velocity and fundus imaging with the Zeiss retinal vessel analyser (RVA) for the assessment of retinal vessel diameters. Arterial pH, pCO(2), and pO(2) were determined with an automatic blood gas analysis system. Retinal blood flow through a major temporal vein was calculated.
Retinal blood velocity, retinal vessel diameter, and retinal blood flow decreased during all breathing periods (p <0.001 each). Administration of 92% O(2) + 8% CO(2) significantly increased SBP, MAP, and PR (p <0.001 each, versus baseline), whereas the other gas mixtures had little effect on systemic haemodynamics. Addition of 2.5%, 5%, and 8% CO(2) to oxygen caused a marked decrease in pH and an increase in pCO(2) (p <0.001 versus pure oxygen).
Breathing of pure oxygen and oxygen in combination with carbon dioxide significantly decreases retinal blood flow. Based on these data the authors speculate that hyperoxia induced vasoconstriction is not due to changes in intravascular pH and cannot be counteracted by an intravascular increase in pCO(2).
British Journal of Ophthalmology 10/2002; 86(10):1143-7. · 2.90 Impact Factor
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ABSTRACT: To characterize the role of the endothelin system in the blood flow control of the optic nerve head and of the choroid in humans.
Two studies were performed in healthy subjects. Study 1 was a randomized, placebo-controlled, double-masked, balanced, two-way crossover design and study 2 a three way-way crossover design. In study 1 twelve healthy male subjects received endothelin (ET)-1 in stepwise increasing doses of 1.25, 2.5, and 5 ng/kg x min (each infusion step occurred over 20 minutes) coinfused with BQ123 (60 microg/kg x min) or placebo on two different study days. In study 2 twelve healthy male subjects received two doses of BQ123 (60 or 120 microg/kg x min over 60 minutes) or placebo on three different study days. Measurements of optic nerve head blood flow (ONHBF) and choroidal blood flow (ChBF) were performed with laser Doppler flowmetry in both studies. In study 2 mean flow velocity (MFV) of the ophthalmic artery was assessed with Doppler sonography.
In study 1, ET-1 significantly decreased ONHBF (-22.8% +/- 4.3% at 5 ng/kg x min, P = 0.003 versus baseline) and ChBF (-21.7% +/- 3.2% at 5 ng/kg x min, P = 0.0001 versus baseline). The effect of the highest administered dose of exogenous ET-1 on ONHBF was significantly attenuated (P = 0.04, ANOVA) by coinfusion of BQ123. Effects of exogenous ET-1 on blood flow (2.5 ng/kg x min ET-1 or higher) also were attenuated in the choroid by coinfusion of BQ123 (ChBF: P = 0.03, ANOVA). In study 2, both dosages of BQ123 significantly increased MFV in the ophthalmic artery (60 microg/kg x min, 12.5% +/- 7.3%; 120 microg/kg x min, 17.2% +/- 9.2%, versus baseline; P = 0.001), but did not change blood flow in the ONH or the choroid.
BQ123 antagonizes the effects of exogenously administered ET-1 on blood flow in the ONH and the choroid. The data indicate, however, that ET-1 does not substantially contribute to the regulation of basal vascular tone in these tissues.
Investigative Ophthalmology & Visual Science 12/2001; 42(12):2949-56. · 3.60 Impact Factor
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ABSTRACT: In the recent years it has been recognized that nitric oxide is an important regulator of ocular blood flow. Nitric oxide is involved in the control of basal blood flow in the choroid, optic nerve and the retina. In addition, nitric oxide mediates a number of vasodilator responses in ocular vessels to agonists such as acetylcholine, bradykinin, histamine, substance P and insulin. Nitric oxide also plays a role in hypercapnia-induced vasodilation in the choroid and is a modulator of pressure autoregulation in this vascular bed. Abnormalities of the L-arginine/nitric oxide system have been observed in a variety of ocular diseases including glaucoma, diabetic retinopathy and retinopathy of prematurity. This makes the L-arginine/nitric oxide pathway an attractive target for therapeutic interventions. Additional research is required, particularly in characterizing the role of the three nitric oxide synthase isoforms in the control of ocular perfusion, to implement this concept into the clinical management of ocular diseases.
