- •Ocular Blood Flow
- •Contents
- •1: Anatomy of the Ocular Vasculatures
- •Core Messages
- •1.1 Limbus and Conjunctiva
- •1.1.1 Cornea
- •1.1.2 Vasculature Distribution in the Anterior Segment
- •1.1.3 The Conjunctiva
- •1.1.3.1 The Conjunctival Arterial Supply
- •1.1.3.2 The Conjunctival Veins
- •1.2 Uveal Tract
- •1.2.1 The Iris
- •1.2.1.1 The Major Arterial Circle of the Iris
- •1.2.2 Ciliary Body and Processes
- •1.2.3 Choroid and Suprachoroid
- •1.2.3.1 Development of the Choroidal Vasculature
- •1.2.3.2 Arteries
- •1.2.3.3 Choroidal Veins (Vortex Veins)
- •1.2.3.4 Choriocapillaris
- •1.3 Optic Nerve Vasculature
- •1.4 Retina
- •1.4.1 Development of the Retinal Vasculature
- •1.4.2 Adult Retinal Vasculature
- •1.4.3 Nonprimate Adult Retinal Vasculatures
- •1.5 Conclusions
- •References
- •Core Messages
- •2.1 Introduction
- •2.3 Stochastic Error in the Entrapment of Microspheres
- •2.4 Methodological Errors and Practical Advice
- •2.4.1 Size of the Microspheres
- •2.4.2 Physical Characteristics of Microspheres
- •2.4.4 Dissection
- •2.4.5 Detection of RM and NAM
- •2.4.6 Detection of CM and FM
- •2.5 Biological Variation
- •2.5.1 Blood Pressure
- •2.5.3 Arterial Blood Gases
- •2.5.4 Other Possible Causes for Biological Variability
- •2.6 Summary for the Clinician
- •References
- •3: Laser Doppler Flowmetry in Animals
- •Core Messages
- •3.1 Introduction
- •3.2 History
- •3.3 Theory
- •3.4 Validation
- •3.5 Calibration
- •3.6 Zero Offset
- •3.7 Effects of Oxygen
- •3.9 Measurement Depth and Sampling Volume
- •3.10 Caveats
- •References
- •4: Oxygen Measurements in Animals
- •Core Messages
- •4.1 Introduction
- •4.2.1 Oxygen Electrodes
- •4.2.2 Hypoxyprobe
- •4.2.3 Magnetic Resonance Imaging
- •4.2.4 Phosphorescence Decay
- •4.2.5 Oximetry
- •4.3.1 Vitreal Oxygen
- •4.3.2 Intraretinal Oxygen
- •4.4 Oxygen in Avascular Retinas
- •4.5 Analysis of Retinal Oxygen Utilization
- •4.5.1 Fick Principle Analyses
- •4.5.4 Other Diffusion Models
- •4.6 Physiological Variations in Retinal Oxygen
- •4.6.1 Light
- •4.6.2 Hypoxia
- •4.6.3 Hyperoxia
- •4.6.4 Hypercapnia
- •4.7 Pathophysiology and Retinal Oxygen
- •4.7.1 Vascular Occlusion
- •4.7.2 Diabetes
- •4.7.3 Retinal Detachment
- •4.7.4 Retinal Degenerative Diseases
- •4.7.5 Retinopathy of Prematurity
- •4.8 Retinal Molecular Changes Related to Oxygen
- •4.9 Oxygen in the Optic Nerve Head
- •References
- •Core Messages
- •5.1 Measuring Technique
- •5.2 Normal Values
- •5.3 Retinal Pathologies
- •5.3.1 Diabetes Mellitus
- •5.3.2 Central Retinal Vein Occlusion
- •5.4 Summary
- •References
- •Core Messages
- •6.1 Introduction
- •6.1.1 Anatomy
- •6.3 Vessel Diameter Measurements Based on Photographic and Digitally Stored Images
- •6.3.1 Basics for Measurements on Stored Images
- •6.3.1.1 Measuring Principle
- •6.3.1.4 Problems and Measuring Errors
- •6.3.1.5 Physiological Variability of Vessel Diameter
- •6.3.2 Methods
- •6.3.2.2 Microdensitometry Based on Photographic Negatives
- •6.3.2.3 Measurements Based on Digital Images
- •6.4 Diameter Assessment for Blood Flow
- •6.4.1 Assessment of Flow by Use of Doppler Technique (CLBF)
- •6.5 Retinal Vessel Analysis
