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Ординатура / Офтальмология / Английские материалы / Atlas of Glaucoma, Second Edition_Choplin, Lundy_2007

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13 Ocular blood flow

Alon Harris, Christian P JonescuCuypers

INTRODUCTION

From the most basic standpoint, the eye offers a unique opportunity to study hemodynamics. It is the only location in the body where capillary blood flow may be observed in humans non-invasively. Over 100 years ago, Wagemann and Salzmann observed vascular sclerosis in many of their glaucoma patients. Through the years, numerous other researchers have uncovered pieces of the ocular blood flow puzzle: documenting reductions in the capillary beds, sclerosis of nutritional vessels, vascular lesions and degeneration, and other circulatory pathologies in many eye diseases including glaucoma. A century of observation and circumstantial evidence suggesting a vascular component in the pathogenesis of glaucoma is now supported by direct experimental evidence. This transition from theory to fact took 100 years because the technology required to make such specialized measurements of hemodynamic function have only recently become available. Now that the link has been established, there has been a focus on ocular hemodynamics in glaucoma and the effect of intraocular pressure (IOP)-reducing medications on ocular perfusion.

OCULAR VASCULATURE

The ophthalmic artery is the source for blood flow to the eye but the left and right ophthalmic arteries derive blood from the heart through slightly different routes. The left carotid artery is one of three branches of the aortic arch. The right carotid artery is a branch of the brachiocephalic artery, itself one of the three branches of the aortic arch (Figure 13.1). Both left and right common carotids split to form the internal and external carotid arteries. The only branch of the internal carotid artery outside the

cranium is the ophthalmic artery (Figure 13.2). The ocular vasculature is exceedingly complex. The various layers of tissue in the retina receive nourishment from both the uveal and the retinal vasculature.

The ophthalmic artery (OA) supplies both major ocular vascular beds: the retinal and uveal systems. Its major branches include branches to the extraocular muscles, the central retinal artery and the posterior ciliary arteries (Figure 13.3). The uveal system, which supplies blood to the iris, ciliary body, and choroid, is supplied by one to five posterior ciliary arteries (PCA). They emerge from the ophthalmic artery in the posterior orbit. Short posterior ciliary arteries (SPCAs) penetrate the sclera surrounding insertion of the optic nerve (Figure 13.4). These vessels supply the peripapillary choroid, as well as the majority of the anterior

Arteria carotis

 

interna

 

Arteria

Arteria carotis

externa

vertebralis

 

Arteria

Arteria carotis

subclavia

communis

 

Arteria (arcus

Heart

aortae)

Figure 13.1 Origin and path of arteria carotis.

183

184 Atlas of glaucoma

Arteria

 

optic nerve. Some SPCAs course, without branch-

pericallosa

 

ing, through the sclera directly into the choroid;

 

Arteria

 

others divide within the sclera to provide branches

Arteria

opthalmica

cerebri anterior

 

to both the choroid and the optic nerve. Often, a

 

 

 

 

non-continuous arterial circle exists within the

Arteria

 

perineural sclera, the circle of Zinn–Haller. This

 

structure is formed by the convergence branches

cerebri

 

media

 

from the short posterior ciliary arteries. The circle

 

 

 

 

of Zinn–Haller provides blood for various regions

 

 

of the anterior optic nerve, the peripapillary

 

 

choroid, and the pial arterial system.

Arteria cerebri posterior

Arteria carotis interna

Arteriae insulares

Figure 13.2 Cerebral vasculature.

Oculus sinister

Arteria

(= left eye)

ciliaris anterior

Arteria lacrimails

Arteria ciliaris posterior longa

VASCULATURE OF THE CHOROID

The outer choroid is composed of large nonfenestrated vessels, while the vessel caliber of the inner choroid is much smaller. The innermost layer of the choroid, the choriocapillaris, is composed of richly anastomotic, fenestrated capillaries beginning at the optic disc margin (Figure 13.5). The capillaries of the choriocapillaris are separate and distinct from the capillary beds of the anterior optic nerve. The SPCAs supply most of the optic nerve head

Arteria supratrochlearis

Arteria dorsails nasi

Arteria ethmoidails anterior

 

Arteria

 

Arteria ciliaris

ethmoidails

Figure 13.3 Branches origi-

posterior

posterior brevis

 

nating from the arteria carotis

 

 

 

 

interna.