Progress in Retinal and Eye Research 12/2001; 20(6):823-47. · 9.45 Impact Factor
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G Rainer,
B Kiss,
S Dallinger,
O Findl,
M Georgopoulos,
C Vass,
R Menapace, K Polak,
H G Eichler,
M Wolzt,
L Schmetterer
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ABSTRACT: To investigate whether nifedipine affects ocular perfusion or visual fields in open angle glaucoma patients.
In a parallel group study nifedipine or placebo was administered for 3 months (n = 30). Ocular fundus pulsation amplitude (FPA), cup blood flow (Flowcup) and visual field mean deviation (MD) were measured.
Five patients receiving nifedipine discontinued due to adverse events. Nifedipine did not affect FPA [difference: 0.3 microm (95% CI -0.3,0.9); P = 0.70], Flowcup: [difference: -9 rel.units (95% CI -133,114); P = 0.99], or MD [difference: 0.2dB (95% CI -2.2,2.7); P = 0.51] vs placebo.
Systemic nifedipine is not well tolerated in glaucoma patients and exerts no effect on visual fields or ocular perfusion.
British Journal of Clinical Pharmacology 09/2001; 52(2):210-2. · 2.96 Impact Factor
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ABSTRACT: The aim of the present study was to investigate the association between systemic blood pressure and retinal blood flow in healthy young subjects.
Three independent study cohorts were included. A cross-sectional study was performed in 420 young male subjects with systolic blood pressure < 160 mmHg and diastolic blood pressure <100 mmHg. Retinal white blood cell flux (n=210) and blood velocity in the central retinal artery (n=210) were measured. In addition, a longitudinal study was performed in 40 young male subjects in whom retinal and systemic haemodynamic parameters were measured thrice within 6 weeks. Retinal white blood cell flux was measured with the blue-field entoptic technique. Blood flow velocity in the central retinal artery was measured by means of colour Doppler imaging.
Retinal white blood cell flux (r=0.262; P<0.001) and mean flow velocity in the central retinal artery (r=0.174, P=0.010) were significantly associated with mean arterial pressure in the cross-sectional study. In the longitudinal study retinal white blood cell flux and mean flow velocity in the central retinal artery were also correlated with systemic blood pressure.
Our data indicate a slight but significant increase in retinal blood flow with blood pressure. Whether this is of clinical relevance in eye diseases with altered retinal perfusion, such as diabetic retinopathy, remains to be established.
Albrecht von Graæes Archiv für Ophthalmologie 09/2001; 239(9):673-7. · 2.17 Impact Factor
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ABSTRACT: There is evidence that insulin and glucose cause renal and ocular vasodilation. There is, however, currently no data on the effect of combined hyperglycaemia and hyperinsulinaemia on the renal and ocular blood flow seen in diabetic patients on insulin therapy.
We carried out two different 3-way crossover studies in healthy subjects (each, n = 9). In study one, hyperglycaemic clamps (5.6 mmol/l, 11.1 mmol/ 1, 16.7 mmol/l) were carried out during placebo or insulin (dose 1: 1 mU/kg/min; dose 2: 2 mU/kg/min) infusion. The second study was identical but endogenous insulin secretion was blocked with somatostatin. The renal plasma flow, glomerular filtration rate and pulsatile choroidal blood flow were measured using the paraaminohippurate method, the inulin method and a laser interferometric measurement of fundus pulsation amplitude, respectively.
Insulin increased renal plasma flow and fundus pulsation amplitude but not the glomerular filtration rate. Hyperglycaemia increased all the renal and ocular parameters studied. Haemodynamic effects of glucose and insulin were additive when somatostatin was co-administered but not under basal conditions.
Glucose and insulin can exert additive vasodilator properties on renal and ocular circulation. To find out whether this observation is related to the increased regional perfusion in diabetes longitudinal studies on patients with Type I (insulin-dependent) diabetes mellitus are needed.