- •6.5.1 Basics of Retinal Vessel Analysis
- •6.5.2 Static Vessel Analysis
- •6.5.3 Results and Limits of Static Vessel Analysis
- •6.5.4 Results and Limits of Dynamic Vessel Analysis
- •6.5.4.1 Stimulation with Flicker Light
- •6.5.4.2 Other Provocation Tests
- •6.5.5 Systems Available for Dynamic Vessel Analysis
- •6.6 Further Perspectives
- •References
- •Core Messages
- •7.1 Introduction
- •7.2 Retinal Laser Doppler Velocimetry
- •7.2.1 The Doppler Effect
- •7.2.2 Electric Field Scattered by Singly Scattering Particles Moving in a Capillary Tube
- •7.2.5 Experimental Test of the Bidirectional LDV Technique
- •7.2.7 The DSPS for RBCs Moving in a Retinal Vessel
- •7.2.7.1 Multiple Scattering of Blood
- •7.2.7.2 DSPS from RBCs Flowing in a Glass Capillary Tube
- •7.2.7.3 DSPS from Human Retinal Vessels
- •7.2.7.4 Exploring the Scattering Process
- •7.2.9 Instrumentation
- •7.2.10 Blood Flow in Retinal Vessels
- •7.2.12 Limitations, Safety, and Future Directions of the LDV Technique
- •7.2.13 Physiologic and Clinical Applications (Brief Overview)
- •7.3.1 The DSPS for RBCs Moving in the Microvascular Bed of a Tissue
- •7.3.2 Hemodynamic Parameters Derived from the DSPS
- •7.3.3 Detection Scheme for Optic Nerve and Subfoveal Choroidal Blood Flow
- •7.3.4 Critical Questions Regarding the Application of LDF to Ocular Blood Flow
- •7.3.4.1 LDF Sample Volume
- •7.3.4.2 Linearity of LDF
- •7.3.4.3 Scattering Scheme
- •7.3.5 Reproducibility of LDF
- •7.3.6 Applications of LDF
- •7.4 Summary for the Clinician
- •References
- •8: Color Doppler Imaging
- •Core Messages
- •8.1 Principles
- •8.2 Instrumentation
- •8.3 Procedure
- •8.4 Outcome Variables
- •8.5 Reproducibility
- •8.6 Physiological and Pharmacological Stimuli
- •8.7 Results in Patients with Disease
- •8.8 Advantages and Limitations
- •References
- •9: Other Approaches
- •Core Messages
- •9.1 Blue Field Entoptic Technique
- •9.1.1 Laser Speckle Technique
- •9.1.2 Pulsatile Ocular Blood Flow
- •9.1.2.1 Laser Interferometry
- •References
- •10: Systemic Determinants
- •Core Messages
- •10.1 Introduction
- •10.1.1 Ocular and Systemic Blood Flow
- •10.2 Local Skin Cooling Effect
- •10.2.1 Choroidal Blood Flow
- •10.2.2 Retinal Blood Flow
- •10.3 Aerobic Exercise
- •10.3.1 Choroidal Blood Flow
- •10.3.2 Macular Blood Flow
- •10.3.3 Retinal Blood Flow
- •10.4 Neural Activation
- •10.4.1 Valsalva Maneuver
- •10.4.2 Nicotine
- •10.5 Blood Pressure Versus Ocular Perfusion Pressure
- •10.5.1 Increased Ocular Perfusion Pressure
- •10.5.1.1 Choroidal Blood Flow
- •10.5.2 Decreased Ocular Perfusion Pressure
- •10.5.2.1 Choroidal Blood Flow
- •10.5.2.2 Optic Nerve Head Blood Flow
- •10.5.3 Neural Retinal Function
- •10.6 Blood Gases
- •10.6.1 Hyperoxia and Blood Flow
- •10.6.3 Hypoxia and Pulsatile Choroidal Blood Flow
- •10.6.4 Hyperoxia, Hypercapnia, and Retinal Function
- •10.6.5 Hypoxia, Hyperoxia, and Retinal Function
- •10.7 Regional Choroidal Perfusion
- •10.7.1 Cones Versus Rods: Structure and Function
- •10.7.2 Choroidal Angioarchitecture
- •10.7.3 Dark Adaptation
- •10.7.4 Protracted Blue Flicker
- •10.8 Aging
- •10.8.1 Structure