Arteria ophthalmica

Arteria

 

centralis

 

 

 

 

retinae

 

Arteria carotis interna

Ocular blood flow 185

Long posterior ciliary

 

artery (arteria cilliaris

 

posterior longa)

 

(LPCA)

 

Short posterior

Posterior ciliary artery

ciliary arteries

(arteria ciliaris posterior)

(Arteriae ciliares

 

posteriores breves)

 

(SPCAs)

 

 

Choriocapillaris

Outer choroid vessels

Figure 13.5 Cross section of choroidal vascular bed.

and the portion of the choriocapillaris posterior to the equator. The choriocapillaris anterior to the equator is supplied by the long posterior ciliary arteries (LPCAs) and the anterior ciliary arteries (ACAs). The LPCAs pierce the sclera and course anteriorly through the suprachoroidal space to branch near the ora serrata. Each LPCA then sends three to five branches posteriorly to supply the choriocapillaris anterior to the equator. The ACAs, branches of the OA, accompany the rectus muscles anteriorly to supply the major circles of the iris (Figure 13.6). Before reaching the iris, 8–12 branches pass posteriorly through the ciliary muscle to supply the anterior choriocapillaris together with the LPCAs (Figure 13.7). Functional anastomoses between the choriocapillaris anterior and posterior to the equator have not been demonstrated. This represents a peripheral choroidal watershed zone.

Venous drainage from the choriocapillaris is mainly through the vortex vein system. Minor

Figure 13.4 Choroidal and retinal vasculature.

Arteria and vena centralis retinae

drainage occurs through the ciliary body via the anterior ciliary veins. The vortex veins drain into the inferior (IOV) and superior (SOV) ophthalmic veins (Figure 13.8). The SOV exits the orbit through the superior orbital fissure and drains into the cavernous sinus. The IOV sends a branch to the SOV and then exits the orbit through the inferior orbital fissure into the pterygoid plexus.

The retinal system is supplied by the central retinal artery (CRA) and sustains the inner retina. The CRA, itself a branch of the ophthalmic artery, penetrates the optic nerve approximately 12 mm behind the globe. The CRA courses adjacent to the central retinal vein through the center of the optic nerve, then emerges from the optic nerve within the globe, where it branches into four major vessels.

The anterior optic nerve may be divided into four anatomic regions: the superficial nerve fiber layer, the prelaminar region, the lamina cribrosa, and the retrolaminar region (Figure 13.9).

The superficial nerve fiber layer, the anteriormost region, is continuous with the nerve fiber layer of the retina and is the only nerve head structure visible by fundus examination (Figure 13.9, yellow shaded). It is supplied by retinal arterioles arising from the branches of retinal arteries. These small vessels originate in the surrounding nerve fiber layer and run toward the center of the optic nerve head. They have been referred to as ‘epipapillary vessels’. The temporal nerve fiber layer may receive additional blood from a cilioretinal artery when it is present. No direct choroidal or choriocapillaris contribution is observed in the superficial nerve fiber layer.

Immediately posterior to the nerve fiber layer is the prelaminar region, which lies adjacent to the peripapillary choroids (Figure 13.9, red shaded). In this region, ganglionic axons group into

186 Atlas of glaucoma

Camera vitrea bulbi (vitreous cavity)

Circulus arteriosus iridis major

Circulus arteriosus iridis minor

Musculus rectus lateralis

Arteriae ciliares

anteriores (anterior Cornea ciliary arteries)

Sclera

Figure 13.6 Anterior segment.

Circulus arteriosus iridis minor

Circulus arteriosus iridis major

Arteria ciliaris anterior (anterior ciliary artery)

Chorioidea

(choroid)

Figure 13.7 Anterior vessels.

bundles for passage through the lamina cribrosa. The prelaminar region is supplied primarily by branches of the SPCAs and by branches of the circle of Zinn–Haller, though some investigators have observed a vascular contribution to the prelaminar region from peripapillary choroidal arterioles. The amount of choroidal contribution may be difficult to ascertain, as there are branches from both the circle of Zinn–Haller and from the SPCAs which course through the choroid and ultimately supply the optic nerve in this region. These vessels do not originate in the choroid, but merely pass through it. The direct arterial supply to the prelaminar region arising from the choroidal vasculature is minimal. This minimal contribution from the choroidal vasculature is limited to small arterioles. There is no vascular contribution from the choriocapillaris.