Diabetologia 02/2001; 44(1):95-103. · 6.81 Impact Factor
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ABSTRACT: The autoregulatory capacity of the human retina is well documented, but the pressure-flow relationship of the human choroid is still a matter of controversy. Recent data, using laser Doppler flowmetry to measure choroidal blood flow, indicate that the choroid has some autoregulatory potential, whereas most data using other techniques for the assessment of choroidal hemodynamics indicate that the choroidal pressure-flow curve is linear. We used a new laser interferometric technique to characterize choroidal blood flow during isometric exercise. Twenty healthy subjects performed squatting for 6 min during normocapnia and during inhalation of 5% CO2 and 95% air. Ocular fundus pulsation amplitude, flow velocities in the ophthalmic artery, intraocular pressure, and systemic hemodynamics were measured in 2-min intervals. To gain information on choroidal blood flow fundus pulsation amplitude was corrected for changes in flow pulsatility using data from the ophthalmic artery and for changes in pulse rate. Ocular perfusion pressure was calculated from mean arterial pressure and intraocular pressure. The ocular pressure-flow relationship was calculated by sorting data according to ascending ocular perfusion pressure values. In a pilot study in 6 healthy subjects comparable ocular pressure flow relationships were obtained when choroidal blood flow was assessed with the method described above and with laser Doppler flowmetry. In the main study isometric exercise caused a significant increase in mean arterial pressure (56%, P < 0.001), pulse rate (84%, P < 0.001), and intraocular pressure (37%, P 0.004), but decreased fundus pulsation amplitude (-36%, P < 0.001). Significant deviations from baseline choroidal blood flow were observed only at ocular perfusion pressures >69% during normocapnia and 70% during hypercapnia. Our data indicate that during isometric exercise the choroid has a high capacity to keep blood flow constant despite changes in perfusion pressure and that this pressure-flow relationship is not altered by moderate changes in arterial carbon dioxide levels.
Microvascular Research 01/2001; 61(1):1-13. · 2.83 Impact Factor
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ABSTRACT: Elevated plasma free fatty acids (FFA) induce skeletal muscle insulin resistance and impair endothelial function. The aim of this study was to characterize the acute hemodynamic effects of FFA in the eye and skin. A triglyceride (Intralipid 20%, 1.5 ml/min)/heparin (bolus: 200 IU; constant infusion rate: 0.2 IU. kg(-1). min(-1)) emulsion or placebo was administered to 10 healthy subjects. Measurements of pulsatile choroidal blood flow with laser interferometry, retinal blood flow with the blue field entoptic technique, peak systolic and end diastolic blood velocity (PSV, EDV) in the ophthalmic artery with Doppler sonography, and subcutaneous blood flow with laser Doppler flowmetry were performed during an euglycemic somatostatin-insulin clamp over 405 min. Plasma FFA/triglyceride elevation induced a rise in pulsatile choroidal blood flow by 25 +/- 3% (P < 0.001) and in retinal blood flow by 60 +/- 23% (P = 0.0125). PSV increased by 27 +/- 8% (P = 0.001), whereas EDV was not affected. Skin blood flow increased by 149 +/- 38% (P = 0.001). Mean blood pressure and pulse rate remained unchanged, whereas pulse pressure amplitude increased by 17 +/- 5% (P = 0.019). Infusion of heparin alone had no hemodynamic effect in the eye or skin. In conclusion, FFA/triglyceride elevation increases subcutaneous and ocular blood flow with a more pronounced effect in the retina than in the choroid, which may play a role for early changes of ocular perfusion in the insulin resistance syndrome.
AJP Regulatory Integrative and Comparative Physiology 01/2001; 280(1):R56-61. · 3.34 Impact Factor
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ABSTRACT: To investigate the reproducibility and sensitivity of the Zeiss retinal vessel analyser, a new method for the online determination of retinal vessel diameters in healthy subjects.
Two model drugs were administered, a peripheral vasoconstrictor (the alpha receptor agonist phenylephrine) and a peripheral vasodilator (the nitric oxide donor sodium nitroprusside) in stepwise increasing doses. Nine healthy young subjects were studied in a placebo controlled double masked three way crossover design. Subjects received intravenous infusions of either placebo or stepwise increasing doses of phenylephrine (0.5, 1, or 2 microg/kg/min) or sodium nitroprusside (0.5, 1, or 2 microg/kg/min). Retinal vessel diameters were measured with the new Zeiss retinal vessel analyser. Retinal leucocyte velocity, flow, and density were measured with the blue field entoptic technique. The reproducibility of measurements was assessed with coefficients of variation and intraclass correlation coefficients.