- •10.8.2 Blood Flow
- •10.8.3 Retinal Function
- •References
- •11: Local Determinants
- •Core Messages
- •11.1 Introduction
- •11.2 Ocular Perfusion Pressure, IOP, and the Ocular Starling Resistor Effect
- •11.3 Types of Local Control
- •11.3.1 Myogenic Local Control
- •11.3.2 Metabolic Local Control
- •11.3.3 Flow-Mediated Vasodilation
- •11.3.4 Flow Control by Intercellular Conduction
- •11.4 Ocular Local Control
- •11.4.1 Optic Nerve Head (ONH)
- •11.4.2 Choroid
- •11.4.3 Retina
- •11.4.4 Ciliary Body
- •11.4.5 Iris
- •11.5 Caveats
- •11.6 Summary for the Clinician
- •References
- •12: Neural Control of Ocular Blood Flow
- •Core Messages
- •12.1 Overview of Ocular Blood Supplies and Their Neural Control
- •12.2 Neural Control of Optic Nerve and Retinal Blood Flow
- •12.3 Neural Control of Iridial and Ciliary Body Blood Flow
- •12.4 Neural Control of Blood Flow in Orbital Glands
- •12.5 Neural Control of Choroidal Blood Flow
- •12.5.1 Importance of the Choroid
- •12.5.2 Choroidal Innervation: Overview of Anatomy
- •12.5.3 Facial Nucleus Parasympathetic Input
- •12.5.3.4 Choroidal Autoregulation and the PPG Input to Choroid – Mammals
- •12.5.3.8 Choroidal Autoregulation and the PPG Input to Choroid – Birds
- •12.5.4 Oculomotor Nucleus Parasympathetic Input
- •12.5.4.1 Ciliary Ganglion Circuitry – Mammals
- •12.5.4.2 Function of the EW-Ciliary Ganglion Circuit – Mammals
- •12.5.4.3 Ciliary Ganglion Circuitry – Birds
- •12.5.4.4 Function of vSCN-EWM-Ciliary Ganglion Circuit – Birds
- •12.5.5 Sympathetic Superior Cervical Ganglion Input
- •12.5.6 Trigeminal Sensory Input
- •12.5.7 Intrinsic Choroidal Neurons
- •12.5.8 Disturbed Neural Control of Choroidal Blood Flow in Aging and Retinal Disease
- •12.5.8.1 Effect of Aging on Retina and Choroid
- •12.5.8.2 Effect of Disease on Retina and Choroid
- •References
- •13: Endothelial and Adrenergic Control
- •Core Messages
- •13.1 Nitric Oxide
- •13.2 Endothelins
- •13.3 Arachidonic Acid Metabolites
- •13.4 Adrenergic Control
- •13.5 Alpha Receptors
- •13.6 Topical Administration
- •13.6.1 Clonidine
- •13.6.2 Brimonidine
- •13.6.3 Beta Receptors
- •13.6.4 Timolol
- •13.6.5 Human Studies
- •13.6.6 Betaxolol
- •13.6.7 Human Studies
- •13.6.8 Levobunolol
- •13.6.9 Carteolol
- •13.6.10 Serotonin
- •13.7 Carbonic Anhydrase Inhibitors
- •13.8 Acetazolamide
- •13.9 Dorzolamide
- •13.10 Retrobulbar Blood Flow
- •13.11 Retinal Blood Flow
- •13.12 Choroidal and Optic Nerve Head Blood Flow
- •13.13 Brinzolamide
- •References
- •Core Messages
- •14.1 Introduction
- •14.2 Retinal Ischemia Basic Mechanisms
- •14.3 Oxidative Stress
- •14.6 Animal Studies Relating Ischemia, Glaucoma, and Neuroprotection
- •14.6.1 Retinal Ischemia
- •14.6.6 Role of Mitochondria (Fig. 14.6)
- •References
- •Core Messages
- •15.1 Introduction
- •15.2 Retinal Blood Flow in Diabetes
- •15.3 Retinal Hypoperfusion
- •15.3.1 Mechanisms of Hypoperfusion
- •15.3.1.1 Glycaemic Control
- •15.3.1.2 Protein Kinase C
- •15.3.1.3 Ion Channel Dysfunction
- •15.4 Retinal Hyperperfusion
- •15.4.1 Mechanisms of Hyperperfusion: A Link to Hypoperfusion, Tissue Hypoxia and Retinal Leukostasis?