More posteriorly, the laminar region is continuous with the sclera and is composed of the lamina cribrosa (Figure 13.9, green shaded). The lamina cribrosa is a structure consisting of fenestrated connective tissue which allows the passage of neural axons through the scleral coat. Like the prelaminar

Ocular blood flow 187

Vena ophthalmica superior

Venae vorticosae

(vortex veins)

Sinus cavernosus

(cavernous sinus)

Vena angularis

Vena ophthalmica

Optic nerve

inferior

head

Figure 13.8 Venous drainage of the orbit and globe.

Optic nerve head

Superficial nerve fiber layer region

Pre-laminar

Retina

Choroid

region

 

Lamina cribrosa

 

region

 

Retro-laminar

region

Central retinal

Sclera artery and vena

Posterior ciliary arteries

Figure 13.9 Optic nerve head vasculature. (Figures 13.1–13.9 from Atlas of Ocular Blood Flow: Vascular Anatomy, Pathophysiology and Metabolism with permission from Elsevier).

region, the lamina cribrosa also receives its blood supply from branches of the SPCAs and branches of the circle of Zinn–Haller. These precapillary branches perforate the outer lamina cribrosa before branching centrally, forming a capillary network throughout the fenestrated connective tissue. Larger vessels of the peripapillary choroid may contribute occasional small arterioles to the lamina cribrosa region.

Finally, the retrolaminar region lies posterior to the lamina cribrosa and, marked by the beginning of axonal myelination, is surrounded by the

meninges of the central nervous system (Figure 13.9, blue shaded). The retrolaminar region has two blood supplies – the CRA and the pial system. The pial system is an anastomosing network of capillaries located immediately within the pia mater. The pial system originates at the circle of Zinn–Haller and may also be fed directly by the SPCAs. Its branches extend into the optic nerve to nourish the axons. The CRA may provide several small intraneural branches in the retrolaminar region. Some of these branches anastomose with the pial system.

188 Atlas of glaucoma

There is a marked interindividual variation in

 

 

 

the vascular patterns of the anterior optic nerve,

 

 

 

peripapillary retina and posterior choroid. The

 

 

 

predominant variability observed among individu-

 

 

 

als is in the arterial supply. Varying numbers of

 

 

 

branches have been found in the posterior ciliary

 

 

 

arteries, the SPCAs, the number of branches from

 

 

 

the LPCAs, and the number of branches from

 

 

 

the ACAs.

 

 

 

The most recent evidence suggests that glau-

 

 

 

coma characteristically damages the photorecep-

 

 

 

tors and the horizontal cells, as well as the retinal

 

 

 

ganglion cells. The retinal ganglion cells are nour-

 

 

 

ished by the retinal circulation, while the photo-

 

 

 

receptors receive their blood supply from the

 

 

 

underlying choroid. Therefore, to define how

Figure 13.10

Pubsatile ocular blood flow device. (OBF

enhanced blood flow improves visual function, it

Labs (UK) Ltd. Malmesbury, Wiltshire, England.)

is essential to evaluate blood flow to the retina and

 

 

 

choroid, for the retinal ganglion cells and photore-

 

 

 

ceptor cells, respectively.

 

 

 

Several soluble vasoactive molecules mediate

 

 

 

retinal vascular autoregulation, including endothe-

 

 

 

lium-derived nitric oxide, endothelins, superoxide

 

 

 

anions, rennin–angiotensin, and vascular endothe-

 

 

 

lial growth factor (VEGF).

 

 

 

TECHNIQUES FOR EXAMINING OCULAR

 

 

 

BLOOD FLOW

 

 

 

Technological revolutions in medical science

 

 

 

have enabled clinicians and researchers to better

 

 

 

visualize ocular blood flow (OBF). In the past two

 

 

 

decades, ocular hemodynamics assessment has

 

 

 

evolved from a subjective description of visible

Figure 13.11 Representation of the principle of pulsatile

vessels to direct quantitative measurement of blood

ocular blood flow measurements.

Blood volume in the

flow parameters. Each technique provides a differ-

eye increases with the systolic pulse and decreased

ent aspect of ocular hemodynamics and therefore

during diastole.

 

different ones are required in order to quantify

 

 

 

the various vascular beds comprising the ocular

unknown, and varies between individual eyes. The

circulation.

 

IOP pulse wave is transformed into an ocular vol-

 

ume wave using the presumed universal relation-

PULSATILE OCULAR BLOOD FLOW

ship. The change in volume over time is reported

 

as the pulsatile ocular blood flow.