Placebo and phenylephrine did not influence retinal haemodynamics, although the alpha receptor antagonist significantly increased blood pressure. Sodium nitroprusside induced a significant increase in retinal venous and arterial diameters (p<0.001 each), leucocyte density (p=0.001), and leucocyte flow (p=0.024) despite lowering blood pressure to a significant degree. For venous and arterial vessel size measurements short term coefficients of variation were 1.3% and 2.6% and intraclass correlation coefficients were 0.98 and 0.96, respectively. The sensitivity was between 3% and 5% for retinal veins and 5% and 7% for retinal arteries.
These data indicate that the Zeiss retinal vessel analyser is an accurate system for the assessment of retinal diameters in healthy subjects. In addition, nitric oxide appears to have a strong influence on retinal vascular tone.
British Journal of Ophthalmology 12/2000; 84(11):1285-90. · 2.90 Impact Factor
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ABSTRACT: To characterize optic disk blood flow in patients with open-angle glaucoma compared with age-matched healthy control subjects.
In this prospective cross-sectional study, 90 eyes of 90 patients with open-angle glaucoma and 61 eyes of 61 age-matched healthy control subjects were evaluated. Flow in the optic disk cup and the neuroretinal rim were assessed with scanning laser Doppler flowmetry. Fundus pulsation amplitude in the cup and the macula were assessed with laser interferometry. Visual field mean deviation was measured with the Humphrey 30 to 2 program.
Flow in the neuroretinal rim (-18%, P =.002), and in the cup (-46%, P <.001) and fundus pulsation amplitude in the cup (-33%, P <.001) and in the macula (-24%, P <.001) were significantly lower in patients with open-angle glaucoma compared with healthy control subjects. A significant association between blood flow measurements in the cup and fundus pulsation amplitudes in the cup was observed in both study cohorts. A significant association was also observed between the mean defect from visual field testing and ocular hemodynamic parameters.
Reduced optic disk perfusion in patients with open-angle glaucoma is evidenced from two independent methods in the present study. Moreover, our data indicate that reduced ocular blood flow in these patients is linked to visual field changes. It remains to be established whether compromised optic disk and choroidal blood flow contributes to optic disk damage in glaucomatous eyes or is a secondary functional phenomenon.
American Journal of Ophthalmology 11/2000; 130(5):589-96. · 4.22 Impact Factor
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ABSTRACT: To investigate the age dependence of perimacular white blood cell flux (WBCF) during isometric exercise.
Fourteen healthy young (age range: 21-29 years; 24 +/- 3 years, mean +/- SD, 12 male and 2 female) and 15 healthy middle-aged (age range: 45-57 years; 53 +/- 4 years, mean +/- SD; 5 male and 10 female) volunteers were studied. Subjects performed isometric handgrip for 10 minutes and squatting for 6 minutes. WBCF was assessed with the blue field entoptic technique, mean arterial pressure (MAP) was measured with an automated oscillometric device, intraocular pressure (IOP) was measured by Goldmann applanation tonometry and ocular perfusion pressure (OPP) was calculated as 2/3 MAP - IOP.
Baseline WBCF was significantly higher in young subjects than in middle-aged subjects (191 +/- 28 vs 142 +/- 23; p = 0.001). Isometric handgrip induced a significant increase in WBCF in the middle-aged subjects (23 +/- 24%; p = 0.005), but not in the young subjects. Squatting significantly increased WBCF in both groups (young: 42 +/- 23%; p = 0.004 and middle aged: 51 +/- 27%; p < 0.001). A significant deviation from baseline WBCF was observed when OPP increased by 42 +/- 4% (p = 0.003) and 35 +/- 4% (p < 0.001) for the young and middle-aged subjects, respectively. The OPP-WBCF relationship was not different between the two study groups.
Altered retinal autoregulation as observed in vascular ocular disease appears to be unrelated to the normal physiological aging process.
Current Eye Research 10/2000; 21(4):757-62. · 1.28 Impact Factor