- •15.4.2 Retinal Autoregulation in Diabetes
- •15.5.1 Basement Membrane Thickening
- •15.5.3 Microaneurysms
- •15.5.4 Capillary Acellularity
- •15.6 Retinal Blood Flow and Vision Loss in Diabetic Retinopathy
- •15.6.1 Diabetic Macular Oedema
- •15.6.2 Proliferative Diabetic Retinopathy
- •15.7 Conclusions
- •15.8 Summary for the Clinician
- •References
- •Core Messages
- •16.1 Introduction
- •16.2 Choroidal Blood Flow
- •16.3 Systemic Vascular Factors and AMD
- •16.5 Choroidal Hemodynamic Changes in AMD
- •16.5.1 Choroidal Histopathological Vascular Changes in AMD
- •16.5.1.1 Choriocapillaris and Bruch’s Membrane in Aging and AMD
- •16.5.2 Choroidal Microcirculation in AMD
- •16.5.2.2 Choroidal Watershed Zones and Neovascularization
- •16.5.2.3 Laser Doppler Flowmetry Evaluation
- •References
- •Core Messages
- •17.1 Introduction
- •17.2 Potential Mechanisms of Ischaemic Damage in Glaucoma
- •17.2.2 Autoregulatory Disturbances
- •17.2.3 Mechanical Compression or Collapse of Vessels
- •17.2.4 Atherosclerosis
- •17.2.5 Vascular Endothelial Factors
- •17.2.6 Barriers to Nutrient Delivery
- •17.2.7 Circulating Vasoconstrictors
- •17.3 Evidence Base Supporting the Importance of Ischaemia in Glaucoma
- •17.3.1 Association and Causality
- •17.3.1.1 Reduction in Optic Nerve Head Blood Flow
- •17.3.1.2 Blood Pressure, Intraocular Pressure and Perfusion Pressure
- •17.3.1.3 Nocturnal Hypotension
- •17.3.1.4 Vasospasm
- •17.3.1.5 Endothelin and Other Circulating Peptides
- •17.3.2 Effects of Treatment
- •17.3.2.1 Calcium Channel Blockers
- •17.3.2.2 Topical Adrenergic Antagonists
- •17.3.2.4 Prostaglandin Analogues
- •17.4 Experimental Models of Ischaemia Relating to Glaucoma
- •17.4.1 Acute Ischaemia
- •17.4.2 Chronic Ischaemia
- •17.5 Summary
- •17.5.1 Diversity of Evidence
- •17.5.2 Evidence Base Compared to Intraocular Pressure
- •17.5.3 Requirements to Strengthen Evidence Base
- •References
- •Core Messages
- •18.1 Retinal Diseases
- •18.2 Uveitis
- •18.3 Optic Nerve Disorders
- •18.4 Systemic Diseases
- •References
- •Core Messages
- •19.1 Atherosclerosis
- •19.1.1 Pathogenesis of Atherosclerosis
- •19.1.2 Internal Carotid Artery Disease (ICA)
- •19.1.3 Effects on the Ocular Circulation
- •19.1.3.1 Retinal Artery Occlusion
- •Clinical Characteristics
- •Diagnosis
- •Mortality/Morbidity
- •19.1.3.2 Retinal Vein Occlusion (RVO)
- •Clinical Characteristics
- •Pathogenesis
- •Diagnosis
- •19.1.3.3 Ischemic Optic Neuropathy
- •Clinical Characteristics
- •Mortality/Morbidity
- •19.1.3.4 Asymptomatic Retinal Emboli
- •Background
- •Pathophysiology
- •19.2 Vasculitis
- •19.2.1 Takayasu’s Arteritis (Aortic Arch Syndrome)
- •19.2.1.1 Pathophysiology
- •19.2.1.2 Clinical Characteristics
- •19.2.1.3 Epidemiology
- •19.2.2 Behcet’s Disease
- •19.2.2.1 Clinical Characteristics
- •19.2.2.2 Pathogenesis
- •19.2.2.3 Diagnosis
- •19.2.2.4 Epidemiology
- •19.2.3 Thromboangiitis Obliterans
- •19.2.3.1 Diagnosis and Clinical Characteristics
- •19.2.3.2 Treatment
- •19.2.4 Temporal Arteritis
- •19.2.4.1 Epidemiology
- •19.2.4.2 Pathogenesis
- •19.2.4.3 Ocular Manifestations
- •19.2.5 Wegener’s Granulomatosis
- •19.2.5.1 Pathogenesis
- •19.2.5.2 Ocular Manifestation
- •19.2.5.3 Diagnosis
- •19.2.6 Kawasaki Disease
- •19.2.6.1 Clinical Characteristics
- •19.2.6.2 Diagnosis
- •19.3 Vascular Malformations
- •19.3.1.1 Diagnosis
- •19.3.1.2 Pathophysiology
- •19.4 Systemic Hypertension and Treatment
- •19.4.1 Etiology
- •19.4.1.1 Primary Hypertension
- •19.4.1.2 Secondary Hypertension
- •19.4.2 Pathophysiology
- •19.4.3 Pathology and Complications
- •19.4.4 Symptoms and Signs
- •19.4.5 Diagnosis of Hypertension
- •19.4.5.1 History
- •19.4.5.2 Physical Examination
- •19.4.5.3 Testing
- •19.4.6 Prognosis
- •19.4.7 General Treatment
- •19.4.7.2 Drugs
- •19.5 Hypertensive Retinopathy
- •19.5.2 Pathophysiology
- •19.5.3 Blood Pressure
- •19.5.3.1 The Risk of Stroke
- •19.5.3.2 The Risk of Coronary Heart Disease
- •19.5.4 Treatment
- •19.5.4.1 ACE Inhibitors and the Eye
- •References
- •Index
138 |
C.E. Riva |
|
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desired site, namely the rim of the optic disk or the fovea, respectively. The light scattered from the illuminated volume of tissue is collected and guided to a photodetector [5, 67].