The pulsatile ocular blood flow (POBF) device (the

 

 

 

OBF Labs (UK) Ltd unit is pictured in Figure 13.10)

OCULO-OPHTHALMODYNAMAMOGRAPHY

is a pneumotonometer that measures IOP in real

time. It is based on the principle (Figure 13.11) that

The oculo-ophthalmodynamamograph (OODG)

blood volume in the eye increases with the systolic

pulse, and decreases during diastole. When the

device is a pneumotonometer that measures IOP in

volume increases, eye pressure increases as well. If

real time, similar to the POBF device (Figure 13.12).

the relationship between eye pressure and eye vol-

The OODG differs from the POBF in that it is used

ume is identical for everyone, then transient

in combination with a scleral suction cup. During

changes in IOP can be used to calculate absolute

the measurement, IOP is increased. With sufficient

transient changes in ocular volume. As with a car

IOP increase, flow ceases within each of the vascu-

tire that is leaking air, however, the true volume of

lar beds within the globe. When blood flow ceases

blood entering the eye is unknown, because the

within a vascular bed, its contribution to the IOP

rate of venous flow (the leak) is not measured, is

waveform

measured by the

pneumotonometer

Ocular blood flow 189

Figure 13.12 Waveform produced by the oculo-ophthalmo- dynamamograph (OODG). This measures IOP in real time.

disappears. The OODG uses this phenomenon to directly quantify the perfusion pressure within the uveal and retinal beds.

COLOR DOPPLER IMAGING

Fundamentals

Ultrasound uses sound waves to locate structures in the body. By timing the delay between sound transmission and echo, ultrasound can measure the depth and location of an anatomic structure, e.g. A-scan ultrasound measurements of axial length. The time between transmission of a sound wave into the eye and the returning echo from the back of the eye provides a precise measurement of axial length. This measurement does not require clear optical media and can be performed in the presence of many ophthalmic diseases. By sweeping the A-scan in a line through the eye, a map of structural locations through a slice is obtained. This is commonly known as B-scan ultrasound and has been used to produce gray-scale images of ophthalmic structures. Color Doppler imaging (CDI) is based on B-scan technology, with an additional processing step (Figure 13.13). The frequency of the returning B-scan sound waves is analyzed. When a wave is reflected by a moving source, such as flowing blood, it is Doppler shifted to a different frequency. The amount of the shift is described by the Doppler equation (Figure 13.14), where VBlood is the blood flow velocity, Wavelength is the wavelength of the incident sound wave, and Cos is the cosine of the angle between the blood velocity vector and the incident sound wave vector. Doppler shifted sound is displayed using color-coded pixels within the gray-scale image. Red pixels represent movement toward the CDI probe, and blue represents movement away from the probe. Samples of Doppler shifts (or velocities as calculated using the

Figure 13.13 Color Doppler imaging ultrasound machine.

(Siemens Quantum 2000, Siemens Ultrasound, Isaquaah, WA.)

Figure 13.14 Formula for calculating blood flow velocities from Doppler shift.

equation in Figure 13.14) may be collected from specified vessels within the image. These data are collected in real time during the cardiac cycle. A number of data may be obtained from the resulting velocity waveform. The peak systolic velocity (PSV) is located by the ultrasonographer and is equal to the greatest observable flow velocity obtained by the blood during systole. The enddiastolic blood flow velocity (EDV) can also be located by the ultrasonographer (Figure 13.15). Using both of these measurements, Pourcelot’s resistive index (RI) may be computed (Figure 13.16); RI is an indication of the resistance to flow in the vasculature distal to the point of measurement.

190 Atlas of glaucoma

Figure 13.15 Peak systolic velocity and end diastolic velocity. These are marked by the ultrasonographer and resistive index is then calculated from these values.

Figure 13.16 Formula for calculation of Pourcelot’s Resistive Index. This uses peak systolic and end diastolic velocities.

Hemodynamic measurements

CDI is used to measure blood flow velocities in the ophthalmic, CRA and SPCAs. Due to the large difference between the ophthalmic and smaller CRA and SPCAs, the system settings are changed to appropriate ranges of depth and velocity. The waveforms of the various vessels provide additional information. The dicrotic notch is clearly evident in the ophthalmic artery waveform (Figure 13.17), while still evident yet less pronounced in the CRA and missing from the SPCA.

In glaucomatous eyes with high resistance to flow, SPCA waveforms take on the appearance of a haystack with almost no end-diastolic flow. CDI thus allows quantification of flow velocities in the retrobulbar vasculature in research and clinical settings. The appearance of waveforms may also provide insight into the condition of the patient’s ocular vascular health.

Figure 13.17 Waveform produced by the ophthalmic artery.

This is distinct from the other vessels by a dicrotic notch.

ANGIOGRAPHY

Fundamentals

Ophthalmic angiography dates back to 1961 when, at the Indiana University School of Medicine, Novotny and Alvis first described a method for photographing fluorescein as it passed through the human retina. Their early technique was limited to one image every 12 seconds. Today fluorescein angiography can be performed with scanning laser ophthalmoscopes (SLO) which are capable of a wide range of imaging applications in ophthalmology. The Rodenstock SLO is an imaging device that produces fundus images (Figure 13.18). The Heidelberg retina angiography (HRA) unit is a digital imaging platform equipped with argon and infrared lasers (Figure 13.19).

Both the HRA and Rodenstock SLO utilize a confocal optical system (Figure 13.20). For each point of the image, light is focused to a point on the fundus. Light reflected from this point is quantified by a photodetector. Confocal systems create

Figure 13.18 Rodenstock Scanning Laser Ophthalmoscope.

Ocular blood flow 191

 

 

 

improvements in image collection are important,

 

 

 

improvements in image interpretation and analysis

 

 

 

continue to provide new insight into the physiology

 

 

 

and pathophysiology of ocular hemodynamics.

 

 

 

Video images obtained from Rodenstock SLO

 

 

 

angiography are analyzed using digital video

 

 

 

analysis equipment. Each frame of a video segment

 

 

 

of interest is digitized. This allows the brightness

 

 

 

in specified areas to be quantified. As dye enters

 

 

 

retinal vessels, it becomes bright. By quantifying

 

 

 

the brightness in two locations on a retinal vessel,

 

 

 

the amount of time for fluorescein dye to move from

 

 

 

a proximal to a distal location may be measured

 

 

 

(Figure 13.21). Utilizing the image-processing

 

 

 

capabilities of the analysis system, the distance

Figure 13.19 Heidelberg Retinal Angiograph.

between the two brightness measurement locations

may also be measured. Combining distance and

 

 

 

 

 

 

time data yields the mean dye flow velocity (MDV)

 

 

 

through retinal vessels. If the same system is used

 

 

 

to measure vessel diameter, volumetric flow

 

 

 

through the retinal arteries may be calculated.

 

 

 

Hemodynamic measurements at 40

 

 

 

In order to obtain an accurate measurement, sam-

 

 

 

ple areas on retinal arteries are located on a length

 

 

 

of vessel void of branches. A plot of the brightness

 

 

 

of a vein in time may be used with the arterial plots

 

 

 

in order to measure the arteriovenous passage

 

 

 

(AVP) time. The AVP time is an indication of the

 

 

 

overall status of the retinal microcirculation,

 

 

 

requiring passage of dye from retinal arteries to

 

 

 

retinal veins (Figure 13.22).

Figure

13.20

Diagrammatic representation of a confocal

Hemodynamic measurements at 20

optical

system. This is utilized in the Rodenstock

Scanning Laser Ophthalmoscope and Heidelberg Retinal

Measurements of blood velocity in the perifoveal

Angiograph.

 

 

retina were first estimated using the blue field

 

 

 

sharp images by blocking scattered light from the

entoptic phenomenon. Illuminated by a bright blue

light, the leukocytes cast a shadow on retinal

image. Only light from the point of interest is

 

focused to a point at the aperture.

 

The HRA and Rodenstock SLO are also used to

 

quantify retinal hemodynamics. By recording fluo-

 

rescein and indocyanine green angiograms, both of

 

the SLO systems provide valuable data concerning

 

the movement of blood through the retinal and

 

choroidal vasculature; however, measurement of

 

volumetric blood flow by angiography is currently

 

impossible.

 

 

Equipped with argon, infrared, and helium–

 

neon lasers, and a number of apertures and filters,

 

the Rodenstock SLO has a large number of imaging

 

modes. Temporal resolution has increased to 30

 

images per second and spatial resolution is maxi-

 

mized by using a scanning laser to illuminate the

 

fundus one point at a time. Images obtained from the

 

Rodenstock SLO are recorded on videotape because

Figure 13.21 Image of fluorescein angiogram indicating the

of the large

amount of image data. While the

appearance of dye arrival in the arteries.

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