Various means have been used to process the output photocurrent. Early studies in cats used the electronic systems of a commercial laser Doppler ßowmeter (PeriFlux PF3, Perimed, Inc., Stockholm,SwedenoraTSILaserFlo,Vasamedics, Minneapolis, USA) [6, 68]. More recent methods process the photocurrent using an algorithm developed for the NeXT computer [29]. Since this computer is no longer available, this algorithm is now implemented on a PC-based system [30].
The LDF parameters are calculated according to the procedure described by Bonner and Nossal [65]. These parameters include (1) the ÒvelocityÓ (Vel) of the RBCs, which is a measure of the broadening of the DSPS. For a tissue where the blood volume represents only a small percentage of the tissue volume (this is the case for the ONH), Vel is proportional to the root mean square of the RBC velocities; (2) ÒvolumeÓ (Vol), the number of moving RBCs in the sampled volume, which is proportional to the area under the DSPS; and (3) Flow, which is proportional to the product Vel ×Vol. Flow is usually referred to as Òblood ßow.Ó However, what Flow actually measures is the flux of the RBCs. Blood ßow is directly proportional to RBC ßux only if the hematocrit remains constant during an experiment. Before the calculation of these parameters, the DSPS is corrected for the shot noise power present in the photocurrent.
The LDF parameter Vel is expressed in Hz. The parameters Vol and Flow are in arbitrary units. The inability of LDF to provide absolute ßow measurements is due to the fact that laser radiation incident on a tissue undergoes scattering and absorption, both processes inßuencing the penetration pattern of the light. Penetration may differ from one region of a tissue to another, depending upon the optical properties of the tissue. Thus, spatial or temporal variations in tissue structure and vascularization, as is the case for example in the ONH in glaucoma, will affect the LDF parameters. Furthermore, direct comparison between the LDF parameters obtained from different tissues may not be valid due to variations in optical properties resulting from differences in tissue structure and
composition. In addition, light scattering by the ocular media will also inßuence the LDF parameters, as demonstrated by scanning laser Doppler ßowmetry performed in the presence of simulated light scatter induced by polystyrene microspheres placed in a cell in front of the eye of volunteers. This scatter induced an artifactual increase in the Flow in the retinal capillaries [69].
In addition to the LDF parameters, the mean of the photocurrent (so-called direct current, DC) is also recorded. The DC is proportional to the intensityofthelightincidentonthedetector(shifted+nonshifted scattered light). For repeated measurements from the same site of the fundus, it is important to maintain this parameter constant (arbitrarily within 10% of the mean) to insure that the variations of the LDF parameters are not due to variations in the intensity of the probing beam at the fundus or changes of the measurement site. Constancy of the DC can be further improved by maintaining constant the location of the entrance of the probing beam at the pupil of the tested subject, particularly in the measurements of ONH blood ßow [70].
7.3.3Detection Scheme for Optic Nerve and Subfoveal Choroidal Blood Flow
Two LDF measurement modes have been implemented. The Þrst is the continuous mode for online, continuous recording of the LDF parameters at a discrete site of the vascular beds of the ONH, subfoveal region of the choroid, or the iris. The second mode was based on a scanning technique, which provides a two-dimensional image of the RBC ßux in the capillaries of the ONH and retina. This technique is no longer available. This chapter describes only the former one.
7.3.3.1Real-Time Recording of the LDF Signal in the ONH and Subfoveal
Choroid (SFCH)
With the fundus-camera-based LDF system, originally described by Riva et al., to record the LDF signal from the ONH and the SFCH [6, 9], a laser beam from a HeNe (623 nm) or diode laser